Association between vitamin D and glycaemic parameters in a multi-ethnic cohort of postmenopausal women with type 2 diabetes in Saudi Arabia.

BACKGROUND: The relationship between vitamin D (VitD) and insulin sensitivity and secretion in type 2 diabetes mellitus (T2D) has been shown to be different amongst different ethnic populations. In Saudi Arabia, where both T2D and VitD deficiency are highly prevalent health concerns, little is known about the relationship between VitD, insulin sensitivity, resistance and the relative importance of ethnicity. Our primary aim in this study was to investigate influence of ethnicity on VitD association with glycaemic profile and to measures of obesity as a secondary outcome, among multiethnic postmenopausal women with T2D in Saudi Arabia. METHODS: A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Postmenopausal females (n = 173, age ≥ 50 years) with T2D were randomly selected in this study. Anthropometric measures and fasting blood samples were obtained for all study participants. Several biochemical parameters were measured including 25-hydroxyvitamin D (25(OH)D), glycosylated hemoglobin (HbA1c), insulin, glucose and c-peptide. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment 2 for insulin resistance and beta cell activity (HOMA2-IR, HOMA2-ß). RESULTS: Overall, 25(OH)D was inversely associated with fasting glucose (r=-0.165, P = 0.037), insulin (r=-0.184, P = 0.02), C-peptide (r=-0.19, P = 0.015) and HOMA2- IR C-peptide (r=-0.23, P = 0.004). Additionally, serum 25 (OH)D showed a negative correlation with body weight (r=-0.173 P = 0.028), waist and hip circumferences (r=-0.167, P = 0.033; r=-0.22, P = 0.004 respectively) but not with body mass index (BMI) or waist hip ratio (WHR). In the white ethnic group but not in black or Asian population groups, 25(OH)D level was also associated with only serum fasting C-peptide and HOMA2-IR C-peptide and BMI (P < 0.05). CONCLUSIONS: Insulin resistance and obesity were associated with VitD status in T2D in this cohort. Our findings also suggest that these VitD associations in women from white ethnic background are different than in those from black/Asian ethnic backgrounds. Whether VitD supplements are able to improve either obesity and/or insulin sensitivity should be further investigated in different ethnic population groups.

Hepato-protective effect of Allium sativum against immobilization stress in rats.

The purpose of the current study was to examine immobilization stress-induced antioxidant defense changes and estimation of the antioxidant potential of pre and post stress treatment of aqueous garlic extract in rat's liver. For this purpose, male Albino Wistar rats were treated with aqueous garlic extract both pre and after 6 h of immobilization stress. Pro-oxidant status of rat liver was evaluated by determining the levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), glucose, uric acid and the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). In response to 6 h of immobilization stress a significant rise in the level of above mentioned liver enzymes were recorded. However, SOD, CAT and GST enzymatic activities showed a sharp decline. The extract treatment before and after stress, almost reverted the activities of studied biochemical parameters towards their control values. Current study highlighted the antioxidant potential of garlic extracts. Based on our study, we recommend the use of garlic extract as nutritional supplement for combating oxidative stress induced damage.

Roles of Natural Compounds from Medicinal Plants in Cancer Treatment: Structure and Mode of Action at Molecular Level.

Every year, cancer takes the life of millions of people. Conventional treatments have produced unsatisfactory results for some types of cancer, and the side effects are extensive, leading to a shift in the focus of treatment towards alternative medicines. Indeed, medicinal plants have long been investigated by scientists for their anti-cancer properties. Some phytochemicals that are important active constituents of plants, including catechins, ursolic acid, silymarin, glycyrrhizin, ellagic acid, gallic acid and various types of flavonoids, have shown promise in future cancer management. The current review covers various aspects of cancer treatment based on medicinal plants at molecular level and sheds light on their structures and modes of action.

Disease associated cellular machinery in anaphylaxis - And the de novo paradigm shift.

Anaphylaxis is a sudden immune reaction against an allergen that can potentially lead to Anaphylactic Shock (AS). This immune reaction is characterized by an increase in Immunoglobulin-E (IgE) type of antibodies that bind with FcεRI receptors on mast cells to release inflammatory mediators. Various intracellular signaling molecules downstream of IgE/ FcεRI axis play a potential role in cytokine, chemokine and eicosanoid secretion as well as degranulation of immune cells causing vasodilation, vascular permeability, and reduction of intravascular volume leading to cardiovascular collapse. Here, we discuss the cellular machinery of anaphylaxis and the de novo paradigm shift in the cellular aspects of AS.

Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABAB1 receptor in adult rats cortex and hippocampus.

Epilepsy is a common neurological disorder that leads to neuronal excitability and provoke various forms of cellular reorganization in the brain. In this study, we investigate the anti-convulsant and neuroprotective effects of thymoquinone (TQ) and vitamin C against pentylenetetrazole (PTZ)-induced generalized seizures. Epileptic seizures were induced in adult rats using systemic intraperitoneal injections of PTZ (50 mg/kg) for 7 days. Animals pretreated with either TQ or vitamin C or in combination attenuated PTZ-induced seizures and mortality in rats as well neurodegeneration in the cells. Compared to PTZ, TQ and vitamin C significantly prolonged the onset of seizures (p > 0.05) as well decrease the high-grade seizures. Analysis of electroencephalogram (EEG) recordings revealed that TQ or vitamin C supplementation significantly reduced polyspike and epileptiform discharges. Epileptic seizures caused a decline in expression of gamma-aminobutyric acid B1 receptor (GABAB1R) (p > 0.05), unchanged expression of protein kinase A (PKA), decreased calcium/calmodulin-dependent protein kinase II (CaMKII) (p > 0.05) and inhibit the phosphorylation of cAMP response element-binding protein (CREB) (p > 0.05) in cortex and hippocampus, respectively, compared with control. Changes in expression of GABAB1R, CaMKII and CREB by PTZ were reversed by TQ and vitamin C supplementation. Moreover, PTZ significantly increased Bax, decreased Bcl-2 expression and finally the activation of caspase-3. TQ and vitamin C pretreatment reversed all these deleterious effects induced by PTZ. TQ and vitamin C showed anticonvulsant effects via activation of GABAB1R/CaMKII/CREB pathway and suggest a potential therapeutic role in epilepsy.

New possibilities in hepatocellular carcinoma treatment.

Hepatocellular carcinoma diagnosis and treatment has witnessed many major changes and challenges in the past two decades. Increasing incidence of HCC has introduced new monitoring systems and increased the efficacy of screening tests, as well as prognosis of the disease, including the staging system, serological testing and diagnostic imaging. Moreover, surgical resection, liver transplantation and herbal therapy have improved treatment. The most encouraging specific serological marker for HCC is alpha fetoprotein (AFP), which, along with ultrasonography, has improved earlier detection of HCC. Most recently, circulating tumor cell measurement has emerged as a promising tool for the prognosis of HCC. Herbal drugs and herbal composite formula drugs are promising towards the prevention of invasion and proliferation of tumor cells. Chemotherapeutic agents, such as sorafenib, bevacizumab and erlotinib, which target growth factor receptors in signaling pathways, are also used as HCC treatments. Furthermore, radiotherapy is employed in the treatment of unresectable tumors. The present report provides an analysis of the above parameters in the management of HCC.

Neuroprotective profile of pyruvate against ethanol-induced neurodegeneration in developing mice brain.

Exposure to ethanol during developmental stages leads to several types of neurological disorders. Apoptotic neurodegeneration due to ethanol exposure is a main feature in alcoholism. Exposure of developing animals to alcohol induces apoptotic neuronal death and causes fetal alcohol syndrome. In the present study, we observed the possible protective effect of pyruvate against ethanol-induced neurodegeneration. Exposure of developing mice to ethanol (2.5 g/kg) induces apoptotic neurodegeneration and widespread neuronal cell death in the cortex and thalamus. Co-treatment of pyruvate (500 mg/kg) protects neuronal cell against ethanol by the reduced expression of caspase-3 in these brain regions. Immunohistochemical analysis and TUNNEL at 24 h showed that apoptotic cell death induced by ethanol in the cortex and thalamus is reduced by pyruvate. Histomorphological analysis at 24 h with cresyl violet staining also proved that pyruvate reduced the number of neuronal cell loss in the cortex and thalamus. The results showed that ethanol increased the expression of caspase-3 and thus induced apoptotic neurodegeneration in the developing mice cortex and thalamus, while co-treatment of pyruvate inhibits the induction of caspase-3 and reduced the cell death in these brain regions. These findings, therefore, showed that treatment of pyruvate inhibits ethanol-induced neuronal cell loss in the postnatal seven (P7) developing mice brain and may appear as a safe neuroprotectant for treating neurodegenerative disorders in newborns and infants.

Time-dependent effect of ethanol on GnRH and GnRH receptor mRNA expression in hypothalamus and testis of adult and pubertal rats.

Chronic exposure to ethanol suppresses the male reproductive activity which is primarily involved in the release of hypothalamic gonadotropin-releasing hormone (GnRH). The testicular GnRH and GnRH receptors (GnRH-R) are found in seminiferous tubules, which are predicted to act as a local regulator of spermatogenesis, although the function is not well known. In this study, we investigated the chronic ethanol effect on GnRH mRNA expression in hypothalamus and testis using in situ hybridization and RNase protection assay (RPA). The effect of ethanol on expressional changes of GnRH and GnRH-R mRNA was observed in adult and pubertal rats according to age and time from 2 weeks (short term) and 4 weeks (long term) periods. The results showed that GnRH mRNA expression in adult and pubertal rats was dramatically decreased in the testis while no significant change was observed in hypothalamus after both short and long term exposure to ethanol. The pubertal rats showed decrease in testicular GnRH and GnRH-R mRNA expression, whereas GnRH mRNA was increased significantly, while GnRH-R mRNA was further decreased after long term exposure in adults. This study suggested that chronic ethanol administration is more effective to testicular GnRH and GnRH-R mRNA expression than hypothalamus and causes a negative effect on the spermatogenesis process. Furthermore, our finding suggests that the deteriorative effects of ethanol on gonadal activity are more lethal in puberty than adults.