Whats Happening to your Blood

Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of

noreply@blogger.com (Research Proteins) — Wed, 19 Aug 2009 19:39:00 +0000

Hemoglobin (Hb) uniquely associates with proinflammatory HDL in atherogenic mice and coronary heart disease (CHD) patients. In this paper, we report that Hb and its scavenger proteins, haptoglobin (Hp) and hemopexin (Hx) are significantly increased in apoA-1-containing particles of HDL both in mouse models of hyperlipidemia and in CHD patients, when compared with wild type mice and healthy donors, respectively. We further demonstrate that the association of Hb, Hp, and Hx proteins with HDL positively correlates with inflammatory properties of HDL and systemic inflammation in CHD patients. Interestingly, HDL from Hp(-/-) mice under atherogenic conditions does not accumulate Hb and is anti-inflammatory, suggesting that (i) Hp is required for the association of Hb with HDL and (ii) Hb.Hp complexes regulate the inflammatory properties of HDL. Moreover, treatment of apoE(-/-) mice with an apoA-1 mimetic peptide resulted in significant dissociation of Hb.Hp complexes from HDL and improvement of HDL inflammatory properties. Our data strongly suggest that HDL can become proinflammatory via the Hb.Hp pathway in mice and humans, and dissociation of Hb.Hp.Hx complexes from apoA-1-containing particles of HDL may be a novel target for the treatment of CHD.

Atherosclerosis Research Unit, Department of Medicine/Cardiology

Experts Recommend Using Haemoglobin A1C Levels for Making a Diabetes Diagnosis

noreply@blogger.com (Research Proteins) — Mon, 08 Jun 2009 15:58:00 +0000

HEMOGLOBIN A1C

By Bruce Sylvester

NEW ORLEANS -- June 6, 2009 -- A patient who reaches a glycosylated hemoglobin (Hb A1C) level of 6.5% should be diagnosed as a diabetic, according to a committee of experts from around the world meeting at the American Diabetes Association (ADA) 69th Scientific Sessions. This measurement, they added, should become a new international standard for the diagnosis of diabetes.

"A1C is a better measurement, technically, and in terms of convenience when compared to current glucose measurements -- and A1C correlates closely with the risk of diabetic retinopathy," said David M. Nathan, MD, Diabetes Center, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. Dr. Nathan chaired the expert committee presentation here on June 5.

There are presently 2 standard tests used to diagnose diabetes: the fasting plasma glucose test or the oral glucose tolerance test. The committee examined the correlation between long-term glycaemic elevations and neuropathic complications like retinopathy, and found that Hb A1C, measuring average blood-glucose control over the past 2 to 3 months, would be a better diagnostic tool.

"We wanted a measure that would indicate where clinical complications could ensue, and elevation above Hb A1C 6.5% is where the danger of diabetic retinopathy actually begins," Dr. Nathan noted.

For individuals with an elevated risk of developing diabetes (genetically or due to obesity), the committee noted that an Hb A1C of 6% but less than 6.5% is likely to put these individuals at highest risk.

Paul Robertson, MD, president for medicine and science of the ADA, added comments at a press briefing after the guidelines were presented. He said that his organisation will develop a task force to study the report and to assess the new recommendation. The ADA did release an announcement on June 5, officially acknowledging the potential significance of Hb A1C as a potential diagnostic tool without officially endorsing the recommendations of the committee yet.

The report of the international expert committee was published online ahead of print on June 5 at http://care.diabetesjournals.org; it will appear in the July issue of Diabetes Care.

Diabetes experts on the committee represented the ADA, the International Diabetes Federation, and the European Association for the Study of Diabetes.

Hemoglobin as a potential source of natural regulatory oligopeptides.

noreply@blogger.com (Research Proteins) — Tue, 12 May 2009 21:32:00 +0000

Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia. aaz@inbi.ras.ru

Theoretical structure-function analysis of all possible hemoglobin molecule fragments was performed to determine sites that could be potential sources of regulatory oligopeptides. Known data on bovine hemoglobin primary structure and information of the EROP-Moscow database concerning structure and functions of natural oligopeptides were used along with a computer program complex. A total of 6750 natural non-hemoglobin oligopeptides with hemoglobin fragments of 2-14 amino acid residues were found. Structures of 20 of them were completely identical to hemoglobin fragments. Most of the revealed oligopeptides exhibit properties of neuropeptides, antimicrobial agents, and hormones. A number of them exhibit functions previously not known for hemoglobin fragments. The possibility of natural formation of regulatory oligopeptides from hemoglobin and other food protein molecules, generation of the exogenous oligopeptide pool, their participation in regulation processes as well as accordance of results obtained here with the oligopeptide continuum concepts are discussed.

Porous nanosheet-based ZnO microspheres for the construction of direct electrochemical biosensors

noreply@blogger.com (Research Proteins) — Fri, 25 Jul 2008 14:39:00 +0000

Nanosheet-based ZnO microsphere with porous nanostructures was synthesized by a facile chemical bath deposition method followed by thermal treatment, which was explored for the construction of electrochemical biosensors. Spectroscopic and electrochemical researches revealed the ZnO-based composite was a biocompatible immobilization matrix for enzymes with good enzymatic stability and bioactivity. With advantages of nanostructured inorganic–organic hybrid materials, a pair of stable and well-defined quasi-reversible redox peaks of hemoglobin was obtained with a formal potential of −0.345 V (vs. Ag/AgCl) in pH 7.0 buffer. Facilitated direct electron transfer of the metalloenzymes with an apparent heterogeneous electron transfer rate constant (ks) of 3.2 s−1 was achieved on the ZnO-based enzyme electrode. Comparative studies demonstrated the nanosheet-based ZnO microspheres were more effective in facilitating the electron transfer of immobilized enzyme than solid ZnO microspheres, which may result from the unique nanostructures and larger surface area of the porous ZnO. The prepared biosensor displayed good performance for the detection of H2O2 and NaNO2 with a wide linear range of 1–410 and 10–2700 μM, respectively. The entrapped hemoglobin exhibits high peroxidase-like activity for the catalytic reduction of H2O2 with an apparent Michaelis-Menten constant of 143 μM. The nanosheet-based ZnO could be a promising matrix for the fabrication of direct electrochemical biosensors, and may find wide potential applications in biomedical detection and environmental analysis.
Xianbo Lua, Haijun Zhanga, Yuwen Nia, Qing Zhanga and Jiping Chen, a,

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China

Blood counts at time of complete remission provide additional independent prognostic information in acute myeloid leukemia

noreply@blogger.com (Research Proteins) — Thu, 17 Jul 2008 19:00:00 +0000

Prognostic relevance of blood counts at complete remission (CR) in acute myeloid leukemia (AML) is not clear. To address this issue, we analyzed 891 AML patients in first CR. From the data of randomly selected 446 patients (training set), we first established optimal cutoffs for neutrophil and platelet counts and hemoglobin level at CR in terms of relapse-free survival (RFS). Patients whose counts were higher than each optimal cutoff were shown to have significantly better RFS (p < 0.01 for neutrophil and platelets, and p = 0.02 for hemoglobin). Then we tested whether these cutoffs were, after accounting for better known prognostic covariates, also predictive of RFS in the remaining 445 patients (validation set). Our data revealed that higher neutrophil count was independently predictive of longer RFS in the validation set (hazard ratio 1.38, p = 0.02), as was higher platelet count (hazard ratio 1.35, p = 0.04). These findings suggest that blood counts at CR, information readily available, are useful in prognostication in AML.

ARTICLE

Non-functionalized carbon nanotube binding with hemoglobin

noreply@blogger.com (Research Proteins) — Tue, 01 Jul 2008 20:40:00 +0000

Carbon nanotube has a high potential to be used as a biosensor and drug carrier. However, its binding behavior with proteins needs to be studied before the full potential of carbon nanotube in biological studies can be realized. Although many studies have been conducted to characterize the affinity of functionalized carbon nanotube to various types of proteins, our present study for the first time reported that hemoglobin can bind with non-functionalized carbon nanotube, and this binding can be identified by Raman spectrum. Further, this binding has not changed Raman luminescence with specific excitation and emission wavelengths. The immediate application of these findings is to use non-functionalized carbon nanotube as a biosensor to measure H2S in blood in which hemoglobin takes about 37% of the total blood volume. Other potential uses of non-functionalized carbon nanotube to bind selective groups of proteins are also hinted.

ARTICLE

Glycated hemoglobin--a public health perspective

noreply@blogger.com (Research Proteins) — Tue, 05 Feb 2008 19:34:00 +0000

The burden of diabetes mellitus across the world especially in India is substantial, and much of the morbidity and mortality is due to development of diabetic complications. Control of blood glucose is important to reduce occurrence of these complications. Measurement of glycated haemoglobin (hemoglobin) values provides valuable information about long term glycemic control, and is recommended for routine monitoring by several clinical guidelines on diabetes. Monitoring and appropriate management have been shown to improve outcomes in patients with diabetes in other parts of the world. However, the adoption of glycated hemoglobin as part of routine monitoring of diabetes patients in India will need to answer issues of availability, affordability and accessibility.

Indian J Public Health. 2007 Apr-Jun;51(2):107-11.Venkataraman K, Kannan AT, Kalra OP, Gambhir JK.
Department of Community Medicine, UVMS & GTB Hospital, Delhi

Researchers discover new hemoglobin function

noreply@blogger.com (Research Proteins) — Wed, 12 Dec 2007 17:53:00 +0000

A team of researchers from Wake Forest University , the National Institutes of Health and other institutions has discovered a previously undetected chemical process within the oxygen-carrying molecule hemoglobin that could have far-reaching implications for the treatment of cardiovascular diseases.

In a paper published online Nov. 4 in the journal Nature Chemical Biology , senior authors Daniel Kim-Shapiro, professor of physics at Wake Forest, and Mark Gladwin, chief of the Vascular Medicine Branch of the National Heart, Lung and Blood Institute of the NIH, describe how hemoglobin , through a catalytic reaction that does not change its own chemical properties, converts nitrite salt to the vasodilator nitric oxide.

The paper further documents how the nitric oxide activity harnessed by hemoglobin escapes the red blood cell to regulate blood flow and how the process, surprisingly, relies on the oxidized, or rusted, form of hemoglobin , previously associated only with diseased states.

“We believe we have solved the paradox of how hemoglobin mediates the conversion of nitrite to nitric oxide in a way that it is not immediately destroyed in the red cell and so it can be effective biologically,” Kim-Shapiro says.

In the bloodstream, iron-rich hemoglobin consumes, on contact, any free nitric oxide released by the blood vessels, so the idea that hemoglobin participates in forming nitric oxide had seemed implausible until recently.

In 2003, Gladwin and collaborators at the NIH, Wake Forest and the University of Alabama discovered that nitrite salt , the same substance used to cure meat and previously thought to be biologically inert, serves in the cell as a storage pool for nitric oxide. Since then, nitrite has been the object of intense study by researchers worldwide in pursuit of new treatments for such conditions as sickle cell disease , myocardial infarction, pulmonary hypertension , stroke and atherosclerosis.

In the most recent study, the researchers conclude that the nitrite-hemoglobin reaction generates dinitrogen trioxide (N2O3), which takes one of several pathways from the red blood cell and later separates into nitric oxide (NO) and nitrogen dioxide (NO2).

The newly discovered chemistry in hemoglobin has eluded scientists for a century because the intermediate molecule, nitrite-methemoglobin , formed during the process cannot be observed by electron paramagnetic resonance spectroscopy, the most sophisticated analysis technique currently available. That has rendered the reaction “invisible” by direct observation, but indirect measurement of the process is possible.

Using a variety of biophysical techniques and by careful examination of the rates of reactions and the products that are made when experimenting with hemoglobin and nitrite , we were able to discover this reaction mechanism,” Kim-Shapiro explains.

An abstract of the paper can be accessed at http://dx.doi.org by entering the digital object identifier number 10.1038/nchembio.2007.46.

Source: Wake Forest University

The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

noreply@blogger.com (Research Proteins) — Fri, 23 Nov 2007 17:05:00 +0000

Purpose
To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT).

Methods and Materials
The records of 835 patients who underwent postoperative radiotherapy between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3–T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median hemoglobin concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (−8.8; 5.0 g/dl). Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival.

Results
Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival.

Conclusion
Individual change in hemoglobin concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients.

International Journal of Radiation Oncology*Biology*Physics
Volume 69, Issue 4, 15 November 2007, Pages 1018-1023

HEMOGLOBIN

noreply@blogger.com (Research Proteins) — Mon, 29 Oct 2007 22:23:00 +0000

Hemoglobin also spelled haemoglobin and abbreviated Hb, is the iron-containing oxygen-transport metalloprotein in the red blood cells of the blood in vertebrates and other animals. In mammals the protein makes up about 97% of the red cell’s dry content, and around 35% of the total content (including water). Hemoglobin transports oxygen from the lungs to the rest of the body, such as to the muscles, where it releases its load of oxygen. Hemoglobin also has a variety of other gas-transport and effect-modulation duties, which vary from species to species, and may be quite diverse in invertebrates.

The name Hemoglobin is the concatenation of heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme (or haem) group; each heme group contains an iron atom, and this is responsible for the binding of oxygen. The most common type of Hemoglobin in mammals contains four such subunits, each with one heme group. In humans, each heme group is able to bind one oxygen molecule, and thus, one hemoglobin molecule can bind four oxygen molecules.

Mutations in the genes for the Hemoglobin protein in humans result in a group of hereditary diseases termed the hemoglobinopathies, the best known of which is sickle-cell disease. Historically in human medicine, sickle-cell disease was the first disease to be understood in its mechanism of dysfunction, completely down to the molecular level. However, not all such globin-gene mutations result in illness. These mutations are formally recognized as hemoglobin variants rather than diseases.CapeceCapece, L., Marti, M. A., , Crespo , A Doctorovich, F. & , Estrin E D. A. , Heme protein oxygen affinity regulation exerted by proximal effects. Journal of the American Chemical Society Society1 128, 12455 , 12455-12461(2006)