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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of normal mitochondria at 45 degrees C results in increases of respiration and of total apparent proton conductance (TAPC, respiration/proton motive force) and in an upward shift of the flow-force relationships. Similar effects are observed during operation of the redox proton pumps at different sites of the respiratory chain. These effects are accompanied by an almost equivalent increase of the passive proton conductance (PPC, proton leakage/proton motive force). In mitochondria from 3,3,5-triiodo-L-thyronine (T3)-treated rats there are also increases of respiration and of TAPC and an upward shift of flow-force relationships, more pronounced at the level of the cytochrome oxidase proton pump. However, at variance from the incubation at 45 degrees C, in mitochondria from T3-treated rats there is only a slight increase of PPC. Addition of bovine serum albumin to normal mitochondria incubated at 45 degrees C results in a marked depression of TAPC in the nonlinear range of the flow-force relationships. An equivalent effect is not observed in mitochondria from T3-treated rats. The experimental results have been compared with computer simulations obtained on the basis of a chemiosmotic model of energy transduction. The increase of TAPC following incubation at high temperature is apparently due to changes of the proton conductance mainly at the level of PPC, while the increase of TAPC following T3 administration is rather due to changes presumably at the level of the redox or ATPase proton pumps.
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PMID:Mechanism of loss of thermodynamic control in mitochondria due to hyperthyroidism and temperature. 163 81

The effect of inhibitors of proton pumps, of uncouplers and of permeant ions on the relationship between input force, delta mu H+, and output flows of the ATPase, redox and transhydrogenase H(+)-pumps in submitochondrial particles was investigated. It is concluded that: (1) The decrease of output flow of the transhydrogenase proton pump, defined as the rate of reduction of NADP+ by NADH, is linearily correlated with the decrease of input force, delta mu H+, in an extended range of delta mu H+, independently of whether the H(+)-generating pump is the ATPase or a redox pump, or whether delta mu H+ is depressed by inhibitors of the H(+)-generating pump such as oligomycin or malonate, or by uncouplers. (2) The output flows of the ATPase and of the site I redox H(+)-pumps exhibit a steep dependence on delta mu H+. The flow-force relationships differ depending on whether the depression of delta mu H+ is induced by inhibitors of the H(+)-generating pump, by uncouplers or by lipophilic anions. (3) With the ATPase as H(+)-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by malonate than by uncouplers; the latter, however, are more inhibitory than lipophilic anions such as ClO4-. With redox site I as proton-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by oligomycin than by uncouplers; again, uncouplers are more inhibitory than ClO4-. (4) The results provide further support for a delocalized interaction of transhydrogenase with other H(+)-pumps.
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PMID:Flow-force relationships during energy transfer between mitochondrial proton pumps. 164 34

Addition of bovine serum albumin to state 4 mitochondria results in a depression of the proton leak and of the resting respiration of 70 and 25%, respectively. The conductance membrane potential diagram, both in the ohmic and in the non-ohmic region, shows that in the presence of bovine serum albumin the level of ohmic conductance is lowered while that of non-ohmic conductance is increased toward higher delta psi values. The same effect is observed during operation of the different proton pumps. Addition of chloroform affects the conductance membrane potential diagram in the following manner: there is no effect in the ohmic region with all pumps, while there is an effect in the non-ohmic region either at site III or at sites II plus III but not at site II. This suggests a possible effect of chloroform at the level of the cytochrome oxidase proton pump. During titration with oligomycin of the ATPase proton pump the conductance potential diagram shows a region of non-ohmicity only in the presence but not in the absence of an ATP-regenerating system. Protonophoric uncouplers such as carbonyl cyanide p(trifluoromethoxy)phenylhydrazone and intrinsic uncouplers such as chloroform have different effects on the relationship between rates of charge translocation and of oxygen consumption, and thus on the pump stoichiometries, in that the slope of the diagram is modified by the latter but not by the former. The differential effects of protonophores and of intrinsic uncouplers on the stoichiometries have been analyzed by computer simulations and represent an additional criterion to distinguish between extrinsic and intrinsic mechanisms of uncoupling.
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PMID:Flux ratios and pump stoichiometries at sites II and III in liver mitochondria. Effect of slips and leaks. 184 85

Addition of gramicidin D to liver mitochondria, incubated in low- or high-salt media, results in stimulation of respiration in the absence or presence of depression of delta muH, respectively. Gramicidin D concentrations 2 orders of magnitude higher are required in the low-salt media with full uncoupling at 1 nmol of gramicidin.mg-1. The stimulation of respiration is not accompanied by increased passive proton influx in low-salt media. In high-salt media, the extent of respiratory stimulation and the extent of delta muH depression differ according to the nature and concentration of cation. The flow-force relationship is very steep when gramicidin D induced uncoupling occurs in low-salt media and much less steep in high-salt media. A multiplicity of flow-force relationship, respiratory rate vs delta muH, is obtained, the slope of which depends on the nature and concentration of cation, and which can be reproduced by computer simulation by introducing a variable extent of proton cycling either in the membrane or in the pump. The apparent proton conductance, as analyzed in the relationship of Je/delta muH vs delta muH, increases in the so-called ohmic and nonohmic regions according to whether gramicidin D is added in high-salt or low-salt media, respectively. Titration with antimycin of the respiratory control ratio (RCR) in gramicidin D treated mitochondria leads to a depression of the RCR in high-salt but not in low-salt media. The view is discussed that in low-salt media the gramicidin D induced uncoupling is due to a cycling of protons within a proton domain operationally located at or near the proton pump.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nature of proton cycling during gramicidin uncoupling of oxidative phosphorylation. 246 64

The activity of H,K-ATPase, the gastric acid producing enzyme, was concentration dependently inhibited by verapamil in the mM range. Verapamil concentration dependently inhibited acid formation in gastric glands, measured as [14C]aminopyrine accumulation or oxygen consumption. The IC50 values were in the microM range. No inhibition of acid secretion by verapamil was observed in Heidenhain-pouch dogs and stomach-lumen-perfused rats. However, in pylorus-ligated rats an inhibition was observed, this effect is related to its cardiovascular effectiveness. To understand the action of verapamil, its physicochemical properties were considered. Verapamil is a highly lipophilic base with a pKa of 8.7. It accumulates in membranes and in the acidic spaces of the parietal cell. We suggest that the inhibition of vesicular bound H,K-ATPase is dependent on a non-specific accumulation of verapamil in the membrane (detergent effect) and that inhibition of acid production in vitro is due to an additional accumulation of the drug in acidic compartments, leading to an impaired function of the proton pump. Verapamil does not decrease acid secretion in vivo by this mechanism as the required dose would be higher than the dose that causes a strong depression of the cardiovascular system.
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PMID:Effects of verapamil on gastric acid secretion in vitro and in vivo. 285 Sep 32

We examined the effect of proton pump inhibitor omeprazole on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintained at about 50% with intravenous (i.v.) bolus and infusion regimens of either atracurium or succinylcholine. Omeprazole, 0.5, 1, and 10 mg/kg i.v., was then administered at 10-min intervals while the infusion of the neuromuscular blocker was continued. Omeprazole at all three doses increased the steady-state neuromuscular paralysis produced with either atracurium (pre-omeprazole versus final post-omeprazole paralysis; mean +/- SE, n = 6, 53.0% +/- 2.3% vs 80.0% +/- 5.3%) or succinylcholine (50.8% +/- 1.5% vs 86.4% +/- 5.1%). Omeprazole, 0.5, 1.0, and 10 mg/kg i.v., given directly and without any neuromuscular blocker, produced approximately 5% depression of the muscle twitch response. Omeprazole, i.v. at human therapeutic doses, alters neuromuscular function and enhances the action of both atracurium and succinylcholine in vivo in rats.
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PMID:Omeprazole potentiates atracurium and succinylcholine paralysis in vivo in rats. 810 72

A total of 34 children with normal renal function underwent either gastrocystoplasty or continent urinary reservoirs with stomach at our institutions. Severe hypochloremic hypokalemic metabolic alkalosis developed in 2 patients, manifested by intractable seizure disorder in 1 and altered mental status with respiratory depression in 1. Symptoms developed at 4 and 6 months, respectively. Despite severe alkalosis, urinary pH was less than 5.0 and fractional excretion of chloride remained high in both patients. Resuscitation with sodium chloride, arginine hydrochloride and potassium chloride restored electrolyte balance in less than 48 hours in both patients. Serum gastrin was slightly elevated in 1 patient (137 pg./ml., normal 0 to 125) who responded to long-term histamine-blocker therapy. The other patient had significant hypergastrinemia (624 pg./ml.) with secondary hyperaldosteronism. Maximum doses of histamine blockers, oral replacement of sodium chloride and potassium chloride, and the proton pump inhibitor omeprazole failed to control recurrent bouts of severe hypochloremic metabolic alkalosis. This patient ultimately underwent removal of three-quarters of the gastric augmentation and replacement with ileum. Postoperatively, serum gastrin levels and electrolytes reverted to normal. The pathophysiology of this potentially lethal complication is further discussed.
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PMID:Metabolic complications of the use of stomach for urinary reconstruction. 832 30

We have analyzed the effects of n-hexane, 1-hexanethiol, and 1-hexanol on the coupled respiration of rat liver mitochondria. Incubation of mitochondria with n-hexane, 1-hexanethiol and 1-hexanol resulted in a stimulation, at low concentrations, and an inhibition, at high concentrations, of the state 4 mitochondrial respiration. Three criteria, all based on the comparison with the effect of DNP, have been used to establish whether the stimulation of respiration, at low concentrations of n-hexane, 1-hexanethiol, and 1-hexanol, depends on protonophoric mechanisms. First, the quantitative relationship between the extents of respiratory stimulation and membrane potential depression: a strong decrease of membrane potential was induced by increasing concentrations of DNP and a negligible depression by increasing concentrations of n-hexane or 1-hexanethiol. Only a slight decrease was induced by 1-hexanol. Second, the quantitative relationship between the extents of respiratory stimulation and of proton conductance increase: at equivalent rates of respiration, the enhancement of the proton conductance induced by DNP was very marked, by n-hexane and 1-hexanethiol practically negligible, and by 1-hexanol much smaller than that induced by DNP. Third, in titrations with redox inhibitors of the proton pumps, the pattern of the relationship between proton pump conductance and membrane potential was markedly different from protonophoric and non-protonophoric uncouplers: almost linear in the case of DNP, highly non-linear in the case of n-hexane, 1-hexanethiol and 1-hexanol. These three criteria support the view that n-hexane, 1-hexanethiol, and partially 1-hexanol, uncouple mitochondrial respiration by a non-protonophoric mechanism.
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PMID:The nature of uncoupling by n-hexane, 1-hexanethiol and 1-hexanol in rat liver mitochondria. 864 93

All patients who are candidates for laparoscopic fundoplication for the treatment of gastroesophageal reflux disease (GERD) should have a symptom review, barium swallow imaging, endoscopy, esophageal manometry, and ambulatory pH monitoring. The presence of a typical primary symptom, an abnormal 24-hour pH score, and a good response to acid-suppression therapy are predictive of a successful surgical outcome. The surgeon should be particularly wary of the following types of patients who may be referred for fundoplication but not have GERD: those who do not respond to proton pump inhibitors, those without esophagitis, those with only atypical symptoms, those in whom pH monitoring was done without previous manometry, and those with a borderline reflux score, severe vomiting, severe dysphagia and heartburn, unusual symptoms, severe depression, or morbid obesity.
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PMID:Preoperative evaluation of patients with gastroesophageal reflux disease. 1181 22

A 65-yr-old man treated for depression was transferred to our hospital. He ingested over 150 ml of formalin for suicidal attempt. On admission, he was hypotensive, developing acute renal failure and liver dysfunction. During first 36 hours, he needed 21 l of lactate Ringer solutions to maintain enough urination. The abdominal computed tomography showed obvious edema of intestine and endoscopic findings of the upper digestive tract were corrosive erosions. We started proton pump inhibiter on the first day. After a week, they changed in many ulcers with smooth-surfaced elevation on the greater curvature of the stomach. On the 15th hospitalized day, he was discharged from our hospital without sequelae. Formalin consists of forty percent solution of formaldehyde and methanol. Ingestion of formaldehyde may cause burning in the digestive systems and harmful effect to major organ such as kidney or liver. Although previous reports said that formalin has direct toxicity to major organs, we could discharge him without sequelae by treatment with large amount of fluid resuscitation.
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PMID:[Intestinal edema caused by ingested formalin]. 1474 May 67


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