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)

Heme oxygenase, the rate-limiting enzyme for heme degradation, can be inhibited by several new synthetic metalloporphyrins. Under certain conditions, a depression in heme oxygenase activity has important clinical significance in the treatment of hyperbilirubinemia, and, in this regard, tin-protoporphyrin has been shown to decrease the production of bilirubin in vitro as well as in vivo. Similarly, our study was concerned with finding a new metalloporphyrin which will inhibit heme oxygenase. Many of the synthetic heme analogs that we analyzed were quite effective inhibitors of heme oxygenase, but the most powerful inhibitor was found to be zinc-deuteroporphyrin IX, 2,4-bisglycol. This metalloporphyrin almost completely inhibits liver heme oxygenase at concentrations as low as 0.5 microM. Its potency as an inhibitor was found to be greater than that of tin-protoporphyrin; the Ki of zinc-deuteroporphyrin IX, 2,4-bisglycol was calculated to be 0.003 microM. In conclusion, we demonstrated that zinc-deuteroporphyrin IX, 2,4-bisglycol has potent inhibitory effects on human liver, kidney and brain heme oxygenase so that this metalloporphyrin can be considered as an alternative to tin-protoporphyrin in the treatment of hyperbilirubinemia.
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PMID:Sensitivity of human tissue heme oxygenase to a new synthetic metalloporphyrin. 275 52

Some parameters of haem synthesis were estimated in 60 uraemic patients (30 non-dialysed, 30 dialysed) and in 30 matched controls. Serum delta-aminolaevulinic acid and erythrocyte coproporphyrin and protoprophyrin were found significantly higher in the non-dialysed uraemics than in the controls. Erythrocyte delta-aminolaevulinic acid dehydrase (ALA-D) activity was 498 +/- 174 mumol/h.l in the non-dialysed patients, 321 +/- 146 in the dialysed (just before haemodialysis) and 833 +/- 281 in the healthy controls, the differences between these groups all being statistically significant (p less than 0.001). After haemodialysis the enzymic activity in the dialysed group increased significantly (380 +/- 167, p less than 0.001), but remained lower than normal (p less than 0.001). A similar pattern - although with less statistical significance of the differences between groups - was observed concerning erythrocyte uroporphyrinogen I synthase activity. Incubation of normal erythrocytes with uraemic plasma resulted in a considerable decrease of their ALA-D activity (from 830 +/- 263 to 616 +/- 126) while incubation of uraemic erythrocytes with normal plasma increased their ALA-D (from 384 +/- 139 to 494 +/- 77). Addition of zinc in the haemolysate caused a similar induction of ALA-D in both controls and uraemics. The zinc-induced uraemic ALA-D practically reached normal levels. The mechanism of enzymic depression and the possible role of elevated delta-aminolaevulinic acid concentrations (to which depressed ALA-D activity considerably contributes) in the pathogenesis of the neurologic manifestations of uraemia, are discussed.
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PMID:Some parameters of haem synthesis in dialysed and non-dialysed uraemic patients. 285 53

The efficacy of evoked ACh release by intact and newly sprouted terminals in response to partial denervation and expansion of the motor neuron terminal field was studied in mouse soleus muscle after section of the L-5 spinal root. From 2 to 4 d after partial denervation until 90 d later, only 3-7 motor units of the normal 21 remained. Regeneration of the dissected nerve was prevented while the remaining motor units were sprouting. The indirect twitch, which was only 20% of direct twitch tension 2-4 d after nerve section, recovered between 28 and 50 d postoperatively. However, the depression of twitch in low Ca/high Mg solution, which was equal to control 2-3 d postoperatively, was 2-3 times more depressed than control by 50 d and remained so up to 90 d. This indicated persistent reduction of the safety factor in sprouted motor units. Intracellular measurement of quantal content in 0.4 mM Ca, 2.75 mM Mg revealed 2 groups of nerve terminals in partially denervated muscle. The quantal content of the first group was greater than contralateral control at earlier times (28-50 d) and only slightly greater than control later (74 and 90 d). This group consisted of the original undenervated terminals, since it was associated with normal miniature endplate potential (MEPP) frequency and end-plate potential (EPP) latency, and presumably with the class of fibers with normal (zinc iodide osmium-stained) nerve terminal morphology and occasional large myelinated preterminal axons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of partial denervation and terminal field expansion on neuromuscular transmitter release and nerve terminal structure. 289 99

A new approach to pathogenetic study of hepatic encephalopathy was recently undertaken in order to identify the neurological alterations of the brain which characterize the coma. In this study attention was firstly addressed to a correct and objective evaluation of the comatose state in rats with fulminant hepatic failure induced by galactosamine. For this purpose visual evoked potentials were utilized since this electrophysiological test proved reliable and sensitive on the basis of an extensive pharmacological study. Two different stages of coma were identified in the rat and they were named mild and severe. Receptor binding studies performed on brain membranes of these rats show in the mild stage an increased number of low and high affinity GABA receptors and a decreased affinity of dopamine receptors. The severe stage is characterized by the persistence of only high affinity GABA receptors and a reduced number of dopamine receptors. This imbalance between inhibitory and excitatory receptor systems may explain the generalized central nervous system depression which characterizes the hepatic encephalopathy while the increased number of benzodiazepine receptors found in both stages of coma may account for the brain supersensitivity to sedative administration of patients with liver disease and for the sedative-induced episodes of coma. These receptor alterations may be attributed to a disuse and/or a partial degeneration of nerve terminals due to peripheral neurotoxins (i.e., ammonia, mercaptans, short chain fatty acids) and the decrease of glutamate decarboxylase activity and of zinc levels in brain tissues seems to be respectively a direct and an indirect demonstration of this phenomenon. Bearing in mind the supersensitivity of the GABA-benzodiazepine receptor system and their reciprocal interaction, a benzodiazepine antagonist was administered to rats in mild stage of encephalopathy. Electrophysiological and benzodiazepine binding studies demonstrated that this treatment can temporarily counteract some of the neurological disturbances of the earlier stage of coma and act as antidote of the sedative-induced episodes of coma.
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PMID:Hepatic encephalopathy. Experimental studies in a rat model of fulminant hepatic failure. 299 24

Zinc ions, which are unevenly distributed in the CNS and can be released from nerve terminals, have been implicated as causative agents in epileptogenesis. The present study has shown that intraventricular administration to anesthetized rats causes seizure activity of the ECOG and convulsions. Since the manner in which zinc influences neuronal activity and triggers convulsions is unclear, studies were also made of its effect on spontaneous and evoked activity in the rat forebrain. It was found that iontophoretic application of zinc to cortical neurons causes slow and often prolonged increases in firing rate, usually accompanied by bursts of high frequency discharge in just under half the studies. Another cation, barium, evoked excitatory responses of a similar type and a reduction in potassium permeability may underlie the effects of both cations. In contrast, calcium, magnesium, manganese and cerium caused short duration depressant effects. The depression induced by calcium, but not by the other cations, could be blocked by zinc. Similarly, in the hippocampus zinc depressed calcium-dependent potentiation in subfield CA3 evoked by paired-pulse stimulation of mossy fibers; excitatory effects (namely an increase in spike amplitude and appearance of multiple population spikes) were seen at higher zinc concentrations. The depressant effects of an enkephalin analog on cortical firing rate were also blocked by zinc, consistent with studies from another laboratory suggesting enkephalin/zinc interactions. In contrast, the depressant effect of GABA could not be blocked by zinc, although an antagonism has been reported in the lobster muscle. Firm conclusions regarding the mechanism(s) underlying the triggering of seizure activity by zinc cannot yet be drawn, but the results of these studies would be consistent with an interference with calcium and/or potassium ion activity rather than with GABA binding sites.
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PMID:Effect of zinc on neuronal activity in the rat forebrain. 302 63

Regulation of zinc metabolism by dibutyryl cAMP, glucagon, and epinephrine was examined in rats fed adequate amounts of zinc. Dibutyryl cAMP, epinephrine, and glucagon each produced an increase in liver metallothionein levels by 10 h after they were first administered. The increase in liver metallothionein was inversely related to the serum zinc concentration. Treatment with dexamethasone, a glucocorticoid, accentuated these effects to some extent. Both metallothionein I and II were induced by dibutyryl cAMP and glucagon. Levels of metallothionein mRNA in total liver RNA extracts were measured by dot blot hybridization using a synthetic 21-base oligonucleotide complimentary to the 5' region of both the metallothionein I and II genes. Individual administration of dibutyryl cAMP, glucagon, and epinephrine increased the number of metallothionein mRNA molecules per cell by up to fourfold. The data suggest that glucagon and epinephrine are primary regulators of metallothionein gene expression acting at least in part via cAMP. In adrenalectomized rats, glucagon, dibutyryl cAMP, and epinephrine had a less potent effect in terms of metallothionein induction and depression of serum zinc concentrations. These effects were largely restored when dexamethasone was also given. Collectively these data suggest that changes in zinc metabolism associated with acute stress involve coordinate regulation mediated by many factors, including glucocorticoids and cAMP.
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PMID:Coordinate regulation of zinc metabolism and metallothionein gene expression in rats. 302 99

The process(es) by which parenteral iron effects the accumulation of hepatic metallothionein (MT) is not known. The present study examined glucocorticoids as potential mediators of this process. Chicks were given either one injection (ip) of iron (+1FE) at 10 mg Fe/kg, two injections of iron (+2FE) given 24 hr apart, or a single injection of saline. Plasma corticosterone was evaluated at various times following the last injection. Plasma corticosterone increased approximately 50% following +1FE but more than 200% at 2 and 4 hr following a second injection of iron (+2FE). Plasma zinc showed a transient increase followed by a considerable depression. Coincidentally, the accumulation (determined at 24 hr) of zinc MT in liver of +2FE chicks was three times higher than that of +1FE chicks. In another experiment, markedly greater changes, at similar time intervals, in plasma corticosterone were effected by multiple subcutaneous injections of adrenocorticotropic hormone (ACTH) (either 5 IU ACTH or 20 IU ACTH/kg). Subsequent analysis of hepatic zinc MT showed only minor changes as a result of ACTH injections. These results indicate that a change in the plasma glucocorticoid corticosterone is not a primary component in the process(es) by which parenteral iron effects an increase in hepatic zinc MT.
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PMID:Iron-induced accumulation of hepatic metallothionein: the lack of glucocorticoid involvement. 303 18

Nutritional modulation is one approach to successful aging. In animals, dietary restriction increases life span. Alterations in the macronutrient and micronutrient constituent of the diet can modulate gene expression. Anorexia is common in elderly persons. The results of studies in animals suggest that aging is associated with a decrease in the opioid feeding drive and an increase in the satiating effect of cholecystokinin. Unrecognized depression is a common, treatable cause of anorexia and weight loss in elderly persons. Protein synthesis decreases in elderly persons; nevertheless, nitrogen balance can be maintained in patients with fairly low intakes of protein. Carbohydrate intolerance is common and may be modulated by nutritional intervention and physical activity. The role of cholesterol in the development of heart disease in very old persons is controversial. Homebound and institutionalized elderly persons often do not expose their skin to sunlight; because the skin of older persons has a decreased ability to form vitamin D, the vitamin D status in these persons is precarious and they are at risk for osteopenia. Vitamins are often abused by elderly persons. Drug administration alters the vitamin requirements of persons. Borderline zinc state has been associated with deteriorating immune function, especially in persons who have diabetes mellitus or who abuse alcohol. Zinc administration appears to protect against the deteriorating vision associated with age-related macular degeneration. Selenium deficiency seems to be associated with an increased prevalence of cancer.
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PMID:Nutrition in the elderly. 305 65

Since their introduction in clinical practice in 1980, ACE inhibitors have been found useful in the treatment of hypertension and CHF. In hypertension, they are effective as monotherapy in 40% to 50% of the patients, and in combination with diuretics or calcium antagonists, they are effective in up to 85% of the patients. They are well tolerated, are not associated with depression, impotence, bronchospasm or metabolic derangements such as hypokalemia, hyperuricemia or hyperglycemia, and do not have adverse effects on the quality of life. As a result, they are preferred in hypertensive patients with CHF, left ventricular dysfunction, mental depression, older age, coronary artery disease, metabolic disorders, chronic destructive pulmonary disease, and peripheral vascular disease. In CHF they cause long-lasting hemodynamic and symptomatic improvement, improve exercise tolerance, and may lower mortality in certain patient subsets. Evolving new indications for ACE inhibitors include the diagnosis of renovascular hypertension, the prediction of surgical success, the treatment of scleroderma renal crisis, the reduction of proteinuria, renal protection, cardioprotection, the improvement of arterial compliance, in Bartter's syndrome and idiopathic edema, etc. ACE inhibitors are usually well tolerated but in some instances they may cause class-specific side effects such as hypotension; usually reversible azotemia or renal failure, especially in patients with renal artery stenosis or with CHF with low blood pressure; cough; angioedema; and hyperkalemia. Differences among ACE inhibitors are emerging and include chemical class (e.g., zinc ligand), biotransformation, potency, pharmacokinetics, prodrugs, tissue effects, additional pharmacologic properties, and drug interactions.
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PMID:Angiotensin converting enzyme inhibitors. II. Clinical use. 305 46

Adolescents with anorexia nervosa were evaluated for clinical and biochemical evidence of zinc deficiency. To assess whether these patients would benefit from zinc supplementation, a double-blind, randomized, controlled trial was conducted. The mean zinc intake of the anorexic group calculated on the basis of three-day dietary records was 7.7 +/- 5.2 mg/day, which is significantly below the recommended daily allowance of 15 mg for adolescents (p less than 0.001). The mean urinary zinc excretion in the anorexic group was 257.1 +/- 212.7 micrograms/24 hours compared to 749.9 +/- 897.8 micrograms/24 hours in the control group (p less than 0.005). This result suggests that the zinc status of anorexia nervosa patients may be compromised due to an inadequate zinc intake. Zinc supplementation (50 mg elemental zinc/day) was followed by a decrease in the level of depression and anxiety as assessed by the Zung Depression Scale (p less than 0.05) and the State-Trait Anxiety Inventory (p less than 0.05), respectively. Our data suggest that individuals with anorexia nervosa may be at risk for zinc deficiency and may respond favorably after zinc supplementation.
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PMID:Zinc deficiency in anorexia nervosa. 331 33


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