Retinoid metabolism in the rat small intestine

Vitamin A (retinol) is essential for epithelial cell growth, differentiation and proliferation. The absorption of retinol occurs in the small intestine, and the metabolism of this vitamin is not well studied in this organ. The intestinal epithelium has a high rate of cell proliferation and differentiation, and the present study looked at the level of retinoids and metabolizing enzymes involved in their interconversion along the villus-crypt axis under normal conditions. Intestine was removed from control rats, and enterocytes at various stages of maturation and differentiation were quantified by the metal chelation method. Using HPLC, various retinoid concentrations in the cell homogenate and the metabolizing enzymes in the cytosol were quantified. The proliferating crypt cells were found to have a higher level of retinoic acid as well as of the enzymes involved in its formation, such as retinaldehyde oxidase and retinol dehydrogenase, compared with the villus cells, suggesting a possible role for this compound in intestinal epithelial cell proliferation and differentiation. The high level of retinol and high retinaldehyde reductase activity in the villus cells suggest the important role played by this enzyme in the conversion of dietary beta-carotene to retinol via retinaldehyde. In summary, this study has given for the first time a detailed analysis of the retinoid levels and metabolizing enzymes in different cell populations in the rat small intestinal epithelium.     

Oral glutamine attenuates indomethacin-induced small intestinal damage

The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract. In the small intestine, the effects these drugs have been shown to produce include inhibition of cyclo-oxygenase, mitochondrial dysfunction and free radical-induced oxidative changes, all of which contribute to the mucosal damage seen. Glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells. In the present study, we investigated the effect of glutamine on indomethacin-induced changes in the small intestinal mucosa. Rats were given 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine or alanine, in the diet for 7 days. Indomethacin was then administered orally at a dose of 40 mg/kg of body weight. After 1 h, the small intestine was removed and used for the measurement of parameters of oxidative stress and mitochondrial and BBM (brush border membrane) function. Evidence of oxidative stress was found in the mucosa of the small intestine of drug-treated rats, as indicated by significantly increased activity of xanthine oxidase (P < 0.001) and myeloperoxidase (P < 0.001), with corresponding decreases in the levels of several free radical scavenging enzymes and alpha-tocopherol (P < 0.001 in all cases). Levels of products of peroxidation were also significantly elevated (P < 0.001 for all the parameters measured). In addition, oxidative stress was evident in isolated intestinal mitochondria and BBMs (P < 0.001 for all the parameters measured), with associated alterations in function of these organelles (P < 0.001 for all the parameters measured). Supplementation of the diet with glutamine or glutamic acid prior to treatment with indomethacin produced significant amelioration in all the effects produced by the drug in the small intestine (P < 0.001 for all the parameters measured). Glycine and alanine were found to be much less effective in these respects.     

Racial differences in the treatment of colorectal cancer: a comparison of surgical and radiation therapy between Whites and Blacks

PURPOSE: To evaluate black to white differences in treatment for colorectal cancer. METHODS: Only whites or blacks diagnosed with colon or rectal cancer between 1988 and 1997 were identified from SEER database. RESULTS: A total of 106,377 (91.3% white, 50.5% male) patients formed the study population. The vast majority of these patients received standard cancer treatment. Although the number of subjects who did not receive such treatment was small, their proportion was higher among blacks than among whites. The odds of non-receipt of surgical treatment was higher among blacks than whites for stage I (OR = 2.08, 95% CI, 1.41, 3.03 among males; OR = 2.38, 95% CI, 1.69, 3.45 among females) and stage IV colon cancer (OR = 1.25, 95% CI, 1.01, 1.56 among males; OR = 1.41; 95% CI, 1.14, 1.72 among females). A similar pattern was also seen for most stages of rectal cancer. CONCLUSIONS: Most black and white colorectal cancer patients received standard treatment. Although the number of subjects without standard treatment was small, their proportion was higher among blacks than among whites. Blacks were also more likely to refuse recommended treatment. Efforts in educating black patients about the benefits of treatment may help to eliminate the remaining racial disparity.     

Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells

The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.     

Studies on dengue in rural areas of Kurnool District, Andhra Pradesh, India

A dengue case was reported for the 1st time in a rural area of Kurnool District, Andhra Pradesh, India. Entomological and serological investigations were carried out to determine the prevalence of dengue vectors and dengue virus. Aedes aegypti was recorded for the 1st time in rural areas of Andhra Pradesh. Breeding of Ae. aegypti was observed only in containers with nonpotable water. Cement cisterns and tanks, stone tubs, and clay pots were the major breeding habitats of Ae. aegypti. Larval indices for Ae. aegypti ranged as follows: house index 28-40%, container index 13-37%, and Breteau index 32-60. A serological survey indicated that humans in Kurnool District have been exposed to dengue virus infections. The potential threat of an outbreak of dengue fever in rural areas because of the prevalence of the vector (Ae. aegypti) and dengue virus is discussed.     

Expression of connective tissue growth factor after glaucoma filtration surgery in a rabbit model

PURPOSE: Connective tissue growth factor (CTGF) appears to play a significant role in mediating fibrosis in several tissues. To gain further understanding of the role of CTGF in the scar formation that occurs after glaucoma filtering surgery (GFS), experiments were performed in a rabbit model. METHODS:. Three experiments were performed: (1) CTGF and transforming growth factor (TGF)-beta expression were measured quantitatively after GFS, using ELISA. (2) After GFS conjunctival bleb tissues were immunostained for the presence of CTGF and TGF-beta. (3) Exogenous CTGF was injected into mitomycin-C (MMC)-treated filtering blebs and the scaring response compared to TGF-beta and physiological saline-injected blebs. RESULTS: CTGF and TGF-beta were expressed maximally by day 5 after surgery and were both shown to be present in the bleb tissues after GFS. The addition of exogenous CTGF and TGF-beta increased the rate of failure of GFS blebs. CONCLUSIONS: These data support the hypothesis that CTGF plays an important role in scarring and wound contracture after GFS. Inhibition of CTGF synthesis or its action may help prevent bleb failure and improve long-term GFS outcomes.     

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction  

Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.     

Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src

In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes.