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

We report a 70-year-old man who had a sudden onset of right hemiparesis and mutism. The lower extremity was more involved than the upper one. He had a long history of diabetes and chronic renal failure for which hemodialysis was necessary. On August 30, 1990, he had an sudden onset of right hemiparesis and mutism. Neurological examination revealed awake but mute in no acute distress. He could only respond to very simple commands such as opening his mouth or protruding his tongue. He did not appear to understand more difficult questions. In addition, he could not answer verbally. He was totally mute. Cranial nerves appeared intact except for slight right central facial paresis and severe diabetic retinopathy. He had complete paralysis of his right leg and a moderate weakness in his right upper extremity. Deep reflexes were diminished in both upper extremities and absent in the lower limbs. Frotal signs such as grasp and snout reflexes were present. Cranial CT scans revealed an ill-defined low density area in the left parasagittal subcortical area and a part of the anterior cerebral artery territory. The supplementary motor area appeared at least in part to be involved. He was treated with glycerol and other supportive cares, however, his clinical course was complicated by pneumonia, heart failure, septicemia, and he expired two months after his stroke. The patient was discussed in a neurological CPC, and the chief discussant arrived at a conclusion that he had an artery-to-artery embolism at the internal carotid bifurcation resulting in the cerebral infarction mainly in the territory of the anterior cerebral artery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A 70-year-old man with right hemiparesis and mutism]. 836 54

Within the past decade an entire family of membrane proteins--aquaporins--which function as transmembrane water channels has been identified; they occur throughout the plant, animal, and bacterial kingdoms. Several family members permit glycerol and urea permeability. Most aquaporins are inhibited by mercury. Constitutively expressed aquaporin 1 is the major permeability channel of the proximal tubule, descending thin limb of the loop of Henle, and it is also found in vasa recta. Aquaporin 2 is expressed in the principal cells of the collecting duct where it shuttles between intracellular vesicles and the apical membrane in response to vasopressin. Aquaporin 2 mutations cause nephrogenic diabetes insipidus; increased aquaporin 2 activity is implicated in the pathophysiology of heart failure, cirrhosis, and nephrotic syndrome. Aquaporins 3 and 4 provide basolateral membrane water channels in the collecting duct. These 4 channels and 6 others are also found elsewhere throughout the body. The physiological importance of several of the channels remains unknown. Aquaporin 1 inhibitors might induce useful diuresis, but humans who lack aquaporin 1 have no significant clinical disease. Inhibition of aquaporin 2 activity by vasopressin receptor antagonists may be useful in heart failure, cirrhosis, nephrotic syndrome, and the syndrome of inappropriate antidiuretic hormone (ADH) release.
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PMID:Aquaporin mediated water flux as a target for diuretic development. 1059 41

Augmentation of circulating noradrenaline concentration stimulates ventilation during the initial stages of exercise and this is accompanied by an increased sensation of dyspnoea and exertion. This previous study [Clark, Galloway, MacFarlane, Henderson, Aitchison and McMurray (1997) Eur. Heart J. 18, 1829-1833] suggested a link between dyspnoea, which commonly limits exercise tolerance in heart failure patients, and high circulating noradrenaline concentration in these patients. The present study investigated this relationship further using sympathetic inhibition. Ten healthy normotensive males performed 10 min of submaximal cycling exercise at approx. 70% of maximal oxygen uptake per min (VO2max) on three occasions one week apart. The first of these sessions was a familiarization session and the other two were experimental study days. On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design. After a 90-min absorption period, subjects undertook the exercise task. Blood was drawn, expired gas was analysed breath by breath, blood pressure, heart rate and ratings of perceived dyspnoea and exertion were obtained. Moxonidine treatment significantly reduced plasma noradrenaline concentration (P < 0.01), mean arterial pressure (P < 0.01), and blood glycerol concentration (P < 0.05), but no differences were observed in heart rate, the ventilatory response to exercise or subjective ratings of dyspnoea and exertion. This study indicates that reducing sympathetic activity does not affect ventilation, perceived dyspnoea or perceived exertion in normotensive males. Therefore it can be concluded that reducing sympathetic activity may not be an appropriate strategy to help reduce perceived dyspnoea.
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PMID:Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans. 1178 75

The aquaporins are a family of small, integral membrane proteins that function as plasma membrane transporters of water and in some cases small polar solutes such as glycerol. There are at least 10 distinct aquaporins in mammals with specific patterns of expression in epithelial, endothelial and other tissues. Recent studies in aquaporin-null mice have indicated key roles for certain aquaporins in the urinary concentrating mechanism, fluid secretion by glands, brain swelling, skin moisture, hearing and vision, and gastrointestinal absorption. The only known inhibitors of some aquaporins are mercurial sulfhydryl-reactive compounds, which are too toxic and nonspecific for use in vivo. Small-molecule or peptide aquaporin blockers have potential applications in the treatment of disorders of fluid/pressure homeostasis such as heart failure, hypertension, brain swelling and glaucoma.
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PMID:Applications of aquaporin inhibitors. 1281 84

Advanced heart failure is characterized by increased activation of the renin-angiotensin system and the development of cachexia. Angiotensin II (Ang II) has been proposed as a lipid metabolism regulator. The effects of exogenous Ang II (osmotic minipump, 525 ng/kg/min for 12 d) on interstitial sc glycerol and norepinephrine levels, indexes of lipolysis, and sympathetic activation, respectively, were measured in Sprague Dawley rats by consecutive microdialysis performed in vivo in white adipose tissue. Higher sustained interstitial glycerol and norepinephrine levels were found after 7 and 12 d of Ang II infusion. Triglyceride to DNA content ratio and adipocyte diameter were reduced in sc and visceral (retroperitoneal and epididymal) fat tissues of Ang II-infused rats, whose body weight was lower and blood pressure higher. Losartan, an Ang II receptor 1 blocker, and carvedilol, an alpha1-nonselective-beta1,2,3-adrenergic blocker, but not doxazosin, an alpha1-selective-adrenergic blocker, lowered glycerol and norepinephrine levels, preventing lipolysis and weight loss. Our results indicate that Ang II stimulates lipolysis in sc and visceral adipocytes by sympathetic activation and beta-adrenergic-receptor stimulation. Nonselective-beta-adrenergic and Ang II-receptor1 blockade markedly attenuated the rise of norepinephrine, preventing catabolic effects. The metabolic benefits of carvedilol and losartan, in addition to recognized protective cardiovascular effects, may be relevant in cachectic patients with advanced heart failure.
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PMID:Sympathetic modulation by carvedilol and losartan reduces angiotensin II-mediated lipolysis in subcutaneous and visceral fat. 1574 Dec 61

Endothelial function is reduced by age, chronic heart failure, coronary artery disease, hypertension or type 2 diabetes, and it is shown that aerobic exercise may reverse this trend. The effect of a high aerobic training status on endothelial function in young, healthy subjects is however less clear. The present study was designed to determine whether endothelial function is improved in highly endurance-trained young women compared to sedentary, healthy controls. Brachial artery diameter was measured in 16 endurance-trained (age: 23.7 +/- 2.5 years, maximal oxygen uptake (VO2max): 60.6 +/- 4.5 ml/kg per min) and 14 sedentary females (age: 23.7 +/- 2.1 years, VO2max: 40.5 +/- 5.6 ml/kg per min) at rest, during flow-mediated dilation (FMD) and after sublingual glycerol trinitrate administration, using high-resolution ultrasound. FMD did not differ between the endurance-trained and the sedentary females (14.8% vs 16.4%, p = NS), despite a substantial difference in VO2max of 50% (p < 0.001). The endurance-trained group possessed however, a 9% larger resting brachial artery diameter when adjusted for body surface area. The results of the present study suggest that endothelial function is well preserved in young, healthy women, and that a high aerobic training status due to long term aerobic training does not improve the dilating capacity any further.
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PMID:Endothelial function in highly endurance-trained and sedentary, healthy young women. 1601 93

Heart failure is associated with alterations in cardiac and skeletal muscle energy metabolism resulting in a generalized myopathy. We investigated the molecular and cellular effects of angiotensin-converting enzyme inhibition (ACEi) on skeletal muscle metabolism in infarcted animals. Myocardial infarction (MI) was obtained by left descending coronary artery ligation. Sham, MI, and MI-treated rats (perindopril, 2 mg.kg(-1).day(-1) given 7 days after MI) were studied 1 and 4 mo after surgery. Oxygen consumption of white gastrocnemius (Gas) muscle was studied in saponin-permeabilized fibers, using the main substrates of mitochondrial respiration. mRNA expression of nuclear factors (PGC-1alpha, NRF-2alpha, and mtTFA), involved in the transcription of mitochondrial proteins, and of MCIP1, a marker of calcineurin activation, were also determined. Echocardiographic left ventricular fractional shortening was reduced in both MI and perindopril group after 1 and 4 mo, whereas systemic blood pressure was reduced by 16% only in the MI group after 4 mo. The capacity of Gas to oxidize glutamate-malate, glycerol-triphosphate, or pyruvate (-30%, P < 0.01; -32%, P < 0.05; -33%, P < 0.01, respectively), was greatly decreased. Furthermore, PGC-1alpha (-54%), NRF-2alpha (-45%), and MCIP1 (-84%) gene expression were significantly downregulated. ACEi improved survival, left ventricular function, and blood pressure. Perindopril protected also totally the Gas mitochondrial function and preserved the mRNAs concentration of the mitochondrial transcriptional factors. Moreover, PGC-1alpha correlated with Gas oxidative capacity (r = 0.48), mitochondrial cytochrome-c oxidase (r = 0.65), citrate synthase (r = 0.45) activities, and MCIP1 expression (r = 0.44). Thus ACEi totally prevented MI-induced alterations of skeletal muscle mitochondrial function and protein expression, halting the development of this metabolic myopathy.
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PMID:ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction. 1661 54

In the human body the mineralocorticoid aldosterone is responsible for maintaining water and electrolyte homeostasis and therefore controlling blood pressure. In addition, aldosterone has recently been associated with severe heart failure. Besides receptor-dependent action, the damaging effects of aldosterone may also be partly mediated through non-genomic mechanisms. The present study focuses on the mineralocorticoid receptor-independent action of aldosterone at the protein level. We chose the fission yeast Schizosaccharomyces pombe as a model organism, since this yeast does not contain nuclear steroid receptors, but many genes and regulatory mechanisms that are close to those of mammals. Using 2D-electrophoresis we identified for the first time protein spots affected by aldosterone in a nuclear receptor-free system. Mass spectrometry analysis using MALDI-TOF MS and nanoLC-MS/MS approaches allowed the unambiguous identification of 11 proteins that showed increased or decreased levels, which may represent newly identified players and pathways of aldosterone-induced action. Two proteins with a connection to osmotic regulation (NAD-dependent malic enzyme and glycerol-3-phosphate-dehydrogenase), as well as two proteins involved in the overall organization of the cytoskeleton, vip1 and glyceraldehyde-3-phosphate dehydrogenase, which was also found to be specifically affected by aldosterone in human HCT116 cells, are discussed.
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PMID:Analysis of aldosterone-induced differential receptor-independent protein patterns using 2D-electrophoresis and mass spectrometry. 1691 42

Changes in thyroid status are associated with profound alterations in biochemical and physiological functioning of cardiac muscle, although its impact on cardiac energy metabolism is still debated. Similarities between the changes in cardiac gene expression in pathological hypertrophy leading to heart failure and hypothyroidism prompted scientists to suggest a role for thyroid hormone status in the development of metabolic and functional alterations in this disease. We thus investigated the effects of hypothyroidism on cardiac energy metabolism. Hypothyroid state (HYPO) was induced by thyroidectomy and propyl-thio-uracyl in male rats for 3 weeks. We examined the effects of hypothyroid state on oxidative capacity and mitochondrial substrate utilization by measuring oxygen consumption of saponin permeabilized cardiac fibers, mitochondrial biogenesis by reverse transcription polymerase chain reaction and energy metabolism, and energy transfer enzymes by spectrophotometry. The results show that maximal oxidative capacity of the myocardium was decreased from 24.9 +/- 0.9 in control (CT) to 19.3 +/- 0.7 micromol O(2) min(-1) g dry weight(-1) in HYPO. However, protein content and messenger RNA (mRNA) of PGC-1alpha and mRNA of its transcription cascade that is thought to control mitochondrial content in normal myocardium and heart failure, were unchanged in HYPO. Mitochondrial utilization of glycerol-3P (-70%), malate (-45%), and octanoate (-24%) but not pyruvate was decreased in HYPO. Moreover, the creatine kinase system and energy transfer were hardly affected in HYPO. Besides, hypothyroidism decreased the activation of other signaling pathways like p38 mitogen-activated protein kinases, AMP-activated protein kinase, and calcineurin. These results show that cellular hypothyroidism can hardly account for the specific energetic alterations of heart failure.
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PMID:Mitochondrial and energetic cardiac phenotype in hypothyroid rat. Relevance to heart failure. 1763 11

Cardiolipin (CL), a tetra-acylated glycerophospholipid composed of two phosphatidyl moieties linked by a bridging glycerol, plays an important role in mitochondrial function in eukaryotic cells. Alterations to the content and acylation state of CL cause mitochondrial dysfunction and may be associated with pathologies such as ischemia, hypothyrodism, aging, and heart failure. The structure of CL is very complex because of microheterogeneity among its four acyl chains. Here we have developed a method for the quantification of CL molecular species by liquid chromatography-electrospray ionization mass spectrometry. We quantify the [M-2H](2-) ion of a CL of a given molecular formula and identify the CLs by their total number of carbons and unsaturations in the acyl chains. This method, developed using mouse macrophage RAW 264.7 tumor cells, is broadly applicable to other cell lines, tissues, bacteria and yeast. Furthermore, this method could be used for the quantification of lyso-CLs and bis-lyso-CLs.
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PMID:Quantification of cardiolipin by liquid chromatography-electrospray ionization mass spectrometry. 1795 37


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