Both cardiac myocytes and cardiac stem cells (CSCs) express the receptor of growth hormone releasing hormone (GHRH), activation of which improves injury responses after myocardial infarction (MI). Here we show that a GHRH-agonist (GHRH-A; JI-38) reverses ventricular remodeling and enhances functional recovery in the setting of chronic MI. This response is mediated entirely by activation of GHRH receptor (GHRHR), as demonstrated by the use of a highly selective GHRH antagonist (MIA-602). One month after MI, animals were randomly assigned to receive: placebo, GHRH-A (JI-38), rat recombinant GH, MIA-602, or a combination of GHRH-A and MIA-602, for a 4-wk period. We assessed cardiac performance and hemodynamics by using echocardiography and micromanometry derived pressure-volume loops. Morphometric measurements were carried out to determine MI size and capillary density, and the expression of GHRHR was assessed by immunofluorescence and quantitative RT-PCR. GHRH-A markedly improved cardiac function as shown by echocardiographic and hemodynamic parameters. MI size was substantially reduced, whereas myocyte and nonmyocyte mitosis was markedly increased by GHRH-A. These effects occurred without increases in circulating levels of growth hormone and insulin-like growth factor I and were, at least partially, nullified by GHRH antagonism, confirming a receptor-mediated mechanism. GHRH-A stimulated CSCs proliferation ex vivo, in a manner offset by MIA-602. Collectively, our findings reveal the importance of the GHRH signaling pathway within the heart. Therapy with GHRH-A although initiated 1 mo after MI substantially improved cardiac performance and reduced infarct size, suggesting a regenerative process. Therefore, activation of GHRHR provides a unique therapeutic approach to reverse remodeling after MI.heart failure | cardiac stem cells | cardiac regeneration
Dilated cardiomyopathy is a serious and life-threatening disorder in children. It is the most common form of pediatric cardiomyopathy. Therapy for this condition has varied little over the last several decades and mortality continues to be high. Currently, children with dilated cardiomyopathy are treated with pharmacological agents and mechanical support, but most require heart transplantation and survival rates are not optimal. The lack of common treatment guidelines and inadequate survival rates after transplantation necessitates more therapeutic clinical trials. Stem cell and cell-based therapies offer an innovative approach to restore cardiac structure and function towards normal, possibly reducing the need for aggressive therapies and cardiac transplantation. Mesenchymal stem cells and cardiac stem cells may be the most promising cell types for treating children with dilated cardiomyopathy. The medical community must begin a systematic investigation of the benefits of current and novel treatments such as stem cell therapies for treating pediatric dilated cardiomyopathy.
Approximately 25% of US 2-to-5-year olds are overweight and ethnic minority groups are disproportionately affected. We explored the relationship between parent demographic characteristics, various perinatal/early childhood (EC) factors, and child body mass index (BMI) to determine possible contributors to these disparities. A preschool-based randomized controlled (N = 28 centers) obesity prevention intervention was conducted among multiethnic 2-to-5 year olds. Baseline assessment of demographic characteristics, various perinatal/EC factors, and child BMI were analyzed via generalized linear mixed models and logistic regression analysis. Foreign-born parents were almost 2.5 times as likely to have an obese child versus children of US-born parents (OR 2.43, 95% CI 1.53-3.87). Families who spoke Spanish only or a combination of Creole/English at home were over twice as likely to have an obese preschool child versus families who spoke English only at home. Parent place of birth and language spoken at home plays a significant role in early childhood obesity. Future early childhood healthy weight initiatives should incorporate strategies that take into account these particular parent characteristics.
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This investigation was carried out to study the hypoglycemic effects of Chromium picolinate and Magnesium sulfate on streptozotocin induced diabetic rats. Chromium at levels of 8 and 10ug/ml, Magnesium at level 10 and 12mg/ml. Furthermore, mixture of (chromium 8u/ml + Magnesium10mg) and (chromium10u/ml + Magnesium12mg/ml) administered to diabetic rats for six weeks. Blood glucose and, body weight gain of rats were determined. Also, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides were determined in the serum of the rats. As well as the activities of serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined.The results indicated that Chromium picolinate and Magnesium sulfate led to a significant reduction in weight gain and blood glucose of diabetic rats. In addition, total cholesterol, LDL-C, triglycerides, creatinine and urea in serum decreased while HDL-C increased after administration Chromium picolinate and Magnesium sulfate.The activities of hepatic markers were significantly decreased in GPT, but GOT no change elevated in diabetic rats as compared to control rats.Finally, it can be concluded that, using different levels of Chromium picolinate, Magnesium sulfate and mixture of them have pronounced effect for lowering blood glucose and cholesterol levels of the serum in experimental diabetic rats.
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