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Biomedical subjects

A Mukherjee

Publications and source records attributed to A Mukherjee.

At least 19 recordsLinked to original sources

Clastogenic effect of fenfluramine in mice bone marrow cells in vivo.

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.

Administration, Oral

Association of HLA antigens with differential responsiveness to Mycobacterium w vaccine in multibacillary leprosy patients.

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness to Mycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium, Mycobacterium w, which has cross-reactive antigens with M. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8 + 9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to the M. w vaccine. However, these associations were not significant after P correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness to M. w vaccine.

Cross Reactions

In vivo effects of anti-leprosy drugs on the rat peritoneal macrophages and lymphocyte subpopulations.

The present study describes the in vivo effects of anti-leprosy drugs on rat peritoneal macrophages and T-cell homeostasis. It was observed that BCG-elicited rat peritoneal macrophages produced more H2O2 and expressed more Ia antigen on their cell surfaces compared with resident peritoneal macrophages. Furthermore, elicited macrophages isolated from rats administered multidrug therapy (MDT), consisting of dapsone, clofazimine and rifampicin in high dose (10 x MDT) released more O2-. On the contrary, there was a significant decrease in the Ia antigen expression on these macrophages. Anti-leprosy drug treatment in high dose (10 x MDT) decreased the total number of blood T-helper (W3/25+) cells and increased the total number of blood T-suppressor (OX-8+) cells which resulted in a significant decrease in a W3/25: OX-8 ratio. Electron microscopy of elicited macrophages isolated from 10 x MDT treated rats showed development of many filipodia compared with control macrophages. These data show that 10 x MDT treatment in rats for 1 month alters the homeostasis of blood T-cell subpopulations which perhaps decreases the Ia expression on macrophages. However, the increase in O2- production and the appearance of filipodia on the macrophages is due to a direct effect of drugs on the macrophages. MDT treatment for 1 month in a therapeutic dose has no effect on the above-mentioned parameters.

Animals

Evaluation of pan masala for toxic effects on liver and other organs.

The acute and chronic oral toxicity of pan masala (betel quid without betel leaf) was assessed in gavage studies in rats. Clinical parameters (liver and serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase and alkaline phosphatase) and organ weights were measured. The results indicate that chronic feeding of pan masala impaired liver function, as indicated by changes in enzyme activity, and decreased relative weights of the gonads and brain.

Animals

Genotoxicity studies of the food additive ester gum.

Ester gum (EG) is used in citrus oil-based beverage flavourings as a weighting or colouring agent. In the present study, concentrations of 50, 100 and 150 mg/kg body weight were administered orally to male Swiss albino mice, and sister chromatid exchange and chromosomal aberration were used as the cytogenetic endpoints to determine the genotoxic and clastogenic potential of the food additive. Although EG was weakly clastogenic and could induce a marginal increase in sister chromatid exchange frequencies, it was not a potential health hazard at the doses tested.

Administration, Oral

Intravesical BCG treatment for superficial bladder cancer: long-term results using two different strains of BCG.

A total of 21 patients received intravesical BCG for the prevention of recurrence of superficial transitional cell carcinoma of the bladder. Twelve patients received the Glaxo strain and 9 the Pasteur strain of the bacillus. Although thought to have different anti-tumour activities owing to a difference in antigenicity, these 2 strains produced similar tumour-free rates at 5 years' mean follow-up with an overall tumour-free rate of 43%.

Administration, Intravesical

Ureteric stone management using a second generation lithotriptor.

A series of 209 consecutive patients with ureteric calculi underwent 296 extracorporeal shock wave lithotripsy treatments on the Siemens Lithostar over a 25-month period; 123 stones were upper ureteric, 30 mid-ureteric and 56 lower ureteric; 46.9% were right-sided stones, 53.6% were left-sided and 0.5% (1 patient) were bilateral. On referral, 60 patients had stents and 15 had nephrostomies for obstruction. All treatments were performed without anaesthesia except for 9 patients in whom stent insertion or ureteroscopic manipulations were attempted concomitant to ESWL. The average number of treatments was 1.42, with 27.5% of patients requiring more than 1 treatment. The average number of shocks per treatment was 3995 and the average hospital stay was 1.79 days. Complete clearance of the stone was achieved in 82% of upper ureteric stones, 89% of mid-ureteric and 80% of lower ureteric stones. The facility for X-ray localisation of stones allows a high proportion of ureteric calculi to be treated successfully by ESWL, including the more taxing middle and lower ureteric calculi.

Adolescent

Extracorporeal shock wave lithotripsy for renal calculi in children.

Fifteen children (8 male and 7 female) with an age range of 18 months to 15 years were treated with extracorporeal shock wave lithotripsy (ESWL) using the Siemens Lithostar. Two children had a history of metabolic stone disease and 1 child had previously undergone open stone surgery. Four children were treated with a ureteric stent in place and 1 nephrostomy was inserted before treatment. All children were treated under general anaesthesia and all of the stones treated were confined to the kidney and ranged in size from 5 mm to a complete staghorn. The number of treatments ranged from 1 to 6 and generator voltage ranged from 16 to 19 kV with a maximum number of 30,000 shocks to a complete staghorn. Complications were minimal, with 3 children presenting with colic, 1 child requiring a stent and none requiring a nephrostomy after treatment. The overall stone clearance rate at 3 months was 65%. ESWL provides an effective treatment for selected calculi in children. In the short term, complications are minimal but the long-term effects on children need to be monitored.

Adolescent

Left ventricular diastolic and systolic performance during chronic experimental aortic regurgitation.

To study the time course of left ventricular structural and functional responses to chronic aortic regurgitation, aortic regurgitation was surgically induced in rabbits, and Doppler echocardiography was performed preoperatively and serially postoperatively for up to 2.5 yr. Twenty-five New Zealand White rabbits underwent surgical induction of aortic regurgitation and 13 control animals underwent sham operation. Left ventricular endocardial and epicardial surfaces were digitized from M-mode echocardiograms to measure the rates of change of cavity dimensions and wall thicknesses during diastolic relaxation and systolic contraction. Aortic regurgitant animals developed left ventricular dilatation and eccentric hypertrophy that remained relatively stable throughout the follow-up period. Compared with baseline values, left ventricular mass increased 120% and left ventricular internal dimension at end diastole increased 40%, whereas posterior wall thickness at end diastole and fractional shortening remained relatively stable. Left ventricular diastolic performance was enhanced at 6 mo after operation, a finding associated with increased volume load and heart rate following induction of aortic regurgitation. Diastolic performance was then reduced at 12 mo after operation and demonstrated no further decline throughout the remainder of the follow-up period. In contrast, left ventricular systolic performance was not altered following operation and remained preserved until the final assessment at up to 2.5 yr. Thus alterations in diastolic performance occurred without impairment of systolic performance during long-term follow-up of chronic experimental aortic regurgitation.

Animals

Silanized silica bound trypsin as analytical probe.

Trypsin immobilized by covalent coupling to silanized silica shows significant activity (30-38%) and greater thermostability as compared to soluble trypsin. Proteolytic processing of albumin at varying periods suggest that the enzyme matrix can be used efficiently for limited proteolysis. Repeated use of the immobilized enzyme in protein digestion produces similar products as seen by electrophoretic analysis. Also, digestion of albumin by the immobilized enzyme follows similar pattern as that by soluble enzyme. The enzyme matrix can be easily removed from the incubation mixture. The results indicate the possibility of the immobilized enzyme for its effective application as analytical tool in peptide mapping and limited proteolytic processing.

Electrophoresis, Polyacrylamide Gel

Shigellosis in children: a prospective hospital based study.

From 1985 to 1988, fecal samples of 950 hospitalized children suffering from diarrhea or dysentery were screened for Shigella species using standard methods. Shigella species were isolated as sole pathogen from 192 (20.2%) cases and S. flexneri type 2 was the predominant serotype. Shigella infection was prevalent throughout the year with high isolation rate during the summer and early monsoon months. Shigella strains isolated during the period were resistant to most of the commonly used drugs for the treatment of shigellosis. Nearly 16% of the Shigella strains were also resistant to nalidixic acid. Presence of blood and mucus in stools (dysentery) was the common clinical presentation of shigellosis cases. Malnutrition was associated with longer duration of illness. High cases fatality rate (16.7%) was observed among hospitalized children infected with Shigella.

Child, Preschool

Effect of five-membered heterocycles against Leishmania donovani infection.

Impact of change of heteroatom in pentavalent heterocycles, viz., pyrroles, isoxazoles, imidazoles and crotonates on the profile of antileishmanial activity against amastigotes of L. donovani using in vivo test system and macrophage-amastigote culture system has been studied. Sixty-three compounds were tested. Nine imidazoles showed marginal activity in vivo, whereas 3 out of 10 compounds of isoxazolone series and 2 out of 4 substituted aminocrotonates exhibited antileishmanial activity. Of the 30 substituted pyrroles, except 8 all showed antileishmanial activity in vivo on day 7 post treatment.

Animals

Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats.

Effect of A. indica leaf extract on serum enzyme levels (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, acid phosphatase and alkaline phosphatase) elevated by paracetamol in rats was studied with a view to observe any possible hepatoprotective effect of this plant. It was interesting to observe that serum enzyme levels were much elevated in paracetamol induced animals than in those receiving a combination of paracetamol and lead extract. It is stipulated that the extract treated group was protected from hepatic cell damage caused by paracetamol induction. The findings were further confirmed by histopathological study of liver.

Acetaminophen

A study on viability of mycobacteria after treating them with complement system.

The effect of complement system on viability of mycobacteria (Mycobacterium vaccae and Mycobacterium bovis-BCG, as models) was studied by using 3H-uracil uptake method. The results showed no killing effect on these mycobacteria. Pretreatment of these mycobacteria with antimycobacterial antibodies also did not result in making them susceptible to complement. These observations were confirmed electronmicroscopically where no ultrastructural changes indicative of cell destruction were seen after treatment with complement in the presence and absence of antibody.

Antibodies, Bacterial

Eating epilepsy: a study of twenty cases.

Twenty cases of eating epilepsy have been studied over a period of 5 years (1985-1989). Males outnumbered females (4:1). Heavy meal comprising conventional Indian diet (viz, rice, vegetables, etc), was found to be the most important provocating factor (14 out of 20 cases). The attacks occurred at lunch time in most cases (15). Thirteen cases had generalised seizures. Electro-encephalogram showed focal changes in 10 cases, generalised changes in 6 cases, while 4 cases had normal electro-encephalogram. Computerised tomography scan was normal in all the cases (7) when it was done.

Adolescent

Histopathological monitoring of an immunotherapeutic trial with Mycobacterium w.

Immunotherapeutic trials with Mycobacterium w (M. w.) on multibacillary patients are in progress at two large hospitals in New Delhi. A total of 380 patients so far have been inducted into the trial. The histopathological profile of the initial 87 patients (52 in the vaccine group, 35 in the control group) who have now completed 2 years of treatment are presented in this report. The vaccine group received multidrug therapy (MDT) and eight intradermal injections of M. w. every 3 months; the control group had MDT with starch injections as a placebo. Skin biopsies were taken at induction and thereafter at every 6 months. The results show a significantly higher proportion of biopsies with histopathological upgrading and/or clearance of dermal granuloma among the vaccinated cases. The number of patients becoming bacteriologically negative was higher in the vaccine group. There was no increase in the degree of neural inflammation in the biopsies showing upgrading. The lepromin site biopsy in patients who converted to positivity after vaccination showed epithelioid cell granulomas as did the biopsies from the nodules developing at the vaccination sites. The histopathological observations confirm the additional immunotherapeutic effect of M. w. used along with standard MDT therapy.

Analysis of Variance

Effect of 'Pan Masala' on the germ cells of male mice.

Cytogenetic analyses of meiotic metaphase I germ cells and abnormalities of head morphology of caudal sperms were conducted in male mice following oral feeding of Pan Masala. The substance was ground to a fine powder, dispersed in polysorbate solution and administered via gavage to the animals at 84, 420 and 840 mg/kg body weight at the rate of 10 ml/kg body weight. Polysorbate and cyclophosphamide served as the vehicle control and positive control respectively. The two higher doses, 420 and 840 mg, gave a significant increase in the frequency of X-Y univalents and breaks over those of the vehicle control. Frequency of sperm head abnormalities were significantly high for all the doses tested. The results indicate that Pan Masala is a potent clastogen, reaches the testes and affects the germinal cells.

Administration, Oral