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Biomedical subjects

D Bhatnagar

Publications and source records attributed to D Bhatnagar.

At least 19 recordsLinked to original sources
PubMed2007

Amino acid supplementation reveals differential regulation of aflatoxin biosynthesis in Aspergillus flavus NRRL 3357 and Aspergillus parasiticus SRRC 143.

Aflatoxins are toxic and carcinogenic secondary metabolites produced by the fungi Aspergillus flavus and Aspergillus parasiticus. To better understand the molecular mechanisms that regulate aflatoxin production, the biosynthesis of the toxin in A. flavus and A. parasticus grown in yeast extract sucrose media supplemented with 50 mM tryptophan (Trp) were examined. Aspergillus flavus grown in the presence of 50 mM tryptophan was found to have significantly reduced aflatoxin B(1) and B(2) biosynthesis, while A. parasiticus cultures had significantly increased B(1) and G(1) biosynthesis. Microarray analysis of RNA extracted from fungi grown under these conditions revealed 77 genes that are expressed significantly different between A. flavus and A. parasiticus, including the aflatoxin biosynthetic genes aflD (nor-1), aflE (norA), and aflO (omtB). It is clear that the regulatory mechanisms of aflatoxin biosynthesis in response to Trp in A. flavus and A. parasiticus are different. These candidate genes may serve as regulatory factors of aflatoxin biosynthesis.

Aflatoxins↗
PubMed2005

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India.

AIMS/HYPOTHESES: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system. MATERIALS AND METHODS: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246). We performed anthropometry and measured fasting plasma insulin, IGF-I, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3. RESULTS: Daily calorie intake, BMI and WHR were significantly higher in UK Gujaratis than in Indian Gujaratis. IGFBP-1 was significantly lower in UK migrants (mean 29.5 [95% CI 25.9-33.0] vs 56.5 [50.6-62.5] microg/l; F=48.4, p<0.001). Conversely, fasting insulin, IGFBP-3 and IGF-I were all higher in UK Gujaratis (mean IGF-I 145.9 [138.1-153.6]ng/ml in UK Gujaratis and 100.9 [94.6-107.3] ng/ml in Navsari Gujaratis; F=76.6, p<0.001). These differences were still apparent when adjustment was made for BMI by location for IGF-I (F=57.4, p<0.001) and IGFBP-3 (F=5.7, p=0.02), but were no longer apparent for IGFBP-1 and insulin. At the population level, the decrease in IGFBP-1 for a given increase in insulin was significantly smaller in UK Gujaratis, suggesting greater hepatic insulin resistance in this group. CONCLUSIONS/INTERPRETATION: Environmental factors have profound effects on circulating IGF system components and on the relationship between IGFBP-1, IGF-I and related metabolic variables. This may have long-term implications for the development of worsening glucose tolerance and cardiovascular disease.

Blood Glucose↗
PubMed2005

Impact of migration on coronary heart disease risk factors: comparison of Gujaratis in Britain and their contemporaries in villages of origin in India.

The causes of the excess coronary heart disease (CHD) risk in South Asian migrants from the Indian subcontinent remain unclear. Comparisons of CHD risk factors amongst South Asian migrants living in Britain with those of the general UK population provide only a partial explanation. We compared Gujaratis in Britain with similar, non-migrant Gujaratis in India, to test the hypothesis that differences in CHD risk factors associated with migration would be more informative. Randomly sampled Gujaratis aged 25-79 years living in Sandwell (n = 242) were compared with age-, gender- and caste-matched contemporaries remaining in their villages of origin in Navsari, India (n = 295). Lifestyle indices, food intake and physical activity, were assessed with standardised questionnaires and energy expenditure and metabolic parameters measured. British Gujaratis had higher, mean body mass indices by 6 (4.5-7.4) kg/m(2) mean (95% CI), and greater dietary energy intake, fat intake, blood pressure, fasting serum cholesterol, apolipoprotein B, triglycerides, non-esterified fatty acid (NEFA) and C-reative protein concentrations than Gujaratis in India. Dietary folate and serum folate and Vitamin B(12) were lower and plasma homocysteine was higher in India. Smoking was less prevalent and high-density lipoprotein cholesterol tended to be higher in Britain. Diabetes prevalence was high in both populations and impaired fasting or 2 h post-glucose challenge plasma glucose was even more prevalent in Gujarat. In India, however, where insulin secretion and NEFA were lower diabetes and impaired glucose tolerance were less frequently accompanied by excess metabolic CVD risk factors. In conclusion, exposure to increased fat intake and obesity related to migration is likely to explain the disproportionate combination of established and emerging CHD risk factors prevalent in Gujaratis in Britain. Strategies to improve nutrition and to identify and treat cardiovascular risk factors such as dyslipidaemia and hypertension are urgently required.

Adult↗
PubMed2005

Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake.

BACKGROUND: The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease. OBJECTIVE: We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate. DESIGN, SUBJECTS AND SETTING: Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured. RESULTS: Total energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1-153.6) vs. 100.9 (94.6-107.3) ng ml(-1); F=76.6, P<0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9-33.0) vs. 56.5 (50.6-62.5) microg l(-1); F=48.4, P<0.001). At both sites, IGF-I correlated positively with total energy (Spearman's rho=0.45, P<0.001) and total fat (rho=0.44, P<0.001) as did IGFBP-3 with total energy (rho=0.21, P<0.05) and fat (rho=0.26, P<0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (rho=-0.27, P<0.001) and fat intake (rho=-0.26, P<0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (beta=0.42, P=0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose. CONCLUSION: In these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

Blood Glucose↗
PubMed2005

Cytomorphological study of soft tissue neoplasms: role of fluorescent immunocytochemistry in diagnosis.

OBJECTIVES: Exact categorization of soft tissue tumours (STTs) on smears requires application of various ancillary techniques. This study was aimed at evaluating the role of fluorescent immunocytochemistry (FICC) in cyto-diagnosis of 30 STT cases. METHODS: Thirty cases of soft tissue tumours were included in the present study. All cases were subjected to routine Giemsa and Papanicolaou stain. Extra smears were made and kept for fluorescent immunostaining. A panel of cytoskeletal antibodies, tagged with FITC (Fluorescein isothyocynate), was employed in all these cases. Fluorescent immunostained smears were examined under Zeiss Confocal Laser scanning microscope, using double immunofluorescence (red-green). Finally, all cases were subjected to biopsy and again immunoperoxidase staining. RESULTS: Among the 30 cases in the present study, unaided cytological diagnoses ranged from 'spindle cell' tumour in four (13.3%) cases, benign and malignant spindle cell tumour in 17 (56.6%) cases, to malignant mesenchymal tumour in nine (30%) cases. FICC helped in further correct categorization of 25/30 (83.3%) cases viz. leiomyoma (three), benign neurogenic tumour (six), schwannoma (one), dermatofibrosarcoma protuberans (three), synovial sarcoma (two), rhabdomyosarcoma (two), malignant fibrous histiocytoma (five) and malignant peripheral nerve sheath tumour (three). Aggressive fibromatosis was found to be a missed diagnosis in two cases. Overall concordance between cyto-diagnosis with FICC, and histopathology results was 83.3% (P < 0.05). CONCLUSION: Fluorescent immunocytochemistry is a significant ancillary technique for making a rapid and specific diagnosis of STT, as required for their timely management. Incorporation of a wide panel of antibody markers with clinico-cytological correlation is recommended in forming an exact diagnosis in these cases.

Biopsy, Fine-Needle↗
PubMed2005

Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes.

Nitrosamines, such as N-nitrosodiethylamine (NDEA), induced oxidative stress due to the generation of reactive oxygen species, which are capable of initiating peroxidative damage to the cell. The present study was designed to establish whether pre-treatment with vitamin E (40 mg/kg body wt, intraperitoneally (ip), twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress caused by NDEA. A single necrogenic dose of NDEA (200 mg/kg body wt) was administered intraperitoneally (ip) to the rats with or without vitamin E pre-treatment and the animals were sacrificed on Day 7, 14 or 21 after NDEA administration. Lipid peroxidation (LPO) and the activities of antioxidant enzymes were determined in erythrocytes as indices of oxidative damage. The result showed elevated levels of LPO in erythrocytes with NDEA treatment, however, vitamin E pre-treated rats administered NDEA showed decreased LPO (Day 14 and 21). Superoxide dismutase (SOD) enzyme activity and the glutathione (GSH) content increased with NDEA treatment and remained high in vitamin E pre-treated group. Catalase (CAT), glutathione reductase (GSH-R) and glutathione-S-transferase (GST) enzyme activities declined with NDEA treatment; however, vitamin E pre-treated rats administered NDEA, showed elevation in the enzyme activities. Glutathione peroxidase (GSH-Px) activity increased in erythrocytes in vitamin E pre-treated rats administered NDEA, while Se-GSH-Px activity was not affected significantly. This study demonstrates that the pre-treatment with vitamin E prior to the administration of NDEA was effective in counteracting and modulating oxidative stress in rat erythrocytes in a time-dependent manner.

Alkylating Agents↗
PubMed2004

POSSUM and P-POSSUM for risk-adjusted audit of patients undergoing emergency laparotomy.

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a scoring system that is used widely to predict 30-day mortality and morbidity rates. The Portsmouth predictor modification (P-POSSUM) was developed to overcome the overprediction of mortality by POSSUM, especially in low-risk patients. In this prospective study, the validity of POSSUM and P-POSSUM was tested in patients undergoing emergency laparotomy in a referral hospital of a developing country. METHODS: Some 120 patients who underwent emergency laparotomy in a single unit were studied. Predicted morbidity and mortality rates were calculated by POSSUM and P-POSSUM equations using both linear regression and the exponential methods of analysis. These were compared with actual outcomes. RESULTS: When the linear method of analysis was used POSSUM overpredicted morbidity, and there was a significant difference between the observed and predicted values (observed to expected (O : E) ratio 0.68). The prediction was more accurate when the exponential method was used (O : E ratio 0.91). POSSUM also significantly overpredicted mortality when analysed by the linear method (O : E ratio 0.39), but the prediction improved when exponential analysis was used (O : E ratio 0.62). Applying linear and exponential analyses for P-POSSUM, the O : E ratios for mortality were 0.66 and 0.88 respectively. CONCLUSION: If analysed correctly POSSUM is a good predictor of morbidity and mortality in patients undergoing emergency laparotomy. P-POSSUM predicts mortality equally well. Both equations may be used for risk-adjusted surgical audit of patients undergoing emergency laparotomy.

Emergencies↗
PubMed2004

The prevalence and management of hyperglycaemia in patients with rheumatoid arthritis on corticosteroid therapy.

BACKGROUND AND AIMS: Corticosteroids are commonly used in the treatment of RA. Hyperglycaemia resulting from corticosteroid use can lead to problems, particularly in those with impaired glucose tolerance and diabetes mellitus. We have examined how rheumatology clinics monitored and managed hyperglycaemia at base line and during treatment of patients with rheumatoid arthritis on corticosteroids. METHODS: Case notes of 102 patients with established RA, on long-term steroids were reviewed. We recorded a) blood glucose level at base line and whilst on steroids b) when and whether hyperglycaemia was addressed. RESULTS: There were 24 males and 78 females, with mean age of 62 +/- 15 years. Patients were on corticosteroids for a median duration of 24 months. Seventy-five per cent of patients were treated with oral prednisolone, the rest, except one patient on deflazacort, were on methylprednisolone. Blood glucose was measured at baseline in 97% of patients with 37% and 38% being monitored at three months and six months respectively and 36% annually thereafter. Nine patients (8.8%) developed diabetes mellitus during treatment, but one patient was detected and managed. There were six patients with existing diabetes mellitus in whom glycaemic control worsened between three to six months, but only one patient had treatment adjusted. CONCLUSIONS AND RECOMMENDATIONS: Physicians need to be aware that corticosteroids can increase blood glucose, worsen pre-existing diabetes and predispose to diabetes mellitus. Patients on long-term corticosteroids should be monitored at regular intervals as corticosteroid induced glycaemic excursions may lead to the development of diabetes mellitus and increased coronary risk.

Adrenal Cortex Hormones↗
PubMed2004

Metaplastic carcinoma of the breast--a rare breast tumour.

Malignant breast neoplasms consisting of mixtures of epithelial and mesenchymal elements, are a rarity. Pathogenesis of such diverse elements within obviously infiltrating carcinomas has been the subject of much controversy. After the advent of immunohistochemistry, it is now generally accepted that metaplasia of the epithelial elements of a carcinoma gives these lesions their pseudosarcomatous appearance. Hence the name metaplastic carcinoma is given to malignant breast neoplasms which show Cytokeratin positivity in both epithelial and mesenchymal elements. We recently encountered such a case, which is being presented here along with relevant review of literature.

Adult↗
PubMed2004

Malaria control using deltamethrin impregnated bed nets in a cantonment area at Allahabad (U. P.).

The study was undertaken to evaluate the impact of deltamethrin impregnated mosquito nets on malaria incidence, mosquito density, any adverse side effect among users and collateral effects on bed bugs and houseflies. A field trial was carried out over a period of three years in two adjacent military stations at Allahabad (UP), keeping one as a trial and other as a control station. During first year, baseline data were collected and during next two years residual spray was replaced with use of deltamethrin impregnated mosquito nets in trial station. The use of deltamethrin-treated bed nets resulted in a significant decline in malaria incidence and annual parasite index (API). The average mosquito density of anopheline mosquitoes decreased by 67.8% and culicine by 49.7%. The insecticide was found safe for use amongst troops and had favourable collateral effects against bed bugs and flies. Use of deltamethrin impregnated bed nets has beneficial impact on integrated control of malaria.

Animals↗
PubMed2003

Molecular genetic analysis and regulation of aflatoxin biosynthesis.

Aflatoxins, produced by some Aspergillus species, are toxic and extremely carcinogenic furanocoumarins. Recent investigations of the molecular mechanism of AFB biosynthesis showed that the genes required for biosynthesis are in a 70 kb gene cluster. They encode a DNA-binding protein functioning in aflatoxin pathway gene regulation, and other enzymes such as cytochrome p450-type monooxygenases, dehydrogenases, methyltransferases, and polyketide and fatty acid synthases. Information gained from these studies has led to a better understanding of aflatoxin biosynthesis by these fungi. The characterization of genes involved in aflatoxin formation affords the opportunity to examine the mechanism of molecular regulation of the aflatoxin biosynthetic pathway, particularly during the interaction between aflatoxin-producing fungi and plants.

Aflatoxins↗
PubMed2003

Substrate-induced lipase gene expression and aflatoxin production in Aspergillus parasiticus and Aspergillus flavus.

AIMS: To establish a relationship between lipase gene expression and aflatoxin production by cloning the lipA gene and studying its expression pattern in several aflatoxigenic and nontoxigenic isolates of Aspergillus flavus and A. parasiticus. METHODS AND RESULTS: We have cloned a gene, lipA, that encodes a lipase involved in the breakdown of lipids from aflatoxin-producing A. flavus, A. parasiticus and two nonaflatoxigenic A. flavus isolates, wool-1 and wool-2. The lipA gene was transcribed under diverse media conditions, however, no mature mRNA was detected unless the growth medium was supplemented with 0.5% soya bean or peanut oil or the fungus was grown in lipid-rich medium such as coconut medium. The expression of the lipase gene (mature mRNA) under substrate-induced conditions correlated well with aflatoxin production in aflatoxigenic species A. flavus (SRRC 1007) and A. parasiticus (SRRC 143). CONCLUSIONS: Substrate-induced lipase gene expression might be indirectly related to aflatoxin formation by providing the basic building block 'acetate' for aflatoxin synthesis. No direct relationship between lipid metabolism and aflatoxin production can be ascertained, however, lipase gene expression correlates well with aflatoxin formation. SIGNIFICANCE AND IMPACT OF THE STUDY: Lipid substrate induces and promotes aflatoxin formation. It gives insight into genetic and biochemical aspects of aflatoxin formation.

Aflatoxins↗
PubMed2003

Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications.

Fatty acids are an important source of energy which can have an influence on serum lipids. Omega-3 and omega-6 fatty acids, both polyunsaturated fatty acids, have been advocated as replacement for saturated fat. Omega-3 fatty acids, derived from fish and certain green plants, lower serum triglycerides, but they have also been shown to have a direct effect on myocardial contractility, blood pressure, platelet function, coagulation factors, cell-mediated immunity and markers of inflammation. Recently available clinical trial data, including those using the concentrated omega-3 fatty acid preparation Omacor, indicate that omega-3 fatty acids are valuable in preventing sudden death following myocardial infarction. Studies indicate that omega-3 fatty acids are just as effective as, or have a benefit superior to, statins in secondary prevention. Omacor is also useful in the treatment of hypertriglyceridaemia, both as monotherapy and in combination with statins.

Blood Pressure↗
PubMed2001

Growth inhibition of a Fusarium verticillioides GUS strain in corn kernels of aflatoxin-resistant genotypes.

Two corn genotypes, GT-MAS:gk and MI82, resistant to Aspergillus flavus infection/aflatoxin contamination, were tested for their ability to limit growth of Fusarium verticillioides. An F. verticillioides strain was transformed with a beta-glucuronidase (GUS) reporter gene (uidA) construct to facilitate fungal growth quantification and then inoculated onto endosperm-wounded and non-wounded kernels of the above-corn lines. To serve as a control, an A. flavus strain containing the same reporter gene construct was inoculated onto non-wounded kernels of GT-MAS:gk. Results showed that, as in a previous study, non-wounded GT-MAS:gk kernels supported less growth (six- to ten-fold) of A. flavus than did kernels of a susceptible control. Also, non-wounded kernels of GT-MAS:gk and M182 supported less growth (two- to four-fold) of F. verticillioides than did susceptible kernels. Wounding, however, increased F. verticillioides infection of MI82, but not that of GT-MAS:gk. This is in contrast to a previous study of A. flavus, where wounding increased infection of GT-MAS:gk rather than M182 kernels. Further study is needed to explain genotypic variation in the kernel response to A. flavus and F. verticillioides kernel infections. Also, the potential for aflatoxin-resistant corn lines to likewise inhibit growth of F. verticillioides needs to be confirmed in the field.

Aflatoxins↗
PubMed2001

Pre-termination in aflR of Aspergillus sojae inhibits aflatoxin biosynthesis.

The aflR gene product is the main transcriptional regulator of aflatoxin biosynthesis in Aspergillus parasiticus and Aspergillus flavus. Although A. sojae strains do not produce aflatoxins, they do have an aflR homologue. When compared with the aflR of A. parasiticus, the A. sojae gene contains two mutations: an HAHA motif and a premature stop codon. To investigate the functionality of the A. sojae aflR gene product, we used a GAL4 one-hybrid system in yeast. The transcription-activating activity of AflR from A. sojae was 15% of that from A. parasiticus. The introduction of an additional aflR from A. sojae into an A. parasiticus strain did not affect aflatoxin productivity. A hybrid aflR comprising the amino-terminal region of A. sojae aflR and the carboxy-terminal region of A. parasiticus aflR suppressed the effect associated with pre-termination of the A. sojae AflR. We conclude that the premature stop codon of the A. sojae aflR is the key to its functionality and leads to prevention of aflatoxin biosynthesis through loss of the transcription of aflatoxin biosynthesis-related genes.

Aflatoxins↗
PubMed2001

Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes.

Organophosphate (OP) pesticides such as dimethoate and malathion intoxication has been shown to produce oxidative stress due to the generation of free radicals and alter the antioxidant defense system in erythrocytes. It is possible that vitamin E being present at the cell membrane site may prevent OP-induced oxidative damage. In the present study, rats were pretreated orally with vitamin E (250 mg/kg body wt, twice a week for 6 weeks) prior to oral administration of a single low dose of dimethoate and/or malathion (0.01% LD(50)). The result showed that treatment with OP increased lipid peroxidation (LPO) in erythrocytes, however, vitamin E pretreated rats administered OP's showed decreased LPO in erythrocytes. The increase in the activities of superoxide dismutase (SOD) and catalase (CAT) and total-SH content in erythrocytes from dimethoate and/or malathion treated rats as compared to control appears to be a response towards increased oxidative stress. Vitamin E pretreated animals administered OP's showed a lowering in these parameters as compared to OP treated rats which indicates that vitamin E provide protection against OP-induced oxidative stress. The glutathione-S-transferase (GST) activity in erythrocytes was inhibited in OP intoxicated rats which partially recovered in vitamin E pretreated animals administered OP's. Inhibition in erythrocyte and serum acetylcholinesterase (AChE) activity was not relieved in vitamin E pretreated rats administered OP's probably due to the competitive nature of enzyme inhibition by OP's. The results show that vitamin E may amelierate OP-induced oxidative stress by decreasing LPO and altering antioxidant defense system in erthrocytes.

Journal Article↗