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)

Blood pressure (BP) decreases significantly in patients with immune complex nephritis and hypertension in the course of therapeutic plasma exchange (TPE). To investigate possible underlying mechanisms of this effect, the variations of supine and upright BP and plasma renin activity (PRA) acutely induced by PE (performed by isovolumetric replacement of plasma with 4% albumin in saline solution) were analyzed in six patients. On the average, both supine and upright BP decreased after TPE; however, statistical significance was obtained only for upright systolic BP. Supine and upright PRA did not change significantly, although a clearly blunted response to posture was observed in three patients. The changes of BP induced by TPE were apparently not due to a functional depression of the renin-angiotensin system, since the more marked decrements in BP were observed in the patients with lower basal PRA.
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PMID:Acute effect of plasma exchange on arterial blood pressure and plasma renin activity. 293 91

Nephrotoxicity is a serious side effect that limits the use of cyclosporine (CyA) as an immunosuppressive agent. The purpose of this study was to develop a model of CyA nephrotoxicity in the isolated perfused rat kidney and to evaluate the effects of adenosine triphosphate (ATP)-MgCl2 and verapamil treatment on this model. Kidneys were perfused for 90 minutes in a 7.5% albumin-Krebs-HCO3 solution containing 3H-inulin (glomerular marker) and 5.0 micrograms/ml 14C-cytochrome C (cyt) (marker of tubular protein absorption). After 10-minute equilibration, perfusate and urine samples were collected with 10-minute clearance periods. After two control clearance periods, 500 ng/ml CyA was added to the perfusate. In some experiments, 1 micrograms/ml of verapamil was added 10 minutes before CyA and in others 2 mmol/l ATP-MgCl2 was added with CyA. Cyt and inulin radioactivity, [Na+] and [K+], were measured in perfusate and urine. Tissue ATP levels were also determined. The results demonstrate that CyA treatment leads to a marked depression of glomerular filtration rate (GFR), tubular absorption of protein, urine output, and renal flow. ATP-MgCl2 cotreatment improved GFR, tubular absorption, and renal perfusate flow but the increase in urine output was not dramatic. Verapamil pretreatment markedly improved GFR and urine and renal perfusate flow but not tubular function. The combination of verapamil and ATP-MgCl2 treatment with CyA returned GFR to control values, significantly improved tubular absorption, urine and renal perfusate flow, and enhanced renal tissue ATP of isolated kidneys to levels seen in vivo. These data lead us to conclude that ATP-MgCl2 cotreatment with CyA after verapamil pretreatment greatly reduces the nephrotoxic potential of this immunosuppressive agent.
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PMID:Treatment with verapamil and adenosine triphosphate-MgCl2 reduces cyclosporine nephrotoxicity. 295 Jun 8

Receptors for polymerized human albumin are found at high titres during high-level hepatitis B virus (HBV) replication and in small amounts in chronic low-level infection. Complexes between hepatitis B surface antigen (HBsAg) and IgM without specificity for HbsAg are expressed in a pattern similar to that of receptors. Anti-albumin antibodies could be involved in their formation. Delta infection depresses the synthesis of gene products of HBV. To assess whether delta modifies the expression of receptors on HBsAg and the level of HBsAg/IgM complexes, and if anti-albumin antibodies are actually part of the complex, we tested sera from 86 subjects with acute and chronic HBV infection. Our findings show that the amounts of circulating receptors and HBsAg/IgM are proportional to the concentration of HBsAg and thus probably to the degree of viral replication. We did not find any correlation between circulating anti-albumin antibodies of the IgM class and HBsAg/IgM complexes. Delta infection depresses HBsAg synthesis and causes a related decrease in receptors and HBsAg/IgM titres if superimposed on the more active stage of HBV infection. When HBsAg, receptors, and HBsAg/IgM are at low levels, no further depression is caused by delta infection. HBsAg/IgM titre is not enhanced by presence of anti-delta antibodies, thus excluding a role of the latter in forming these complexes.
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PMID:Polyalbumin receptors, hepatitis B surface antigen (HBsAg), and HBsAg/IgM complexes in HBsAg positive patients with and without delta superinfection. 298 29

In our clinical trial we have compared the effect of high doses of prednisone, ACTH alone or ACTH and cyclophosphamide on plasma and CSF albumin and IgG levels. We have found that the treatment with high doses of prednisone is more effective in the suppression of CNS IgG synthesis than ACTH, or cyclophosphamide. However the significance of this immunological phenomenon in the pathogenesis of MS is a very complex problem, since we have not observed any correlation between the depression of the intrathecal IgG synthesis and clinical results of MS treatment.
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PMID:Therapeutic trials of multiple sclerosis and intrathecal IgG production. 301

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.
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PMID:Buspirone: an update on a unique anxiolytic agent. 304 84

The lipid peroxidation product 4-hydroxynonenal (HNE) and homologous aldehydes have been found to possess chemotactic activity for rat neutrophil leukocytes in the micromolar to picomolar range, depending on the compound. Such an activity is displayed only in the presence of albumin. The mechanisms by which aldehydes could interact with neutrophils are discussed. It is proposed that albumin acts as a carrier for the aldehyde and releases them to a neutrophil receptor. At concentrations around 10(-4) M, 4-hydroxyalkenals have been found to exert toxic effects on a number of cells, including a strong depression of neutrophil motility. Finally, HNE has been found at chemotactic concentrations in the inflammatory site. The possibility that HNE is involved in the neutrophil influx into the inflammatory site is considered.
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PMID:Interaction between neutrophils and 4-hydroxyalkenals and consequences on neutrophil motility. 306 19

The size of the soluble form of the human cerebrospinal fluid (CSF) neural cell adhesion molecule, NCAM-sol, was by gel permeation chromatography estimated to 160-250 kDa. Within the CSF the concentration of NCAM-sol was found about 15-25% increased in lumbar fluid and 25% increased in ventricular fluid, both compared to cisternal fluid. Whereas prealbumin was found evenly distributed in CSF, albumin was relatively enriched in lumbar fluid. The concentrations of NCAM-sol and prealbumin were measured in lumbar CSF from psychiatric patients. Prealbumin was increased 7.2% and NCAM-sol was decreased 15.1% in depressed patients. The changes were partially normalized during recovery from the depression. The findings can be explained by hypothesizing that endogenous depression is associated with an increased choroid plexus activity and CSF production.
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PMID:Neural cell adhesion molecule (NCAM) and prealbumin in cerebrospinal fluid from depressed patients. 306 38

A concern for the possible role of the blood-brain barrier (BBB) in the epilepsies was based on ultrastructural studies that demonstrated increased micropinocytosis in cerebral capillaries during seizures. Continued interest in the structure of the BBB has led to the demonstration that, in human psychomotor epilepsy, there is a thickening of the capillary basement membrane. These studies also suggest that an increase in capillary mitochondria and interendothelial tight junctions may characterize seizure-traumatized brain regions. These studies forecast an increased interest and understanding of the ultrastructural events associated with capillaries in seizure states. Additional focus on the BBB comes from the clinical use of anticonvulsant drug levels in the control and treatment of seizures. Debate as to whether free drug levels are appropriate continues. The brain capillary is the interface between blood-borne drug and the target site, and thus an increased understanding of the events associated with brain-plasma exchange has been sought. The concept that only that fraction of drug that is freely dialyzable is available for equilibration across the BBB is not supported by recent studies, which demonstrate that protein-bound ligands are able to dissociate and gain access to the brain in the course of a single capillary transit. It has been established that albumin-bound fatty acids, steroids, and anticonvulsant drugs more readily distribute into tissues than previously believed. Thus, traditional free drug hypotheses need to be expanded to account for the fact that dissociation constants measured in vitro are not the same as those measured in vivo. The BBB also regulates nutrient availability to the brain, and under normal conditions excess substrate is made available to the brain for metabolism. Indirect evidence is available to suggest that during seizures, BBB transport may indeed be the rate-limiting step. Specifically, glucose availability to the seizing brain may be restricted to such a degree that brain glucose utilization rates are no longer independent of plasma glucose levels. If it can be proven that BBB transport is the rate-limiting step during seizures, then it would be possible to augment brain glucose utilization rates by increasing plasma glucose levels. In addition, a depression of brain glucose utilization could be achieved by inducing hypoglycemia. It is not fully understood whether BBB rate limitation would persist postically, nor is it known whether BBB alterations may be global or restricted to the seizure focus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epilepsy and the blood-brain barrier. 308 37

A micro-technique was developed to measure fatty acid oxidation in vitro and to investigate its possible derangement in alcoholic fatty liver disease. Percutaneous liver biopsy specimens were obtained from nine control subjects and 28 alcoholic patients with mild to severe fatty liver. Fresh tissue (10-15 mg) was incubated at 37 degrees C for 90 min in a sealed reaction flask containing 1.92 mmol/l [1-14C]palmitic acid (1-2 microCi) and 1% essentially fatty acid free albumin in Krebs-Henseleit buffer, pH 7.4. Radiolabelled CO2 and perchloric acid-soluble ketone bodies were isolated and counted. CO2 production was markedly reduced in alcoholic patients with mild and severe fatty liver compared with controls. This depression was reversed by the addition of malate to the reaction flask but not by carnitine or coenzyme A. Ketone body production was similar in controls and patients with mild and severe fatty liver. After the incubation in vitro, the tissue was extracted with chloroform/methanol and the triglyceride fraction isolated by thin layer chromatography and counted for radioactivity. The rate of palmitic acid incorporation into triglyceride was higher in alcoholic patients, particularly those with severe fatty infiltration, compared with controls. It is suggested that alcoholic fatty liver is accompanied by a progressive reduction in palmitic acid oxidation with the major defect occurring in the tricarboxylic acid cycle. In contrast, the rate of palmitic acid esterification into triglyceride is enhanced.
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PMID:Palmitic acid oxidation and incorporation into triglyceride by needle liver biopsy specimens from control subjects and patients with alcoholic fatty liver disease. 309 34

Hyperoxia and severe hypoxia are known to depress tracheal mucus flow in vivo. It is not clear, however, whether this is also seen in bronchial mucociliary transport system. The author attempted to ascertain acute effects of hyperoxia and moderate hypoxia on bronchial mucociliary clearance by analyzing the regional clearance of aerosolized radioactive tracers within the lung. Eleven healthy persons were exposed to pure oxygen or moderate hypoxia (mean end-tidal PaO2 57.5 mmHg) for 30 min. Twenty four patients with chronic pulmonary emphysema were studied for the chronic effect of hypoxemia on regional mucociliary clearance. They had slight hypoxemia (mean PaO2 76 mmHg). After inhalation of 99mTc-albumin aerosols, clearance of deposited aerosols was quantified as a function of time. The results were analyzed for whole right lung in the acute hyperoxic and hypoxic studies, and for 3 concentric areas representing central, mid, and peripheral regions of the right lung in the study of patients. In healthy subjects, breathing pure oxygen caused significant depression that started 30 min after the initiation of oxygen exposure and was kept up even after stopping the exposure. The clearance was significantly impaired during exposure to moderate hypoxia, though it seemed to be transient. The patients with chronic pulmonary emphysema had a significantly lower clearance in the central region than that in asymptomatic smokers (p less than 0.01). There was no significant correlation, however, between the degree of hypoxemia and the regional clearance. These results suggest that 1) acute exposure to pure oxygen and moderate hypoxia causes bronchial mucociliary dysfunction in humans, 2) the patients with chronic pulmonary emphysema have a lower clearance in the central region of the lung than asymptomatic smokers, and 3) chronic slight hypoxemia has no apparent effect on bronchial mucociliary clearance.
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PMID:[Influence of hyperoxia and hypoxia on bronchial mucociliary clearance]. 322 Apr 40


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