Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS). Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans) model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains

Valproate, thalidomide and ethyl alcohol alter the migration of HTR-8/SVneo cells

BACKGROUND: Valproate, thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta. METHODS: In the present study, the effects of sodium valproate, thalidomide and alcohol on the migration of human first trimester trophoblast cell line (HTR-8/SVneo) were examined in vitro. Cells were cultured in the wells of 48-well culture plates as mono or multilayers. Circular patches of cells were removed from the center of the wells by suction, and the migration of cells into the wound was studied using microscopy. Effects of low and high concentrations of valproate, thalidomide and alcohol were examined on the healing of wounds and on the migration rate of cells by determining the wound areas at 0, 3, 6, 12, 24 and 48 h. Effects of drugs and alcohol on the proliferation and the expression levels of integrin subunits beta1 and alpha5 in cells were examined. RESULTS: The migration rates of trophoblast differed between wounds created in mono and multilayers of cells. Exposure to teratogens altered the migration of trophoblast into mono and multilayer wounds. The effects of valproate, thalidomide and alcohol on the proliferation of cells during the rapid migratory phase were mild. Drug exposure caused significant changes in the expression levels of beta1 and alpha5 integrin subunits. CONCLUSION: Results suggest that exposure to valproate, thalidomide or alcohol during the first trimester of pregnancy may change the ultrastructure of the placenta by altering the migration of trophoblast cells and this effect may be mediated by drug- or alcohol-induced changes in the expression levels of beta1 and alpha5 integrin subunits

Does the 3-aminobenzamide effect on bacterial translocation affect experimental acute necrotizing pancreatitis?

Background/aims: One of the most important complications of acute pancreatitis is the secondary bacterial infections of the pancreas and gut. Translocation of bacteria from the gut is accepted as being responsible for the development of septic complications in acute pancreatitis. In this study, our aim was to investigate the effect of PARP inhibition via 3-aminobenzamide on the bacterial translocation in acute pancreatitis. Methods: 45 male Sprague-Dawley rats were randomly allocated into three groups. Group I (Sham+saline) received normal saline infusion into the common biliopancreatic duct. Acute pancreatitis was induced in Group II (acute pancreatitis+saline) and Group III (acute pancreatitis+3-aminobenzamide) by the retrograde injection of taurocholate into the common biliopancreatic duct. Six hours after induction of pancreatitis, the rats in Group I and II were treated with saline (1 ml, every 12 hours), while the rats in Group III were treated with 3-aminobenzamide (10 mg/kg/day every 12 hours), intraperitoneally. In the 54(th) hour of the study, blood and tissue samples were taken for biochemical, microbiological and histopathological analysis. Results: Acute pancreatitis developed in Groups II and III. Pathologic score [median (25-75% percentiles). of the pancreatitis in Group III [8 (7-9)] was significantly lower than in Group II [19 (18-21)] (p0.05). Improvement in bacterial translocation was correlated with reducing oxidative stress. Conclusions: We demonstrated that 3-aminobenzamide therapy improved histopathologic score and oxidative stress in experimental pancreatitis. In addition, it was demonstrated microbiologically and histopathologically that 3-aminobenzamide therapy improves bacterial translocation. Further survival studies demonstrating the efficacy of 3-aminobenzamide therapy and explaining the potential mechanisms of bacterial translocation prevention in acute necrotizing pancreatitis will be beneficial

The role of allopurinol in experimental acute necrotizing pancreatitis

Background & objectives: Acute pancreatitis (AP) in its severe form can lead to severe complications and death. Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Oxygen-derived free radicals have been suggested to play a major role in the pathogenesis of AP. Xanthine oxidase enzyme is an important source of reactive oxygen metabolites. We undertook this study to evaluate the effect of allopurinol on bacterial translocation, oxidative stress and the course of AP in a rat model

The effect of combination therapy of hyperbaric oxygen, meropenem, and selective nitric oxide synthase inhibitor in experimental acute pancreatitis

Despite the new diagnostic and therapeutic advancements, acute pancreatitis has still high rate of morbidity and mortality. We aimed to evaluate the effects of hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT), and meropenem (MER) therapy in an experimental rat model of acute necrotizing pancreatitis. Rats were randomly divided into 8 groups, and acute pancreatitis was induced in all groups except group 1. Treatment protocols were saline for group 2, SMT for group 3, SMT+MER for group 4, SMT+HBO for group 5, HBO for group 6, HBO+MER for group 7, and MER for group 8. All surviving animals were killed 48 hours after the induction of pancreatitis, and specimens were collected. Oxidative stress parameters, histopathologic scores and amylase levels were better in treatment groups than in the positive control group (group 2). The most favorable results were obtained in HBO treatment groups, especially in HBO+MER group (group 7). Our results indicate that adding HBO therapy to the antibiotic therapy will decrease oxidative stress parameters, serum amylase levels, and histopathological score. We suggest that adding the HBO therapy as an adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield improvement in the morbidity and mortality of the disease

Pegylated interferon-alpha plus taurine in treatment of rat liver fibrosis

AIM: To investigate the antifibrotic effects of peginterferon-alpha 2b and taurine on oxidative stress markers and hepatocellular apoptosis