Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in microcirculation, the NAD/NADH redox state, and electrical activity during 2 hours of ischemia and 4 hours of reperfusion produced by middle cerebral artery occlusion and release were studied in cats. Twelve animals were classified into three groups of ischemia (mild, moderate, and severe) based on the severity of electrocorticographic (ECoG) depression at the end of the recovery period. Four animals were studied as controls. Occlusion of the middle cerebral artery (MCAO) resulted in a marked but similar degree of reduction in cerebral blood flow (CBF) in all three groups. After this initial change, CBF increased continuously during occlusion in the mild group. CBF in the moderate and severe groups remained at the same low level during the entire period of MCAO. Immediately after MCAO, NAD reduction was increased by approximately 50% in all groups. At the end of MCAO, while the NAD/NADH redox state returned to its pre-ischemic reference level in the severe group, it remained markedly reduced in the mild and moderate groups. Removal of the clip led to slight reactive hyperemia in the mild and severe groups but not in the moderate group. Immediately after recirculation, NAD/NADH redox was shifted toward oxidation in all groups. However, this reoxidation of NADH was only partial in the mild and moderate groups, and a pronounced hyperoxidation occurred in the severe group. In spite of the similar behavior of CBF in the recovery period, a marked secondary NAD reduction occurred in the moderate group during the recirculation period. It is suggested that this represents cessation of mitochondrial electron transport in the dying cells, accompanied by stimulated anaerobic glycolysis in other cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of microcirculatory, NAD/NADH, and electrocorticographic changes in cat brain cortex during ischemia and recirculation. 372 9

The effect of acute hypoxia on adenine nucleotides, glutamate, aspartate, alanine and respiration of heart mitochondria was studied in rats. The losses of intramitochondrial adenine nucleotides (ATP+ADP+AMP) during hypoxia were related to depression of state 3 respiration supported by glutamate and malate, as well as decrease in uncoupled respiration. Hypoxia had less prominent effect on succinate-dependent state 3 respiration. Non-phosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by oxygen deprivation. Glutamate fall in tissue and mitochondria of hypoxic hearts was concomitant with significant increase in tissue alanine and mitochondrial aspartate. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during hypoxia were related to a decrease in mitochondrial glutamate. The results suggest that hypoxia-induced impairment of complex I of respiratory chain and a loss of glutamate from the matrix may limit energy-producing capacity of heart mitochondria.
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PMID:Adenine nucleotides, glutamate and respiratory function of heart mitochondria during acute hypoxia. 375 8

Local cerebral glucose utilization (lCMRgl), NADH fluorescence, cerebral blood flow (CBF), electrocortical activity (ECoG) and histology were studied during a 4 hr recovery period following 2 hrs of left middle cerebral artery (MCA) occlusion in cats. Changes in relative reduced pyridine nucleotides and CBF were measured by fluororeflectometry, ECoG was obtained from the left middle ectosylvian gyrus (MEG), and lCMRgl was measured at the end of the recovery period autoradiographically with 14-C-2-deoxyglucose. A sham group was comprised of 4 cats. The ten animals subjected to the stroke were classified into 3 groups based on the mean amplitude of the ECoG at the end of the ischemic period. At the end of the recovery period, the relative reduced pyridine nucleotides showed a 22.5% oxidation (oxidation of NADH), a 66.2% reduction (reduction of NAD) and a 3.0% reduction compared to the sham group in the severe, moderate and mild groups, respectively. LCMRgl of the left MEG in the severe group was 64.2% of the corresponding sham value, whereas lCMRgl in the moderate and mild groups were 124.8% and 132.0% of the sham, respectively. CBF at the end of the recovery period ranged from 28.1% to 83.0% of the sham value, although there was no significant difference among these groups. Histologically, a large portion of the neurons in the left MEG in the severe group showed ischemic neuronal changes, while the damage was less severe in the moderate and mild groups. On the basis of these data, it is suggested that a relative substrate deficiency and/or a loss of mitochondrial enzymatic pool size may occur in the animals comprizing the severe group. Conversely, anaerobic glycolysis may be activated in the moderate group, while the mild group exhibits an increase in glucose metabolism that is most likely aerobic. A gradient in the magnitude of changes in lCMRgl was noted from the central MCA territory to the surrounding brain regions in the ischemic hemisphere. In addition, there was a mild, but statistically significant (p less than 0.05), depression in lCMRgl with no histological damage in the non-ischemic hemisphere of the severe group.
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PMID:Cerebral glucose metabolism during the recovery period after ischemia--its relationship to NADH-fluorescence, blood flow, EcoG and histology. 376 74

In anaesthetized rats kept on normal diet an i.v. infusion of NAD (200 nmole X kg-1 X X min-1) induced a decrease in renal plasma flow (CPAH), glomerular filtration rate (GFR) and electrolyte excretion accompanied by an increase in plasma adenosine concentration. Separate infusions of a small dose of NAD (50 nmole X kg-1 X min-1) or dipyridamole (25 micrograms X kg-1 X min-1) did not affect renal function or plasma adenosine concentration. However, when the above small doses of both agents were given simultaneously, GFR, CPAH and electrolyte excretion fell significantly, indicating potentiation of NAD action by dipyridamole, associated with increased plasma adenosine level. An i.v. infusion of furosemide failed to abolish the depression of renal function in response to NAD. The data suggest that the causal factor of this depression was adenosine and not NAD itself.
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PMID:Effects of dipyridamole and furosemide on renal function during adenine dinucleotide infusion in rats. 378 6

Anti-My-26, a mouse monoclonal IgG1 antibody, was raised against human granulocytes and has been shown to inhibit luminol-enhanced, glucose-independent chemiluminescence (CL) of human granulocytes (or monocytes) responding to the soluble secretagogues A23187 or ionomycin (calcium ionophores) and phorbol myristate acetate (PMA). Anti-My-26 inhibition of CL was reversible and was dependent on both secretatogue and monoclonal antibody concentration. This inhibition appeared to be directed at the component of granulocyte CL that is independent of NAD(P)H-oxidase-catalyzed formation of superoxide anion, because neither opsonized zymosan-stimulated CL nor the PMA-induced decrease in NAD (P)H-associated autofluorescence was affected by anti-My-26. In addition, ionomycin, over a wide concentration range, failed to generate any decrease in granulocyte autofluorescence. The A23187-induced CL inhibited by anti-My-26 was correlated with its depression of oxygen consumption. Furthermore, anti-My-26 was not cytotoxic and did not itself induce oxidative metabolism when used as a stimulant. Binding of anti-My-26 to phagocytic cells was not decreased by pre-exposure of cells to either A23187 or PMA. Evidence is presented to suggest that the binding of anti-My-26 to the granulocyte surface inhibits the oxidative response to calcium ionophore and PMA by blocking a common pathway(s) stimulated by these different secretagogues.
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PMID:Anti-My-26: a monoclonal antibody inhibiting human phagocyte chemiluminescence. 391 9

Implantation of cobalt-agar rods into the visual cortex of 16 adult rats induced in some of the animals epileptiform bioelectrical activity and provoked in all of them histological and histochemical changes in the region of the implantation (primary focus) as well as in some ipsilateral projection sites of the visual cortex (secondary foci). The changes within the secondary foci are demonstrated in the Corpus geniculatum laterale, pars dorsale (dLGN), by means of 18 histochemical and 5 histological methods. Together with the appearance of hyperactive and degenerating neurones combined with neuronophagy and diminution of the number of synapses a marked gliosis developed, especially an increase of microglia. The destruction of the tissue induced a depression of energy and transmitter metabolism and intensified lytic processes. This is confirmed by the decreased activities of LDH, SDH, GPDH, G6PDH, NAD(P)H-TR, GABA-T and GDH and the increased activity of acid phosphatase in the neuropil of the secondary foci. Single hyperactive nerve and glial cells were accented by high activities of those enzymes which had a reduced activity in the neuropil. Since in our experiments agar-rods without cobalt never induced histological or histochemical changes in subcortical grisea of the visual system, the secondary foci seem to result from the direct influence of the cobalt, migrating in the corticothalamic projection pathway and identifiable in the dLGN by the TIMM technique.
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PMID:[Morphologic and histochemical changes in the secondary focus following cobalt-induced epileptogenic bioelectrical activity of the visual cortex in the adult rat]. 393 55

1. Two-day-old rats were exposed at constant temperature to atmospheres containing air and nitrogen with the air content varied in steps from 100 to 0%. By using this system of graded hypoxia a comparison was made between rates of gluconeogenesis from lactate, serine and aspartate in the whole animal and the concentrations of several liver metabolites. 2. Gluconeogenesis, expressed as the percentage incorporation of labelled isotope into glucose plus glycogen, proceeds linearly for 30min when the animals are incubated in a normal air atmosphere, but is completely suppressed if the atmosphere is 100% nitrogen. 3. Preincubation of animals for between 5 and 30min under an atmosphere containing 19% air results in the attainment of a new steady state with respect to gluconeogenesis and hepatic concentrations of ATP, ADP, AMP, lactate, pyruvate, beta-hydroxybutyrate and acetoacetate. 4. When lactate (100mumol), aspartate (20mumol) or serine (20mumol) was injected, it was shown that the more severe the hypoxia the greater the depression of gluconeogenesis. Under conditions when gluconeogenesis was markedly inhibited there were no changes in the degree of phosphorylation of hepatic adenine nucleotides, but free [NAD(+)]/[NADH] ratios fell in both cytosol and mitochondrial compartments of the liver cell. 5. Measurements of total liver NAD(+) and NADH showed that the concentrations of these nucleotide coenzymes changed less with anoxia, in comparison with the concentration ratio of free coenzymes. 6. Calculations showed that the difference in NAD(+)-NADH redox potentials between mitochondrial and cytosol compartments increased with the severity of hypoxia. 7. From the constancy of the concentrations of adenine nucleotides it is concluded that liver of hypoxic rats can conserve ATP by lowering the rate of ATP utilization for gluconeogenesis. Gluconeogenesis may be regulated in turn by the changes in mitochondrial and cytosol redox state.
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PMID:Regulation of gluconeogenesis during exposure of young rats to hypoxic conditions. 433 87

The diabetogenic activity of streptozotocin has been correlated with a reduction in pyridine nucleotide synthesis in the mouse pancreatic islet. To determine the specificity of this reduction for diabetogenicity, a comparative study of streptozotocin, its cytotoxic moiety, 1-methyl-1-nitrosourea, and alloxan was performed. Streptozotocin administered intraperitoneally (i.p.) producd a dose-related reduction in islet NAD which was proportional to the degree of diabetogenicity. A diabetogenic dose, 200 mg/kg, attained a peak plasma N-nitroso intact streptozotocin concentration of 0.224 mumol/ml and reduced the mean islet NAD from a control of 0.78 to 0.15 pmol. At borderline, 150 mg/kg, and nondiabetogenic, 100 mg/kg, doses, plasma concentrations reached 0.161 and 0.136 mumol/ml, and NAD was 0.36 and 0.86 pmol/islet, respectively. 1-Methyl-1-nitrosourea, 100 mg/kg, attained a maximum N-nitroso intact 1-methyl-1-nitrosourea concentration of 0.162 mumol/ml and reduced the mean NAD to 0.58 pmol/islet, and was nondiabetogenic; 200 mg/kg attained a peak plasma concentration of 0.344 mumol/ml and depressed NAD to 0.38 pmol/islet, and was inconsistently diabetogenic. Islet NAD of 0.4 pmol/islet or greater is required for integrity of the beta cell. A diabetogenic dose of alloxan, 500 mg/kg, did not depress NAD, 0.85 pmol/islet, therefore confirming that its mechanism of diabetogenicity differs from that of streptozotocin. In vivo uptake of [methyl-(14)C]streptozotocin by islets was 3.8 times that of [methyl-(14)C]-1-methyl-1-nitrosourea, whereas uptake by the exocrine pancreas favored 1-methyl-1-nitrosourea over streptozotocin 2.4:1. The decreased islet uptake of 1-methyl-1-nitrosourea correlates with the 3.5 times increased molar dosage required to produce islet NAD depression comparable to that of streptozotocin, 150 mg/kg. These studies indicate that the glucose carrier of streptozotocin facilitates uptake of its cytotoxic group, 1-methyl-1-nitrosourea, into islets.
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PMID:Streptozotocin diabetes. Correlation with extent of depression of pancreatic islet nicotinamide adenine dinucleotide. 436 17

Rats fed a synthetic diet containing 0.25% benzamide, 0.1% phenobarbital, separately or in combination, for two weeks showed a significant augmentation in the activity of nuclear poly(ADP-ribose) polymerase as well as changes in various nuclear, microsomal and cytosolic liver enzymes involved in the metabolism of xenobiotics. A selective depression of microsomal styrene oxide hydrolase activity by benzamide feeding, and a contrasting augmentation by phenobarbital, were confirmed by immunological titration of the enzyme-protein content suggesting actual enzyme repression and induction. The NAD content of these livers is not altered significantly as a result of benzamide and phenobarbital feeding, indicating that the changes in enzymes are not a result of non-specific toxic effects.
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PMID:The in vivo effect of benzamide and phenobarbital on liver enzymes: poly(ADP-ribose) polymerase, cytochrome P-450, styrene oxide hydrolase, cholesterol oxide hydrolase, glutathione S-transferase and UDP-glucuronyl transferase. 608 14

Using histochemical techniques, the reactivities of selected enzymes and other metabolic components were examined in the myocardium, coronary arteries, and coronary arterioles of normal, two-week-sympathectomized, and sham-operated canine hearts. There were no differences in the histochemistry of coronary arteries in any of the hearts, but important differences were noted in the myocardium and especially in the arterioles. The reactivities of the enzyme glucose-6-phosphate dehydrogenase and the nucleic acids were increased in arterioles of the sympathectomized heart, possibly indicating an increased protein synthesis. The reactivities of succinate dehydrogenase, NAD-isocitrate dehydrogenase, and cytochrome oxidase were reduced in myocardium and arterioles of sympathectomized hearts as well as in arterioles of sham-operated hearts; the changes were greater in the sympathectomized arterioles where there was also observed an increase in reactivity of lactate dehydrogenase. These findings suggest a depression in aerobic metabolic capacity and, in the case of the sympathectomized arteriole, imply a possible shift in adaptation from aerobic to anaerobic metabolism.
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PMID:The myocardium and its vasculature: a histochemical comparison of the normal and chronically sympathectomized dog heart. 615 74


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