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)

Mitomycin (MMC), like many antineoplastic drugs, induces a predictable, dose-related, bone marrow depression in man and laboratory animals; this change is generally reversible. However, there is evidence that MMC may also cause a late-stage or residual bone marrow injury. The present study in female CD-1 mice investigated the haematological and bone marrow changes induced by MMC in a repeat dose study lasting 50 days. Control and MMC-treated mice were dosed intraperitoneally on eight occasions over 18 days with vehicle, or MMC at 2.5 mg/kg, autopsied (n = 6-12) at 1, 7, 14, 28, 42 and 50 days after the final dose and haematological changes investigated. Femoral nucleated bone marrow cell counts and levels of apoptosis were also evaluated and clonogenic assays carried out; serum levels of FLT3 ligand (FL) were assessed. At day 1 post-dosing, MMC induced significant reductions in RBC, Hb and haematocrit (HCT) values, and there were decreases in reticulocyte, platelet, and femoral nucleated cell counts (FNCC); neutrophil, lymphocyte and monocyte values were also significantly reduced. On days 7 and 14 post-dosing, all haematological parameters showed evidence of a return towards normal values, but at these times, and at day 28, values for RBC and FNCC remained significantly reduced in comparison with controls. At days 42 and 50 post-dosing, many haematological parameters in MMC-treated mice had returned to control levels; however, there remained evidence of late-stage effects on RBC, Hb and HCT values, and FNCC also continued to be significantly decreased. Results for granulocyte-macrophage colony-forming units and erythroid colonies showed a profound decrease immediately post-dosing, but a return to normal values was evident at day 50. Serum FL concentrations demonstrated very significant increases in the immediate post-dosing period, but a return to normal was seen at day 50 post-dosing; a relatively similar pattern was seen in the number of apoptotic femoral marrow nucleated cells. The histopathological examination of kidney tissues from MMC animals at day 42 and 50 post-dosing showed evidence of hydronephrosis with cortical glomerular/tubular atrophy and degeneration. It is therefore concluded that MMC administered on eight occasions over 18 days to female CD-1 mice at 2.5 mg/kg induced profound changes in haematological and bone marrow parameters in the immediate post-dosing period with a return to normal levels at day 50 post-dosing; however, there was evidence of mild but significant late-stage/residual effects on RBC and FNCC, and on cells of the erythroid lineage in the bone marrow.
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PMID:The haemotoxicity of mitomycin in a repeat dose study in the female CD-1 mouse. 1630 46

Observational studies have shown that allergic infants, irrespective of the type of diet, show various degrees of growth depression in the first year of life. We investigated whether the type of milk in the complementary feeding period (6-12 months of age) is associated with differences in the increase of standardized growth indices (weight-for-age, WA; length-for-age, LA; and weight-for-length, WL, z-scores) in infants with cow's milk allergy (CMA). Infants with immunoglobulin E-mediated CMA breastfed at least 4 months and progressively weaned in the 5- to 6-month period were randomly assigned to three special formulas, a soy formula (n = 32), a casein hydrolysate (n = 31), and a rice hydrolysate (n = 30). A fourth, non-randomized group was made up by allergic infants still breastfed up to 12 months (n = 32). Groups were compared for WA, LA, and WL z-scores at 6, 9 and 12 months of age. All groups showed low WA and LA z-scores at 6 months of age. Infants fed hydrolyzed products showed a trend toward higher WA z-score increments in the 6- to 12-month period. The use of casein- and rice-based hydrolyzed formulas resulted in higher changes in WA compared with soy formula. Further research should be aimed at optimizing the dietary needs and feeding regimens for infants with CMA.
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PMID:Growth of infants with IgE-mediated cow's milk allergy fed different formulas in the complementary feeding period. 1756 27

This study focused on assessing the psychosocial effects of the long standing, high intensity, and guerrilla-style of warfare among displaced children in Southern Darfur. The goal was to better understand the etiology, prognosis, and treatment implications for traumatic reactions, depression, and grief symptoms in this population. Three hundred thirty-one children aged 6-17 from three IDP Camps were selected using a quota sampling approach and were administered a Demographic Questionnaire, Child Post Traumatic Stress Reaction Index, Child Depression Inventory, and the Expanded Grief Inventory. Forty-three percent were girls and 57% were boys. The mean age of the children was 12 years. Results found that children were exposed to a very large number of war experiences with no significant differences between genders for types of exposure, including rape, but with older children (13-17 years) facing a larger number of exposures than younger children (6-12 years). Out of the 16 possible war experiences, the mean number was 8.94 (SD = 3.27). Seventy-five percent of the children met the DSM-IV criteria for PTSD, and 38% exhibited clinical symptoms of depression. The percentage of children endorsing significant levels of grief symptoms was 20%. Increased exposure to war experiences led to higher levels of: (1) traumatic reactions; (2) depression; and (3) grief symptoms. Of the 16 war experiences, abduction, hiding to protect oneself, being raped, and being forced to kill or hurt family members were most predictive of traumatic reactions. Being raped, seeing others raped, the death of a parent/s, being forced to fight, and having to hide to protect oneself were the strongest predictors of depressive symptoms. War experiences such as abduction, death of one's parent/s, being forced to fight, and having to hide to protect oneself were the most associated with the child's experience of grief. In addition to Total Grief, Traumatic Grief, Existential Grief, and Continuing Bonds were measured in these children. Although trauma, depression, and grief often exist as co-morbid disorders, the mechanisms and pathways of these is less understood. In this study we used Structural Equation Modeling to better understand the complex interaction and trajectories of these three symptoms evolving from war exposure and loss. This study is the first of its kind to assess the psychosocial effects of war experiences among children currently living in war zone areas within Sudan. It identifies some of the most prevalent war-related atrocities and their varying impact on the children's psychological well-being and overall adjustment. Implications for planning mental health interventions are discussed.
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PMID:Psychosocial effects of war experiences among displaced children in southern Darfur. 1830 Jun 49

A greater depression of the action potential (AP) of the ventricular epicardium (Epi) versus endocardium (Endo) is readily observed in experimental models of acute ischemia and Brugada syndrome. Endo and Epi differences in transient outward K(+) current and/or ATP-sensitive K(+) channel current are believed to contribute to the differential response. The present study tested the hypothesis that the greater sensitivity of Epi is due in part to its functionally distinct early fast Na(+) current (I(Na)). APs were recorded from isolated Epi and Endo tissue slices and coronary-perfused wedge preparations before and after exposures to elevated extracellular K(+) concentration ([K(+)](o); 6-12 mM). I(Na) was recorded from Epi and Endo myocytes using whole cell patch-clamp techniques. In tissue slices, increasing [K(+)](o) to 12 mM reduced V(max) to 51.1 +/- 5.3% and 26.8 +/- 9.6% of control in Endo (n = 9) and Epi (n = 14), respectively (P < 0.05). In wedge preparations (n = 12), the increase in [K(+)](o) caused selective depression of Epi APs and transmural conduction slowing and block. I(Na) density was not significantly different between Epi (n = 14) and Endo (n = 15) cells, but Epi cells displayed a more negative half-inactivation voltage [-83.6 +/- 0.1 and -75.5 +/- 0.3 mV for Epi (n = 16) and Endo (n = 16), respectively, P < 0.05]. Our data suggest that reduced I(Na) availability in ventricular Epi may contribute to its greater sensitivity to electrical depression and thus may contribute to the R-ST segment changes observed under a variety of clinical conditions including acute myocardial ischemia, severe hyperkalemia, and Brugada syndrome.
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PMID:Functionally distinct sodium channels in ventricular epicardial and endocardial cells contribute to a greater sensitivity of the epicardium to electrical depression. 1845 29

Depression in children and adolescents was accepted as an entity only 40 years ago, primarily because it was considered that children lacked the mature psychologic and cognitive structure necessary to experience the symptoms. There is a large body of evidence which confirmed the existence of disorder, but it was also shown that children and adolescents experience the whole spectrum of mood disorders, the incidence is increasing and the age at onset has fallen. Compared with adult depression, in children (6-12 years) and adolescents (13-18 years) a more insidious onset is seen, irritability is more frequent than sadness and association with other conditions (anxiety, conduct disorder, ADHD, learning disorder) is more often.
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PMID:Is the child an adult in miniature? Analysis of the role of regulatory decisions on antidepressive treatment for children and adolescents. 1876 7

Non-selective inhibition of monoamine oxidase (MAO) enzymes (ie, isoforms A and B) in the brain are associated with clinically significant antidepressant effects. In the US, the selegiline transdermal system (STS; EMSAM) is the first antidepressant transdermal delivery system to receive Food and Drug Administration (FDA) approved labeling for the treatment of major depressive disorder (MDD). Currently, the use of orally administered MAO inhibitor antidepressants (eg, phenelzine, tranylcypromine) is limited by the risk of tyramine-provoked events (eg, acute hypertension and headache, also known as the "cheese reaction") when combined with dietary tyramine. The selegiline transdermal system is the only MAOI available in the US for the treatment of MDD that does not require dietary restriction at the clinically effective dose of 6 mg/24 hours. Delivery of selegiline transdermally (EMSAM((R))) bypasses hepatic first pass metabolism, thereby avoiding significant inhibition of gastrointestinal and hepatic MAO-A activity (ie, reduced risk of tyramine-provoked events) while still providing sufficient levels of selegiline in the brain to produce an antidepressant effect. At dosages of 6-12 mg/24 hours, EMSAM has been shown to improve symptoms of depression, have good tolerability, and have high rates of medication adherence. However, at higher doses of EMSAM (ie, 9 mg/24 hours or more), dietary restriction of tyramine intake is recommended. The introduction of EMSAM overcomes many of the safety concerns affiliated with the conventional oral MAO inhibitors and EMSAM may be considered another strategy for the treatment of MDD, especially in patients who cannot tolerate oral antidepressants, are poorly adherent, who present with atypical depressive symptoms, or have failed other antidepressants.
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PMID:Transdermal selegiline for the treatment of major depressive disorder. 1930 May 83

We review three studies of omega-3 fatty acids in the treatment of depression that were carried out by our research group at the Beer Sheva Mental Health Center. The first study examined eicosapentaenoic acid (EPA) versus placebo as an adjunct to antidepressant treatment in 20 unipolar patients with recurrent major depression. The second study used omega-3 fatty acids in childhood major depression; 28 children aged 6-12 were randomized to omega-3 fatty acids or placebo as pharmacologic monotherapy. The third study was an open-label add-on trial of EPA in bipolar depression. Twelve bipolar outpatients with depressive symptoms were treated with 1.5-2.0 g/day of EPA for up to 6 months. In the adult unipolar depression study, highly significant benefits were found by week 3 of EPA treatment compared with placebo. In the child study, an analysis of variance (ANOVA) showed highly significant effects of omega-3 on each of the three rating scales. In the bipolar depression study, 8 of the 10 patients who completed at least 1 month of follow-up achieved a 50% or greater reduction in Hamilton depression (Ham-D) scores within 1 month. No significant side effects were reported in any of the studies. Omega-3 fatty acids were shown to be more effective than placebo for depression in both adults and children in small controlled studies and in an open study of bipolar depression. (This review discusses three studies, all from our group, completed before the clinical trial registry was initiated.)
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PMID:Omega-3 fatty acids in depression: a review of three studies. 1949 25

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.
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PMID:Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. 2035 Mar 37

This study aimed to investigate the role of sleep physiology in recovery from burnout, in particular the relation between sleep and changes in fatigue and whether those changes would be related to return to work. 23 white-collar workers on long-term sick leave (>3 months) due to a burnout related diagnosis and 16 healthy controls were subjected to polysomnographic recordings at baseline and after 6-12 months' rehabilitation. Occupational status, subjective sleep quality, fatigue, anxiety and depression were assessed. Recovery from burnout was accompanied by improved sleep continuity. Significant interaction effects were seen for number of arousals, sleep fragmentation, sleep latency, sleep efficiency and time of rising. The burnout group improved significantly on all symptom variables although the post-treatment levels did not reach the levels of the controls. Recovery from fatigue was related to a reduction of the arousal from sleep and was the best predictor of return to work.
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PMID:Sleep physiology in recovery from burnout. 1969 75

The combination of pegylated-interferon (PEG-IFN)/ribavirin is currently the standard of care antiviral treatment for chronic hepatitis C (CHC), but optimal results require an individual approach. Key issues are to deliver doses that confer optimal antiviral efficacy against hepatitis C virus (HCV) for a time sufficient to minimise relapse. Viral monitoring during therapy guides the subsequent treatment course, particularly HCV RNA results at 4 weeks (rapid viral response [RVR]) and 12 weeks (complete early viral response [cEVR]). There is strong evidence that for most patients with genotypes 2 or 3 HCV infection, RVR allows truncation of treatment to 16 weeks, provided ribavirin dose is weight-based. However, those patients with cirrhosis, insulin resistance/diabetes or older than 50 years need 6-12 months treatment. For "difficult-to-treat" CHC (genotypes 1 and 4), RVR is infrequent (approximately 15% in European studies), but allows treatment to be truncated from 48 to 24 weeks. Without RVR, there is some evidence that longer treatment (72 weeks) improves sustained viral response (SVR). However, "induction dosing" first 12 weeks of PEG-IFN clearly does not improve SVR. To prevent dose reductions and complete therapy, it is critical to detect and treat depression and other disabling side-effects, including judicious use of growth factors for severe anemia or neutropenia and possibly, thrombocytopenia. Another potentially important aspect may be attempts to counter central obesity and insulin resistance, which confer suboptimal antiviral response with any HCV genotype. Treatment partnerships with specialist nurses, psychological therapists and other healthcare workers are also essential for optimal individual management of patients with CHC.
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PMID:Individualisation of antiviral therapy for chronic hepatitis C. 2059 46


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