Biomedical subjects

P Raman

Publications and source records attributed to P Raman.

8 recordsLinked to original sources

PubMed2006

The Membrane Protein Data Bank.

The Membrane Protein Data Bank (MPDB) is an online, searchable, relational database of structural and functional information on integral, anchored and peripheral membrane proteins and peptides. Data originates from the Protein Data Bank and other databases, and from the literature. Structures are based on X-ray and electron diffraction, nuclear magnetic resonance and cryoelectron microscopy. The MPDB is searchable online by protein characteristic, structure determination method, crystallization technique, detergent, temperature, pH, author, etc. Record entries are hyperlinked to the PDB and Pfam for viewing sequence, three-dimensional structure and domain architecture, and for downloading coordinates. Links to PubMed are also provided. The MPDB is updated weekly in parallel with the Protein Data Bank. Statistical analysis of MPDB records can be performed and viewed online. A summary of the statistics as applied to entries in the MPDB is presented. The data suggest conditions appropriate for crystallization trials with novel membrane proteins.

Databases, Protein↗

PubMed2004

Managing equipment for emergency obstetric care in rural hospitals.

In resource-poor countries, substantial sums of money from governments and international donors are used to purchase equipment for health facilities. WHO estimates that 50-80% of such equipment remains non-functional. This article is based on experience from various projects in developing countries in Asia and Africa. The key issues in the purchase, distribution, installation, management and maintenance of equipment for emergency obstetric care (EmOC) services are identified and discussed. Some positive examples are described to show how common equipment management problems are solved.

Africa↗

PubMed2000

Role of glucose and insulin in thiazolidinedione-induced alterations in hepatic gluconeogenesis.

Previous studies from our laboratory as well as from others have suggested that the thiazolidinediones have the capacity to act as insulinomimetic agents, especially in the liver. In order to further characterize this insulinomimetic action, we evaluated the effect of troglitazone, a representative thiazolidinedione, on lactate- and glucagon-stimulated gluconeogenesis, in the presence or absence of insulin (10 nM) in isolated rat hepatocytes. The antigluconeogenic effect of troglitazone under basal (lactate-stimulated) conditions was found to be due to an elevation in the fructose 2,6-bisphosphate content, which was, however, not mediated by an activation of 6-phosphofructo 2-kinase. Troglitazone (125 and 250 microM) in the absence of insulin, produced a dose-dependent reduction in glucagon-stimulated gluconeogenesis, thereby suggesting an insulinomimetic effect. In addition, troglitazone (125 and 250 microM), in combination with insulin, produced an additive inhibition of gluconeogenesis during glucagon-stimulated conditions. However, unlike insulin, the metabolic mechanism responsible for these effects (in the presence or absence of insulin) does not involve fructose 2,6-bisphosphate.

Animals↗

PubMed2000

Titanium(IV)-mediated tandem deprotection-cyclodehydration of protected cysteine N-amides: biomimetic syntheses of thiazoline- and thiazole-containing heterocycles.

The scope and limitations of TiCl(4)-mediated Delta(2)-thiazoline synthesis via tandem deprotection-dehydrocyclization of trityl-protected cysteine N-amides is presented. While chemical yields are acceptable (53-96%), the stereochemical outcomes vary on the basis of structural considerations and reaction conditions (22-99% ee). Racemization at the C(2)-exomethine position limits the utility of this method for the formation of a thiazoline within a peptide. Treatment of a tritylated Cys-Cys dipeptide with TiCl(4) afforded the corresponding thiazole-thiazoline heterocycle 12 (38% yield, 97% ee).

Amides↗

PubMed2000

Rational design of potent human transthyretin amyloid disease inhibitors.

The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases.

Amino Acid Sequence↗

PubMed1998

Comparative effects of englitazone and glyburide on gluconeogenesis and glycolysis in the isolated perfused rat liver.

Englitazone (CP 68,722, Pfizer) is a member of a family of drugs known as thiazolidinediones. One member of this family, troglitazone (Rezulin), is currently utilized in the treatment of Type 2 diabetes. Previous studies have focused on the ability of englitazone to increase insulin sensitivity in various tissues. However, little information is available regarding the direct effect of englitazone on hepatic glucose metabolism in the absence of insulin. Therefore, the following studies were conducted to comparatively evaluate the effect of englitazone and glyburide (a representative sulfonylurea) on gluconeogenesis and glycolysis from various substrates in the isolated perfused rat liver (IPRL). In isolated perfused rat livers of 24-hr fasted rats infused with lactate (2 mM), englitazone (6.25 to 50 microM) produced a concentration-dependent decrease (32-93%) in hepatic gluconeogenesis. When dihydroxyacetone (1 mM) and fructose (1 mM) were used as metabolic substrates, englitazone inhibited gluconeogenesis by 31 and 15%, respectively, while increasing glycolysis by 42 and 50%. Similar effects on gluconeogenesis and glycolysis were observed with glyburide, even though the effects with glyburide were more acutely evident, reversible, and of a greater magnitude. Such data suggest alterations in hepatic glucose production may contribute to the decrease in plasma glucose concentrations observed in individuals treated with englitazone and glyburide. These alterations may include effects on several regulatory enzymes (e.g. fructose-1,6-bisphosphatase, pyruvate kinase, and phosphoenolpyruvate carboxykinase), which warrant further investigation.

Animals↗

PubMed1998

Effect of troglitazone (Rezulin) on fructose 2,6-bisphosphate concentration and glucose metabolism in isolated rat hepatocytes.

The effect of troglitazone, an orally effective thiazolidinedione, on lactate- and glucagon-stimulated gluconeogenesis (in the absence of insulin) was examined in hepatocytes isolated from rats under different nutritional states. Hepatocytes obtained from fed or 20-24 hr fasted male Sprague-Dawley rats were incubated in Krebs-Henseleit Bicarbonate buffer (KHBC) (in presence or absence of 10.0 mM glucose) containing 2.0 mM [U-14C]lactate (0.1-0.25 microCi) with or without 10.0 nM glucagon and troglitazone (30.0 microM) or the appropriate vehicle. Aliquots were removed at specified endpoints and assayed for glucose and fructose 2,6-bisphosphate (F-2,6-P2) concentrations. In 20-24 hour starved hepatocytes, troglitazone produced a 26.1% inhibition of lactate-stimulated gluconeogenesis. This inhibitory effect of troglitazone on hepatic gluconeogenesis was further potentiated by incubation of the cells with glucose in vitro. In hepatocytes obtained from fasted rats (and incubated with 10 mM glucose in vitro) troglitazone reduced lactate-and glucagon-stimulated gluconeogenesis by 53% and 56%, respectively. This reduction in hepatic glucose production was associated with 1.06 and 1.04 fold increase in the hepatocyte F-2,6-P2 content. In isolated hepatocytes from fed animals and incubated with 10 mM glucose in vitro, troglitazone (15 and 30 microM) did not have any effect on either lactate- or glucagon-stimulated gluconeogenesis. However, 30 microM troglitazone significantly enhanced (36%) F-2,6-P2 concentrations during lactate-stimulated gluconeogenesis. These findings demonstrate that troglitazone decreases hepatic glucose production through alterations in the activity of one or more gluconeogenic/glycolytic enzymes, depending upon the nutritional state of the animal and the presence or absence of hormonal modulation. All of the effects of troglitazone in the present study were observed in the absence of insulin, suggesting an "insulinomimetic" effect. However, this does not exclude the possibility that troglitazone may also function as an "insulin sensitizer" in hepatic and certain other tissues.

Animals↗

PubMedDate not supplied

Simultaneous occurrence of toxic epidermal necrolysis and neuroleptic malignant syndrome.

Toxic epidermal necrolysis (TEN) is an acute life-threatening blistering disease characterized by involvement of the skin, multiple mucous membranes and internal organs. It is most commonly precipitated by the administration of medications like anticonvulsants. Neuroleptic malignant syndrome (NMS) is a rare complication of neuroleptic therapy characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction. An 18-year-old girl presenting with simultaneous appearance of TEN and NMS following anti-psychotic drugs given for bipolar mood disorder, is reported for the rare association and her complete recovery.

Adolescent↗