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)

Multinucleate cells are found frequently in rheumatoid synovium. In this study, polyethylene glycol was used to fuse rabbit synovial fibroblasts. Approximately 40% of the cells developed more than one nucleus in a 24 hour period, during which time cell membranes had increased permeability. In cultures containing multinucleate cells, 3H-thymidine incorporation was depressed for 24 hours although 3H-leucine incorporation into TCA precipitable material was unaffected; autoradiography showed that depression of 3H-thymidine continued for at least 4 days. Collagenase production by cultures containing fused cells was increased more than 10-fold over control cultures during a 28 day period.
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PMID:Collagen production by cultures containing multinucleated cells derived from synovial fibroblasts. 21 86

The properties of succinate uptake in succinate-grown Kluyveromyces cells were examined. The rate of succinate transport at 15C exhibits an approximate V-max of 1.2 mumol times h-1 times mg-1 dry weight of cells and an apparent K-m of 18 muM. The uptake process appears to be tightly coupled to metabolism. L-Malate, fumarate, and alpha-ketoglutarate were the only other dicarboxylates tested, which were found to inhibit succinate transport. The aggreement between the order of inhibition of succinate transport by these dicarboxylates and their rates of uptake, as well as the competitive nature of the inhibition are all consistent with the existence of a common carrier system showing specificity for dicarboxylates of the TCA cycle. Cells transferred from succinate to glucose medium rapidly lose their ability to transport succinate. Glucose-grown cells also exhibit an inability to oxidize dicarboxylates or to use them for growth without a very long lag. The dicarboxylate uptake system, therefore, appears to be subject to a strong catabolite repression. The depression of the succinate transport system requires the presence of succinate, as well as low concentrations of glucose.
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PMID:Dual effects of glucose on dicarboxylic acid transport in Kluyveromyces lactis. 23 57

A study of 112 psychogeriatric admissions identified seventy patients sufficiently depressed to require biologic treatment. Twenty-four patients completed a primary treatment trial with TCA's and seventeen with ECT. ECT proved to be more effective, (81.4% versus 62.5%), even though overtly psychotic and medically unstable patients preferentially received this treatment. The ECT response rate is comparable to other reports of its efficacy in the treatment of delusional depression. A higher morbidity rate of 27 percent in the TCA-treated group was observed. The authors conclude that ECT is a highly beneficial treatment modality for the carefully selected elderly patient with major depressive illness. They found that a higher number of ECT treatments than expected were required in their psychogeriatric patients, but did not find a higher morbidity other than increased confusion with more treatments. Careful repeated assessment of response to treatment combined with readiness for assertiveness, in spite of the advanced age of the patient, seem to be indicated. Conversely, excessive hesitance when caring for the elderly patient may lead to a premature termination of treatment, causing the patient to remain in a chronic mentally compromised state.
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PMID:Empirical study on an inpatient psychogeriatric unit: biological treatment in patients with depressive illness. 286 28

1. One aspect of using MAO-inhibitors - combining them with tricyclic antidepressants in the treatment of therapy resistant depression - has always been controversely discussed in regard to its unusual toxicity and efficacy. 2. To obtain detailled information about safety and efficacy of such a combined treatment, the charts of 94 inpatients treated with a tranylcypromine - tri- (tetra) cyclic antidepressant combination were reviewed. 3. Within a mean treatment period of 21.9 days, 68% of the patients demonstrated a very good or good improvement to combined treatment, the most effective combination being tranylcypromine + amitriptyline. 4. The incidence of side effects among the patients on the combined regimen was slightly, but not significantly lower as compared to the patients on single tri- (tetra) cyclic antidepressant treatment. 5. Our retrospective study supports the general safety and efficacy of combined MAOI-TCA treatment and suggests that combined treatment, if properly administered, leads to neither serious complications nor an inordinate number of side effects.
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PMID:Combined MAO-inhibitor and tri- (tetra) cyclic antidepressant treatment in therapy resistant depression. 340 29

Other studies have reported the use of TCA antidepressants in the treatment of depressed children (Frommer 1967; Ossofsky 1974; Stack 1972; Polvan and Cebiroglu 1972). However, these studies did not meet criteria for inclusion in this review. In studies, other medicines were given concurrently with TCAs. Several did not specify the number of subjects and/or the number who responded. Sometimes subjects who were not diagnosed as depressed were included. Also studies of childhood depression tend to include adolescents; thus many samples were a mixture of adolescents and prepubertal children with the adolescents frequently predominating. As the purpose of this review was depression in prepubertal children, only studies comprised predominantly of prepubertal children were included. Although not included in this review, many such studies reported TCAs were useful in treating depression in children. After reviewing these studies, it is obvious that their sophistication has improved dramatically in recent years. Standard diagnostic criteria such as Feighner's Research Diagnostic Criteria, the Research Diagnostic Criteria, and more recently DSM-III (all of which are similar) have permitted a more objective and standardized diagnosis of depression. Likewise, the development of the Children's Depression Inventory and the Childhood Depression Rating Scale have allowed more objective measurement of severity of depression and of improvement in depression in children. Plasma drug level monitoring has allowed for pharmacokinetic studies of TCAs, more precise dose adjustment and equivalent drug treatment of subjects involved in clinical research studies. Studies to date indicate TCAs were helpful in treating depressed prepubertal children. However, double-blind placebo/control studies of tricyclic antidepressants in depressed prepubertal school-aged children have not been published. Ideally a study of antidepressants in children should include: objective standardized diagnostic criteria for diagnosing depression; objective rating of severity of depression; explicit exclusion criteria; steady-state plasma blood level monitoring; assured compliance; adequate duration of treatment so sufficient time is allowed for response to occur; a double-blind study design. Unfortunately the ideal study has not been done. TCAs may be an effective treatment for prepubertal major depressive disorder. However, further study is necessary to clearly establish their efficacy.
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PMID:Tricyclic antidepressants in prepubertal depressed children: review of the literature. 352 32

Drug-induced nephrotoxicity (NT) has become an increasingly significant clinical problem. An in vitro model of drug-induced NT was therefore developed using gentamicin and the effects of ATP-MgCl2 on reduction or prevention of NT were determined. To study this, non-pulsatile perfusion in isolated rat kidneys was maintained at 100 mm Hg during 2 hr of perfusion at 37 degrees C. The oxygenated Krebs-HCO3 perfusate contained 7.5 g/dl albumin as colloid, glucose, creatinine, amino acids, trace amounts of [3H]inulin and 125I-lysozyme, and either 0, 0.4, 0.8, or 1.2 mg/ml of gentamicin. In some studies, 2 mM ATP-MgCl2 was added with 0.8 mg/ml of gentamicin at 0 and 60 min of perfusion. During each 10-min clearance period, glomerular filtration rates, sodium absorption, water absorption, and fractional clearance of TCA-precipitable lysozyme were measured. The results indicate that renal perfusate flow, glomerular filtration rate, urinary flow and tubular absorption of protein (a sensitive indicator of tubular function), sodium, and water were affected by gentamicin in a dose-dependent manner. An isolated kidney preparation can therefore be used to study gentamicin-induced NT. Higher in vitro perfusate concentrations of the drug were needed, however, to acutely mimic the in vivo cumulative effects. Nonetheless, renal perfusate flow, glomerular filtration rate, and the depression in protein reabsorption which occurred with gentamicin treatment were markedly improved by simultaneous treatment with ATP-MgCl2. Thus, ATP-MgCl2 may be useful in reducing drug-induced nephrotoxicity.
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PMID:Reduction of the drug-induced nephrotoxicity by ATP-MgCl2. II. Effects on gentamicin-treated isolated perfused kidneys. 387 64

A double-blind crossover study in 53 psychiatric outpatients compared the safety and efficacy of triazolam and placebo in relieving insomnia refractory to treatment with a tricyclic antidepressant. Patients with a depressive disorder who had been taking a TCA for at least 6 weeks received triazolam or placebo for 4 days, neither medication for 1 day, and the alternative treatment for 4 days. The antidepressant regimen was maintained throughout the study. Sleep measurements showed triazolam to be consistently more effective than placebo in promoting and maintaining sleep and enabling the patient to awaken feeling rested. No worsening in depression or anxiety was seen with either triazolam or placebo; some measures indicated improvement in anxiety and depression symptoms on triazolam. One patient on triazolam dropped out because of side effects. The most common side effect was mild to moderate drowsiness.
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PMID:Triazolam treatment of insomnia in depressed patients taking tricyclics. 613 64

While frank hypothyroidism can precipitate depression, most depressed patients are euthyroid. Nevertheless, there is evidence that a resilient HPT axis favors recovery from depression. Clearly small amounts of the thyroid hormones accelerate the antidepressant action of TCA, at least in women, and usually remedy TCA failure in both men and woman. Athough TRH appears to produce mood elevation in many kinds of patients as well as in normal subjects, this property cannot presently be exploited therapeutically. The present value of TRH in psychiatry is as a psychoendocrine diagnostic tool. Used in this way it has revealed a subpopulation of depressed patients and a subpopulation of alcoholic patients who show a blunted TSH response in the absence of usual endocrinological explanations.
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PMID:Some endocrine aspects of affective disorders. 625 53

The addition of many oxidizable substrates to the medium of incubating rat renal slices decreases ammoniagenesis from glutamine and glutamate. Interestingly, lactate and beta-hydroxybutyrate depress ammoniagenesis less in renal slices from acidotic rats compared with normal-control rats. In this study, the effects of an expanded panel of substrates on ammoniagenesis in kidney slices from control and acidotic rats were followed to discern patterns of inhibition. In addition to lactate and beta-hydroxybutyrate, acetate, pyruvate, and perhaps acetoacetate caused relatively less depression of ammoniagenesis in acidotic slices. Citrate, succinate, fumarate, octanoate, and alpha-ketoglutarate decreased ammoniagenesis to the same extent or more in acidotic slices compared with that in normal-control slices. Glycerol had little effect on ammoniagenesis under either condition. From the substrates tested, it can be generalized that those outside the TCA cycle (with exception of octanoate) depress ammoniagenesis less during acidosis, while those in the TCA cycle depress ammoniagenesis equally or even more during acidosis. We hypothesize from the pattern of our results that changes in renal intermediary metabolism at or before citrate formation occur during acidosis and are important regulatory mechanisms for ammoniagenesis.
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PMID:The regulation of renal ammoniagenesis in the rat by extracellular factors. III. Effects of various fuels on in vitro ammoniagenesis. 688 70

MIA is an effective antidepressant, comparable in therapeutic efficacy to the TCAs. Further, because of its weak antimuscarinic effects. Further, because of its weak antimuscarinic effects, MIA produces no significant cognitive impairment, alteration of cardiovascular function of anticholinergic side effects compared to the TCA's. While drowsiness is the most frequently reported adverse reaction with MIA, an h.s. dosing schedule can provide relief of insomnia and improve the quality of sleep (47,61). Therefore, because of MIA's advantageous pharmacodynamic profile, it offers an improvement in therapeutic index over the TCAs in the treatment of depression in the elderly.
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PMID:Treating the depressed elderly patient: the comparative behavioral pharmacology of mianserin and amitriptyline. 704 64


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