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)

Twenty-one patients treated for depression with iprindole developed evidence of liver damage: 15 were jaundiced, five had bilirubinuria, and one had pruritus. These complications occurred between four and 21 days after initial exposure to the drug. All patients recovered. Light and electron microscopic findings in liver biopsies of one of these patients were those of cholestasis without inflammation.
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PMID:Jaundice due to iprindole. 410 21

Oral contrceptives (OCs), usd by over 30% of reproductive aged women in Belgium, are by far the most widely used contraceptive in that country. The various types of OCs include monophasic, biphasic, and triphasic combinations of an estrogen and a progestin, sequentials containing estrogen only for 7-14 days followed by a progestin through the 21st day; macrodose or microdose progestin only formulations, 3-month injectable progestins, and the morning after pill. Side effects of OCs are mainly due to metabolic effects on coagulation factors, the renin-angiotensin system, glucose tolerance, or the lipid profile. Users of OCs face increased risks of cholelithiases, thrombophlebitis, thromboembolism, cerebrovascular accidents, myocardial infarcts (among smokers over 35 years of age), and hepatic adenomas. The most troubling secondary effect is the excess cardiovascular morbidity and mortality show by contraceptive users, not just those who are obese, hypertensive, or who have histories of vascular pathology, but also those over 40 years of age and smokers. Lenght of use of OCs does not increase vascular risks. Epidemiologic studies demonstrate that vascular risks are reduced in lower dose formulations. Absolute contraindications to OC use include serious cardiovascular problems, severe hepatic pathology, estrogen-dependent tumors, pregnancy and undiagnosed gynecologic problems, and significant hyperlipidemia. Relative contraindications include severe headaches, cholelithiase, previous cholestasis of pregnancy, severe renal disease, fibromyomas, benign breast disease, age over 40 years, smoking, surgery anticipated within 4 weeks, infectious mononucleosis, falciform anemia, and immediate postpartum and lactation. Epilepsy, diabetes, depression, and varicose veins are not strictly speaking contraindications but require additonal surveillance. Lower dose formulations should be prescribed if possible. OC users should be followed up every 6-12 months. Among other steroidal contraceptive methods, sequential OCs and high dose progestin-only formulations are used for short-term treatment of specific conditions. Progestin-only minipills are used when an OC is desired but estrogens are contraindicated. Injectable progestins should be reserved for patients who for cultural or medical reasons can use no other type of contraceptive. Morning-after pills should not be considered a regular form of contraception. If OCs are used in adolescents, a low dose pill is indicated. Low dose OCs may be indicated for diabetics because of the danger of infection with IUDs and the lesser efficacy of barrier methods. If OCs are used in epileptics, they should be regular dosed because of the danger of drug interactions. Only low-dose formulations and progestin-only minipills should be used by women over 40.
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PMID:[The choice of oral contraception in 1984: general indications and specific cases]. 672 93

Suppurative cholangitis in 5 aged cats was characterized clinically by weight loss, depression, dehydration, icterus, and fever. The major abnormal laboratory findings were a severe left shift of WBC and a high, conjugated bilirubin concentration consistent with an inflammatory process and cholestasis. Gross pathologic findings included periductal biliary fibrosis (4 cats), periductal pancreatic fibrosis (2 cats), cholelithiasis (2 cats), deformation of the gallbladder (2 cats), and chronic interstitial pancreatitis (2 cats). Histopathologic findings in all cases were portal hepatic fibrosis, biliary hyperplasia, and suppurative exudate within dilated intrahepatic biliary ducts. Weight loss and portal fibrosis were suggestive of chronic, intermittent illness. The pathogenesis appeared to involve invasion of the bile duct by enteric bacteria. Cholangitis was observed to occur in association with pancreatitis, cholelithiasis, or anatomic abnormalities of the biliary tract.
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PMID:Suppurative cholangitis in cats. 686 38

The effect of bile acids on E rosette formation and lymphocyte response to PHA was studied. Pooled conjugated and unconjugated bile acids decreased normal lymphocyte E rosette formation in vitro. This inhibition is related to bile acid concentration. Unconjugated bile acids induced a depression of PHA stimulation in comparison to controls. These findings suggest that bile acids can play a role in the depression of cellular immunity observed in patients with cholestasis.
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PMID:Effect of bile acids on E rosette formation and PHA stimulation. 745 18

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.
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PMID:[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report]. 763 62

Central fatigue commonly occurs in patients with primary biliary cirrhosis (PBC) and correlates closely with depression, and cholestatic rats exhibit central fatigue. Therefore, we undertook a series of experiments in both rats with cholestasis caused by bile duct resection (BDR) and sham-resected controls (15 days after surgery) to determine if experimental cholestasis is associated with symptoms of depression that can be modeled in rats, namely anhedonia (loss of pleasure) and the loss of social interest. BDR rats exhibited significant anhedonia compared with sham controls as indicated by a loss in their preference for consuming a saccharin solution, a highly desirable drink for rats. Furthermore, social interest was examined by determining the time BDR or sham rats spent investigating a juvenile rat in an open-field apparatus compared with the time spent on nonsocial behaviors. BDR rats exhibited significantly reduced time spent in social investigation and significantly more time in nonsocial behaviors than did sham rats. Major depression in humans is often associated with elevated circulating glucocorticoid levels and impaired glucocorticoid feedback. Therefore, we measured these parameters in BDR and sham rats and found a striking elevation in circulating glucocorticoid levels in BDR compared with sham animals. However, elevated circulating glucocorticoid levels in BDR rats suppressed normally in response to exogenous dexamethasone, indicating intact glucocorticoid feedback control at the pituitary level in BDR rats. In summary, we have identified behaviors in cholestatic rats that are consistent with those seen in depression.
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PMID:Chronic cholestasis in rats induces anhedonia and a loss of social interest. 965 89

The organic hydroperoxide, tertiary-butylhydroperoxide (tBOOH), causes oxidative damage in a number of cell types. It is used here in an isolated rat hepatocyte couplet preparation to study adverse hepatobiliary effects of peroxidative damage in vitro. At subcytotoxic concentrations (as determined by lactate dehydrogenase release and maintenance of cytoplasmic ATP concentrations) tBOOH caused decreased accumulation of a fluorescent bile acid analogue, cholyl-lysyl-fluorescein (CLF), in the canalicular vacuole of couplets (a hepatobiliary effect; cholestasis). This was dose dependent in the range 100-200 microM. At the same concentrations it brought about release of preaccumulated CLF, suggesting that its effect was more likely to be on sealing properties of the vacuole than processes of uptake, transcytosis, and secretion. Pretreatment of tBOOH-treated couplets with the antioxidants deferoxamine mesylate (iron chelator) and dimethyl sulfoxide (free radical scavenger) resulted in the prevention of both canalicular vacuolar accumulation (cVA, which assesses canalicular function) and canalicular vacuolar retention (cVR, which assesses the retaining ability of couplets) depression at 100 microM tBOOH but not at higher concentrations. This indicates that the cholestatic effect of tBOOH has a preventable and nonpreventable phase and that free radicals are involved in these processes. By selectively generating the two types of tBOOH radical, peroxyl (tBOO.) and alkoxyl (tBO.), using suitable catalysts, we were able to determine that the peroxyl radical was most probably involved in tBOOH-induced cholestasis. This was further supported by experiments employing specific peroxyl and alkoxyl radical scavengers; only the peroxyl scavenger reduced the effect of tBOOH upon canalicular function under the conditions studied.
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PMID:Hepatobiliary effects of tertiary-butylhydroperoxide (tBOOH) in isolated rat hepatocyte couplets. 977 22

Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infancy. We have previously shown that the TPN solution is directly toxic to the liver, and that this toxicity appears to be mediated by one or more amino acids. Elevated serum methionine levels, without corresponding increases in its metabolites, suggest that accumulation of this toxic amino acid may cause TPN cholestasis. Nine-week-old rabbits (n = 28) were divided into three groups. The FED group was fed standard rabbit chow ad libitum. The TPN group was not fed and received only i.v. TPN (including methionine 121 mg.kg-1.d-1), and lipids. The EXP group was fed chow ad libitum and received i.v. methionine (121 mg.kg-1.d-1). After 14 d, we evaluated bile flow, bromosulfophthalein excretion, serum liver enzymes, liver histology, and serum amino acid levels. Bile flow was significantly depressed in the TPN and EXP groups compared with FED controls (32.9 +/- 9.4 and 45.7 +/- 14.4 versus 82.9 +/- 13.8). Excretion of the bilirubin analog bromosulfophthalein tended to be delayed by methionine infusion (p = 0.15). Serum liver enzymes (aspartate transaminase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase) were normal in all groups. Histologic liver injury in the EXP group was similar to that caused by TPN. Balloon degeneration, and portal inflammation were seen in both groups. Homocysteine, an early metabolite of methionine, was elevated in the TPN and EXP groups compared with FED controls. Intravenous methionine is hepatotoxic. Despite full oral feeding, it produces a depression of bile flow and histologic liver injury similar to that seen with TPN. Elevated homocysteine levels suggests an enzymatic block early in the pathway of methionine metabolism. We believe that methionine may be an important factor in the pathogenesis of TPN cholestasis.
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PMID:Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. 1023 61

A 75-year-old woman was admitted with a two-week history of anorexia and vague abdominal pain. She had been taking amitriptyline 75 mg at night for depression for four months before her admission. On presentation she was jaundiced, but with no stigmata of chronic liver disease. Initial liver function tests showed a slightly raised bilirubin, but were otherwise normal. Over the next three weeks her bilirubin concentration continued to rise without evidence of biliary obstruction on ultrasound examination. Her condition continued to deteriorate, and she later developed renal failure consistent with hepatorenal syndrome. Seven weeks after admission she died following a large gastrointestinal bleed. At autopsy, liver histology confirmed pure cholestasis consistent with amitriptyline ingestion.
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PMID:Fatal cholestatic jaundice associated with amitriptyline. 1109 17

Pruritus, fatigue and metabolic bone disease represent three major extrahepatic manifestations of chronic cholestatic liver disease that considerably affect the patient's quality of life. The present article reviews pathogenetic aspects of and current therapeutic approaches to extrahepatic manifestations of cholestatic liver disease. Pathogenesis of pruritus of cholestasis remains poorly understood. The involvement of putative peripherally acting pruritogens, such as bile acids or endogenous opioids, is being discussed. More recently, central mechanisms, including an increased central opioidergic tone and pertubations in the serotonergic system have been proposed. Treatment of the underlying disease is beneficial also for the control of cholestasis-associated pruritus. Current therapeutic recommendations include ursodeoxycholic acid, cholestyramine, rifampicin and opioid antagonists. Liver transplantation may be indicated when severe pruritus is refractory to medical treatment. Fatigue is being recognized as the most frequent and one of the most disabling complaints in chronic cholestasis. Fatigue is presumably of central origin and its association with other neuropsychiatric disorders (e.g. depression, obsessive-compulsive disorders) is consistent with defective central neurotransmission. No specific therapies are currently available and a healthy lifestyle, regular sleep and avoidance of unnecessary stress and other precipiting factors are recommended. Antidepressant therapy may be warranted in selected patients. Osteopenia and osteoporosis are common in chronic cholestatic liver disease, whereas osteomalacia is rare. The pathophysiology of cholestasis-associated metabolic bone disease is regarded as multifactorial. Therapeutic recommendations include regular exercise, calcium and vitamin D supplementation in late stage disease, hormone replacement therapy in postmenopausal women and bisphosphonates.
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PMID:Extrahepatic manifestations of cholestasis. 1216 13


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