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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (PcsO2), myocardial oxygen consumption (MVO2), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% +/- 3.7% (mean +/- SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% +/- 3.2% of the nonperfused area was ischemic (p less than 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 +/- 78 micrometers in the H hearts and 504 +/- 35 micrometers in the untreated heart (p less than 0.0001). In the H hearts PcsO2 increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p less than 0.0001). MVO2 decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p less than 0.0001). We conclude that H increases coronary flow while decreasing MVO2 during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.
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PMID:Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart. 711 92

The metabolic demands of the newborn heart are met primarily by glucose and lactate. Mitochondria are impermeable to the NADH produced by these cytosolic reactions. The malate/aspartate and alpha-glycerophosphate (alpha-GP) shuttles provide two pathways to transport reducing equivalents into mitochondria. The goals of this study were to compare the capacity of these shuttles in newborn and adult cardiac mitochondria and to measure the maximal activity of the mitochondrial enzymes involved in these shuttles. Shuttle and enzyme capacities were measured in isolated mitochondria from the left and right ventricular free wall of 0-3-d-old and adult pig hearts. Malate/aspartate shuttle capacity was nearly three times greater in the newborn left ventricle compared with adult (newborn, 616 +/- 24; adult, 232 +/- 28 nmol/min/mg; mean +/- SEM; n = 8; p < 0.00001). The capacity of the malate/aspartate shuttle of the right ventricular free wall was greater than the left in the adult heart. Despite a decrease in malate/aspartate shuttle capacity, maximal activity of mitochondrial matrix enzymes involved in this pathway were increased in adult mitochondria. alpha-GP shuttle activity was absent in adult myocardium. Newborn left ventricular myocardium had significant alpha-GP shuttle activity (44 +/- 4 nmol/min/mg) due to enhanced flavin-linked mitochondrial alpha-GP dehydrogenase activity compared with adult. Interventricular differences in the alpha-GP shuttle capacity were not found in newborn or adult hearts. These findings suggest a mechanism for the substrate preference of neonatal myocardium.
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PMID:Reducing equivalent shuttles in developing porcine myocardium: enhanced capacity in the newborn heart. 747 20

We have previously demonstrated (M. Stubbs, Z. M. Bhujwalla, G. M. Tozer, L. M. Rodrigues, R. J. Maxwell, R. Morgan, F. A. Howe, and J. R. Griffiths, NMR Biomed., 5: 351, 1992) that the intracellular pH (pHi) of several rat tumors is higher (> pH 7.0) than that of the tumor extracellular fluid (pHe), in contrast to normal tissues (e.g., liver) in which pHi is lower than pHe. In this paper we confirm a pHe of 6.8 +/- 0.07 (SEM) in Morris hepatoma 9618a by an independent method and report the tissue content of other ions by both 31P magnetic resonance spectroscopy and by conventional analysis in hepatomas and livers in rats. Compared with liver, tissue Na+ was 2-fold higher and tissue K+ was lower. Tissue Ca2+ was 8-fold higher (7.4 +/- 4.3 mumol/g wet weight) and tissue Pi was 2-fold higher (8.5 +/- 1.3 mumol/g wet weight) suggesting the presence of insoluble calcium phosphate. Cl- was unchanged (approximately 40 mumol/g wet weight), whereas HCO3- was lower in the hepatoma (12.4 +/- 0.83 compared to 15.5 +/- 0.76 mumol/g wet weight). Total tissue Mg2+ was similar in both tissues, but free [Mg2+] (calculated by two different methods) was approximately 5-fold lower in the hepatoma. The ATP values were 3.5-fold and [NAD]/[NADH] 9-fold lower in the hepatoma. The results are compatible with the hypothesis that the chronic partial hypoxia of tumor tissue involves changes in the linked equilibria of many ions and metabolites and may help explain such pathologies as calcification.
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PMID:Metabolic consequences of a reversed pH gradient in rat tumors. 803 32

The effects of 2,3-butanedione monoxime (BDM) on isometric force and myofibrillar adenosine 5'-triphosphatase (ATPase) activity were studied in skinned cardiac trabeculae from the rat. ATP hydrolysis was enzymatically coupled to the breakdown of reduced nicotinamide adeninedinucleotide (NADH). The NADH concentration was monitored photometrically. Measurements were performed at a sarcomere length of 2.1 microm, 20 degrees C and pH 7.0. Without BDM, isometric force was 45 +/- 3 kN/m2 and the isometric ATPase activity 0.49 +/- 0.04 mM/s (mean +/- SEM, n = 31). Force gradually decreased as a function of [BDM] to 2.8 +/- 0.4% at 100 mM BDM. ATPase activity was also depressed by BDM, but to a lesser extent than force. BDM therefore has a marked effect on myofibrillar tension cost. The rate of tension redevelopment after unloaded shortening decreased from 29 +/- 2 s-1 (n = 10) without BDM to 22 +/- 1 s-1 (n = 5) at 20 mM BDM. These results, modelled in a two- and three-state scheme of cross-bridge interaction, indicate that, in cardiac muscle, BDM not only affects cross-bridge formation but, especially at high concentrations (>/= 20 mM), also causes a marked increase in the apparent rate of cross-bridge detachment.
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PMID:Effects of 2,3-butanedione monoxime on cross-bridge kinetics in rat cardiac muscle. 877 44

High levels of lactate dehydrogenase (LDH; EC 1. 1. 1. 27) activity have been detected in the filarial worm Molinema dessetae. The two major LDH isoenzymes (LDH1 and LDH2) from female worms were purified by successive chromatography on diethylaminoethyl (DEAE)-Sepharose, carboxymethyl (CM)-Sepharose, and hydroxyapatite columns followed by fast protein liquid chromatography (FPLC)-gel filtration. LDH1 and LDH2 isoenzymes were found to be dimers with subunits of 58 kDa. They had similar properties with regard to substrate and coenzyme affinity. The apparent Michaelis constants (K(m) values; mean +/- SEM, n = 10) were 0.34 +/- 0.04 mM for pyruvate, 0.25 +/- 0.02 mM for reduced nicotinamide adenine dinucleotide (NADH), 2.5 +/- 0.21 mM for lactate, and 0.18 +/- 0.02 mM for NAD, which suggested that pyruvate reduction was the favored reaction. LDH1 and LDH2 were affected by p-chloromercuribenzoate and Hg2+, and such inhibitory effects could be reversed by the addition of thiol compounds (L-cysteine or beta-mercaptoethanol) as observed for mammalian LDH. Oxalate acted as a noncompetitive inhibitor of pyruvate reduction (Ki = 4.7 +/- 0.35 mM; mean +/- SEM, n = 10) and as a competitive inhibitor with lactate (Ki = 2.3 +/- 0.21 mM), whereas oxamate acted as a competitive inhibitor with pyruvate (Ki = 3.3 +/- 0.28 mM) and was noncompetitive with lactate (Ki = 19 +/- 1.2 mM). These substrate analogues exerted similar effects on mammalian LDH, but the inhibition constants were significantly different. The existence of structural and kinetic differences between mammal and filarial LDH isoenzymes prompted us to evaluate them as targets for chemotherapeutic attack.
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PMID:Purification and characterization of lactate dehydrogenase isoenzymes 1 and 2 from Molinema dessetae (Nematoda:Filarioidea). 889

A gradual increase in blood pressure (BP), often attaining hypertensive levels, is common during aging--"age-related hypertension." Therefore, means to prevent or ameliorate this elevated BP safely are important. Although oral B-nicotinamide adenine dinucleotide (NADH), a natural coenzyme, is used principally to treat various neurologic disorders, we wished to investigate whether this agent had the same potential to lower BP and benefit the cardiovascular system as does coenzyme Q10, a similar-type agent. As a first approximation, spontaneously hypertensive rats (SHR) were used to determine effects of oral NADH. In a blinded, placebo-controlled study, ten rats received placebo; and ten, NADH for ten weeks. Systolic BP was measured by tail plethysmography. Blood was collected terminally, and chemistries were performed by routine methodologies. Thiobarbituric acid reactive species (TBARS) (an estimate of lipid peroxidation/free radical formation) was measured in renal and hepatic tissues. The following was noted: water and food intake were comparable, and the steady weight gain of young SHR were similar in the placebo and NADH groups. Although systolic BP did not differ between the two groups over the first month, it decreased and stayed markedly lower for the remainder of study in SHR receiving oral NADH. At the end of 60 days, SBP in NADH-treated SHR was 184 mm Hg +/- 2.8 (SEM) compared to 201 mm Hg +/- 2.1 (SEM) in control SHR (p < 0.001). No significant differences were seen in blood levels of glucose, insulin, triglyceride, and HDL levels but NADH intake lowered total cholesterol (p < 0.002) and LDL (p < 0.02). Renal TBARS were also significantly lower in SHR receiving NADH (P < 0.001). Accordingly, supplementation with the natural coenzyme NADH theoretically could prove to be useful in preventing age-related increases in BP and, thus, various cardiovascular maladies.
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PMID:Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR). 989 17

An improved method for the measurement of tissue metabolites associated with cellular energetic state by capillary electrophoresis is described. This method allows 17 compounds present in a mixture of standards to be determined simultaneously within 43 min with good reproducibility. ATP, ADP, AMP, UTP, IMP, inosine, hypoxanthine, creatine, phosphocreatine, UDP-galactose, NAD and NADH were detected in samples of either rat heart tissue or rat neonatal cardiomyocytes. This method can detect compounds at concentrations of 5 microm in samples. Recoveries for ATP and phosphocreatine added to cardiomyocyte samples were 99.4 +/- 2.1% and 103.1 +/- 3.3%, respectively (mean +/- SEM, n = 3). Our method has been comprehensively validated and is capable of measuring a wider range of tissue metabolites important in assessing cellular energy status than existing methods.
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PMID:An improved capillary electrophoresis method for measuring tissue metabolites associated with cellular energy state. 1021 91

Thiols like glutathione may serve as reducing cofactors in the production of nitric oxide (NO) and protect NO from inactivation by radical oxygen species. Depletion of thiol compounds reduces NO-mediated vascular effects in vitro and in vivo. The mechanisms underlying these actions are not clear, but may involve decreased synthesis of NO and/or increased degradation of NO. This study investigates the effect of glutathione depletion on the response to NO-mediated vasodilation induced by acetylcholine (Ach, 10 micrograms/kg), endothelial NO synthase (eNOS) activity and potential markers of vascular superoxide anion (O2.-) production in conscious chronically catheterized rats. Thiol depletion induced by buthionine sulfoximine (BSO, 1 g i.p. within 24 h) decreased the hypotensive effect of Ach by 30% (MAP reduction before BSO 27 +/- 3 mmHg, 19 +/- 3 mmHg after BSO, (mean +/- SEM), p < .05, n = 8). The impaired effect of Ach was associated with a significant reduction in eNOS activity (control: 7.7 +/- 0.8, BSO: 3.9 +/- 0.4 pmol/min/mg protein (p < .05), n = 6). In contrast, neither NADH/NADPH driven membrane-associated oxidases nor lucigenin reductase activity were significantly (p < .05) affected by BSO (BSO: 4415 +/- 123, control: 4105 +/- 455 counts/mg; n = 6) in rat aorta. It is concluded that in vivo thiol depletion results in endothelial dysfunction and a reduced receptor-mediated vascular relaxation. This effect is caused by reduced endothelial NO formation.
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PMID:Endothelium-dependent vasorelaxation in inhibited by in vivo depletion of vascular thiol levels: role of endothelial nitric oxide synthase. 1169 35

The fabrication and attractive performance of carbon nanotube (CNT)/Teflon composite electrodes, based on the dispersion of CNT within a Teflon binder, are described. The resulting CNT/Teflon material brings new capabilities for electrochemical devices by combining the advantages of CNT and "bulk" composite electrodes. The electrocatalytic properties of CNT are not impaired by their association with the Teflon binder. The marked electrocatalytic activity toward hydrogen peroxide and NADH permits effective low-potential amperometric biosensing of glucose and ethanol, respectively, in connection with the incorporation of glucose oxidase and alcohol dehydrogenase/NAD(+) within the three-dimensional CNT/Teflon matrix. The accelerated electron transfer is coupled with minimization of surface fouling and surface renewability. These advantages of CNT-based composite devices are illustrated from comparison to their graphite/Teflon counterparts. The influence of the CNT loading upon the amperometric and voltammetric data, as well as the electrode resistance, is examined. SEM images offer insights into the nature of the CNT/Teflon surface. The preparation of CNT/Teflon composites overcomes a major obstacle for creating CNT-based biosensing devices and expands the scope of CNT-based electrochemical devices.
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PMID:Carbon nanotube/teflon composite electrochemical sensors and biosensors. 1272 Mar 43

Studies were performed on ejaculated human spermatozoa (32 subjects with normal sperm motility and 25 subjects with low sperm motility). Morphology of sperm midpiece was evaluated in light, fluorescent and transmission or scanning electron microscope. Changes in mitochondrial membrane potential (delta(psi)m) and mass of mitochondria were analysed by flow cytometry using mitochondrial specific probes JC-1 and Mito Tracker Green FM. Moreover, oxidoreductive capability of sperm mitochondria was assessed using cytochemical reaction for NADH-dependent dehydrogenases. In flow cytometry analysis of JC-1-stained spermatozoa, two asthenozoospermic subpopulations were distinguished: patients with a high percentage (76 +/- 11%, 13 subjects) and patients with a low percentage (29 +/- 14%,12 subjects) of spermatozoa with functional-polarized mitochondria with high delta(psi)m. Our microscopic investigations of spermatozoa of seven asthenozoospermic patients reveal that the deformed and unusually thickened sperm midpieces (50-70% of cells), occasionally with persistent cytoplasmic droplet, contain supernumerary mitochondria with normal substructure, full oxidoreductive capability and high delta(psi)m. The midpiece deformations cause nonprogressive movement or immotility. They can also appear in smaller number of spermatozoa (5-35% of cells) in patients with normal sperm motility. Moreover, in three cases of asthenozoospermia midpiece malformations were accompanied by abnormal morphology of outer dense fibers and axoneme. The cytochemical, fluorescence and SEM studies showed the absence of midpieces in many (60-80%) spermatozoa in some other cases of asthenozoospermia. The morphological observations corresponded with flow cytometry analysis of Mito Tracker Green FM-stained spermatozoa. Our results suggest that in some cases of asthenozoospermia the sperm mitochondria can be functionally active and display high delta(psi)m in large number of cells. The results may suggest that asthenozoospermia does not necessarily result from energetic disturbances of sperm mitochondria. The low sperm motility may be associated with deformations of the mitochondrial sheath containing functional mitochondria. The combination of fluorescence microscopy and flow cytometry with electron microscopic investigations is a sensitive, precise and comprehensive examination which helps discover sperm abnormalities responsible for asthenozoospermia.
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PMID:Sperm mitochondria of patients with normal sperm motility and with asthenozoospermia: morphological and functional study. 1367 31


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