[Effects of hydro- alcoholic extract of falcaria vulgaris on pancreas tissue in streptozotocin-induced diabetic rats]

Introduction: Diabetes, as a chronic disease, is the third leading cause of death in developing countries. Hyperglycemia and oxidative stress have been recognized as the main factors involved in pathogenesis of diabetes. On the other hand, the antioxidant system is the first defense mechanism of body against oxidative stress. Falcaria Vulgaris possesses hypoglycemic and antioxidant effects. This study surveyed the effects of different doses of Falcaria vulgaris extract [50,100,150 mg/kg] on histological changes of Langerhans islets andserum insulin, nitric oxide and glucose levels

Materials and Methods: A total of 64 male Wistar rats were divided into 8 groups [control, diabetic with STZ, treatment with Falcaria Vulgaris [50,100,150 mg/kg] and diabetic treated with Falcaria Vulgaris] [50,100,150 mg/kg]. Data were analyzed by one-way ANOVA, and p value<0.05 was considered significant

Results: Falcaria Vulgaris extract [100 and 150 mg/kg] significantly decreased serum glucose level [p<0.01] and improved the diameter of islets [p<0.05] in diabetic rats treated with Falcaria Vulgaris extract, compared with the diabetic group. Moreover, at dose of 150 mg/kg, the extract improvedserum insulin [p<0.01], decreased nitric oxide [p<0.01] and increased the weight [p<0.01] and number of islets of diabetic rats [p<0.05]. Histopathological studies also confirmed these changes

Conclusion: F. vulgaris can improve insulin secretion and serum glucose levels in an animal model of STZ induced diabetes, possibly by reducing nitric oxide production and preventing pancreatic tissue oxidative damage

Síndrome de Stevens-Johnson e Necrólise Epidérmica Tóxica em um hospital do Distrito Federal / Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a hospital in Distrito Federal / Síndrome de Stevens-Johnson y necrólisis epidérmica tóxica en un hospital en Distrito Federal

Objetivou-se analisar as características demográficas e clínicas dos clientes diagnosticados com Síndrome de Stevens Johnson (SSJ) e Necrólise Epidérmica Tóxica (NET), bem como identificar as ações dos profissionais de saúde para o manejo das Reações Adversas a Medicamentos (RAM) em um hospital público do Distrito Federal. Pesquisa descritiva, retrospectiva, com abordagem quantitativa. Dados coletados em todos os prontuários de 22 clientes internados de janeiro de 2005 a setembro de 2012. Análise mediante estatística descritiva. Houve aumento gradativo de casos, com maior número nos anos de 2007 e 2012. Dos casos analisados, 9 foram diagnosticados com NET e 7 com SSJ; predominaram as mulheres (14) e a faixa etária de 21 aos 40 anos (10); 21 obtiveram cura. Os fármacos associados a RAM mais frequentes foram os antiepilépticos (10). Observou-se fragilidade nos registros clínicos nos prontuários e nas ações de monitoramento de RAM no serviço estudado.

This study aimed to analyze demographic and clinical aspects of patients diagnosed with Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), as well as identifying the actions of health professionals for the management of Adverse Drug Reactions (ADR) in a public hospital in Distrito Federal, Brazil. A descriptive and retrospective research was held, with quantitative approach. Data collected from all the records of 22 patients admitted with diagnosed with SJS and TEN, from January 2005 to September 2012. Data were analyzed using descriptive statistics. Of these cases, 9 were diagnosed with NET and 7, with SJS; there were more females (14); aged from 21 to 40 years (10); 21 were cured; the drugs more used were the antiepileptic ones (10). Fragility in clinical registers and in the actions to monitor the cases of ADR in this health service was observed.

Este estudio tuvo como objetivo analizar aspectos demográficos y clínicos de clientes con diagnóstico de Síndrome de Stevens Johnson (SSJ) y Necrólisis Epidérmica Tóxica (NET), así como la identificación de las acciones de los profesionales de la salud para el manejo de reacciones adversas a medicamentos (RAM) en un hospital público del Distrito Federal. Se realizó investigación descriptiva, retrospectiva con enfoque cuantitativo. Datos recogidos de prontuarios clínicos de los 22 clientes ingresados con diagnóstico de SJS y NET, de enero de 2005 a septiembre de 2012. Fueron analizados utilizando estadística descriptiva. De estos casos, 9 fueron diagnosticados con NET, 7 con SJS; había más mujeres (14); edad entre 21 y 40 años (10); 21 se curaron; predominaran los antiepilépticos (10). Fue observado que hay fragilidad en registros clínicos en los prontuarios y en las acciones de monitoreo de las RAM en este servicio de salud.

[Metformin effect on the mouse pancreatic langerhans islets volume]

Metformin is a widely used medicine for treatment of type 2 diabetes. In this study, the effect of various doses of metformin on the mouse islets of langerhans volume was investigated. Twenty four C57BL/6 adult male mice weighting 30 +/- 5 gr were randomly divided into 4 groups. Normal saline was given to the control group [group 4] and the experimental groups [groups 1-3] received 75, 150 and 300 mg/kg metformin daily by intraperitoneal injection for seven days. One day after the last injection the mice were sacrificed by cervical dislocation and their pancreases were fixed in 10% formalin for histological studies. The volume of the islets of langerhans was estimated by using Cavalieri method. Volume of the islets of langerhans in doses of 75 and 150 mg/kg Metformin showed a nonsignificant difference in comparison to control group [P>0.05]. 300 mg/kg metformin treated mice showed a significant increase in islets of langerhans volume compared to the control group [P<0.05]. Metformin increases in the islets of langerhans volume in a dose-dependent manner. Increasing effects of Metformin on the islets of langerhans volume may be due to proliferation or hypertrophy of beta cells

Pancreatic islet allograft in spleen with immunossuppression with cyclosporine. Experimental model in dogs / Alotransplante de ilhotas pancreáticas no baço com imunossupressão com ciclosporina. Modelo experimental em cães

PURPOSE: To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. METHODS: Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. RESULTS: The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. CONCLUSIONS: In the animals with immunosupression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

OBJETIVO: Avaliar o comportamento funcional do alotransplante com imunossupressão de ilhotas pancreáticas no baço. MÉTODOS: Foram utilizados cinco grupos de 10 cães mestiços: grupo A (controle) submetido aos exames bioquímicos; grupo B, submetido à pancreatectomia total; grupo C (autotransplante) submetido à pancreatectomia total e autotransplantação de ilhotas pancreáticas no baço; grupo D, submetido à alotransplantação de ilhotas pancreáticas no baço sem terapia imunossupressiva; grupo E, submetido à alotransplantação de ilhotas no baço e imunossupressão com ciclosporina. Todos os animais transplantados receberam ilhotas pancreáticas isoladas pelo método mecânico-enzimático, digestão estacionária com colagenase e purificação com gradiente de densidade descontínua de dextran e foram implantadas no baço. RESULTADOS: Animais autotransplantados e alotransplantados com imunossupressão que se tornaram normoglicêmicos apresentaram testes de tolerância à glicose intravenosa alterados (p<0,001) e o nível de insulina plasmática periférica e na veia esplênica foram significantemente menores (p<0,001) nos animais alotransplantados com imunossupressão em relação aos autotransplantados. CONCLUSÃO: Nos animais submetidos ao alotransplante de ilhotas pancreáticas com imunossupressão com ciclosporina e preparadas pelo método mecânico-enzimático, digestão estacionária com colagenase e purificação com gradiente de densidade descontínua de dextran, a produção de insulina está diminuída e a resposta à sobrecarga de glicose intravenosa alterada.

Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid

Chronic administration of glucocorticoids induces insulin resistance that is compensated by an increase in p-cell function and mass. Since insulin signaling is involved in the control of p-cell function and mass, we investigated the content of insulin pathway proteins in pancreatic islets. Rats were made insulin resistant by daily administration of dexamethasone (1mg/kg, b.w., i.p.) for 5 consecutive days (DEX), whilst control rats received saline (CTL). Circulating insulin and insulin released from isolated islets were measured by radioimmunoassay whereas the content of proteins was analyzed by Western blotting. DEX rats were hyperinsulinemic and exhibited augmented insulin secretion in response to glucose (P < 0.01). The IRa-subunit, IRS-1, Shc, AKT, p-p70S6K, ERK1/2, p-ERK1/2, and glucocorticoid receptor protein levels were similar between DEX and CTL islets. However, the IRp-subunit, p-IRp-subunit, IRS-2, PI3-K, p-AKT and p70S6K protein contents were increased in DEX islets (P < 0.05). We conclude that IRS-2 may have a major role, among the immediate substrates of the insulin receptor, to link activated receptors to downstream signaling components related to islet function and growth in this insulin-resistant rat model.

Bilirubin protects grafts against nonspecific inflammation-induced injury in syngeneic intraportal islet transplantation

Nonspecific inflammatory response is the major cause for failure of islet grafts at the early phase of intraportal islet transplantation (IPIT). Bilirubin, a natural product of heme catabolism, has displayed anti-oxidative and anti-inflammatory activities. The present study has demonstrated that bilirubin protected islet grafts by inhibiting nonspecific inflammatory response in a syngeneic rat model of IPIT. The inflammation-induced cell injury was mimicked by exposing cultured rat insulinoma INS-1 cells to cytokines (IL-1beta, TNF-alpha and IFN-gamma) in in vitro assays. At appropriate lower concentrations, bilirubin significantly attenuated the reduced cell viability and enhanced cell apoptosis induced by cytokines, and protected the insulin secretory function of INS-1 cells. Diabetic inbred male Lewis rats induced by streptozotocin underwent IPIT at different islet equivalents (IEQs) (optimal dose of 1000, and suboptimal doses of 750 or 500), and bilirubin was administered to the recipients every 12 h, starting from one day before transplantation until 5 days after transplantation. Administration of bilirubin improved glucose control and enhanced glucose tolerance in diabetic recipients, and reduced the serum levels of inflammatory mediators including IL-1beta, TNF-alpha, soluble intercellular adhesion molecule 1, monocyte chemoattractant protein-1 and NO, and inhibited the infiltration of Kupffer cells into the islet grafts, and restored insulin-producing ability of transplanted islets.

Effects of alcoholic extract of Momordica charantia (Linn.) whole fruit powder on the pancreatic islets of alloxan diabetic albino rats.

Alcoholic extract of whole fruit of Momordica charantia was prepared. Adult healthy albino rats were divided into four groups and received a dose of 6 mg/l00 gm. body weight of alloxan monohydrate. Animals of group I served as diabetic control group. The animals of II, III, and IV groups received 25 mg, 50 mg and 75 mg doses of the extract respectively for different durations. 75 mg dose showed increase in body weight. All doses of alcoholic extract of M. charantia were able to decrease the blood sugar level significantly. Extract feeding showed definite improvement in the islets of Langerhans. No toxic effect was observed in the liver The significant features of the study have been blood glucose once lowered by the treatment with M. charantia fruit extract remained static even after discontinuation of drug for 15 days. Blood sugar never fell below normal values even with a high dose, in pancreatic islets, beta cells showed definite improvement.

Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody

Pancreatic islet transplantation can correct the abnormal glucose metabolism of Type 1 diabetes. Although immunosuppressants greatly reduce the acute rejection rate in transplant patients, the long-term side effects can be debilitating. Therefore, researchers are seeking to develop new immunosuppressive regimens that induce maximal levels of immunosuppression with minor side effects. Rosmarinic acid (Ros A) is a secondary metabolite of certain herbs and has multiple biological activities, including anti-inflammatory effects. Here, we have investigated whether treatment of mice with a combination of Ros A and anti-CD154 monoclonal antibody (MR1) improves islet allograft survival in a murine model. After transplantation, the mice were treated with either Ros A, MR1, or both (the "double" treatment). Allograft survival was prolonged in the double-treated animals compared to animals that received only Ros A or MR1. As is the case with the single-treated animals at 15 days after transplantation, the double-treated recipients did not display a significant decrease in the expression of cytokines or the population of activated T cells. Infiltrating CD3+ T cells were reduced in the MR1- or double therapy relative to control or RosA group. However, at the same time point, double-treated graft showed fewer apoptotic cells and increased expression of insulin and glucagons, compared to the single-treatment groups. Furthermore, long-term (>150 days) allografts that were received with double therapy exhibited larger islet clusters and contained more insulin- and glucagon-positive cells, relative to the MR1-treated grafts. In conclusion, treatment with both Ros A and MR1 has a synergistic effect in murine islet allotransplantation.

Effects of ethanolic extract of Syzygium cumini (Linn) seed powder on pancreatic islets of alloxan diabetic rats.

The ethanolic extract of seeds of S. cumini increased body weight and decreased blood sugar level in alloxan diabetic albino rats. Level of significance for decrease in blood sugar after feeding alcoholic extract of S. cumini seeds in various doses was highly significant. The extract feeding showed definite improvement in the histopathology of islets. The most important finding is that the blood sugar level, which once dropped to normal levels after extract feeding was not elevated when extract feeding was discontinued for 15 days.

Hypoglycemic and hypolipidemic effects of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic rats: a comparative study with T. terrestris (Caltrop).

The extracts of both T. alatus and T. terrestris significantly decrease fasting glucose level in diabetic rats. After 4 and 6 hr, T. alatus extract showed significant reduction in glucose level as compared to T. terrestris. After 3 weeks of treatment with T. alatus extract, glucose level was significantly decreased to the normal level. Both the extracts also caused a significant decrease in the levels of glycosylated hemoglobin, total cholesterol, triglycerides and LDL-cholesterol. The percent of reduction in rats treated with T. alatus extract was significantly higher than that of the rats treated with T. terrestris. The results indicate that alcoholic extract of T. alatus possesses hypoglycemic activity in type-1 model of diabetes.

Estrogen increases glucose-induced insulin secretion from mouse pancreatic islets cultured in a prolonged high glucose condition.

BACKGROUND: It is known that males are more susceptible to develop type 2 diabetes than females. Estrogen has a protective effect on pancreatic islet against toxic agent such as amyloid. The role of estrogen in protection pancreatic islet against high glucose is still unknown. OBJECTIVE: Administration of estrogen in an ovariectomised animal shows a protective effect against type 2 diabetes. The present study aimed to determine the direct effect of estrogen on the islet function after prolonged culture in high glucose. MATERIAL AND METHOD: Estrogen (10-1 M in ethanol) was co-cultured with mouse pancreatic islets in normal glucose medium (11.1 mM) for 3 hours or with normal and high glucose medium (40 mM) for 10 days. RESULTS: Estrogen increased glucose-induced insulin secretion in islet culture in normal glucose medium for both 3-hour and 10-day culture. Prolonged exposure of pancreatic islet to high glucose generated impaired glucose-induced insulin secretion, which was partially abrogated by the presence of 10(-5) M estrogen. CONCLUSION: These results indicated a direct effect of estrogen on improving insulin secretion from mouse pancreatic islets that has been impaired by prolonged exposure to high glucose.

Avaliação morfológica e dos mecanismos de mobilização de Ca2+ pela glicose e acetilcolina em células pancreáticas humanas / Morphologic evaluation and Ca2+ mobilization by glicose and acetylcholine in human pancreatic cells

OBJETIVOS: Avaliar a morfologia das organelas e do citoesqueleto em células pancreáticas humanas cultivadas e a mobilização de Ca2+ em resposta à glicose e ACh por medidas fluorimétricas. MATERIAL E MÉTODOS: As células foram semeadas em lamínulas, fixadas e marcadas com uma combinação de fluoróforos: o núcleo foi corado com DAPI e as mitocôndrias, com Mytotracker Red. Foram utilizados faloidina e anticorpos secundários conjugados com Alexa Fluor verde e vermelho fluorescentes (488 e 594) para identificar proteína actina F e receptor muscarínico tipo M3, respectivamente. Para estudar a mobilização de Ca2+, as células foram incubadas com fura-2/AM. RESULTADOS: As células pancreáticas humanas apresentaram morfologia preservada com grande quantidade de mitocôndrias. Na região de maior densidade celular, evidenciou-se as pseudo-ilhotas e os receptores muscarínicos M3. Por meio da elevação da [Ca2+]c, devido à ação da glicose e ACh, mostrou-se preservação da capacidade responsiva a esses estímulos e foi dependente de concentração desses agonistas. A glicose promoveu uma resposta sustentada e a ACh induziu uma resposta bifásica. CONCLUSÃO: As células pancreáticas humanas cultivadas conservaram sua morfologia. A mobilização de Ca2+ em resposta à glicose e a ACh confirma a sua funcionalidade. Os receptores muscarínicos M3 estão presentes nessas células.

AIMS: The proposal of this study was to analyze morphology of the organelles and cytoskeleton in human pancreatic cells cultured and the mobilization of the cytosolic calcium ([Ca2+]c) in response to glucose and ACh by fluorimetry method. MATERIAL AND METHODS: The cells were plated on glass coverslips, fixed and stained with a combination of fluorophores: the nuclei were stained with DAPI and mitochondria with Mytotracker Red. It was used phalloidin and the secondary antibodies Alexa Fluor conjugated green and red-fluorescent (488 and 594) to identify the protein cell actin F and type M3 muscarinic receptor respectively. The cells also were loaded with fura-2/AM to study Ca2+ mobilization. RESULTS: The human pancreatic cells show characteristics morphologically preserved with great amount of mitochondria. In region major cell density was evidenced pseudo-islets and type M3 muscarinic receptors. Through increase of [Ca2+]c due to action of glucose and ACh were shown that the cellsÆ capacity to respond to these stimuli were conserved. The elevation of the [Ca2+]c depended on concentration by glucose-induced promoting sustained phase and ACh-induced a biphasic response. CONCLUSION: The morphologic characteristics of human pancreatic cells cultured were preserved. The Ca2+ mobilization in response to glucose and ACh confirmed its functionality. The expression of the M3 muscarinic receptors in human pancreatic cell cultured was demonstrated.

Protein kinase C isoform specificity of cholinergic potentiation of glucose-induced pulsatile 5-HT/ insulin release from mouse pancreatic islets

Thymeleatoxin (TMX), an activator of Ca2+-sensitive protein kinase C (cPKC) isoforms, was used to assess the PKC isoform specificity of cholinergic potentiation of glucose (11 mM)-induced pulsatile 5-HT/insulin release (PIR) from single mouse pancreatic islets. TMX (100 nM) and carbachol (Cch, 50 mM) enhanced PIR ~ 3-fold while reducing the underlying [Ca2+]i oscillations (duration and amplitude) by ~ 40-50 percent. Both effects were ablated by the specific PKC inhibitor bisindolylmaleimide and chronic TMX pretreatment. Cch also evoked an initial transient [Ca2+]i rise and surge of 5-HT release, which remained unaffected by chronic TMX pretreatment. It is concluded that the immediate cholinergic responses are insensitive to cPKC. In contrast, specific activation of a cPKC isoform mediates sustained cholinergic potentiation of glucose-induced insulin secretion.

Increased expression of SNARE proteins and synaptotagmin IV in islets from pregnant rats and in vitro prolactin-treated neonatal islets

During pregnancy and the perinatal period of life, prolactin (PRL) and other lactogenic substances induce adaptation and maturation of the stimulus-secretion coupling system in pancreatic â-cells. Since the SNARE molecules, SNAP-25, syntaxin 1, VAMP-2, and synaptotagmins participate in insulin secretion, we investigated whether the improved secretory response to glucose during these periods involves alteration in the expression of these proteins. mRNA was extracted from neonatal rat islets cultured for 5 days in the presence of PRL and from pregnant rats (17th-18th days of pregnancy) and reverse transcribed. The expression of genes was analyzed by semi-quantitative RT-PCR assay. The expression of proteins was analyzed by Western blotting and confocal microscopy. Transcription and expression of all SNARE genes and proteins were increased in islets from pregnant and PRL-treated neonatal rats when compared with controls. The only exception was VAMP-2 production in islets from pregnant rats. Increased mRNA and protein expression of synaptotagmin IV, but not the isoform I, also was observed in islets from pregnant and PRL-treated rats. This effect was not inhibited by wortmannin or PD098059, inhibitors of the PI3-kinase and MAPK pathways, respectively. As revealed by confocal laser microscopy, both syntaxin 1A and synaptotagmin IV were immunolocated in islet cells, including the insulin-containing cells. These results indicate that PRL modulates the final steps of insulin secretion by increasing the expression of proteins involved in membrane fusion.

Effect of glurenorm on immunohistochemical changes in pancreatic beta cells of rats in experimental diabetes.

Immunohistochemical localization of islets of Langerhans of streptozotocin (65 mg/kg, ip) induced diabetic + glurenorm (10 mg/kg, po) treated female albino rats revealed increase in number of beta cells and insulin immunoreactivity of beta cells. The results suggest that glurenorm can cause the stimulation of beta cells of endocrine pancreas in diabetic rats.

Effect of extracts of Murraya koenigii leaves on the levels of blood glucose and plasma insulin in alloxan-induced diabetic rats.

The effect of daily oral administration of aqueous extract (600 mg/kg b.wt.) and methanol extract (200 mg/kg b.wt.) of Murraya koenigii Spreng leaves for a period of eight weeks was studied on blood glucose and plasma insulin level in alloxan-induced diabetic rats. Blood glucose levels of diabetic rats treated with aqueous and methanol extracts of Murraya koenigii Spreng showed significant reduction (P<0.05) as compared to diabetic control groups. Plasma insulin showed significantly high on 43rd and 58th days of treatment in aqueous and methanol extracts of Murraya koenigii treated groups. This suggests that the hypoglycemic effect may be mediated through stimulating insulin synthesis and/or secretion from the beta cells of pancreatic islets of Langerhans.

Islet Transplantation and Regeneration for Treatment of Diabetes

Islet transplantation has the potential to restore normoglycemia and prevent the development of diabetic complications such as retinopathy, nephropathy and neuropathy, and could therefore ve a valuable treatment for diabetic patients. The scarcity of available islets is an obstacle for clinically successful islet transplantation. To resolve the problems, we have examined the two methods, islet transplantation with extracellular matrix1 and in vivo expansion of islets with electrically- transfection of growth factors.

Isolation of ethanol-induced genes in pancreatic beta-cells by representational difference analysis (RDA)

Recent epidemiological studies suggest that alcohol consumption is one of the risk factors leading to type 2 diabetes, but the direct effect of ethanol on beta-cell gene expression is not known. Here, using cDNA RDA method, we isolated 43 ethanol-induced genes in pancreatic beta-cells, and confirmed their differential expression by Northern blot or semi-quantitative RT-PCR. These genes were further categorized by the functional criteria based on the published data; Translation, Transcription, Metabolism, Signal transduction, Transport, Structure, Cytoskeleton, Regulation, or Putative/Unknown genes. The effects of each gene on beta-cell function need to be further investigated, however, the present data strongly suggest that these genes might be related to the metabolic alterations caused by ethanol as indicated in earlier study. In particular, RPS3 gene expression was increased by ethanol, glucosamine, and cytokines, implying that ethanol might decrease the metabolic activity by oxidative stress in beta-cells. Therefore, cloning of these genes in full-length and the detailed studies of each gene on beta-cell functions might provide clues on the pathophysiology of type 2 diabetes caused by alcohol.

Histological and immunohistochemical study of pancreatic islet beta cells of diabetic rats treated with oral vanadyl sulphate

Vanadium salts have been suggested as a possible therapeutic agent for the treatment of diabetes. The aim of the present study was to clarify histological and immunohistochemical changes that occur in the pancreatic [beta] cells of vanadyl sulphate [VS]-treated streptozotocin [STZ] induced diabetic rats. Male Wistar rats were made diabetic by injecting a single intravenous dose of STZ [40 mg/kg] and were divided into two groups seven days after STZ injection. In the first group VS was administered via drinking water at a concentration of 1 mg/mL and treatment was maintained until normoglycemia appeared [DT]. A second group of diabetic animals received distilled water for the same period and were considered as control diabetic [DC]. One group of animals [NC] was injected intravenously with the same amount of vehicle as the diabetic rats and was considered as non-diabetic control. VS treatment was accompanied by amelioration of the signs of diabetes in DT rats while DC animals remained diabetic during this period. Hemotoxylin - Eosin stained pancreatic sections of DC rats showed a decrease in the number and size of islets and a disruption in their architecture. In DT rats the histological appearance of the islets was normal, their shape and size being within normal limits. In horseradish peroxidase procedure [using guinea pig antiserum to insulin as primary antibody] performed on pancreatic islet paraffin sections of rats, insulin immunoreactivity was found in the majority of the islets in DT rats while in the islets of DC rats immunoreactivity was rare. The results of this study indicated that amelioration of diabetes in vanadyl sulphate treated diabetic rats was accompanied with well preservation of islet structure and insulin immunoreactivity

Pancreatic islet-cell viability, functionality and oxidative status remain unaffected at pharmacological concentrations of commonly used antibiotics in vitro.

Environmental factors such as diet, physical activity, drugs, pollution and life style play an important role in the progression and/or precipitation of diseases like diabetes, hypertension, obesity and cardiovascular disorders. Indiscriminate use of antibiotics to combat infectious diseases is one of the commonest forms of misuse of drugs. Antibiotics seem to have a correlation with diabetes and pancreatic function. There are controversial reports about the effect of antibiotics on the pancreatic islets; some suggesting their harmless action, some depicting a beneficial role and others indicating deleterious effect. Moreover, use of antibiotics is mandatory during islet isolation and cultivation to reduce incidences of microbial contamination. It is likely that antibiotic treatment may adversely affect islet viability and its functioning leading to failure of islet transplantation. The present in vitro study was undertaken to examine the effect of commonly used antibiotics such as gentamycin, penicillin, streptomycin, tetracycline, neomycin, erythromycin and chloramphenicol on islet viability, its functioning and induction of oxidative stress if any. The viability and insulin production data showed that none of the antibiotics used in the present study affect the viability and the functioning of the islets at their pharmacological concentrations. Free radical levels measured in terms of melonyldialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) reveal that except for a marginal increase in lipid peroxidation with tetracycline and slight increase in NO levels with streptomycin, none of these antibiotics affect the oxidative status of the cells. Antioxidant enzymes such as superoxide dismutase and catalase remain unaffected after this treatment. Our results reveal the innocuous nature of the antibiotics used at pharmacological concentrations, suggesting their safety whenever prescribed to combat infections and also during islet isolation procedures.