The beneficial effects of agonists of growth hormone-releasing hormone receptor (GHRH-R) in heart failure models are associated with an increase in the number of ckit + cardiac stem cells (CSCs). The goal of the present study was to determine the presence of GHRH-R in CSCs, the effect of GHRH-R agonists on their proliferation and survival, and the mechanisms involved. We investigated the expression of GHRH-R in CSCs of different species and the effect of GHRH-R agonists on their cell proliferation and survival. GHRH-R is expressed in ckit + CSCs isolated from mouse, rat, and pig. Treatment of porcine CSCs with the GHRH-R agonist JI-38 significantly increased the rate of cell division. Similar results were observed with other GHRH-R agonists, MR-356 and MR-409. JI-38 exerted a protective effect on survival of porcine CSCs under conditions of oxidative stress induced by exposure to hydrogen peroxide. Treatment with JI-38 before exposure to peroxide significantly reduced cell death. A similar effect was observed with MR-356. Addition of GHRH-R agonists to porcine CSCs induced activation of ERK and AKT pathways as determined by increased expression of phospho-ERK and phospho-AKT. Inhibitors of ERK and AKT pathways completely reversed the effect of GHRH-R agonists on CSC proliferation. Our findings extend the observations of the expression of GHRH-R by CSCs and demonstrate that GHRH-R agonists have a direct effect on proliferation and survival of CSCs. These results support the therapeutic use of GHRH-R agonists for stimulating endogenous mechanisms for myocardial repair or for preconditioning of stem cells before transplantation.cardiac stem cells | growth hormone-releasing hormone | agonists | cell proliferation | cell survival
For the management of hydrocephalus with ventricular cerebrospinal fluid (CSF) shunting, multiple therapeutic options are available. Among these routes, the most commonly used are ventriculo-peritoneal, ventriculo-atrial, and ventriculo-pleural, while ventriculo-cholecystic is a less common option. Although ventriculo-peritoneal is accepted as the first option, ventriculo-cholecystic shunting may be performed in patients who are poor candidates for other routes of shunt placement. Open cholecystic shunt placement may be contraindicated in patients who have undergone previous surgeries or other comorbidities. Here, we present the case of a 25-year-old female with a complex medical history who presented with a posterior fossa intraparenchymal hemorrhage and subsequent hydrocephalus. She was unable to undergo a ventriculo-peritoneal, atrial, or pleural shunt placement, and thus, a cholecystic shunt placement was chosen. Due to a history of previous surgeries and comorbidities as well as a large volume of idiopathic and recurrent ascites, open placement was contraindicated in this patient. To the best of our knowledge, we present the first successful adult case of a minimally invasive ventriculo-cholecystic shunt placement under ultrasound and fluoroscopic guidance.
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