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)

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.
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PMID:Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes. 843 80

There has been a resurgence of interest in the use of monoamine oxidase (MAO) enzyme inhibitors for the treatment of depression. Unlike the first-generation MAO inhibitors, the current drugs are readily reversible in their action, resulting in far less concern about interactions with certain foods and drugs which could lead to serious pressor effects. Furthermore, the current drugs are far more selective in their actions as a result of the ability to affect either the MAO-A or the MAO-B isoenzyme. Moclobemide is an example of a reversible MAO-A inhibitor which has been extensively studied and whose pharmacokinetic, clinical pharmacological and toxicological profiles have been thoroughly defined. Moclobemide has a short disposition half-life and intermediate values for systemic clearance and volume of distribution; half-life increases somewhat with dose. The drug is completely metabolised by the liver. Moclobemide is rapidly and completely absorbed following oral administration in a variety of dosages and forms. The drug has a high intrinsic (apparent oral) clearance which results in a substantial hepatic first-pass effect and, while there is marked interindividual variation, differences within an individual are small. A time- and dose-dependence is observed with multiple oral administration: clearance decreases with administration during the first week and thereafter remains constant. The exact mechanism of this effect is not known, but it may reflect inhibition of elimination by metabolites (the kinetics may always be described as being first-order). Moclobemide disposition is not affected by renal disease, nor is there substantial alteration with advanced age. Liver disease causes a dramatic reduction in clearance; dosage must be adjusted for patients with liver disease. There is minimal transfer of the drug into breast milk, such that breast-feeding neonates are exposed to only a very small dose of the drug. Moclobemide administration results in a minimal interaction with exogenous amines (e.g. tyramine and pressor amine drugs); the so-called 'cheese effect' is therefore of little concern. As a result, the drug has an excellent tolerability profile both within the therapeutic dose range and in overdose (no deaths have been attributed to moclobemide intoxication per se). Cimetidine inhibits the elimination of moclobemide. Moclobemide appears to affect several isoenzymes of the cytochrome P450 (CYP) system (CYP2C19, CYP2D6 and CYP1A2). The adverse events profile of moclobemide indicates only mild and transient effects at a relatively low rate of occurrence.
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PMID:Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide. 858 17

Kupffer cells (KC) and gut-derived bacterial endotoxin have been implicated in the aetiology of alcoholic liver disease. Using in vivo microscopic methods, we have shown that ethanol ingestion in mice causes a dose dependent increase in leucocyte adhesion and endothelial cell swelling in hepatic sinusoids. Activation of KC is elicited at low doses while depression occurs at high doses and with chronic exposure. The responses are exacerbated in the presence of endotoxaemia or sepsis and are not seen in endotoxin-resistant animals, implicating a role for endotoxin in the ethanol-induced inflammatory response. In addition, the responses are abolished with anti-TNF alpha suggesting that TNF alpha is a primary mediator of these events. Nitric oxide (NO) initially appears to play an important role in these events by stabilizing the TNF alpha-mediated hepatic microvascular inflammatory response to acute ethanol ingestion, thereby helping to protect the liver from ischaemia and leucocyte induced oxidative injury. Finally, an ongoing clinical study has confirmed a mild systemic endotoxaemia in patients hospitalized for alcoholic liver disease. All of these results support important roles for endotoxin, cytokines, nitric oxide and sinusoidal lining cells in the pathophysiology of liver injury resulting from ethanol alone or in combination with infection.
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PMID:Role of endotoxin in the hepatic microvascular inflammatory response to ethanol. 858 35

Demographic trends reveal the elderly to be the fastest growing segment of the population. Physicians can therefore anticipate encountering increasing numbers of older patients with alcohol-related problems. These problems include liver disease, dementia, confusion (masquerading as dementia), peripheral neuropathy, insomnia, late-onset seizure disorder, poor nutrition, incontinence, diarrhea, myopathy, inadequate self-care, macrocytosis, depression, fractures, and adverse reactions to medications. Despite the prevalence of alcohol use in older people, their risks and problems are often unrecognized. We reviewed published literature on the determinants and consequences of alcohol-related problems in persons aged 65 years and older and the usefulness of available screening measures. Thirteen of 25 eligible studies on determinants and consequences met quality criteria and were reviewed. Nine additional studies on screening tests were also evaluated. Determinants include history of alcohol use and abuse, social isolation, and reduced mobility; consequences consist of risks of hip fracture from falls, neoplasms, and psychiatric illness. Currently accessible screening tests focus on high levels of alcoholic beverage use and abuse and dependence. They are not useful in screening for hazardous consumption that may result from relatively low levels of alcohol use alone or in combination with medications, medical illness, or preexisting diminished physical, emotional, or social function. Research is needed on the consequences of lower levels of alcohol consumption on the physical and psychosocial health of older individuals and on methods for distinguishing alcohol-related from age-related problems. Existing screening tests should be expanded or new screening methods developed in anticipation of a growing public health problem.
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PMID:Alcohol-related problems in older persons. Determinants, consequences, and screening. 900 85

Alcohol withdrawal syndrome (AWS) may result in nausea, vomiting, diarrhea, weakness, sweating, tremors, tachycardia, hypertension, agitation, delirium, hallucinations, seizures, and death beginning 6 hours after alcohol cessation in alcoholics. Benzodiazepines are cross-tolerant with ethanol and are considered first-line therapy for treating AWS. Chlordiazepoxide and diazepam are first metabolized by hepatic oxidation, then glucuronidation. Lorazepam and oxazepam undergo only hepatic glucuronidation. Benzodiazepine oxidation is decreased in persons with liver disease and the elderly. Accumulation with resultant excessive sedation and respiratory depression may be significant when administering chlordiazepoxide or diazepam to patients with impaired oxidative metabolism. Lorazepam and oxazepam metabolism is minimally affected by age and liver disease. Chlordiazepoxide and diazepam are erratically absorbed by the intramuscular route. Lorazepam is predictably absorbed by the intramuscular route. Oxazepam is not available in parenteral form. Lorazepam appears to be the safest empiric choice among the various benzodiazepines for treating AWS in the elderly and in patients with liver disease, or those who require therapy by the intramuscular route.
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PMID:Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease. 870 Jul 92

We studied the morbidity of chronic hepatitis C in patients referred to a tertiary care medical facility. The medical records of 500 consecutive cases of chronic hepatitis C were examined for the following: (1) source and time of exposure, (2) signs and symptoms of liver disease, (3) degree of alcohol intake, (4) liver biopsy findings, (5) extrahepatic disease manifestations, and (6) coexisting illnesses that could have an impact on morbidity. Morbidity and histologic findings were evaluated in relation to the duration of hepatitis C. The onset of infection could be determined in 376 patients (75%). A close relationship between the length of infection and disease features was not observed. Fatigue was common at all stages of infection. Whereas cirrhosis occurred more frequently in patients with disease of long duration, 15-24% of patients had signs of advanced liver disease (ascites, encephalopathy, thrombocytopenia) within six years of exposure. Overt extrahepatic manifestations of chronic hepatitis C occurred infrequently, and depression was reported in 24% of untreated patients. In conclusion, in patients referred to a tertiary care setting, chronic hepatitis C is often associated with significant morbidity.
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PMID:Morbidity of chronic hepatitis C as seen in a tertiary care medical center. 900 36

It has often been suggested that mood and personality predispose to peptic ulcer, but little prospective evidence exists. We used longitudinal data from the Alameda County Study to seek associations of psychological characteristics with later ulcer development, taking into account the possible confounding or mediating, taking into account the possible confounding or mediating roles of nonpsychological factors. Among 4,595 Alameda County Study subjects ulcer-free in 1965, we studied five baseline psychological measures (depression, hostility, ego resiliency, social alienation or anomy, and personal uncertainty) with respect to reported ulcer in 1973-1974. All five measures had significant age-adjusted associations with incident ulcer [odds ratio (O.R.) 1.8-2.6]. After adjustment for smoking, drinking, skipping breakfast, lack of sleep, painful medical conditions, and liver disease, three measures remained significant: depression, anomy, and hostility. The age-adjusted O.R. of 2.8 [95% confidence interval (C.I.) 1.6, 4.8] for an upper versus a lower tertile index of independently predictive psychological factors fell to 2.1 with adjustment for health-related behaviors and medical conditions, and reached 1.7 (C.I. 1.0, 3.1) after addition of education to the model. We conclude that depression, maladjustment, and hostility are prospectively associated with peptic ulcer. These associations are partially accounted for by confounding or mediation by standard risk factors, and are to some extent related to socioeconomic status.
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PMID:Psychological predictors of peptic ulcer incidence in the Alameda County Study. 917 31

As many as 15% of community-dwelling older persons are heavy drinkers, but their alcoholism is often hidden from their physicians. Depression, loneliness, and lack of social support are the most frequently cited antecedents to drinking for older alcoholics. Clinically, the same amount of alcohol once consumed with impunity may cause clinical symptoms in late life. Physiologic changes in volume of distribution make older patients susceptible to acute alcohol toxicity, with its CNS effects and metabolic disturbances. Liver disease, nutritional deficiencies, and impotence are consequences of chronic alcohol abuse.
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PMID:Alcohol abuse: medical effects of heavy drinking in late life. 919 88

The impact of depression (assessed by the Beck Depression Inventory) on quality of life and outcome was prospectively assessed in adult patients with cirrhosis. Patients with depression had significantly poorer perceived quality of life (P = 0.006), poorer adaptive coping (P = 0.001), and lower functional status, i.e., Karnofsky performance score (P = 0.06), as compared to the nondepressed patients. Survival after transplantation was not different between depressed and nondepressed patients. However, the patients with depression were significantly more likely to die while awaiting transplantation than the nondepressed patients (P = 0.02). The difference in mortality between the depressed and the nondepressed patients with end-stage liver disease could not be explained by the severity of illness variables; Child-Pugh score, complications of liver disease, renal function, serum albumin, prothrombin time, frequency and duration of hospitalizations were not significantly different for depressed and nondepressed patients. Symptoms of depression should be sought in patients with cirrhosis since depression is a modifiable illness that is amenable to treatment.
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PMID:Depression in patients with cirrhosis. Impact on outcome. 924 40

Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury. These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease.
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PMID:Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats. 927 63


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