The Effect of Pioglitazone on the Alzheimer’s Disease-Induced Apoptosis in Human Umbilical Vein Endothelial Cells.

The effect of pioglitazone on the Alzheimer’s disease-induced apoptosis in human umbilical vein endothelial cells.

Int J Prev Med. 2013 May; 4(Suppl 2): S205-10
Dehghani L, Meamar R, Askari G, Khorvash F, Shaygannejad V, Pour AF, Javanmard SH

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and nowadays the role of endothelial cell (EC) injury has been proposed in pathological process in AD. Peroxisome proliferator-activated receptor-? (PPAR-?) agonist has anti-inflammatory properties through activation in glial cells and improves vascular function and prevent atherosclerotic disease progression. The aim of this study is evaluation of pioglitazone effects as a drug of PPAR-? agonist on endothelial apoptosis induced by sera from AD patients.Human umbilical vein endothelial cells (HUVECs) were treated with sera from AD patients (n = 10) and sera from controls (n = 10). Apoptosis was identified by annexin V-propidium iodide staining and cell death detection kit. Apoptosis was evaluated after and before adding of 10 ?M pioglitazone on EC. Nitrite (NO2 (-)) levels were determined in the culture supernatants.Induced apoptosis by the serum of patients was inhibited markedly when pioglitazone used before treating HUVECs with the sera of AD. Also, the measurement of nitrite concentration showed significantly greater levels of dissolved NO2/NO3 metabolite in the culture media of HUVECs treated by sera of AD patients (P < 0.05), while the rate of nitric oxide significantly decreased when pioglitazone exists in culture media.Further studies are justified to investigate the novel role of the PPARs in the prevention of the neuronal and endothelial damage in neurological disorder and present a new therapeutic approach for Alzheimer's patients. HubMed – drug


Restless legs syndrome in Iranian multiple sclerosis patients: a case-control study.

Int J Prev Med. 2013 May; 4(Suppl 2): S189-93
Shaygannejad V, Ardestani PE, Ghasemi M, Meamar R

Restless legs syndrome (RLS) is a common movement disorder. The occurrence of this syndrome is due to genetic factors and lifestyle. This study performed to determine restless legs syndrome (RLS) prevalence in Iranian multiple sclerosis (MS) patients and the possible risk factors.This cross-sectional study was conducted with MS patients, and the age- and sex-matched control group comprised healthy persons. Then, all subjects were asked about RLS symptoms. After the diagnosis of RLS, the patients were divided into two groups: With and without RLS. In both groups, the following variables were evaluated: Age, sex, other underlying disease, duration of MS, MS course, family history of RLS, history of anemia, and drug intakes. The severity of the disease in subjects diagnosed with RLS was also evaluated.A total of 126 patients in the MS group and 126 healthy controls were included in the study, with no statistically significant differences between them in terms of age and gender. In MS group, 82 (65.1%) and, in control group, 16 (12.7%) had RLS. The frequency of RLS in the MS patients was significantly higher than that in the control group. Among MS patients, 60 male (73.2%) and 22 female (26.8%) had RLS. Mean age of MS patients with RLS was significantly higher than that in MS patients without RLS. MS patients and higher EDSS score had more RLS symptoms.We suggest that RLS always be considered during neurological examinations of MS patients. HubMed – drug


Bioavailability and Efficacy of a Gap Junction Enhancer (PQ7) in a Mouse Mammary Tumor Model.

PLoS One. 2013; 8(6): e67174
Shishido SN, Prasain K, Beck A, Nguyen TD, Hua DH, Nguyen TA

The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline (PQ7), on the normal tissue was evaluated in healthy C57BL/6J mice in a systemic drug distribution study. Immunoblot analysis of the vital organs indicates a reduction in Cx43 expression in PQ7-treated animals with no observable change in morphology. Next the transgenic strain FVB/N-Tg(MMTV-PyVT) 634Mul/J (also known as PyVT) was used as a spontaneous mammary tumor mouse model to determine the biological and histological effects of PQ7 on tumorigenesis and metastasis at three stages of development: Pre tumor, Early tumor, and Late tumor formation. PQ7 was assessed to have a low toxicity through intraperitoneal administration, with the majority of the compound being detected in the heart, liver, and lungs six hours post injection. The treatment of tumor bearing animals with PQ7 had a 98% reduction in tumor growth, while also decreasing the total tumor burden compared to control mice during the Pre stage of development. PQ7 treatment increased Cx43 expression in the neoplastic tissue during Pre-tumor formation; however, this effect was not observed in Late stage tumor formation. This study shows that the gap junction enhancer, PQ7, has low toxicity to normal tissue in healthy C57BL/6J mice, while having clinical efficacy in the treatment of spontaneous mammary tumors of PyVT mice. Additionally, gap junctional intercellular communication and neoplastic cellular growth are shown to be inversely related, while treatment with PQ7 inhibits tumor growth through targeting gap junction expression. HubMed – drug