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)

Abdominal eumycotic mycetoma caused by Pseudallescheria boydii was diagnosed in a 3-year-old male Siberian Husky. The dog was examined because of weight loss and signs of depression. Initially, pyrexia was the only clinical finding. Antibiotic and corticosteroid treatment was ineffective. Two weeks later, the dog's appetite had decreased, it had vomited a few times, and the caudal portion of the abdomen was sensitive to palpation. Hematologic and serum biochemical abnormalities consisted of anemia, leukocytosis, hypoglycemia, hypoalbuminemia, hyperglobulinemia, and high alkaline phosphatase activity. One week later, the dog's condition continued to worsen, and testicular swelling was observed. The dog was castrated. Microscopic examination of specimens obtained at surgery revealed pyogranulomatous periorchitis with mycetoma granules. Ketoconazole treatment was initiated and continued until the dog died one month later. Necropsy revealed multifocal duodenal ulcers, with transmural pyogranulomatous enteritis, pancreatitis, and peritonitis. This case is unique because the etiologic agent apparently entered via the intestinal tract rather than by contamination of an external wound.
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PMID:Eumycotic mycetoma caused by Pseudallescheria boydii in a dog. 246 20

Three cases of osteoarthritis due to dematiaceous fungi are reported. The first case, a Drechslera longirostrata spondylitis complicating prosthetic valve fungal endocarditis responded only to the association of Amphotericin B and Ketoconazole. The second patient had chronic osteoarthritis of the knee due to Phialophora parasitica resistant to medical and surgical treatment after renal transplantation. These two cases are the first and the second known reports of clinical infection with these fungi. The third patient had osteoarthritis of the patella complicating a skin infection by a thorn prick. This was cured by surgical excision and 3 months' medical treatment. These cases of infections osteoarthritis of the knee followed subcutaneous abscesses. Deep tissue infections with dematiaceous fungi with osteoarthritic involvement are very rare (6 cases of Drechslera and 8 cases of Phialophora have been reported). These fungi are opportunist saprophytes of plants in subtropical regions. They are characterised on culture by their brown and black pigmentation and microscopy shows septated filaments. Cutaneous effraction is the usual portal of entry in man; patients commonly have depression of their immune systems. Osteoarthritis is generally due to local extension of a subcutaneous abscess. The functional sequellae can be very serious. Treatment comprises surgical excision of the infected tissues with antifungal drugs which may have to be given in association.
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PMID:[Osteoarthritis caused by dematiaceous fungi. Apropos of 3 cases]. 406 37

Ketoconazole, a new oral drug used to treat systemic and superficial mycoses, inhibits sterol synthesis in fungi. The development of gynecomastia in two patients prompted us to investigate the effect of the drug on testosterone production. After a 200-, 400-, or 600-mg dose, volunteer male testosterone serum concentrations fell markedly, but returned toward baseline eight to 24 hours later as ketoconazole serum concentrations waned. A marked but transient drop in testosterone levels occurred in patients receiving long-term therapy, and continuous testosterone depression was noted in one. A block of synthesis was demonstrated in vitro. Ketoconazole at concentrations achievable in serum with currently used doses blocked basal and gonadotropin-stimulated testosterone production by rat Leydig cells. The diminution of testosterone synthesis could be significant as further therapeutic trials may use larger doses or more than once-daily administration. The paucity of reports of endocrinologic toxicity may relate to the "escape" from the block demonstrated in vivo.
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PMID:Ketoconazole blocks testosterone synthesis. 629 75

Acid aspiration leads to an inflammatory response characterized by the activation and pulmonary entrapment of platelets and while blood cells (WBCs. We speculate that thromboxane (Tx) produced by these activated cells alters lung permeability and diminishes cardiac performance. The lungs of dogs were aspirated with 0.1N HCl (3 ml/Kg). Within 30 minutes in six untreated controls, cardiac index (CI) decreased from 121 to 104 ml/min . kg (P less than ).05), mean arterial pressure decreased from 142 to 120 mm Hg (P less than 0.05), Pao2 decreased from 91 to 73 mm Hg (P less than 0.05), and TxB2 levels increased from 70 to 130 pg/ml (P less than 0.05). Pulmonary WBC sequestration occurred after 2 hours, while at 21/2 hours edema fluid was noted in the endotracheal tube. Six dogs were treated with infusion of the imidazole derivative ketoconazole 1 hour after aspiration (2.5 mg/kg bolus followed by 10 mg/kg . hr for 2 hours). After 30 to 60 minutes of treatment, CI rose from 106 to 143 ml/min . kg (P less than 0.05), TxB2 decreased from 130 to 70 pg/ml (P less than 0.05). At 21/2 hours, plasma from treated animals used to incubate a papillary muscle led to developed tension 8% higher than that in controls (P less than 0.05). Sequestration of WBC was not observed. After 4 hours, 24 ml endotracheal edema fluid was collected in contrast to 127 ml in controls (P less than 0.05). A hamster cheek pouch used for bioassay of microvascular permeability yielded 78 leakage sites/cm2 with control edema fluid and 26/cm2 with fluid from treated animals (P less than 0.05). The importance of WBC Tx synthesis in the induction of permeability was tested by stimulation of isolated WBCs with ionophore in the presence or absence of ketoconazole (0.4 Microgram/ml). Ketoconazole reduced the number of leakage sites in the hamster cheek pouch from 196/cm2 noted in controls to 28/cm2 (P less than 0.05). These data support our hypothesis that Tx directly or indirectly lead to cardiac depression and WBC-mediated permeability.
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PMID:Thromboxane mediation of cardiovascular dysfunction following aspiration. 630 43

Evidence exists that oversecretion of cortisol may be responsible for the clinical manifestations and serotonergic abnormality in depressive illness. Using the cortisol synthesis inhibitor ketoconazole, we investigated the effects of directly lowering cortisol on the symptoms and the response of prolactin (PRL) to d-fenfluramine in eight patients suffering from major depression. Prolactin responses to d-fenfluramine were measured, and patients were treated with 400-600 mg of ketoconazole for 4 weeks, after which they were retested. Five patients treated with ketoconazole recovered from their depression, while the other three had decreases in their Hamilton Depression Rating Scale (HAMD) scores of < or = 50% and were deemed partial responders. Posttreatment prolactin responses to d-fenfluramine were higher than pretreatment values. Ketoconazole normalizes the blunted prolactin responses to d-fenfluramine and may be an effective method by which to treat depression. This implies that hypercortisolemia may be responsible for the clinical features and serotonergic subsensitivity observed in depression.
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PMID:Cortisol synthesis inhibition: a new treatment strategy for the clinical and endocrine manifestations of depression. 777 44

Ketoconazole, an antiglucocorticoid drug, was administered to 10 hypercortisolemic depressed patients for up to 6 weeks. Three patients dropped out because of side effects or intercurrent illness. The remaining seven had significant ketoconazole-associated decreases in serum cortisol levels and in depression ratings. Antiglucocorticoid agents may be useful probes for investigating the sequelae of hypercortisolemia in patients with major depression.
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PMID:Ketoconazole administration in hypercortisolemic depression. 848 Aug 29

Reboxetine is a novel selective norepinephrine inhibitor that has been evaluated in the treatment of patients with depression. Reboxetine is a racemic mixture, and the (S,S)-(+)-enantiomer appears to be the more potent inhibitor. However, the ratio of the areas under the concentration-time curves of the (S,S)-(+)- and (R,R)-(-)-enantiomers in vivo is approximately 0.5. There is no evidence for chiral inversion. Differences in the clearances of the 2 enantiomers may be explained by differences in protein binding. The pharmacokinetics of reboxetine are linear following both single and multiple oral doses up to a dosage of 12 mg/day. The plasma concentration-time profile following oral administration is best described by a 1-compartment model, and the mean half-life (approximately 12 hours) is consistent with the recommendation to administer the drug twice daily. Reboxetine is well absorbed after oral administration. The absolute bioavailability is 94.5%, and maximal concentrations are generally achieved within 2 to 4 hours. Food affects the rate, but not the extent, of absorption. The distribution of reboxetine appears to be limited to a fraction of the total body water due to its extensive (>97%) binding to plasma proteins. The primary route of reboxetine elimination appears to be through hepatic metabolism. Less than 10% of the dose is cleared renally. A number of metabolites formed through hepatic oxidation have been identified, but reboxetine is the major circulating species in plasma. In vitro studies show that reboxetine is predominantly metabolised by cytochrome P450 (CYP) 3A4; CYP2D6 is not involved. Reboxetine plasma concentrations are increased in elderly individuals and in those with hepatic or renal dysfunction, probably because of reduced metabolic clearance. In these populations, reboxetine should be used with caution, and a dosage reduction is indicated. Ketoconazole decreases the clearance of reboxetine, so that the dosage of reboxetine may need to be reduced when potent inhibitors of CYP3A4 are coadministered. Quinidine does not affect the in vivo clearance of reboxetine, confirming the lack of involvement of CYP2D6. There is no pharmacokinetic interaction between reboxetine and lorazepam or fluoxetine. Reboxetine at therapeutic concentrations has no effect on the in vitro activity of CYP1A2, 2C9, 2D6, 2E1 or 3A4. The lack of effect of reboxetine on CYP2D6 and CYP3A4 was confirmed by the lack of effect on the metabolism of dextromethorphan and alprazolam in healthy volunteers. Thus, reboxetine is not likely to affect the clearance of other drugs metabolised by CYP isozymes.
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PMID:Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. 1119 74

This article was aimed to investigate the interest of the combination allopregnanolone plus ketoconazole in depression with the time-sampling method in the forced swimming task. Dose-response curves for fluoxetine (0.5, 1.0 or 2.0 mg/kg, twice day, during 2 weeks; i.p.), desipramine (0.5, 1.0 or 2.14 mg/kg, twice a day, during 2 weeks; i.p.), ketoconazole (6.25, 12.5, 25.0 and 37.5 mg/kg, once a day, during 2 weeks; i.p.) and allopregnanolone (0.5, 1.5, 2.0 mg/kg; once a day, during 2 weeks; s.c.) were established. Fluoxetine (1.0 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) or ketoconazole (25.0 mg/kg, p < 0.05; 37.5 mg/kg, p < 0.05) produced antidepressant-like behavioral changes in swimming, highlighting a serotonergic mechanism while desipramine (1.0 mg/kg, p < 0.05; 2.14 mg/kg, p < 0.05) or allopregnanolone (1.5 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) increased climbing behavior highlighting noradrenergic or dopaminergic effects. Subthreshold doses of fluoxetine (p < 0.05), desipramine (p < 0.05) or ketoconazole (p < 0.05) synergized with subthreshold doses of allopregnanolone and reduced immobility by increasing climbing. In conclusion, fluoxetine, desipramine, ketoconazole and allopregnanolone produced differential antidepressant-like actions in ovariectomized rats forced to swim. Ketoconazole, fluoxetine or desipramine synergized with allopregnanolone.
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PMID:Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim. 1558 61

Treatment resistant depression (TRD) is a common clinical occurrence among patients treated for major depressive disorder. A significant proportion of patients remain significantly depressed in spite of aggressive pharmacological and psychotherapeutic approaches. Management of patient with treatment resistant depression requires thorough evaluation for physical causes. We report a case of recurrent depressive disorder, who presented with severe depressive episode without psychotic symptoms, not responding to multiple adequate trials of antidepressants, who on investigation was found to have Cushing's syndrome and responded well to Ketoconazole.
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PMID:Cushing's Syndrome Masquerading as Treatment Resistant Depression. 2733 21