Fluctuations in Serum magnesium and Systemic Arterial Blood Pressures during the Menstrual Cycle in young reproductive women

Introduction: The menstrual cycle involves a sequence of structural, functional, and hormonal changes in the reproductive system. This is linked and controlled by cyclical fluctuations in the levels of FSH, LH, estrogen, and progesterone. Because of these cyclical fluctuations, there might also be associated cyclical changes of magnesium and systemic arterial blood pressures during the menstrual cycle. Purpose: To assess the changes in serum magnesium level and systemic arterial blood pressures during the menstrual cycle in young reproductive women. Methodology: the sample population is 40 apparently healthy young reproductive-aged 18- 25years female students from the University of Medicine, Magway participated in this study. Systemic arterial blood pressures were measured by indirect method. The serum magnesium level was measured by spectrophotometry. These measurements were done in the early follicular phase (EF), the peri-ovulatory phase (PO), and the midluteal phase (ML) of the menstrual cycle. The serum magnesium levels were significantly (p <0.001) lower, and the systolic blood pressures were significantly higher (p <0.05) in the PO than the EF and the ML. In the EF, there was a significant negative correlation between serum magnesium level and diastolic blood pressure (r= - 0.374, p <0.05) and mean arterial pressure (r = -0.354, p < 0.05) but no significant correlation with systolic blood pressure. In the PO, there was no significant correlation between serum magnesium level and systemic arterial blood pressures. In the ML, there was significant negative correlation between serum magnesium level and systolic blood pressure (r = -0.651, p <0.001), diastolic blood pressure (r = -0.607, p <0.001), and mean arterial pressure (r = -0.661, p <0.001). Conclusion: The study concludes that serum magnesium level has a negative effect on blood pressure changes and the blood pressure-lowering effect of magnesium. These changes are related to the fluctuation of estrogen levels during the menstrual cycle. KEYWORDS: Serum magnesium, systemic arterial blood pressures, menstrual cycle reproductive syste

Delayed-Onset Continuous Bruxism with Olivary Hypertrophy After Top of the Basilar Syndrome

Delayed-onset continuous bruxism due to brain stem infarction has not yet been reported. A 49-year old man presented with quadriplegia and ophthalmoplegia. Brain MRI showed acute infarction in the bilateral midbrain, right thalamus and the superior cerebellum. One month later, the patient developed bruxism which persisted during sleep. A palatal myoclonus was not observed. Follow up MRI taken 4 months later showed bilateral olivary hypertrophy. We suggest that the patient's bruxism may be related to the olivary hypertrophy. The bruxism generator may be located in the pontine-reticular-formation (PRF). Bilateral large midbrain lesions interrupting the cortical inhibition may have produced bilateral olivary hypertrophy, which could stimulate the PRF, producing continuous bruxism

Phosphodiesterase 4D Gene and Risk of Noncardiogenic Ischemic Stroke in a Korean Population

Recently published studies from different populations provide apparently conflicting evidence on the association between the phosphodiesterase 4D (PDE4D) gene and ischemic stroke. The relationship between a representative PDE4D genotype and ischemic stroke was explored in a case-control study of 205 consecutive Korean patients with noncardiogenic ischemic stroke and 103 healthy controls who were neurologically and radiologically proven to be stroke-free. We selected and genotyped a PDE4D single nucleotide polymorphism (SNP 41, rs152312) as a candidate marker for susceptibility to ischemic stroke because SNP 41 has shown the most significant association with stroke in both a meta-analysis and the original Icelandic study of the PDE4D gene. No significant difference was observed between the cases and controls in the distribution of the PDE4D SNP 41 genotypes. The results from the adjusted conditional logistic regression analysis (adjusted for age, hypertension, diabetes and smoking status) showed no significant association between PDE4D SNP 41 genotypes and an increased risk of noncardiogenic ischemic stroke. The PDE4D gene is not a major risk factor for noncardiogenic ischemic stroke in a Korean population, which supports the recent evidence suggesting that the causative genetic variants of ischemic stroke may differ across populations

WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth

ABSTRACT: INTRODUCTION: In breast cancer deregulation of the WNT signaling pathway occurs by autocrine mechanisms. WNT ligands and Frizzled (FZD) receptors are coexpressed in primary breast tumors and cancer cell lines. Moreover, many breast tumors show hypermethylation of secreted Frizzled-related protein 1 (sFRP1)'s promoter region, causing low expression of this WNT antagonist. We have previously shown that the WNT pathway influences proliferation of breast cancer cell lines via activation of canonical signaling and epidermal growth factor receptor (EGFR) transactivation, and that interference with WNT signaling reduces proliferation. Here we examine the role of WNT signaling in breast tumor cell migration and on xenograft outgrowth. METHODS: The breast cancer cell line MDA-MB-231 was used to study WNT signaling. We examined the effects of activating or blocking the WNT pathway on cell motility by treatment with WNT ligands or by ectopic sFPR1 expression, respectively. The ability of sFRP1 expressing MDA-MB-231 cells to grow as xenografts was also tested. Microarray analyses were carried out to identify targets with roles in MDA-MB-231/sFRP1 tumor growth inhibition. RESULTS: We show that WNT stimulates the migratory ability of MDA-MB-231 cells. Furthermore, ectopic expression of sFRP1 in MDA-MB-231 cells blocks canonical WNT signaling and decreases their migratory potential. Moreover, the ability of MDA-MB-231/sFRP1 expressing cells to grow as xenografts in mammary glands and to form lung metastases is dramatically impaired. Microarray analyses led to the identification of two genes, CCND1 and CDKN1A, whose expression level is selectively altered in vivo in sFRP1 expressing tumors. The encoded proteins, Cyclin D1 and p21Cip1 were down- and up-regulated, respectively, in sFRP1 expressing tumors, suggesting that they are downstream mediators of WNT signaling. CONCLUSIONS: Our results show that the WNT pathway influences multiple biological properties of MDA-MB-231 breast cancer cells. WNT stimulates tumor cell motility; conversely sFRP1 mediated WNT pathway blockade reduces motility. Moreover, ectopic sFRP1 expression in MDA-MB-231 cells has a strong negative impact on tumor outgrowth and blocked lung metastases. These results suggest that interference with WNT signaling using sFRP1 to block the ligand-receptor interaction may be a valid therapeutic approach in breast cancer

TXNIP Regulates Peripheral Glucose Metabolism in Humans

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. METHODS AND FINDINGS: We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic β-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM

Integrated Expression Profiling and Genome-Wide Analysis of ChREBP Targets Reveals the Dual Role for ChREBP in Glucose-Regulated Gene Expression

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator