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Biomedical subjects

S Joshi

Publications and source records attributed to S Joshi.

At least 37 records · Page 2Linked to original sources

Comparative bioavailability of a novel timed release and powder-filled glucosamine sulfate formulation--a multi-dose, randomized, crossover study.

OBJECTIVE: The absorption of 2 different formulations of glucosamine sulfate were studied in a randomized, multi-dose, two-way, crossover study. MATERIALS AND METHOD: In this study, a novel timed release pellet-filled hard gelatin shell capsule (TimeOsamine) was compared with a powder-filled hard gelatin shell capsule. The timed release capsule was used in a double dose with an interval of 12 h whereas the powder-filled hard gelatin capsule was used in a triple dose schedule with an interval of 8 h after 10 h pre-dose fasting. Twelve healthy male subjects were administered a 1,000 mg (2 x 500 mg) dose of timed release glucosamine sulfate (TimeOsamine) or a 1,500 mg (3 x 500 mg) dose of the powder-filled glucosamine sulfate formulation. The concentration of glucosamine was measured over the next 24 h. Pharmacokinetics properties including area under the curve (AUC), maximum concentration in plasma (C(max)), time to maximum plasma concentration (t(max)) were measured. RESULTS: The C(max) of the powder-filled and timed release formulation (TimeOsamine) was 543.12 ng/ml and 520.98 ng/ml, respectively. The t(max) of TimeOsamine was delayed by 4.13 h, whereas the powder-filled preparation was 1.00 h. The AUC0-24 of the 2 doses of TimeOsamine (2 x 500 mg = 1,000 mg) and the 3 doses of the powder-filled formulation (3 x 500 mg = 1,500 mg) was 6,263.32 ng x h/ml and 6,499.55 ng x h/ml, respectively. CONCLUSION: After reduction in the dose by 33%, the AUC0-24 of TimeOsamine is 96.37% with respect to the powder-filled formulation AUC0-24, which is comparable.

Adult↗

Lens aldose reductase inhibiting potential of some indigenous plants.

Cataract is the leading cause of blindness worldover. Diabetes is one of the major risk factors for cataractogenesis and aldose reductase (AR) has been reported to play an important role in sugar-induced cataract. In the present study, the AR inhibitory activity of Ocimum sanctum (OS), Withania somnifera (WS), Curcuma longa (CL), Azadirachta indica (AI) were studied together with their effect on sugar-induced cataractogenic changes in rat lenses in vitro. Aqueous extracts of the plants, procured from Dabur, India, were reconstituted with double distilled water to make various dilutions. AR inhibitory activity of these extracts and their anticataract potentials were evaluated in vitro in rat lenses. AR inhibitory activity of the aqueous extract of different plants was calculated considering the AR activity of normal rat lenses as 100%. The concentration of the plant extract that showed maximum AR inhibitory activity was selected to further study its effect on galactose-induced lens swelling and polyol accumulation in vitro. All the four plants were found to inhibit lens AR activity but to different extent. From dose-response curve, OS was found to be the most effective AR inhibitor followed by CL, AI and WS. The IC(50) values of OS, CL, AI and WS were calculated to be 20, 55, 57 and 89 microg/ml, respectively. OS showed a significant inhibition (38.05%) in polyol accumulation followed by CL and AI (28.4 and 25.04%, respectively). WS did not show any effect on polyol level in rat lenses. None of the plant extracts showed any significant effect on lens water content.OS possesses a significant anticataract activity in vitro and its anticataract potential could be related with its AR inhibitory effect.

Aldehyde Reductase↗

Phase I safety & preliminary acceptability of nonoxynol-9 vaginal pessary as a vaginal microbicide in low risk women in Pune, India.

BACKGROUND & OBJECTIVES: Though nonoxynol-9 (N-9) is available in India as a spermicidal pessary, data on its safety as a potential microbicide among Indian women are not available. Nonoxynol-9 containing compounds have shown anti-HIV activity in in vitro studies and protection against cervical infections. Nonoxynol-9 is being extensively evaluated as a vaginal microbicide world-wide. We assessed the safety and preliminary acceptability of nonoxynol-9 pessary as a vaginal microbicide in women at low risk for human immunodeficiency virus (HIV) infection and sexually transmitted diseases (STDs). METHODS: Twenty three HIV seronegative women enrolled in the study were given Today pessarys containing 5 per cent of nonoxynol-9 for vaginal use at bedtime for 14 days. Colposcopy was done at enrollment and on day 14 and speculum examination on day 7 to assess the local toxicity. RESULTS: Most of the women (16/23, 69.6%) did not experience any symptoms of genital irritation. The remaining 7 (30.4%, 95% CI 11.6-49.2) women reported 11 episodes of mild irritative symptoms of short duration. On clinical examination, three adverse events were reported of which one could have been product related. Eight (34.8%) women showed willingness to use the product for protection against HIV transmission if it was approved. INTERPRETATION & CONCLUSION: Nonoxynol-9 vaginal pessary was found to be safe and acceptable in once daily dose in low risk women after consecutive use for 14 days. Willingness for future use, if found safe and effective for HIV prevention was shown by 8 (34.8%) women.

Administration, Intravaginal↗

A pilot study on CD4 & CD8 cell counts in healthy HIV seronegative pregnant women.

CD4 and CD8 counts are widely used prognostic markers to assess the degree of immune impairment in HIV seropositive individuals and to monitor anti-retroviral therapy (ART). Pregnancy is considered as a physiologically immunocompromised state, hence alterations in T lymphocyte subsets may occur during pregnancy. There is a need to establish base-line values of these counts, especially in healthy pregnant women. One hundred healthy HIV seronegative pregnant women (mean age 22.5 +/- 2.99 yr) in their third trimester of pregnancy and 30 non-pregnant women (mean age 22.7 +/- 3.01 yr) were tested for their CD4 and CDS counts. In pregnant women, the CD4 and CD8 cell counts/microl were 764 +/- 249 and 547 +/- 196 and the CD4 and CD8 per cent were 56.49 +/- 8.3 and 38.03 +/- 7.2 respectively. In the non-pregnant women CD4 and CD8 counts/microl were 965 +/- 267 and 639 +/- 211 whereas the CD4 and CD8 per cent were 55.27 +/- 5.99 and 36.17 +/- 6.44 respectively. Absolute counts were significantly lower (P < 0.05) in the pregnant group as compared to the controls. A wide variation was seen in the CD4 and CD8 counts in both the groups. However, the variations in the mean CD4 and CD8 per cent were much smaller. Thus CD4 and CD8 per cent may be considered as a useful indicator of immune function rather than absolute counts, in pregnant women.

Adolescent↗

A multicentric study to evaluate efficacy and safety of cefetamet pivoxyl in lower respiratory tract infections in Indian patients.

This multicentric, open label, non-comparative study was designed to evaluate the extended spectrum of third generation oral cephalosporin, cefetamet pivoxyl in the treatment of patients with lower respiratory tract infections. This study was conducted among 111 patients with clinical, radiological and bacteriological findings consistent with the diagnosis. After obtaining written informed consent, patients were given cefetamet 500 mg tablet twice a day for 7 days. Cefetamet consistently decreased all clinical signs and symptoms at post-therapy visit. All the treated patients were either cured or improved. Cefetamet was well tolerated with a low incidence of drug related adverse events. The findings of this study indicate that cefetamet pivoxyl was well tolerated and is suitable option for the treatment of patients with lower respiratory tract infection.

Adult↗

A low prevalence of the C677T mutation in the methylenetetrahydrofolate reductase gene in Asian Indians.

The prevalence of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in Asian Indians from India was determined and the association of the mutant allele with coronary artery disease (CAD) was evaluated in a case-control study. The case group consisted of 251 patients with CAD; 195 male and 56 female aged from 29 to 82 years (mean age +/- SD, 57.5 +/- 10.6 years). The control group consisted of 216 apparently healthy individuals without evidence of CAD; 161 male and 55 female aged from 30 to 83 years (mean age +/- SD, 54.9 +/- 10.4 years). All the patients were assessed by coronary angiography. While 33 patients had normal coronaries, 23, 25 and 39 patients had single-vessel, two-vessel and triple-vessel disease, respectively. Eighty-three patients (33%) had suffered myocardial infarction less than a year to five years earlier. The C677T polymorphism in the MTHFR gene was assessed. While 31% of the controls and 38% of the patients had the heterozygous genotype, 2% of the control group and none of the patients had the mutant homozygous genotype. The overall 'T' allelic frequencies were comparable in control and patient groups (0.18 and 0.19, respectively), but the association of the sum of heterozygous and homozygous genotypes with CAD (1, 2 or 3-vessel disease) was statistically significant for females only [Odds ratio (95% confidence intervals), 2.8 (1.1-6.9), p = 0.023]. No association was found between genotype distribution and previous myocardial infarction or severity of atherosclerosis.

Adult↗

Comparative proteomic analysis of extracellular proteins of Edwardsiella tarda.

A comparison of extracellular proteins of virulent and avirulent Edwardsiella tarda strains revealed several major, virulent-strain-specific proteins. Proteomic analysis identified two of the proteins in the virulent strain PPD130/91 as flagellin and SseB, which are virulence factors in bacterial pathogens. PCR amplification and DNA sequencing confirmed the presence of the genes that encode these proteins. Our results clearly demonstrated the potency of the proteomic approach in identifying virulence factors.

Amino Acid Sequence↗

Differential role of cytosolic phospholipase A2 in the invasion of brain microvascular endothelial cells by Escherichia coli and Listeria monocytogenes.

Invasion of brain microvascular endothelial cells (BMECs) is a key step in the pathogenesis of meningitis due to Escherichia coli and Listeria monocytogenes. Although host cell actin cytoskeletal rearrangements are essential in BMEC invasion by E. coli K1 and L. monocytogenes, the underlying signaling mechanisms remain unclear. This study demonstrates that host cell cytosolic phospholipase A2 (cPLA2) contributes to E. coli K1 invasion of BMECs but not to L. monocytogenes invasion of BMECs. This difference was observed with 4-bromophenacyl bromide, a nonselective PLA2 inhibitor, and arachidonyl trifluoromethyl ketone, a selective cPLA2 inhibitor, and was confirmed with BMEC derived from cPLA2 knockout mice. Activation of cPLA2 leads to generation of intracellular arachidonic acid, which is metabolized via cyclooxygenase (COX) and lipo-oxygenase (LOX) pathways into eicosanoids. COX and LOX inhibitors also significantly inhibit E. coli K1 invasion of BMECs.

Alkaloids↗

Low carotenoid concentration and the risk of HIV seroconversion in Pune, India.

Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the integrity of the genital epithelium or by immunologic dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid levels in patients who were at risk of subsequent HIV infection. In a nested case-control study in individuals attending two sexually transmitted disease (STD) clinics in Pune, India, serum micronutrient levels were measured in 44 cases with documented HIV seroconversion (11 women and 33 men) and in STD patients matched for gender and length of follow-up with no subsequent HIV seroconversion (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low serum beta-carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with beta-carotene levels less than 0.075 micromol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio = 21.1; p =.01). No such association was observed in case of other non-provitamin A carotenoids. This study reports the first evidence of an association between low serum provitamin A carotenoid levels and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.

Adolescent↗

Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites.

AIM: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial. METHODS: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator ( approximately 5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. RESULTS: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. CONCLUSION: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

Acrylic Resins↗

Chemopreventive activity of Withania somnifera in experimentally induced fibrosarcoma tumours in Swiss albino mice.

The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties.

Administration, Oral↗

Cardioprotective potential of ocimum sanctum in isoproterenol induced myocardial infarction in rats.

Myocardial infarction (MI) was produced in rats with 85, 200 and 300 mg/kg of isoproterenol (ISO) administered subcutaneously (sc) twice at an interval of 24 h. Shift in antioxidant parameters, lactate dehydrogenase (LDH) together with morphological and histopathological changes were investigated. Two hundred mg/kg ISO dose was selected for the present study as this dose offered significant alteration in biochemical parameters along with moderate necrosis in heart. Effect of pre- and co-treatment of hydroalcoholic extract of Ocimum sanctum (Os) at different doses (25, 50, 75, 100, 200 and 400 mg/kg) was investigated against ISO (200 mg/kg) induced myocardial infarction in rats. Modulation of various biochemical parameters and membrane integrity was studied. Os at the dose of 25, 50, 75 and 100 mg/kg reduced significantly glutathione (GSH), superoxide dismutase (SOD) and LDH levels. It also inhibited the lipid peroxidation as observed by the reduced thiobarbituric acid reactive substances (TBARS) levels. In the present study Os at the dose of 50 mg/kg was found to demonstrate maximum cardioprotective effect. Above results were further confirmed by histopathological findings. Thus from the present study it is concluded that Os may be of therapeutic and prophylactic value in the treatment of MI.

Animals↗

Pattern of malignant lymphoma in the United Arab Emirates--a histopathologic and immunologic study in 208 native patients.

The aim of this study was to analyze the distribution of the various pathologic types of lymphoma in a native Arab population of the United Arab Emirates (UAE). Two hundred and eight patients with malignant lymphoma diagnosed over a 12-year period (1988-1999) were retrospectively studied morphologically and immunohistochemically with a panel of monoclonal antibodies and classified according to the revised European-American classification of lymphoid neoplasms (REAL). Of the 208 patients in the study, 41% had Hodgkin's disease (HD) and 59% had non-Hodgkin's lymphoma (NHL). The distribution of HD showed a predominance of nodular sclerosis and mixed cellularity types. Among NHLs, the most frequent type was diffuse large B cell (59% of all NHLs) followed by the Burkitt's type (13%). The proportion of primary extranodal NHL was 29%. Immunologically, the percentages of NHL with B-cell and T-cell phenotypes were 83 and 11, respectively. When the International Working Formulation was used, 34% of NHLs were classified as high grade, 59% as intermediate grade and only 7% as low-grade lymphomas.

Adolescent↗

Recovery of brain function during induced cerebral hypoperfusion.

We used the setting of clinically indicated internal carotid artery balloon test occlusions in 44 patients with inoperable carotid cavernous aneurysms or head and neck tumours to examine real-time changes in higher cerebral function that correlate with specific levels of cerebral blood flow. By making detailed haemodynamic and neurobehavioural measurements during the 30 min the carotid artery was occluded, we were able to quantify higher cerebral function patterns in relation to absolute cerebral blood flow (CBF) levels. We found that once the carotid artery was occluded, patients whose CBF averaged 47 ml/100 g/min (no different from baseline) maintained consistent performance on a sustained attention task; those whose CBF dropped to an average 37 ml/100 g/min had a reversible deterioration of sustained attention, and those whose CBF fell to 27 ml/100 g/min had impaired sustained attention that persisted until the carotid occlusion was reversed. The relevance of these results to the pathological state of clinical stroke is discussed with respect to the haemodynamic and physiological mechanisms that may determine how brain function is lost and regained in the setting of acute cerebral hypoperfusion.

Attention↗

Intake of micronutrient-rich foods in rural Indian mothers is associated with the size of their babies at birth: Pune Maternal Nutrition Study.

One third of the Indian babies are of low birth weight (<2.5 kg), and this is attributed to maternal undernutrition. We therefore examined the relationship between maternal nutrition and birth size in a prospective study of 797 rural Indian women, focusing on macronutrient intakes, dietary quality and micronutrient status. Maternal intakes (24-h recall and food frequency questionnaire) and erythrocyte folate, serum ferritin and vitamin C concentrations were measured at 18 +/- 2 and 28 +/- 2 wk gestation. Mothers were short (151.9 +/- 5.1 cm) and underweight (41.7 +/- 5.1 kg) and had low energy and protein intakes at 18 wk (7.4 +/- 2.1 MJ and 45.4 +/- 14.1 g) and 28 wk (7.0 +/- 2.0 MJ and 43.5 +/- 13.5 g) of gestation. Mean birth weight and length of term babies were also low (2665 +/- 358 g and 47.8 +/- 2.0 cm, respectively). Energy and protein intakes were not associated with birth size, but higher fat intake at wk 18 was associated with neonatal length (P < 0.001), birth weight (P < 0.05) and triceps skinfold thickness (P < 0.05) when adjusted for sex, parity and gestation. However, birth size was strongly associated with the consumption of milk at wk 18 (P < 0.05) and of green leafy vegetables (P < 0.001) and fruits (P < 0.01) at wk 28 of gestation even after adjustment for potentially confounding variables. Erythrocyte folate at 28 wk gestation was positively associated with birth weight (P < 0.001). The lack of association between size at birth and maternal energy and protein intake but strong associations with folate status and with intakes of foods rich in micronutrients suggest that micronutrients may be important limiting factors for fetal growth in this undernourished community.

Adolescent↗

Evidence of increased endothelial cell turnover in brain arteriovenous malformations.

OBJECTIVE: We hypothesized that human brain arteriovenous malformations (BAVMs) are nonstatic vascular lesions with active angiogenesis or vascular remodeling. To test this hypothesis, we assessed endothelial cell turnover in BAVMs. METHODS: We identified nonresting endothelial cells by use of immunohistochemistry for the Ki-67 antigen. From archived paraffin blocks, we selected BAVM vessels without intravascular thrombosis or embolic material in areas nonadjacent to the nidus edge. For controls, we used 50- to 100-microm diameter cortical vessels from temporal lobe cortex removed for epilepsy treatment. The Ki-67 index was calculated as a percentage of Ki-67-positive endothelial cells. The data were analyzed by the nonparametric Mann-Whitney test and reported as mean +/- standard deviation. RESULTS: Thirty-seven specimens that met the above criteria were selected. There were 26 +/- 15 vessels counted in each BAVM specimen versus 18 +/- 5 in each control cortex (n = 5). The mean Ki-67 index was higher for BAVM vessels than control cortical vessels (0.7 +/- 0.6 versus 0.1 +/- 0.2%; P = 0.005), which represented an approximately seven-fold increase in the number of nonresting endothelial cells. In the BAVM group, there was a trend for younger patients to have a wider variation and higher Ki-67 index than older patients; no trend was evident in the control group. CONCLUSION: Compared with control vessels, BAVM vessels have higher endothelial cell turnover, which suggests the presence of active angiogenesis or vascular remodeling in BAVMs.

Adult↗

Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension.

This study assessed the feasibility of augmenting cerebral blood flow (CBF) and decreasing hemispheric cerebrovascular resistance (CVR) by intracarotid papaverine during acute cerebral hypotension. Awake patients (n = 10) undergoing transfemoral balloon occlusion of an internal carotid artery (ICA) with nitroprusside (SNP)-induced systemic hypotension (10% reduction of mean arterial pressure) were studied. We measured mean femoral artery pressure (MAP), mean distal ICA pressure (P(ica)), and CBF (intracarotid 133Xe) at two time points: before and after intracarotid papaverine infusion (1 or 7 mg/min). Two patients became symptomatic immediately after ICA occlusion and were excluded. One patient developed a focal seizure during papaverine infusion. In another, the occlusion balloon deflated prematurely. Of the remaining six patients, two of the three patients who received high-dose papaverine (7 mg/min) developed transient obtundation. The remaining three patients, who received low-dose papaverine (1 mg/min), did not develop any neurologic symptoms. There was a trend for intracarotid papaverine to increase hemispheric CBF by 36% (33 +/- 10 versus 45 +/- 22 ml x 100 g(-1) x min(-1), P = .084, n = 6); papaverine decreased CVR from 1.3 +/- 0.4 to 1.0 +/- 0.3 mm Hg x ml(-1) x 100 g(-1) x min(-1) (P = .049). There was no significant change in heart rate, MAP, or P(ica) during experimental protocol. Manipulation of CVR by intracarotid papaverine during acute hemispheric arterial hypotension appears to be feasible. Further studies are needed to establish safety and efficacy.

Aged↗