Review: myocardial physiological effects of taurine and their significance.
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Biomedical subjects
Publications and source records attributed to J Azuma.
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We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group.
Serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans ATCC 29523 (serotype a) and NCTC 9710 (serotype c) were extracted from whole cells by autoclaving and purified by ion-exchange chromatography and gel filtration. Analysis of component sugars by gas-liquid chromatography-mass spectrometry, high performance liquid chromatography, and NMR together with optical rotation data showed that the serotype a antigen was composed solely of 6-deoxy-D-talose, whereas the serotype c antigen consisted of 6-deoxy-L-talose. Structural analysis indicated that both of these antigens were composed of closely related repeating units, -3)-6-deoxy-alpha-D-Talp-(1-2)-6-deoxy-alpha-D-Talp-(1-(sero type a) and -3)-6-deoxy-alpha-L-Talp-(1-2)-6-deoxy-alpha-L-Talp-(1-(sero type c). 1H and 13C NMR analysis showed that both of these serotype antigens contained one acetyl group/2 sugar residues. These acetyl groups localized at the O-2 position of 3-linked 6-deoxy-D-talose (serotype a) or O-4 position of 3-linked 6-deoxy-L-talose residues (serotype c), respectively. These results coupled with our previous findings on the serotype b antigen (Amano, K., Nishihara, T., Shibuya, N., Noguchi, T., and Koga, T. (1989) Infect. Immun. 57, 2942-2946) showed that the serotype antigens from A. actinomycetemcomitans are a group of novel polysaccharides with structural features closely related biosynthetically.
Endothelin, an endothelium-derived vasoconstrictive peptide, has a strong potency of coronary artery constriction. However, the role of endogeneous endothelin under pathophysiological conditions has not yet been known. In this study, we examined plasma endothelin concentration in dogs with myocardial ischemia and reperfusion. Anesthetized open-chest dogs underwent either 45 minutes occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion, or 4-10 hours of continuous occlusion. Plasma concentration of endothelin from the central vein was measured by the highly sensitive enzyme-immunoassay. Plasma endothelin concentration increased 2.2-fold with the peak level at 60 minutes after release of the ligated artery, but occlusion per se caused no remarkable change. These data suggest that reperfusion of the occluded artery might be needed to increase the plasma concentration of endothelin in case of myocardial infarction.
MAb C23, a human immunoglobulin G1 (IgG1) monoclonal antibody (MAb) against cytomegalovirus, was administered to 20 healthy volunteers. Sixteen of them received a single infusion of a dose ranging from 5 to 80 mg. The plasma clearance curves fit a two-compartment model, with half-lives of 31.0 +/- 23.6 h in the diffusion phase and 24.2 +/- 5.8 days in the equilibration phase. The plasma after administration had the virus neutralization activities that were equivalent to the plasma MAb C23 levels. The remaining four subjects, who received three infusions of 60, 20, and 20 mg at 1-week intervals, showed pharmacokinetics that were very consistent with those of the single infusion. No antibody response against MAb C23 was observed in any of the subjects at any time, when monitored for approximately 60 days after the single infusion or the third infusion of the three repeated doses. None of the 20 subjects showed any treatment-related clinical signs or changes. These results suggest that a human IgG MAb has the same pharmacokinetic characteristics as those of natural human serum IgG, and that it is not immunogenetic and is safe in humans.
Perfusion of isolated, working rat heart with buffer containing 300 microM methionine in the presence of 2.5 U/L insulin led to a 15% decrease in cardiac work and a four-fold decrease in sarcolemmal Na(+)-Ca2+ exchange activity. These effects of methionine were largely prevented by inclusion of 10 mM taurine in the buffer supplemented with methionine and insulin. Taurine also reduced the extent of 3H-methyl group incorporation from radioactive methionine into myocardial phospholipids by approximately 45%. Assays of sarcolemmal phospholipid methyltransferase activity at catalytic sites I, II, and III revealed that taurine inhibited N-methylation activity approximately 30%. The data imply that the ability of taurine to modulate myocardial contraction and calcium transport may be related to taurine-mediated inhibition of phospholipid N-methylation.
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Proliferative responses to the costimulation with phorbol-12-myristate-13-acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. The degree of the age-related decline was more significant in T cells than in B cells. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. The augmentation of the proliferative response by taurine was more marked in old T cells than in young ones. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in the old T cells under the stimulation with PMA and ionomycin than that in the young ones. In the presence of taurine, the concentration of [Ca2+]i in the old T cell significantly increased under the stimulation. The results indicate that taurine improved the proliferative response of old T cells by the restoration of the increment of the concentration of [Ca2+]i under the stimulation.
An anticancer drug, doxorubicin, and a naturally occurring beta-amino acid, taurine, exert opposing actions on myocardial calcium content and lipid peroxidation. Thus, we tested the hypothesis that the two agents may interact to modify cardiac calcium metabolism and indices of lipid peroxidation. Cardiac taurine levels were reduced by half in rats given tap water containing a beta-amino transport inhibitor, beta-alanine. Taurine deficiency was associated with an increased susceptibility of the heart to doxorubicin-mediated calcium accumulation, a phenomenon commonly associated with doxorubicin cardiotoxicity. Taurine deficiency also predisposed the heart to enhanced formation of malondialdehyde caused by doxorubicin administration. While increases in malondialdehyde levels are often associated with lipid peroxidation, the failure of doxorubicin to cause changes in oxidized glutathione content makes peroxidative mechanisms a less likely explanation for the potentiation of doxorubicin-mediated myocardial calcium accumulation in taurine-deficient rats. A more likely possibility is the interaction between taurine deficiency and doxorubicin to inhibit the sarcolemmal calcium pump. The data also suggest that the interaction between doxorubicin and taurine deficiency does not involve alterations in the pharmacokinetics of doxorubicin or the cardiotoxic metabolite, doxorubicinol. It is concluded that reduction in sarcolemmal calcium pump activity by taurine deficiency may contribute to myocardial calcium accumulation in hearts whose calcium homeostasis has been compromised by doxorubicin.
The effects of taurine on the inward Ca2+ current (ICa) were investigated by means of the whole-cell voltage-clamp technique in isolated single guinea pig ventricular myocytes. ICa were elicited by 200-ms test pulses from a conditioning holding potential of -45 mV to various test potentials at a rate of 0.5 Hz. Taurine (10-20 mM) had different effects on ICa, depending on the extracellular Ca2+ concentration [( Ca]o). A small stimulatory effect of taurine was found in low [Ca]o (0.8 mM), and a small inhibitory effect was found in high [Ca]o (3.6 mM). Taurine had no significant effect on ICa in normal [Ca]o (1.8 mM). Such dual effects on ICa may explain the various effects reported for taurine especially its dual inotropic actions on cardiac muscle depending upon [Ca]o. Thus, taurine acts in a manner to keep ICa relatively constant. Taurine increased the resting potential irrespective of [Ca]o, suggesting that, in addition, taurine increased K+ conductance and/or ion exchange systems such as the Na/Ca and Na/K exchange.
The clinical features of acute non-Q wave myocardial infarction (NQMI) with R wave regression and no ST segment depression are distinct from those of acute Q wave myocardial infarction (QMI). NQMI patients showed ST segment elevation at admission, and significantly earlier regression of the ST segment elevation and appearance of coronary T waves were observed compared to QMI patients. In addition to the significantly lower level of mean peak serum creatine kinase activity and the significantly lower incidence of pump failure during the acute phase, the incidences of in-hospital mortality and multivessel disease were significantly lower in the NQMI patients. With respect to acute-phase coronary angiographic features within 48 h after the onset, the rate of spontaneous opening of infarct-related vessels was significantly higher in the NQMI patients. Thirteen of the 19 NQMI patients responded to urokinase infusion. These facts suggest that transient, intermittent or incomplete obstruction may favor this type of NQMI over QMI, and that thrombus might be an important factor in the pathogenesis of this type of NQMI.
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