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Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure.  相似文献   
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Six very premature babies (born at 26–28 weeks gestational age) have been studied in hospital for 11–17 weeks, while in intensive care and in an incubator. Apart from suffering occasionally from the neonatal disorders of haemolytic jaundice and ‘respiratory distress of the newborn’, the babies were healthy and developed normally. Initially, the babies were continuously fed intravenously, and the lighting in the ward was on continuously. Routine care was given round the clock. When their medical condition permitted it, the babies were moved in their incubator to an adjacent ward, where they took frequent (2–4 hourly) small meals by mouth, the lighting was dimmed at night, and routine care tended to be given more in the daytime. Hourly recordings of insulated skin temperature were taken throughout the study, and it is the detection of rhythmicity in these measurements that has been the subject of the present study. The methods used were Phase-weighted Stacks, Phasor Walkout and Power Spectral Analysis. These methods have previously been used mainly in geophysical studies, and their value is that they can detect weak signals in noisy data and do not assume a particular waveform of any signal. Circadian rhythmicity was found in all babies for much of the time that were in the constant environment provided by the incubator. Ultradian rhythms were sometimes present also, but they were shorter-lived, and showed a wide range of changing periods, generally in excess of 8 h. When the babies were being treated for jaundice or respiratory distress, there was a tendency for the circadian rhythms to become weaker and for a broader spectrum of ultradian periods to appear. Placing babies in the 12 h : 12 h light : dark environment provided by the ward, and instituting feeding by mouth, had, in most cases, only modest effects upon either circadian or ultradian rhythms. Thus, circadian rhythms continued (but generally with a period not exactly equal to 24 h), and ultradian rhythms, when present, often did not show periods that could be related easily to feeding or care-giving. These results are discussed in terms of evidence for endogenous and exogenous origins of the observed rhythms, and of theories that have postulated the relationship between circadian and ultradian rhythms. It is concluded that the results from the present analyses are difficult to reconcile with the view that circadian rhythms develop from interactions between ultradian oscillators. We suggest that they indicate a matu-ration of the circadian system as a consequence of increasing associations between the circadian elements that are present in the suprachiasmatic nuclei and in other oscillators of the circadian system. The new analytical methods used here also indicate that the results obtained from time-frequency analysis depend to some extent upon the method used.  相似文献   
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Abstract: This study focuses on the sex ratio and spatial distribution of males and females in three populations of the endemic and restricted tropical dioecious shrub, Baccharis concinna (Asteraceae) in the mountainous region of Serra do Cipó, southeastern Brazil. The proportion of female plants in the population at lower elevation (1000 m a.s.l.) was significantly greater than of male plants. At this elevation of P/N and Ca/Al ratios in the soil were also greater indicating better nutritional status of the soils. The concentration of aluminium increased significantly with the elevation ( p < 0.001), perhaps rendering soils less conducive to female plants at higher elevations. Female plants are possibly adversely affected to a greater extent by soil quality than male plants. The spatial distribution of the populations within habitat was tested by the K(t) function, where the neighbourhood of a given individual was defined by a circle with a radius (t) up to 3 m. Despite the strong tendency for aggregation, the distribution of the sexes within habitats was random and the hypothesis was not supported. The independent distribution of the sexes within habitats may be explained by nutrient homogeneity of the soils, as well as by an absence of antagonism between the sexes. Nevertheless, we found a trend for males and females to be aggregated according to their gender.  相似文献   
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At variance with Cr(III), Cr(VI) compounds easily cross cell membranes and exert genotoxic effects. No metabolic oxidation of Cr(III) could be detected, whereas Cr(VI) reduction was observed in the presence of body fluids and subcellular fractions of various tissues from several animal species. The differential efficiency of this process may account for the selection of target tissues in Cr(VI) carcinogenesis. For instance, reduction by saliva and gastric juice may explain a lack of carcinogenicity by the oral route; reduction inside erythrocytes may explain a lack of carcinogenicity at a distance from administration sites; reduction by the epithelial-lining fluid of terminal airways and by alveolar macrophages may be consistent with the occurrence of thresholds in lung carcinogenesis. Liver preparations displayed the top efficiency in reducing Cr(VI), whereas skeletal muscle, i.e., a typical target in experimental Cr(VI) carcinogenesis, had no detectable activity. Bronchial tree and peripheral lung parenchyma preparations from almost 100 individuals reduced Cr(VI) to a variable extent. The efficiency of lung parenchyma and of isolated alveolar macrophages was enhanced in cigarette smokers. In rats, Cr(VI) reduction by lung preparations was significantly stimulated by the repeated i.t. instillation of Cr(VI) itself. Among the electron donors (chiefly GSH) and enzymatic mechanisms responsible for the intracellular Cr(VI) reduction, such as cytochrome P-450 reductase, glutathione redactase, and aldehyde oxidase, an important role can be ascribed to cytosolic DT diaphorase activity, usually catalyzing a 2-electron reduction.  相似文献   
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l-Tyrosine decarboxylase (EC 4.1.1.25) activity was induced in cell suspension cultures of Thalictrum rugosum Ait. and Eschscholtzia californica Cham. with a yeast polysaccharide preparation (elicitor). The highest l-tyrosine decarboxylase activity in extracts from 7-day-old cell cultures of E. californica was observed 5 hours after addition of 30 to 40 micrograms elicitor per gram cell fresh weight. The enzyme extracted from cells of E. californica was purified 1540-fold to a specific activity of 2.6 micromoles CO(2) produced per minute per milligram protein at pH 8.4 and 30 degrees C. Purified enzyme from T. rugosum showed a specific activity of 0.18 micromoles per minute per milligram protein. The purification procedure involved ammonium sulfate fractionation, anion-exchange fast protein liquid chromatography, ultrafiltration, and hydrophobic interaction chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the enzyme from the two plant cell cultures had subunits of identical molecular weight (56,300 +/- 300 daltons.  相似文献   
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The endopeptidase 22.19 (EC 3.4.22.19) has been associated with the metabolism of neuropeptides by its ability to convert small enkephalin-containing peptides (8 to 13 amino acids) into enkephalins. In addition, this enzyme cleaves the Arg8-Arg9 bond of neurotensin and the Phe5-Ser6 bond of bradykinin. We analyzed the circadian variation of endopeptidase 22.19 in the whole and individual areas of the rat brain. Endopeptidase 22.19 activity was analyzed by high-performance liquid chromatography (HPLC) using bradykinin as an operative substrate. Enzymatic specific activities were analyzed by rhythmometric methods and indicate a circadian fluctuation of endopeptidase 22.19 specific activity (mU of enzyme/mg of protein) in the whole brain [p less than 0.001, mesor (M) = 7.62, amplitude (A) = 2.89, and acrophase (phi) = 23:08 h], striatum (p less than 0.001, M = 2.92, A = 0.62, phi = 23:03 h), hypothalamus (p less than 0.001, M = 3.15, A = 0.86, phi = 01:12 h), periaqueductal gray matter (p less than 0.005, M = 2.62, A = 0.34, phi = 22:35 h), and cerebellum (p less than 0.014, M = 4.27, A = 0.88, phi = 17:12 h). The circadian rhythmicity in endopeptidase 22.19 specific activity suggests that light may have an effect on the peptidase activity in whole brain and in areas of the central nervous system and may be essential for the mechanisms of circadian fluctuations of neuropeptides in the brain.  相似文献   
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