Samarth Pharma

DIABETES MELLITUS

2018-08-30T21:09:00.000+05:30

INTRODUCTION

Diabetes Mellitus is a group of metabolic disorder characterized by hyperglycaemia associated with abnormalities in carbohydrate, fat and protein metabolism resulting in chronic complications.

It is a serious and economically devastating illness that is reaching epidemic proportions in both industrialized and developing countries and poses a major threat to public health in the 21^st century. Diabetes was the fifth leading cause of death in the US in the year 2000. Diabetes is associated with an increased incidence of stroke, heart failure, new-onset blindness, limb amputations, End-Stage Renal Disease (ESRD), birth complications and sexual dysfunction. Persons with diabetes often have associated Cardio Vascular Disease (CVD) risk factors including hypertension, dyslipidaemia, and obesity.

Diabetes is one of the leading causes of morbidity and mortality due to specific microangiopathy and the associated macroangiopathy. It is the leading cause of blindness and visual impairment in adults in the western hemisphere and the risk of cardiovascular disease is two to five times in persons with diabetes, as compared to normal adults. For the purpose of rational management, it is appropriate to classify diabetes as the following.

Type 1 (also called Insulin-Dependent Diabetes Mellitus or IDDM),
Type 2 (also called Non-Insulin-Dependent Diabetes Mellitus or NIDDM).

Other specific types of diabetes are :

Genetic defects of b-cell function (eg.MODY)
Genetic defects in insulin action
Diseases of the endocrine pancreas
Endocrinopathies
Drug or chemical induced
Infections
Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus

Defined as any degree of glucose intolerance that has its onset or is first detected during pregnancy.

Occurs in approximately 2% - 4% of pregnant women, generally during the second or third trimester.
Occurrence of GDM increases future risk for developing type 2 diabetes.

CHART 1: DIFFERENCE BETWEEN TYPE 1 AND TYPE 2 DIABETES

Characteristics	Type 1	Type 2
Other names	Previously : insulin-dependent diabetes mellitus (IDDM) : juvenile-onset diabetes mellitus	Previously : non-insulin-dependent diabetes mellitus (NIDDM): adult onset diabetes mellitus
% of diabetic population	5-10%	90%
Age of onset	Usually <30 yr, peaks at 12-14 yr, rare before 6 months, some adults develop type 1 during the fifth decade	Usually >40 yr, but increasing prevalence among obese children.
Pancreatic function	Usually none, although some residual C-peptide can sometimes be detected at diagnosis, especially in adults	Insulin present in low, "normal", or high amounts
Pathogenesis	Associated with certain HLA types; presence of islet cell antibodies suggests autoimmune process	Defect in insulin secretion, tissue resistance to insulin; ↑ hepatic glucose output.

CHART 1: continued

Family history	Generally not strong	Strong
Obesity	Uncommon unless "overinsulinized" with exogenous insulin	Common (60-90%)
History of ketoacidosis	Often present	Rare, except in circumstances of unusual stress (eg.infection)
Clinical presentation	Moderate to severe symptoms that generally progress relatively rapidly (days to weeks): polyuria, polydipsia, fatigue, weight loss, ketoacidosis	Mild polyuria, fatigue, often diagnosed on routine physical or dental examination
Treatment	Insulin Diet Exercise	Diet Exercise Oral antidiabetic agents and insulin

PREVALENCE

The prevalence of diagnosed diabetes has increased dramatically over the past 40 years both in the US and worldwide. In 1985, there were approximately 30 million people with diabetes worldwide; by 1995, this number had escalated to 135 million and by 2025, it is projected that there will be an increase in the incidence of diabetes, affecting 300 million people. Most of the expected increase will be in type 2 diabetes, which accounts for >90% of cases of diabetes, while the incidence of type 1 diabetes is anticipated to remain stable. By 2025 the countries with largest number of people with diabetes will be in India (>57 million, prevalence 6%), China (>37 million, prevalence 3.4%), and the United States (>21 million, prevalence 8.9%).

REVIEW OF MANAGEMENT OF DIABETES

Three methods of treatment are available for diabetic patients: diet alone, oral hypoglycaemic drugs, and insulin. Approximately 50% of new cases of diabetes can be controlled adequately by diet alone, 20-30% will require insulin. Regardless of aetiology, the type of treatment required is determined by the circulating plasma insulin concentration. In clinical practice the age and weight of the patient at diagnosis are closely related to the plasma insulin and usually indicate the type of treatment required.

Fig 1: Long-term treatment of diabetes

DIETARY MANAGEMENT

Dietary measures are required in the treatment of all diabetic patients to achieve the overall therapeutic goal: i.e. normal metabolism. The aims of dietary treatment are the following.

Abolish symptoms of hyperglycaemia.
Reduce overall blood glucose and minimize fluctuations.
Achieve weight reduction in obese patients to reduce insulin resistance, hyperglycaemia and dyslipidaemia.
Avoid hypoglycaemia associated with therapeutic agents

(Insulin, sulfonylureas).

Avoid weight gain associated with therapeutic agents

(Insulin, sulfonylureas, thiazolidinediones).

Avoid 'atherogenic' diets or those, which may aggravate diabetic complications

(e.g. high protein intake in nephropathy).

TYPES OF DIABETIC DIET

Two basic types of diet are used in the treatment of diabetes: low-energy, weight-reducing diets and weight maintenance diets.

Low-energy, weight-reducing diets

Dietary prescriptions, which cause a daily deficit of 500kcal, provide a realistic diet and induce a weekly weight loss of around 0.5kg. Rapid weight reduction may provoke loss of lean body tissue, and care must be taken in the elderly to avoid the omission of essential nutrients, vitamins and minerals. Caloric restriction is essential for the obese diabetic patient treated with insulin and most oral agents, to try to minimize the weight gain, which these can promote. In such individuals, the omission of snacks between meals is often necessary.

Weight maintenance diets

These are necessary for individuals with a normal Body Mass Index (BMI) and should be high in carbohydrate and low in fat, with particular attention being paid to the type of fat ingested.

ORAL DRUG TREATMENT OF TYPE 2 DIABETES MELLITUS

The main stay of treatment for patients with type 2 diabetes who fail diet therapy are the oral antidiabetic agents. There are 5 classes of oral antidiabetic agents available in the United States: Sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolid-inediones and non-sulfonylurea secretagogues. They have differences and similarities with respect to their pharmacology and role in diabetes.

The oral antidiabetic drug classes differ in their sites and mechanisms of action to lower plasma glucose. The sulfonylureas and non sulfonylurea (non-SU) Secretagogues primarily work in the pancreas to stimulate insulin release. The biguanides primarily work in the liver to decrease glucose production. The alpha-glucosidase inhibitors primarily work in the small intestine to slow carbohydrate absorption. The thiazolidinediones (TZDs) primarily work in the peripheral tissues and act as insulin sensitizers.Chart 2 lists the mechanism and site of action for each class of drugs.

Chart 2

The oral antidiabetic agents also differ in their effects on the patient's lipid profile. Sulfonylureas, non-SU secretagogues, and alpha-glucosidase inhibitors do not appreciably affect the lipid profile. Biguanides can improve the complete lipid profile, whereas TZDs can improve some lipid levels while adversely affecting the others. Chart 3 lists the effects the oral antidiabetic agents have on lipid profile.

Chart 3

Sulfonylureas

Sulfonylureas are classified as first and second-generation agents based on when they became available. The generations differ in their potency, Pharmacokinetics, and safety. The second-generation agents are more potent and in general have better pharmacokinetic and safety profiles. The first-generation agents include acetohexamide, chlorpropamide, tolazamide, and tolbutamide. The second-generation agents include glimepiride, glipizide, and glyburide. It is well known that sulfonylureas (available since 1954) lower plasma glucose primarily by increasing the release of insulin from functioning pancreatic b-cells. One concern with these agents is the loss of efficacy over time, which may be related to the potential to exhaust b-cell function. Because these agents increase plasma levels of insulin, they may cause of hypoglycaemia. The addition of other antidiabetic agents can further increase the risk of hypoglycaemia.

Biguanides

Metformin (available since 1995) is the only biguanide available in the United States. It is in the same class of drugs as phenformin, which was available but was removed from the United States and European markets in the 1970s because of its association with lactic acidosis. The long-term benefit of metformin was shown in the United Kingdom Prospective Diabetes Study, (UKPDS). Metformin has several mechanism of action, but its primary mechanism for lowering plasma glucose is to decrease hepatic gluconeogenesis. To a smaller extent, it also improves insulin sensitivity of peripheral tissues. Recent studies suggest that metformin may reduce the risk of cancer in diabetic patients.

Alpha-glucosidase Inhibitors

The alpha-glucosidase inhibitors (available since 1996) include acarbose and miglitol. These agents decrease the rate of ingested carbohydrate absorption in the small intestine. They act as competitive, reversible inhibitors of alpha-glucosidases (hydrolase enzymes found in the brush border of the small intestine), and alpha-amylase (found in the pancreas). Inhibition of these enzymes slows digestion of carbohydrates, which results in slower absorption and a reduction in postprandial plasma glucose levels.

TZDs (Thiazolidinediones)

TZDs (available since 1997) include pioglitazone and rosiglitazone. These agents act primarily to improve insulin sensitivity of muscle and adipose tissue. To a lesser extent, these agents decrease hepatic glucose production. TZDs are selective and potent agonists for the proxisome proliferator-activated receptor-gamma (PPARg) nuclear receptors. The action of these agents requires the presence of insulin. A study by found rosiglitazone to decrease the proinsulin-insulin ratio in patients with type 2 diabetes mellitus, indicating an improvement in b-cell function.

Non-SU Secretagogues

The non-SU secretagogues include repaglinide (which is a member of the meglitinide family) and nateglinide (which is a derivative of d-phenylalanine). Like the sulfonylureas, the non-SU secretagogues (available since 1998) lower plasma glucose by increasing the release of insulin from functioning pancreatic b-cells. The mechanism is exactly same as the sulfonylureas, except the non-SU secretagogues bind to different receptors on the b-cells. Unlike SU, non-SU secretagogues have a very short half-life and duration of action, so they stimulate insulin secretion for brief periods. Therefore, they are dose with meals and are most helpful in decreasing postprandial hyperglycaemia. The quick "on and off" helps to decrease the incidence of hypoglycaemia compared to SU.

EFFICACY

All 5 classes of oral antidiabetic agents lower fasting plasma glucose and A1c, but they do so to different extents. Chart 5 lists the efficacy in lowering fasting plasma glucose and A1c for the 5 classes of antidiabetic agents.

In general, sulfonylureas, biguanides, and non-SU secretagogues lower fasting plasma glucose and A1c to a similar extent.

Chart 5

Insulin

Insulin is required for treatment of all patients with IDDM and many patients with NIDDM. No single standard exists for patterns of administration of insulin, and treatment plans vary from physician to physician and, with a given physician, for different patients. Three treatment regimens will be described: Conventional, Multiple subcutaneous injections (MSI), and Continuous subcutaneous insulin infusion (CSII). MSI or CSII is required in intensive treatment schedules designed to protect against complications. Conventional insulin therapy involves the administration of one or two injections a day of intermediate-acting insulin such as Zinc insulin (Lente insulin) or Isophane insulin (NPH) with or without the addition of small amounts of regular insulin.

Insulin is considered the most effective treatment for lowering extremely high glucose. This is important because inhibition of glucotoxicity may be beneficial in preserving functional b-cell mass. Oral agents do not work as quickly or lower glucose enough to effectively address glucotoxicity in many patients.

Insulin therapy may actually protect against endothelial damage. Observational and interventional evidence consistently indicates that glycaemic control with insulin therapy in the hospital setting can improve clinical outcomes. demonstrated that the unfavourable long-term prognosis for myocardial infarction could be improved by insulin treatment.

CHART 6: CONVENTIONAL (STANDARD) PREPARATIONS OF INSULIN ( Tripathi KD 2003)

Type	Appearance	Onset (hr)	Peak (hr)	Duration (hr)	Can be mixed with
*Short Acting*
Regular (soluble) insulin	Clear	0.5-1	2-4	6-8	All preparations
Prompt Insulin Zinc Suspension (amorphous) or semilente	Cloudy	1	3-6	12-16	Regular, Lente preparations
*Intermediate Acting*
Insulin zinc Suspension or Lente (ultra: Semi: 7:3)	Cloudy	1-2	8-10	20-24	Regular, semilente
Neutral Protamine Hagedorn (NPH) or Isophane Insulin	Cloudy	1-2	8-10	20-24	Regular
*Long Acting*
Extended Insulin Zinc Suspension (Crystalline) or Ultralente	Cloudy	4-6	14-18	24-36	Regular, semilente
Protamine Zinc Insulin (PZI)	Cloudy	4-6	14-20	24-36	Regular

PATIENT EDUCATION IN DIABETES

Pharmacists Role

Pharmacists in all practice settings are in a key position to start providing care to people, who have diabetes or are at risk of developing it, or to expand and improve their care. Pharmacy programs for patients with diabetes involve activities ranging from identifying and referring at-risk patients, to supporting American Diabetes Association - recognized multi-disciplinary diabetes care programs.

Pharmacists can help identify patients with diabetes through screening and should target patients at high risk, people with a family history of the disease, and women with a history of gestational diabetes or who delivered a baby weighing more than nine pounds. Patient education should be provided immediately after diagnosis, at a second stage at which time a patient assessment can be performed, and at a third stage during which patients can receive continuing education to reinforce concepts and motivational boost. One of the pharmacist's most important roles is the referral of patients to the other members of the diabetes care team. Although the role of the pharmacist in monitoring diabetes is not well defined, it might include such things as ascertaining whether physician visits and testing to assess long-term glycaemic control.

The pharmacist can play an important role in diabetes care by screening patients at risk for diabetes, assessing patient health status and adherence to standards of care, educating patients to empower them to care for themselves, referring patients to other health care professionals as appropriate, and monitoring outcomes. Providing diabetes management services requires communication skills, and a commitment of time, effort, and resources. Pharmacists who obtain training in diabetes management reap rewards in professional satisfaction and financial reimbursement.

Patient involvement is paramount for the successful care of diabetes. Patients require education and information about a wide range of subjects. The following areas are to be considered for patient education.

The disease

Signs and symptoms

Hyperglycaemia

Signs, symptoms and treatments

Hypoglycaemia

Signs, symptoms and treatments

Exercise

Benefits and effect on blood glucose control

Diet
Insulin therapy

Injection technique
Types of insulin
Onset and peak actions
Storage
Stability

Urine testing

Glucose
Ketones

Home blood glucose testing

Technique
Interpretation

Oral hypoglycaemic agents

Mode of action
Dosing
Need for multiple therapies

Foot care
Management during illness
Cardiovascular risk factors

Smoking
Hypertension
Obesity
Hyperlipidaemia

Regular medical and ophthalmologic examinations

The patient must be involved in the decision making process and must learn as much about the disease and associated complications as possible. Emphasis should be placed on the evidence that indicates complications can be prevented or minimized with glycaemic control and management of risk factors for cardiovascular disease. Recognition of the need for proper patient education to empower them into self-care has generated certification in diabetes education.

CONCLUSION

The current approach to management of drug therapy in patients with type 2 diabetes is to begin insulin therapy if a combination of two oral agents fails to provide adequate glycaemic control. For every 10 units of insulin administered, an average of 1 kg of weight may be gained. This weight gain, associated with the lipotrophic effect of insulin, promotes greater insulin resistance in patients with severe disease. The result of escalating doses of insulin is a perpetual cycle of weight gain and uncontrolled diabetes. With the advent of the newer oral agents, combination therapy may delay insulin use in patients who traditionally would require insulin early in the course of the disease. Reasonable combinations of oral agents based on mechanism of action include sulfonylurea plus metformin, sulfonylurea plus an alpha-glucosidase inhibitor, sulfonylurea plus glitazone, repaglinide plus metformin, glitazone plus metformin, insulin plus metformin, and insulin plus glitazone. The frequency and timing of glucose monitoring should be individualized for each patient. The optimal frequency of self-monitoring of blood glucose in patients with type 2 diabetes is not known, but monitoring should be performed often enough to facilitate reaching treatment goals. Efforts should be made to substantially increase appropriate use of self-monitoring, providing both the patient and the practitioner with substantial information necessary to achieve glycaemic goals. When possible, sulfonylureas should be prescribed as initial therapy in non-obese patients since they are less expensive than the newer oral agents. Metformin is an excellent initial agent for obese patients (i.e., those greater than 120 percent of ideal body weight) or as add-on therapy in patients whose disease is not controlled with sulfonylurea therapy. An alpha-glucosidase inhibitor or glitazone may be an alternative to a sulfonylurea or metformin as add-on therapy in patients with uncontrolled disease or significant renal dysfunction.

As health care providers with knowledge of the illness, its treatments, and monitoring tools, pharmacists are vital members of the diabetic health care team in both the outpatient and the inpatient settings. Clinical pharmacists in all practice settings are in a key position to start providing care to people, who have diabetes or are at of developing it, or to expand and improve their care.

Important U.S. Laws and Regulations

2012-07-16T00:44:00.000+05:30

Important U.S. Laws and Regulations

Helpful guidelines for foreign students studying in the U.S.

Social Security Numbers
A Social Security number (SSN) is a nine-digit identification number assigned by the U.S. government. All U.S. citizens have unique Social Security numbers, which they provide to employers for tax purposes. If you are temporarily visiting the United States and do not plan to work off campus, you do not need an SSN. If you desire to work off campus, however, you may need an SSN. The first step in determining whether you'll need an SSN is to establish your visa classification. According to the Social Security Administration, visa holders classified as F-1, J-1, Q-1, Q-2, and M-1 who perform work tied to their studies or closely connected to the purpose of their visit are not subject to Social Security tax and do not need an SSN.
Driver's Licenses
If public transportation is not available in the city where your school is located, you may need a driver's license. All states require you pass a vision test, a written exam, and a driving test. Regulations pertaining to the issuance of driver's licenses to international students vary by state. For example, international students living in Ohio must present to the Bureau of Motor Vehicles a valid passport; visa; I-94 card, I-20, IAP-66, or I-9; and proof of six-month residency in Ohio. Contact the governing department that oversees the issuance of driver's licenses in your state to find out how to obtain a license.
Alcohol Regulations
The age at which U.S. residents may legally consume alcohol is 21. Underage drinking is a crime, and punishment can include fines, suspension of driver's license, court-ordered community service, and incarceration. To show proof of legal drinking age, most people present a driver's license. If you do not have a driver's license, you can present an identification card, which is available from the local license office.
Classified Information
Your visa classification will be provided by the Department of Homeland Security. You can use your classification status to determine the circumstances under which you're required to have a Social Security number.

F-1	foreign student
J-1	exchange visitor
M-1	vocational student
Q-1	admitted to the United States to participate in a cultural exchange program
Q-2	visitor under the Irish Peace Process Cultural Training Program Act

Understanding American Cultural Values

2012-07-16T00:08:00.004+05:30

Understanding American Cultural Values

Five attributes of Americans that are often misunderstood

Shared history and geography often give rise to the perceptions that become incorporated into a nation's identity. Although America's communal history is relatively short, many U.S.-born citizens inherently display values that are rooted in historical events. As with any culture, Americans have distinguishable values that international students should try to understand so they can successfully adjust. While there are many American perceptions and behaviors that are worthy of discussion, the focus of this article is on five attributes of Americans that sometimes result in confusion or even clashes with members of outside cultures.
1. Equality - Considered important enough to be written into the U.S. Declaration of Independence, this concept has given rise to some of the nation's deepest beliefs, aspirations, and rights. Although it is not always achieved, Americans strive for equality. We commonly use the first names of our elders, professors, and lawyers—a lack of deference to age and authority that is commonly mistaken for disrespect or laziness by foreigners. Similarly, our sensitivity to disparity and unfairness causes us to be outraged when someone receives special privilege due to their family's wealth or notoriety.
2. Hard Work - Americans believe that through hard work and human endeavor, one can improve their status in life. Values such as thriftiness, hard work, and ingenuity go back to a time when pioneers began settling the western United States. There was so much land and so many opportunities, but it was dangerous and difficult. These conditions led to an adopted mentality of "work hard or perish" that has withstood the test of time and been passed down through generations.
3. Directness/Transparency - Americans are often perceived (sometimes negatively) as bold, especially in their professional dealings. One theory about this phenomenon is that, because the earliest U.S. citizens had vastly different backgrounds, languages, and expectations, they adopted a very direct approach so as to avoid misunderstandings. This characteristic can be seen as overbearing or rude in certain contexts.
4. Time-focused - Punctuality is another American quality that was likely transmitted from our northern European ancestors who resettled in the 1800s. Time-focused societies think that people who show up late are being disrespectful or unprofessional. Americans believe in deadlines and sticking to the agenda.
5. Individualism - This is also most likely rooted in America's history of immigrants who left families and support systems behind to start a new life. They needed to rely on themselves in order to be successful and thus became independent minded. Many Americans believe that this individualism translates directly to the freedoms outlined by the U.S. Declaration of Independence—the right to "life, liberty, and the pursuit of happiness." While the dogged pursuit of happiness can be viewed as childish or foolish in some cultures, Americans cherish the right to live according to one's own ideas of success and satisfaction.
Understanding the history behind common American values helps to put them into perspective. Schools can help their incoming foreign students by matching them up with a cultural mentor—another student from the local culture—who can explain the cultural roots of the American qualities that are often difficult to understand.

DEALING WITH HOME SICKNESS

2012-07-16T00:02:00.000+05:30

Dealing with Homesickness While Away at College in the U.S.

There's a lot to do before leaving home to study in the United States. Unfortunately, many international students simply don't have time to prepare for the emotional impact that comes with entering an entirely different culture.
Homesickness is very common among international students, so if you find yourself feeling displaced or lonely, know that you are not alone and try to be patient. While there's no specific time limit, rest assured that those feelings will eventually pass. In the meantime, use these guidelines to start taking an active part in adjusting to your new surroundings.
Identifying Homesickness
Homesickness is a feeling or feelings that occur naturally when a person experiences a sudden change in environment or routine. It can manifest as vague sadness or uncertainty, anxiety, change in sleeping/eating patterns, feelings of isolation, inability to concentrate, and/or a desire to stay in close contact with people from home. For some people, these feelings pass quickly and for others it takes longer, but identifying homesickness is often the first step in resolving it.
Taking Actions
As difficult as it might seem at first, making an effort to meet new people can help tremendously when dealing with homesickness. Opportunities for positive social interaction at your new university can include:

Visiting your international student union
Attending sporting events
Signing up for campus activities
Checking out local music and arts venues
Joining clubs and groups

With practice, you'll find it easier to make friends and get involved. Look to teachers, advisors, RAs, and other international students for tips on what's happening around campus.
Making Room for It All
Studying in the United States will put plenty of physical space between you and your home, but it's also important to distance yourself psychologically—at least for now. Try to focus on creating new routines and setting bigger academic goals. For starters, try to speak English exclusively, and limit phone calls and/or e-mail communication with friends and family back home to one day a week.
At the same time, you don't want to lose your connection to the familiar altogether; in fact, maintaining close friendships and keeping a few personal items from home within reach can help lift your spirits on those not-so-great days. Remember that by exploring other cultures you are not abandoning your own—you may even be surprised to learn that you're not missing out on much back home. You're simply allowing yourself to grow academically and gain experiences that will shape you for a brighter future..

AIR TRAVEL TIPS FOR F1 STUDENTS

2012-07-15T23:54:00.001+05:30

This post will help you understand the flight booking process and provide you with some air travel tips. Cheap flight ticket from India to USA might not be the best always.

Find a travel companion to the same university from your departing city.
Book flights together (India to USA), if not get same connecting flight from second flight (if you have connections).
Search for best airfare deal not the cheapest airfare (don’t just ask one travel agent)
After you ding the lowest priced ticket through travel agent, then shop online (or vice versa).
Negotiate to get the lowest air fare to US
One way fare is about 70% to 80% value of round trip fare.
Register for frequent flyer account with the airline which you plan to book ticket.
Provide the frequent flyer number to travel agent while issuing the ticket.
Don’t forget about registering for frequent flyer account. After accumulating 25,000 miles, you can get 1 round trip ticket within US.
Find baggage allowance.
You may have to pay $50 for second suitcase
Some airlines will allow students to carry 2 checked bags for free (23kgs or 50 lbs each)
Avoid certain airlines (know for poor customer service and frequently delayed flights)
Lowest fare doesn’t always provide best flight connections and options.
First time travelers ask for Window seat. If you are tall, ask for aisle seat.

Flight Connections

Most likely you will have to get connecting flight within US before you reach your final destination.
Universities located in Major cities will have direct flight from India (Mumbai to New Jork) or direct entry from second connecting flight.
Port of entry in US will be the first city where you land (not your final destination)
You have to clear Immigration and Custom procedures before boarding the next flight within US
Allow atleast 3 hours between connecting flight, that will give enough time to clear customs and immigration procedures.
You will have to take your suitcase and clear customs and check the bags-in for local domestic connection.
If you miss the connection, don’t panic.
Airline will get you on the next flight to your destination.
Have some US Dollars in hand and atleast $1 bill to make phone calls.
Find a way( phone or email) to inform the party who will be waiting to pick you from the airport, if there is a flight delay.

General tips for INDIAN STUDENT

2012-07-15T23:27:00.002+05:30

General Tips:

Ok, so you have finally made it to the land of your dreams!! But you dont wanna make a bad impression do you? So here are a few tips to help you begin your life in America on the right note.

1) Guess what's the first thing Americans notice about us desis? Surprise!!....THE SMELL!
FACT: Most desis smell horrible to Americans.We smell of fried food and curry coz most of us cook at home and do not care to shower and change before we go out. Keep your clothes away from the kitchen, in a closet. Use a deodorant. Change before you go out. And for heavens sake dress decently when you go out. I've seen desis go shopping in malls in the raggediest of outfits.

2) Ok, so now you smell good...you think you're COOL.... Next thing to remember, Americans are very friendly people. So you will see total strangers greeting you or smiling at you. Return the smile or greeting. Question: How're you doin? Answer: How're you doin or Doing Good. how about yourself. When americans ask you how you are doing,they do not expect a lengthy answer. Its just a polite greeting. If you want to be cool, you'd say "Whats up"...and expect a "Not much".

3) Try to speak clearly. Many Americans can't understand what you are saying because of your bad pronunciations or because you speak too fast. Try to smoothen out those rrrr's. Also try not to use your native tongue when there are people of other nationalities around. And stop nodding your head like a bobblehead when you agree with something! It realllly looks funny to non-Indians!!

4) Hold doors open for people. Its common courtesy here to hold the door open for people who are following you through a doorway.

5) Don't be cheap. Always tip cab drivers, waiters, hair dressers etc. Don't do things like stealing carts from the local store to bring home your grocery.
All stores have a return policy . Don't misuse it! For example, don't buy a camera coz your friends are coming, and return it to the store after they leave as you don't need it anymore!

6) Most desis are secure in their own community. They don't make efforts to meet people from other communities. Don't be shy...go out, meet people. Some of my best friends are Americans and other international students.

7) Never ask another person how much money he makes or other such personal questions. Americans value their privacy a lot. Don't be too inquisitive. Also, keep a good distance when you speak to people. Its called "personal space". At least an arms length.

8) Use "thank you" and "please" a lot. For example if a host asks you if you would like more coffee, don't say Yeah!. Say "Yes please" or "please". "Yeah" will do if you are with close friends !

9)Don't dig your nose in pubic! Its disgusting! Also, you may be caught on camera as many places in the US have security cameras! Always wash your hand before leaving a restroom. Do not litter. As you may have noticed, there are plenty of dust-bins all over America. So don't throw stuff on the ground.
10) Professors prefer to be called "Professor His Name" or "Doctor His Name" rather than just Sir.

11) DO NOT use any illegal means in exams. Do not copy each other's assignments!
If caught, you will not only bring a bad name to the Indian community, you will also be in deep shit! Americans value honesty. Do not try to cheat the system. YOU WILL GET CAUGHT.

12) Finally, try to blend into the American way of life. The best part is you don't have to give up being an Indian to live here. The greatest thing about America is its tolerance. Most people who come here will never go back because of the high quality of life and the freedom to be who you are.
So stop complaing, stop judging Americans by your values and morals. If you want to stick to your traditions and values, nobody is stopping you.

All of us need to work toward fighting the 'desi stereotype'. We Indians already have a good impression in America as far as academics is concerned. We need to extend that to all walks of life.

Above all, have fun! America is THE PLACE to realize all your dreams. Work hard, live life to the fullest and believe me, you will never go back!

HOW TO BECOME SUCCESSFUL STUDENT IN USA

2012-07-15T23:19:00.002+05:30

8 Things to remember to be successful student in the US University

You are all set to leave India & pursue your higher education in the US. All bags are packed and you are ready to go. Your mind is cluttered with all sorts of questions about the journey you are going to embark. How are you going to manage it all alone? Is the education system similar to that of India’? and so on. There is no cookie cutter formula to be a successful student in the US, but we have 8 suggestions which if followed, we feel, will make your experience a more memorable one, if not easier. We will break this blog into 2 parts & below are 4 of those suggestions
Cleanse your mind … at the airport terminal:
There is a reason why America is known as the land of opportunities- It is because people over there follow their passion. And you are about to become one of them … you have burnt the midnight oil to get where you are right now & there are a million students who would love to have your visa stamped passport. So take a deep breath & feel good about what you have achieved so far … you are about to begin a very exciting adventure … So before you board your flight, our sincere advice to you is to dump all the useless gyaan (you know what I’m talking about;) ) about life in the US, which you got from your friends & relatives who have never been to the US & have heard it from their friends & relatives who also have never been to the US, in the garbage can at the airport terminal.
Do not have any pre-conceived notions about what life in the US is … go with an empty mind which is ready to absorb & learn … remember, studies will just be a small subset of your education. Follow your passion & success will follow (all right .. I did take that last line from 3 Idiots)
Learn to listen to others:
To survive in the cut throat competitive Indian education system, it is natural to adopt an attitude where a student is always voicing his/her opinions, so that he/she may stand out among others. In order to be successful, one of the first things you will have to do is let go of that habit & start practicing the art of listening. For those of you, who already do that, further hone that skill. You will be amazed by the quantity of information you can assimilate, just by being an attentive listener. It is always beneficial to learn new views and perspectives, especially in a new country and this will surely help you in the long run.

STOP cramming & START understanding:
Partly due to the nature of India’s educational system, more importance is given to the quantity of information one can regurgitate on the answer sheet than on the knowledge which a student possess. In the US, things are the opposite. Thorough understanding of a concept is far more important than just knowing it. More stress is given on the Why and How rather than on the What. To every Why there is a Why Not? So when you make your course selection, choose the subjects which genuinely interest you otherwise, you will end up not far from what you were as a student in India.
No Cheating:
Once you leave the motherland for US, please relinquish your habits of cheating & copying from others. If you have spent your engineering years copying journals from your seniors and keeping chits in your socks during exams, dump this habit with the useless gyaan which I described above. There is zero tolerance for plagiarism & if proven guilty, not only do you get immediately suspended but that blot stays with you for rest of your life (YES … I mean it trickles into your professional life also)

COLONIC DRUG DELIVERY SYSTEM

2012-07-15T23:10:00.003+05:30

INTRODUCTION

Traditionally solid oral dosage firms have been designed to release their drug load in upper regions of G.I.T. Where conditions are generally more suited to drug dissolution and absorption. Recently greater emphasis has been placed on controlling the rate and site of drug release from oral formulations for the purpose of patient compliance and treatment efficiency.

The colonic region of G.I.T is one that would benefit from the development and such modified release technologies. Although considered by many to be an innocence organ that may simple functions in the form of water and electro light absorption and the formation storage and explosion of fecal material, the colon is valuable to a No of disorders including alternative qualities corn's disease irritable bower syndrome and carcinomas. Targeted drug delivery to the colon would there fore ensure direct treatment at the disease site lower closing and favour systemic side effects.

In addition to local therapy, the color can also be utilized as a portal for entry of drug into the systemic circulation. eg:- molecules that are degraded parry absorbed in upper get, such as peptides and proteins, may be better absorbed from more being environment of colon . In addition systemic absorption from colon can also be used as a means of achieving chemotherapy for diseases that are sensitive to circadian rhythms such as asthma angina, orthotics.

Successful colonic drug delivery careful consideration of a large number of factors, including the properties of drug, the type of delivery system and in interaction with the healthy or diseased gut for instance, regardless of whether a local or systemic effect is required, the administrate drug must first dissolve in lonely fluid of colon. Overseas, there is less free fluid in colon than is small intestine and hence, dissolution could be drug may need to be delivered in a pre-established form, or delivery should be directed to proximal colon, as a fluid gradient exists in colon with more free water present in proximal colon than is distal colon.

Aside from drug solubility, the stability of drug in colonic environment is a further factor that warrants attention. The drug could bind in a non specific manner to directory residues, intestinal secretions, or general faucal matter, thereby reducing the connection of free drug. Moreover, the resident microflora caved also effect colonic performance via degradation of drug.

In terms of systematic therapy via the colon, the small internal surface area and relative 'tightness' of tight junction is colon could restrict drug transport across mucosa a enzymes that are capable of metabolizing endogenous and exogenous subtracts such as carbohydrates , proteins, that escape digestion in upper G.I tract ,.Therefore materials that are recalcitrant to the conditions of stomach and small intensive, yet suspicious to degradation by bacterial enzymes within colon, can be utilized as carriers for drug delivery to colon.

Eg:- This principle has been exploited commercially to deliver 5 anniosalicylic acid to the colon by way of a prodrug career. The prodrug sulphasalazine consists of two separate moieties, sulphaphyridine and 5-aminosalcylic acid, linked by as azo-bond. The prodrug posses through the upper gut intract, but once in colon the azo-bond is cleave by the host bacteria, liberating the carrier molecule sulphaphyridine and pharmacologically active agent 5- aminosalicyclic acid and its systematic circulation. To a certain earnest, the longer residence time in colon (up to 5 says) may compensate for these limitations. There is also evidence to suggest that the activity of the cyclo chrome p 450 3A class of drug metabolizing enzymes is lower is mucosa of colon than small intensive. Therefore colonic delivery may lead to elevated plasma levels and improved oral bioavailability for drugs that are substrates for this enzyme class.In relation to delivery modified release formulations are usually based on either a single unit tablets and bicapsular) or multi unit (Pellets & granules) plat form design.

TARGETTING MECHANISM OF DRUG ACTING ON COLON

1. Pre-dependent delivery

2. Time-dependent delivery

3. Pressure-dependent delivery

4. Bacteria dependent delivery

Successful colonic drug delivery requires careful considerations of a number of factors, including the properties of drug, the type of delivery system and its interaction with the healthy or diseased gut.

1. PH-DEPENDENT DELIVERY

Pre-sensitive enteric coatings have been used routing to deliver drugs to small intensive. These polymer coatings are insensitive to the acidic conditions of stomach yet dissolve at the higher PH environment of small intestine. This Ph differential principle has also been attempted for colonic delivery purposes although polymers used for solenoid targeting and to have a threshold PH for dissolution that is HIGHER than those used in conventional enteric coating applications. Most commonly co-polymers of methacrylic acid and methyl metha crylate that dissolve at PH 5 PH 7 have been investigated./ This approach is based on assumption that G.I PH increases progressively from the small intestine to colon. In fact, the in distal small intestine is usually around 7.5, while the H in proximal colon is closer to 6 These delivery systems therefore have a tendency to release their drug load prior to reaching colon.

To overcome the problem of premature drug release a copolymer of methacrylic, acid, methyl methacrylate and ethy threshold OH, has been developed recently.

The inter subject variability in G>I PMand possibly certain other intersect various such as electrolite concentration.and transit time will therefore impact on in vivo behaviour of PH responsive systems, ranging from early drug release is small intensive to are release at all with the formulation passing throughout gut intact. The latter situation will also arise when PH of colon, and possibility the small intensive is considerably lower than normal as the case in patients with creative qualities.. In spite of their limitations, PH sensitive delivery systems are commercially available for mesalazine in and budesonide for treatment of ulcerative colitis & crohn's disease, respectively.

2. TIME DEPENDENT DELIVERY

It has also been proposed as a means of targeting the colon. Time dependence systems release their drug load after a pre programmed time delay. To attain colonic release, the log, time should equateto time taken for system to react the colon. This time is difficult to predict in advance,although a log time of five hours is usually considerated sufficient, given that small intential transit time is reported to be relatively consitant at three to four hours. One of the earliest system to utilise this principle was the pulsincap device. System consisit of an importable capsule fined with drug and stoppered at one end with a hydroges plug, on contact with gastrointential fluids, the plug hydratres and swells and after a set log time, ejects from the capsule body, thereby allowing drug release to occur. The log time is controlled by the size and composition of play. The influ

BACTERIA DEPENDENT DELIVERY

The resident g.i.bacteria provide a further means of effecting drug release in colon, Thesse bacteria predoninatly colonise the distas region of g.i tract where baterial count in the colon is 10' per gramme as compared with 10'per gramme in uper small inestine moreover, 400 different species are present colonic bacteria are pre dominantly in nature and produce ence of gastric copying on performance of pulsincap was reduced by a application of an outer enteric coat. The outer enteric coat dissolves on entering the small intenstine to reveal by either swelling, eroding or dissolving over a period of time equivalant to small intential transit.

Although the use of an over enteric coat overcomes to a certain attent the availability in G.I emptying, the intrisic problems with such systems is over all inter and intra subject variability in transit. Transit is slower in evening as compared with morning.

3. PRESSURE DEPENDENT DELIVERY

G.I pressure has also been utilised drug release in destal gut.This pressure which is generated via muscular contraction of gut wall for gtinding and proposition of intestial contents, varioes in intesity and duration throught the g.itract, with the colon considered to have a higher internal pressure due to process that ocur during stool formation. The system have therefore been developed to resisst the pressure of upper g.i tract but in rupture response to the raised pressure of colon.capsule shells fabricated from water insolube polymer entry cellulose have been used for this purpose. The system can be modified to withstand and rupture at different pressors by changing the size of capsule and thicknessof capsule shell wall.

enzynes that are capable of metabolishing endogenous and exogeneous substracts such as carbohydrates ,protines,that escape digestion in upper g.i tract ,.Therefore materials that are recalcitrant to the conditions of stonach and small intensive, yet suspecious to degradation by bacterial enzynes within colon, can be ulilised as carriers for drug delivery to colon.

Eg:- This principle has been expoited commercially to deliver 5 anniosalicylic acid to the colon by way of a prodrug career. The prodrug sulphasalazinc consists of two separate moities, sui phaphyridine and 5-aminosalcylic acid, linked by as azo-bond. The prodrug posses through the upper gut intract,but once in colon the azo-bond is cleaveal by the host bacteria, liberting the carrier molecule sulphaphyridin and pharmacologicary active agent 5- aminosalicyclic acid.

PHARMACEUTICAL APPROACH TO COLON TARGETED DRUG DELIVERY

COATING WITH BIODURABABLE POLYMERS

The bio environment inside the human G.I.T is characterized by presence of complex microflora especially the colon that is rich in micro organizing that are involved in the process of reduction of dietary component or other materials. Drugs that are coated with polymers, which are showing degradability due to influence of colonic micro organisms, can be exploited in designing drugs for colon targeting. These bacterial degradable polymers especially also polymers have been explored in order to release as orally administrated drug in colon. Actually upon passage of dosage from through G.I.T it remains intact in stomach and small intestine where very little microbially degrades activity is present that is quiet insufficient for cleavage of polymer coating, Release of the drugs from azo polymer coated formulation is supposed to take place after reductionism thus degradation of azo bonds by azo reductase enzymes released by azo batters in colonic microflora.

Mesalazine is the active component of sulfasalazine exerting a predominant local topical action independent of blood levels. Its effectiveness depends on the site of ulceration in relation to the drug's dissolution profile. This is very important when choosing aminosalicylate preparations, as illustrated in Figure 11.4.

The optimal dose of sulfasalazine to achieve and maintain remission is usually in the range of 2-4g pe day in four divided doses. Acute attacks require 4-8g per day in divided doses until remission occurs, but at these doses associated side-effects begin to appear.

Of patients taking sulfasalazine, 30% experience adverse effects that are either dose-related, dependent on acetylator phenotype or idiosyncreatic non-dose, related reactions. The first group includes nausea, vomiting, headache, malaise, haemolytic anaemia, reticulocytosis, and methamemoglobulinaemia. The second includes skin rash, hepatic and pulmonary dysfunction, aplastic anaemia and reversible azoospermia. Adverse effects usually occur during the first 2 weeks of therapy, the majority being related to serum sulfapyridine levels.

Many of the adverse effects listed above can be avoided by using one of the aminosalicylate formulations now available.

Formulation. As mesalazine is unstable in acid medium and rapidly absorbed from the gastrointestinal tract, the new preparations have been developed using three different approaches.

A mesalazine tablet coated with a pH-dependent acrylic resin

Ethylcellulose-coated mesalazine granules diazotization of mesalazine to itself or to an inert carrier.

Asacol contains 400 mg of mesalazine coated with an acrylic resin, Eudragit-S, that dissolves at pH 7 and releases mesalazine in the terminal ileum and the colon. Salofakd tablets are similar fo;umulation containing 250 mg mesalizine with sodium carbonate-glycine and a cellulose ether, coated with Eudragit-L which dissolves at pH 6 and above, releasing mesalaxine in the jejunum and ileum.

Table 11.4 comprasion of available oral aminosalicylate premations for patients with inflammatory bowel disease

Generic (proprietary) name	Formulation	Release profile	Site of release
Sulfasalazine (Salazpyrin)	Compressed tablet. Plain and film coated	Azo-linked, independent at pH	Terminal ileum and colon
Mesalazine (Asacol)	Compressed tablet, acrylic coating	Acrylic coating dissolving at pH 7	Terminal ileum and colon
Mesalazine (Salofalk and generic forms)	Compressed tablet and/or capsule acrylic coating	Acrylic coating dissolving at pH 6	Mid-jejunum ileum and colon
Mesalazine (Pentasa)	Microgranules coated with ethycellulose and compressed into tablets. Granules also available	Disintegration not dependent on pH. Slow dissolution rate	Stomach, duodenum, jejunum, ileum and colon
Olsalazine (Dipentum)	Hard gelatin capsules and tablets, uncoated	Azo-linked disintegration independent of pH	Terminal ileum and colon
Balsalazide (Colazide)	Hard gelatin caplules	Azo-linked disintegration independent of pH	Terminal ileum and colon
Polyasa	Compressed tablet	Azo linked disintegration in dependent of ph	Terminal ileum and colon

COVALENT LINKAGE OF THE DRUG WITH A CARRIER

It involves the formation of a covalent linkage between drug and carrier in such a manner that upon oral administration the moiety remains intact in the stomach and small intestine.

This approach chiefly involves the formation of prodrug, which is a pharmacologically inactive derivative of a parent drug molecule that requires spontaneous or enzymatic transformation in the biological environment to release the active drug. Formation of prodrugs has improved delivery properties over the parent drug molecule. The problem of stability of certain drugs from the adverse environment of the upper GIT can be eliminated by prodrug formation, which is converted into parent drug molecule once it reaches into the colon. Site specific drug delivery through site specific prodrug activation may be accomplished by the utilization of some specific property at the target site, such as altered pH or high activity of certain enzymes relative to the non-target tissues for the prodrug-drug conversion.

AZO BOND CONJUGATES

The intestinal microflora is characterized by a complex and relatively stable community of microorganism, many with physiological functions, which play vital roles in health and disease. In addition to protection of the patient against colonization of the intestinal tract by potentially pathogenic bacteria, the indigenous microflora are responsible for a wide variety of metabolic processes, including the reduction of nitro and azo groups in environmental and therapeutic compounds.

Sulphasalazine was introduced for the treatment of rheumatoid arthritis and anti-inflammatory disease. Chemically it is salicylazosulphapyridine (SASP), where sulfapyridine is linked to a salicylate radical by an azo bond. When taken orally, only a small proportion of the ingested dose is absorbed from the small intestine and the bulk of the sulphasalazine reaches the colon intact. There it is split at the azo bond by the colonic bacteria with the liberation of sulphapyridine (SP) and 5 ASA. However sulphapyridine is seems to be responsible for most of the side effects of sulphasalazine and hence various new approaches for the treatment of IBD have emerged.

GLYCOSIDE CONJUGATES

Steroid glycosides and the unique glycosidase activity of the colonic microflora frorm the basis of a new colon targeted drug delivery system. Drug glycosides are hydrophilic and thus, poorly absorbed from the small intestine. Once such a glycoside reaches the colon it can be cleaved by bacterial glycosidases, releasing the free drug to be absorbed by the colonic mucosa.

The major glycosidases identified in human feces are b-D-galactosidase, b-D glucosidase, a--L-arabinofuranosidase, b-D-xylopyranosidase. These enzymes are located at the brush border and hence access to the substrate is relatively easy. In the plant kingdom numerous compounds are found as glycosides. Certain drugs act as glycon and can be conjugated to different sugar moieties which results in the formation of glycosides. Due to the bulky and hydrophilic nature of these glycosides, they do not penetrate the biologicl membrane upon ingestion. Various naturally occurring glycosides, e.g the sennosides, have been used for laxative action for ages. When taken orally, intact sennosides are more efficient as laxative than sugar free aglycones. These sennosides are activated are activated by colonic microflora to generate rhein anthones, which gives the desired laxative effect. Glycosidase activity of the GIT is derived from anaerobic microflora in the large bowel or the sloughed or exfoliated cells of the small intestine.

GLUCURONIDE CONJUGATES

Glucuronide and sulphate conjugation is the major mechanisms for the inactivation and preparation for clearance of a variety of drugs. Bacteria of the lower GIT, however, secrete b-glucuronidase and can deglucuronidate a variety of drugs in the intestine. Since the deglucuronidation process results in the release of active drug and enables its reabsorption, glucuronide prodrugs would be expected to be superior for colon targeted drug delivery.

Morphine-dependent rats were used to evaluate the effects of the narcotic antagonists, naloxone and nalmefene, and their glucuronide conjugates on the gastrointestinal tract and various parameters of brain-mediated withdrawal. When administered subcutaneously nalmefene hydrochloride caused a dose-dependent tail skin temperature increase, whereas nalmefene glucuronide was ineffective Malmefene precipitated brain-mediated morphine with drawal at doses as low as 10mg/kg, whereas nalmefene glucuronide was ineffective at doses as high as 1mg/kg. After per oral administration of the drugs, nalozone hydrochloride and nalmefene hydrochloride caused diarrhea, withdrawal behavior and tail skin temperature responses by 15 minutes. In contrast, after per oral administration of the glucuronide conjugate of either narcotic antagonist, diarrhea was delayed for 75 to 203 minutes. This latency probably reflects the required transit time to the lower gastrointestinal tract. About 0.2 to 0.5% of the dose of the narcotic antagonist administered orally as the glucuronide was absorbed systemically. These results indicate that per oral administration of the glucuronide conjugates of nalox one and nalmefene results in delivery of the narcotic antagonists to the colon. Haeberlin et al. prepared a dexamethasone b-D-glucuronide prodrug.

CYCLODEXTRIN CONJUGATES

Cyclodextrins (CyDs) are clyclic oligosaccharides consisted of six to eight glucose units through a-1,4 glucosidic bonds and have been utilized to improve certain properties of drugs such as solubility, stability and bioavalability. The interior of these molecules is relatively lipophilic and the exterior relatively hydrophilic, they tend to form inclusion complexes with various drug molecules. They are known to be barely capable of being hydrolyzed and only slightly absorbed in passage through the stomach and small intestine, however, they are fermented by colonic microflora into small saccharides and thus absorbed in the large intestine. Because of their bioadaptability and multi functional characteristics, CyDs are capable of alleviating the undesirable properties of drug molecules in various routes of administration through the formation of inclusion complexes. In an oral drug delivery system, the hydrophilic and ionizable CyDs can serve as potent drug carriers in the immediate release and delayed release formulations, respectively, while hydrophobic CyDs can retard the release rate of water-soluble drugs. Since CyDs are able to extend the function of pharmaceutical additives, the combination of molecular encapsulation with other carrier materials will become effective and a valuable tool in the improvement of drug formulation. Moreover, the most desirable attribute for the drug carrier is its ability to deliver a drug to a targeted site, conjugates of a drug with CyDs can be a versatile means of constructing a new class of colon targeting prodrugs.

It has been proved through a study in healthy human volunteers that b CyDs are meagerly digested in small intestine but are completely degraded by the microflora of the colon. Most bacterial strains that are isolated from human being are capable of degrading CyDs. It has been proved by their ability to grow on cyclodextrins by utilizing them as the sole carbon source and by the stimulation of cyclodextrinase activity by as low as 2-4h of exposure to cyclodextrins. This property of the drug may be exploited for the formation of colon targeted drug delivery systems. Several CyD conjugates have been prepared and the enantioselective hydrolysis has described.

DEXTRAN CONJUGATES

Dextran ester prodrug was prepared and in vitro release revealed that release of naproxen from prodrug was several folds higher in caecum homogenates than in control medium or homogenates of the small intestine of pig. The bioavailability of naproxen after oral administration of a dextran T-70 naproxan ester prodrug in pigs was assessed by Harboe et al. compared to the administration of an oral solution of an equivalent dose of naproxen the average absorption fraction for the conjugate amounted to 91%. It was established that several features of the prodrug indicated that naproxan was released from the prodrug prior systemic absorption and that drug activation involved the action of one or more enzyme systems located in the gastrointestinal tract. It was observed in rabbits, the plasma concentration-time curves for the conjugate were characterized by an initial lag time of about 2-3h, whereas naproxan was detected in plasma immediately after per oral administration of the drug compound per sec. The distribution of the prodrug along the GIT at various times after conjugate administration was assessed qualitatively by HPLC analysis of conjugated and free naproxan in various segments of the GIT. From these experiments it was suggested that drug regeneration was effective in the bowel below the ileum.

AMINO-ACID CONJUGATES

Due to the hydrophilic nature of polar groups like NH2 and COOH, that is present in the proteins and their basic units, they reduce the membrane permeability of amino acids and proteins. Various prodrugs have been prepared by the conjuagation of drug molecules to these polar amino acids. Non-essential amino acids such as tyrosine, glycine, methionine and glutamic acid were conjugated to SA. The salicyluric acid was found to be metabolized to SA by the microorganisms of the intestinal flora of rabbit and dog. The prodrug was absorbed into the systemic circulation from the upper GIT and hence it was proved unsuitable for delivery of drugs to the colon. By increasing the hydrophilicity and chain length of the carrier amino acid and decreasing the membrane permeability of conjugates. This conjugate showed splendid results with minimal absorption and degradation in the upper GIT and proved suitable for colon targeted delivery of SA.

POLYMERIC PRODRUGS

Azo-linked polymeric prodrugs of 5-ASA were prepared and evaluated in simulated human intestinal microbial ecosystem. Polyamides containing azo grups in the backbone were prepared and tested in vitro in a reductive buffer or in the bioreactor medium. It was demonstrated that for the hydrophobic polymer, reduction stops at the hydrazine stage whereas for a hydrophilic analogue reduction with formation of amine occurred. The amount of the drug released depend on the nature of the polymer and can approach that of low molecular weight prodrugs.

USES

I.
LOCAL ACTIONS

1. Ulcerative colities.

2. CHRON'S disease.

3. Irritable bower syndrome

4. Metastatic human colon cancer

II. SYSTEMIC ACTIONS

Molecules degraded/poorly absorbed from upper G.I.T such as peptides and proteins are better absorbed from colon,
For achieving chemotherapy for diseases that are sensitive to circadian rhythm such as Asthma, angina, arthritis

ADVANTAGE AND DISADVANTAGE

ADVANTAGE

Patient compliance and treatment efficacy
Useful in treatment of ulcerative colitis, chron's disease, irritable bowel syndrome and carcinomas
Low dose is required ,so less side effect
Used for local and systemic action
Gastric irritation can be avoided

DISADVANTAGE
there is less fluid in colon than in small intestine and hence dissolution is a problem for water soluble drugs
binding of drug to dietry residues ,intestinal secretions etc reduce concentration of free drugs
some micro flora may degrade the drug
small luminal surface area and relative tightness of tight Jouncions in colon, delay the systemic absorption.

Onset of action is slow.CONCLUSION

The colonic region of gastro intestinal tract become and increasingly important site for drug delivery and absorption. The targeted drug delivery would offer considerable therapeutic benefits to patients, in terms of both local and systemic treatment. Systems that rely on gastrointestinal P4 transit tine or pressure for release are unlikely to function as reachable and effective colon specific delivery vehicles colon specialty is more likely to be achieved to systems that utilize natural materials that are degraded by bacterial enzymes of colonic origin. Moreover the cost and case of manufacture delivery system are further considerations that will impact on its likely commercialization and hence, availability to patient .A bacteria sensitive natural film coating that can be applied to a range of solid oral dosage forms using conversional processing technology would therefore appear to be delivery system of choice.

In summary two controlled release mechanism, i.e, time and p4-dependent, could achieve colonic-specific drug delivery following oral administration. In addition, both CDDS were relatively in expensive and easy to be manufactured using conventional pharmaceutical coating technique, and provided the promising candidates for specifically delivering drug to targeted colon region, in particular for DS and 5-ASA in this study, respectively

TO DO AFTER GETTING VISA

2012-07-04T16:40:00.000+05:30

Once you get a student Visa, you should now prepare for your trip to the US. You need to take care of various issues such as booking a ticket, immunizations, transferring money to USA, arranging for accommodation in the US, etc. In this section, we address various issues that will guide you on what you should do and prepare before coming to the US.

College / University related issues
Health related issues
Finance related issues
Things to Learn
Flying to USA

Arrange for your pick up from the Airport and Accommodation

College / University related issues

Go on your college / university's web site and browse through information about the program that you plan to attend. Get some sense of how many credits you need to take to complete your program, and how long you will have to stay in the college / university. Get some idea of what classes are you going to take or will have to take in the first semester. Of course you can always wait until you see your academic advisor, but it does not hurt to have some idea of what you will do in your first semester.
Make at least 5 -6 certified copies of your transcripts, certificates and recommendation letters. That way you will be ready in case you want to transfer to another university, or apply for a scholarship after you are in the US.
If your GRE / GMAT / SAT scores are low as compared to your college / university's average score, you may be asked to rewrite the exam to better the score. Be prepare to re-take the exam if you are told to do so. You can also take your GRE / GMAT / SAT books and cds along with you to the US.

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Health related issues

As an international student in the US you need to have a student health insurance plan. Please check out our health insurance section for more information. Also check out additional topics such as travel insurance and family insurance.
Some US colleges / universities require you to take immunizations (such as measles / rubella, etc.) and / or health tests (such as TB test). You may do the immunizations or health tests before coming to the US or within a certain period of time after you arrive in the US. If you plan to do so before coming to the US, make sure you bring the proof of immunization or health test with you. You can bring a certificate from the doctor or the hospital as a proof of immunization and health tests.
You might want to do general check up for yourself, including vision and dental check up. It is not required, but we recommend it because the health cost in the US is very high, and usually student health insurance plan does not cover dental and vision, unless you purchase a separate insurance plan for that.
If you wear glasses, get at least 2 extra pairs, just in case. If you wear disposable contact lenses, get a couple of extra pairs and eye drops. Again it is not necessary, but recommended as these things are costly in the US.
Bring along with you medicines for general health issues such as head aches, body aches, cold, fever, water proof band aids, etc. If you suffer from some kind of ailment, please bring along related medicines and certificates of medical history from your doctor. Please note that if you are bringing any medicine from your home country, you need to bring a certificate from a doctor or the hospital explaining the purpose of these medicines. Otherwise, they might be confiscated by the customs officers at the airport .
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Finance related issues
- You will need to bring money from your home country to the US. You can do so by converting the money to US dollars and then get the US dollars converted to Traveler’s Checks. Once you arrive in the US, you will have to open a bank account and deposit the Traveler’s Checks in your account. You should also keep some money in plain US dollars because you will need them during your travel to the US as well as to use before you open a bank account.
- If you are going to get a scholarship from your home country, find out how your scholarship provider is going to transfer the money to the US.
- Check out our Banking section on how to open a bank account in the US
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Things to Learn

Based on our experience, below are two important things that that you should learn before coming to the US:

Cooking

In order to survive in the US, you should learn how to cook the dishes you eat in your home country. In the US, grocery stores will carry most of the different ingredients found throughout the world. Even you will find specialty stores such as the Indian spice stores, chinese markets, south American shops, European market, etc., where can buy all the ingredients you need to prepare your dish. In the US you will find all kinds of restaurants and fast food places. However, as an international student, most likeky you won't be able to afford eating outside everyday. Therefore, it will be better if you learn to cook some of your country's typical dishes. We suggest that you also bring cooking books or recipes along with you.

Driving

Before coming to the US, if you like you can learn how to drive and get a driver license from your home country. At some point of time during your life in the US, you will most likely buy a car. If you don't know driving at all, then it will be tough for you to get a driving permit in the US. In the US, the driving schools are very costly. Otherwise, you will have to request one of your friends to teach you driving. In order to avoid all this trouble, it is better of if you learn how to drive in your home country itself. Please note that in the US, cars have a left wheel drive and vehicles travel on the right side of the road. However, it should not be a big problem if you have learnt driving a right wheel drive vehicles that run on the left side of the road (mostly former British colonies) as it is relatively easy to adapt.

Once you get a driving license in your home country, you should also get an International Driving Permit (IDP). An International Driving Permit (IDP) allows an individual to drive their private motor vehicle in another nation only when the individual also has a valid driver license from their country. For more details, please check the IDP section in the 'Getting a Driving License' section.

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Flying to USA

Please check out the 'Traveling to USA' section for details on topics such as booking a ticket, airport codes, luggage limits, documents to bring, air port pick up, etc.

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Arrange for your pick up from the Airport and Accommodation

Airport pick up means that someone will come to the airport to pick you and drop off at the college / university or to your temporary accommodation location.
When you are coming to the US for the first time, and if you don't know anyone, contact your International Students Office (ISO) of your university a few weeks in advance and ask them if they can arrange your airport pick up and provide a temporary accommodation for you. If so, you need to provide them your arrival details such as date, time, schedule, number and other details of your flight.
Sometimes the ISO will provide you a list of on-campus student associations (such as Indian Students Association, Chinese Students Association, Hispanic Students Association, European Students Association, etc). You will have to contact the officers of these associations and they will make some arrangements for you (a student will come to pick you at the airport and you will probably be provided accommodation at some senior students' houses). Sometimes, some American families may also provide you temporary accommodation.

Free temporary accommodation can be anywhere from 2 days to 2 weeks. The hosts will provide you a bed to sleep and also provide you food. You should use this time to complete college formalities and find an apartment / roommates for yourself. We strongly advice you against taking undue advantage of the generosity of your hosts.

In case, no one is available to pick you up from the airport, you will have to take a bus or a taxi to your University or temporary housing. Check out in advance how much it costs or whether there are any buses from the airport. In case no one is able to arrange temporary accommodation for you, we suggest that you book a hotel near your University. You can find more information about hotels in the US, in the 'Book a Hotel' section.

Please check out our 'Finding Apartments' section for detailed information on arranging for temporary as well as permanent accommodation in the US.

VORAXAZE

2012-05-27T11:15:00.002+05:30

Voraxaze( glucarpidase):

Date of Approval: 17^th january 2012.

Mechanism of Action

VORAXAZE (glucarpidase) is a recombinant bacterial enzyme that hydrolyzes the carboxyl-terminal glutamate residue from folic acid and classical antifolates such as methotrexate. VORAXAZE converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N¹⁰-methylpteroic acid (DAMPA) and glutamate. VORAXAZE provides an alternate non-renal pathway for methotrexate elimination in patients with renal dysfunction during high-dose methotrexate treatment.

Pharmacodynamics

Plasma methotrexate concentrations within 48 hours following administration of VORAXAZE can only be reliably measured by a chromatographic method because DAMPA interferes with the immunoassays. Following administration of VORAXAZE 50 Units/kg to patients in Study 1, methotrexate concentration measured by a chromatographic method was reduced by ≥ 97% within 15 minutes in all 22 treatment-evaluable patients, and was maintained at a > 95% reduction up to 8 days in 20 of the 22 patients.

Pharmacokinetics

The pharmacokinetics of glucarpidase in the absence of methotrexate were studied in eight healthy subjects following an intravenous injection of VORAXAZE 50 Units/kg over 5 minutes. Serum glucarpidase activity levels were measured by an enzymatic assay and serum total glucarpidase concentrations were measured by ELISA.

Serum glucarpidase activity levels declined with a mean elimination half-life (t_1/2) of 5.6 hours. The mean Cmax was 3.3 µg/mL and the mean area under the curve (AUC_0-inf) was 23.3 µg·h/mL. The mean systemic clearance (CL) was 7.5 mL/min. The mean volume of distribution (V_d) was 3.6 L, suggesting that glucarpidase distribution is restricted to plasma volume. The pharmacokinetic parameters derived from the serum total glucarpidase concentrations were similar to those generated by serum glucarpidase activity levels except for a longer t_1/2 of 9 hours.

Among the 290 patients included in the safety evaluation of VORAXAZE, there were 8 deaths within 30 days of VORAXAZE exposure that were not related to progressive disease. Twenty-one of 290 patients (7%) experienced adverse reactions that were assessed as related to VORAXAZE. Most were Grade 1 or 2 events. One patient experienced related Grade 3 flushing. The most common related adverse reactions that were not hematologic, hepatic or renal events were paresthesia, flushing, and nausea and/or vomiting, which each occurred in 2% of patients (Table 1).

Table 1: Per Patient Incidence of Grade 1 and 2 Adverse Reactions Assessed as Possibly, Probably, or Definitely Related to VORAXAZE Excluding Hematologic, Hepatic, or Renal Adverse Reactions

Adverse Reaction	N= 290 n (%)
Paresthesias	7 (2%)
Flushing^1,2	5 (2%)
Nausea/Vomiting	5 (2%)
Headache	2 (1%)
Hypotension	2 (1%)
Blurred Vision	1 ( < 1%)
Diarrhea	1 ( < 1%)
Hypersensitivity	1 ( < 1%)
Hypertension	1 ( < 1%)
Rash	1 ( < 1%)
Throat irritation/Throat tightness	1 ( < 1%)
Tremor	1 ( < 1%)
¹ This incidence includes the following terms: flushing, feeling hot, burning sensation. ² One of these reactions was classified as Grade 3 in severity.

Immunogenicity

In clinical studies, 96 patients were evaluated for anti-glucarpidase antibodies. One (n=78) or two (n=18) doses of VORAXAZE were administered intravenously to these patients. Sixteen patients (17%) developed anti-glucarpidase antibodies following VORAXAZE administration. Antibody titers were determined using a validated bridging enzyme-linked immunosorbent assay (ELISA) for anti-glucarpidase antibodies. Twelve of the 16 patients who developed anti-glucarpidase antibodies had received a single dose of VORAXAZE, and four of the patients had received two doses of VORAXAZE.

Immunogenicity assay results are highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to VORAXAZE with the incidence of antibodies to other products may be misleading.

DRUG INTERACTIONS

Use of VORAXAZE with Leucovorin

Leucovorin is a substrate for VORAXAZE. Do not administer leucovorin within 2 hours before or after a dose of VORAXAZE. No dose adjustment is recommended for the continuing leucovorin regimen because the leucovorin dose is based on the patient¡¦s pre-VORAXAZE methotrexate concentration

CONTRAINDICATIONS

None

FDA APPROVED USES:

The U.S. Food and Drug Administration today approved Voraxaze (glucarpidase) to treat patients with toxic levels of methotrexate in their blood due to kidney fa

US VISA COUNSALTE OFFICE AT MUMBAI

2012-05-27T10:52:00.000+05:30

US Visa Process at the new US consulate Office @ Bandra Kurla Complex (BKC)

For all who are planning to apply for US visa or others thinking about it or who are just plain curious to know about "What happens at the consulate office?" - Read on then :) !!
Last week my company processed my US visa related to my work. It was a nice experience. After struggling to get the visa appointment, finally we got one in November early morning 9 am. Being in Pune I was suppose to drive to Mumbai consulate office early morning.

Just wanted to share the visa processing experience - What happens at the consulate office - with all of you !!

Lets go through them step by step.

I reached the American Consulate General Mumbai office at 7:30 am, the new office at BKC (Bandra Kurla Complex). Since it moved this November 18th 2011. The new BKC address is as follows:
C-49, G-Block,Bandra Kurla Complex,Bandra (East), Mumbai 400051.
Since the appointment was a 9 am, I had my breakfast at a nearby restaurant.
I picked up all my documents and joined the queue at 8:15am. It was a long queue.
After this point, no one without visa appointment confirmation are allowed.
The office opens at sharp 9am.
By 8:45 we had some Consulate officers come out and announced..
"please keep following document ready"
1. Original Passport.
2. Confirmation of appointment letter.
3. Invitation letter from the company.
4. HDFC receipt original.
They verified all the 4 documents. HDFC receipt has a small barcode sticker, they remove one from the set and paste it on the back side of your passport.
After this the main consulate office gate open and you are allowed to go in.
Immediately entering the Consulate office main door, you are placed in a queue, where you need to submit all the 4 documents. They scan the barcode of appointment confirmation. This generates another barcode. They paste that receipt on the front of your passport. This receipt also has the token number. Mine was N266.
Once this is done, they return you your passport and all your documents. You are now asked to proceed for the security check.
This is the general security check just like the one that we go through at the airport. You need to place all your belongings ie: document folder, watch, belt etc in the box and put that box through a scanner and stand in queue for body check.
After your turn comes, you will be scanned by the Consulate security officer. once this is done everything is in place now.
You need to collect your belongings and rush towards the counters, fearing your token will be called out.
After you leave the security room, you will be rushed to an office where actual interview happens.
Once you enter the door, you will asked for type of visa you are applying and will be directed accordingly to a proper queue.
In your new queue, First thing they do is Biometrics. They scan your left hand's 4 fingers excluding your thumb, then same with right hand. then lastly both of ur thumb impressions together.
Then you will be asked to sit and wait for your token to be called out.
Its a big hall with lotts of seating arrangement. Interview counters are exactly opposite to the seating arrangements.
You will see 10 counters labelled 31 32, 33 upto 40. For different Visa type counter numbers may differ.
There are two LCD screens displaying the next token number and the counter that token number is suppose to go to. i.e. something like
Counter 33
Token N256
Also at the top of each counter, the current processing token number as well as next token number to be processed is displayed.
All interviewing officers are foreigners. All Americans.
Once your token number is displayed and called out on the LCD display, You are supposed to head straight towards that counter and stand in queue. Unless the interviewer calls you at the window. Queue is generally quiet short, couple of people.
Finally the time arrives and you are called by the interviewer and you head straight for that counter window.
Counter has a big glass window completely bullet proof. At the right hand side you will notice a Speaker. The interviewer generally has a mike through which he speaks out load, you need to pay attention to the speaker to understand the questions asked.
At the counter hand over only the passport. If You have re-issued and gotten a new passport, carry both the old and new passport and hand over both to the interviewing officer. Especially if you have visas on your old passport.
Now the Question and answer session starts. This will typically last for 5-10mins. depending totally on the interviewer and how you answer his questions.
I will only list out here question that were asked to me.
Q1. Why do you want to go to US.
Q2. Whose going to finance you.
Q3. Where do you work.
Q4. What do you work on.
Q5. How much do you earn.
Q6. Why is it that you are traveling to US for 1st time in so many years.
Q7. Where will you stay in US.
Q8. How long you will be staying in US.
Q9 Why xyz months/week.
Q10. Question about my Europe and UK visa
Q11. Where are you going in US ( city and state name in US).
Q12. what are you going to bring back for your team from US ( in terms of work /knowledge base).
After all those massive questions and answer sessions ends, if the interviewer keeps you passport then its all done. Yipeeeee !!.
Your have successfully handled it. Within 3 days your passport along with US visa will be delivered by Bluedart to your mailing address. Also you have an option to collect the same by 5pm same day at the Mumbai VFS office. You get an SMS about this in couple of hours as well.
If for some other reason the interviewer hands your passport back to you, then you did not clear the interview "According to the Interviewer". So you will have to apply again. Don't get disheartened because its complete luck and the officers mood/questions. cheer up and apply a second time.
After this you can take the exit door and leave the consulate office.

Some odd things to keep in mind :-
1. Carry all your documents like education certificates, work related documents, identity proof etc. Originals as well as a copy. Trust me you don't want to run at the last moment. They didn't ask me for any documents, that would not be the case always.
2. Reach early. Even though its mentioned that your appointment is at 9 am, 10, 11 etc .. still try to go there atleast 45 min early. There are lottts of people having an appointment the same day same time. So early you reach, closer you are.
3. Don't carry bagpacks, suitcase, rack etc . they are not allowed inside.
4. The new consulate office is very near to the TRIDENT hotel. I mentioned it incase you need a landmark. Consulate is a landmark in itself .. so don't worrry. lotts of people go to work in BKC, also people jogging early morning .. all are aware of the place :) so be relaxed !!
5. Last but not the least. Smile, Be Confident and come back with nice experience :) that is all that matters the most !!

Now Geared with all the new experience about US visa processing, share your experience with your close ones and just blog it - like the way I did !!

All the best :) !

Evaluation of strip and blister packaging

2012-05-02T00:09:00.000+05:30

Procedure for Leak testing of strips / blisters

1.0 OBJECTIVE
To lay down a procedure for leak testing of strips / blisters.
2.0 SCOPE
All packing areas.
3.0 RESPONSIBILITY
Production officer.
4.0 ACCOUNTABILITY
Production executive
5.0 PROCEDURE
5.1 Take the required number of strips / blisters as mentioned in the Annexure – I. Check the quality of strips/ blisters for any damages.
5.2 Tie the collected strips / blisters with a rubber band.
5.3 Ensure that all strips / blisters are dipped in water and close the lid.
5.4 Connect opening of the desiccator to the vacuum pump.
5.5 Apply a vacuum of 300 mm of Hg and close the knob of the desiccator.
5.6 Keep the vacuum for 30sec.
5.7 Release the vacuum by opening the knob of the desiccator slowly and open the lid remove the strips / blisters.
5.8 Wipe out the traces of water from the strips / blisters by using lint free duster .
5.9 Open the pocket of strips by using scissors to remove the tablets / capsules.
5.10 Open the blisters manually.
5.11 Check for any traces of water inside the strips / blisters.
5.12 Number of tablets or capsules, which have become wet, should not be more than 1%. If the leakage is more than the above percentage repeat the leak test.
5.13 Record it in the respective batch packing record, with signature and date.
ANNEXURE -I

Note:
1. Perform leak test at the starting of blistering / strip sealing, operation.
2. If there is machine break down more than 1/2 hour perform leak test immediately after starting the operation.
3. Whenever leakage observed during leak test, ensure that rectification is done.
4. If leak test failure is occurring repeatedly, bring to the notice of Executive / Sr. Executive for corrective action.

F1 VISA

2012-04-04T23:35:00.000+05:30

F1 Visa Questions & Suitable Answers

Trust me other than the following 21 Questions, they cant ask anything more. But yes they can be Rephrased! Firstly the interviewer will be busy updating your information in her/his records. Secondly its just a max 2 minutes interview {mite increase if & only if you are unable to comprehend what he/she is saying i.e more of "Excuse me" or "Pardon me" or "Come again"} :)

Questions:

Why are you going to US?
Why US & not India?
Why not IIT?
Why xxx university only?
How many university's did you apply to? How many accepts & How many rejects?
Why xxx specialization? Whats its scope in India?
What was major in Bachelors?
What were your grades in Bachelors?
Tell about your project.
Schooling?
Gre & Toefl Scores.
What did you do since you graduated?
Would you work on/off campus?
Wont recession affect you?
Who's sponsering you?
What are you parents? Their Income?? Their Savings?
I see recent transactions in the bank certificate, how would you explain?
If you utilise all their money, how would they run the family?
How many siblings? Is there sufficient funds for them?
What are your plans after masters?
Where would you want to work in future? Where do you see yourself after 5 years? What salary do you expect?

Answers :

To pursue masters in CS in xxx university.
a) International Exposure b) Flexibility(can complete a course in 15-18 months) c) Pratical approach d)Advanced Technology
IIT is excellent, but its intake is around 100 for 20/30000 students who write. Plus my interest is in xxx University.
a) Rank of the university chosen (Courtesy: USNews) b) Seniors gave excellent feedback c) My area of interest is found here d) Professor MrABC has done amazing research in field i want.
You need not tell complete truth. If u have more rejects, put it across as "waitin"/"on hold".
You gottu surf about your interest. Tell its scope in US, India its advancements and one/two applications.
Your turn.
Here we use a % system i.e its calucated for 100. My % is blah blah.
Use technical jargons That will work :)
Your turn.
Tell truth. If they are less use the standard answer " I made mistake in the first 10 questions which are very crucial and carry high score. Hence i got less. Future i will take care i wont mess up."
{This question changed the entire course of my interview}Its ur say. Better to carry certificates as proof for the work/course you have done.
A definite NO. I want to study hard and complete my masters soon.
I am going to enhance my technical knowledge and skills. It is no where realated to recession.
My blah, blah and an education loan are sponsoring me.
Your turn.
My blah blah had invested money in other accounts and also lent them to needy friends and relatives. Now for the purpose of my education he has pooled them into this account.
My course needs x lakhs. My loan covers x-n lakhs. My blah blah hav the savings which is more than n lakhs. Hence its sufficient for them.
Your turn. If you have you could say, he/she is interested in working. If he/she changes plans after working for 2/3 years, by then i would hav started repayin the loan so it wont be a problem for him/her.
Return to India and work in the company of my choice which has xxx specialization.
Your turn. tell a salary which is more than the EMI you gottu return to bank

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

TIP:

"Smile" is the mantra!
Try explaining in points than long sentences.
Answer to point. An Extra word will lead to a new thread of questions.
While talkin abt money talk in terms of indian money than dollars.
Remenber the interviewer is an American, they wont be familiar with Indian terms. "% --> gpa", "puc --> preuniversity", "Btech/BE --> Bachelors" etc.
Write down the exact answers & read them once o twice. It will definitely help you.
All the best. ;)

GTU students shown answer sheets under RTI

2012-04-02T20:11:00.000+05:30

GTU students shown answer sheets under RTI

After two months of waiting ten students of GTU, who had applied under RTI, were invited to view the answer sheets they had requested for

(http://www.ahmedabadmirror.com/article/3/20120105201201050223092647d8736e7/GTU-students-shown-answer-sheets-under-RTI.html
Finally, Gujarat Technological University has taken the necessary steps to make answer sheets available to the students. Ten students, who had appealed under Right to Information Act, were called by the university to check their answer sheets on Wednesday.
Five of the students were of Bachelor of Engineering, one of Diploma Engineering, two of MBA and two students of Bachelor of Pharmacy. Overall, the university had to distribute 15 answer sheets among these students.
A GTU source said, “Ten students had applied to see their answer sheets between September and October under RTI Act. But, we had declined the offer at that time. The applicants appealed and following the supreme court order, we sent out letters for them to be present on Wednesday. We had opted for the open method system were they could check their original answer sheets.”
The students and parents were pleased by GTU’s move. One of the parents Rohit Desai said, “Often due to small mistakes by evaluators, the career path of the student changes entirely. This system could ensure that evaluators remain alert while grading. If they grade unfairly, they would be caught eventually.”
Saloni Dhawal, one of the students present on Wednesday, said, “I thought I had written the exam well but I ended up scoring very low. I wanted to know if I had made mistakes or the evaluator had. I am glad I can spot the mistakes and learn from them.”
Vice Chancellor Akshai Aggarwal said, “This facility is great for both the students and faculty. But the problem is that it requires manpower to stay active. For universities that have lakhs of students, this system is difficult to implement. For universities with few students, the system can be put into practice easily. The number of students applying is bound to increase as awareness of the system grows.”

Setbacks
Sources in GTU said, “The university has a student body of more than 5 lakh students. If even a mere 5 per cent of the students applied for the system, the time needed to retrieve their papers will be phenomenal. A multi-storeyed building and an extensive number of people will be needed to run the system in the future years.”

SC ruled pro RTI
The Supreme Court ruled in August that students unhappy with their examination scores — class X and XII, entrance exam for professional courses as well as job recruitment tests — can take a look at their answer-sheets by moving an application under the Right to Information Act. So far, only re-tabulation of marks was possible. Now, the court has provided for re-evaluation of answersheets, which will factor in whether the examiner missed out on awarding marks for some answers

Control Drug Delivery System

2012-03-25T20:35:00.001+05:30

Control Drug Delivery System

2012-03-25T20:17:00.001+05:30

ENDOCRINE SYSTEM

2011-12-31T23:18:00.003+05:30

Endocrine System

The nervous system sends electrical messages to control and coordinate the body. The endocrine system has a similar job, but uses chemicals to “communicate”. These chemicals are known as hormones. A hormone is a specific messenger molecule synthesized and secreted by a group of specialized cells called an endocrine gland. These glands are ductless, which means that their secretions (hormones) are released directly into the bloodstream and travel to elsewhere in the body to target organs, upon which they act. Note that this is in contrast to our digestive glands, which have ducts for releasing the digestive enzymes.
Pheromones are also communication chemicals, but are used to send signals to other members of the same species. Queen bees, ants, and naked mole rats exert control of their respective colonies via pheromones. One common use for pheromones is as attractants in mating. Pheromones are widely studied in insects and are the basis for some kinds of Japanese beetle and gypsy moth traps. While pheromones have not been so widely studied in humans, some interesting studies have been done in recent years on pheromonal control of menstrual cycles in women. It has been found that pheromones in male sweat and/or sweat from another “dominant” female will both influence/regulate the cycles of women when smeared on their upper lip, just below the nose. Also, there is evidence that continued reception of a given man’s pheromone(s) by a woman in the weeks just after ovulation/fertilization can significantly increase the chances of successful implantation of the new baby in her uterus. Pheromones are also used for things like territorial markers (urine) and alarm signals.
Each hormone’s shape is specific and can be recognized by the corresponding target cells. The binding sites on the target cells are called hormone receptors. Many hormones come in antagonistic pairs that have opposite effects on the target organs. For example, insulin and glucagon have opposite effects on the liver’s control of blood sugar level. Insulin lowers the blood sugar level by instructing the liver to take glucose out of circulation and store it, while glucagon instructs the liver to release some of its stored supply to raise the blood sugar level. Much hormonal regulation depends on feedback loops to maintain balance and homeostasis.
There are three general classes (groups) of hormones. These are classified by chemical structure, not function.

steroid hormones including prostaglandins which function especially in a variety of female functions (aspirin inhibits synthesis of prostaglandins, some of which cause “cramps”) and the sex hormones all of which are lipids made from cholesterol,
amino acid derivatives (like epinephrine) which are derived from amino acids, especially tyrosine, and
peptide hormones (like insulin) which is the most numerous/diverse group of hormones.

The major human endocrine glands include:
(clipart edited from Corel Presentations 8)

the hypothalamus and pituitary gland
The pituitary gland is called the “master gland” but it is under the control of the hypothalamus. Together, they control many other endocrine functions. They secrete a number of hormones, especially several which are important to the female menstural cycle, pregnancy, birth, and lactation (milk production). These include follicle-stimulating hormone (FSH), which stimulates development and maturation of a follicle in one of a woman’s ovaries, and leutinizing hormone (LH), which causes the bursting of that follicle (= ovulation) and the formation of a corpus luteum from the remains of the follicle.
There are a number of other hypothalamus and pituitary hormones which affect various target organs.
One non-sex hormone secreted by the posterior pituitary is antidiuretic hormone or ADH. This hormone helps prevent excess water excretion by the kidneys. Ethanol inhibits the release of ADH and can, thus, cause excessive water loss. That’s also part of the reason why a group of college students who go out for pizza and a pitcher of beer need to make frequent trips to the restrooms. Diuretics are chemicals which interfere with the production of or action of ADH so the kidneys secrete more water. Thus diuretics are often prescribed for people with high blood pressure, in an attempt to decrease blood volume.
Another group of non-sex hormones that many people have heard of is the endorphins, which belong to the category of chemicals known as opiates and serve to deaden our pain receptors. Endorphins, which are chemically related to morphine, are produced in response to pain. The natural response to rub an injured area, such as a pinched finger, helps to release endorphins in that area. People who exercise a lot and push their bodies “until it hurts” thereby stimulate the production of endorphins. It is thought that some people who constantly over-exercise and push themselves too much may actually be addicted to their own endorphins which that severe exercise regime releases.
the thyroid gland
Thyroid hormones regulate metabolism, therefore body temperature and weight. The thyroid hormones contain iodine, which the thyroid needs in order to manufacture these hormones. If a person lacks iodine in his/her diet, the thyroid cannot make the hormones, causing a deficiency. In response to the body’s feedback loops calling for more thyroid hormones, the thyroid gland then enlarges to attempt to compensate (The body’s plan here is if it’s bigger it can make more, but that doesn’t help if there isn’t enough iodine.). This disorder is called goiter. Dietary sources of iodine include any “ocean foods” because ocean-dwelling organisms tend to accumulate iodine from the seawater, and would include foods like ocean fish (tuna) and seaweeds like kelp. Because of this, people who live near the ocean do not have as much of a problem with goiter as people who live inland and don’t have access to these foods. To help alleviate this problem in our country, our government began a program encouraging salt refiners to add iodine to salt, and encouraging people to choose to consume this iodized salt.
the pancreas
This organ has two functions. It serves as a ducted gland, secreting digestive enzymes into the small intestine. The pancreas also serves as a ductless gland in that the islets of Langerhans secrete insulin and glucagon to regulate the blood sugar level. The -islet cells secrete glucagon, which tells the liver to take carbohydrate out of storage to raise a low blood sugar level. The -islet cells secrete insulin to tell the liver to take excess glucose out of circulation to lower a blood sugar level that’s too high. If a person’s body does not make enough insulin (and/or there is a reduced response of the target cells in the liver), the blood sugar rises, perhaps out of control, and we say that the person has diabetes mellitus.
the adrenal glands
These sit on top of the kidneys. They consist of two parts, the outer cortex and the inner medulla. The medulla secretes epinephrine (= adrenaline) and other similar hormones in response to stressors such as fright, anger, caffeine, or low blood sugar. The cortex secretes corticosteroids such as cortisone. Corticosteroids are well-known as being anti-inflammatory, thus are prescribed for a number of conditions. However, these are powerful regulators that should be used with caution. Medicinal doses are typically higher than what your body would produce naturally, thus the person’s normal feedback loops suppress natural secretion, and it is necessary to gradually taper off the dosage to trigger the adrenal glands to begin producing on their own again. Because the corticosteroids suppress the immune system, their use can lead to increased susceptibility to infections, yet physicians typically prescribe them for people whose immune systems are hard at work trying to fight off some pathogen. For example, back when I was in grad school, I was diagnosed with mono, and the campus doctor prescribed penicillin and cortisone. Since mono is a virus and penicillin only is effective against some bacteria, about all it did was kill off the friendly bacteria in my body, therefore causing me to develop a bad case of thrush. At the same time, the cortisone was supressing my immune system so my body could not as efficiently fight off the mono and the thrush. People with high blood pressure should be leery of taking prescription corticosteroids: they are known to raise blood pressure, thus can cause things like strokes. My mother-in-law had high blood pressure and was being treated with diuretics. Her physician also had her on large doses of cortisone for her arthritis. While he was on vacation, she started having significant back pain and was referred to an orthopedic surgeon. This man decided the back pain was just due to arthritis, and without carefully checking on what dosage she was already taking, prescribed more cortisone. Simultaneously, because of difficulty walking due to her arthritis, she decided to decrease the amount of diuretics she was taking so she didn’t have to make as many “long” trips to the other end of the house. The combination of lowered dose of diuretics and high dose of cortisone raised her blood pressure to the point where a blood vessel in her brain burst, causing a stroke. When the EMTs took her blood pressure, as I recall the systolic was way over 200 mm Hg.
the gonads or sex organs
In addition to producing gametes, the female ovaries and male testes (singular = testis) also secrete hormones. Therefore, these hormones are called sex hormones. The secretion of sex hormones by the gonads is controlled by pituitary gland hormones such as FSH and LH. While both sexes make some of each of the hormones, typically male testes secrete primarily androgens including testosterone. Female ovaries make estrogen and progesterone in varying amounts depending on where in her cycle a woman is. In a pregnant woman, the baby’s placenta also secretes hormones to maintain the pregnancy.
the pineal gland
This gland is located near the center of the brain in humans, and is stimulated by nerves from the eyes. In some other animals, the pineal gland is closer to the skin and directly stimulated by light (some lizards even have a third eye). The pineal gland secreted melatonin at night when it’s dark, thus secretes more in winter when the nights are longer. Melatonin promotes sleep (makes you feel sleepy). It also affects reproductive functions by depressing the activity of the gonads. Additionally, it affects thyroid and adrenal cortex functions. In some animals, melatonin affects skin pigmentation. Because melatonin production is affected by the amount of light to which a person is exposed, this is tied to circadian rhythm (having an activity cycle of about 24 hours), annual cycles, and biological clock functions. SAD or seasonal affective disorder (syndrome) is a disorder in which too much melatonin is produced, especially during the long nights of winter, causing profound depression, oversleeping, weight gain, tiredness, and sadness. Treatment consists of exposure to bright lights for several hours each day to inhibit melatonin production. It has also been found that melatonin levels drop 75% suddenly just before puberty, suggesting the involvement of melatonin in the regulation of the onset of puberty. Studies have been done on blind girls (with a form of blindness in which no impulses can travel down the optic nerve and reach the brain and pineal gland), which showed that these girls tended to have higher levels of melatonin for a longer time, resulting in a delay in the onset of puberty. While some older people, who don’t make very much melatonin, thus don’t sleep well, might benefit from a melatonin supplement, I’m skeptical of the recent melatonin craze in this country. When so many people apparently are suffering from SAD, I question the wisdom of purposly ingesting more melatonin, especially since the pineal gland is one of the least-studied, least-understood of the endocrine glands.

Local regulators are hormones with target cells nearby or adjacent to the endocrine gland in question. For example, neurotransmitters are secreted in the synapses of our nervous system and their target cells are in the same synapses.

GLUCOMA

2011-12-28T23:55:00.000+05:30

Glaucoma is not a single eye disorder but a group of disorders that affect the eye. The optic nerve is made up of 1 million nerve fibers. It carries visual images from the retina, the layer of light-sensitive tissue at the back of the eyeball, to the brain. Untreated glaucoma may lead to vision loss or even complete blindness. In most cases of glaucoma, the optic nerve is damaged by increased fluid pressure inside the eyeball. However, reduced blood supply to the optic nerve, caused by the increased pressure, can also be a factor.

Glaucoma is often categorized as either primary or secondary. Primary glaucoma refers to glaucoma that is not triggered by an injury or other medical condition. It accounts for about 90 percent of cases. There are several major types of primary glaucoma:
• Open-angle glaucoma. This term refers to the angle in the front portion of the eye where the cornea meets the iris. In normal circumstances, fluid flows in and out of the front of the eye through a meshwork of tissue at the angle that acts like a drain. In openangle glaucoma, the angle remains open and fluid continues to pass through the meshwork, but not quickly enough. As a result, fluid builds up inside the eye, and the fluid pressure may rise high enough to damage the optic nerve. Open-angle glaucoma is the most common type of primary glaucoma.
• Closed-angle glaucoma. Closed-angle glaucoma is a disorder in which the angle between the iris and the cornea is blocked, usually because the iris becomes swollen from pressure and moves forward to touch the meshwork directly, thus preventing fluid from draining out of the eye. Closed-angle glaucoma can develop either gradually or suddenly. Acute closed-angle glaucoma is a medical emergency.
• Congenital glaucoma. This is a type of glaucoma that is present at birth and is usually noticeable within the first year of life. It is more common in boys than in girls. In congenital glaucoma, there is a defect in the structure of the baby’s eye that slows down the normal drainage of fluid.
• Normal-pressure glaucoma. Also called normal-tension glaucoma, this is a type of primary glaucoma in which the optic nerve is damaged even though the fluid pressure within the eye is within normal range. Doctors do not yet understand the causes of this type of glaucoma, although one theory suggests that the optic nerve is damaged by normal fluid pressure because its blood supply has been reduced.
• Pigmentary glaucoma. This is a type of glaucoma that develops when pigment granules from the iris flake off and block the drainage meshwork in the angle between the iris and cornea. About 10 percent of cases of glaucoma are secondary, meaning that they develop as a result of injury to the eye or another disease, most commonly diabetes, leukemia, or sickle cell anemia. Secondary glaucoma may result from a blow to the eye, a tumor, cataract surgery, or the use of corticosteroid medications.

People’s experience of glaucoma varies considerably depending on which type they have and whether it is chronic (developing slowly) or acute (sudden onset). In addition, glaucoma can affect both eyes or only one.

Children with congenital glaucoma are usually diagnosed within the first few months after birth because their eyes look cloudy, are unusually sensitive to light, and secrete large amounts of tears. Chronic open-angle glaucoma, the single most common type, develops over a period of years and is related to the aging of the drainage meshwork in the angle between the iris and cornea. In the early stages, patients with this type of glaucoma may have no symptoms at all. Gradually, however, they find it more difficult to see objects to the side or on the edges of their visual field. They may also develop tunnel vision, in which they can see only objects straight in front of them.

Closed-angle glaucoma can come on suddenly, often in dim light, with eye pain, reddening of the eye, a sudden severe headache, and nausea and vomiting. The person may also see colored or rainbow-like halos around lights.

Glaucoma is largely an eye disorder of adults. Congenital glaucoma is rare and childhood glaucoma is also unusual. Glaucoma in middle-aged adults, however, is a common eye disorder and the second leading cause of blindness in the United States. According to Prevent Blindness America, more than 2.2 million Americans over age forty have open-angle glaucoma, but only half of them know that they have it. In North America and Europe, glaucoma affects one person in every two hundred aged fifty or younger, but one in ten over the age of eighty.

Some people are at increased risk of glaucoma:
• Those with increased fluid pressure in the eye, sometimes called ocular hypertension. A high level of fluid pressure inside the eye is the greatest single risk factor for glaucoma. However, as noted earlier, some people develop the disorder even though their eye fluid pressure is normal.
• Age. The risk of glaucoma increases over age sixty for most Americans; it rises over age forty for African Americans.
• Race and ethnicity. African Americans have six to eight times the risk of glaucoma as Caucasians. Mexican Americans over the age of sixty are also at increased risk. Asian Americans and Alaskan Inuit have a higher than average risk of acute closed-angle glaucoma, and Japanese Americans have an increased risk of normal-pressure glaucoma. The reasons for these differences are not yet understood.
• Family history of glaucoma.
• Certain diseases or conditions, including high blood pressure, diabetes, heart disease, hypothyroidism, and sickle cell anemia.
• Myopia (nearsightedness).
• A history of injury to the eye, inflammation of the eye, tumors in the eye, or cataract surgery.
• Long-term use of corticosteroid medications.

Signs and Symptoms

The most important cause of glaucoma is increased fluid pressure within the eye resulting from overly slow drainage of fluid through the meshwork in the angle between the iris and cornea or complete blockage of the angle. This buildup of fluid pressure damages the optic nerve. In some cases inadequate blood supply to the optic nerve is also a factor.

There is some evidence that genetic factors are also involved in glaucoma because the disorder is known to run in some families. Several genetic mutations have been linked to primary open-angle glaucoma, but no single gene has been shown to cause the disorder. The symptoms of the various types of glaucoma were described earlier.

Diagnosis

The diagnosis of chronic primary glaucoma is usually made during a routine eye examination by an ophthalmologist, who is a doctor specializing in the diagnosis and treatment of eye disorders. A complete eye examination, depending on the individual patient’s history and risk factors, will include most or all of the following tests:
• Dilation of the eye. The doctor will dilate the pupil of the eye by placing drops in the eyes that keep the iris from narrowing the pupil when the doctor shines a bright light directly into the eye. The doctor will then be able to see directly to the back of the eye to check for damage to the optic nerve.
• Tonometry. This is a test for measuring the level of fluid pressure inside the eye. It can be performed either by resting an instrument briefly on the surface of an anesthetized eye, or by blowing a puff of air onto the surface of the eye while the patient’s chin is held steady. The fluid pressure is estimated by measuring the response of the eye to the puff of air.
• Tests of peripheral vision. Since open-angle glaucoma often starts with gradual loss of side vision, doctors may measure whether such loss has occurred by asking patients to look at a set of blinking lights and indicate when they can see the lights. The patients’ answers allow doctors to map how much, if any, of the patients’ visual field has been lost.
• Tests to measure the thickness of the cornea. This test is done to rule out the possibility that a cornea that is either unusually thick or unusually thin is affecting the measurement of the fluid pressure inside the eye.
• Gonioscopy. This is a test than uses a gonioscope, an instrument with a mirror as well as a light source. It allows the doctor to tell whether the angle between the iris and the cornea is open or closed.

A patient with acute closed-angle glaucoma will usually be treated by an ophthalmologist in a hospital emergency department. Emergency treatment consists of medications to quickly reduce the fluid pressure inside the eye and laser surgery to cut a drainage hole in the iris.

Treatment

Glaucoma can be treated with medications, surgery, or both. The medications used include special eye drops or oral medications. In some cases the patient may be asked to use more than one type of eye drop. There are several different types of drugs that may be prescribed; some work to lower the fluid pressure inside the eye by decreasing the amount of fluid produced. Other drugs work by increasing the outflow of fluid. All of these medications have side effects, however, and must be used exactly according to the doctor’s instructions. Surgery is usually used to treat congenital glaucoma and acute closed angle glaucoma. The procedure used to treat closed-angle glaucoma is called an iridotomy. The surgeon uses a laser to cut a hole in the iris to relieve the increased pressure inside the eye. Surgery can also be performed to treat open-angle glaucoma. There are two major types of laser surgery that can be done. One technique involves using the laser to open clogged portions of the drainage network.

Another approach is called filtering surgery. The surgeon uses the laser to cut a small hole in the sclera (white part of the eyeball) and remove a small portion of the clogged meshwork. The extra fluid can then leave the eye through the hole in the sclera. Children with glaucoma and adults with secondary glaucoma can be treated with drainage implant surgery. The implant is a small silicone tube that the doctor inserts inside the eye to help drain the excess fluid.

Prognosis

The prognosis of glaucoma depends on its type and the stage at which it is diagnosed. Vision that has been lost to any type of glaucoma cannot be restored. Without treatment, acute glaucoma results in permanent vision loss within days. Untreated chronic glaucoma can progress to blindness within several years.

Prevention

The best prevention for glaucoma is regular eye exams. Anyone over age eighteen should be screened periodically for glaucoma. The schedule of eye examinations recommended by the National Eye Institute (NEI) is as follows:
• Eighteen to sixty years of age: Every two years.
• Over sixty: Every year.
• One or more risk factors other than age: Every year before and after age sixty. Other preventive steps that people can take include getting treatment
(special eye drops) if diagnosed with high fluid pressure inside the eye; controlling one’s

ANEMIA

2011-12-25T22:52:00.000+05:30

Anemia

Introduction

The function of red blood cells is to transport oxygen to tissues. This is accomplished by the hemoglobin. The hemoglobin protein is composed of two alph and two beta subunits. Each of the subunits contains a central iron containing protein called a heme protein. It is the iron atom in the heme protein that binds to molecular oxygen. As a result of the four iron-containing heme groups, each molecule of hemoglobin can carry four atoms of oxygen.

Definition

Anemia is a condition in which there is a reduced number of red blood cells or decreased concentration of hemoglobin in those cells or both.

Pathophysiology

Anemia can be caused by:

1- Decreased red cell production, which may be due to lack of nutrient (B₁₂, folic acid, iron) or bone marrow failure.

2- Increased red cell destruction secondary to hemolysis.

3- Increased red cell loss caused by acute or chronic bleeding.

Morphologic classification of anemias by red blood cell size (microcytic, normocytic, macrocytic) and hemoglobin content (hypochromic, normochromic, hyperchromic) is as follows (see figure-1):

Macrocytic (Megaloblastic) anemia: Vitamin B₁₂ deficiency (pernicious) and folic acid deficiency anemia.

Microcytic, hypochromic anemia: Iron deficiency

Normochromic, normocytic: Recent blood loss and Hemolysis

Figure-1: illustrating microcytic hypchromic and macrocytic hyperchromic anemia

Signs and Symptoms

Onset of anemia can be acute or can develop slowly, resulting in tissue hypoxia caused by the decreased oxygen-carrying capacity of the reduced red cell mass.

Slowly developing anemias can be asymptomatic initially or include symptoms such as slight exertional dyspnea, and fatigue. In severe anemia, heart rate, and stroke volume often increase in an attempt to improve oxygen delivery to tissues. These changes in heart rate and stroke volume can result in angina pectoris and high output congestive heart failure.

Microcytic hypochromic anemias (Iron Deficiency Anemia)

Iron deficiency is the most common cause of anemia worldwide. Iron deficiency is a state of negative iron balance in which the daily iron intake and stores are unable to meet the RBC and other body tissue needs.

Only about 0.5 to 1 mg/day of iron is lost from urine, sweat, and the sloughing of intestinal mucosal cells that contain ferritin. Menstruating women lose approximately 0.6% to 2.5% more iron per day.

Iron is absorbed from the duodenum and upper jejunum by an active transport mechanism. Dietary iron, which is primarily in the ferric state, is converted to the more readily absorbable ferrous form in the acid environment of the stomach.

Animal sources of iron are better absorbed than plant sources. A gastrectomy may decrease the conversion of the ferric form of iron to the ferrous state, thereby diminishing iron absorption.

Etiology and pathophysiology

Iron deficiency anemia can be caused by:

1- Chronic blood loss due to peptic ulcer disease, hemorrhoids, menstruation and ingestion of GI irritants such as NSAIDs.

2- Decreased absorption due to gastrectomy, or ingestion of medications that complex with iron, decreasing its absorption.

3- Increased requirement during infancy, pregnancy and lactation.

4- Inadequate dietary intake of iron (less than 1 to 2 mg/day), as in prolonged non supplemented breast-feeding or bottle-feeding of infants.

Because iron is the functional component of hemoglobin, lack of available iron will result in a decreased hemoglobin synthesis and subsequent impairment of red blood cell oxygen-carrying capacity.

Treatment (Iron Therapy)

Oral Administration

The goals of iron therapy are to normalize the Hb concentrations and to replete iron stores.

The preferred route of iron administration is oral route. Oral iron is most readily absorbed in the absence of food,

The ferrous form of iron is absorbed three times more readily than the ferric form. Although ferrous sulfate (contain 20% of elemental iron ), ferrous gluconate (contain 11% of elemental iron), and ferrous fumarate (contain 33% of elemental iron) are absorbed almost equally, each contains a different amount of elemental iron.

The usual adult dose of ferrous sulfate is 325 mg (one tablet) administered three times daily, between meals.

Hematologic response is usually seen in 2 to 3 weeks with a 1 g/dL increase in hemoglobin, anemia can be resolved in 1 to 2 months; however, iron therapy should be continued for 3 to 6 months after the hemoglobin is normalized to replete iron stores.

Side effects

Oral iron therapy produces dark stools. Gastric side effects, which occur in 5% to 20% of patients, include nausea, epigastric pain, constipation, abdominal cramps, and diarrhea.

Drug-drug interactions

Food, especially dairy products, decreases the absorption of iron by 40% to 50%. Drugs that increase the pH of the stomach (antacids, proton pump inhibitors, and H2 blockers) will decrease the solubility of ferrous salts and thus reduce iron absorption.

Because the absorptions of both iron and tetracycline are decreased when administered concomitantly, the iron should be taken 2 hours before or 3 hours after the tetracycline and drugs that increase gastric pH.

Parenteral Iron Therapy

Parenteral iron therapy is indicated when there is failure to respond to oral therapy (due to nonadherence, or malabsorption). Iron can be given parenterally in the form of ferric gluconate, iron dextran, and iron sucrose.

Iron dextran can be administered undiluted intramuscularly or by very slow intravenous infusion after dilution in 0.9% NaCl.

Ferric gluconate and iron sucrose can be administered undiluted as a slow IV injection or as an IV infusion after dilution in 0.9% NaCl.

Side effects of parentral iron

Anaphylactoid reactions can occur in about 1% of patients treated with parenteral iron therapy. Other side effects seen with parenteral iron agents include hypotension, nausea and vomiting, cramps, and diarrhea.

Megaloblastic Anemias

Megaloblastic anemia is a common disorder that caused by either vitamin B₁₂ deficiency or folic acid deficiency. Megaloblastic anemia results from impaired DNA synthesis in replicating cells, which is signaled by a large immature nucleus.

Folic Acid Deficiency Anemia

Etiology

Folate deficiency can result from decreased intake or increased requirement (during pregnancy). Folate deficiency also can occurs due to ingestion of drugs that alter folate metabolism (e.g., trimethoprim, pyrimethamine, methotrexate, sulfasalazine anticonvulsants)

Pathogenesis and symptoms

Once absorbed, the inactive dihydrofolate is methylated and reduced to methyl tetrahydrofolate (folinic acid) by dihydrofolate reductase. Within the cells the methyl group is removed (in a reaction requiring vitamin B₁₂) to form the active tetrahydtofolate which acts as a coenzyme involved in a number of reactions including DNA and RNA symthesis. Defect in DNA synthesis mainly affect cells with rapid turnover such as red blood cells and gastrointestinal cells, hence sore tongue and anemia seen in folate deficiency.

Treatment

Folate deficiency is usually managed by replacement therapy. The normal daily requirement of folic acid is about 100 mcg/ day. Despite this, the usual treatment doses given are 1-5 mg /day of oral folic acid. Even in malabsorption states sufficient folate is absorbed because of these large doses.

The RBC morphology should begin to revert back to normal within 24 to 48 hours after therapy is initiated, and the anemia should be corrected in 1 to 2 months.

Large doses of folate can partially reverse hematologic abnormalities caused by vitamin B₁₂ deficiency; however, folate cannot correct neurologic damage caused by vitamin B₁₂ deficiency. Therefore, folate deficiency absolutely must be differentiated from vitamin B₁₂ deficiency before folate therapy is initiated. Otherwise, the progression of the neurologic sequelae of vitamin B₁₂ deficiency can occur.

Vitamin B₁₂ Deficiency Anemia

The typical diet contains 5 to 15 mcg/day of vitamin B₁₂, an amount sufficient to replace the 2 mcg lost daily. The total body stores of vitamin B₁₂ range from 2,000 to 5,000 mcg. Because body stores are extensive, 3 to 4 years are required before symptoms of vitamin B₁₂ deficiency develop (the onset of the vitamin B₁₂ deficiency anemia is slow).

In the stomach, the vitamin B₁₂ bound to intrinsic factor, which protects it from degradation by GI microorganisms. Intrinsic factor is essential for the absorption of vitamin B₁₂. Specific mucosal receptors in the distal ileum allow for attachment of the intrinsic factor-B₁₂ complex. In the liver, vitamin B₁₂ is converted to coenzyme B₁₂, which is essential for hematopoiesis, maintenance of myelin throughout the entire nervous system, and production of epithelial cells.

Aetiology

Vitamin B₁₂ deficiency can result from decreased intake or malabsorption. Malabsorption occur if the distal ilium is removed. In addition, the gastric mucosa may be unable to produce intrinsic factor under conditions such as total and partial gastrectomy or autoimmune destruction (Pernicious anemia).

Pathogenesis and symptoms

Vitamine B12 is acoenzyme for the removal of a methyl group from methyltetrahydrofolate. Lack of vitamin B₁₂ traps the folate as methyltetrahydrofolate and prevents DNA synthesis. So vitamin B₁₂ is a coenzyme essential for hematopoiesis, maintenance of myelin throughout the entire nervous system, and production of epithelial cells. Therefore, vitamin B₁₂deficiency is associated with sore tongue, and numbness or tingling in the extremities (peripheral neuropathy)

Treatment

Parenteral vitamin B₁₂ in a dose sufficient to provide the daily requirement of approximately 2 mcg, and to replenish tissue stores (about 2,000 to 5,000 mcg;) is given for treatment of vitamin B₁₂ deficiency anemia. To replete vitamin B₁₂ stores, cyanocobalamin (1,000 mcg) IM once a week for 4 to 6 weeks followed by 1,000 mcg/month for lifetime maintenance therapy in case of pernicious anemia .

Sickle Cell Anemia

Patients with sickle cell anemia have HbS (normal Hb is HbA). HbS has valine substituted for glutamic acid as the sixth amino acid in the beta chain of Hb.

The hemoglobin produced from such a substitution has a more negative charge than normal HbA, and the deoxygenated state favors hemoglobin aggregation and polymerization, which forms sickled RBC. Sickled RBCs are more rigid and may become “lodged” when passing through microvasculature, resulting in vascular occlusions. In addition, the sickled RBCs surface contains aminophospholipids, which augments the ability of the RBC to initiate coagulation and adhere to vascular endothelium leading to vaso-occlusive episodes and multiorgan damage.

Symptoms and treatment

The kidney is commonly affected by microinfarction. Although, vaso-occlusive events are uncommon. If they do occur, they usually are caused by hypoxic conditions resulting from excessive exercise or high altitudes.

Treatment of sickle cell anemia is largely directed toward prophylaxis against infections and supportive management of vaso-occlusive crises.

The following are symptoms and complications of sickle cell disease

Hemolytic Anemia

Hemolytic anemia in patients with sickle cell disease is caused by splenic sequestration of abnormal RBC. Sequestration reduces the RBC life span from 120 days to 15 to 25 days. Management of the underlying anemia may include splenectomy following the first splenic sequestration event. Alternatively, patients can be treated with transfusions and careful observation.

Infections

Patients with sickle cell disease have a high incidence of infections especially pneumococcal infections, due to altered B-cell immunity and granulocyte function.

Pneumonia caused by S. pneumoniae can worsen hypoxia, causing progression to vaso-occlusion. Because of such complications, the prophylactic administration of penicillin has significantly reduced morbidity and mortality from pneumonia in children <3 years of age, but prophylaxis is recommended to be continued through age 5.

Vascular Occlusion Episodes

Vascular occlusion episodes, or “sickle cell crises,” cause severe pain and organ damage. The pain typically lasts 2 to 6 days and should be managed with narcotic analgesics.

Treatment for Frequent Vaso-occlusive Crises

Hemoglobin F (HbF) has a protective effect against hemoglobin polymerization. Hydroxyurea has been found to increase HbF synthesis, which, in turn, may decrease sickling of RBC and the occurrence of disease-related complications. Hydroxyurea is used prophylactically in patients with recurrent vaso-occlusive crises, but not in treatment of the crises.

Thallasemia.

Pathophysiology

Patients with α-thalassemia have a decrease in α-globin chain production relative to β-globin chain, with the formation of β₄ (HbH) inclusion bodies. Red blood cells bearing these inclusion bodies are removed rapidly from the circulation by the reticuloendothelial system, shortening their survival. The resulting mild anemia is compensated partially by an increase in red blood cell production.

In contrast, patients with β-thalassemia have a decrease in β-globin chain production relative to α-globin chain production, which leads to an excess of α-globin chains. Unbound α-globin chains are extremely insoluble and precipitate in red blood cell precursors leading to defective erythroid maturation (ineffective erythropoiesis). The few cells that do emerge into the peripheral circulation are removed rapidly in the spleen and liver.

Clinical manifestation

The resulting profound anemia increases circulating levels of erythropoietin and causes a massive expansion of bone marrow. In sever cases this lead to bone abnormalities and growth retardation. The spleen is actively involved in removing the abnormal mature cells from the circulation and become enlarged (spleenomegaly).

Treatment

There is currently no effective treatment for thalassemia. Many patients with sever forms are blood transfusion dependant from early age. Although intensive blood transfusion programs have led to markedly improved survival, patients die from iron overload unless chelation therapy is instituted and maintained. Desferrioxamine and deferiprone are used for chelation of iron.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency anemia

Pathophysiology

G6PD is essential for the production of the reduced form of NADPH in erythrocytes. NADPH is needed to keep glutathione in a reduced form. Reduced glutathione maintain Hb in a reduced form and help erythrocytes deal with oxidative stress. In G6PD deficiency, if the erythrocytes are exposed to an oxidizing agent, the Hb becomes oxidized and forms what are known as Heinz bodies. The cell membrane damaged and some red cells hemolysed and removed from ciculation by the spleen.

Clinical manifestations

The milder form of G6PD deficiency that occurs in black population results in an acute self limiting hemolytic anemia following exposure to an oxidizing agent e.g. infection, acute illness, fava beans or some drugs. The hemolytic anemia is self limiting because the younger cells produced by the bone marrow have higher level of G6PDactivity than older cells.

In the Mediterranean form of G6PD deficiency, the enzyme activity is very low and the hemolysis is not usually self limiting and so some patients have chronic hemolytic anemia despite the absence of an obvious causative factor

Drugs to be avoided in all types of G6PD deficiencies include ciprofloxacine, nalidixic acid, sulphonamides including trimethoprim, dapsone and primaquine,

Drugs to be avoided only in sever type of G6PD deficiencies are aspirin, chloramphenicol, chloroquine, probenicid, quinidine and quinine.

Treatment

There is no specific treatment for this disorder. It is important to avoid known precipitating factors to prevent acute episode. During the acute episode the causative factor should be stopped and the patient must kept well hydrated to ensure good urine flow and prevent renal damage. Some times blood transfusions may be necessary.

Renal Insufficiency-Related Anemia

The cause of the anemia is complex but involves reduced erythropoietin (EPO) production and a shortened RBC life span. Because EPO is secreted in the kidney in response to anoxia and is responsible for normal differentiation of RBC from other stem cells, EPO is used to treat anemia in patients with renal failure.

Visa Interview

2011-12-17T00:54:00.002+05:30

Visa interview

me : Goodmorning officer
VO: good morning
vo:pass ur documents
me : passed
vo: how many universities you have applied?
me:i applied for 3 universities.they are ytu,wright sate,ltu.
vo : what is your undergraduate?
me:I have done electrical & electronic engineering with an agregate of 70.3%&.with no backlogs
vo: no backlogs?
me: yes sir
vo: which university you are going?
me :i am going to wright state university.
vo :why this university?
me:It has been ownded in the name of world famous wright brothers so it continues their spirit of innovation.i wish to specalize in electrical engineering the unversity has an excellent track on this. A part from this it has an intellectual,highly qualified faculty faculty like che in henry who is a proffesor in elec department with an experience of 11 years as a professor.university provides necessary infrastructure to support the students.
vo: sorry i cant give visa.

liposome drug delivery system

2011-12-04T00:07:00.000+05:30

SAMARTH PHARMA

Liposomal drug delivery system

What is liposome:
Liposomes are small vesicles made up of phospholipids , the very similar constituent of cell membrane, so that the pospholipid vesicles behave more or less as a micro cell inside which drug molecules can be loaded .
The phospholypid molecule is made up of hydrophylic head( containing choline, phosphate, and glycerol) , to which two long lypopylic chains(essential fatty acid chain) are attached, because of which these molecule aline themselves together in water in a very peculiar manner so as to form a membrane like bilayer.

Formation of phospholypid bilayer.
When phospholypid come in contact with aqueous solution,first they form film like alignment, water soluble head of molecule (hydrophylic ) aline and attache with water molecule, the fat soluble (hydrophobic fatty acid chains ) part of molecule is stay away from water molecules , projecting outwards.
This is a peculiar monolayer formation , up on which anther layer of phospholypid molecule aline themselves , hydrophobic chains attache to hydrophobic chains in first film , now in second layer of phospholypid hydrophobic heads are projecting outwards , this is a peculiar billayer of phospholypid.

All lypopilic heads of pospholipid molecule are aligned inside forming a spherical capsules of varying size, these vesicles may be single layered pospholipid or multi layered pospholipid.They are further categorised in to MLV (multilamellar vesicles) SUV (Small Unilamellar Vesicles) and LUV (Large Unilamellar Vesicles) each one has its unique application, depending up on the requirements of drug delivery and required targeting.

Application of liposome:
1) Drug delivery: Both water soluble and water insoluble, and peptide drug molecules can be delivered with the help of liposome. Liposome’s are used for delivering drug directly in to cells, owning to the property of liposomal membrane which is similar in properties with that of cell wall, liposome’s tend to fuse with the cell wall and can deliver a drug directly inside the cells.

How drug is carried by liposome:
Hydrophilic drug (water soluble) can be encapsulated inside the hydrophilic inner core of liposome, from where it can not come out easily as outer core is hydrophobic , which serves as a protective membrane. A hydrophobic drug can be trapped inside the lipid bi layer of liposome.

Targeted drug delivery system:
Liposome’s can be attached with antibodies against particular cells or tissue, these antibodies along with liposome’s wherein drug is loaded are then attracted by those cells or tissue against which the antibodies work, after attachment of the antibodies with the particular cell, liposome membrane fuses with cell wall and drug molecules entrapped inside the liposome are delivered inside the cell.

Application of liposome’s in anticancer drug delivery system:
Liposome’s of size smaller than 200 nm can enter cancer cells in the tumor and deliver anticancer drug directly in to affected cells, by mechanism explained above.
Liposome’s can be tagged with antibodies against cancerous tissue , and a drug against those cancer cell can be entrapped inside the liposome , these antibody tagged liposome’s get attracted to cancerous cells wall get fused with liposomal wall, and anticancer drug entrapped inside liposome’s is delivered directly inside affected cells.

Application of liposome’s in gene therapy in gene delivery RNA, DNA peptide drug delivery:
Liposomes have great application in gene therapy, as genes can be successfully delivered inside cells for desired incorporation of a gene. Also DNA and RNA and peptide drugs can be delivered directly in to cells for their desired effect on those cells.

Application of liposome’s in protecting drug from external environment:
Drugs which are highly sensitive for external environment, like PH and oxygen, and get degraded easily can be formulated in to liposome’s, for example vitamins can be formulated in liposome’s, which enhances self life of these drugs.

Optimization of cytotoxic drug treatments:
Some drugs are very toxic , for example anticancer drugs like doxorubicin, cisplatin, cytarabine, these drugs when given in conventional dosage form also have cytotoxic side effect on other body tissues and cells, therefore produce more undesired toxic side effects, with liposomal drug delivery systems , the concentration of drug required for desired effect is reduced to very low concentration , which also keeps other body tissue and cells away from such drugs harmful cytotoxic effects.

Long circulation Liposome’s:
Liposome’s can be treated with polyethylene glycol , so that they keep them selves intact for long time in blood circulation with which we can achieve long duration of drug delivery.

Phospholipids used in liposome formulation:
Natural origin: Sphingomyelin , Egg yolk Phospholipids , Soybean Phospholipids
Synthetic origin: Phosphatidylcholine, Lyso-Phosphatidylcholine , Phosphatidylserine ,Phosphatidylethanolamine , Phosphatidic Acid,

SKIN PENETRATION

2011-11-20T15:03:00.001+05:30

ANTI HERPS Agent/ anti viral drugs

2011-10-28T22:59:00.000+05:30

Like antibiotics for bacteria, antiviral drugs are a class of antimicrobials used specifically for treating viral infections. They are relatively harmless to host because they inhibit the development of pathogens instead of destroying them. Most of the antiviral agents need to be activated by viral and cellular enzymes before exerting antiviral effect. Hence, activity of enzymes and concentration of substrates will influence the efficacy of these drugs.
In majority of acute infections, viral replication is already at its peak when symptoms appear. To be effective, antiviral therapy has to be started in the incubation period, i.e has to be prophylactic.

Antiviral

CLASSIFICATION:
1. Anti-herpes virus: Idoxuridine, acyclovir, valacyclovir, famciclovir, ganciclovir, forscarnet
Except forscarnet which is an inhibitor of DNA polymerase and reverse transcriptase, others are purine and pyrimidine anlaogues.
2. Anti-retrovirus:
a. Nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Didanosine, Zalcitabine, Stavudine, Lamivudine, Abacavir
b. Non-nucleoside reverse transcriptase inhibitors (NNRTIs):Nevirapine, Efavirenz, Delaviridine
c. Protease inhibitors: Ritonavir, Indinavir, Nelfinavir, Saquinavir, Lopinavir
3. Anti-influenza virus: Amatidine, Rimantadine
4. Nonselective antiviral drugs: Ribavirin, Lamivudine, Interferon alpha
General Mechanism of Action of Nucleoside Analogues:
1. Taken up by cells
2. Converted by viral and cellualr enzymes to the triphosphate form
3. The triphosphate form inhibits:
a. DNA polymerase
b. Reverse transcriptase
c. RNA polymerase
4. Or it may get incorporated into growing DNA leading to abnormal proteins or breakage.

ANTI-HERPES VIRUS DRUGS:

1. Acyclovir and Valaciclovir: These are guanine analogues with antiviral activities against Herpes group only.
Mechanism of action:
Acyclovir –viral thymidine kinase–> AcycloGMP –cellular kinases–> AcycloGTP
AcycloGTP performs 2 functions:
a. Inhibits viral DNA polymerase competitively
b. Termination of DNA synthesis by incorporation into DNA
Mechanism of resistance development:
a. Reduced activity of viral thymidine kinase
b. Altered DNA polymerase
Use:
The activity of acyclovir on herpes group:
Herpes simplex type I > Herpes simplex type II > (Varicella-zoster virus = Epstein-Barr virus)
Cytomegalovirus (CMV) are practically not affected.
a. Genital Herpes simplex (type II)
b. Mucocutaneous H. simplex (type I) : remains localized to lips and gums
c. H.simplex encephalitis (type I)
d. H. simplex (type I) keratitis : because of good corneal penetration
e. Herpes zoster
f. Chickenpox
Adverse effects:
a. Topical: stinging and burning sensation
b. Oral: headache, nausea, malaise
c. Intravenous: rashes, sweating, emesis and fall in BP
d. Other toxicities:
i. Renal insufficiency (normalization on discontinuation of drug)
ii. Encephalopathy : tremors, lethargy, disorientation, hallucinations, convulsions and coma
Valaciclovir is an ester prodrug of acyclovir with improved oral bioavailability. It is the drug of choice in herpes zoster.
2. Famciclovir: It is used an alternative to acyclovir for genital or orolabial herpes and herpes zoster.
3. Ganciclovir:
a. Analogue of acyclovir
b. Active against all herpes viruses including CMV
c. CMV can develop ganciclovir resistance by mutation
d. Low oral bioavailability given I.V.
e. Drug of choice for CMV infection in immunosupressed patients (eg. AIDS) : pneumonia, colitis, retinitis
Adverse effects:
a. Bone marrow supression : leukopenia and thrombocytopenia
b. CNS effects: headache, behavioral psychosis, coma, convulsions
c. Rashes, fever, vomiting
4. Idoxuridine and Trifluridine:
a. Topical agent for Herpes keratitis
b. Triflurdine (also for CMV) is better for H.simplex II keratoconjunctivits
5. Forscarnet:
a. Direct inhibitor of DNA polymerase and reverse transcriptase
b. An inorganic pyrophosphate analogue
ADR:
a. Nephrotoxicity (Renal diabetes like condition, acute renal failure)
b. Hypocalcemia, hypokalemia and hypomagnesemia
c. Anemia
d. Tremor, convulsions
e. Phlebitis (administered i.v.)
Use:
a. CMV retinitis and other CMV infections resistant to gancyclovir
b. H.simplex and Varicella Zoster resistant to acyclovir
c. HIV

Read more ANTIVIRAL DRUGS: Classification and Anti-Herpes Virus drugs | Medchrome

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