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)

Chronic hepatitis C (HCV) infection affects more than 170 million people throughout the world and 2 to 3 million Americans. End-stage liver disease secondary to chronic HCV infection is the most frequent indication for liver transplantation in this country. Currently, the gold standard for treatment for immunocompetent patients is a combination of peginterferon (PEG-IFN) and ribavirin for 6 to 12 months depending on the genotype. This treatment achieves a sustained virological response (SVR) in 54% to 61% of patients overall. Almost 50% of patients do not respond or have recurrences posttreatment and progress in over 10 to 20 years into chronic liver disease and its complications. Liver transplantation is the only therapeutic modality that impacts on quality of life and survival of these patients. However, recurrence of HCV in the new allograft is universal with accelerated progression to cirrhosis in 5 to 10 years. Response to treatment is usually low (20% to 30%), and associated with significant side effects and depression. A significant percentage of patients with recurrent HCV after transplantation require retransplantation to control the complications of end-stage liver disease. Other solid organ transplants recipients already HCV-positive, or infected at the time of transplantation from blood transfusions or an infected graft, develop accelerated, progressive liver disease facilitated by the adverse effects of immunosuppression in addition to HCV replication. To prevent morbidity, mortality, and high costs related to the consequences of HCV infection, all solid organ transplant candidates should be tested for HCV infection and treated appropriately with PEG-IFN and ribavirin prior to transplantation.
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PMID:Should patients with chronic hepatitis C infection be transplanted? 1525 56

Protein-energy malnutrition (PEM) is a prevalent observation in cirrhotic patients. In advanced cirrhotic patients with hepatic encephalopathy, dietary protein should be restricted to the low level of 0.5 g/kg/day. In such a strictly protein restricted diet, branched amino acid-enriched nutritious products should be prescribed to improve PEM. Avoidance of day-time or nocturnal fasting by frequent meals and late evening snacks is another recommendation for prevention of PEM. The n-3 polyunsaturated fatty acids (PUFA) modulate lymphocyte proliferation and eicosapetaenoic acid (EPA) up-regulates the metabolic action of insulin. The dietary n-6/n-3 PUFA ratio should be maintained between 2.8 and 3.2 in chronic liver disease. Oxidative stress is suggested as a trigger in the progression of chronic liver disease. Antioxidant vitamins; Vitamins A, E and C and carotenes may be useful to prevent the progression of chronic liver disease. Zinc depression occurs in advanced liver disease and it reduces taste and immune function. A goal of dietary management in chronic liver disease should be preventing PEM and blocking progression to hepatic cancer, and improving quality of life.
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PMID:Chronic hepatic disease and dietary instruction. 1560 46

The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters. New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented. Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism.
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PMID:Glutamate in CNS disorders as a target for drug development: an update. 1561 69

Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N-acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited.
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PMID:Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. 1579 53

The authors review the psychosocial aspects of transplantation. They first review psychosocial risk factors that place transplant patients at higher risk for noncompliance and negative outcomes. They then discuss what assessments should be included in a pretransplantation psychosocial evaluation. Goals of the psychosocial evaluation include selection of candidates most likely to benefit from transplantation and identification of areas for psychosocial intervention, both before and after transplantation. The assessment should address the patient's premorbid psychiatric state, past adaptation to stressors, history of compliance with treatment, substance abuse history, and level of social support, including community and faith-based support systems. Results of psychometric assessments may be helpful when considered in conjunction with a clinical interview and other sources of information about the patient. It may also be helpful to use a screening tool developed specifically to evaluate psychosocial factors relevant to transplantation, such as the Psychological Assessment of Candidates for Transplantation (PACT) scale and the Transplantation Evaluation Rating Scale (TERS). The authors then review issues related to psychopharmacologic interventions in transplant patients, including the use of antidepressant medication pre- and post-transplant, strategies for avoiding delirium associated with immunosuppressive medications immediately post-transplantation, neuropsychiatric symptoms associated with interferon alpha therapy for hepatitis C, and interactions between over-the-counter and herbal agents (e.g., St. John's Wort) and immunosuppressive agents. Although limited research has been done on nonpharmacologic interventions, such as transplant support groups, it appears that certain types of group therapy, in particular, cognitive-behavioral groups that target specific risk factors such as depression, distress, and compliance, may also offer promising approaches for dealing with the problems of transplant patients. The authors then focus on two special situations that create particular problems for transplantation teams: liver transplantation in patients with alcoholic liver disease (ALD) and obesity in transplant patients. The authors conclude that the prognosis for patients with ALD who receive liver transplantation is similar to that of non-alcoholics and that alcoholism is not a contraindication for liver transplantation. However, careful preliminary psychosocial assessment is essential to review candidates for factors that are predictive of relapse, while close follow-up post-transplantation can help improve outcomes. It appears that obesity can increase the risk of negative outcomes in transplant patients, although there is currently no consensus on the use of obesity as an exclusion criteria. Interventions that take into account the special psychological and medical needs of transplant patients need to be developed for treating obesity both pre- and post-transplantation. Improved strategies for identifying high-risk patients and finding ways to intervene both pre- and post-transplantation can not only help lengthen transplant recipients' life spans, but also improve their adaptation to transplantation and lead to improved quality of life.
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PMID:Psychosocial challenges in transplantation. 1599 May 53

S-Adenosylmethionine (SAM) is an important metabolite that participates in many reactions as a methyl group donor in all organisms, and has attracted much interest in clinical research because of its potential to improve many diseases, such as depression, liver disease, and osteoarthritis. Because of these potential applications, a more efficient means is needed to produce SAM. Accordingly, we developed a positive selection method to isolate SAM-accumulating yeast in this study. In Saccharomyces cerevisiae, one of the main reactions consuming SAM is thought to be the methylation reaction in the biosynthesis of ergosterol that is catalyzed by Erg6p. Mutants with deficiencies in ergosterol biosynthesis may accumulate SAM as a result of the reduction of SAM consumption in ergosterol biosynthesis. We have applied this method to isolate SAM-accumulating yeasts with nystatin, which has been used to select mutants with deficiencies in ergosterol biosynthesis. SAM-accumulating mutants from S. cerevisiae K-9 and X2180-1A were efficiently isolated through this method. These mutants accumulated 1.7-5.5 times more SAM than their parental strains. NMR and GC-MS analyses suggested that two mutants from K-9 have a mutation in the erg4 gene, and erg4 disruptants from laboratory strains also accumulated more SAM than their parental strains. These results indicate that mutants having mutations in the genes for enzymes that act downstream of Erg6p in ergosterol biosynthesis are effective in accumulating SAM.
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PMID:A new method for isolation of S-adenosylmethionine (SAM)-accumulating yeast. 1601 May 71

Injection drug users (IDUs) acquire the majority of new hepatitis C virus (HCV) infections and frequently use alcohol. Alcohol abuse accelerates liver disease among HCV-infected persons, can reduce the effectiveness of treatment for HCV infection and may be a contraindication for HCV treatment. HCV seropositive, HIV-negative IDUs aged 18-35 years in Baltimore, New York City and Seattle who were enrolled in a behavioral risk-reduction intervention trial underwent computerized self-interviews to assess baseline alcohol use and dependence and medical history. We measured problem alcohol use using the 10-item Alcohol Use Disorders Identification Test (AUDIT) scale. Of 598 participants, 84% responded "false" to: "it is safe for a person with HCV to drink alcohol". Problem drinking, defined as score > or =8 on AUDIT, was identified in 37%. Correlates of scoring > or =8 on AUDIT included homelessness, male gender, primarily injecting speedballs, having injected with used needles, prior alcohol treatment and depression. Although most HCV seropositive IDUs in our sample appear informed about their increased risk of liver disease from alcohol, two-fifths screened positive for problem alcohol use. These findings underscore the importance of referring HCV-positive persons to effective alcohol treatment programs to reduce future liver damage and improve eligibility for and effectiveness of treatment of HCV.
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PMID:High prevalence of alcohol use among hepatitis C virus antibody positive injection drug users in three US cities. 1612 67

It has been reported that hepatitis C virus (HCV) infection is associated with cognitive dysfunction, fatigue and depression, which do not correlate with the severity of liver disease and cannot be accounted for by hepatic encephalopathy or drug abuse. There is also emerging evidence that HCV infection can have negative neurocognitive effects in HIV-infected cohorts. Magnetic resonance spectroscopy has suggested the likely existence of a biological basis for these effects. HCV replicative forms have recently been detected in autopsy brain tissue and the infected cells have been identified as CD68-positive (macrophages/microglia). These findings raise the possibility that HCV infection of the brain could be directly related to the reported neuropsychological and cognitive changes. HCV is not strictly hepatotropic, as it can also replicate in leukocytes, including monocytes/macrophages. The latter cells could provide access of HCV into the central nervous system ('Trojan horse' mechanism) in a process similar to that postulated for HIV-1. In support of this hypothetical mechanism come reports showing a close relationship between HCV sequences present in the brain and cerebrospinal fluid and sequences found in lymph nodes and peripheral blood mononuclear cells. However, despite some similarities there is a fundamental difference between HIV-1 and HCV infection as the latter does not progress into AIDS-type dementia.
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PMID:Emerging evidence of hepatitis C virus neuroinvasion. 1625 11

Treatment for hepatitis C virus (HCV) is rarely received by injection drug users (IDU), particularly those co-infected with HIV. We propose a framework for understanding factors that affect utilization and adherence to HCV therapy among HCV mono-infected and HIV/HCV-co-infected IDU. Provision of treatment requires calculation of risks and benefits including evaluation of a number of time-varying factors that collectively determine a gradient of treatment eligibility, advisability and acceptability, the relative importance of which may differ in co-infected and mono-infected IDU. Treatment eligibility is determined by a number of non-modifiable and modifiable contraindications, the latter of which can change over time rendering patients who were once ineligible eligible. Among those eligible, treatment need can be assessed by liver biopsy and therapy may be deferred in those with no liver disease and started in those with significant liver disease. Among those with moderate disease, further consideration of treatment advisability (medical factors that affect treatment response) and acceptability (individual, provider and environmental barriers) is needed before treatment decisions are made. These factors are dynamic and thus should be continually evaluated even among those who may not initially appear to be ready for treatment. An evaluation of this framework is needed to determine applicability and feasibility. Until then, treatment decisions should be made on an individual basis after careful consideration of these issues by provider and patient and efforts to develop novel strategies for identifying IDU who need treatment most (alternatives to liver biopsy) and multidimensional approaches to deliver treatment for HCV while addressing other factors including HIV infection, depression and drug use should be continued.
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PMID:A framework for understanding factors that affect access and utilization of treatment for hepatitis C virus infection among HCV-mono-infected and HIV/HCV-co-infected injection drug users. 1625 16

Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.
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PMID:A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection. 1625 29


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