Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congestive heart failure is one of the leading causes of disability in long-term survivors of cancer. The anthracycline antibiotic doxorubicin (DOX) is used to treat a variety of cancers, but its utility is limited by its cumulative cardiotoxicity. As advances in cancer treatment have decreased cancer mortality, DOX-induced cardiomyopathy has become an increasing problem. However, the current means to alleviate the cardiotoxicity of DOX are limited. We considered that vascular endothelial growth factor-B (VEGF-B), which promotes coronary arteriogenesis, physiological cardiac hypertrophy, and ischemia resistance, could be an interesting candidate for prevention of DOX-induced cardiotoxicity and congestive heart failure. To study this, we administered an adeno-associated viral vector expressing VEGF-B or control vector to normal and tumor-bearing mice 1 wk before DOX treatment, using doses mimicking the concentrations used in the clinics. VEGF-B treatment completely inhibited the DOX-induced cardiac atrophy and whole-body wasting. VEGF-B also prevented capillary rarefaction in the heart and improved endothelial function in DOX-treated mice. VEGF-B also protected cultured endothelial cells from apoptosis and restored their tube formation. VEGF-B increased left ventricular volume without compromising cardiac function, reduced the expression of genes associated with pathological remodeling, and improved cardiac mitochondrial respiration. Importantly, VEGF-B did not affect serum or tissue concentrations of DOX or augment tumor growth. By inhibiting DOX-induced endothelial damage, VEGF-B could provide a novel therapeutic possibility for the prevention of chemotherapy-associated cardiotoxicity in cancer patients.
 ...
PMID:VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection. 2779 59

Duchenne muscular dystrophy (DMD) is caused by defects in the DMD gene and results in progressive wasting of skeletal and cardiac muscle due to an absence of functional dystrophin. Cardiomyopathy is prominent in DMD patients, and contributes significantly to mortality. This is particularly true following respiratory interventions that reduce death rate and increase ambulation and consequently cardiac load. Cardiomyopathy shows an increasing prevalence with age and disease progression, and over 95% of patients exhibit dilated cardiomyopathy by the time they reach adulthood. Development of the myopathy is complex, and elevations in intracellular calcium, functional muscle ischemia, and mitochondrial dysfunction characterise the pathophysiology. Current therapies are limited to treating symptoms of the disease and there is therefore an urgent need to treat the underlying genetic defect. Several novel therapies are outlined here, and the unprecedented success of phosphorodiamidate morpholino oligomers (PMOs) in preclinical and clinical studies is overviewed.
 ...
PMID:Dystrophic Cardiomyopathy-Potential Role of Calcium in Pathogenesis, Treatment and Novel Therapies. 2833 6

The use of robotic techniques in laparoscopic donor nephrectomy currently tends to involve a longer ischemia time without clear advantages, and the cost of robotic surgery is significantly higher. If only one robot is available, then unnecessary prolongation of cold ischemia time also occurs, as the donor must first be undocked to dock the recipient. The combination of laparoscopic donor nephrectomy with parallel initiation of robot-assisted situs preparation and exposure of the renal vessels appears to be the best current approach to safe and cost-effective donor nephrectomy and subsequent robot-assisted kidney transplantation without wasting any time.
 ...
PMID:Robotic Donor Nephrectomy: Against. 3008 29

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by a mutation in the dystrophin gene. Numerous gene therapies have been developed to replace or repair the defective dystrophin gene; however, these treatments cannot restore the full-length protein or completely resolve dystrophic symptoms. Secondary pathological mechanisms, such as functional ischemia and fibrosis, are thought to exacerbate the primary defect and cause the profound muscle degeneration found in dystrophic muscle. Surrogate therapies utilizing alternative therapeutic genes, or "booster genes," such as VEGFA and utrophin, seek to address these secondary mechanisms and have shown impressive benefit in mdx mice. A skeletal muscle-specific microRNA, miR-206, is particularly overexpressed in dystrophic muscle and inhibits the expression of known booster genes. Thus, we aimed to determine if miR-206 contributes to dystrophic pathology by repressing beneficial gene expression. Here, we show that AAV-mediated expression of a miR-206 decoy target effectively downregulated miR-206 expression and increased endogenous therapeutic gene expression in mature mdx muscle. Furthermore, treatment significantly improved motor function and dystrophic pathology in mdx mice. In summary, we have identified a contributing factor to the dystrophic phenotype and characterized a novel therapeutic avenue for DMD.
 ...
PMID:MicroRNA-206 Downregulation Improves Therapeutic Gene Expression and Motor Function in mdx Mice. 3019 67

The Final Rule mandates that organ allocation not be based on the transplant candidate's place of residence or listing, except as required by sound medical judgment and best use of donated organs, to avoid wasting organs and futile transplants, and to promote access and efficiency. Current Organ Procurement and Transplantation Network (OPTN) policies use donation service areas and OPTN regions to distribute and allocate organs for transplant. These policies have recently been called into question as not meeting the requirements of the Final Rule. Therefore, we propose using borderless allocation scores that combine medical priority scores with geographic feasibility scores. Medical priority scores are currently used in OPTN allocation policy, for example, the model for end-stage liver disease and the lung allocation score. Geographic feasibility scores can be developed to account for the effects of ischemia due to travel times, donor characteristics that modify the feasibility of traveling due to organ outcomes, and the costs of shipping organs over long distances. A borderless distribution and allocation system could address the goals of equity and utility, while fulfilling the mandates of the Final Rule and providing optimal use of a scare resource.
 ...
PMID:Organ distribution without geographic boundaries: A possible framework for organ allocation. 3020 12

Mammalians have recognition-behavioral stress-coping neuronal module system followed by some humoral glycolipids. A sulfated Galbeta1-4GlcNAc-lipid promotes the serotonergic module regulating the emotional behaviors for not-wasting the physical strength; GalNAcalpha1-3GalNAc-lipid promotes the adrenergic module inducing the behaviors escaping from the uneasy situation, and sulfated Fucalpha1-2Gal-lipid protects the cholinergic module keeping the stressor-memory from the ischemia-stress. Mouse given bathing recognizes the stressors to be coped with in the treatment. We previously observed mouse given CO2-microbubble-bathing increased the behavior escaping from the bathing situation. Mouse given CO2-microbubble-bathing would recognize the other stressors to be coped with in the treatment. We examined stress-coping glycolipids produced by mice given controlled bathing treatments, and got the following results. A sulfated Galbeta1-4GlcNAc-lipid production was increased by the acidic bathing condition and the dissolved CO2, GalNAcalpha1-3GalNAc-lipid production was increased by the dissolved CO2, and sulfated Fucalpha1-2Gal-lipid production was increased by the acidic bathing condition. We understood the mice treated with CO2-microbubble-bathing would recognize the acidic bathing condition and the dissolved CO2, but not the microbubble, as the other stressors to be coped.
 ...
PMID:Stress-Coping Humoral Glycolipids Produced by Mice Given Controlled Bathing Treatments. 3178 86


<< Previous 1 2 3 4