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MUC5AC is a secretory mucin aberrantly expressed in various cancers. In lung cancer, MUC5AC is overexpressed in both primary and metastatic lesions; however, its functional role is not well understood. The present study was aimed at evaluating mechanistic role of MUC5AC on metastasis of lung cancer cells. Clinically, the overexpression of MUC5AC was observed in lung cancer patient tissues and was associated with poor survival. In addition, the overexpression of Muc5ac was also observed in genetically engineered mouse lung adenocarcinoma tissues (Kras(G12D); Trp53(R172H/+); AdCre) in comparison with normal lung tissues. Our functional studies showed that MUC5AC knockdown resulted in significantly decreased migration in two lung cancer cell lines (A549 and H1437) as compared with scramble cells. Expression of integrins (α5, ß1, ß3, ß4 and ß5) was decreased in MUC5AC knockdown cells. As both integrins and MUC5AC have a von Willebrand factor domain, we assessed for possible interaction of MUC5AC and integrins in lung cancer cells. MUC5AC strongly interacted only with integrin ß4. The co-localization of MUC5AC and integrin ß4 was observed both in A549 lung cancer cells as well as genetically engineered mouse adenocarcinoma tissues. Activated integrins recruit focal adhesion kinase (FAK) that mediates metastatic downstream signaling pathways. Phosphorylation of FAK (Y397) was decreased in MUC5AC knockdown cells. MUC5AC/integrin ß4/FAK-mediated lung cancer cell migration was confirmed through experiments utilizing a phosphorylation (Y397)-specific FAK inhibitor. In conclusion, overexpression of MUC5AC is a poor prognostic marker in lung cancer. MUC5AC interacts with integrin ß4 that mediates phosphorylation of FAK at Y397 leading to lung cancer cell migration.

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BACKGROUND: A number of experimental studies have been put forth suggesting an important role of the hemostatic system in acute pancreatitis (AP) in the recent past. However, meaningful studies on clinical values of parameters of the hemostatic system in predicting pancreatitis associated complications are still scarce. In the current investigation, we evaluated the role of D-dimer to predict the severity of acute pancreatitis on day 1 of admission to the hospital. METHODS: A total of 160 subjects (75 mild AP + 35 severe AP + 50 healthy controls) were examined in the study. Biochemical and hemostatic parameters were compared between various groups of subjects on day 1 and day 3 of admission to the hospital. RESULTS: Levels of prothrombin time (PT), fibrinogen, D-dimer, and C-reactive protein (CRP) were significantly higher in the severe AP group than in the mild AP group. Antithrombin III (AT III) levels were significantly lower in the severe AP group than in the mild AP group. D-dimer levels were 5 times higher than the reference limit in the severe group and 1.7 times higher than the reference limit in the mild group. This difference was statistically highly significant (< 0.0001). A positive correlation between D-dimer and CRP, D-dimer and fibrinogen, and between D-dimer and PT was recorded. CONCLUSIONS: Estimation of the levels of D-dimer on admission day provides an accurate method for the identification of patients who will develop systemic complications in the further course of AP.

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Azolla microphylla Kaulf. is an aquatic nitrogen fixing pteridophyte commonly found in aquatic habitats including paddy fields. Methanolic extract of the fronds of A. microphylla was subjected to partial purification by solvent partitioning with diethyl ether and ethyl acetate followed by hydrolysis, and further partitioning with ethyl acetate. The two fractions, thus obtained were tested for antibacterial activity. It was observed that the ethyl acetate fraction inhibited the growth of the pathogenic bacterium Xanthomonas oryzae. The GC-MS analysis of the ethyl acetate fraction showed several prominent peaks with retention time ranging from 8.83 to 45.54 min. A comparison of these peaks with the GC-MS libraries revealed that it could be eicosenes and heptadecanes with potential of antimicrobial activity.

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BACKGROUND: Individuals with obesity and abdominal adiposity are at higher risk for hyperinsulinaemia, insulin resistance, and diabetes. This study was, therefore, designed to evaluate the association of both generalized and regional obesity with metabolic variables and biochemical indices. METHODS: 200 confirmed patients of type-2diabetes of either gender were studied. RESULTS: A statistically significant degree of dyslipidemia was depicted in obese class-II subjects; however, females had a lower degree of dyslipidemia as compared to male subjects with statistically significant results only for HDL-C. Further, multiple logistic regression analysis revealed that BMI is a stronger predictor of FPG and HbA1c as compared to WHR. CONCLUSIONS: Higher plasma glucose levels were depicted at a lower BMI, which turned out to be stronger predictor of glycemic control as compared to WHR. Moreover, BMI, WHR and male gender was significantly correlated with the metabolic parameters and even much more pronounced association with BMI.

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Oxidative stress is a leading cause of male infertility. To combat this, germ cells and spermatozoa are endowed with various enzymes, vitamins and proteins. Certain other components of food, including bioflavonoids, also provide protection against free radicals. This study analysed the effect of quercetin, a bioflavonoid, on male reproductive function in adult mice, after intraperitoneal treatment with varying concentrations of quercetin (2, 8 and 20 mg kg(-1) b.wt.) for 2 weeks. Quercetin increased the generation of reactive oxygen species and lipid peroxidation in the testis with concomitant decrease in sperm count and motility in a dose-dependent manner. Activities of antioxidant enzymes catalase, superoxide dismutase and levels of reduced glutathione were found to be decreased in a dose-dependent manner. Also, the levels of oxidised glutathione were increased leading to a shift in redox ratio. The testicular histomorphology was also altered dose dependently. Germ cell kinetic study revealed significant loss of various germ cell populations with increasing dose of quercetin. Interestingly, there was a reduction in germinal epithelium thickness concomitant with an increase in seminiferous tubule lumen diameter. In conclusion, the deleterious effects of quercetin on germ cells could be attributed to its pro-oxidant ability that might affect the Sertoli cell functions.

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BACKGROUND: To find out the incidence of hyperprolactinemia in infertile women and to find its correlation with hypothyroidism. METHODS: One hundred infertile women attending the out patient Department of Obstetrics and Gynaecology formed the subject matter of the study. Hormone levels of prolactin and thyroid stimulating hormone (TSH) were studied in all the subjects. The exclusion criterion was male factor infertility. Amongst the female factors leading to exclusion from the study were tubal factor, congenital abnormality of the urogenital tract, and any organic lesions. RESULTS: Of the one hundred infertile women, sixty (60%) had primary infertility and forty women (40%) had secondary infertility. Galactorrhea was present in 15% of the women. The incidence of hyperprolactinemia i.e. serum prolactin level > 15 ng/mL was 46%. Out of forty six, thirty women had primary infertility and sixteen women had secondary infertility. The mean serum prolactin level in hyperprolactinemic women was 79.40 +56.59 ng/mL (range: 25.0-230.0 ng/mL). The mean serum prolactin level was not significantly different in the primary and secondary infertile group. The incidence of hypothyroidism in hyperprolactinemia was 28.26%. The mean serum TSH level in hypothyroid women with hyperprolactinemia was 32.06 +/- 23.00 (range: 7.92-78.00 microIU/mL). The TSH level was not significantly different in primary and secondary infertile women. CONCLUSIONS: A high incidence of hyperprolactinemia was found in infertile women and a positive correlation was found between hyperprolactinemia and hypothyroidism.

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BACKGROUND: Individuals with obesity and abdominal adiposity are at higher risk for hypeinsulinaemia, insulin resistance, and diabetes. This study was therefore designed to investigate the relationship of obesity with oxidative stress and the role of abdominal adiposity on obesity induced oxidative stress, and further to explore the possible mechanism of obesity associated metabolic syndrome. METHODS: A total of 150 subjects (120 men and 30 women), aged 17-26 years of both genders, were studied. Body Mass Index and Waist-to-Hip Ratio were taken as a measure of generalized obesity and abdominal adiposity. The biochemical tests done included fasting blood glucose (FBG), lipid profile parameters, serum malondialdehyde (as a biomarker of oxidative stress), and serum adiponectin. RESULTS: The concentration of serum malondialdehyde (MDA) increased with increasing levels of BMI (as per the NIH classification), which was found to be non-significant statistically in overweight subjects while obese class-I and class-II subjects exhibited a statistically significant (p < 0.001) higher level of serum malondialdehyde as compared to normal-weight subjects. Furthermore, according to the present study groups, on comparison with normal-weight subjects (Group-I), obese subjects with abdominal adiposity (Class-2) had statistically significant (p < 0.001) higher serum concentration of malondialdehyde while a non-significant difference was observed in obese subjects without abdominal adiposity (Class-1). Even within the subset of obese subjects, a statistically significant (p < 0.001) difference was depicted, suggesting the role of abdominal adiposity. Karl Pearson coefficient of correlation revealed a statistically significant negative correlation of malondialdehyde with adiponectin (r = - 0.587; p < 0.001). CONCLUSIONS: Obese subjects exhibit increased systemic oxidative stress, which is enhanced when obesity is associated with abdominal adiposity and, moreover, increased oxidative stress is associated with adiponectin deficiency.

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BACKGROUND: Subclinical hypothyroidism (SH) represents the mildest form of thyroid hormone deficiency and may be associated with adverse consequences [Subclinical hypothyroidism was defined as a TSH level > 4.0 mIU/L and a normal free thyroxine level 0.6-1.8 ng/dL]. The identification of patients with subclinical hypothyroidism having an increased cardiovascular risk (CVR) is important. The aim of the study was to evaluate atherosclerotic risk factors in patients with subclinical hypothyroidism. METHODS: Forty patients with subclinical hypothyroidism and forty healthy euthyroid controls, age and gender matched were included in the study. Serum total triiodothyronine (T3), thyroxine (T4), TSH, free T3 (FT3) and free T4 (FT4) were measured by enzyme linked immunosorbent assay (ELISA). Atherosclerotic risk factors measured were high sensitivity-CRP (hs-CRP), Lipoprotein (a) [Lp (a)] and lipid parameters. Lipid parameters (triglycerides, total cholesterol and high density lipoprotein cholesterol) were analysed by enzymatic colorimetric, endpoint method whereas the hs-CRP and Lp (a) were measured by quantitative latex turbidimetric method. RESULTS: Patients with subclinical hypothyroidism had significantly higher levels of serum hs-CRP, Lp (a), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) when compared to same parameters of controls. Further, a significant positive correlation was observed between TSH and hs-CRP, Lp (a), LDL-C and TC in subjects with subclinical hypothyroidism. However, TG levels showed no significant correlation with TSH levels. CONCLUSIONS: We concluded that the SH patients presented increased concentration of some CVR factors. The potential benefits of diagnosis and treatment of subclinical hypothyroidism may have possible advantages firstly by preventing the progression to overt hypothyroidism and secondly decrease the risk of death from cardiovascular disease (CVD) by starting appropriate therapy to improve lipid parameters. Further research is needed on subclinical hypothyroidism and the associated atherosclerotic risk factors.

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BACKGROUND: Increasing evidence in both experimental and clinical studies suggests that free radical mediated oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Proteins and lipids are among the prime targets for oxidative stress. In this study we evaluated oxidative stress in Type 1 Diabetes Mellitus (insulin dependent diabetes mellitus, IDDM) patients by estimating lipid peroxidation and the effect of vitamin E on oxidative stress and metabolic parameters. METHODS: A total of 40 children (20 Type 1 Diabetes Mellitus patients + 20 healthy controls) were examined in the study. Oxidative stress parameters malondialdehyde (MDA), antioxidants, reduced glutathione (GSH), vitamin E and metabolic parameters were studied. All the type 1 Diabetes Mellitus patients were supplemented with 600 mg/daily vitamin E for three months. After three months of supplementation all the parameters mentioned above were studied again. RESULTS: Reduced glutathione and vitamin E levels were lower and malondialdehyde levels were higher in Type 1 Diabetes Mellitus patients compared to healthy controls (p < 0.05). After supplementation with vitamin E in diabetic patients a significant decrease (p < 0.05) in MDA levels and significant increase in GSH (p < 0.05) and vitamin E (p < 0.05) levels were found. A negative correlation between MDA and vitamin E, between MDA and GSH and a positive correlation between vitamin E and GSH was found. Significant changes were not observed in metabolic parameters in Type 1 Diabetes Mellitus patients after vitamin E supplementation (p > 0.05). CONCLUSIONS: Vitamin E ameliorates oxidative stress in Type 1 Diabetes Mellitus patients and improves antioxidant defense system. However, vitamin E does not have any advantage for metabolic parameters.

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Esophageal carcinoma has a high incidence in India but its etiology remains unknown. In the present study the correlation between apoptosis regulatory proteins and anti-oxidant enzymes in 40 esophageal carcinoma patients was examined. Patients in one group were operated by transhiatal esophagectomy and in the second group were administered cisplatin (30 mg/m2/day) and 5-fluorouracil (5-FU) (750 mg/m2/day) daily for three days followed by surgery after four weeks of neo-adjuvant therapy (NAT). Complete pathological response was achieved in 15% of patients. Results obtained by Western blot analysis showed over-expressed p53 and COX-2 protein levels in the tumor tissues as compared to the adjoining tissue and its paired normal mucosa in both groups of patients. Immunohistochemical studies showed heterogenous p53 staining pattern with sections showing both nuclear and cytoplasmic staining with 36.8% mild, 10.5% moderate and 52.6% intense p53 immunoreactivity. Both COX-2 and iNOS immunostaining revealed 25% negative and 75% mild to strongly positive immunoreactivity. Correlation studies demonstrated a positive relationship between p53 and COX-2 (P=0.030; r = +0.70) in surgically treated patients. The association of COX-2 and p53 with various anti-oxidant enzymes showed a significantly positive correlation between COX-2 expression and catalase activity and an inverse correlation between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given NAT. In addition, we observed a negative trend between p53 expression levels and GPx enzyme levels in both the adjoining and tumor tissue of patients having undergone surgery as main mode of treatment.

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PURPOSE: To evaluate the effect of low-dose (<50 cGy) whole body ?-irradiation on the antioxidant defense system in the liver and the lungs of mice at various post-irradiation intervals. MATERIALS AND METHODS: Male Balb/c mice, 5 - 6 weeks of age, were divided into irradiated and non-irradiated groups. Whole body irradiation was done with gamma-rays from a (60)Co source at doses of 10, 25 and 50 cGy (48.78 cGy/min). Lipid peroxidation and antioxidant status were measured in the liver and the lungs at 4, 12 and 24 h after irradiation. RESULTS: Lipid peroxidation increased by 1.38 and 2.0 fold in lung and liver respectively at 12 h after exposure to 25 cGy. Whole body exposure to 25 and 50 cGy significantly (p < 0.05) increased the hepatic reduced glutathione at 4 h. Reduced glutathione continued to rise until 12 h and returned to the basal level at 24 h, whereas in the lungs it remained elevated until 24 h at 10 and 25 cGy. Antioxidant enzymes activities for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase increased by 1.22, 1.13, 1.22 and 1.11 fold respectively (p < 0.05) in the liver at 4 h after exposure to 50 cGy and remained elevated at almost the same level up to 12 h after exposure. Surprisingly these antioxidant defense enzymes remained unaltered in the lung at the above radiation doses. CONCLUSIONS: Low-dose whole body gamma-irradiation differentially modulates the antioxidant defense system in the liver and lungs of mice. The induction of endogenous glutathione, immediately after exposure to low-dose -irradiation, may be beneficial in protecting the cells from reactive oxygen species (ROS) induced oxidative stress.

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OBJECTIVES: To compare oral versus intravenous iron in pre-dialysis patients of chronic renal failure (CRF) receiving recombinant human erythropoietin (rHuEPO). METHODS: The study was undertaken in 40 adult patients of chronic renal failure. The patients were randomly divided into two groups A and B of 20 patients each. Group A patients were given oral iron and group B patients were given intravenous iron. All patients in both groups were given recombinant human erythropoietin 2000 IU twice weekly subcutaneously. The study was carried for up to three months. Patients were monitored every month for renal parameters and haematological parameters which included haemoglobin, reticulocyte count and packed cell volume. Ferrokinetic studies were done at baseline and at three months. RESULTS: It was observed that haematological parameters showed significant statistical improvement in the intravenous iron group as compared to group A (oral iron group). The ferrokinetic studies revealed that serum iron, serum ferritin and transferrin saturation, decreased significantly in oral iron group, whereas significant increase was seen in group B (intravenous iron group). None of the patients developed any adverse effects because of erythropoietin or iron therapy. CONCLUSIONS: Concomitant use of intravenous iron is better than oral iron in CRF patients treated with rHuEPO. The intravenous route of iron administration may be a preferred route along with rHuEPO therapy, more so in the Indian context where prevalence of iron deficiency anaemia is fairly high.

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