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Biomedical subjects

V Gupta

Publications and source records attributed to V Gupta.

At least 181 records · Page 10Linked to original sources

MR imaging of tubercular spinal arachnoiditis.

OBJECTIVE: The purpose of our study was to examine the spectrum of abnormalities seen on MR imaging in patients with tubercular spinal arachnoiditis. MATERIALS AND METHODS: A retrospective analysis of MR findings in 22 cases of tubercular spinal arachnoiditis was carried out. The diagnosis had been established on the basis of clinical features, evidence of associated tubercular meningitis or of tubercular spondylitis, and CSF analysis. RESULTS: Nineteen (86%) patients had involvement of more than one spinal region, with the dorsal region being most commonly involved. CSF showed increased signal intensity on T1-weighted images in 17 (77%) patients, leading to complete loss of cord-CSF interface in seven patients and shaggy cord outline in 10 patients. As suggested by increased signal intensity on T2-weighted images, we saw cord involvement in 18 (82%) patients. Three of these patients had evidence of cord cavitation. Other findings seen on unenhanced images were CSF loculations in five patients, nodules in subarachnoid space in six patients, and clumping of cauda equina nerve roots in six patients. Contrast-enhanced studies were available in 20 patients. Meningeal enhancement was seen in 16 (80%) of 20 patients, and nerve root enhancement was seen in six (30%) patients. Cord enhancement was seen in four (20%) of 20 patients. Enhancement was observed along the surface of the cord in two of these patients, whereas the other two patients showed central enhancement. Associated findings were tubercular spondylitis in two patients, basal exudate in eight patients, and intracranial granulomas in five patients. CONCLUSION: MR imaging revealed several pathologic changes that occur in patients with tubercular spinal arachnoiditis and, hence, may play an important role in the diagnosis of this entity.

Adult↗

The defective glucagon response from transplanted intrahepatic pancreatic islets during hypoglycemia is transplantation site-determined.

The optimal site for pancreatic islet cell transplantation is presently unclear, although the liver has been the most commonly used. However, glucagon secretion from islets that have been autotransplanted in liver has been reported to be unresponsive to hypoglycemia yet responsive to arginine. To determine whether this selective glucagon secretory defect is related to the intrahepatic site of islet implantation or to the process of transplantation per se, we studied counterregulatory responses to hypoglycemia in dogs with pancreatic islet autotransplantation in the hepatic parenchyma (the intrahepatic [IH] group, n = 9) or the peritoneal cavity (the intraperitoneal [IP] group, n = 9), following total pancreatectomy, and compared them with the responses in normal controls (n = 10). Dogs were subjected to a hypoglycemic hyperinsulinemic (5 mU x kg-1 x min-1) clamp for 90 min under general anesthesia. Arterial glucose concentrations were clamped at 2.7 mmol/l for the final 45 min of the clamp. Immediately following the clamp, glucagon responses to IV arginine (5 g) were also assessed. During hypoglycemia, glucagon responses in the IH group (maximal incremental glucagon = 33 +/- 21 ng/l; glucagon area under curve [AUC] = 713 +/- 1,022 ng x l-1 x min-1) were significantly lower than either the IP (maximal incremental glucagon = 92 +/- 32 ng/l; glucagon AUC = 4,090 +/- 1,600 ng x l-1 x min-1) or control (maximal incremental glucagon = 154 +/- 71 ng/l; glucagon AUC = 6,943 +/- 2,842 ng x l-1 x min-1) group (IH vs. IP group, P < 0.05; control vs. IH group, P < 0.01). Glucagon responses in the IP group did not differ significantly from the control group. Epinephrine responses to hypoglycemia were similar in all groups, whereas neither of the transplanted groups (IH and IP) had pancreatic polypeptide responses. There was a prompt rise in plasma glucagon after intravenous arginine in all groups. These data indicate that glucagon unresponsiveness to hypoglycemia is specific to intrahepatically transplanted islets, rendering the liver a disadvantageous site for optimal alpha-cell function.

Animals↗

Optimization of sustained-release tablet formulations: a four-component mixture experiment.

Sustained-release tablet formulations containing chlorpheniramine maleate were prepared using a mixture of two hydrophilic gums, gamma-carrageenan and cross-linked carboxymethylcellulose sodium, and two filler materials, alpha-lactose monohydrate and dibasic calcium phosphate in different ratios. The objective of the experiment was to find an optimum formulation with the most desirable properties. In order to achieve this, the matrices were evaluated for the time taken to release 80% drug (t80), the release exponent (n), and the crushing strength (h). Several formulations produced near zero-order release of the model drug over a time period of up to 10 hr. Response surface plots for the three dependent variables were generated over the experimental region. the effect of different levels of the components on the response variables was thus visualized. Upon superimposition of the plots it was possible to graphically find a region where the responses were in an optimum range of values. To pinpoint the best formulation, a simultaneous optimum point within this region was located by arbitrarily defining optimum values for each of the responses and using a multi-objective function that combined the three response variables. The observed response variables of the optimum formulation were in good agreement with the predicted values.

Carrageenan↗

Elevated levels of anti-proteus antibodies in patients with active rheumatoid arthritis.

We carried out this study to determine if our patient population with rheumatoid arthritis (RA) has elevated levels of antibodies to gut bacteria. Seventy patients with RA were categorised as being either active or inactive on clinical grounds. Antibodies to the H and O antigens of Proteus mirabilis and Salmonella typhi were determined by tube agglutination method in these patients, 18 patients with osteoarthritis and 82 healthy controls. There was no significant difference in the anti-proteus antibody titres between both the control groups and patients with inactive disease. However, antibody levels among patients with active disease were significantly higher than controls (P < 0.001). There was no significant difference in anti-salmonella antibody titres among the various disease and control groups. Elevated antibody levels could suggest a role for Proteus as an etiological agent in RA.

Adult↗

Trends in reproductive health knowledge following a health education intervention among adolescents in Zimbabwe.

BACKGROUND: Unwanted teenage pregnancy, sexually transmitted infections and the attendant morbidity and mortality necessitate the need for understanding factors influencing adolescent sexuality and the implementation of programmes designed to improve their knowledge, reproductive behaviour, sexual and reproductive health. OBJECTIVE: To determine the impact of an intervention package on knowledge levels of various reproductive health issues through trend analysis. DESIGN: Randomized controlled trial of a health education intervention in schools stratified for representativeness. SETTING: Rural and urban secondary schools in Zimbabwe. SUBJECTS: 1,689 students recruited from 11 secondary schools in Mashonaland Central. MAIN OUTCOME MEASURE: Knowledge level before and after intervention. RESULTS: The demographic characteristics of the pupils at baseline, five months and nine months were comparable between the two groups. There was an overall increase in knowledge on menstruation. Students from the intervention schools were more likely to have correct knowledge over time on aspects of reproductive biology. A significant linear trend (p = 0.017) was observed in the area of family planning and contraception. A linear decreasing trend (p = 0.001) was observed on pregnancy risk. Though not significantly linear, the general trend of knowledge levels in all the areas of reproductive health, pregnancy risk, STDs and HIV/AIDS showed an upward trend, from 20% to 96%. Worth noting was that in all the areas the intervention group had knowledge above that in the control group. CONCLUSION: The reproductive health education intervention had an impact on aspects of reproductive biology and contraception as measured by the increased scoring at follow up when comparing intervention and control schools. The overall findings point to the need for early school based reproductive health education programmes incooperating correct information on reproductive biology and the prevention of subsequent reproductive morbidity by imparting information on non-risk behaviour during the early developmental years.

Adolescent↗

Zimbabwean teenagers' knowledge of AIDS and other sexually transmitted diseases.

A cross sectional anonymously administered questionnaire was used amongst 1689 secondary school girls and boys to determine their knowledge of AIDS and other sexually transmitted diseases (STDs). Their knowledge was found to be very low. While 80% could name an STD in an open question, only 16% could recognise the important symptoms of the common and treatable diseases such as gonorrhoea and syphilis. This finding is worrying in view of the fact that these common STDs facilitate transmission of HIV/AIDS. The awareness of AIDs was high but when it came to the mode of transmission of AIDS the large majority were not aware of the risk of intercourse with an infected person. Furthermore, despite an intensive AIDS awareness campaign programme mounted by the government of Zimbabwe a large number of students thought that one can contract HIV/AIDS by shaking hands, sharing a toilet and witchcraft. Misconceptions on transmission abound. The data show that there is a need to review strategies of disseminating information to teenagers regarding STD, including AIDS, reproductive biology, sexuality and contraception. The best strategy may be the introduction of a reproductive health education curriculum in all schools starting at an early age.

Acquired Immunodeficiency Syndrome↗

Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic.

This study characterizes glutathione (GSH) S-transferase (GST) isoenzymes of the liver and forestomach of the female A/J mouse and compares their specificities in catalyzing the conjugation of GSH with 7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10-tetrahydrobenzo[a] pyrene (anti-BPDE), the ultimate carcinogenic metabolite of benzo[a]pyrene (BP). The GST activity in female A/J mouse liver was expressed by a minimum of seven isoenzymes which arose from different homo- or heterodimeric combinations of at least two alpha class (designated as alpha1 and alpha4), four micro class (micro1 to micro4), and one pi class GST subunit. The GST isoenzyme composition of A/J mouse forestomach appeared to be different from that of the liver. For example, while GST isoenzymes containing micro3 and micro4 type subunits were selectively expressed in the liver, an alpha class heterodimeric GST isoenzyme (containing alpha2 and alpha3 subunits) was expressed in the forestomach but could not be detected in the liver. The (+)-anti-BPDE appeared to be a better substrate than the (-)-enantiomer for all GSTs, except for isoenzymes containing the alpha4 type GST subunit. The murine pi class GST isoenzyme displayed relativey higher specific activity toward (+)-anti-BPDE compared to other GSTs. The specific activities of mouse GSTs toward (+)-anti-BPDE were in the order of pi > micro > alpha. These results suggest that the pi class GST isoenzyme may play an important role in providing protection against BP-induced cancer. Therefore, it seems logical to postulate that the ability of a chemoprotector to increase the expression of GST pi may be an important determinant of its effectiveness against BP-induced cancer. To test the validity of this contention, we have determined the effects on hepatic and forestomach GST isoenzyme/subunit expression of three naturally occurring organosulfides (OSCs) from garlic, which significantly differ in their effectiveness against BP-induced forestomach cancer. Treatment of mice with diallyl sulfide (DAS) and diallyl trisulfide (DATS), which are potent inhibitors of BP-induced fore- stomach cancer in mice, resulted in a significant increase in hepatic and forestomach GST activity toward anti-BPDE. On the contrary, this activity was not increased in either organ by dipropyl sulfide (DPS), which is ineffective against BP-induced forestomach cancer. The chemopreventive efficacy of these OSCs correlated with their ability to increase the expression of GST pi. For example, DAS treatment resulted in approximate increases of 1.7- and 2.2-fold in hepatic and forestomach GST pi expression, respectively, over the control. Treatment of mice with DATS, which is a relatively more potent inhibitor of BP-induced forestomach cancer than DAS, resulted in about 3.8- and 3.2-fold increases, respectively, in hepatic and forestomach GST pi expression over the control. On the contrary, the expression of hepatic and forestomach GST pi was increased only marginally (10-20%) upon DPS administration. In conclusion, the results of the present study suggest that induction of GST pi can be used as a bioassay for screening potential inhibitors of BP-induced cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Novel anti-carcinogenic activity of an organosulfide from garlic: inhibition of H-RAS oncogene transformed tumor growth in vivo by diallyl disulfide is associated with inhibition of p21H-ras processing.

In this study, we report a novel anticarcinogenic activity of an organosulfur compound from garlic, diallyl disulfide (DADS). DADS treatment significantly inhibited the growth of H-ras oncogene transformed tumors in nude mice. As compared to controls, the appearance of tumors was also delayed markedly by oral administration of DADS. The inhibition of tumor growth by DADS treatment correlated with the inhibition of p21H-ras membrane association in the tumor tissue. The levels of membrane associated p21H-ras were markedly lower in the tumor tissues of DADS treated mice as compared to controls. An opposite trend, however, was evident for cytosolic p21H-ras. Furthermore, DADS treatment resulted in a significant inhibition of hepatic as well as tumoral 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. These results indicate that DADS suppresses the growth of H-ras oncogene transformed tumors in nude mice by inhibiting the membrane association of tumoral p21H-ras.

Allyl Compounds↗

Lack of a role of glutathione in cellular nonenzymatic activation of BMS-181174, a novel analogue of mitomycin C.

Recent studies, using a cell-free system, have suggested that thiol-dependent nonenzymatic bioactivation may be responsible for the superior antitumor activity of the mitomycin C analogue BMS-181174 [N-7-[2-(4-nitrophenyldithio)ethyl]mitomycin C] when compared to the parent compound. If operational in tumor cells, this pathway could have enormous clinical implications since tumor cell resistance to a variety of anticancer agents is often associated with increased glutathione (GSH) levels and BMS-181174 may be used to reverse this mechanism of resistance. The present study was undertaken to determine the role of GSH in cellular activation of BMS-181174 using a pair of well-characterized human bladder cancer cells (J82 and SCaBER) as a model. A 20-h pretreatment of J82 and SCaBER cells with a nontoxic concentration of D,L-buthionine-S,R-sulfoximine (BSO) caused about 80-88% reduction in cellular GSH levels. Surprisingly, the sensitivity of both cells to BMS-181174 was increased, not reduced, by BSO-induced GSH depletion. On the other hand, the cytotoxicity of BMS-181174 was significantly reduced in both cells by a 4-h pretreatment with 1 mM GSH. Like BSO, a 4-h pretreatment with another thiol compound (cysteine) resulted in a statistically significant sensitization of both cells to BMS-181174. Cellular GSH levels were not affected in either of the cell lines by pretreatment with GSH or cysteine. In conclusion, the results or the present study argue against a role of GSH in cellular nonenzymatic activation of BMS-181174 in J82 and SCaBER cells.

Antineoplastic Agents, Alkylating↗

Biochemical characterization of a mitomycin C-resistant human bladder cancer cell line.

This study describes characteristics of a mitomycin C (MMC)-resistant human bladder cancer cell line, J82/MMC-2, which was established by repeated in vitro exposures of a 6-fold MMC-resistant variant (J82/MMC) to 18 nM MMC. A 9.6-fold higher concentration of MMC was required to kill 50% of the J82/MMC-2 sub-line compared with parental cells (J82/WT). NADPH cytochrome P450 reductase and DT-diaphorase activities were significantly lower in J82/MMC-2 cells compared with J82/WT, suggesting that reduced sensitivity of J82/MMC-2 cells to MMC resulted from impaired drug activation. Consistent with this hypothesis, the formation of MMC-alkylating metabolites was significantly lower in J82/MMC-2 cells compared with J82/WT. Furthermore, DT-diaphorase activity in J82/MMC-2 cells was significantly lower compared with the 6-fold MMC-resistant variant. Glutathione (GSH) levels were comparable in all 3 cell lines. Although GSH transferase (GST) activity was significantly higher in the J82/MMC-2 cells compared with J82/WT, this enzyme activity did not differ between 6- and 9.6-fold MMC-resistant variants. Whereas DNA polymerase alpha mRNA expression was comparable in these cell lines, levels of DNA ligase I mRNA were slightly lower in both MMC-resistant variants relative to J82/WT. However, the DNA polymerase beta mRNA level was markedly higher in the J82/MMC-2 cell line compared with either J82/WT or J82/MMC. Thus, emergence of a higher level of resistance to MMC in J82/MMC-2 cells compared with J82/MMC may be attributed to (i) impaired drug activation through further reduction in DT-diaphorase activity and (ii) enhanced DNA repair through over-expression of DNA polymerase beta.

Antibiotics, Antineoplastic↗

Surface EMG measurements at the throat during dry and wet swallowing.

Within the sphere of dysphagia management, there is a growing need for the development of noninvasive methods of quantification of swallowing disorders. The purpose of the present investigation was to determine if surface electromyogram (EMG) at the throat could be measured during swallowing. Surface EMG was measured from 35 normal human subjects during dry and wet swallowing. The EMG signals recorded were highpass filtered using digital fourth order highpass Butterworth filter to eliminate baseline variations. Spectral analysis was performed on the filtered signals. The mean power values of the surface EMG signals were then calculated. Paired t-test between the mean power values of surface EMG during dry and wet swallowing showed a statistically significant difference (p < 0.005). The results of the study confirmed the hypothesis that surface EMG at the throat during swallowing could be measured. Mean power of surface EMG measurement provides a reliable noninvasive measure of swallowing.

Deglutition↗

A compendium of potential energy maps of zeolites and molecular sieves.

We present potential maps of xenon in 20 different zeolites and molecular sieves. The potential maps reveal both the accessible pore volume and localized adsorption sites and so are important in understanding adsorption and diffusion processes in nanoporous materials. We examine zeolites and molecular sieves with one-dimensional channel-like nanopores (zeolite-Theta 1, AlPO4-5, zeolite-Omega, zeolite-L, ZSM-12, AlPO4-8, and VPI-5), with two-dimensional intersecting channel-like nanopores (ZSM-5 [silicalite], ZSM-11, ferrierite, mordenite, and zeolite-Beta), and with three-dimensionally connected cagelike nanopores (zeolite-A, zeolite-Rho, zeolite-Y, sodalite, chabazite, cloverite, cation-poor zeolite-A, and cation-rich zeolite-A). We report the fraction of pore volume accessible, the maximum energy well depth at the adsorption sites, and the activation energy to move between sites. We note several examples of surprising similarities and differences between various molecular sieves. In several instances, we show that these potential profiles are relevant for other small Lennard-Jones-like molecules. By comparison with published Monte Carlo and molecular dynamics simulations, we show that the density distributions of adsorbates at low density are well predicted by the potential maps.

Cations↗

Effect of 24 hours of starvation on plasma glucose and insulin concentrations in subjects with untreated non-insulin-dependent diabetes mellitus.

Adherence to a low-calorie diet often results in a decrease in blood glucose concentration in persons with non-insulin-dependent diabetes mellitus (NIDDM). Whether this is due to the resultant weight loss or to a decrease in caloric intake has been uncertain. We have obtained data previously that indicated a very short-term reduction in caloric intake (5 hours) resulted in a significant decrease in plasma glucose concentration in subjects with NIDDM. The purpose of the present study was to determine if a further decrease in glucose would occur if the fast was extended from 5 to 24 hours. Seven male subjects with untreated NIDDM were studied after an 11-hour overnight fast. For the subsequent 24-hour period, subjects were given only water. Blood was obtained for glucose, insulin, C-peptide, triglycerides, nonesterified fatty acids (NEFA) alpha-amino acid nitrogen, urea nitrogen, and glucagon at hourly intervals for 24 hours beginning at 8 AM. The amount of glycogen degraded was calculated based on the potassium balance. Plasma glucose decreased from 158 mg/dL at 8 AM to a nadir of 104 mg/dL at 7 PM. It then increased by 30 mg/dL. Corresponding changes occurred in insulin and C-peptide. Serum glucagon remained unchanged. Serum alpha-amino acid nitrogen and urea nitrogen decreased. Triglycerides and NEFA increased. The calculated glycogen utilized over this period was approximately 167 g. This would provide approximately 700 kcal energy. The elevated blood glucose concentration in mild to moderately severe untreated NIDDM subjects was normalized following short-term fasting. Plasma insulin concentrations also decreased to within normal limits. These decreases were highly significant. Glycogenolysis is an important source of fuel during this period.

Aged↗

Vitamin A status in early childhood diarrhoea, respiratory infection and in maternal and cord blood.

Serum vitamin A levels were estimated in (i) 125 rural children (0-36 months old) with diarrhoea, and/or acute lower respiratory tract infection and (ii) 61 pregnant rural women and their off-springs. Mean serum vitamin A levels were 127.3, 112.1 and 94.0 mu g/dl, respectively, in diarrhoea, acute lower respiratory infection, and in children having both the illnesses. These levels were lower than the control (148.0 mu g/dl). However, level <20 mu g/dl diagnostic of deficiency was not observed in any child. The malnutrition and duration of illness over 4 days significantly decreased the mean serum vitamin A level. The vitamin A levels of children who died were not significantly different than those who recovered. The maternal mean levels of serum vitamin A were higher than the cord levels, both being within normal range.

Child, Preschool↗

Surface electromyogram for the control of anthropomorphic teleoperator fingers.

Growing importance of telesurgery has led to the need for the development of synergistic control of anthropomorphic teleoperators. Synergistic systems can be developed using direct biological control. The purpose of this study was to develop techniques for direct biocontrol of anthropomorphic teleoperators using surface electromyogram (EMG). A computer model of a two finger teleoperator was developed and controlled using surface EMG from the flexor digitorum superficialis during flexion-extension of the index finger. The results of the study revealed a linear relationship between the RMS EMG and the flexion-extension of the finger model. Therefore, surface EMG can be used as a direct biocontrol for teleoperators and in VR applications.

Computer Simulation↗