Assessment of dose-effect and therapeutic time window in preclinical studies of rhEGF and GHRP-6 coadministration for stroke therapy.

Background: Stroke continues to be a leading cause of mortality and morbidity worldwide, and novel therapeutic options for ischaemic stroke are urgently needed. In this context, drug combination therapies seem to be a viable approach, which has not been fully explored in preclinical studies.

Objectives: In this work, we assessed the dose-response relationship and therapeutic time window, in global brain ischaemia, of a combined therapeutic approach of recombinant human epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP-6).

Heberprot-P: a novel product for treating advanced diabetic foot ulcer.

Diabetic foot ulcer is a principal diabetic complication. It has been shown that diabetic patients have decreased growth factor concentrations in their tissues, particularly epidermal growth factor. Growth factor shortage impairs wound healing, which leads to chronic nonhealing wounds and sometimes eventual amputation.

Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers.

GHRP-6 is a growth hormone secretagogue that also enhances tissue viability in different organs. In the present work, we studied the pharmacokinetics of this short therapeutic hexapeptide (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH(2,) MW=872.44 Da) in nine male healthy volunteers after a single intravenous bolus administration of 100, 200 and 400 μg/kg of body weight.

Coadministration of epidermal growth factor and growth hormone releasing peptide-6 improves clinical recovery in experimental autoimmune encephalitis.

Purpose: Multiple sclerosis is a complex and devastating autoimmune disease of the central nervous system. Up to now, a constellation of candidate drugs have been evaluated with no major success. Experimental Autoimmune Encephalitis (EAE) is the animal counterpart that reproduces critical features of the human MS process.

Therapeutic effect of the combined use of growth hormone releasing peptide-6 and epidermal growth factor in an axonopathy model.

Amyotrophic lateral sclerosis (ALS) is a disease of the central nervous system characterized by loss of spinal motor neurons, for which no effective treatment exists. Epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP-6) have been considered as good candidates for the treatment of this disease, due to their well documented effects in eliciting pleiotrophic and cell survival mechanisms. The aim of the present work was to evaluate the separate and combined effects of both peptides in an experimental animal model of ALS, the proximal axonopathy induced by 1,2 diacetylbenzene (1,2 DAB) in mice.

Boosting controlled autoimmunity: a new therapeutic target for CNS disorders.

In most tissues, the immune system plays an essential role in protection, repair and healing. Although immunologically privileged, the CNS remains subject to a highly regulated form of immunosurveillance that is of increasing interest. There is evolving evidence that repair mechanisms within the CNS may be enhanced by exploiting an innate process of protective immunity.

Ozone oxidative preconditioning is mediated by A1 adenosine receptors in a rat model of liver ischemia/ reperfusion.

The liver is damaged by sustained ischemia in liver transplantation, and the reperfusion after ischemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the role of A(1) adenosine receptor on the protective actions conferred by OzoneOP in hepatic I/R.

Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction.

Therapies aimed at enhancing cardiomyocyte survival following myocardial injury are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has been shown to stimulate GH secretion and has beneficial cardiovascular effects, the aim of the present study was to determine whether GHRP6 administration reduces myocardial infarct size following acute coronary occlusion in vivo. Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h reperfusion/survival period.

Ozone/oxygen mixture modifies the subcellular redistribution of Bax protein in renal tissue from rats treated with cisplatin.

Background: Cellular events in cisplatin-mediated nephrotoxicity include apoptosis induction, decreased protein synthesis, changes in the subcellular redistribution of Bax mitochondrial dysfunction, DNA injury, increased lipid peroxidation, depletion of glutathione and decrease in enzymatic activity of renal antioxidant enzymes. In previous papers we have shown that intra-rectal (i.r.

Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure.

Novel therapies for the treatment of MOF (multiple organ failure) are required. In the present study, we examined the effect of synthetic GHRP-6 (growth hormone-releasing peptide-6) on cell migration and proliferation using rat intestinal epithelial (IEC-6) and human colonic cancer (HT29) cells as in vitro models of injury. In addition, we examined its efficacy when given alone and in combination with the potent protective factor EGF (epidermal growth factor) in an in vivo model of MOF (using two hepatic vessel ischaemia/reperfusion protocols; 45 min of ischaemia and 45 min of reperfusion or 90 min of ischaemia and 120 min of reperfusion).

Ubiquitous expression of human SCA2 gene under the regulation of the SCA2 self promoter cause specific Purkinje cell degeneration in transgenic mice.

The objective of this work was the generation of an animal model of the SCA2 disease for future studies on the benefits of therapeutic molecules and neuropathological mechanisms that underline this human disorder. The transgenic fragment was microinjected into pronuclei of B6D2F1 X OF1 mouse hybrid strain. For Northern blots, RNAs were hybridized with a human cDNA fragment from the SCA2 gene and a mouse beta-actin cDNA fragment.

Role of protein synthesis in the protection conferred by ozone-oxidative-preconditioning in hepatic ischaemia/reperfusion.

The liver is damaged by sustained ischaemia during liver transplantation, and the reperfusion after ischaemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischaemia/reperfusion (I/R) injury through different mechanisms. The aim of this study was to investigate the influence of the inhibition of protein synthesis on the protective actions conferred by OzoneOP in hepatic I/R.

Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds.

Increased formation of MG (methylglyoxal) and related protein glycation in diabetes has been linked to the development of diabetic vascular complications. Diabetes is also associated with impaired wound healing. In the present study, we investigated if prolonged exposure of rats to MG (50-75 mg/kg of body weight) induced impairment of wound healing and diabetes-like vascular damage.

Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage.

Ischemia/reperfusion of mesenteric vessels is a useful model for acute vascular insufficiency and the early stages of multiorgan failure, conditions associated with high morbidity and mortality. Epidermal growth factor (EGF) is a potent mitogen that shows potential for use in intestinal injury. We therefore examined its influence on this model.

Attenuation of internal organ damages by exogenously administered epidermal growth factor (EGF) in burned rodents.

Major burns are associated with multiple internal organ damages, including necrosis of the gastrointestinal mucosa. Failure of the intestinal barrier is a serious complication in burned patients. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair and affords protection to the gastric mucosa.