The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Comparative Study between the Attenuation of Cardiac Fibrosis by Mesenchymal Stem Cells versus Colchicine.

Introduction: Considered as an end-stage for all cardiovascular diseases, cardiac fibrosis leads to the development of heart failure, thus the ultimate goal is to prevent the progression of fibrosis. Indeed, heart can regenerate itself but to a certain limit based upon the number of resident stem cells which is limited. Thus, stem cells transplantation is considered as a promising therapy. This study aims to examine if MSC transplantation can inhibit the progression of myocardial fibrosis in rat model compared to Colchicine treatment; and if the timing of treatment with MSCs or COL affect the progression of fibrosis. Material & Methods: To induce cardiac fibrosis in 48 female albino rats, Isoproterenol hydrochloride was used. These rats were divided into 2 models: COL-treated group that were treated after 1,2,3 weeks of the last ISO injection by colchicine orally. MSCtreated group that were injected intravenously after 1,2,3 weeks of last ISO injection by MSC. Heart rate and Systolic blood pressure were measured and the levels of Creatine phosphokinase, Lactate dehydrogenase, Matrix Metalloproteinase II and Collagen I were assessed. Moreover, cardiac tissues were examined hitopathologically. Results & Conclusion: MSC were proved to enhance the effect of anti-remodeling of extracellular matrix significantly by modulating the expression of matrix metalloproteinases, which is superior to COL treatment.

Oxidative Stress and Arsenic Exposure among Copper Smelters.

Copper is widely used in industry. It has been associated with several health hazards among exposed workers. Aim: to measure the indicators of oxidative stress as malondialdehyde level and superoxide dismutase enzyme activity and their association with copper and arsenic levels among copper smel=ter workers. Subjective and methods: This study was conducted on forty workers in a secondary copper smelting factory, who were occupationally exposed to copper. They were compared with forty non-exposed individuals. Full history, clinical examinations were done. Serum copper, serum arsenic, urinary arsenic, malondialdehyde and superoxide dismutase were measured. Environmental measurements of copper and arsenic dusts were carried out at different workplace areas. Results: Environmental measurements in the workplace were within the normal permissible limits in Egypt. Statistically significant differences were found between exposed and control as regards the prevalence of the respiratory and neurological symptoms. Compared to the control group, serum copper, serum arsenic, urinary arsenic and malondialdehyde blood levels were significantly higher among the exposed worker (P<0.01). Each one was positively correlated with the duration of employment. Superoxide dismutase activities in blood were significantly decreased and negatively correlated with the duration of employment. Conclusion: The disruption of hemostasis induced by oxidative stress may promote the development of health hazards with continued occupational exposure to copper fumes. Recommendation: Blood levels of malondialdehyde and superoxide dismutase enzyme activity can be used as indicators of oxidative stress among exposed workers.