Wolcott–Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature*

Ozbek MN, Senée V, Aydemir S, Kotan LD, Mungan NO, Yuksel B, Julier C, Topaloglu AK. Wolcott–Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. Wolcott‐Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early‐infancy‐onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3‐W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype.     

The role of epidermal growth factor in prevention of oxidative injury and apoptosis induced by intestinal ischemia/reperfusion in rats

Intestinal ischemia/reperfusion is a major problem which may lead to multiorgan failure and death. The aim of the study was to evaluate the effects of epidermal growth factor (EGF) on apoptosis, cell proliferation, oxidative stress and the antioxidant system in intestinal injury induced by ischemia/reperfusion in rats and to determine if EGF can ameliorate these toxic effects. Intestinal ischemia/reperfusion injury was produced by causing complete occlusion of the superior mesenteric artery for 60 min followed by a 60-min reperfusion period. Animals received intraperitoneal injections of 150 μg/kg human recombinant EGF 30 min prior to the mesenteric ischemia/reperfusion. Mesenteric ischemia/reperfusion caused degeneration of the intestinal mucosa, inhibition of cell proliferation, stimulation of apoptosis and oxidative stress in the small intestine of rats. In the ischemia/reperfusion group, lipid peroxidation was stimulated accompanied by increased intestinal catalase and glutathione peroxidase activities, however, glutathione levels and superoxide dismutase activities were markedly decreased. EGF treatment to rats with ischemia/reperfusion prevented the ischemia/reperfusion-induced oxidative injury by reducing apoptosis and lipid peroxidation, and by increasing antioxidant enzyme activities. These results demonstrate that EGF has beneficial antiapoptotic and antioxidant effects on intestinal injury induced by ischemia/reperfusion in rats.     

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats

The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ⁹-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ⁹-THC treated, (3) diabetic, and (4) diabetic + Δ⁹-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ⁹-THC and Δ⁹-THC treated diabetic groups received 3 mg/kg/day of Δ⁹-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin–biotin–peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic + Δ⁹-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic + Δ⁹-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes + Δ⁹-THC group showed a decrease compared to the diabetic group. These results indicate that Δ⁹-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.     

Effects of chard (Beta vulgaris L. var. Cicla) extract on pancreatic B cells in streptozotocin-diabetic rats: a morphological and biochemical study

Chard (Beta vulgaris L. var. cicla) is used as a hypoglycemic agent by diabetic patients in Turkey. The present study was carried out in order to detect whether this plant, used in folk remedies for decreasing blood glucose levels, affects pancreatic B cells and blood glucose. In the diabetic group, a decrease in the number of B cells of Langerhans islets and in the secretory materials, a swollen granular endoplasmic reticulum cisternae and widened intercellular areas in some of B cells were observed. But, in a diabetic group given chard extract, an increase in the number of B cells of Langerhans islets and in the secretory granules were noted, together with many hypertrophic Golgi apparatus and granules of low densities. The extract while having no effect on blood glucose and body weight in the normal group, reduced the blood glucose value in streptozotocin-induced hyperglycemic animals. But, in a diabetic group given chard, the body weight significantly increased in comparison to the diabetic group; maximum reduction in blood glucose levels was observed on the 42nd day. According to the morphological and biochemical results obtained, it is concluded that the extract of this plant when administered by gavage may reduce blood glucose levels by regeneration of the B cells.     

Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study

Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats.     

The morphological and biochemical effects of glibornuride on rat liver in experimental diabetes

Glibornuride is a sulphonylurea derivative used as an oral hypoglycaemic drug in diabetics. The aim of this study was to examine the histological, ultrastructural and biochemical effects of glibornuride in streptozotocin (STZ)-treated rats. The animals were rendered diabetic by intraperitoneal injection of 65 mg/kg STZ. Fourteen days later, glibornuride was given at 5 mg/kg by gavage, daily for 28 days, to one STZ-diabetic and one control group. In the STZ-diabetic group, remarkable degenerative changes were observed. On the other hand, in the STZ-diabetic group given glibornuride, the degenerative changes decreased. In the STZ-diabetic group, blood glucose levels, serum aspartate transaminase activity, and total lipid levels increased, whereas the blood glutathione levels decreased. In contrast, in the STZ-diabetic group given glibornuride blood glucose levels, serum aspartate transaminase activity and total lipid levels decreased and blood glutathione levels increased. Significant changes in total protein levels in the serum were not observed in any group. As a conclusion, we can say that glibornuride has a protective effect against the hepatotoxicity produced by STZ-diabetes.     

The Role of Vitamin C,Vitamin E,and Selenium on Cadmium-Induced Renal Toxicity of Rats

The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl₂) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The tissue and blood samples were taken from the rats for histological evaluation and biochemical analyses on the Day 9. Lipid peroxidation (LPO) and glutathione (GSH) determination were made in kidney tissue. In addition, urea and creatinine levels were determined in serum. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. LPO levels significantly increased and GSH levels decreased in kidney tissues following cadmium administration. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.     

Protective effect of vanadyl sulfate on the pancreas of streptozotocin-induced diabetic rats

The aim of this study is to examine from a biochemical and histological perspective, whether vanadium has a protective effect on the pancreas of diabetic rats. Male, 6-6.5 months old, Swiss albino rats were divided into four groups. Group I: control (intact) animals (n=13). Group II: control rats given vanadyl sulfate (n=5). Group III: streptozotocin-induced diabetic animals (n=11). Group IV: streptozotocin-induced diabetic animals given vanadyl sulfate (n=11). Vanadyl sulfate was given by gavage technique to rats in a dose of 100mg/kg daily for 60 days, after experimental animals were made diabetic. On day 60, the pancreas tissue and blood samples were taken from the animals. In the streptozotocin-induced diabetic group, blood glucose levels significantly increased in contrast to the loss of body weight, but vanadyl sulfate in streptozotocin-diabetic rats reduced blood glucose levels and increased both blood glutathione levels and body weight. Tissue sections were immunostained using an insulin antibody. The control group given vanadyl sulfate was no different from the other intact control group considering the insulin immunoreactivity in B cells. In pancreatic islets of the diabetic group, a decrease in the number of immunoreactive B cells was observed in comparison to the control group. On the other hand, pancreatic islets of the diabetic group given vanadyl sulfate showed a higher number of immunoreactive B cells in comparison to the diabetic group. According to the immunohistochemical and biochemical results obtained, it was concluded that vanadyl sulfate can regenerate B cells of endocrine pancreas in experimental diabetes.