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Potential New Therapy (potential + new_therapy)
Selected AbstractsGoing for Gold, from Beijing to Munich, Highlights from the ESC 2008 Congress: BEAUTIFUL, GISSI-HF, and Potential New Therapies for Acute Decompensated Heart FailureCARDIOVASCULAR THERAPEUTICS, Issue 4 2008Paul Kalra Formerly Cardiovascular Drug Reviews http://www.blackwellpublishing.com/CATH [source] Pressor Therapy in Critically III PatientsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2000ACVECC, ACVIM, James S. Wohl DVM Diplomate Summary Vasopressors are agents that increase systemic vascular resistance by increasing vasoconstriction. Therapy with intravenous vasopressors may be required in critically ill patients when efforts to optimize cardiac output and blood pressure with intravascular fluid therapy fail. Increasing systemic vascular resistance can promote a favorable perfusion pressure gradient to vital organs in critically ill patients with severe, unresponsive vasodilation. Improperly administered, vasopressors may impede cardiac output and reduce oxygen transport to vital tissue sites. The understanding of systemic and regional effects of vasopressors is currently evolving. Recent literature of the commonly used agents is reviewed. Individual drugs, drug combinations, and potential new therapies are discussed. (Vet. Emerg. & Crit. Care, 10:19,33, 2000) [source] The Effect of Intracavernous Injection of Adipose Tissue-Derived Stem Cells on Hyperlipidemia-Associated Erectile Dysfunction in a Rat ModelTHE JOURNAL OF SEXUAL MEDICINE, Issue 4pt1 2010Yun-Ching Huang MD ABSTRACT Introduction., Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. Aim., To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. Methods., Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2,-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function, and penile histology. Main Outcome Measures., Erectile function was assessed by intracavernous pressure (ICP) measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. Results., Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. Conclusions., Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED. Huang Y-C, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, and Lin C-S. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med 2010;7:1391,1400. [source] Targeting MEK1/2 blocks osteoclast differentiation, function and cytokine secretion in multiple myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Iris Breitkreutz Summary Osteolytic bone disease in multiple myeloma (MM) is associated with upregulation of osteoclast (OCL) activity and constitutive inhibition of osteoblast function. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway mediates OCL differentiation and maturation. We hypothesized that inhibition of ERK1/2 could prevent OCL differentiation and downregulate OCL function. It was found that AZD6244, a mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, blocked OCL differentiation and formation in a dose-dependent manner, evidenced by decreased ,V,3-integrin expression and tartrate-resistant acid phosphatase positive (TRAP+) cells. Functional dentine disc cultures showed inhibition of OCL-induced bone resorption by AZD6244. Major MM growth and survival factors produced by OCLs including B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL), as well as macrophage inflammatory protein (MIP-1,), which mediates OCL differentiation and MM, were also significantly inhibited by AZD6244. In addition to ERK inhibition, NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1) and c-fos were both downregulated, suggesting that AZD6244 targets a later stage of OCL differentiation. These results indicate that AZD6244 inhibits OCL differentiation, formation and bone resorption, thereby abrogating paracrine MM cell survival in the bone marrow microenvironment. The present study therefore provides a preclinical rationale for the evaluation of AZD6244 as a potential new therapy for patients with MM. [source] | ||||||||||