Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study

OBJECTIVES: In a randomized, double-blind, crossover design, we compared the efficacy of sildenafil with placebo in patients with primary pulmonary hypertension (PPH). The primary end point was the change in exercise time on treadmill using the Naughton protocol. Secondary end points were change in cardiac index and pulmonary artery systolic pressure as assessed by Doppler echocardiography and quality of life (QOL) as assessed by a questionnaire. BACKGROUND: Primary pulmonary hypertension is a disorder with limited treatment options. Uncontrolled studies had shown sildenafil to be beneficial in the treatment of PPH. METHODS: After initial clinical evaluation, including Doppler echocardiography and treadmill exercise test, patients were randomized to placebo or sildenafil with dosages ranging from 25 to 100 mg thrice daily on the basis of body weight. The evaluation was repeated after six weeks. Then patients were crossed over to alternate therapy. Final evaluation was performed after another six weeks of treatment. RESULTS: Twenty-two patients completed the study. Exercise time increased by 44% from 475 +/- 168 s at the end of placebo phase to 686 +/- 224 s at the end of sildenafil phase (p < 0.0001). With sildenafil, cardiac index improved from 2.80 +/- 0.9 l/m2 to 3.45 +/- 1.1 l/m(2) (p < 0.0001), whereas pulmonary artery systolic pressure decreased insignificantly from 105.23 +/- 17.82 mm Hg to 98.50 +/- 24.38 mm Hg. There was significant improvement in the dyspnea and fatigue components of the QOL questionnaire. During the placebo phase, one patient died and another had syncope. There were no serious side effects with sildenafil. CONCLUSIONS: Sildenafil significantly improves exercise tolerance, cardiac index, and QOL in patients with PPH.     

Chronic granulocytic leukemia after renal transplantation

Chronic granulocytic leukemia (CGL) developed in a 31-year-old man after he underwent a third renal transplant. The leukemia was initially controlled with azathioprine sodium and prednisone therapy, but eventually it entered blast cell crisis. This was controlled with an adult acute lymphocytic leukemia protocol with an excellent response. Despite discontinuing treatment with azathioprine and with the use of busulfan to control the peripheral WBC count, the patient maintained stable renal function for one year following treatment of the blast cell crisis and subsequently died of sepsis. We suggest that CGL after renal transplantation is similar to that observed in the general population and can be treated with the usual chemotherapeutic agents for the disorder without sacrificing renal function.     

Statistical Optimization of Bioprocess Parameters for Improved Production of L-Asparaginase from Lactobacillus plantarum

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - L-asparaginase (ASNase), a tetrameric enzyme, holds comprehensive applications in food industries as a...     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

HELLP or Help: A Real Challenge

Objectives

To ascertain the prevalence, presentation, diagnosis, severity, and complications of HELLP syndrome.

Materials and Methods

This is a prospective observational study analyzing the conditions and the data of 24 cases of HELLP syndrome in a tertiary care hospital. The analysis was done for the demographic characteristics, presentation of these patients, complications associated, and the perinatal outcome.

Results

0.45 % of the patients admitted for delivery developed HELLP syndrome. Majority of the patients developed the condition in 30–36 weeks period of gestation, while five patients developed it in the postpartum period. The condition led to 12.5 % of maternal and 45.8 % of perinatal mortality.

Conclusion

HELLP syndrome is an important cause for maternal and perinatal morbidity and mortality.     

Correlation of human S100A12 (EN-RAGE) and high-sensitivity C-reactive protein as gingival crevicular fluid and serum markers of inflammation in chronic periodontitis and type 2 diabetes

Objective

The aim of the present study was to evaluate the levels and correlation of human S100A12 and high-sensitivity C-reactive protein (hs-CRP) in gingival crevicular fluid (GCF) and serum in chronic periodontitis (CP) subjects with and without type 2 diabetes mellitus (DM).

Materials and methods

A total of 44 subjects were divided into three groups: group 1 had 10 periodontally healthy subjects, group 2 consisted of 17 CP subjects and group 3 had 17 type 2 DM subjects with CP. GCF and serum levels of human S100A12 and hs-CRP were quantified using enzyme-linked immunosorbent assay and immunoturbidimetric analysis, respectively. The clinical outcomes evaluated were gingival index, probing depth and clinical attachment level and the correlations of the two inflammatory mediators with clinical parameters were evaluated.

Results

Both human S100A12 and hs-CRP levels increased from group 1 to group 2 to group 3. The GCF and serum values of both these inflammatory mediators correlated positively with each other and with the periodontal parameters evaluated (p < 0.05).

Conclusion

Human S100A12 and hs-CRP can be considered as possible GCF and serum markers of inflammatory activity in CP and DM.     

Design and synthesis of 5‐(5‐nitrothiophen‐2‐yl)‐3‐phenyl‐4,5‐dihydro‐1H‐pyrazole derivatives with improved solubility and potential antituberculosis activity

We report the design‐synthesis of several nitrothiophene containing molecules as antituberculosis agents. The molecules were designed on the basis of previously reported nitrofuran molecules in our laboratory, and the α,β‐unsaturated linker was modified to cyclized linker in order to overcome the challenge of low solubility and possible toxicity. The stereo‐electronic properties such as HOMO, LUMO, and HOMO‐LUMO gap along with other properties such as aqueous solvation energies and QPLogS values were studied. The designed molecules were synthesized and tested for in vitro antituberculosis activity, and some molecules were found to be highly active comparable to standard drugs. Further, the aqueous solubility was determined using visual inspection method and the designed molecules were found to be more soluble than their chalcone counterparts. Cytotoxicity studies were performed and the molecules were found to be non‐cytotoxic. Electroanalytical studies proved nitro reduction as the mechanism of action for these molecules. Thus, this study provides potential nitrothiophene containing hits with improved solubility and reduced chances of toxicity.