Dietary factors and cancer chemoprevention: an overview of obesity-related malignancies.

Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium), fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids), which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

Etiology and management of obscure gastrointestinal bleed--an appraisal from eastern India.

OBJECTIVES AND METHOD: Forty patients (mean age 45 years; 24 men) attending a tertiary care hospital in eastern India during the period 1996-2000 were investigated to evaluate the etiology and clinical spectrum of obscure gastrointestinal bleed. RESULTS: The patients presented to hospital after mean symptom duration of 2.5 years. They had received an average of 15 units of blood transfusion. Most patients presented with recurrent melena (85%); all had iron-deficiency anemia. A total of 230 investigations (89 gastroscopies, 54 colonoscopies, 25 double-contrast meal and follow-through studies, 14 small bowel enemas, 24 radionuclide scans, 16 mesenteric angiographies and 8 intraoperative endoscopies) yielded positive diagnosis in 87.5% of cases. The diseases encountered were small bowel and colonic angiodysplasias (32.5%), ileal Crohn's disease (20%), intestinal tuberculosis (10%), intestinal tumors (10%), nonspecific small bowel ulcers and strictures (7.5%), Meckel's diverticulum (5%) and hemobilia (2.5%). The etiology remained obscure in 5 (12.5%) cases. Overall success of surgery was 63%; in-hospital mortality was 7.5%. CONCLUSION: Though obscure gastrointestinal bleed is commonly caused by angiodysplasias, it can be an atypical presentation of Crohn's disease.

Percutaneous transluminal coronary angioplasty with stenting of anomalous right coronary artery originating from left sinus of Valsalva using the Voda guiding catheter: a report of two cases.

Coronary arteries of anomalous origin are uncommon and some forms seem to be predisposed to atherosclerosis. We report two cases of successful stent implantation in an anomalous right coronary artery originating from the left sinus of Valsalva using the Voda guiding catheter.

Extents of contamination of top milk and their determinants in an urban slum of Varanasi, India.

A community based study to examine the extent of contamination of supplementary milk feeds of 149 children aged 6-24 months was conducted in a semi urban slum of Varanasi, India. Out of 201 children, 149 top milk samples were collected directly from the feeding utensils into a sterile vial and subjected to bacteriological analysis. Overall, 53.7% of milk samples were contaminated by bacteria and among them 16.1% were potentially enteropathogenic in nature. The distribution of pathogens was E. coli (13.4%), Klebsiella spp (5.4%), Enterobacter spp. (5.4%), Pseudomonas aeruginosa (4.7%), Shigella spp. (2.7%) and others (22.1%). The rate of contamination was significantly higher (p < 0.001) in lower income group (73.4%), lower caste (69.6%) and in case of illiterate mothers (69.3%). Bivariate analysis indicated that wherever the afore mentioned parameters of hygiene were adverse, isolation rates increased multifoldely. Multiple logistic regression analysis indicated that the probability of a milk sample being positive for bacterial contamination was higher by 20 times when unclean utensils were used, by 3 times if mothers hands were dirty and by 2.8 time if the mothers were illiterate. The odds of contamination by pathogens was 25.7 times higher if the feeding utensils were dirty.

CSF interleukin-1 beta, tumor necrosis factor-alpha and free radicals production in relation to clinical outcome in acute bacterial meningitis.

OBJECTIVE: To study the relationship of CSF IL-1 beta and TNF-alpha with free radicals in acute bacterial meningitis (ABM) and to evaluate the clinical outcome in relation to the levels of these cytokines and free radicals in CSF. DESIGN: Prospective with controls. SETTING: Referral unit of a teaching hospital. METHODS: 32 children between 3m-12 yrs of age with proven acute bacterial meningitis comprised the study group. In the control group, 20 children with febrile seizures were included. CSF cytokines- Interleukin Ib and tumour necrosis factor a,free radicals O(2)-, H(2)O(2) and enzymes SOD and CPK were measured in all the children. RESULTS: CSF IL-Ib and TNF-a concentration were markedly elevated in children with ABM (441.5 +/- 216.1 pg/ml, and 1009 +/- 529.1 pg/ml, respectively) as compared to controls (52.67 +/- 6.92 pg/ml, and 86.42 +/- 16.24 pg/ml) (p <0.0001). Free radicals viz., superoxide anion, hydrogen peroxide production and enzymes creatinine phosphokinase and superoxide dismutase were also significantly elevated in ABM as compared to controls. There was direct correlation of CSF cytokines with CSF cytology, protein and free radicals production in ABM. Patients who expired or had neurological sequelae had markedly elevated concentrations of cytokines and free radicals. CONCLUSION: IL-I beta, TNF-alpha and free radicals are significantly elevated in CSF of patients with ABM. The concentration of these cytokines correlated well with free radical production, and with routinely measured CSF parameters and had a direct bearing on outcome of ABM

Aetiological spectrum of chronic liver disease in eastern India.

AIM: To evaluate the aetiologic spectrum of chronic liver disease (CLD) in a tertiary referral center in Eastern India. METHODS: A total of 175 patients (cirrhosis 166, chronic hepatitis 9) diagnosed by clinical, biochemical, radiological and histopathological (42 cases) parameters were evaluated for aetiology. Investigations included: HBsAg and anti HCV (third generation) by ELISA. HBeAg and HBV DNA were tested in HBsAg positive patients. HCV RNA was tested in anti-HCV positive patients. Markers for autoimmune and Wilson's disease (anti-nuclear antibody, anti smooth muscle antibody, serum ceruloplasmin, urinary copper and slit lamp examination for KF ring) were done where clinically indicated. RESULTS: A total of 62 (35.4%) patients had HBV related CLD and 6 (9.7%) of them had pre-core mutant. HCV was present in 17/114 (14.9%) cases and none had infection with both viruses. Autoimmunity, Wilson's disease and alcohol were the aetiological factors in 5 (2.8%), 5 (2.8%) and 3 (1.7%) patients respectively. No aetilogy could be found in 18/114 (15.8%) patients. CONCLUSIONS: It is concluded that HBV is the commonest cause of CLD in Eastern India. Alcohol and HCV are uncommon in this part of the country.

Free oxygen radicals in acute renal failure.

OBJECTIVE: To assess the levels of free oxygen radicals in acute renal failure and their predictive value in clinical outcome. DESIGN: Prospective. SETTING: Intensive care unit. METHODS: Study was conducted in 50 children (25 with acute renal failure and 25 age and sex matched controls). Blood urea, serum creatinine, serum protein, uric acid and free oxygen radical markers were estimated in both groups. Superoxide dismutase (SOD), glutathione peroxidase(GPx) and lipid peroxide (LPO) were estimated in blood by standard techniques. RESULTS: Hemolytic uremic syndrome (HUS) was a major cause of acute renal failure (52%), rest were due to acute glomerulonephritis (AGN), septicemia and renal venous thrombosis. In the renal failure group 56% of the patients were dialyzed (peritoneal) and the mortality was 28% (7/25). The levels of SOD, GPx and LPO were significantly raised in renal failure group. Higher values of LPO, SOD and GPx were documented in subjects who expired. The most important independent variable for predicting clinical outcome was LPO with a sensitivity of 89.4%, specificity of 93%, positive predictive value of 95%. CONCLUSION: Levels of free oxygen radicals (SOD, LPO and GPx) are raised in acute renal failure and these enzymes can be used as marker of renal injury. LPO levels are highly sensitivity and specific for predicting the clinical outcome

Seroepidemiology of hepatitis A in Delhi.

A prospective study was done to determine the age specific prevalence of antihepatitis A antibodies (anti HAV Abs) among children in Delhi. Four hundred and twenty children aged 0-12 years attending outpatient department for vaccination or any minor illness were studied. Sera was tested by ELISA for anti HAV Abs using a commercial kit (Hepvase A 96 TMB). Thirty samples of cord blood were similarly analyzed. All samples of cord blood were positive for anti HAV Abs. Prevalence of anti HAV Abs was 80% by 5 years of age. The most vulnerable age group was 0.5-1.5 years (anti HAV Ab positivity). Cord blood had 100% positivity. Univariate and multivariate analyses taking anti HAV antibody positivity as dependant variable demonstrated that age and father's education (socioeconomic status) significantly affect prevalence of anti HAV Abs. Sex, water supply, history of jaundice in self or family did not have any significant effect on anti HAV antibody positivity. Prevalence of anti HAV antibodies is 80% by 5 years of age. Further studies in different strata of society and different regions in the country are required to assess the need and age for vaccination.

Serum TNF-alpha and free radical scavengers in neonatal septicemia.

Tumor necrosis factor-alpha (TNF-alpha) and free radicals have been implicated in the pathogenesis of neonatal septicemia and its complications. This case control study was conducted between November 1996 to July 1997 to determine the levels of TNF-alpha and free radical scavengers viz. superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the serum of 30 septic neonates and 20 healthy controls. Patients with neonatal sepsis registered significantly higher levels of TNF-alpha, SOD and GPX in comparison to controls (p < 0.05). The neonates with septic shock had five fold increase in TNF-alpha levels (2262 +/- 605.8 pg/ml) as compared to those without shock (738.8 +/- 728.8 pg/ml). There was no statistically significant difference in levels of antioxidant enzymes between neonates with shock and without shock. The levels of TNF-alpha and antioxidant enzymes were not affected by the type of organism isolated in blood culture.

Status of lipid peroxidation and antioxidant enzymes in hypoxic ischemic encephalopathy.

OBJECTIVE: To compare the activities of key antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase] and the level of malonyl dialdehyde (MDA) in neonates with hypoxic ischemic encephalopathy (HIE) and controls. DESIGN: Prospective cross sectional study. SETTING: Tertiary care level II neonatal unit of teaching hospital. METHODS: Fifteen term new borns with HIE were registered for the study whereas normal term appropriate for gestational age babies were enrolled as controls. Clinical features were recorded. Activities of SOD, GPx, catalase and the content of MDA were estimated at 24 hours of age. The results obtained were statistically analyzed. RESULTS: Activities of SOD and Catalase and the level of MDA were significantly higher in cases as compared to the controls. There was however no significant alternation in the activity of GPx levels in both the groups. CONCLUSION: The increased activities of antioxidant enzymes are unable to counteract the excessively generated oxidants in vivo, as is evident from the increased MDA levels. Hence, oxygen free radicals may play a significant role in the pathogenesis of HIE.

Changes in anti-oxidant enzymes and lipid peroxidation in hyaline membrane disease.

This study was conducted to elucidate the changes in key antioxidant enzymes e.g. Superoxide dismutase (SOD), Catalase and Glutathione peroxidase (GPx) along with lipid peroxidation (LPO) in preterm newborns having hyaline membrane disease (HMD) and thus to find out role of free radicals mediated injury in this disease. Twenty one preterm appropriate for gestational age newborns were included in the study. Eleven of them had hyaline membrane disease and ten were controls without any disease. Status of superoxide dismutase, glutathione peroxidase and catalase, the three main antioxidant enzymes and lipid peroxidation was monitored at 12-24 hours of age. SOD and catalase were found significantly elevated in cases having hyaline membrane disease along with significantly more lipid peroxidation. It is evident that free radicals result in the induction of the antioxidant enzymes; however, the elevated enzymes are unable to counteract the high concentration of the free radicals which are being produced in the diseased cases and leads to increase in lipid peroxidation in hyaline membrane disease. It is concluded that free radicals play a significant role in hyaline membrane disease and the preterm newborns have ability to induce antioxidant enzymes in response to oxidative stress.

Free oxygen radicals--predictors of neonatal outcome following perinatal asphyxia.

The study was undertaken to evaluate the role of free oxygen radicals in asphyxiated neonates. Thirty term neonates appropriate for gestational age and with severe birth asphyxia (Apgar score of 3 or less at 1 minute of life) formed the study subjects. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), creatine phosphokinase (CPK) and lipid peroxidase (LPO) in the CSF of these neonates were estimated between 12 and 48 hrs of life. Enzyme estimation was performed by standard methods and the results were analysed statistically using Multivariate Logistic Regression analysis and non parametric tests namely Kruskal Wallis test and Wilcoxon's rank sum test. Out of the thirty babies, 14 were observed to be neurologically normal, 9 had significant morbidity and 7 died. The SOD levels ranged from 12.4 to 140 units/ml, GPx from 128 to 1933 nmol/min/dl, CPK from 2 to 2098 IU/dl and LPO from 5.4 to 30.8 umol/hr/dl. The SOD and GPx levels had an inverse relationship whereas rise in LPO and CPK levels were directly proportional to the extent of neurological damage and ultimate clinical outcome. CPK levels higher than 140 IU/ml were lethal and associated with 100% mortality whereas all normal neonates had CPK below 37 IU/ml. The levels of antioxidant enzymes can reliably and significantly predict mortality and morbidity whereas level of an enzyme cannot confidently confer normalcy. Hence antioxidant enzyme levels with a cut off value can be a useful marker and serve as a prognostic indicator in times to come.