Emergence of omentin as a pleiotropic adipocytokine.

"Less is more" - this is becoming the global quote on event of alarming rise in the prevalence of obesity among all age groups. The perspective of adipose tissue as merely a fat depot has changed in recent times. Focus is now being laid on the metabolic and inflammatory functions of the adipose tissue which is modulated through adipocytokines. Adipocytokines have been found to control insulin sensitivity, inflammatory activity, neuroendocrine activity, cardiovascular function, food and water intake, breeding, and bone metabolism. Few of these adipokines play a role in the positive metabolism promoting good health, while few of them pose adverse effects. Omentin is a recently identified novel adipocytokine and it falls under the category of being a good adipokine. Plasma omentin-1 levels are significantly decreased in patients with obesity, insulin resistance, and diabetes that contribute to the major components of the metabolic syndrome and other disease conditions like atherosclerosis, autoimmune disorders etc and that the review focuses on the comprehensive effects of omentin on all the major systems of the body.

Serum myeloperoxidase: a novel biomarker for evaluation of patients with acute coronary syndrome.

OBJECTIVES: Myeloperoxidase, an abundant leucocyte enzyme, is elevated in culprit lesions that have ruptured in patients with sudden cardiac injury. Multiple lines of evidence suggest an association between myeloperoxidase and inflammation and acute coronary syndrome. Myeloperoxidase has been proposed as a potent risk marker and diagnostic tool in acute coronary syndrome (ACS). Recent studies have reported the potential use of myeloperoxidase in acute coronary syndrome, but limited reports are available on its utility in different groups of ACS in the emergency department. Therefore the circulating levels of serum myeloperoxidase in patients with acute coronary syndrome and control subjects were studied. DESIGN AND SETTING: The levels of serum myeloperoxidase were measured by ELISA in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as non-cardiac chest pain (NCCP). The levels of myeloperoxidase were significantly increased in patients with ACS when compared with controls and NCCP. From the receiver operator characteristic (ROC) curve analysis, the optimum value above which myeloperoxidase can be considered positive was found to be 48.02 U/ml. The area under the curve was found to be 0.956 with 95% CI (0.934 to 0.973) (p<0.0001). A combination analysis of ROC curves of troponin, creatine kinase MB (CK-MB) and myeloperoxidase showed myeloperoxidase to be highly significant. Multivariate analysis revealed myeloperoxidase to be an independent diagnostic marker for early diagnosis of ACS. CONCLUSION: Myeloperoxidase, in contrast to troponin and CK-MB, identified patients at risk of ischaemic events, even in the absence of myocardial necrosis, thus highlighting its potent usefulness for risk stratification among patients presenting with chest pain.

Process development for the synthesis of 5'-O-(4,4'-dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)-guanosine--a potential precursor for the second generation antisense oligonucleotides: an improved process for the preparation of 2'-O-alkyl-2,6-diaminopurine riboside.

An efficient four step process for the preparation of 5'-O-(4,4'-dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)-guanosine 1 was developed. Direct 2'-O-alkylation of 2,6-diaminopurine riboside 2 was accomplished via inexpensive and commercially available reagents such as KOH, DMSO and alkyl halides at room temperature in 4-6 hrs. Pure 2'-O-(2-methoxyethyl)-DAPR 3 was isolated by crystallization from methanol. Enzymatic deamination of 3 followed by selective N2-isobutyrylation and 5'-O-dimethoxytritylation furnished desired 1 in high yield and purity. Fully optimized four step synthetic process has been scaled up to the pilot plant level.

Dose related pharmacokinetics of ofloxacin in healthy volunteers.

OBJECTIVE: To evaluate the pharmacokinetic profile of ofloxacin in healthy volunteers after single oral doses of 600 and 800 mg. DESIGN: Seven healthy volunteers were administered 600 and 800 mg of ofloxacin on two occasions with an interval of one week. Paired samples of blood and saliva were collected after 1, 2, 3, 6, 9, 12, 24, 32 and 48 hours post-dose. Urine samples were collected over a period of 0-6, 6-12 and 12-24 hours. Concentrations of ofloxacin in plasma, saliva and urine were assayed by high performance liquid chromatography. RESULTS: Increases of 22% in peak plasma concentration (Cmax) and 40% in area under the concentration-time curve (AUC0-24) were observed with the 800 mg dose. The other parameters, namely time to attain Cmax, half-life, the apparent volume of distribution, plasma and renal clearance and percentage of dose excreted in urine over 24 hours were independent of doses. The mean ratios of the concentration in saliva to the concentration in plasma ranged from 0.4-0.6, and the correlation coefficient was 0.94. CONCLUSIONS: Dose proportionality was observed in Cmax and AUC0-24 when 600 and 800 mg doses of ofloxacin were given. Ofloxacin determined in saliva seems to be suitable for therapeutic drug monitoring.

Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drug formulation: comparison of plasma and urine kinetics.

SETTING: The present study assesses bioavailability indices for rifampicin, isoniazid and pyrazinamide when administered to healthy volunteers separately or in a fixed triple-drug formulation, Rifater 125 SCT. OBJECTIVE: To compare the pharmacokinetics of rifampicin, isoniazid and pyrazinamide based on their blood concentrations up to 12 hours with the proportions of the doses of the drugs and their metabolites excreted in urine up to 12 hours, and to assess the bioavailability indices for the free and fixed triple drug formulations. DESIGN: An open cross-over study was conducted in 18 healthy volunteers with normal hepatic and renal functions to whom the drug combinations were administered in free and fixed dose formulations a week apart, to the same subject. RESULTS: Concentrations of the three drugs/metabolites were assessed in blood and urine. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both the free and the new fixed triple drug formulation. CONCLUSION: Human bioavailability studies provide direct straightforward information, particularly when studying compounds such as rifampicin and other major anti-tuberculosis drugs. The results of the present study indicate that the pharmacokinetic properties of rifampicin, isoniazid and pyrazinamide as assessed after individual and combined administration do not change when combined in a single pharmaceutical preparation. The bioavailability indices calculated based on plasma concentrations and urinary levels for all three drugs compared well.

Salivary levels of isoniazid and rifampicin in tuberculous patients.

Concentrations of isoniazid and rifampicin were determined in time-matched samples of saliva and serum from 30 tuberculous patients (18 with pulmonary tuberculosis and 12 with intestinal tuberculosis), comprising 18 slow and 12 rapid acetylators of isoniazid, following administration of isoniazid 300 mg and rifampicin 12 mg/kg. The diffusion of isoniazid into saliva was quite rapid and the salivary concentrations were similar to those in serum, suggesting that saliva could be used in place of serum for all pharmacokinetic studies with isoniazid. The salivary concentrations of rifampicin were much lower than those in serum, the mean peak concentrations being 0.9 and 8.5 microgram/ml, respectively. Further, there was evidence of a significant delay in the diffusion of rifampicin from serum to saliva.

Membrane bound cytochrome P-450 determines the optimal temperatures of NADPH-cytochrome P-450 reductase and cytochrome P-450-linked monooxygenase reactions in rat and trout hepatic microsomes.

The hepatic monooxygenase systems largely responsible for the biotransformation of drugs and other xenobiotics are comprised of NADPH-cytochrome P-450 reductase and multiple forms of cytochrome P-450. Optimal temperatures for these systems in the trout and rat are 26 degrees and 37 degrees, respectively. Purified trout and rat reductases are optimally functional at 26 degrees and 37 degrees, respectively, when added to trout and rat microsomes. However, rat reductase was shown to function optimally at 26 degrees when added to trout microsomes and trout reductase functioned optimally at 37 degrees when added to rat microsomes. Corresponding shifts in optimal temperatures of cytochrome P-450-linked 0-deethylation of 7-ethoxycoumarin occurred when these reductases were added to rat or trout microsomes. It is proposed that the phospholipid annulus surrounding the active site of membrane-bound cytochrome P-450 determines the optimal temperature of cytochrome P-450 systems.

Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis.

The results are presented of a retrospective analysis of the incidence of jaundice among 3,000 patients with pulmonary tuberculosis and of the activities of serum aspartate aminotransferase among 850 according to their isoniazid acetylator phenotype. The patients had been treated with a variety of isoniazid-containing regimens in a series of controlled clinical trials in South India. The results show that rapid acetylators are no more prone to develop isoniazid-induced hepatic toxicity than are slow acetylators.

Pyrazinamide deamidase activity in tuberculous disease.

To investigate whether pyrazinamide deamidase activity is suppressed in tuberculosis, serial serum concentrations of pyrazinamide, following 40 mg of pyrazinamide per kg, were determined in 10 patients with sputum positive pulmonary tuberculosis and in 10 control subjects without disease. The concentrations and the half-lives of pyrazinamide were similar in the 2 groups, suggesting no suppression of the deamidase activity in tuberculous patients.