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Biomedical subjects

P B Shah

Publications and source records attributed to P B Shah.

15 recordsLinked to original sources

Stability of rifampicin in dissolution medium in presence of isoniazid.

Rifampicin (RIF) hydrolyzes in acidic medium to form insoluble and poorly absorbed 3-Formyl rifamycin SV (3-FRSV). This study describes development of two principally different methods, Dual Wavelength UV-Vis. spectrophotometry (DW spectrophotometry) and HPTLC, to determine 3-FRSV in presence of RIF. Using DW spectrophotometry, RIF was estimated by using wavelengths 475.0 and 507.0 nm and 3-FRSV was estimated using 457.0 and 492.0 nm. In HPTLC method, a mixture of chloroform:methanol:water (80:20:2.5 v/v) was used as the mobile phase to resolve 3-FRSV from RIF and 3-FRSV was quantified at 333 nm. The linearity range for 3-FRSV was 2-10 microg/ml and 50-250 ng/spot for DW spectrophotometric method and HPTLC method, respectively, and 5-50 microg/ml for RIF using DW spectrophotometric method. Both the methods were found to be specific, accurate and reproducible. The proposed methods were successfully applied to determine the rate of degradation of RIF to 3-FRSV in dissolution medium (0.1 N HCl) and also in presence of isoniazid (INH). The rate of degradation of RIF in presence of INH was almost two times more than that of RIF alone. These methods were utilized to study the stability of RIF in market formulations of RIF and RIF with INH in dissolution medium. It has been observed that RIF degrades by 12.4% to form 3-FRSV (RIF formulations) while in presence of INH the degradation is catalyzed to about 21.5% (RIF+INH formulations), in 45 min. Thus, lower concentration of RIF may be available for absorption leading to poor bioavailability of RIF from combination dosage forms (RIF+INH) as compared to formulations containing only RIF. It is proposed that specific analytical method should be used to measure RIF in presence of 3-FRSV in a dissolution study.

Antitubercular Agents↗

The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation.

Bone morphogenetic protein 4 (BMP-4) is a vital regulatory molecule that functions throughout human development in mesoderm induction, tooth development, limb formation, bone induction, and fracture repair and is overexpressed in patients who have fibrodysplasia ossificans progressiva. The human gene encoding bone morphogenetic protein 4 (BMP-4) has been isolated and its structural organization characterized. The complete DNA sequence of an 11.2 kb region has been determined. BMP-4 mRNA is transcribed from four exons, although there is evidence that alternate first exons may be used. Transcript initiation occurs at variable positions within a GA-rich region of the DNA. The promoter region is GC-rich with no obvious TATA or CAAT consensus sequences, and contains both positive and negative transcriptional regulatory elements within the 3 kb 5' flanking region of the RNA start site. Comparison of the human and murine BMP-4 genes reveals highly conserved sequences not only in the exon-coding regions but also within the introns and 5' flanking regions. BMP-4 localizes to human chromosome 14q21 by fluorescence in situ hybridization, a location more centromeric than that recently reported. These studies provide a foundation for understanding the genetic regulation of this important gene in human development.

Animals↗

Bivalirudin compared with heparin during coronary angioplasty for thrombus-containing lesions.

OBJECTIVES: We investigated whether bivalirudin is more effective than heparin in preventing ischemic complications in high risk patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. BACKGROUND: Heparin is administered during coronary angioplasty to prevent closure of the dilated vessel. Bivalirudin (Hirulog) is a direct thrombin inhibitor that can be safely substituted for heparin during angioplasty. Bivalirudin has several theoretic advantages over heparin as an anticoagulant agent. METHODS: We performed an observational analysis of the Hirulog Angioplasty Study in which 4,098 patients with unstable or postinfarction angina were randomized to receive either bivalirudin or heparin during coronary angioplasty. The study group for this analysis consisted of 567 patients who had thrombus-containing lesions on angiography. The primary end point was death, myocardial infarction, emergency coronary artery bypass graft surgery or abrupt vessel closure before hospital discharge. RESULTS: Patients with thrombus-containing lesions had a higher incidence of myocardial infarction (5.1% vs. 3.2%, p = 0.03) and abrupt vessel closure (13.6% vs. 8.3%, p < 0.001) than those without thrombus. In patients with thrombus-containing lesions, however, the incidence of the primary end point was not different between the bivalirudin and heparin treatment groups. Furthermore, no difference in the incidence of ischemic events at 6 months was seen between the treatment groups. CONCLUSIONS: Bivalirudin is not more effective than heparin in preventing ischemic complications in patients undergoing coronary angioplasty for thrombus-containing lesions detected by angiography. Other approaches, perhaps involving potent anti-platelet agents, should be considered for patients with thrombus-containing lesions.

Aged↗

Water dynamics and population pressure in the Nepalese Himalayas.

The authors investigate the impact of water shortages, especially water for irrigation, on development in Nepal. "The problems associated with hydropower development will be illustrated by using the Kulekhani watershed project as a case study." The possible future effects on food supplies and health are discussed.

Asia↗

Rabbit complement lyses tumor cells without massive C3 deposition.

These experiments were performed to determine why rabbit complement lyses tumor cells very efficiently, while not having particularly strong activity in hemolytic assays or in any other complement assay. The target cells used were human tumor cells coated with three different mouse IgG(2a) monoclonal antibodies, and complement from 5 mammalian species were tested. In antibody titration experiments, rabbit complement was found to lyse target cells at a relatively low antibody concentration, insufficient to allow lysis by complement of other species. Since this result was still observed after absorption of rabbit serum with target cells, the potency of rabbit complement cannot be attributed to the presence of natural antibodies. We then assayed C3 deposition on target cells, using two types of (125)I-labeled anti-C3 Abs to measure C3 deposition: goat antibodies specific for C3 of the human, guinea pig, rabbit, rat or mouse, and chicken antibodies to human C3 which cross-react with C3 of other mammals. Unexpectedly, complement of the human, rat, guinea pig, and BUB mouse deposited large amounts of C3 on the surface of target cells, while rabbit complement deposited 100-1,000 fold less. We discuss the possible reasons that C3 deposition does not correlate with cytotoxicity, and may indeed be inversely related. These data indicate that there is a fundamental difference in the complement cascade between rabbits and the other species tested. The potent lytic activity of rabbit complement is likely to be related to this difference, although the mechanism is not yet understood.

Animals↗

Spinal deformity in patients who have fibrodysplasia ossificans progressiva.

We reviewed roentgenograms and clinical records in order to characterize the spinal deformity in forty patients who had an established diagnosis of fibrodysplasia ossificans progressiva. Twenty-six (65 per cent) of the patients had scoliosis, which, according to the clinical records and the recollection of the patients, had been present during childhood. Twenty-three (88 per cent) of the twenty-six curves were unbalanced c-shaped curves, while the remaining three (12 per cent) were balanced s-shaped curves. Twenty-one (91 per cent) of the twenty-three c-shaped curves involved the thoraco-lumbar or lumbar spine. The c-shaped curves ranged in magnitude from 15 to more than 80 degrees. Curves became rigid by early adulthood and many resulted in severe pelvic obliquity with impaired sitting or standing balance. An osseous bridge developed between the posterolateral aspect of the iliac crest and the posterolateral aspect of the rib cage in twenty-two (55 per cent) of the forty patients. Nineteen (86 per cent) of these twenty-two patients had scoliosis; there was a significant association between the development of scoliosis and the presence of the osseous bridge (p < 0.005). Ossification of the paravertebral muscles and fascia during the first decade of life limited the development of a normal thoracic kyphosis in ten (42 per cent) of twenty-four patients for whom lateral roentgenograms of the spine were available. A spinal orthosis was used to treat the scoliosis in two patients, but this method resulted in breakdown of the skin and failed to halt progression of the curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Correlation between dissolution characteristics and absorption of methaqualone from solid dosage forms.

A methaqualone tablet in two strengths, 150 and 300 mg, was developed. The dissolution rate of an experimental formulation in pH 7.0 phosphate buffer, measured by the resin flask method, was shown to correlate with bioavailability in humans. The dissolution rate criterion was used to develop the final tablet formulation. Bioavailability of this formulation in two strengths was compared with a commercial capsule formulation and a slowly dissolving tablet formulation. Correlation between dissolution rate and bioavailability was shown in freshly prepared methaqualone tablet formulations. Bioavailability of tablets under accelerated stability testing conditions remained unaltered, whereas the dissolution rates in pH 7 phosphate buffer decreased, using the resin flask method. A rotating-flask method was developed, and dissolution in 0.1 N HCl at 2 rpm correlated with the bioavailability of both new and aged tablet formulations.

Absorption↗