Effect of superparamagnetic iron oxide nanoparticles on glucose homeostasis on type 2 diabetes experimental model.

AIMS: Evaluation of the anti-diabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs) on Type 2 diabetic rats and compared their effect to metformin treatment. MAIN METHODS: Diabetic rats were treated with different doses of nanoparticles one time per week for 4 weeks. Fasting blood glucose level was determined for studied groups during the experimental period (30 days). At the end of the experiment, oral glucose tolerance test was carried out, serum samples were collected for biochemical assays. Then animals were sacrificed to obtain tissues for assessment of glucose transporters, insulin receptors and insulin signaling proteins. KEY FINDING: SPIONs treatment normalized fasting blood glucose and lowering insulin level in diabetic rats compared to untreated diabetic rats. SPIONs significantly ameliorate the glucose sensing and the active components of insulin signaling pathway. The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better. SIGNIFICANCE: To our knowledge, this is the first study that explores the anti-diabetic effects of SPIONs on diabetic model.

Similar and additive effects of ovariectomy and diabetes on insulin resistance and lipid metabolism.

Type 2 diabetes mellitus (T2DM) is among the leading causes of death in postmenopausal women. The disruption of ovarian function may contribute to the incidence of T2DM. The purpose of this study was to investigate the effects of ovariectomy and T2DM on glucose and lipid homeostasis, perilipin levels in adipose tissues, as a lipolytic regulator, and levels of certain adipokines. Ovariectomized (OVX) rats were used as a model for postmenopausal women. The study was performed on sham, OVX, sham diabetic, and OVX diabetic female rats. The results indicated that ovariectomy alters adipose tissue metabolism through reducing perilipin content in white adipose tissue (WAT); however it has no effect on perilipin level in brown adipose tissue (BAT). OVX diabetic females suffer from serious metabolic disturbances, suggested by exacerbation of insulin resistance in terms of disrupted lipid profile, higher HOMA-IR, hyperinsulinemia, higher leptin, and lower adiponectin concentrations. These metabolic derangements may underlie the predisposition for cardiovascular disease in women after menopause. Therefore, for efficient treatment, the menopausal status of diabetic female should be addressed, and the order of events is of great importance because ovariectomy following development of diabetes has more serious complications compared to development of diabetes as result of menopause.

Impaired peripheral glucose sensing in F1 offspring of diabetic pregnancy

Maternal diabetes can induce permanent changes in glucose homeostasis that can occur pre- and post-natal and leads to type 2 diabetes in adulthood. This study aimed to investigate the effect of maternal diabetes on the F1 offspring peripheral glucose sensing and mitochondrial biogenesis in an attempt to clarify the mechanism of diabetogenic programming. Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks, OGTT was constructed, and serum and tissues were obtained for the assessment of mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (phospho-IR), and GLUT4. The result indicated impaired glucose tolerance (IGT) and insulin resistance in the offspring under control diet at the 15th week of age and thereafter while those offspring under HCD showed IGT at 10th week, and diabetes was evidenced at the 25th week of age. This defect in glucose metabolism was preceded by impairment in the phosphorylation of IR and decreased IR and Glut4 that cause impaired glucose sensing together with inhibited mitochondrial biogenesis in muscle and adipose tissues. This study indicated that maternal diabetes caused impaired glucose sensing and insulin resistance in the peripheral tissues and caused change in the expression of genes involved in mitochondrial biogenesis and function. Post-natal feeding with HCD may accelerate these changes. Male F1 offspring appears to be more sensitive than females for fetal programming of T2D (AU)

Impaired peripheral glucose sensing in F1 offspring of diabetic pregnancy.

Maternal diabetes can induce permanent changes in glucose homeostasis that can occur pre- and post-natal and leads to type 2 diabetes in adulthood. This study aimed to investigate the effect of maternal diabetes on the F1 offspring peripheral glucose sensing and mitochondrial biogenesis in an attempt to clarify the mechanism of diabetogenic programming. Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks, OGTT was constructed, and serum and tissues were obtained for the assessment of mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (phospho-IR), and GLUT4. The result indicated impaired glucose tolerance (IGT) and insulin resistance in the offspring under control diet at the 15th week of age and thereafter while those offspring under HCD showed IGT at 10th week, and diabetes was evidenced at the 25th week of age. This defect in glucose metabolism was preceded by impairment in the phosphorylation of IR and decreased IR and Glut4 that cause impaired glucose sensing together with inhibited mitochondrial biogenesis in muscle and adipose tissues. This study indicated that maternal diabetes caused impaired glucose sensing and insulin resistance in the peripheral tissues and caused change in the expression of genes involved in mitochondrial biogenesis and function. Post-natal feeding with HCD may accelerate these changes. Male F1 offspring appears to be more sensitive than females for fetal programming of T2D.

The levels of vascular endothelial growth factor-A and placental growth factor-2 in embryopathy associated with experimental diabetic gestation.

The objective of this study was to investigate the role of vascular endothelial growth factor-A (VEGF-A) and placental growth factor-2 (PlGF-2) in fetal malformations associated with maternal diabetes. Diabetes was induced in female rats. Diabetic and control female rats were made pregnant. On Day 15 of gestation, rats were sacrificed and embryos and their placentas and membranes were dissected out of the uterine horns. Following morphological examination, embryos and their placentas and membranes were homogenized and used for assayed of VEGF-A and PlGF-2 levels. Embryos of diabetic mothers, exhibited significantly (P < 0.05) shorter crown-to-rump lengths, smaller weights, and heavier placental weights. Experimentally induced maternal diabetes was accompanied by decreased VEGF-A in embryos and associated structures. The levels of PlGF-2 in non-malformed embryos of diabetic gestation and their placentas were significantly (P < 0.05) lower than the average of controls. These results might indicate defective vascularization with a consequent morphological or anatomical anomalies or more subtle biochemical or metabolic changes. In diabetic mothers, a statistically significant (P < 0.05) decrease was noted in the level of VEGF-A in plasma of diabetic rats with a small non-significant decrease in PlGF-2. Like many other diabetic complications, diabetes-induced embryopathies might have vascular origin and correcting the disturbances in these angiogenic factors might help decrease the incidence of malformation in diabetic gestation.

Effects of Bacillus thuringiensis toxin on hepatic lipid peroxidation and free-radical scavengers in rats given alpha-tocopherol or acetylsalicylate.

The effect of Dipel (D), a Bacillus thuringiensis-based bioinsecticide, on hepatic antioxidant enzyme activities and lipid peroxidation in rat liver was investigated. Administration of D in a dose of 1 mg/100 g body mass for 4 successive days increased the activities of glutathione peroxidase (GPx), glutathione reductase (GR) and the level of malondialdehyde (MDA) in rat hepatocytes. The activity of superoxide dismutase (SOD) and glutathione (GSH) level were decreased. Administration of D in rats pretreated with alpha-tocopherol (alphaT) or acetylsalicylic acid (ASA) decreased the activities of GPx, GR and MDA levels, while the GSH level was increased compared with rats treated with D alone. The SOD activity was increased in rats pretreated with alphaT before D, but decreased on pretreatment with ASA, compared with rats treated with D alone. The results indicated that D induced oxidative stress in rat liver that has been protected by prior administration of alphaT or ASA.

Improved purification and yield of the Egyptian snake Cerastes cerastes antitoxin by the use of caprylic acid.

The aim of this study was to obtain anti-snake antiserum by optimizing the conditions of extraction and purification and test its ability to neutralize local myonecrosis. Extraction and purification was achieved through adjustment of the pH, pepsin concentration, time of digestion, and caprylic acid concentration. Our results indicate that the best conditions to obtain anti-snake antiserum from ammonium sulfate fractionated plasma are pH 3.3, 3.5 g/l pepsin, digestion for 90 min at 37 degrees C, and 0.5% caprylic acid. Antiserum purified using this method has greater neutralizing ability of myonecrosis than ammonium sulfate (ammSO4) fractionated product.

Cross neutralization of dangerous snake venoms from Africa and the Middle East using the VACSERA polyvalent antivenom. Egyptian Organization for Biological Products & Vaccines.

This study was performed to assess the ability of polyvalent snake venom anti-serum, produced by the Egyptian Organization for Biological Products & Vaccines (VACSERA), to neutralize several toxic activities of snake venoms, not only of those included in the antivenom mixture, but also some additional venoms of snakes from Egyptian, African, and Middle Eastern habitats. In general, the results revealed that polyvalent snake venom anti-serum from VACSERA is highly effective in neutralizing Egyptian snake venoms, especially Naja haje, Naja nigricolles, Naja pallida, Cerastes cerastes, Cerastes cerastes cerastes, Cerastes vipera, Pseudocerastes persicus fieldi, and Walterinnisia egyptia. The antivenom was also effective against Naja haje, Walterinnisia egyptia, and Bites aritans from Saudi Arabia. High activity was obtained against venoms from Naja haje, Naja nigricolles, and Naja pallida of Sudan, as well as the African Naja melanoleuca, Naja mossambica, Naja naja oxiana, Bites gabonica, and Vipera lebetina. Only moderate effectiveness was obtained with Echis coloratus and Echis carinatus, and the polyvalent antiserum was ineffective against the venom of Naja nivea.

Development of an improved method for production of antiscorpion F(ab')2 fragment of IgG with high yield and potency.

The main objective of the present work was to obtain a stable and highly purified scorpion antitixon, rich in specific antibodies, free of immunologically irrelevant plasma proteins or gross proteins. Our results indicate that the most potent yielded and purified F(ab')2 antivenom preparation was obtained when the first discarded precipitate was washed with 14% ammonium sulphate saline; then after the second addition of ammonium sulphate, the mixture was stirring overnight followed by precipitation of most non-immunoglobulin proteins with the aid of caprylic acid to produce antivenom rich in specific antibodies with higher yield and potency compared to the method commonly used.

Molecular and immunological characterisation of Fasciola species.

Fasciola hepatica and F. gigantica are polymorphic liver flukes that show considerable overlap between species, and various protein separation techniques have been used as alternative means of differentiation. Acid and alkaline polyacrylamide gel electrophoresis (PAGE) show differences between F. hepatica and F. gigantica. Following SDS-PAGE, F. hepatica proteins are characterised by the presence of eight major peptide bands, with molecular weights estimated as 48, 45, 43.5, 37, 33, 29, 27 and 25.5 kDa. In contrast, F. gigantica shows only five major protein bands of 57.6, 54, 48, 29 and 27 kDa. Isoelectric focusing (IEF) demonstrates 17 bands from F. hepatica and 22 bands from F. gigantica between pH 3.5 and pH 10. Although many bands appear common to both species, some are species-specific. Six cases of human acute fascioliasis diagnosed clinically, haematologically and immunologically are also studied. Gel immunodiffusion and immunoelectrophoresis, using adult F. hepatica and F. gigantica antigens, are used to determine the species, and indicate that the antisera are more specific for F. hepatica.