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)

Molsidomine, coronary drug which acts similar to organic nitrates, belongs to the drug class of sydnones . SIN-1A metabolite of Molsidomine has pharmacologically active group of NO, which by increasing levels of cGMP, decreases levels of intracellular calcium ions in smooth muscle cells. This effect leads to relaxation of smooth muscle vasculature, inhibits platelets aggregation and has indirect antiproliferative effect. In clinical observations no effect of tolerance to the drug was observed. Experimental data show additional mechanism of action of the drug: SIN-1C metabolites protects the reoxygenated cardiomyocyte from post-reperfusion damage. Indications for use of Molsidomine are: ischaemic heart disease, chronic heart failure and pulmonary hypertension. Effects of Molsidomine use in acute myocardial infarction and unstable angina were compared in clinical trials to effects of nitroglycerin use. Both drugs were found equally potent, but authors underline the fact of better Molsidomine tolerability comparing NTG, but longer serum half-time of Molsidomin effects that control of the treatment is worse. In clinical trials it was suggested that intravenous use of Molsidomine metabolite SIN-1 during PTCA procedures is more effective than use of isosorbide dinitrate in the same procedures. In other clinical trials molsidomin was found to produce beneficial effects in patients with heart failure due to ischaemic cardiomyopathy, dilatative cardiomyopathy, in essential hypertension, pulmonary artery hypertension in COPD patients and in congestive heart failure.
 ...
PMID:[Molsidomine: importance in treatment of circulation disorders]. 1022 68

The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy, denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.
 ...
PMID:[Clinical relevance of myosin isoforms in the diaphragm]. 1093 18

A woman aged 87 and three men aged 87, 86 and 83, respectively, lived at home or in an old-people's home, in poor physical condition due to old age and diseases such as COPD and heart failure. One man was demented, the others did not wish hospital admission in case of further deterioration. When the condition worsened due to infections and fractures, the GP to a limited extent performed diagnostics and treatment. The four patients died, three of them after admission and intensive treatment because the restricted policy had not been communicated clearly. In decision-making about the management of geriatric patients, it is important that the GP knows the patient's wishes, correctly assesses his physical condition and prognosis and communicates well with the patient's next of kin and other care-givers.
 ...
PMID:[Decision making concerning very old patients with deteriorating health living at home]. 1103 77

Indices of atmospheric particulate matter (PM) have been reported to be associated with daily mortality and morbidity in a large number of recent time-series studies. However, the question remains as to which components of PM are responsible for the reported associations. Multiple PM components rarely are measured simultaneously. To investigate PM effects on mortality and morbidity, we used the multiple PM components measured in Windsor, Ontario, at a site only a few miles from downtown Detroit, Michigan. This study focused primarily on two study periods in which multiple PM components were measured in Windsor: 1985 to 1990, when levels of total suspended particles (TSP), sulfate from TSP (TSP-SO4(2-)), PM less than 10 microns in diameter (PM10), and nonthoracic TSP (TSP-PM10) were measured throughout the year; and 1992 to 1994, when data on PM10, PM2.5 (PM less than 2.5 microns in diameter), PM10-2.5 (PM10 minus PM2.5), particle acidity (H+), and artifact-free sulfates (SO4(2-)) were available for mostly summer months. Mortality data were analyzed for the 1985 to 1990 study period, and data on both mortality and hospital admissions of elderly patients were analyzed for the 1992 through 1994 period. Poisson regressions were used to estimate the effects of these PM components and gaseous criteria pollutants on mortality (nonaccidental, circulatory, respiratory, and nonaccidental without circulatory and respiratory) and on hospital admissions of elderly patients (for pneumonia, chronic obstructive pulmonary disease [COPD], ischemic heart disease, dysrhythmias, heart failure, and stroke), adjusting for temperature and humidity, trends and seasonal cycles, and day of the week. Both PM10 and TSP were associated significantly with respiratory mortality for the 1985 to 1990 period, with similar relative risk (RR) estimates for PM10 (RR = 1.123; 95% confidence interval [CI] 1.0361-1.218) and TSP (RR = 1.109; 95% CI 1.028-1.197), per 5th to 95th percentile increment. The effect-size estimates for TSP-SO4(2-) and TSP-PM10 were smaller and less significant. In two-pollutant models, simultaneous inclusion of gaseous pollutants with PM10 or TSP reduced PM coefficients by 0 to 34%. The effect-size estimates for total mortality, circulatory mortality, and total minus circulatory and respiratory mortality were less than those for respiratory mortality. Ozone (O3) and nitrogen dioxide (NO2) also were associated significantly with total and circulatory mortality, but a simultaneous consideration of these pollutants with PM10 reduced PM10 coefficients only slightly, or even increased them. In these results, pollution coefficients often were positive at multiple lag days (0-day through 3-day lags were examined), but for PM indices, 1-day lag coefficients were most significant. However, when all combinations of multiple-day average exposures were examined, for cases in which multiple lag days were positive, the choice of single-day or multiple-day average exposure did not appreciably change the estimated effect sizes. An examination of temporal correlation showed that the order of spatial uniformity as expressed by the median site-to-site correlation was O3 (0.83), PM10 (0.78), TSP (0.71), NO2 (0.70), carbon monoxide (CO) (0.50), and sulfur dioxide (SO2) (0.49), which suggests less exposure error for O3 and PM10 than for the other measured pollutants. Thus, these results suggest that spatially homogeneous pollution indices show higher associations with measured health outcomes.
 ...
PMID:Association of particulate matter components with daily mortality and morbidity in urban populations. 1124 87

Older males are known to carry, more likely than younger people, one or more chronic diseases with an expected impact on mortality. This study was aimed at identifying the relationship of prevalent chronic diseases in elderly populations of different countries with all-cause mortality. Men aged 65-84 from defined areas were enrolled in Finland (N=716), the Netherlands (N=887) and Italy (N=682). They were survivors of cohorts studied for 25 years within the Seven Countries Study. Major chronic diseases were diagnosed at entry. Ten-year follow-up for mortality was completed. Entry prevalence of selected chronic diseases was higher in Finland (56%) than in Italy (51%) and the Netherlands (44%). Ten-year age-adjusted death rates from all causes were higher in Finland (565 per 1000) and lower in the Netherlands (478 per 1000) and Italy (445 per 1000). The absolute risk of death related to chronic disease was high in the three countries, but was higher in Finland than in the Netherlands and Italy. The most lethal condition was stroke, with 10-year death rates of 806 per 1000 in Finland and 707 and 729 per 1000 in the Netherlands and Italy, respectively. The relative risk of all-cause mortality for a set of seven chronic diseases (coronary heart disease, heart failure, claudicatio intermittens, cerebrovascular accidents, diabetes, COPD and cancer) adjusted by age, other diseases and cohort was less than two for each condition, except cerebrovascular accidents in the Netherlands (RR 2.20). In general, relative risk was higher in Finland, intermediate in the Netherlands and lower in Italy, where only cerebrovascular accidents, intermittent claudication, diabetes and the presence of any chronic condition had a significant relative risk. About one third of men had one chronic disease, and between 10% and 15% had two diseases. The coexistence of any two or three chronic conditions was associated with a relative risk of 2 or more in Finland and the Netherlands and less than 2 in Italy. In these elderly men prevalent morbidity and comorbidity was relatively common and it explained a large proportion of excess in all-cause mortality in 10 years of follow-up.
 ...
PMID:Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: The FINE study (Finland, Italy, Netherlands, Elderly). 1143 8

Acute exacerbation of chronic bronchitis (AECB) is a very common condition, which presents with deteriorating sputum production and dyspnoea in a patient with pre-existing COPD or chronic bronchitis. As these symptoms are relatively non-specific and also the presenting feature of a wide range of other conditions, the physician should carefully consider the differential diagnosis before deciding on whether or not a patient indeed has AECB. The differential diagnosis can be summarised as pneumonia, pneumothorax, cardiac failure/cor pulmonale, bronchiectasis, asthma, tuberculosis, sinusitis and other forms of upper respiratory tract sepsis, diffuse panbronchiolitis, lung cancer, gastro-oesophageal reflux, the presence of a foreign body in the airway, melioidosis, and lung abscess. This article aims to discuss these conditions, with brief presentation of clinical cases, in the evaluation of differential diagnosis of AECB.
 ...
PMID:Solutions for difficult diagnostic cases of acute exacerbations of chronic bronchitis. 1158 3

Chronic obstructive pulmonary disease, COPD is a highly prevalent disorder of increasing medical and socio-economical importance. It is characterized by irreversible airflow obstruction. Besides airflow obstruction also other features are present. One of these is respiratory muscle weakness. Inspiratory muscle weakness is caused by hyperinflation and by generalized muscle weakness causing both respiratory and peripheral muscle dysfunction. The expiratory muscles partake in this generalized muscle weakness. Hyperinflation shortens the inspiratory muscles although in chronic hyperinflation sarcomere adaptation occurs. Generalized muscle weakness is caused by deconditioning, malnutrition, electrolyte disturbances, cardiac failure, systemic inflammation and treatment with corticosteroids causing steroid-induced myopathy. The latter disease was studied intensively both in patients and in animal models of disease. The major findings were that microscopically a myopathic pattern was present associated with generalized fiber atrophy. This is in contrast to classical belief that the atrophy would be confined to type IIx fibers. We noted severe down-regulation of the IGF-I mRNA expression, without important changes in the expression of the binding proteins. This may be responsible for the observed muscle atrophy and the myopathy. The latter is likely to be caused by a simultaneous upregulation of the ubiquitin protease pathway attacking structural proteins. Presently, we study the relationship between local and systemic cytokine expression and respiratory and peripheral muscle dysfunction in COPD patients. Respiratory and peripheral muscle dysfunction have significant consequences for COPD patients. Both respiratory and peripheral muscle dysfunction are associated with reduced exercise tolerance and reduced quality of life. Both are independent determinants of survival, in addition to the degree of airflow obstruction as measured by FEV1. Finally, also the utilization of health care resources appeared to be related to respiratory and peripheral muscle weakness. Treatment of respiratory and peripheral muscle weakness in COPD patients is possible. Respiratory and peripheral muscle training have been shown to produce beneficial effects. Nutritional intervention and anabolic steroids are only useful in combination with muscle training. Systemic administration of growth hormone and IGF-I only produces small effects. In animal models, local administration of IGF-I and transfer of the IGF-I gene transfer appear more promising for the future. Lung volume reduction surgery, LVRS, improves the force-generating capacity of the inspiratory muscles, presumably because of the geometrical alterations it causes in these muscles. It does not appear to improve intrinsic inspiratory muscle function.
 ...
PMID:Respiratory muscles in COPD: regulation of trophical status. 1181 11

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
 ...
PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

The aim of this review is to outline the characteristics of pulmonary circulation in health and disease and to define the value of exhaled NO (eNO) as a means to assess the involvement of pulmonary circulation in pathology. The discovery of the endocrine role of the endothelium has generated great interest in its potential role in regulating the vascular tone of the pulmonary vascular bed. Nitric oxide (NO)-mediated, endothelium-dependent relaxation has been demonstrated in the pulmonary arteries of animals and humans. Changes in the NO pathway in pulmonary hypertension are not completely understood. It is clear that NO has an important role in modulating the response to acute hypoxia, increased flow, and shear stress. The amount of exhaled NO (eNO) in different species may be easily measured, reflecting the overall NO metabolism from the lung (thus including epithelial, endothelial and other cell activity). The development of pulmonary hypertension secondary to systemic (systemic sclerosis, chronic heart failure) or pulmonary (COPD) diseases appears to be associated with a decrease in eNO production both at rest and during exercise. Chronic inhalation of NO appears to protect against pulmonary hypertension in animal models. Exhaled NO is attracting interest for its in vivo ability to represent the features of pulmonary circulation in pathology.
 ...
PMID:Nitric oxide and pulmonary circulation. 1216 55

Patients hospitalized with community acquired pneumonia were studied prospectively in two hospitals located in the surroundings of Buenos Aires city. Fifty two patients from General Hospital Manuel Belgrano (HMB) were included from March 1998 to February 1999 and 23 patients from Hospital Dr A. Cetrangolo (HCET) for respiratory disease, were included from June 2000 to May 2001. Patients with lung tuberculosis, lung neoplasia and HIV infection were excluded. Clinical background, signs and symptoms were recorded. Microbiological examinations performed included bacteria, respiratory viruses and mycobacteria. Studies for "atypical" bacteria (Chlamydia spp., Coxiella burnetii, Mycoplasma pneumoniae and Legionella spp.) were carried out by serological methods. No differences in age and gender were observed between both groups. Most frequently observed comorbidities in the HMB group included COPD, diabetes and cardiac failure while in the HCET group these were COPD, asthma and lung fibrosis. Etiology was established in 48% and 65.2% of the patients in the first and second group, respectively. Most frequent agents were Mycoplasma pneumoniae, Streptococcus pneumoniae, influenza A and Legionella spp.; the last one was detected in 12% of the patients. Most of these patients were from HMB and presented a good outcome. Mortality was similar in both groups (13.3%). In the HBM group it was related to the presence of comorbidities in 7 out of 8 cases, and in the HCET group it was a consequence of the worsening of their chronic respiratory failure.
 ...
PMID:[Community-acquired pneumonia in patients in 2 hospital populations]. 1267 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>