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Biomedical subjects

S R Das

Publications and source records attributed to S R Das.

At least 19 recordsLinked to original sources
PubMed2006

A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV-positive patients.

BACKGROUND: Atazanavir (ATV), an HIV protease inhibitor (PI) that may be preferred for the treatment of HIV-infected patients with cardiovascular comorbidities because of its favourable effects on plasma lipids, has been associated with cardiac rhythm disturbances. OBJECTIVE: To quantify the effect of ATV on corrected QT (QTc) and QTc dispersion (QTd), markers of the potential for cardiac dysrhythmia, in patients switching from other PIs to ATV. METHODS: In this prospective, single-centre, open-label study, 12-lead electrocardiograms were performed for subjects at baseline, 2 h after the first dose of ATV, and 1 month after initiation of ATV. RESULTS: Twenty-one patients (19 received ritonavir-boosted ATV) completed the study. There was a trend towards an increase in the QTc at 2 h after the first dose [mean+/-standard deviation 3.19+/-8.0 ms; 95% confidence interval (CI) -0.47 to 6.85 ms; P=0.084]. There was no difference between QTc values at baseline and at 1 month (-1.5+/-8.75 ms; 95% CI -5.50 to 2.46; P=0.43). There was a nonsignificant decrease in the QTd between baseline and 2 h (-5.1+/-15.19 ms; 95% CI -13.22 to 2.96; P=0.197) and between baseline and 1 month (-0.61+/-15.04 ms; 95% CI -8.1 to 6.87; P=0.865). A significant increase in the PR interval (7.4+/-10.7 ms; 95% CI 2.5 to 12.25 ms; P=0.005) was observed at 1 month. CONCLUSIONS: The use of ATV did not result in increases in the QTc interval or QTd. However, PR interval monitoring may be warranted in patients with underlying heart block or those treated with atrioventricular nodal blocking agents.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Mandibular invasion in oral squamous cell carcinoma: investigation by clinical examination and orthopantomogram.

Assessing the relationship of oral squamous carcinoma with the mandible prior to definitive therapy poses a perplexing problem for the head and neck oncologist. We carried out a prospective open study of 51 (21 female and 30 male; mean age of 53.4 years) patients undergoing mandibular resections for oral squamous cell carcinoma to examine the incidence of mandibular bone invasion and to assess the predictive capabilities of clinical and radiological examination in detecting bone involvement. A detailed clinical examination was followed by radiographic evaluation of mandible for bone invasion. After resection, the mandible was sectioned serially at every cm to find the pathological bone involvement. Sensitivity, specificity, and positive and negative predictive values of clinical and radiological findings were calculated. Specimens from 25 patients (49%) (4 segmental 21 hemi) demonstrated tumour invasion on histological examination. Clinical impression of mandibular invasion showed a sensitivity of 96% and specificity of 65%, whereas radiological examination had a sensitivity of 92% and specificity of 88%. When considered together, clinical and radiological examinations were able to detect all the cases of bone invasion, but specificity was only 58%. This study advocates careful correlation of clinical and radiological findings prior to definitive therapy, as clinical examination tends to over diagnose bone invasion in tumours adjacent to the mandible. The specificity of imaging was also found to be low pointing towards the need for more specific diagnostic tools in doubtful cases. Aggressive surgical therapy, namely segmental or hemi resection of mandible is warranted in case of tumours of the lower alveolus with definite bone invasion. In case of carcinomas of the buccal mucosa and tongue the mandibular resection can be limited to that required for clearance of margins provided the radiology is negative.

Adult↗
PubMed2003

Use of telemedicine in evading cholera outbreak in Mahakumbh Mela, Prayag, UP, India: an encouraging experience.

Telemedicine (TM) services a process in which expert medical advice from afar is provided using electronic signals to transfer the medical data from one site to another. As a pilot project to assess the efficacy of TM in developing countries like India, a telemedicine center was set up at the main hospital of Mahakumbh mela--a grand religious fair, at Prayag, a city in north India. The daily reporting of the in-patient and outpatient cases at the fair revealed a surge of diarrhea cases among the pilgrims at the fair. This information was communicated to the referral center at Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), which, with the help of its microbiology department, conducted microbiological examinations of stool samples and rectal swabs of patients along with various water samples. Vibrio cholerae was isolated in 22.6% (7/31) of the samples. This information was immediately relayed to the Main Hospital at the fair online, and then to the health authorities, who took strict and prompt measures to improve hygiene. Subsequently, the number of diarrhea cases decreased considerably in a matter of a few days, and thus an epidemic disaster was averted, which could have created havoc in such a large gathering.

Aged↗
PubMed2001

The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK.

The hepatitis E virus (HEV) is the causative agent of hepatitis E, an acute form of viral hepatitis. The biology and pathogenesis of HEV remain poorly understood. We have used in vitro binding assays to show that the HEV ORF3 protein (pORF3) binds to a number of cellular signal transduction pathway proteins. This includes the protein tyrosine kinases Src, Hck, and Fyn, the p85alpha regulatory subunit of phosphatidylinositol 3-kinase, phospholipase Cgamma, and the adaptor protein Grb2. A yeast two-hybrid assay was used to further confirm the pORF3-Grb2 interaction. The binding involves a proline-rich region in pORF3 and the src homology 3 (SH3) domains in the cellular proteins. Competition assays and computer-assisted modeling was used to evaluate the binding surfaces and interaction energies of the pORF3.SH3 complex. In pORF3-expressing cells, pp60(src) was found to associate with an 80-kDa protein, but no activation of the Src kinase was observed in these cells. However, there was increased activity and nuclear localization of ERK in the pORF3-expressing cells. These studies suggest that pORF3 is a viral regulatory protein involved in the modulation of cell signaling. The ORF3 protein of HEV appears to be the first example of a SH3 domain-binding protein encoded by a virus that causes an acute and primarily self-limited infection.

Amino Acid Sequence↗
PubMed2001

5'-Nor carbocyclic 5'-deoxy-5'-(isobutylthio)adenosine and a 2',3'-dideoxy-2',3'-didehydro derivative.

The inhibition of biochemical processes requiring S-adenosylmethionine as a co-factor have led to many nucleoside-based medicinal agents. Included in this group are 5'-deoxy-5'-(isobutylthio)adenosine (SIBA), a nucleoside with antiparasitic, antiviral and antiproliferative effects, and 5'-noraristeromycin, a carbocyclic-derived nucleoside with potent antiviral properties. This report brings together the structural components of these two compounds by describing both enantiomers of carbocyclic 5-nor SIBA (3 and 4). Owing to the recent interest in 2',3'-dideoxy-2',3'-didehydro nucleosides as antiviral agents, this derivative of 3 (5) is also described. All three compounds were screened against a variety of viruses and were found to be inactive at high concentrations or at limiting concentrations for the screening methods. The viruses subjected to 3-5 were herpes simplex virus types 1 and 2, human cytomegalovirus, vaccinia virus, vesicular stomatitis virus, respiratory syncytial virus, varicelIa zoster virus, coxsackie virus, parainfluenza-3 virus, sindbis virus, punta toro virus, reovirus-1, human immunodeficiency virus, influenza virus types A and B, adenovirus type 1 and measles virus. These results suggest that the C-5' methylene of the C-5' thio-based carbocyclic nucleosides is important for their antiviral properties.

Adenosine↗
PubMed2001

Inhibition of measles virus replication by 5'-nor carbocyclic adenosine analogues.

Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world, sometimes as the result of severe, chronic, lethal disease. In an effort to develop therapies to supplement immunization strategies, a number of 5'-nor carbocyclic adenosine analogues were evaluated for anti-MV activity in CV-1 monkey kidney cells. Of those compounds tested, those either unsubstituted at C4 or possessing a hydroxyl, azido or amino substituent at that position were the most active, with particularly significant inhibition of MV, strain Chicago-1. The EC50 values against this strain ranged from <0.1 to 1 mg/ml, as determined by cytopathic effect reduction assay, and confirmed by neutral red uptake. By virus yield reduction assay (+)-(1S,25,3R,4S)-4-(6'-amino-9'H-purin-9'-yl)cyclopentane-1,2,3-triol (2) (-)-(1R,2S,3R)-1-(6'-amino-9'H-purin-9'-yl)-2,3-dihydoxycyclopent-4-ene (3) (-)-(1R,2S,3R)-1-(6'-amino-9'H-purin-9'-yl)cyclopentane-2,3-dihydoxycyclopentane (5) and (-)-(1R,2R,3R,4S)-4-amino-1-(6'-amino-9'H-purin-9'-yl)cyclopentane-2,3-diol (8) were the most potent compounds tested, all with EC90 values of < or =0.4 mg/ml. Compounds 3 and 5 were also tested against other MV strains, and similarly inhibited those strains except for four designated as Bil, Edmonston, SA and X-1108. Compound 8 did not potently inhibit these other MV strains. In addition, 3, 5 and 8 demonstrated synergistic (additive) inhibition of MV replication in combination with ribavirin at several concentrations. Compounds 3, 5 and 8 were also potent MV inhibitors even when added to infected cells 24 h after virus exposure. None of these three compounds was virucidal at concentrations that inhibited viral replication as determined by virus yield reduction assay. Most compounds tested were also not toxic at concentrations >100 mg/ml in actively growing and stationary-phase cells. Results suggest that these compounds may be clinically useful anti-MV virus agents.

Adenosine↗
PubMed2001

Cyclosporine A-induced mammary hyperplasia and hyperprolactinemia in New Zealand White rabbits.

PURPOSE: To investigate the potential activity of cyclosporin A (CsA) to induce mammary hyperplasia in New Zealand White (NZW) rabbits. METHODS: Female NZW rabbits were used throughout experiments. To simulate the conditions of immunosuppression, CsA (10 mg/kg of body weight/d) was administered intravenously on a daily basis for 14 days and methylprednisolone (5 mg/kg/d) was administered on the first two days. The CsA (10 mg/kg/d) also was administered without methylprednisolone for 14 days to another cohort of rabbits. Mammary tissue of each rabbit was palpated and serially measured during this treatment period. The CsA was discontinued, and rabbits were monitored for 14 more days during the washout period. Sequential plasma concentrations of prolactin, 17beta-estradiol, and progesterone in each blood sample were determined by use of radioimmunoassay. RESULTS: All NZW rabbits treated with CsA and methylprednisolone for immunosuppression consistently developed striking mammary tissue hyperplasia. At the end of treatment with CsA and methylprednisolone, mammary glands had extensive changes consistent with actively lactating glands. Similar but less extensive hyperplasia developed in response to CsA alone. Plasma concentration of prolactin increased during treatment and decreased during the washout period. Plasma concentration of 17beta-estradiol increased during treatment and continued to increase during the washout period. Plasma progesterone concentration decreased at the end of treatment. On discontinuation of CsA, mammary hyperplasia regressed. CONCLUSIONS: Cyclosporine A, with or without methylprednisolone, induces mammary hyperplasia and hyperprolactinemia in NZW rabbits. This rabbit model may be a reliable in vivo system by which to study immunosuppressant-induced structural and functional changes of mammary glands similar to those observed in humans.

Animals↗
PubMed1998

Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery.

Acute renal failure (ARF) is one of the major complications after cardiopulmonary bypass for open heart operations. The present study was undertaken to identify the risk factors for the development of ARF following cardiopulmonary bypass (CPB). Four hundred and forty-seven consecutive patients who underwent open heart procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean age was 55.6 +/- 14.2 (SD) years (range, 18 to 80). Dialysis was instituted whenever a patient exhibited inadequate urine output (<0.5 mL/kg/hr) for 2 to 3 hours despite correction of hemodynamic status and diuretic therapy, especially if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty variables were analyzed by univariate analysis; these included nine preoperative variables--age, sex, hypertension, atherosclerosis, diabetes mellitus, left ventricular end-diastolic dimension (LVEDD) >5 cm, preoperative congestive heart failure, renal insufficiency (serum creatinine > or =130 micromol/L on two occasions), and sepsis--10 intraoperative variables--duration of CPB, redo procedures, emergency surgery, use of intraaortic balloon pump (IABP) in operating room, use of gentamicin, use of ceftriaxone, use of sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest, duration of low mean perfusion pressure (mean pressure <50 mmHg for more than 30 minutes), operation on multiple valves--and one postoperative variable--significant hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour). Significant variables or the variables having a trend (p<0.1) to be associated with ARF were included in stepwise multiple logistic regression analyses. Three regression analyses were performed separately. The incidence of ARF requiring dialysis in the study period was 15.0%. Significant risk factors for whole group of patients (regression I) were preoperative renal insufficiency (p<0.0001), postoperative hypotension (p<0.0001), cardiopulmonary bypass time more than 140 min (p<0.005), preoperative congestive heart failure (p<0.01), and history of diabetes mellitus (p<0.01). The risk factors in the valve group of patients (regression II) were preoperative renal insufficiency (p<0.0001) and postoperative hypotension (p<0.05). Risk factors in the CABG patients (regression III) were postoperative hypotension (p=0.0001), CPB time more than 140 min (p<0.05), preoperative renal insufficiency (p<0.05), and age (p<0.05). The authors conclude that preoperative renal insufficiency and postoperative hypotension are the most important independent risk factors for ARF in postcardiac surgical patients. In addition, CPB time greater than 140 minutes and old age are also independent risk factors for ARF in CABG patients. CPB time more than 140 minutes, history of diabetes mellitus, and preoperative congestive heart failure are independent risk factors for development of ARF in our total group of patients. These findings may have important clinical implications in the prevention of ARF in postcardiac surgical patients.

Acute Kidney Injury↗
PubMed1997

Characterization of nucleoside uptake and transport in Entamoeba histolytica.

The uptake and transportation of purine and pyrimidine based nucleosides by trophozoites of axenically grown Entamoeba histolytica (HMI-IMSS) were studied. The trophozoites transported adenosine and its analog tubercidin (1 microM) at a significant rate but poor transportation was observed in case of uridine (about 10% relative rate), inosine (3%), thymidine (2%) and formycin B (1%). The Km for adenosine was 160 +/- 42 microM. Unlabeled nucleosides (100 microM) inhibited adenosine and tubercidin transport. Adenosine related compounds 5'-deoxyadenosine and nebularin inhibited adenosine and tubercidine transport by 50% or more. However, inosine related compounds guanosine, 3'-deoxyinosine and formycin B were less inhibitory. The pyrimidine nucleosides uridine, thymidine and cytidine were poorly inhibitory. 6-[(4 nitrobenzyl)-mercapto] purine ribonucleoside, an inhibitor of mammalian nucleoside transporter, inhibited adenosine or tubercidin transport in E. histolytica variably between 0-30% at 10 microM, but dilazep, a known inhibitor, was inactive upto 10 microM. Increase in temperature from 22 degrees C to 33 degrees C enhanced the rate of transport of adenosine 4.5 fold, tubercidin 7.3 fold and of inosine 4 fold. These findings along with the structure activity figures suggested that transport was mediated and not passive.

Animals↗
PubMed1995

Alloxan diabetes in Swiss mice: activity of Na(+)-K(+)-ATPase and succinic dehydrogenase.

The activities of two enzymes viz: Na(+)-K(+)-ATPase and succinic dehydrogenase (SDH) in brain and liver of alloxan diabetic Swiss albino mice are reported. Alloxan diabetes caused significant decrease in the activity of Na(+)-K(+)-ATPase reflecting reduced glucose transport across the cell membrane. On the contrary, the observed enhanced activity of the enzyme SDH is attributed to increased supply of TCA cycle substrates from accelerated oxidation of fatty acids.

Animals↗
PubMed1993

In vitro effect of alloxan on Na(+)-K(+)-ATPase and succinate dehydrogenase activities in brain and liver of mice.

The present study reports in vitro inhibition of the activities of enzymes Na(+)-K(+)-ATPase and succinate dehydrogenase by alloxan in brain and liver homogenates of Swiss mice. The Vmax of both the enzymes was reduced in presence of alloxan without any substantial alteration in Km for substrate. Lineweaver Burk's plots showed higher 1/Vmax for alloxan treated samples and convergence of both slopes to intercept-1/Km. The observations pointed to non-competitive type inhibition of the enzymes by alloxan. This may be due to the modification of essential--SH groups present within/adjacent to substrate binding sites by alloxan.

Alloxan↗
PubMed1993

Isoenzyme pattern of clones of Entamoeba histolytica.

The isoenzyme pattern of clones of E. histolytica isolated from symptomatic and asymptomatic patients of amoebiasis were determined by starch gel electrophoresis. Ten parent cultures (uncloned), 5 from symptomatic and 5 from asymptomatic patients were isolated and established in Robinsons medium as xenic cultures. A total of 100 clones were isolated from parent cultures but only 65 could be established. Starch gel electrophoresis was carried out on the uncloned and cloned cultures. The analysis showed that the 5 uncloned culture from symptomatic patients had 4 isolates with pathogenic zymodeme and 1 isolate with non-pathogenic zymodeme pattern. The presence of beta band and absence of alpha band for phosphoglucomutase (PGM) and a fast moving Hexokinase (HK) band were taken as markers of pathogenicity. The 5 cloned cultures from asymptomatic patients had three isolates with pathogenic and 2 with non-pathogenic pattern. The cloned isolates from symptomatic patients (35) had 20 pathogenic zymodemes and asymptomatic patients (30) had 15 pathogenic zymodemes. Non-pathogenic zymodeme obtained in the present study were I, IV, V, X and XIII and the pathogenic zymodemes obtained were II and XIV. The data of the study indicated that (i) asymptomatic patients also harbour pathogenic zymodemes; and (ii) zymodeme II also coexsist with zymodeme XIV in the Indian population.

Animals↗
PubMed1992

Muller cells of chicken retina synthesize 11-cis-retinol.

The amounts of endogenous retinyl palmitate, retinol and retinaldehyde were measured in the neural retina and retinal pigment epithelium (RPE) of predominantly cone (chicken), rod (rat) and more mixed (cat, human) retinae. The ratio of 11-cis to all-trans isomers of retinyl palmitate and retinol in the neural retina and the RPE increases progressively with the increase in diurnality of the species from rat to chicken. The membrane fractions of both chicken and bovine RPE enzymically isomerize all-trans retinol to 11-cis-retinol. Chicken neural retina membranes enzymically form 11-cis-retinol and all-trans-retinyl palmitate from all-trans-retinol. Light and electron microscopy revealed no contamination of chicken neural retina by RPE. Muller cells from chicken retina were isolated, cultured and characterized by immunocytochemical localization of cellular retinaldehyde-binding protein. Cultured chicken Muller cells form all-trans-retinyl palmitate, 11-cis-retinol and 11-cis-retinyl palmitate from all-trans-retinol and release most of the 11-cis-retinol into the medium. The results indicate that chicken neural retina and Muller cells in particular synthesize 11-cis-retinoids from all-trans-retinol.

Animals↗
PubMed1991

Protective and curative effects of rifampicin in Acanthamoeba meningitis of the mouse.

BALB/c mice inoculated nasally with Acanthamoeba culbertsoni, resulting in amebic encephalitis and death 3-7 days, were treated with rifampicin prophylactically (daily for 2 days with 75 and 100 mg/kg) and after infection (daily for 5 days with doses of 10-100 mg/kg). Prophylactic treatment resulted in full protection against infection, as assessed by absence of symptoms of central nervous system malfunction and negative brain culture 10 days after inoculation. Curative treatment was effective at the same doses; however, at doses of 10, 25, and 50 mg/kg, only two of six animals were free of symptoms and infection.

Acanthamoeba↗
PubMed1991

An improved PVC strip ML-ELISA technique for diagnosis of recent cases of amoebiasis.

Conventional plate ML-ELISA technique for diagnosis of recent cases of amoebiasis was converted into a simple polyvinyl chloride strip multilayer-enzyme linked immunosorbent assay (PVC strip ML-ELISA). This report details the development and preliminary characterization of the PVC strip ML-ELISA method for Entamoeba histolytica antigen detection in human fecal samples. In addition, we evaluated the relative efficacies of the PVC strip ML-ELISA and the conventional plate ML-ELISA methods by screening different categories of amoebiasis patients and other intestinal parasites. A significant correlation was found (P less than 0.01) between the two assay methods with reference to sensitivity and specificity of detecting E. histolytica antigens. However, with reference to operational case and economy, the PVC strip ML-ELISA may be performed even by paramedical technical personnel under field conditions.

Animals↗
PubMed1991

Pathogenicity and antigenic components of excysted Giardia lamblia isolated from patients in Riyadh, Saudi Arabia.

Giardia lamblia cysts were isolated from patients in Riyadh, Saudi Arabia. Cysts and trophozoites (from axenically excysted cysts) were given orally by gavage to mice to establish the pathogenicity of the Riyadh isolate. There was no effect of varying the dose of administered parasite on parasite excretion or morbidity. A typical pathologic pattern of giardiasis was demonstrated by histologic methods and electron microscopy. Antigenic components of the Riyadh isolate were compared with the Portland strain and with Entamoeba histolytica by gel diffusion immunoprecipitation and immunoblotting. There were few antigens in common between Riyadh isolate and the Portland strain, and little cross-reactivity of the Riyadh isolate with Entamoeba histolytica was observed.

Animals↗