Most medical research, before the 20th century, consisted of reporting cases on an individual basis to determine cause and effect (usually not very accurately). But the first know clinical trial occurred in 1747. James Lind, a Royal Navy (British) surgeon was looking for a cure/prevention for scurvy (in short, spongy gums, sores and loose and the loss of teeth in advanced cases). This was a huge problem in navys around the world, since sailors could be at sea for months.

Lind fed sailors afflicted with scurvy six different treatments and determined that a factor in citrus fruit (vitamin C) cured the disease while other foods did not. Decades later, limes were stocked on all ships, and the incidence of scurvy decreased dramatically. This is how British sailors got the nickname “limeys,” although they still had their teeth!

Lind published his results in 1753 in “A Treatise on the Scurvy” (London: A. Millar.)

Waters is actually an amazing substance. Given its small size and molecular weight, it should have a really low boiling point –but it doesn’t because of hydrogen bonding. Hydrogen bonding is not like a covalent bond like the bonds from oxygen to hydrogen in water. Hydrogen bonding is a strong attraction between the hydrogens of water which are slightly positively charged and the neighboring oxygen atoms of other water molecules which are slightly negatively charged. It’s kind of like a sticky interaction. A simple explanation for water boiling is when molecules of water escape the H-bonding web and escape into the air. This happens when water is 100 °C and more heat is applied to it.

When one adds sodium chloride to water, you create a different molecular structure than what you have with liquid water. In water containing sodium chloride, water oxygen atoms surround the positively charge sodium ions and water hydrogen atoms surround the negatively charged chloride ions. As stable as the molecular structure is for pure liquid water, the structure for liquid water containing sodium chloride is even more stable. Thus it takes an even higher temperature for a salt water solution to boil – hence salt raises the boiling point of water. It’s not a large effect, about 2 oz of salt raises the boiling point of water by 1-2 °C, but it’s real.

Varias personas me han preguntado sobre las propiedades medicinales y químicas del té. Después de todo, el resto del mundo que no toma café, lo más probable es que beba té. Resulta que el procesamiento de té también involucra un apasionante mundo de reacciones químicas. Esta bebida ha sido consumida durante miles de años y este largo historial sin producir efectos adversos, hace que los compuestos producidos en el proceso de extracción sean atractivos para el descubrimiento de fármacos. Ha habido muchos esfuerzos de investigación que reportan que el té verde es útil para combatir procesos como la arteriosclerosis, el colesterol LDL, el cáncer, enfermedad inflamatoria intestinal, diabetes, enfermedad hepática, pérdida de peso, enfermedades neurodegenerativas, e incluso la halitosis. Sin embargo, estudios controlados bien diseñados son necesarios para una confirmación científica absoluta en vivo.

El té blanco, té verde, té Oolong y el té negro provienen exactamente de la misma planta: Camelia sinensis, sin embargo, el sabor y el contenido químico se desarrolla por una “oxidación química” durante la elaboración del té. Esta oxidación se detiene mediante la aplicación de calor porque el calor inactiva las enzimas. Las enzimas y moléculas pequeñas (como los flavonoides) ocupan compartimentos específicos dentro de las células.

El proceso de oxidación se inicia inmediatamente después de “arrancar” las hojas del árbol (para más detalles sobre el té procesamiento revise Wikipedia). El té blanco y verde no se somete a la oxidación ya que el calor se aplica poco después cortar las hojas del árbol. El té blanco se hace de los brotes y hojas jóvenes y el té verde requiere hojas más maduras. Las hojas se secan a continuación y están listas en 1-2 días después de la cosecha. Aparte de la cafeína, los componentes más importantes en el té blanco y el verde son llamados flavonoides que en las plantas vivas muchas veces son responsables de los diferentes colores que atraen a los insectos y aves para la polinización y también actúan como antioxidantes para proteger contra el estrés. La inmensa mayoría de los estudios de salud se han realizado en el té verde.

Echa un vistazo a la estructura de los flavonoides en la figura de abajo. Su estructura es muy similar y al mirarlos casi se siente como estar jugando el juego de “encuentra la diferencia”. Los flavonoides se caracterizan por 3 anillos etiquetados como A, B y C y pequeños cambios en los anillos (en color rojo), permiten ser sub-clasificados en flavonas, flavanoles, flavanonas, catequinas, antocianidinas e isoflavanoides. Todos estos compuestos también se encuentran en muchas frutas (tales como los arándanos) y verduras (como brócoli) y su consumo parece promover la buena salud.

 El té Oolong es un “té semi-oxidado”, ya que se permite oxidar por un período breve antes de aplicar calor. El proceso completo tarda de 2 a 3 días.

Por último el té negro se permite oxidar en un 100%. La principal diferencia es que las hojas se cortan y se magullan para perturbar las estructuras de las células por lo que todos los jugos de la hoja (que contiene flavonoides) y enzimas (como la polifenol oxidasa) se mezclan permitiendo una oxidación completa. El proceso de oxidación toma hasta tres horas bajo una alta humedad y una temperatura óptima para la función de la enzima. Una vez que el proceso está completo, las hojas rotas se secan y se preparan para su empaque.

La siguiente figura muestra un ejemplo de oxidación de las catequinas (un flavonoide) en teaflavinas y thearubiginas por medio de la enzima polifenol oxidasa. Ahora si se puede observar que las estructuras comienzan a cambiar más. Thearubigina es la que da el color y sabor característico al té negro.

En resumen, el té blanco y verde es una mezcla de todas las clases de flavonoides y es el más cercano a lo que se encuentra en la naturaleza, de esta manera entiendo por qué muchas personas prefieren beber té verde. El té negro contiene muy pocos flavonoides y la mayoría son teaflavinas y thearubiginas. Aunque la composición química del té verde y el negro es diferente, el Departamento de Agricultura de los EE.UU ha medido y sugerido que los niveles de antioxidantes en el té verde y el negro son muy similares porque el té verde tiene una capacidad de absorción de oxígeno radical (ORAC) de 1253 y el té negro un valor ORAC de 1128 (medido en μmolTE/100g). Así que los dos tipos de té tienen la capacidad de ejercer un efecto antioxidante eliminando los radicales libres en el cuerpo.

Una cuestión de reciente debate es si la adición de leche, que es una práctica generalizada en el Reino Unido, modifica las actividades biológicas del té. Un estudio publicado en el European Heart Journal (2007) llegó a la conclusión de que la leche puede contrarrestar los efectos sobre la salud en la función vascular, tal vez debido al hecho de que los flavonoides del té se ligan a las proteínas presentes en la leche (por ejemplo, caseína) pudiendo afectar su capacidad antioxidante. Sin embargo otros estudios indicaron que aunque la concentración plasmática de catequina se reduce en el té con leche en comparación con el té negro, no afectó su actividad antioxidante beneficiosa. Vale la pena señalar que ha habido otros estudios que no han establecido un efecto negativo de la leche en las propiedades antioxidantes del té. Por lo tanto, experimentos mejor diseñados son necesarios para confirmar los hallazgos.

Hay mucho más que aprender sobre el té, así que no duden en ir a leer acerca de su origen e historia. No es de extrañar que el té se percibe como una de las bebidas culturales del Reino Unido e India y ha sido incorporado en muchas culturas, como la ceremonia del té en China y Japón. Todo lo que podemos hacer es apreciar otra maravilla medicinal regalo de nuestra madre naturaleza.

*  Por favor tengan en cuenta que este blog ha sido acerca de tés procedentes de la planta Camelia sinensis. Los tés de frutas y otras plantas se llaman “té de hierbas”.  También hay una gran variedad de tés mezclados como el ” Earl grey “, que aparte de la planta de té contiene aceite extraído de la cáscara de la naranja, bergamota.

Enlaces de interés:

http://www.nal.usda.gov/fnic/foodcomp/Data/Other/EB03_VegFlav.pdf

http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/ORAC/ORAC_R2.pdf

Several people have asked me about the medicinal and chemical properties of tea.  After all, the rest of the world that doesn’t drink coffee, most probably drinks tea. It turns out that there is also an exciting world of chemical reactions going on during tea processing.

This drink has been consumed for thousands of years and this long safety record makes the compounds produced in the extraction process attractive for drug discovery. There have been many research endeavors claiming green tea to be helpful for atherosclerosis, LDL cholesterol, cancer, inflammatory bowel disease, diabetes, liver disease, weight loss, neurodegenerative diseases and even halitosis. However, well designed controlled studies are still needed for an absolute scientific confirmation in vivo.

White tea, green tea, Oolong tea and black tea come from the exact same plant: Camelia sinensis, however the flavor and chemical content develops by a “chemical oxidation” during tea processing. This oxidation is stopped by applying heat because heat inactivates the enzymes. Enzymes and small molecules (such as flavonoids) occupy many specific compartments inside the living cells.

The process of oxidation starts immediately upon “plucking” the leaves from the tree (for details on tea processing check Wikipedia). White and Green  tea  do not undergo oxidation because heat is applied soon after picking. White tea is made from young leaves and buds and green tea requires more mature tea leaves. The leaves are then dried and are ready about 1-2 days after harvesting. Apart from caffeine, the most important components in white and green tea are called flavonoids  which give live plants the various colors that attract insects and birds for pollination and also act as antioxidants to protect them from stress.  The vast majority of health studies have been performed of green tea.

Check out the flavonoids  in the figure below. Their structure is very similar and by looking at them it almost feels like one is playing the game “spotting the difference”. Flavonoids are characterized by 3 rings labeled as A, B and C and depending on small changes in the rings (colored in red), they can be sub-classified into flavones, flavanols, flavanones, catechins, anthocyanidins and isoflavanoids. All these compounds are also found in many fruits (such as blueberries) and vegetables (such as broccoli) and their consumption appears to promote good health.

The Oolong tea is a “semi-oxidized tea” because it is allowed to oxidize for short period before applying heat. The whole process from withering to drying takes 2 to 3 days.

Finally the black tea is allowed to oxidize 100%.  The main difference is that  the leaves are cut and bruised disrupting the cell structures so all the leaf juices (containing flavonoids) and enzymes (like polyphenol oxidase) mix up allowing a complete oxidation. The oxidation process takes up to three hours under a high humidity and a optimal temperature for enzyme function. Once the process is complete, the broken leaves are dried and shaped for packing.

The figure below shows an example of oxidation of catechins (a flavonoid alsho shown above) to theaflavin and thearubigin by the enzyme polyphenol oxidase. You can see that now the structures really start looking different.  Thearubigin is what gives black tea its characteristic color and taste.

So, in summary, white and green tea contain a mixture of all kinds of flavonoids and is the closest you will get to nature, so I can appreciate why many people prefer to drink green tea. Black tea contains very few flavonoids and mostly theaflavins and thearubigins. Caffeine is present in both. Although the chemical composition of green and black tea is different, research by the U.S. Department of Agriculture has measured and suggested that levels of antioxidants in green and black tea do not differ greatly, as green tea has an oxygen radical absorbance capacity (ORAC) of 1253 and black tea an ORAC of 1128 (measured in μmolTE/100g). So both kinds of tea have the capability to exert antioxidant effect by scavenging free radicals in the body.

A question of recent debate is whether or not the addition of milk, as widely practiced in the UK, modifies the biological activities of tea. A study published in the European Heart Journal (2007) concluded that milk may counteract the health effects on vascular function, perhaps due to the fact that flavonoids in tea bind to proteins present in milk (eg. Caseine) affecting their antioxidant capacity.

However, other studies indicated that although the plasma catechin concentration is reduced in tea with milk compared to black tea, it did not affect the beneficial antioxidant activity. It is worthy to note that there have been other studies failing to establish an effect of milk on antioxidant properties of tea. Therefore, better-designed experiments are needed to confirm the findings.

There is so much more to learn about tea, so don’t hesitate to go read about its origin and history.  No wonder tea is perceived as one of Britain’s and India’s cultural beverages and has been incorporated in so many cultures, such as tea ceremonies in China and Japan.   All we can do is appreciate the medicinal wonders of another gift from mother nature.

*Please note that this blog has been about teas proceeding from the plant Camelia sinenis.  Teas made from fruits and other plants are called “herbal teas”. There are also many mixed teas like the “Earl grey” which apart from tea plant contains oil extracted from the rind of the bergamot orange.

Interesting links:

http://www.nal.usda.gov/fnic/foodcomp/Data/Other/EB03_VegFlav.pdf

http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/ORAC/ORAC_R2.pdf

Clark et al conducted a meta-analysis of 20 published studies that showed differences in systolic blood  pressure (SBP) between arms.¹ Pooled findings from non-invasive studies demonstrated that a difference in SBP of 15mmHg or more between arms correlated with a high risk of peripheral vascular disease (PVD)  and a weaker but significant association with cerebrovascular disease and cardiovascular (CV) mortality. A difference of 10mmHg or higher was associated with a high risk of PVD.  The authors concluded that a difference in SBP of 10-15 mmHg between arms might need further vascular assessment.¹

 There are several confounding factors related to this study including the fact that this was a meta-analysis, method of BP measurement (sequential vs. simultaneous) and presence of pre-existing CV risk factors as stated in an editorial by McManus et al.² Nonetheless, this study brings to light a couple of interesting points:

(1) Both the JNC 7 (seventh report of the joint national committee on prevention, detection, evaluation and treatment if high blood pressure) and ESC (European Society of Cardiology) guidelines on hypertension recommend measurement of blood pressure in both arms – I don’t think most primary care doctors are aware of that and I certainly wasn’t.

(2) This study demonstrates the importance of not only measuring blood pressure in both arms on a more routine basis but also evaluating the patient as a whole from a clinical standpoint for additional risk factors for developing CV disease. It may be beneficial checking BP in both arms in people who may be at risk of developing CV disease. Large differences in BP may prompt further evaluation and/or aggressive management of CV risk factors.

 Refs: 

1. Clark CE, et al. Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis. Lancet 2012; 6736(11): 61710-8.
2. McManus RJ, et al. Do differences in blood pressure between arms matter? Lancet 2012;6736(11): 61926-0.

This drug counters the effect of one specific mutation in the gene (G551D mutation) that accounts for 4 percent — or about 1,200 — cystic fibrosis cases in the United States.  About 30,000 Americans have cystic fibrosis. Patients with CF tend to have thick mucus in the lungs, which leads to infections and lung damage.

While this is not a cure for all CF patients, it certainly is a breakthrough in the sub-group of CF patients with the G551D mutation.

Pfizer, together with Janssen Alzheimer Immunotherapy and the Geoffrey Beene Gives Back Alzheimer’s initiative hope that an unmet need will be met through the development of simple, cost-effective, consistent tools that could be easily used to assess memory, mood, thinking and activity level over time to help improve diagnosis and monitoring of people with Alzheimer’s disease.

This is a great initiative to spur the entrepreneurial spirit of those individuals and groups who work with Alzheimer’s patients and desire a way to deliver better care to Alzheimer’s patients.  Who knows, perhaps the care you impact is the care of a loved one or someone close to you!

http://www.pfizer.com/news/press_releases/pfizer_press_releases.jsp#guid=20120126005694en&source=RSS_2011&page=1

https://www.alzheimerschallenge2012.com/

Ibuprofen ((RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid) works much the same way that aspirin works. It inhibits two enzymes called COX-1 and COX-2 (COX = cyclooxygenase). COX-1 and COX-2 are key enzymes in the production of prostaglandins which are key mediators of inflammation and fever. Excess inflammation in your body causes pain. Most of the anti-inflammatory activity of ibuprofen is due to COX-2 inhibition. Inhibition of COX-1 can cause stomach bleeding in some people although this is usually not a problem.

Acetaminophen is quite different, and it’s mechanism of action is still not completely clear. Instead of being an anti-inflammatory, acetaminophen is mostly an analgesic or anti-pain medication. Only recently has TRPA1, the Transient Receptor Potential cation channel A1 and a key ion channel involved in sensing pain, has been proposed as the target of acetaminophen. Thus if one wants to reduce swelling, acetaminophen is not the way to go. Acetaminophen does reduce fever – for reasons that aren’t apparent to me….just something else for scientists to figure out.

These aren’t the only differences. While both medications are very safe when taken as prescribed, acetaminophen hepatotoxicity (often exacerbated by alcohol consumption) is the most common cause of acute liver failure in the US…something that I should blog more about in the future. Still it’s quite amazing that these two medications that people assume are similar have such different biologies.

For instance, the writer talks about having access to her health record once entered in the clinic’s EMR with a log in and password. Historical information is critical — what the author didn’t mention was whether the EMRs could be updated remotely e.g. the exact name of the whooping cough medication she was allergic to.

Also, the article discusses that only 10% of physicians are completely digital. More and more physicians are using smart phones and social media so the comfort levels in use of digital media is there. Still, with all the incentives, uptake is slow.

But I digress from what I really wanted to write about.

Yes, EMR uptake is critical, but where are EMRs without mobile health? Connecting the patient and their health care provider to their personal health information is paramount.   To read another opinion about the obstacles to digital health records click here.

Without dialogue can we achieve better health outcomes?

How helpful is a real-time alert system to help patients remember to take their medications and a support network with the availability of care management from anywhere! (Using mHealth to Improve Quality of Life ).

Without the additional aspect of a social support network (Social Health Networks ), are we missing an opportunity to improve health outcomes?

I might be missing some “dots” but seems to me that the confluence of EMRs, mHealth, and social networking are an approach to improving outcomes through empowering the patient.

Personal experiences are quite insightful. Anyone in healthcare must listen to the voice of the patient if we are to improve health outcomes.

NOTE: The further evolution of EMRs to electronic health records (EHRs) is a topic to address in a future blog. (Here is a link for more information about the difference between EMRs and EHRs http://www.healthit.gov/buzz-blog/electronic-health-and-medical-records/emr-vs-ehr-difference)

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