Cognitive and physical disability in Egyptian patients with multiple sclerosis: genetic and optical coherence tomography study.

Objectives: The aim of this study was to explore the relationship between cognitive dysfunction, neurodegeneration, and genetic factors among multiple sclerosis (MS) patients. Methods: Fifty patients of definite MS were included. Physical disability was assessed by expanded disability status scale (EDSS). Cognitive functions were assessed by using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). For each eye, optical coherence tomography (OCT) was used to track thickness of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), respecting the previous history of optic neuritis (ON). All patients were genotyped for glutamate N-methyl-D-aspartate receptors (NMDARs). Results: A statistically significant negative correlation was found between scores of EDSS and each of neuropsychological tests scores and thickness of both RNFL and GCC. The predictor for progressive disability assessed by EDSS was Symbol Digit Modalities Test (SDMT) (P = 0.021), that is dependent on the educational level of the patients (P = 0.016). A statistically significant positive correlation was found between scores of all neuropsychological tests and the thickness of both RNFL and GCC. Eighty-three percent of MS patients with CC genotype reported previous attacks of ON with significant thinning in RNFL and GCC despite their higher cognitive performance in comparison to other genotypes. Discussion: Deficit in information processing speed measured by SDMT is a predictor of early progressive disability in MS patients. Thinning of RNFL and GCC is a potential biomarker for cognitive and physical disability in MS. The CC genotype of glutamate NMDAR gene has a divergent effect on visual and cognitive functions.

Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling.

BACKGROUND: The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. METHODS: Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl(4), rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. RESULTS: Histopathological examination of liver tissue from animals which received DENA-CCl(4) only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated ß-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. CONCLUSIONS: Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.

Effect of hemin and carbon monoxide releasing molecule (CORM-3) on cGMP in rat penile tissue.

INTRODUCTION: Cyclic guanosine monophosphate (cGMP) levels can be regulated by heme oxygenase-1 and 2 (HO-1 and HO-2)-derived carbon monoxide (CO). AIMS: Assessment of the effect of upregulating CO in rat corpora cavernosa (CC) on cavernous cGMP. METHODS: Three experimental groups were studied: first group (N = 40), short-term HO induction over 2 weeks by injection of intraperitoneal increasing doses of hemin; the second group (N = 40) was subjected to intracavernosal injection of CO donor, CORM-3, or its inactive form (iCORM-3) over 2 weeks; the third group (N = 60) was subdivided into three subgroups: the first one received a combined hemin and CORM-3, the second one received hemin and its inhibitor stannus mesoporphyrin (SnMP), and third one received a combined hemin, CORM-3, and SnMP. MAIN OUTCOME MEASURES: In CC, HO-1 and HO-2 gene expression, Northern blot and Western blot, cGMP levels, and HO enzyme activity. RESULTS: In the first group, maximum induction of HO-1 gene expression, HO enzyme activity, and cGMP occurred with 4-mg hemin dose with a successive increase over 2 weeks. In the second group, CORM-3 increased cGMP by twofold compared with iCORM-3, and also increased HO-1 protein. In the third group, SnMP inhibited the enhancing effect of CORM-3 and HO on erectile signaling molecules; i.e., HO-1 gene, enzyme activity, and cGMP. CONCLUSIONS: CORM-3- or hemin-mediated CO release could increase cavernous tissue cGMP.