Improvement of heart failure by human amniotic mesenchymal stromal cell transplantation in rats

Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells [hAMSCs] in rats with heart failure [HF]

Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups [7 rats each] as 1- Control 2- Heart Failure [HF] 3- Sham 4- Culture media 5- Stem Cell Transplantation [SCT]. Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×106 cells in 150 microl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done

Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 +/- 9% to 81/25 +/- 6/05% in SCT group [p value < 0.001]. Fraction shortening in HF group was increased from 27/53 +/- 8/58% into 45/55 +/- 6/91% in SCT group [p value < 0.001]. Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group [p value < 0.001] compared with the animals in the HF group

Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters

A role for endocannabinoids in acute stress-induced suppression of the hypothalamic-pituitary-gonadal axis in male rats / 대한생식의학회지

OBJECTIVE: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. METHODS: Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 microg/rat). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. RESULTS: Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. CONCLUSION: These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.

Reducing creatine kinase-MB levels following oxytocin administration during ischemia-reperfusion periods in isolated rat heart

Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide [NO], prostacyclin and mitochondrial ATP-dependent potassium channels in this regard. Male wistar rats [n=8] were anesthetized with sodium thiopental and their hearts were transferred to a Langendorff perfusion apparatus. All animals were randomly divided into nine groups as follow; in the ischemia-reperfusion group, hearts underwent 30 min of regional ischemia followed by 120 min of reperfusion. In oxytocin group, hearts were perfused with oxytocin 5 min after ischemia induction for 25 min. In other groups, 35 min prior to oxytocin perfusion, atosiban [a non-specific oxytocin receptor blocker], L-NAME [an NO synthase inhibitor], indomethacin [a non-specific cyclooxygenase blocker] and 5-HD [a specific mKATP channel blocker] were perfused for 10 min. In all groups, we measured CK-MB levels in the coronary effluent at the end of reperfusion. Moreover, coronary flow [mL/min] was measured at baseline, during ischemia period and 60 and 120 min after reperfusion. Oxytocin administration significantly reduced CK-MB level in oxytocin group as compared to ischemia-reperfusion group. Administration of atosiban, L-NAME, indomethacin and 5-HD prior to oxytocin perfusion abolished the effects of oxytocin on CK-MB levels. Administration of oxytocin during ischemia and reperfusion periods deceased CK-MB levels but infusion of atosiban, L-NAME, 5-HD and indomethacin inhibited oxytocin from exerting its effects