Myricitrin and Its Solid Lipid Nanoparticle Increase Insulin Secretion and Content of Isolated Islets from the Pancreas of Male Mice

Abstract Glucose exposure induces toxic effects on the function of the pancreatic islets. Moreover, myricitrin as a flavonoid glycoside may have favorable effects on insulin secretion of Langerhans islets. The present study aimed to investigate the effect of Myricitrin and its solid lipid nanoparticles (SLN) on the insulin secretion as well as the content of isolated pancreatic islets from male mice. In this experimental study, Langerhans islets were separated from adult male NMRI mice using the collagenase method. The insulin secretion and content of islets were assessed in glucose-containing medium (2.8, 5.6, and 16.7mM). Further, islets treated were prepared by the administration of Myricitrin and its SLN (1, 3 and 10µM). Myricitrin 3µM, and SLN containing Myricitrin 3 and 10µM increased insulin secretion in medium containing glucose concentration 2.8mM. Accordingly, this variable increased in Myricitrin 3 and 10µM, SLN containing Myricitrin 1, 3, and 10µM utilization as well as glucose concentration 5.6mM. Afterward, the insulin secretion increased in medium containing 16.7mM glucose after the addition of Myricitrin and SLN containing Myricitrin 1, 3, and 10µM. Also, the insulin content increased in Myricitrin and SLN containing Myricitrin 1, 3, and 10µM administered groups in all medium containing glucose concentrations. Myricitrin and its SLN increased islets insulin secretion and content in low, moderate, and high glucose concentration mediums

Effects of exogenous ghrelin on the tissue structure and somato-statin secretion in the pancreas of African ostrich chicks / Efectos de la grelina exógena en la estructura del tejido y la secreción de somato-estatinas en el páncreas de los polluelos de avestruz africanos

SUMMARY: This study aimed to investigate the effect of exogenous ghrelin on pancreatic growth and development in African ostrich chicks. Sixteen 40-day-old African ostrich chicks (male or female) were randomly divided into four groups and injected intravenously metatarsal vein with saline (control) or ghrelin (10, 50, and 100 μg/kg) for 6 days. Body and pancreas weight were determined, structural characteristics were observed using HE staining, somatostatin-immunopositive cells were detected using immunohistochemistry. The results were as follows: 1. The 50 and 100 μg/kg groups showed lower relative pancreas weight than the control group (P 0.05. Moreover, compared with the control, the islet cells in treatment groups were loosely arranged and showed reduced cytoplasm. In the exocrine pancreas, the volume of acinar cells in the 10, 50, and 100 μg/kg groups all decreased to varying degrees. 3. Somatostatin immunopositive cells were mainly located around the periphery of the islets and sporadically distributed in the center. The density of the somatostatin immunopositive cells in the 10, 50, and 100 μg/kg groups was higher than that in the control (P < 0.05). These findings suggest that exogenous ghrelin increases the area and number of islets and number of somatostatin immunopositive cells but reduces relative pancreas weight and effects the morphological and structural development of the pancreas, which may inhibit the pancreatic growth and development in African ostrich chicks.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de la grelina exógena sobre el crecimiento y desarrollo del páncreas en polluelos de avestruz africana. Dieciséis pollos de avestruz africana de 40 días (machos o hembras) se dividieron al azar en cuatro grupos y se inyectaron por vía intravenosa con solución salina (control) o grelina (10, 50 y 100 μg / kg) durante 6 días. determinadas, se observaron las características estructurales mediante tinción Hematoxilina-Eosina, se detectaron células inmunopositivas a somatostatina mediante inmunohistoquímica. Los resultados fueron los siguientes: ¨Los grupos de 50 y 100 μg / kg mostraron un menor peso relativo del páncreas que el grupo de control (P <0,05). El área de islotes por unidad de área del páncreas fue mayor en los grupos de 10, 50 y 100 μg / kg grupos que en el grupo de control (P <0,05). El número de islotes por unidad de área del páncreas fue menor en el grupo de 10 μg / kg que en el control (P <0,05). Además, en comparación con el control, las células de los islotes en los grupos de tratamiento estaban dispuestas de forma holgada y mostraban un citoplasma reducido. En el páncreas exocrino, el volumen de células acinares en los grupos de 10, 50 y 100 μg / kg disminuyó en diversos grados. Las células inmunopositivas de somatostatina se ubicaron principalmente alrededor de la periferia de los islotes y se distribuyeron esporádicamente en el centro. La densidad de las células inmunopositivas a la somatostatina en los grupos de 10, 50 y 100 μg / kg fue mayor que la del control (P <0,05). Estos hallazgos sugieren que la grelina exógena aumenta el área y el número de islotes y el número de células inmunopositivas a la somatostatina, pero reduce el peso relativo del páncreas, lo que puede inhibir el crecimiento y desarrollo pancreático en los polluelos de avestruz africana.

Suppression of L-arginine-induced acute necrotizing pancreatitis in rats by metformin associated with the inhibition of myeloperoxidase and activation of interleukin-10 / Supresión de la pancreatitis necrotizante aguda inducida por L-arginina en ratas por metformina asociada con la inhibición de mieloperoxidasa y activación de interleucina-10

SUMMARY: Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreatitis in an animal model of L-arginine-induced acute pancreatitis, and whether this is associated with the augmentation of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibition of the enzyme that promotes tissue damage, myeloperoxidase (MPO). Rats were either injected with two doses of the amino acid L-arginine (2.5 gm/kg; i.p., at one-hour intervals) before being sacrificed after 48 hours (model group) or were pretreated with metformin (50 mg/kg) daily for two weeks prior to L- arginine injections and continued receiving metformin until the end of the experiment (protective group). Using microscopic examination of the pancreas and blood chemistry, we observed that L-arginine induced acute pancreatic injury. This is demonstrated by an enlarged pancreas with patchy areas of haemorrhage, vacuolated cytoplasm and pyknotic nuclei in the acini, disorganized lobular architecture with infiltration of inflammatory cells within the interlobular connective tissue (CT) septa, and the presence of congested blood vessels that were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited L-arginine-induced MPO, lactate dehydrogenase (LDH), and the inflammatory biomarker tumor necrosis factor alpha (TNF-α). Whereas, metformin significantly (p<0.05) increased IL-10 levels that were inhibited by pancreatitis induction. We further demonstrated a significant (p<0.001) correlation between the scoring of the degree of pancreatic lobules damage tissue damage and the blood levels of TNF-α, IL-10, LDH, and MPO. Thus, metformin effectively protects against L-arginine-induced acute pancreatitis, which is associated with the inhibition of MPO and augmentation of IL-10.

RESUMEN: La pancreatitis aguda es una enfermedad inflamatoria del páncreas que amenaza la vida y se caracteriza por un dolor abdominal intenso que dura de días a semanas. Buscamos determinar si la metformina, fármaco antidiabético y antiinflamatorio, puede proteger contra la pancreatitis aguda en un modelo animal de pancreatitis aguda inducida por L-arginina. Además se estudió la asociación con el aumento de la citocina antiinflamatoria interleucina-10. (IL-10) e inhibición de la enzima que promueve el daño tisular, mieloperoxidasa (MPO). Las ratas se inyectaron con dos dosis del aminoácido L-arginina (2,5 g / kg; ip, a intervalos de una hora) antes de ser sacrificadas des- pués de 48 horas (grupo modelo) o se pre trataron con metformina (50 mg / kg) durante dos semanas antes del tratamiento de L- arginina y continuaron recibiendo metformina hasta el final del experimento (grupo protector). Mediante el examen microscópico del páncreas y la química sanguínea, se observó que la L- arginina inducía una lesión pancreática aguda. Se observó un aumento significativo de tamaño del páncreas con áreas hemorrágicas, citoplasma vacuolado y núcleos picnóticos en los acinos, arquitectura desorganizada con infiltración de células inflamatorias dentro de los tabiques del tejido conjuntivo interlobulillar (TC) y la presencia de vasos sanguíneos congestionados mejorados por metformina. Se observó que la metformina inhibió significativamente (p <0,05) la MPO inducida por L- arginina, la lactato deshidrogenasa (LDH) y el factor de necrosis tumoral alfa (TNF-α). Además, demostramos una correlación significativa (p <0,001) entre la puntuación del grado de daño tisular de los lóbulos pancreáticos y los niveles sanguíneos de TNF-α, IL-10, LDH y MPO. Por tanto, la metformina protege eficazmente contra la pancreatitis aguda inducida por L-arginina, que se asocia con la inhibición de MPO y el aumento de IL-10.

Antidiabetic effect of Momordica charantia saponins in rats induced by high-fat diet combined with STZ

Background: The harmful effects of type 2 diabetes mellitus and its complications have become a major global public health problem. In this study, the effects of Momordica charantia saponins (MCS) on lipid metabolism, oxidative stress, and insulin signaling pathway in type 2 diabetic rats were investigated. Results: MCS could attenuate the tendency of weight loss of the model rats. It could also improve glucose tolerance; reduce fasting blood glucose, nonesterified fatty acid, triglyceride, and total cholesterol; and increase the insulin content and insulin sensitivity index of the rats. The activity of superoxide dismutase and catalase increased, and the content of malondialdehyde decreased in the liver and pancreas tissues of rats in MCS-treated groups significantly. In addition, the expression of p-IRS-1 (Y612) and p-Akt (S473) increased, and the expression of p-IRS-1 (S307) decreased in the liver tissues and pancreas tissues of rats in MCS-treated groups significantly. Conclusion: MCS has an antidiabetic effect, which may be related to its improving the lipid metabolism disorder, reducing oxidative stress level, and regulating the insulin signaling pathway.

Metabolic dysregulation in early onset psychiatric disorder before and after exposure to antipsychotic drugs

Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.

Effect of wheatgrass on DNA damage, oxidative stress index and histological findings in diabetic rats / Efecto del pasto de trigo sobre el daño del ADN, el índice de estrés oxidativo y los hallazgos histológicos en ratas diabéticas

This study was aimed to search the effect of wheatgrass on the Total Antioxidan (TAS)-Oxidan Status (TOS) and DNA damage in rat with diabetes. The rats used in the study were randomly divided into 4 groups that each of has 10 rats: Control group; 1 ml single dose phosphate-citrate buffer injected i.p (pH: 4.5), Diabetes group; 45 mg/kg single dose streptozotocin injected i.p., Wheatgrass group; was given oral wheatgrass (10 ml/kg/day) for 6 weeks, Diabetes +Wheatgrass group; 45 mg/kg single dose streptozotocin injected i.p. and wheatgrass (10 ml/kg/day) was given by oral during 6 weeks. After the process of experiment during 6 weeks, blood sample and pancreas tissue were taken. The analysis were done of blood glucose levels, TAS, TOS levels by colorimetric kits; DNA damage by ELISA kits in serum. The pancreas tissues were examined histopathologically. In the group of Diabetes+Wheatgrass was determined that the levels of glucose levels (p<0.001), TOS (p<0.05) and OSI (p<0.01) statistically decreased and heal histopatolojical compared to diabetes group. In the group of Wheatgrass was determined that the levels of TAS p<0.05 statistically increased from other groups. The statistical significance were not found in the level of serum 8OHdG differences between the groups. The beta cells were seen to increase in the group receiving wheatgrass for therapeutic purposes.As a conclusion, it was determined that wheatgrass strengthened the anti-oxidant defense system and reduced the glucose level in diabetic rats.

El objetivo de este estudio fue buscar el efecto del pasto de trigo sobre el estado total de antioxidantes (TAS) -Oxidan Status (TOS) y el daño del ADN en ratas con diabetes. Las ratas analizadas en el estudio se dividieron aleatoriamente en 4 grupos de 10 ejemplares cada uno: grupo control; 1 ml de tampón fosfato-citrato de dosis única inyectado i.p. (pH: 4,5)., Grupo diabetes; 45 mg / kg de estreptozotocina en dosis única inyectada i.p., grupo pasto de trigo; se administró pasto de trigo oral (10 ml / kg / día) durante 6 semanas, grupo diabetes + pasto de trigo; 45 mg / kg de estreptozotocina en dosis única inyectada i.p. y pasto de trigo (10 ml / kg / día) por vía oral durante 6 semanas. Después del proceso experimental durante 6 semanas, se tomaron muestras de sangre y tejido de páncreas. Se midieron los niveles de glucosa en sangre, TAS, y TOS mediante kits colorimétricos; El daño al ADN fue realizado por kits de ELISA en suero. Los tejidos del páncreas se examinaron histopatológicamente. En el grupo de diabetes + pasto de trigo se determinó que los niveles de glucosa (p <0,001), TOS (p <0,05) y OSI (p <0,01) disminuyeron estadísticamente y curaron histopatológicamente en comparación con el grupo de diabetes. En el grupo de pasto de trigo se determinó que los niveles de TAS p <0,05 se incrementaron estadísticamente con respecto a otros grupos. No fue estadísticamente significativo el nivel de las diferencias séricas de 8OHdG entre los grupos. Se observó que las células beta aumentaron en el grupo que recibió pasto de trigo con fines terapéuticos. Como conclusión, se determinó que el pasto de trigo fortaleció el sistema de defensa antioxidante y redujo el nivel de glucosa en las ratas diabéticas.

Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats

Risperidone is an atypical antipsychotic acting mainly as a dopamine D2 and serotonin 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various affective disorders. Risperidone has been reported to be associated with weight gain, panreatitis and type 2 diabetes mellitus. Various mechanisms of risperidone-induced toxicities have been reported but the histology of tissues especially pancreas has never been studied. Therefore, the current study was designed to elucidate the toxic effects of chronic administration of risperidone on pancreas, liver and kidneys. Animals (rats) of either gender were divided into two groups, the risperidone and control groups. Risperidone was administered in a dose of 2.5 mg/kg/d for three weeks. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase and amylase were determined at the conclusion of the experiment. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Risperidone showed no weight gain, hyperglycemia or rise in the level of lipase (P> 0.05); however, the level of amylase was raised (***P<0.05). Histological examination under light microscope showed no hepatotoxicity, nephrotoxicity but did show damage to the pancreas. The findings of this study indicated that the incidence of adverse effects associated with risperidone could be prevented/alleviated/delayed by allowing restricted diet.

Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARgamma expression

Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

Crab shell extract improves serum biochemical markers and histological changes of pancreas in diabetic rats / El extracto de cáscara de cangrejo mejora los marcadores bioquímicos del suero y los cambios histológicos del páncreas en ratas diabética

SUMMARY: Diabetes mellitus is a common metabolic disease. There are many natural agents available to control and treat diabetes. Crab shell extract has antioxidant properties. The aim of present study was to investigate the effect of crab shell hydroalcoholic extract on blood glucose, liver enzymes, nitric oxide and antioxidant capacity of serum and histological structure of pancreas in diabetic rats. In this experimental study, thirty five male Wistar rats (180-220 g) were divided into control, diabetic and experimental groups (n=7). Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Rats were treated for 14 days by crab shell extract with 100, 200 and 400 mg/kg doses. Fasting blood glucose, serum levels of liver enzymes, nitric oxide (NO) and total antioxidant capacity were evaluated. Changes of pancreatic tissue were determined using a modified aldehyde fuchsin staining method. Data were analyzed using one-way ANOVA. Differences were considered statistically significant at P<0.05. Crab shell extract induced a significant reduction in blood glucose, serum levels of nitric oxide and ALT (P=0.033). Also, there were a significant increase in total antioxidant capacity (FRAP) (P=0.007), and insignificant decrease in serum levels of AST. The extract improved pancreatic tissue changes caused by diabetes. In conclusion, antioxidant and anti-diabetic effects of crab shell increase total antioxidant capacity of serum and decreased blood glucose, serum nitric oxide and ALT levels.

RESUMEN: La diabetes mellitus es una enfermedad metabólica común. Hay muchos agentes naturales disponibles para controlar y tratar la diabetes. El extracto de cáscara de cangrejo tiene propiedades antioxidantes. El objetivo del presente estudio fue investigar el efecto del extracto hidroalcohólico de la cáscara de cangrejo sobre la glucosa sérica, las enzimas hepáticas, el óxido nítrico y la capacidad antioxidante del suero y la estructura histológica del páncreas en ratas diabéticas. En este estudio experimental, treinta y cinco ratas Wistar machos (180220 g) se dividieron en cinco grupos: control, diabéticos y experimentales (n = 7). La diabetes se indujo por inyección intraperitoneal de estreptozotocina (60 mg / kg). Las ratas se trataron durante 14 días con extracto de cáscara de cangrejo con dosis de 100, 200 y 400 mg / kg. Se evaluaron la glucosa en sangre en ayunas, las enzimas hepáticas, el óxido nítrico sérico y la capacidad antioxidante total. Los cambios en el tejido pancreático se determinaron usando un método de tinción de aldehído fucsina modificado. Los datos se analizaron utilizando ANOVA unidireccional. Las diferencias se consideraron estadísticamente significativas a P <0,05. El extracto de cáscara de cangrejo indujo una reducción significativa en la glucosa en sangre, en los niveles séricos de óxido nítrico y ALT (P = 0,033). Además se observó un aumento significativo en la capacidad antioxidante total (FRAP) (P = 0.007), y una disminución insignificante en los niveles séricos de AST. El extracto mejoró los cambios en el tejido pancreático causados por la diabetes. En conclusión, los efectos antioxidantes y antidiabéticos de la cáscara de cangrejo aumentan la capacidad antioxidante total de suero y la disminución de la glucosa en la sangre, el óxido nítrico sérico y los niveles de ALT.

Ethanol intake and toxicity: in search of new treatments / Ingesta de etanol y toxicidad: en búsqueda de nuevos tratamientos

Prolonged alcohol consumption has consequences on the liver, producing necrotic precipitates and fibrosis, on the pancreas, causing the pancreatic acini to atrophy and destroying insulin-producing cells, and on the central nervous system (CNS), causing the gray and white matter in the frontal lobes of the brain and cerebellum to atrophy. Generally, alcohol is metabolized via oxidative pathways, where the enzymes alcohol dehydrogenase and aldehyde dehydrogenase participate during its metabolization in the liver and CNS, or via non-oxidative pathways during its metabolization in the pancreas. Ethanol metabolism can produce oxidative stress and tissue damage mediated by free radicals, causing morphological and functional alterations in the liver. In the pancreas, it can cause progressive and irreversible damage affecting the endocrine and exocrine functions, a result of the activation of the stellate cells, which are activated directly by alcohol, causing pancreatic fibrosis. In the CNS ethanol can bind directly to proteins, nucleic acids and phospholipids to develop its pathogenesis. The effects produced by alcohol can be counteracted by supplementation with antioxidants, which reduce the inflammation and areas of focal necrosis in the liver, inhibit the activation of pancreatic stellate cells, and reduce oxidative stress in the CNS. Additionally, in order to reduce the negative effects associated with alcohol consumption, recent studies have suggested the administration of antioxidants as a treatment strategy.

El consumo prolongado de alcohol tiene consecuencias en hígado, produciendo precipitados necróticos y fibrosis; en páncreas, provocando atrofia del acino pancreático y destrucción de las células productoras de insulina, y en Sistema Nervioso Central (SNC) generando atrofia de la sustancia gris y blanca en lóbulos frontales del cerebro y cerebelo. En general, el metabolismo del alcohol se consigue mediante las vías oxidativas, donde participan las enzimas alcohol-deshidrogenasa y aldehído deshidrogenasa durante su metabolización en hígado y SNC; o bien, mediante las vías no oxidativas durante su metabolización en páncreas. El metabolismo del etanol es capaz de producir estrés oxidativo y daño tisular mediado por radicales libres, causando alteraciones morfológicas y funcionales del hígado; en el páncreas, puede causar daño progresivo e irreversible afectando las funciones endocrinas y exocrinas de este órgano producto de la activación de las células estrelladas que son activadas directamente por el alcohol generando fibrosis pancreática; mientras que, en SNC se puede unir directamente a proteínas, ácidos nucleicos y fosfolípidos para desarrollar su patogenia. Los efectos producidos por el alcohol pueden contrarrestarse mediante la suplementación con antioxidantes, que reducen la inflamación y las zonas de necrosis focal en el hígado, inhiben la activación de células pancreáticas estrelladas, y reducen el estrés oxidativo en SNC. Asimismo, para reducir los efectos negativos asociados al consumo de alcohol, estudios recientes han propuesto la administración de antioxidantes como estrategia terapéutica.

Evaluation of the toxicity and hypoglycemic effect of the aqueous extracts of Cnidoscolus quercifolius Pohl

Diabetes mellitus is one of the most common chronic degenerative diseases, and it is estimated to increase worldwide to around 415 million and to impact 642 million in 2040. Research shows that some plants are sources of bioactive compounds against diabetes. Thus, the objective of this work was to evaluate the oral toxicity and the hypoglycemic effect of the aqueous extract of the leaves of Cnidoscolus quercifolius Pohl. Diabetes was induced in Swiss mice with streptozotocin and the mice were treated with an aqueous extract of C. quercifolius leaves for a period of 30 days. Phytochemical analysis showed that the extract was rich in flavonoids, catechins and triterpenoid, which did not show any mortality and behavioral alterations in mice treated with 200, 1000, and 2000 mg/kg body weight of the extract for 14 days. Histopathological analysis of organs (kidney, pancreas, liver) from mice treated with the 2000 mg/kg extract revealed no architectural change. In the present study, we found a 29% reduction in glucose levels in animals receiving 200 mg/kg body weight. These results are very promising because they showed that C. quercifolius had a hypoglycemic effect and did not present oral toxicity, thus being a new source of compounds for the control of diabetes.

Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats

Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg-1·day-1 for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines.

developmental gross morphology of pancreas in chick embryo after prenatal administration of valproic acid

To determine the effects of prenatal administration of valproic acid on the developmental gross morphology of pancreas in chick embryo. Experimental study. Anatomy Department, Regional Centre, College of Physicians and Surgeons, Islamabad, from February 2010 to February 2011. An experimental group-A and control group-B, comprised of 30 eggs each. Freshly laid fertilized chicken eggs of experimental group were injected with valproic acid, incubated and hatched. Eggs of control group underwent sham treatment using normal saline. The chicks were sacrificed on hatching or day 22 of incubation, whichever was earlier. The pancreata of only alive chicks of both groups were dissected out, and evaluated for gross morphology in terms of length and weight by statistically comparing with control ones. Then pancreata were stained with aldehyde fuchsin and orange-G stain to study other obvious histological effects, if any. Chicken embryos exposed to valproic acid in ovo, showed significant decrease in length and weight of pancreata. The mean of length [cm] of pancreata in group-A was 2.208 +/- 0.166, and group-B was 2.300 +/- 0.102 [p=0.008]. The mean of weight [g] of pancreata in group-A was 0.032 +/- 0.009, and group-B was 0.048 +/- 0.005 [p=0.001]. Valproic acid exposure showed retarding effect on the gross development of pancreas as depicted by decrease in the length and weight of pancreata

Intervenção nas situações de crise psíquica: dificuldades e sugestões de uma equipe de atenção pré-hospitalar / Intervention in situations of psychic crisis: challenges and suggestions of a prehospital care staff / Intervención en situaciones de crisis psíquica: problemas y sugerencias de un equipo de atención prehospitalaria

Pesquisa descritiva, qualitativa, que objetivou conhecer como os profissionais de atenção pré-hospitalar percebem as intervenções nas pessoas em crise psíquica. O estudo foi realizado, no estado de Santa Catarina, com quatro equipes das Unidades de Suporte Básico do Serviço de Atendimento Móvel de Urgência, mediante entrevista, no período de abril a junho de 2011. Utilizou-se como método de análise o Discurso do Sujeito Coletivo. Dos resultados emergiram dois temas: Percepção das dificuldades no atendimento à pessoa em crise psíquica e Sugestões na busca por um atendimento mais próximo do desejado à pessoa em crise psíquica. As dificuldades apontadas se relacionam à falta de capacitação e de um local para encaminhamento e sugerem treinamento e sistematização do atendimento. Conclui-se que se faz necessário investir em processo de formação pautado em novas estratégias de cuidado norteadas pelos princípios do SUS e no paradigma psicossocial, além de rediscutir a estratégia de protocolos como sistemas norteadores e não padronizadores.

A qualitative and descriptive research, aimed at knowing how the pre-hospital care professionals perceive the interventions towards people in mental crisis. The study was developed in Santa Catarina with four teams of basic life support units of the Department of Mobile Emergency Care, during April to June 2011. The Collective Subject Discourse was used as the method of analysis. Two themes emerged: Awareness of the difficulties in meeting a person in mental crisis and Suggestions in the search for a closer attention to the person in mental crisis. The difficulties mentioned were related to the lack of training and a local to forward the patients, suggesting a better training and systematization of care. We conclude that it is necessary to invest in the educational process, based on new care strategies guided by the principles of SUS and of the psychosocial paradigm, and revisit the strategy of protocols as guidelines and not as standardizing systems.

Investigación descriptivo-cualitativa, que objetivó conocer como los profesionales de la atención pre-hospitalaria perciben las intervenciones en personas con crisis mental. El estudió fue realizado en Santa Catarina con cuatro equipos de las Unidades de Soporte Vital Básico, mediante entrevista realizada de abril a junio de 2011. El Discurso del Sujeto Colectivo fue utilizado como método de análisis; surgiendo dos temas: Percepción de las dificultades en la atención a la persona en crisis mental y Sugerencias en la búsqueda de una mejor atención a la persona en crisis mental. Las dificultades mencionadas se relacionan con la falta de capacitación y lugar para la atención, sugiriendo un mejor entrenamiento y sistematización de la atención. Se resalta la necesidad de invertir en el proceso de formación basado en nuevas estrategias de atención guiadas por los principios del SUS y el paradigma psicosocial, y revisar la estrategia de protocolos como nortes no estandarizados.

Preventive effect of garlic [Allium sativum L.] on serum biochemical factors and histopathology of pancreas and liver in streptozotocin-induced diabetic rats

Antidiabetic action of garlic is established in animal studies. Since all of the pervious studies have focused on the therapeutic role of garlic, this study investigated the preventive effect of garlic juice on biochemical factors and histological features in Streptozotocin [STZ]-induced diabetic rats. Forty male rats were divided into five groups [n = 8]: 1-Normal group [N], 2-Normal+Garlic group [N+G] received garlic juice [1 mL/100g BW] for 6 weeks, 3-Diabetic group [D] was injected with STZ [60 mg/kg, IP], 4-Diabetic+Garlic before group [D+G[b]] received garlic juice for 3 weeks before STZ injection and continued for another 3 weeks, 5-Diabetic+Garlic-after group [D+G[a]], three days after STZ injection, they received garlic juice for 3 weeks. Serum biochemical factors were measured by the enzymatic methods and H and E stained sections of pancreas and liver were prepared for light microscopy. In diabetic rats, elevated levels of glucose, cholesterol and triglycerides, the increment of the activities of ALT and AST, increased food and water consumption were observed. The abnormal increases were significantly [p < 0.05] decreased in D+G[b] groups compared to D group. In D group, scattered degeneration of the hepatocytes with lymphocytic infiltration in the portal areas, decrease of pancreatic islets numbers and diameter, atrophy of pancreatic islets were observed. These abnormal histological signs were dramatically ameliorated in D+G[b] group compared to D group. In D+G[a] group compared to D+G[b] group slighter effects of garlic juice on histopathological and biochemical changes were seen. These results indicate that garlic juice may help in the prevention of the complications of diabetes

A Case of Acute Pancreatitis and Acute Hepatitis Caused by Ingestion of Ceramium kondoi / 대한소화기학회지

In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoi for 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement.

Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis? / Existe uma janela terapêutica para a pentoxifilina após o início da pancreatite aguda?

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.

Antihyperglycemic and antioxidant effect of hydroethanolic extract of Butea monosperma bark in diabetic mice.

The antihyperglycemic, antihyperlipidemic and antioxidative properties of hydroethanolic extract of Butea monosperma bark were investigated in alloxan-induced diabetic mice. Alloxan administration resulted in higher blood glucose level and reduced hepatic glycogen content as compared to normal animals. Besides, serum lipid profile parameters such as total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol were also found to be significantly elevated, whereas the level of high density lipoprotein (HDL) cholesterol was markedly reduced in diabetic animals. Oxidative damage in the tissues of diabetic mice was evidenced by a marked increase in the level of thiobarbituric acid reactive substances (TBARS), distinct decrease in reduced glutathione (GSH) content and declined activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). The daily treatment of diabetic animals with crude extract of B. monosperma bark (300 mg kg-1) for 45 days significantly lowered blood glucose level and elevated hepatic glycogen content, bringing the values close to those observed in normal control and glibenclamide-treated diabetic mice. Furthermore, the level of various lipid profile parameters was also reversed towards normal. TBARS and GSH also restored towards normal and the declined activity of antioxidant enzymes in diabetic animals was also normalized in crude extract administered mice, thus indicating the antioxidant efficacy of the drug in diabetes-induced oxidative damage. Significant antihyperglycemic and antioxidant potential of the crude extract of B. monosperma bark indicated that it may find use in the management of diabetes and resultant oxidative stress.

[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

Beneficial effects of n-acetyl cysteine on pancreas and kidney following experimental pancreatic ischemia-reperfusion in rats

OBJECTIVE: To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model. METHODS AND MATERIALS: Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion. RESULTS: There were significant differences in amylase levels between Group 1 (6.11±0.55) and Group 2 (10.30±0.50) [p=0.0002] as well as between Group 2 (10.30±0.50) and Group 4 (7.82±0.38) [p=0.003]; creatinine levels between Group 1 (0.52 ± 0.07) and Group 2 (0.77±0.18) [p=0.035] as well as between Group 2 (0.77±0.18) and Group 3 (0.48±0.13) [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27±0.96) and Group 2 (2.60±3.01) [p=0.026] as well as between Group 2 (2.60±3.01) and Group 4 (0.52±0.56) [p=0.002]. A decrease in pancreatic tissue GST-á3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006), and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively). CONCLUSION: This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model.