Gestational Diabetes Mellitus and its Effects on the Developing Cerebellum: A Narrative Review on Experimental Studies.

Diabetes mellitus during pregnancy is a common complication of gestation, but its effects on the offspring's development are poorly understood. Recently, some studies reported that gestational diabetes mellitus (GDM) impairs cerebellar development, and some genetic alterations have been described as consequences. Cerebellum, one of the hindbrain derived structures in the posterior cranial fossa, plays a crucial role in cognition and behavioral functions. In recent years, some surveys stated that gestational diabetes has adverse effects on the fetus's cerebellum. Disruption of cerebellar cortex morphogenesis, reduce the volume of the cerebellum, reduce the thickness of cerebellar cortex layers, and its neuronal cells and effects on the expression of synaptophysin, insulin, and insulin-like growth factor -1 receptors are some of the maternal diabetes effects on developing cerebellum. On other hand, GDM, as a neurotoxic agent, impaired cerebellar development and could be a cause for the behavioral, functional, and structural anomalies observed in pups of diabetic mothers. Based on the literature review, most studies have pointed out that administering insulin in patients with GDM decreased the cellular and molecular alterations that induced by GDM in the developing cerebellum. Undoubtedly, screening strategies for all pregnant women are necessary.

Alterations in lipid peroxidation, lipid profile, insulin sensitivity, and hepatic histopathological changes in diabetic rats following the treatment with Salvadora persica.

We examined the effects of various partitions of Salvadora persica extract on lipid profile (LP), lipid peroxidation, and insulin sensitivity (IS) of diabetic rats. The rats were divided into normal control, diabetic control (DC), standard, sham, and test groups. The test groups were treated with an oral dose of 200, 400, and 600 mg/kg of crude, aqueous, and ethyl acetate partition of S. persica extract. After 21 days of experiment, the fasting blood glucose (FBS), LPs, lipid peroxidation, IS, liver enzymes levels, liver histopathology, and body weight alteration were evaluated. A significant decrease in FBS and lipid profile (except HDL) were observed in rats treated with various dose of extract compared with the DC rats ( P < 0.05). Treating diabetic rats with various extracts of S. persica meaningfully decreased the level of malondialdehyde ( P < 0.05). Animals treated with various dose of aqueous extract showed better results ( P < 0.01). On the basis of used indirect indexes to determine IS, all partitions of extracts showed anti-insulin resistance effects in diabetic rats. On the basis of our statistical analyzing, treating diabetic rats with all of the three extracts of S. persica decreased the elevated levels of alanine phosphatase, aspartate aminotransferase, and alanine transferase. Also, pathological changes in the liver tissue were reduced following treatment with the S. persica. In conclusion, our results give evidence that the S. persica extract, especially aqueous partition, has a healing effect on diabetes and can be considered as an alternative therapy for this disease.

Molecular aspects of pancreatic ß-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA.

Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic ß-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic ß-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the ß cell via activation or inhibition of several processes and targets, such as receptor-signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic ß-cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic ß-cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic ß-cell dysfunction.

Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome.

Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation, and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (eg, PI3 kinases, PPARγ co-activator-1, microRNAs, serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of various factors involved in DM pathogenesis, microRNAs, and exosomes have been emerged as effective factors in initiation and progression of DM. A variety of studies indicated that deregulation of these molecules could change behavior of various types of cells and contribute to progression of DM. Resistin is other main factor which is known as signal molecule involved in insulin resistance. Multiple lines evidence indicated that resistin exerts its effects via affecting on glucose metabolism, inhibition of fatty acid uptake and metabolism with affecting on a variety of targets such as CD36, fatty acid transport protein 1, Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized various molecular aspects are associated with DM particularly the molecular pathways involved in insulin resistance and resistin in DM. Moreover, we highlighted exosomes and microRNAs as effective players in initiation and progression of DM.

Protective effect of hydroalcoholic extract of Teucrium polium on diabetes-induced testicular damage and serum testosterone concentration.

BACKGROUND: Diabetes has an adverse effect on spermatogenesis by rising oxidative stress. OBJECTIVE: The aim of this study was to investigate the effect of Teucrium Polium extract administration on spermatogenesis and testicular structure in diabetic rats induced with Streptozotocin. MATERIALS AND METHODS: 32 male Wistar rats were randomly divided into four groups (n=8/each): control group, diabetic group received distilled water, and two experimental groups included diabetic rats treated with 50 and 100 mg/body weigh of Teucrium Polium extract for 6 six weeks. After six weeks, the left testis had been removed and the morphometrical study was performed. Blood samples were collected from the ophthalmic veins of the rats and plasma levels of glucose and testosterone hormone were measured afterward. RESULTS: The reduction in diameters of the seminiferous tubules and thickening of the wall of the seminiferous tubules (p=0.05) were seen in diabetic rats. Also, the degenerative changes in cells arrangement have been observed. Statistical analysis showed the use of Teucrium Polium significantly improved the above disorders in treatment group (100 mg/BW) in contrast to the non treated diabetic group (p=0.05), but no significant difference was seen between the experimental group treated with 50 mg/BW of Teucrium polium and diabetic group (p=0.08). These data also revealed that treatment of diabetic rats with 100 mg/BW of Teucrium Polium extract significantly improves the change in serum glucose (p=0.001) and testosterone (p=0.03). CONCLUSION: The results of the present study indicate that diabetes produces degenerative changes in the testis of rats and administration of Teucrium polium reduces complications resulted from diabetes.

Childhood Laryngeal Dystonia Following Bilateral Globus Pallidus Abnormality: A Case Study and Review of Literature.

INTRODUCTION: Dystonia is a disorder of movement caused by various etiologies. Laryngeal dystonia is caused by the spasm of laryngeal muscles. It is a disorder caused by vocal fold movement in which excessive adduction or abduction of the vocal folds occurs during speech. The pathophysiology of this type of dystonia is not fully known. Some researchers have suggested that basal ganglia structures and their connections with cortical areas have been involved in the pathogenesis of dystonia. CASE REPORT: In this paper a 7.5-year-old boy suffering from laryngeal dystonia with bilateral lesions in Globus Pallidus is presented. The patient also suffered from swallowing problems, monotone voice, vocal tremor, hypersensitivity of gag reflex, and stuttering. Drug treatment failed to cure him; therefore, he was referred to rehabilitation therapy. CONCLUSION: In conclusion, special attention should be brought upon laryngeal dystonia, especially in patients showing Extra-pyramidal symptoms and/or abnormalities of the basal ganglia. In children, laryngeal dystonia may be potentially fatal. Lack of consideration for this condition during rehabilitation therapy can lead to serious consequences for a child.

The Effects of Administrated Sildenafil Citrate on Uterine Luminal Epithelium Height Associated with Ovarian Angiogenesis: An Experimental Animal Study.

BACKGROUND: Ovarian angiogenesis (OA) remains in lifetime and normal ovarian function depends to this continual remodeling of a complex vascular system. Endometrial thickness (ET) is one of the strongest predictors of successful implantation and pregnancy. Appropriate OA effects on ET by facilitating of ovarian hormone delivery. MATERIALS AND METHODS: Thirty adult female mice and twenty adult male mice were purchased. The female mice were divided into three groups: (1) control group without any intervention (n = 10), (2) gonadotropin group: receiving human menopausal gonadotropin (HMG) and human chorionic gonadotropin (n = 10), and (3) gonadotropin and sildenafil citrate (SC) group: receiving HMG and SC administration (n = 10). After mating, animals were deeply anesthetized, and the ovary and uterus was rapidly removed for histology and immunohistochemistry process. RESULTS: Four days after ovarian induction, all three layers of the uterus with specified thickness can be clearly seen. The heights of endometrial epithelial cells in gonadotropin group were not significantly different than those in control group. In gonadotropin and SC group, heights of the cells were significantly (P < 0.05) shorter than control and gonadotropin groups. ETs in all groups were not significantly deferent from each other (P > 0.05 each). Our results of immunohistochemistry survey for ovarian CD31 demonstrated that administrated SC increased OA but not significantly (P > 0.05 each). CONCLUSION: It may finally conclude that administration of SC does not cause notable alterations in OA and ET; although for realistic decision about the SC effects on aforementioned parameters, more molecular investigations and longer drug consumption period are necessary.

Evaluation of Bax and Bcl-2 Proteins Expression in the Rat Hippocampus due to Childhood Febrile Seizure.

OBJECTIVE: Simple Febrile Seizure (SFS) is the most common seizure disorder in childhood, and is frequently described as inoffensive disorder. Nevertheless, there is evidence suggesting the association between neonatal febrile seizures and hippocampal abnormalities in adulthood. This study was conducted at evaluating the hippocampal expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins following SFS induction in rat neonates. MATERIALS & METHODS: Febrile seizure was modeled by hyperthermia-induced seizure in 22-dayold male rats by a hot water bath. The animals were divided into two groups based on the presence or absence of seizure behaviors: Hyperthermia without seizure (n=10) and hyperthermia with seizure (n=10). To control the effects of environmental stress a sham-control group was also added (n=10). The rats' hippocampi were dissected 2 or 15 days after hyperthermia. The expression of Bax and Bcl-2 proteins were measured using Western Blotting technique. RESULTS: The hippocampal expression of Bcl-2 protein was significantly lower in the hyperthermia with seizure animals than that of the sham-control and hyperthermia without seizure groups. The expression of pro-apoptotic Bax protein also significantly increased in the hippocampus of hyperthermia with seizure group rats compared to the sham-control and hyperthermia without seizure animals. CONCLUSION: The simple febrile seizure markedly disturbed the hippocampal expression of both Bcl2 and Bax proteins, resulting in apoptosis promotion in hippocampi of juvenile rats, which were measurable for at least 15 days.