Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Felodipine is a potent arteriolar vasodilator. Its possible myocardial effects were studied by placing dogs anaesthetized with chloralose on cardiopulmonary bypass. A balloon was then inserted into the left ventricular cavity with a vent alongside it. Isovolumic contractions (developed pressure or maximal rate of rise of pressure) were studied as the intraventricular balloon was inflated to various levels. Total coronary venous return was collected to measure coronary blood flow and felodipine concentrations. In seven vagotomized and beta-blocked preparations, a small positive inotropic effect was found [32 +/- 11 (SEM)%, p less than 0.05]; the maximum effect was reached at arterial plasma felodipine concentrations of between 7 and 20 nM and was accompanied by appreciable coronary vasodilatation. In five dogs, infusion of the solvent vehicle (5% polyethylene glycol) alone had no effect. In three more dogs, an infusion of nitroprusside caused coronary vasodilatation, but no positive inotropic effect. The results show that at low concentrations, felodipine has a positive inotropic effect in vivo. These findings suggest that the properties of myocardial calcium agonist and vascular smooth muscle antagonist properties may coexist in the same dihydropyridine molecule. The favorable effects of this drug in the treatment of heart failure can be explained not only by reduction of peripheral resistance, but also by a moderate positive inotropic effect.
 ...
PMID:The positive inotropic effect of felodipine in isovolumically beating dog heart. 244 2

Many patients find polyethylene glycol-based preparations (PEG) difficult to take because of the large volume of fluid they are required to consume. One hundred and sixteen predominantly elderly patients were randomized to receive either sodium phosphate (n = 61) or PEG (n = 55) bowel preparations before colonoscopy. Patients with a history of symptomatic ischaemic heart disease or cerebrovascular disease in the preceding 6 months, severe liver disease or heart failure, or serum creatinine above 200 micrograms/L were excluded from the study. Each patient filled in a questionnaire about the bowel preparation prior to the procedure. The colonoscopists, who were not aware which preparation had been used, were asked to complete a questionnaire about the quality of the bowel preparation after the procedure. The patients found the sodium phosphate preparation slightly more tolerable than PEG. Side effects were slightly more common with sodium phosphate. Neither difference was statistically significant. However, 91% of patients who had previously had PEG found sodium phosphate easier to take. Approximately 25% of patients in each group experienced at least one episode of incontinence. The colonoscopists found no difference in the overall quality of the bowel preparation. The amount of fluid in the colon was greater in patients prepared with PEG. As expected, patients taking sodium phosphate developed hyperphosphataemia (mean phosphate level before colonoscopy 1.56 mmol/L, normal 0.8 -1.3). They also had a lower mean serum potassium level (3.8 mmol/L) than the PEG group (4.2 mmol/L). However, there were no clinically significant consequences. Sodium phosphate was a safe and effective bowel preparation for colonoscopy in this carefully selected group of patients. It was preferred by patients who had previously had PEG. Many elderly patients were found to develop faecal incontinence, irrespective of the type of bowel preparation used.
 ...
PMID:Bowel preparation for colonoscopy: a randomized prospective trail comparing sodium phosphate and polyethylene glycol in a predominantly elderly population. 867 52

A 36-year-old man known as chronic alcohol abuser presently suffered from arthralgia and showed bilateral petriefied kidneys by sonography and computed tomography. Because of an unclear renal failure a kidney biopsy was performed and presented typical chronic renal oxalosis with massive oxalate crystal deposits, tubular atrophy and interstitital fibrosis. Since the man had never shown signs of hyperoxaluria in his life before, a secondary oxalosis was supposed. The subsequently prompted exploration established a three to four times abuse of rocket fuel with cola lemonade 12 years before during the patient's army time as a marine soldier. Such fuels contain ethylene glycol (glysantin) as antifreeze commonly known to cause in toxic doses acute renal tubular necrosis with hyperoxaluria. The presented case, however, suggests a rare sublethal ethylene glycol poisoning with initial renal tubular damage, oxalate crystal deposition and subsequent chronic interstitial oxalate nephritis with tubular atrophy, interstitial fibrosis and chronic renal failure. Undergoing chronic hemodialysis, the patient died 5 months after the kidney biopsy diagnosis by acute heart failure. At autopsy, progressed chronic renal oxalosis could be confirmed. Decompensated oxalate cardiomyopathy with disseminated myocardial oxalate crystal deposits caused acute heart failure promoted by myocardial hypertrophy in renal hypertension.
 ...
PMID:[Fatal chronic oxalosis after sublethal ethylene glycol poisoning]. 938 Jun 7

Ethylene glycol intoxication is a rare but dangerous type of poisoning. It causes a severe acidosis with high anion and osmolal gaps. Clinical manifestations of the ethylene glycol intoxication can be divided in three phases: a neurologic stage, with hallucinations, stupor and coma; the second stage is cardiovascular with cardiac failure. Renal failure characterizes the third stage, due to acute tubular necrosis. After aggressive gastric emptying, the main treatment is ethanol or 4-methypyrazole, which can be given either orally or intravenous, with supportive measures for all symptoms or diseased organ.
 ...
PMID:Diagnosis and treatment of an unusual cause of metabolic acidosis: ethylene glycol poisoning. 1103 83

Poisonings with industrial products represent approximately 7% of the cases reported to the poison centres. Ingestion of petroleum distillates induces irritation of the gastrointestinal tract, central nervous system depression and aspiration pneumonitis which may be severe; treatment is mainly supportive. Ethylene and diethylene glycol poisonings produce central nervous system depression, anion gap metabolic acidosis, osmolar gap and acute tubular necrosis; in severe cases, hypocalcaemia, cerebral oedema and heart failure may be observed; treatment often associates supportive measures, haemodialysis and administration of competitive inhibitors of alcohol dehydrogenase (ethanol or 4-methylpyrazole). Glycol ethers induce central nervous system depression and metabolic acidosis; in addition, ethylene glycol monobutyl ether produces haemolysis; monomethyl and monoethyl ethers are responsible for bone marrow and lymphoid organ toxicity, they adversely affect spermatogenesis and are teratogens.
 ...
PMID:[Acute poisoning with industrial products]. 1074 68

Heart failure evokes diaphragm weakness, but the mechanism(s) by which this occurs are not known. We postulated that heart failure increases diaphragm free radical generation and that free radicals trigger diaphragm dysfunction in this condition. The purpose of the present study was to test this hypothesis. Experiments were performed using halothane-anesthetized sham-operated control rats and rats in which myocardial infarction was induced by ligation of the left anterior descending coronary artery. Animals were killed 6 wk after surgery, the diaphragms were removed, and the following were assessed: 1) mitochondrial hydrogen peroxide (H2O2) generation, 2) free radical generation in resting and contracting intact diaphragm using a fluorescent-indicator technique, 3) 8-isoprostane and protein carbonyls (indexes of free radical-induced lipid and protein oxidation), and 4) the diaphragm force-frequency relationship. In additional experiments, a group of coronary ligation animals were treated with polyethylene glycol-superoxide dismutase (PEG-SOD, 2,000 units x kg(-1) x day(-1)) for 4 wk. We found that coronary ligation evoked an increase in free radical formation by the intact diaphragm, increased diaphragm mitochondrial H2O2 generation, increased diaphragm protein carbonyl levels, and increased diaphragm 8-isoprostane levels compared with controls (P < 0.001 for the first 3 comparisons, P < 0.05 for 8-isoprostane levels). Force generated in response to 20-Hz stimulation was reduced by coronary ligation (P < 0.05); PEG-SOD administration restored force to control levels (P < 0.03). These findings indicate that cardiac dysfunction due to coronary ligation increases diaphragm free radical generation and that free radicals evoke reductions in diaphragm force generation.
 ...
PMID:Diaphragmatic free radical generation increases in an animal model of heart failure. 1610 20

Because cardiomyocytes lose the ability to divide upon differentiation, myocardial failure is assumed to be generally irreversible. For terminal cardiac insufficiency, the potential for regenerative treatment by stem cells, especially embryonic stem (ES) cells, offers hope for the future. Recent studies showed that stem cells fuse spontaneously with cells remaining in damaged tissues, and restore tissue function. To imitate spontaneous fusion in vivo, we used polyethylene glycol (PEG) in vitro to fuse mouse ES cells and fetal cardiomyocytes and analyzed the cytochemical properties of the fused cells. Confocal laser scanning microscopy coupled with lipophilic dye labeling of the living cell membranes showed that there were fused cells of ES cells and cardiomyocytes after PEG treatment. By flow cytometry, the fusion efficiency between ES cells and cardiomyocytes was estimated to be about 45% of the total resulting cells. When green fluorescent protein (GFP)-expressing ES cells were fused with cardiomyocytes, the fused cells had immunoreactivity for GFP in their cytoplasm and cardiac troponin I in their myofibrils. Some of these cells also expressed proliferating cell nuclear antigen up to 11 days after fusion, the last time point examined. This study shows that PEG-induced fusions of mouse ES cells and cardiomyocytes have the cardiomyocyte phenotype and proliferation potential.
 ...
PMID:Phenotype-specific cells with proliferative potential are produced by polyethylene glycol-induced fusion of mouse embryonic stem cells with fetal cardiomyocytes. 1640 81

A solid-phase sandwich fluorescence immunoassay using nanocrystals of a fluorogenic precursor, fluorescein diacetate (FDA), conjugated with monoclonal antibodies for the detection of C-reactive protein (CRP), is described. FDA nanocrystals were coated with distearoylglycerophosphoethanolamine (DSPE), modified with amino(poly(ethylene glycol))(PEG(2000)-Amine) as an interface for coupling biomolecules. CRP was chosen as a model analyte because of its widely accepted role as a marker for acute inflammation and prospective heart failure. A low limit of detection (1.10 microg l(-1)) and high precision (CV = 2.72-9.48%) were achieved. Following the immunoreaction, the monoclonal anti-CRP conjugated nanocrystals were released by hydrolysis and dissolution instigated by the addition of a large volume of organic solvent-sodium hydroxide mixture. Using human serum samples from 66 patients with high heart attack risk and 19 healthy blood donors, this CRP fluorescence immunoassay showed a good correlation to the commercially available, turbidimetric immunoassay for CRP. This result was corroborated by the Bland-Altman plot that showed a mean difference between the two methods of only 0.36+/-1.46 mg l(-1). The study demonstrates that the organic fluorogenic FDA nanocrystals can be applied for the detection of CRP, which is a clinically interesting plasma protein with a low limit of detection.
 ...
PMID:Fluorogenic nanocrystals for highly sensitive detection of C-reactive protein. 1679

Endothelial function is impaired by oxidative stress in chronic heart failure (HF). Mechanisms that protect against increases in oxidative stress in HF are not clear. The goal of this study was to determine whether manganese superoxide dismutase (MnSOD) plays a key role in protecting against endothelial dysfunction in HF. Endothelial function and gene expression were examined in aorta from wild-type mice (MnSOD(+/+)) and mice deficient in MnSOD (MnSOD(+/-)) 12 wk after ligation of the left coronary artery (LCA). LCA ligation produced similar size myocardial infarctions in MnSOD(+/+) and MnSOD(+/-) mice and reduced ejection fraction to approximately 20% in both groups. Maximal relaxation in response to acetylcholine was 78 +/- 3% (mean +/- SE) and 66 +/- 8% in sham-operated MnSOD(+/+) and MnSOD(+/-) mice, respectively. Expression of antioxidant enzymes increased in MnSOD(+/+) mice with HF, and maximal relaxation to acetylcholine was slightly impaired (68 +/- 4%). Greater endothelial dysfunction was observed in MnSOD(+/-) mice with HF (46 +/- 5%, P < 0.05), which was significantly improved by polyethylene glycol-catalase but not Tempol. Incubation with the nonspecific cyclooxygenase (COX) inhibitor indomethacin or the COX1 inhibitor valeryl salicylate, but not the COX-2 inhibitor NS-398, significantly improved relaxation to acetylcholine in HF mice (maximum relaxation = 74 +/- 5, 91 +/- 1, and 58 +/- 5%). These data suggest that MnSOD plays a key role in protecting against endothelial dysfunction in HF. A novel mechanism was identified whereby chronic increases in oxidative stress, produced by mitochondrial SOD deficiency, impair vascular function via a hydrogen peroxide-dependent, COX1-dependent, endothelium-derived contracting factor.
 ...
PMID:MnSOD protects against COX1-mediated endothelial dysfunction in chronic heart failure. 2030 15

Biologic therapies have revolutionized the treatment of Crohn's disease (CD). Targeting TNF-alpha with monoclonal antibodies has changed the therapeutic landscape for tackling refractory and complicated CD. Intravenous use of infliximab, a chimeric monoclonal antibody to TNF-alpha is, however, limited by the occurrence of adverse events, infusion reactions, infectious complications, aggravation of heart failure, the occurrence of neurological demyelinating conditions and induction of rare malignancies. The incremental development of next-generation TNF-alpha antibodies and binding proteins through antibody-engineering techniques has followed, with the aim of producing efficacious drugs that are less expensive to produce, have a convenient route of administration and have fewer side effects. Certolizumab pegol (CDP870, Cimzia) is an engineered humanized anti-TNF-alpha antibody Fab fragment that minimizes the protein component and is conjugated to polyethylene glycol. Clinical studies have demonstrated efficacy in the treatment of moderate-to-severe active CD. Reported adverse events in the clinical trial program have been largely of mild-to-moderate severity, and occurred at similar frequencies in the active-treatment and placebo groups. Certolizumab pegol will be a useful addition to the armamentarium of biologic agents that can be used for the long-term treatment of CD.
 ...
PMID:Treatment of Crohn's disease with certolizumab pegol. 2047 19


1 2 3 4 Next >>