A comparison of topical Phenytoin with Silverex in the treatment of superficial dermal burn wounds

Burn injuries constitute a major health problem causing considerable morbidity and mortality in Tanzania and around the world. It is a common surgical problem and leading cause of death (20% mortality) in our paediatric surgical ward (Morbidity/Mortality report 2000 — Muhimbili National Hospital). Mzezewa et al. reported an overall mortality of 22% in a three year study at the Harare Burn Units. Inappropriate treatment facilities lead to severe complications like wound infections and septicaemia, anaemia and contracture deformities resulting in prolonged hospitalization with enormous economic impact in medical cost and loss of time from school and work. Socio-economic factors contributing to increased incidence of burns especially in children include domestic accidents resulting from explosion of cheap kerosene stoves, poor architectural design of the kitchen in low-income families and cooking on open fires at floor level often in the open where children are playing

A comparison of topical Phenytoin with Silverex in the treatment of superficial dermal burn wounds

Burn injuries constitute a major health problem causing considerable morbidity and mortality in Tanzania and around the world. It is a common surgical problem and leading cause of death (20% mortality) in our paediatric surgical ward (Morbidity/Mortality report 2000 — Muhimbili National Hospital). Mzezewa et al. reported an overall mortality of 22% in a three year study at the Harare Burn Units. Inappropriate treatment facilities lead to severe complications like wound infections and septicaemia, anaemia and contracture deformities resulting in prolonged hospitalization with enormous economic impact in medical cost and loss of time from school and work. Socio-economic factors contributing to increased incidence of burns especially in children include domestic accidents resulting from explosion of cheap kerosene stoves, poor architectural design of the kitchen in low-income families and cooking on open fires at floor level often in the open where children are playing

Taurine Supplementation Restores Insulin Secretion And Reduces Er Stress Markers In Protein-malnourished Mice

Endoplasmic reticulum (ER) stress is a cellular response to increased intra-reticular protein accumulation or poor ER function. Chronic activation of this pathway may lead to beta cell death and metabolic syndrome (MS). Poor nutrition during perinatal period, especially protein malnutrition, is associated with increased risk for MS in later life. Here, we analyzed the effects of taurine (TAU) supplementation upon insulin secretion and ER stress marker expression in pancreatic islets and in the liver from mice fed a low-protein diet. Malnourished mice had lower body weight and plasma insulin. Their islets secreted less insulin in response to stimulatory concentrations of glucose. TAU supplementation increased insulin secretion in both normal protein and malnourished mice. Western blot analysis revealed lower expression of the ER stress markers CHOP and ATF4 and increased phosphorylation of the survival protein Akt in pancreatic islets of TAU-supplemented mice. The phosphorylation of the mitogenic protein extracellular signal-regulated kinase (ERK1/2) was increased after acute incubation with TAU. Finally, the ER stress markers p-PERK and BIP were increased in the liver of malnourished mice and TAU supplementation normalized these parameters. In conclusion, malnutrition leads to impaired islet function which is restored with TAU supplementation possibly by increasing survival signals and lowering ER stress proteins. Lower ER stress markers in the liver may also contribute to the improvement of insulin action on peripheral organs. © Springer Science+Business Media New York 2013.776129139Amaral, A.G., Rafacho, A., Machado De Oliveira, C.A., Batista, T.M., Ribeiro, R.A., Latorraca, M.Q., Boschero, A.C., Carneiro, E.M., Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice (2010) Pancreas, 39, pp. 847-855Batista, T.M., Ribeiro, R.A., Amaral, A.G., De Oliveira, C.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from lowprotein diet rats: Involvement of Ach-M3R, Synt 1 and SNAP-25 proteins (2012) J Nutr Biochem, 23, pp. 306-312Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Carneiro, E.M., Latorraca, M.Q., Araujo, E., Beltra, M., Oliveras, M.J., Navarro, M., Berna, G., Martin, F., Taurine supplementation modulates glucose homeostasis and islet function (2009) J Nutr Biochem, 20, pp. 503-511Chen, J.H., Martin-Gronert, M.S., Tarry-Adkins, J., Ozanne, S.E., Maternal protein restriction affects postnatal growth and the expression of key proteins involved in lifespan regulation in mice (2009) PLoS One, 4, pp. e4950Cherif, H., Reusens, B., Ahn, M.T., Hoet, J.J., Remacle, C., Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet (1998) J Endocrinol, 159, pp. 341-348Cnop, M., Foufelle, F., Velloso, L.A., Endoplasmic reticulum stress, obesity and diabetes (2012) Trends Mol Med, 18, pp. 59-68Da Silva, P.M., Batista, T.M., Ribeiro, R.A., Zoppi, C.C., Boschero, A.C., Carneiro, E.M., Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: Effect of leucine supplementation (2012) Metabolism, 61, pp. 721-732Eizirik, D.L., Cardozo, A.K., Cnop, M., The role for endoplasmic reticulum stress in diabetes mellitus (2008) Endocr Rev, 29, pp. 42-61Filiputti, E., Ferreira, F., Souza, K.L., Stoppiglia, L.F., Arantes, V.C., Boschero, A.C., Carneiro, E.M., Impaired insulin secretion and decreased expression of the nutritionally responsive ribosomal kinase protein S6K-1 in pancreatic islets from malnourished rats (2008) Life Sci, 82, pp. 542-548Filiputti, E., Rafacho, A., Araujo, E.P., Silveira, L.R., Trevisan, A., Batista, T.M., Curi, R., Carneiro, E.M., Augmentation of insulin secretion by leucine supplementation in malnourished rats: Possible involvement of the phosphatidylinositol 3-phosphate kinase/mammalian target protein of rapamycin pathway (2010) Metabolism, 59, pp. 635-644Gentile, C.L., Nivala, A.M., Gonzales, J.C., Pfaffenbach, K.T., Wang, D., Wei, Y., Jiang, H., Maclean, K.N., Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease (2011) Am J Physiol Regul Integr Comp Physiol, 301, pp. R1710-R1722Hales, C.N., Barker, D.J., Type 2 (non-insulin-dependent) diabetes mellitus: The thrifty phenotype hypothesis (1992) Diabetologia, 35, pp. 595-601Hotamisligil, G.S., Endoplasmic reticulum stress and the inflammatory basis of metabolic disease (2010) Cell, 140, pp. 900-917Jaquet, D., Gaboriau, A., Czernichow, P., Levy-Marchal, C., Insulin resistance early in adulthood in subjects born with intrauterine growth retardation (2000) J Clin Endocrinol Metab, 85, pp. 1401-1406Lin, J.H., Walter, P., Yen, T.S., Endoplasmic reticulum stress in disease pathogenesis (2008) Annu Rev Pathol, 3, pp. 399-425Lytton, J., Westlin, M., Hanley, M.R., Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps (1991) J Biol Chem, 266, pp. 17067-17071Maturo, J., Kulakowski, E.C., Taurine binding to the purified insulin receptor (1988) Biochem Pharmacol, 37, pp. 3755-3760Nakaya, Y., Minami, A., Harada, N., Sakamoto, S., Niwa, Y., Ohnaka, M., Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes (2000) Am J Clin Nutr, 71, pp. 54-58Ozanne, S.E., Dorling, M.W., Wang, C.L., Nave, B.T., Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats (2001) Am J Physiol Endocrinol Metab, 280, pp. E534-E539Ozcan, U., Cao, Q., Yilmaz, E., Lee, A.H., Iwakoshi, N.N., Ozdelen, E., Tuncman, G., Hotamisligil, G.S., Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes (2004) Science, 306, pp. 457-461Pan, C., Prentice, H., Price, A.L., Wu, J.Y., Beneficial effect of taurine on hypoxia- and glutamateinduced endoplasmic reticulum stress pathways in primary neuronal culture (2012) Amino Acids, 43 (2), pp. 845-855Petry, C.J., Dorling, M.W., Pawlak, D.B., Ozanne, S.E., Hales, C.N., Diabetes in old male offspring of rat dams fed a reduced protein diet (2001) Int J Exp Diabetes Res, 2, pp. 139-143Reis, M.A., Carneiro, E.M., Mello, M.A., Boschero, A.C., Saad, M.J., Velloso, L.A., Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats (1997) J Nutr, 127, pp. 403-410Remacle, C., Dumortier, O., Bol, V., Goosse, K., Romanus, P., Theys, N., Bouckenooghe, T., Reusens, B., Intrauterine programming of the endocrine pancreas (2007) Diabetes Obes Metab, 9 (SUPPL. 2), pp. 196-209Ribeiro, R.A., Bonfleur, M.L., Amaral, A.G., Vanzela, E.C., Rocco, S.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets (2009) Diabetes Metab Res Rev, 25, pp. 370-379Ribeiro, R.A., Santos-Silva, J.C., Vettorazzi, J.F., Cotrim, B.B., Mobiolli, D.D., Boschero, A.C., Carneiro, E.M., Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells (2012) Amino Acids, 43 (4), pp. 1791-1801Ribeiro, R.A., Vanzela, E.C., Oliveira, C.A., Bonfleur, M.L., Boschero, A.C., Carneiro, E.M., Taurine supplementation: Involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets (2010) Br J Nutr, 104, pp. 1148-1155Sparre, T., Reusens, B., Cherif, H., Larsen, M.R., Roepstorff, P., Fey, S.J., Mose Larsen, P., Nerup, J., Intrauterine programming offetal islet gene expression in rats-effects of maternal protein restriction during gestation revealed by proteome analysis (2003) Diabetologia, 46, pp. 1497-1511Theys, N., Bouckenooghe, T., Ahn, M.T., Remacle, C., Reusens, B., Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat (2009) Am J Physiol Regul Integr Comp Physiol, 297, pp. R1516-R1525Tsuboyama-Kasaoka, N., Shozawa, C., Sano, K., Kamei, Y., Kasaoka, S., Hosokawa, Y., Ezaki, O., Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity (2006) Endocrinology, 147, pp. 3276-3284Vo, T., Hardy, D.B., Molecular mechanisms underlying the fetal programming of adult disease (2012) J Cell Commun Signal, 43 (4), pp. 1791-1801Zhang, Y., Xia, Z., La Cour, K.H., Ren, J., Activation of Akt rescues endoplasmic reticulum stress-impaired murine cardiac contractile function via glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeation pore opening (2011) Antioxid Redox Signal, 15, pp. 2407-2424Zhou, Y., Lee, J., Reno, C.M., Sun, C., Park, S.W., Chung, J., Lee, J., Ozcan, U., Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction (2011) Nat Med, 17, pp. 356-36