Hypolipidemic effect of tibric acid. A comparison with clofibrate and placebo in type IV hyperlipoproteinemia.

The effects of tibric acid, clofibrate, and placebo were compared in type IV hyperlipidemic patients for a 6-month period. The patients were divided into two pathological level groups according to their baseline triglyceride levels. Compared to the placebo, both tibric acid and clofibrate reduced the mean serum triglyceride concentration in the high pathological level group; however, clofibrate was also effective in the low pathological level group. The effects on total cholesterol were less pronounced with the two drugs. No effect was observed on esterified cholesterol, phospholipids, free fatty acids, and fasting blood sugar. After a 6-week follow-up period under placebo, no rebound of the triglyceride and cholesterol levels could be observed after discontinuation of the two active drugs. The other biochemical changes observed after each active treatment are discussed in relation to the different degree of activity of each active drug and to the different baseline levels of triglycerides.     

Profile and prevalence of aspirin resistance in Indian patients with coronary artery disease

BACKGROUND: Aspirin resistance is considered to be an enigma and the data available on aspirin resistance is scarce. This study was initiated to prospectively evaluate the prevalence of aspirin resistance in patients with stable coronary artery disease by using an established method of optical platelet aggregation. METHODS AND RESULTS: We studied 50 patients who were on 150 mg of aspirin for the previous 7 days. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). The mean platelet aggregation with 10 microm of adenosine diphosphate in our patient group was 49.42 +/- 23.29% and with 0.5 mg/ ml of arachidonic acid it was 13.58 +/- 21.40%. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microm of adenosine diphosphate and a mean aggregation of > or =20% with 0.5 mg/ml of arachidonic acid. Aspirin semi responders were defined as those meeting only one of the criteria. Based on these criteria, 2.08% patients were found to be aspirin-resistant, 39.58% were aspirin semi responders and 58.33% were aspirin responders. Females tended to be more aspirin semi responsive (p = 0.08). All other parameters tested, namely, age, smoking, diabetes mellitus, hypertension, obesity, lipids, hemoglobin, platelet count, ejection fraction and drug intake did not show any statistically significant difference among the groups. Thus, in our group 41.66% patients showed inadequate response to aspirin. Conclusions: This study shows that aspirin resistance and aspirin semi responsiveness do occur in the Indian patients and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.     

Potent, orally active corticotropin-releasing factor receptor-1 antagonists containing a tricyclic pyrrolopyridine or pyrazolopyridine core

Two new classes of tricyclic-based corticotropin-releasing factor (CRF(1)) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based molecules 19g and 22a, respectively, were discovered that potently bind the recombinant CRF(1) receptor (K(i) = 3.5, 2.9 nM) and inhibit adrenocorticotropic hormone (ACTH) release from rat pituitary cell culture (IC(50) = 14, 6.8 nM). These compounds show good oral bioavailabity (F = 24%, 7.0%) and serum half-lives in rats (t(1/2) = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] = 0.27, 0.52) but tend toward large volumes of distribution (V(D) = 38, 44 L kg(-1)) and rapid clearances (CL = 70, 43 mL min(-1) kg(-1)). When given orally, both the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg(-1) doses.     

Extra-anatomic aorto-femoral graft for acute limb ischemia after type a aortic dissection repair

We report an alternative approach to revascularization of the leg in a patient with acute type A aortic dissection, where other options were not feasible. An aorto-femoral extra-anatomic conduit was used to salvage the leg after major aortic surgery where further surgery or endovascular grafting would have lead to increased morbidity.     

Re-emerging chikungunya fever: some lessons from Asia

Chikungunya is an arboviral infection that re-emerged in several Asian countries during 2005–2006 after a long period of quiescence. Several microbial, climatic, social and economic factors influenced the occurrence of this disease as well as the rapidity with which it swept across many countries resulting in significant morbidity. Prevention and control of such diseases require not only a strong public health infrastructure but also a precise understanding of the factors that provide a conducive environment for the virus to propagate and infect a large number of people in a short time period. A multipronged response with an active role by the communities is critical for combating chikungunya and other emerging infectious diseases. The paper discusses important lessons that can be learned from the recent outbreaks of chikungunya fever in Asia.     

Nucleolar staining cannot be used as a screening test for the scleroderma marker anti-RNA polymerase I/III antibodies

OBJECTIVE: Anti-RNA polymerase I/III (anti-RNAP I/III) antibodies are clinically useful markers of scleroderma, and their presence is associated with diffuse skin disease and an increased risk of cardiac and kidney involvement. Although RNAP I antibodies localize to the nucleolus, nucleolar staining by many anti-RNAP antibody-positive sera is not always observed. Nucleolar staining by anti-RNAP antibody-positive sera was examined by double staining with antifibrillarin antibodies to evaluate whether nucleolar staining can be used as a screening test for anti-RNAP I/III antibodies. In addition, the relationships between nucleolar staining and levels of anti-RNAP III antibodies were examined by enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation (IP) assay. METHODS: Sera were tested using immunofluorescent antinuclear antibodies on HEp-2 cell slides, by anti-RNAP III ELISA, and by IP assay using (35)S-labeled K562 cell extract. Nucleolar staining by anti-RNAP antibody IP-positive sera was confirmed by double staining using antifibrillarin monoclonal antibodies. The levels of anti-RNAP III antibodies were quantitated by ELISA and by IP assay using a serially diluted reference serum as a standard, and their relationship was analyzed. RESULTS: All 18 anti-RNAP I/III antibody-positive sera showed nuclear speckled patterns, but nucleolar staining was readily noticeable in only 44% of the sera. A positive correlation was found between ELISA and IP units for anti-RNAP III antibodies. The levels of anti-RNAP III antibodies and anti-RNAP I antibodies correlated well, with the exception of a few sera. Levels of anti-RNAP III antibodies were low in sera with nucleolar staining, whereas several sera with high levels of anti-RNAP I antibodies clearly showed nucleolar staining. CONCLUSION: Although some sera positive for anti-RNAP I/III antibodies clearly stain nucleoli, nucleolar staining is inconsistent and cannot be used to screen for anti-RNAP I/III antibodies.     

Preventing avian influenza in humans: the role of simple public health interventions

An influenza pandemic due to influenza virus A H5N1 subtype is considered highly likely. Strategies for prevention and control of a pandemic include actions that need to be taken by the national authorities and communities. The availability of a vaccine and antiviral drugs in sufficient quantities for billions of people in the developing world is doubtful. Simple cost effective public health interventions can significantly reduce the risk of contracting infection. These interventions include precautions that will prevent people from contracting infection from sick or dying poultry and their products, human cases and a contaminated environment. Specific measures are based on principles of cutting short the transmission of infection in humans and inactivating the virus at its source. The paper describes context specific actions that can be implemented in both rural and urban settings by the communities themselves.