Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02288 (NADH)
 21,914 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In six dogs ligature of the main pulmonary artery was performed, and in five other ligature of the pulmonary veins was carried out, while in five other animals combined simultaneous ligatures were made. Extensive infarcization was noted, of the pulmonary tissue, with an evolution toward death, in all types of ligatures. Death occured earlier in ligatures of the pulmonary veins. All the interventions were performed on the left lung, under general anesthesia, orotracheal intubation and assisted respiration. Electron-optic investigation revealed mitochondrial alterations 30 minutes after ligature of the pulmonary veins and 2 hours after that of the pulmonary arteries. The lesions were extensive in time. In the infarction areas the activity of the energetic enzymes (SDH, NADH2, G6PD, LDM) appears to be reduced, and even completly abolished. This occurs earlier when pulmonary veins are closed. On the basis of clinical and surgical data already mentioned in the literature, as well as on that of the experimental studies performed, the authors consider that ligature of the pulmonary artery, either therapeutically or due to various necessities, an intervention that is recommended by some surgeons, is not a functional type of intervention, and can even have ill-fated results, especially if the pulmonary venous circulation is also involve in the pathological process.
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PMID:[Morphological (Macro-, micro-electronoptical) changes and cytoenzyme changes after ligation of the pulmonary artery, pulmonary veins and both in dogs]. 19 55

In 14 patients operated upon for focal cerebral seizures under local anesthesia, cortical electrical activity was compared with the levels of nicotinamide adenine dinucleotide (NADH) observed fluorometrically. NADH levels fell 3 to 15% in response to 5-second intervals of cortical stimulation in 42 of 70 observations. Although a rough correlation was seen between the quantity of current delivered (milliamperes X seconds) and the NADH decrease, this varied from case to case. The presence of cortical afterdischarge often, but not invariably, corresponded to a greater percentage of change in the NADH levels. Averaging the NADH response to sporadic interictal epileptiform discharges failed to demonstrate concomitant NADH reductions. A similar lack of change was seen in four patients in whom low frequency spike foci were induced by topically applied penicillin in cortex destined for excision. Preliminary studies of the topography of spread of NADH change after cortical stimulation indicate that this is usually asymmetrical in human epileptogenic cortex. Under experimental conditions in cats, it seemed possible to differentiate primary from projected epileptiform activity, in that the projected activity had little or no concomitant fall in the NADH level after the electrographic spike. Pathological examination of the excised sites of NADH recording showed, with one exception, fibrous astrocytic transformation of the central cortex layers.
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PMID:Fluorometric monitoring of NADH levels in cerebral cortex: preliminary observations in human epilepsy. 21 33

1. The effects of halothane (CF3CHBrCl), a volatile anaesthetic agent, on electron transfer in isolated rat liver microsomal preparations were examined. 2. At halothane concentrations achieved in tissues during clinical anaesthesia (1-2mM), halothane shifts the redox equilibrium of microsomal cytochrome b5 in the presence of NADPH towards the oxidized form. Halothane accelerates stoicheiometric consumption of NADPH and O2, increases the rate of reoxidation of NADH-reduced microsomal ferrocytochrom b5, but does not affect NADPH- or NADH-cytochrome c reductase activity. The enhanced microsomal electron flow seen in the presence of halothane is not diminished by CO nor is it increased by pretreatment of the animals with phenobarbital. 3. The effects of halothane are maximum in microsomal preparations isolated from animals fed on a high-carbohydrate diet to induce stearate desaturase activity. Changes in microsomal electron transfer caused by halothane are in all cases abolished by low concentrations (1-2mM) of cyanide. Microsomal stearate desaturase activity is unaffected by halothane. 4. The first-order rate constant for oxidation of membrane-bound ferrocytochrome b5 in the absence of added substrate (k1 equals 1.5 times 10(-3)A-1) is similar to that for autoxidation of purified ferrocytochrome b5(k1 equals 7 times 10(-3)S-1) the rate of autoxidation of soluble ferrocytochrome b5 is unaffected by halothane. 5. It is concluded that the effects of halothane on microsomal electron transfer are not related to cytochrome P-450 linked metabolism but rather arise from the interaction of halothane with the cyanide-sensitive factor of the stearate desaturase pathway.
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PMID:The effects of halothane on hepatic microsomal electron transfer. 23 6

Liver microsomal enzyme activities and glutathione (GSH) contents of fasted male rats pretreated with phenobarbital (PBT) or vehicle controls were measured during and after exposure to trichloroethylene (TRI) (1% x 2 hr). TRI caused morphologic liver injury only in the pbt animals. Cytochrome P-450 and b5 contents were diminished by the end of the first hr of TRI exposure and NADH-cytochrome c reduction increased three-fold by eight hr in the PBT animals. The only change in vehicle animals exposed to TRI was a decrease in NADPH-cytochrome c reductase activity by eight hr. Hepatic GSH contents of vehicle animals, constant during TRI exposure, rose with time. In contrast, in PBT animals, hepatic GSH contents decreased during TRI exposure and then rebounded. Decreases in GSH were most profound in the microsomal fraction. When fed animals with approximately two-fold higher hepatic GSH levels than fasted animals were exposed to TRI, they had shorter anesthesia recovery times and less liver injury, although excreting similar or slightly more trichlorinated metabolite into their urine in 24 hr than their fasted counterparts. We suggest that the hepatoxic effects of trichloroethylene are caused by inadequate detoxification of its reactive intermediates.
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PMID:Trichloroethylene-induced deactivation of cytochrome P-450 and loss of liver glutathione in vivo. 84 Nov 73

The inhalational anesthetics reversibly inhibit mitochondrial electron transport from NADH-linded substrates at the level of the enzyme NADH-dehydrogenase. The effect of this inhibition on ATP production is probably not the basis of the anesthetic state, as the level of high-energy phosphate in the brain does not decrease during anesthesia. Anesthetics, therefore, interfere with brain energy untilization, in addition to brain energy production. Inhibition by anesthetics of mitochondrial calcium uptake, which results from the inhibition of electron transport, may be an important anesthetic effect if it raises the intracellular calcium level. Other areas of investigation which have not been discussed here include the effects of anesthetics on glycolytic and other enzyme systems, ion fluxes, neurotransmitter synthesis and release, and on the structure of natural and artificial membranes. It is now appreciated that most of the inhalational anesthetics are metabolized by the endoplasmic reticulum of hepatocytes. The biotransformation of several anesthetics can be increased by drugs which induce hepatic microsomal enzymes. The organ toxicities of chloroform, trichloroethylene, fluroxene, methoxyflurane, and possibly of halothane and enflurane are related to their intermediary or final metabolites. It is of anesthetic drugs for an individual patient.
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PMID:The biochemical basis of anesthetic toxicity. 110 11

The development of fatigue was investigated by electrical stimulation in 15 domestic pigs (1 yr old, 70-90 kg body weight) and seven adult dogs (3 yr old, 45 kg body weight). After anaesthesia, silver electrodes were implanted in the anterior and posterior parts of the right masseter muscles. The contralateral muscle was used as control. The bite force was measured. Muscle biopsies were obtained from the anterior, central and posterior parts, and were immediately frozen in liquid nitrogen. A fluorometrical analysis by enzymatic methods for glycogen, glucose, creatine phosphate, NAD, NADH, lactate and pyruvate was made. Blood flow was measured by 133Xe wash-out; oxygen consumption was monitored with an oxygen electrode. The porcine masseter was continuously stimulated for 60 min (100 V, 4 Hz and 2 ms). The canine masseter was intermittently stimulated (100 V, 20 Hz and 2 ms). The contraction was repeated four times, with a 10-min rest between. The porcine masseter could sustain longer endurance times than the canine masseter, which was easily fatigued. A marked substrate depletion was evident. The precontractional contents of glycogen, glucose and creatine phosphate were reduced. Lactate accumulation was evident (2-4 times more in the porcine and 4-8 times more in the canine masseter). The NADH concentration increased and the NAD content decreased. Blood-flow impairment (80% reduction in the dog, 60% in the pig) was observed. After the contraction phase, there was a hyperaemia (58% elevation of blood flow in the pig masseter, 45% in the canine). The oxygen tension followed in magnitude and time the blood-flow changes. These circulatory variables returned to normal after recovery. The high degree of substrate depletion, blood-flow impairment and a simultaneous decrease in oxygen transport to the contracted muscle, in combination with a prominent lactate accumulation, may induce a decrease in bite-force production.
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PMID:Bite-force development, metabolic and circulatory response to electrical stimulation in the canine and porcine masseter muscles. 147 60

Acute and residual effects of blood-brain barrier disruption and bilirubin on brain metabolism were studied in a rat model after osmotic opening of the blood-brain barrier under pentobarbital anesthesia. Arabinose (1.5 M) was infused via the right external carotid artery over 30 s, resulting in opening of the barrier within the right hemisphere. Two min later, bilirubin was infused i.v. over 3 min, raising the serum bilirubin concentration to 37-44 mg/dL (633-752 mumol/L). The animals were euthanized at 15 min or 4 h by freezing the brain in situ. Opening the blood-brain barrier produced small changes in cerebral energy metabolism in some animals at 15 min. Compared with saline-infused control animals, two out of nine rats had decreased brain phosphocreatine and three out of nine developed increased brain lactate levels. Infusion of bilirubin in rats with a disrupted blood-brain barrier produced profound decreases in brain energy metabolites, glucose, and glycogen and a markedly increased lactate/pyruvate ratio at 15 min. The markedly increased lactate in the presence of normal or low pyruvate in bilirubin-treated animals indicates accumulation of NADH and probably reflects severe mitochondrial dysfunction. Four h after the arabinose/bilirubin infusions, the barrier would be expected to be repaired and bilirubin levels were negligible, but two out of five arabinose and three out of six bilirubin rats continued to have severely altered brain metabolism indicating residual brain injury in some animals.
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PMID:Bilirubin-induced changes in brain energy metabolism after osmotic opening of the blood-brain barrier. 175 4

The fuel preference of human muscle mitochondria has been given. Substrates which are oxidized with low velocity cannot be used to detect defects in oxidative phosphorylation. After general anaesthesia, the oxygen uptake with the different substrates is much lower than after local analgesia. The latter was therefore used in the subsequent study. In 15 out of 18 patients with ocular myopathy, defects in oxidative phosphorylation could be detected in isolated muscle mitochondria prepared from freshly biopsied tissue. Measurement of the activity of segments of the respiratory chain in homogenate from frozen muscle showed no, or minor defects. In two of these patients showing exercise intolerance, decreased oxidation of NAD(+)-linked substrates and apparently normal mitochondrial DNA, further study revealed deficiency of pyruvate dehydrogenase in a girl with ptosis and a high Km of complex I for NADH in a man. Both patients responded to vitamin therapy.
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PMID:Oxidative phosphorylation in human muscle in patients with ocular myopathy and after general anaesthesia. 211 84

Changes in brain tissue pH, ATP and NADH contents in the cerebral embolization model of Wistar rat were investigated by bioluminescence method. Under light anesthesia, main trunk of cerebral artery was embolized with a silicone cylinder (500 microns in diameter and 1 mm in length) through the cervical internal carotid artery. Rat brain was frozen in situ at 1 or 3 hours after embolization. In some rats Evans blue was injected into the peritoneal cavity 30 minutes before freezing. Caudate putamen and cortex were often acidotic but thalamus, hypothalamus, and hippocampus were composed of both acidotic and alkalotic area. Exudation of Evans blue was frequently detected in the alkalotic area. ATP was decreased partially in the acidotic area. In the alkalotic area ATP was decreased to mild to severe degree. Decreased ATP region in the acidotic area showed increased NADH content, whereas in the alkalotic area NADH was diffusely decreased. From these results, alkalosis may be induced by cerebral edema due to plasma exudation. The decrease of ATP and increase of NADH in the acidotic area may demonstrate the disturbance of oxidative phosphorylation under anaerobic glycolysis, and the decrease of ATP and decrease of NADH in the alkalotic area may demonstrate impairment of glycolysis mainly due to brain edema.
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PMID:[Tissue pH and energy metabolism in cerebral embolization model of rat]. 235 18

The influence of hyperthermia on liver mitochondrial respiration and liver metabolites levels was studied by increasing body temperature to 41.0 degrees C in rats under oxygen and nitrous oxide anesthesia maintaining constant PaCo2. At 41.0 degrees C, the increase in ATP and energy charge level (EC) by Atkinson and the increase of state 3 and RCR in NADH linked substrate were observed. After maintaining body temperature at 41.0 degrees C for 30 minutes, the decrease in ATP, EC, state 3, RCR and ADP/O were observed. The degree of change from 38.0 degrees C to 41.0 degrees C in state 3, state 4, RCR and ADP/O was greater in NADH linked substrate than in non-NADH one. After keeping body temperature at 38.0 degrees C for 30 minutes by the whole body cooling, the recovery of EC, state 3 and RCR was observed. The effects of cooling with drugs (dantrolen or methyl-prednisolone) had no consistent effect. These findings suggest that the hyperthermic stress on mitochondrial respiration is focused on complex I in electron transport system.
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PMID:[Liver mitochondrial respiration during hyperthermia]. 257 74


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