Kidney function
GFR is best measured by injecting compounds such as inulin, radioisotopes such as 51chromium-EDTA, 125I-iothalamate, 99mTc-DTPA or radiocontrast agents such as iohexol, but these techniques are complicated, costly, time-consuming and have potential side-effects. Creatinine is the most widely used biomarker of kidney function. It is inaccurate at detecting mild renal impairment, and levels can vary with muscle mass and protein intake. Formulas such as the Cockcroft and Gault formula and the MDRD formula try to adjust for these variables.
Cystatin C has a low molecular weight (approximately 13.3 kilodaltons), and it is removed from the bloodstream by glomerular filtration in the kidneys. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise. Serum levels of cystatin C are a more precise test of kidney function (as represented by the glomerular filtration rate, GFR) than serum creatinine levels. This finding is based mainly on cross-sectional studies (on a single point in time). Longitudinal studies (that follow cystatin C over time) are scarcer; some studies show promising results. Cystatin C levels are less dependent on age, sex, race and muscle mass compared to creatinine. Cystatin C measurements alone have not been shown to be superior to formula-adjusted estimations of kidney function. As opposed to previous claims, cystatin C has been found to be influenced by body composition. It has been suggested that cystatin C might predict the risk of developing chronic kidney disease, thereby signaling a state of 'preclinical' kidney dysfunction.
Studies have also investigated cystatin C as a marker of kidney function in the adjustment of medication dosages.
Cystatin C levels have been reported to be altered in patients with cancer, (even subtle) thyroid dysfunction and glucocorticoid therapy in some but not all[ situations. Other reports have found that levels are influenced by cigarette smoking and levels of C-reactive protein. Levels seem to be increased in HIV infection, which might or might not reflect actual renal dysfunction. The role of cystatin C to monitor GFR during pregnancy remains controversial. Like creatinine, the elimination of cystatin C via routes other than the kidney increase with worsening GFR.
cardiovascular disease
Kidney dysfunction increases the risk of death and cardiovascular disease. Several studies have found that increased levels of cystatin C are associated with the risk of death, several types of cardiovascular disease (including myocardial infarction, stroke, heart failure, peripheral arterial disease and metabolic syndrome) and healthy aging. Some studies have found cystatin C to be better in this regard than serum creatinine or creatinine-based GFR equations. Because the association of cystatin C with long term outcomes has appeared stronger than what could be expected for GFR, it has been hypothesized that cystatin C might also be linked to mortality in a way independent of kidney function. In keeping with its housekeeping gene properties, it has been suggested that cystatin C might be influenced by the basal metabolic rate.
Neurological disorders
Mutations in the cystatin 3 gene are responsible for the Icelandic type of hereditary cerebral amyloid angiopathy, a condition predisposing to intracerebral haemorrhage, stroke and dementia. The condition is inherited in a dominant fashion.
Since cystatin 3 also binds amyloid β and reduces its aggregation and deposition, it is a potential target in Alzheimer's disease. Although not all studies have confirmed this, the overall evidence is in favor of are role for CST3 as a susceptibility gene for Alzheimer's disease. Cystatin C levels have been reported to be higher in subjects with Alzheimer's disease.
The role of cystatin C in multiple sclerosis and other demyelinating diseases (characterized by a loss of the myelin nerve sheath) remains controversial.
OTHER ROLES
Cystatin C levels are decreased in atherosclerotic (so-called 'hardening' of the arteries) and aneurysmal (saccular bulging) lesions of the aorta. Genetic and prognostic studies also suggest a role for cystatin C. Breakdown of parts of the vessel wall in these conditions is thought to result from an imbalance between proteinases (cysteine proteases and matrix metalloproteinases, increased) and their inhibitors (such as cystatin C, decreased).
A few studies have looked at the role of cystatin C or the CST3 gene in age-related macular degeneration. Cystatin C has also been investigated as a prognostic marker in several forms of cancer. Its role in pre-eclampsia remains to be confirmed.
LONGER THE BELT , LESSER THE LIFE SPAN!
10 March, 2011
06 March, 2011
CYSTATIN C ASSAY
This post is specially for my esteemed colleague Dr.Deepa from M.V Hospital for Diabetes.
Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin or neuroendocrine basic polypeptide), a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's disease.
In humans, all cells with a nucleus (cell core containing the DNA) produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and bodily fluids. It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) and probably one of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes). Cystatin C belongs to the type 2 cystatin gene family.
Cystatin C was first described as 'gamma-trace' in 1961 as a trace protein together with other ones (such as beta-trace) in the cerebrospinal fluid and in the urine of patients with renal failure. Grubb and Löfberg first reported its amino acid sequence. They noticed it was increased in patients with advanced renal failure. It was first proposed as a measure of glomerular filtration rate by Grubb and coworkers in 1985.
i will be posting more details on Cystatin c assay in my next post...
Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin or neuroendocrine basic polypeptide), a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's disease.
In humans, all cells with a nucleus (cell core containing the DNA) produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and bodily fluids. It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) and probably one of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes). Cystatin C belongs to the type 2 cystatin gene family.
Cystatin C was first described as 'gamma-trace' in 1961 as a trace protein together with other ones (such as beta-trace) in the cerebrospinal fluid and in the urine of patients with renal failure. Grubb and Löfberg first reported its amino acid sequence. They noticed it was increased in patients with advanced renal failure. It was first proposed as a measure of glomerular filtration rate by Grubb and coworkers in 1985.
i will be posting more details on Cystatin c assay in my next post...
02 March, 2011
NONINVASIVE GLUCOMETER PROTOTYPE DREAMS OF FUTURE!!
Designer Tobias Förtsch has created a virtual prototype for a noninvasive (and nonexistent) glucose monitor that seems to be inspired by iPod MP3 players. The only problem, of course, is that the search goes on for technology that can properly do glucose measurements without having people prick themselves for a drop of blood.
The small device measures sugar levels using a display with an LED scale between a low result and a high result in different colors. Low sugar levels are shown in red. A normal level appears in white white and a high level goes orange. It stores the result and transfers it via bluetooth to a mobile phone and computer so your doctor has instant access.
The flexibility comes in how you measure your levels. A detachable sensor clips to your earlobe and gives you auditory feedback when your levels get to high. The same info gets transfered to your phone and computer. If your blood chemistry gets out of hand, a call can be made via your mobile to alert your doctor.
The small device measures sugar levels using a display with an LED scale between a low result and a high result in different colors. Low sugar levels are shown in red. A normal level appears in white white and a high level goes orange. It stores the result and transfers it via bluetooth to a mobile phone and computer so your doctor has instant access.
The flexibility comes in how you measure your levels. A detachable sensor clips to your earlobe and gives you auditory feedback when your levels get to high. The same info gets transfered to your phone and computer. If your blood chemistry gets out of hand, a call can be made via your mobile to alert your doctor.
NEW AGENTS FOR Rx OF DIABETES - BASIC PRINCIPLE!!
Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from the beta cells of the islets of Langerhans after eating, even before blood glucose levels become elevated. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. As expected, they also inhibit glucagon release from the alpha cells of the Islets of Langerhans. The two main candidate molecules that fulfill criteria for an incretin are glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (also known as: glucose-dependent insulinotropic polypeptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
GLP-1 (7-36) amide is not very useful for treatment since it must be administered by continuous subcutaneous infusion. Several long-lasting analogs that have insulinotropic activity have been developed and two, exenatide (Byetta) and liraglutide (Victoza), have been approved for use in the U.S. The main disadvantage of these GLP-1 analogs is that they must be administered by subcutaneous injection.
Another approach is to inhibit the enzyme that inactivates GLP-1 and GIP, DPP-4.
Several DPP-4 inhibitors that can be taken orally as a tablet have been developed.
Few available in India are
Sitagliptin
Vildagliptin
Saxagliptin
GLP-1 (7-36) amide is not very useful for treatment since it must be administered by continuous subcutaneous infusion. Several long-lasting analogs that have insulinotropic activity have been developed and two, exenatide (Byetta) and liraglutide (Victoza), have been approved for use in the U.S. The main disadvantage of these GLP-1 analogs is that they must be administered by subcutaneous injection.
Another approach is to inhibit the enzyme that inactivates GLP-1 and GIP, DPP-4.
Several DPP-4 inhibitors that can be taken orally as a tablet have been developed.
Few available in India are
Sitagliptin
Vildagliptin
Saxagliptin
TASPOGLUTIDE
Taspoglutide is a pharmaceutical drug. It is a glucagon-like peptide-1 analog, under investigation for treatment of type 2 diabetes being co-developed by Ipsen and Roche.
Two phase II trials reported it was effective and well tolerated.
Of the eight planned phase III clinical trials of weekly taspoglutide (4 against exenatide, sitagliptin, insulin glargine, and pioglitazone) at least five were active in 2009. Preliminary results in early 2010 were favourable. (At least one of the 8 planned phase III trials had not started recruiting by end 2009.)
As of September 2010, Roche had halted Phase III clinical trials due to a incidences of serious hypersensitivity reactions and gastrointestinal side effects.
Two phase II trials reported it was effective and well tolerated.
Of the eight planned phase III clinical trials of weekly taspoglutide (4 against exenatide, sitagliptin, insulin glargine, and pioglitazone) at least five were active in 2009. Preliminary results in early 2010 were favourable. (At least one of the 8 planned phase III trials had not started recruiting by end 2009.)
As of September 2010, Roche had halted Phase III clinical trials due to a incidences of serious hypersensitivity reactions and gastrointestinal side effects.
ABLIGLUTIDE
Albiglutide is a GLP-1 analog drug under investigation by GlaxoSmithKline for treatment of type 2 diabetes. It is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin.
Albiglutide has a half life of 4 to 7 days, which is considerably longer than the other two GLP-1 analogs approved for market use, exenatide (Byetta) and liraglutide (Victoza). GLP-1 drugs are currently only available for subcutaneous administration on a daily basis, so a GLP-1 drug with a longer half-life is desirable. Such a drug would only need to be injected biweekly or weekly instead of daily, reducing the discomfort and inconvenience of GLP-1 administration considerably.
It has not yet been determined whether albiglutide is as effective an antidiabetic agent as GLP-1 drugs currently on the market, and final data remains to be published regarding the incidence of adverse effects related to the drug. To evaluate the efficacy and safety of the drug, albiglutide is undergoing eight Phase III clinical trials.
Albiglutide has a half life of 4 to 7 days, which is considerably longer than the other two GLP-1 analogs approved for market use, exenatide (Byetta) and liraglutide (Victoza). GLP-1 drugs are currently only available for subcutaneous administration on a daily basis, so a GLP-1 drug with a longer half-life is desirable. Such a drug would only need to be injected biweekly or weekly instead of daily, reducing the discomfort and inconvenience of GLP-1 administration considerably.
It has not yet been determined whether albiglutide is as effective an antidiabetic agent as GLP-1 drugs currently on the market, and final data remains to be published regarding the incidence of adverse effects related to the drug. To evaluate the efficacy and safety of the drug, albiglutide is undergoing eight Phase III clinical trials.
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