Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
 ...
PMID:Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. 204 24

Human immunodeficiency virus type 1 (HIV) infection of the central nervous system is characterized by neuronal loss in discrete areas of the central nervous system. We have previously demonstrated that HIV-infected monocytes in culture with astroglial cells produce high levels (> or = 200 pg/ml) of the cytokine tumor necrosis factor-alpha (TNF alpha). We now demonstrate that TNF alpha (> or = 200 pg/ml) is neurotoxic to cultured primary human fetal cortical neurons at both light and electron microscopic levels. Subtoxic doses of TNF alpha (50 pg/ml) are neurotoxic in combination with the glutamate (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) subtype receptor agonist AMPA (100 microM). The neurotoxic effects of TNF alpha (200 pg/ml) are blocked in part by the AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione (10 microM). This suggests that TNF alpha may exert neurotoxic effects on human neurons by indirect activation of AMPA receptors, which may be important in the pathogenesis and treatment of HIV-mediated encephalopathy.
 ...
PMID:Neurotoxic effects of tumor necrosis factor alpha in primary human neuronal cultures are mediated by activation of the glutamate AMPA receptor subtype: implications for AIDS neuropathogenesis. 783 47

Immunological and viral studies were conducted on cerebrospinal fluid from 31 HIV-1-infected children, of whom 23 were neurologically asymptomatic and 8 had progressive encephalopathy. After AZT treatment, a second cerebrospinal fluid specimen was obtained from 15 children, 11 of whom were neurologically asymptomatic and 4 had progressive encephalopathy. Virus isolation and p24Ag detection were more frequent in children with progressive encephalopathy than in asymptomatic children (66% versus 12%) and were inversely correlated with intrathecal HIV-1-antibody detection (anti-gag AB: 25% versus 70%). High concentrations of interleukin-1 beta (IL-1 beta) and IL-6 were found in children with progressive encephalopathy (50% and 37%, respectively), but low levels were also detected in some asymptomatic children (13% and 9%, respectively). Tumour necrosis factor-alpha (TNF alpha) was not found. AZT treatment induced disappearance of p24Ag in cerebrospinal fluid, as well as a marked reduction in cytokine levels. Cytokine determination may be useful in monitoring AZT treatment in children with progressive encephalopathy.
 ...
PMID:Cerebrospinal fluid analysis in HIV-1-infected children: immunological and virological findings before and after AZT therapy. 784 99

The cytokine release syndrome (CRS) accompanying OKT3 therapy is a major cause of posttransplant morbidity. The pathogenesis of this syndrome has been attributed to the synthesis of tumor necrosis factor, interleukin 2 (IL-2), interleukin 6 (IL-6), and gamma-interferon in response on T lymphocyte stimulation by OKT3. The hemorrheologic agent pentoxifylline (PTX) inhibits the synthesis of TNF alpha in vitro in response to a variety of stimuli, including OKT3. We performed a randomized, double-blinded trial of PTX during OKT3 induction in recipients of cadaveric renal allografts. Patients received either PTX 800 mg or placebo 2 hr before the initial dose of OKT3 and every 8 hr thereafter during the first 3 posttransplant days. Serum TNF alpha and IL-6 concentrations were measured pre-OKT3 and at 2 and 6 hr post-OKT3 on the first 3 posttransplant days. Despite the achievement of apparently adequate plasma levels of PTX and its active metabolites, no difference was observed in the incidence or severity of clinical manifestations of CRS. Serious manifestations of CRS--including acute pulmonary edema, encephalopathy, and aseptic meningitis--were not seen in either group. Serum TNF alpha and IL-6 concentrations were similar in PTX and control patients throughout the course of the study. Plasma levels of PTX and its active metabolites did not correlate with serum TNF alpha levels, serum IL-6 levels, or the incidence and severity of clinical manifestations of CRS.
 ...
PMID:The effects of oral pentoxifylline on the cytokine release syndrome during inductive OKT3. 811 37

In the literature the separation between RS and RLS is confusing and makes it difficult to plan an appropriate preventive action or to develop new therapeutic approaches. We suggest that the generalized damage and encephalopathy seen in both RS and RLS may be due to a wide variety of causative agents that contribute to a common derangement, principally involving mitochondrial oxidative pathway. Fasting status and infections increase the catabolism and the subsequent flux of metabolites from peripheral tissues to the liver (FA and amino acids); cytokines (TNF, IL-1, and IL-6), in particular, mediate this effect during infection and experimental endotoxemia. Some drugs and other toxic compounds induce functional and morphological liver mitochondrial derangement. Oxidative metabolism is impaired, with subsequent stimulation of alternative pathways of oxidation, following production of unusual toxic acyl CoAs and dicarboxylic acids. Toxic compounds accumulate in the liver, deranging its functions and causing energy depletion, and are also released in the circulation from which they reach other tissues, including the brain. Neurons and astrocytes in the brain may be affected differently: Neurons suffer from the lack of energy and the effect of toxic compounds arriving from the bloodstream, and astrocytes may be directly affected by the beta-oxidation derangement. Very important may be genetic predisposition, which, by making the patient more sensitive to a particular causative agent, may facilitate the onset of RS and RLS. The therapeutic approach is, presently, mainly symptomatic, directed as it is to counteracting each alteration shown, depending by the clinical gravity. Other pharmacological approaches are only studied experimentally, like carnitine supplementation and PGE2 administration, or theoretically envisaged, like monoclonal antibody therapy directed at LPS or at pro-inflammatory cytokines or treatment with interferon-alpha.
 ...
PMID:Reye's and Reye-like syndromes, drug-related diseases? (causative agents, etiology, pathogenesis, and therapeutic approaches). 852 53

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are important cytokines in the development of brain inflammation during pathological process. During rabies virus infection, the level of these proinflammatory cytokines are enhanced in the brain. In the present study we determined the cellular localization of these two cytokines by immunocytochemistry in brains of rats infected with rabies virus, at different time-intervals of the disease (day 1, 3, 4, 5 and at final stage day 6 post-infection (p.i.)). Cellular identification of IL-1 beta (irIL-1 beta) and TNF alpha (irTNF alpha) immunopositive cells was studied using a polyclonal antibody against these cytokines and against glial fibrillary acidic protein (GFAP) to detect astrocytes and GSA-I-B4 isolectin to detect microglial cells and/or infiltrating macrophages. In brains of control and early infected rats, irIL-1 beta was only detected in fibers located in the hypothalamus, supraoptic and tractus optic nuclei and infundibular nucleus. From day 4 onwards until day 6 p.i., enhanced irIL-1 beta was found and identified either in activated ameboid and/or infiltrated macrophages (amygdala, thalamus, internal capsula, subtantia nigra, septal nuclei and around blood vessels), or in activated ramified cells (hypothalamus and periventricular nucleus, piriformis and cingulate cortex, hippocampus). IrTNF alpha was observed in the brains of rats at a final stage of disease (day 5 and 6 p.i.): in the hypothalamus, the amygdala, the internal capsula, the thalamus, the septal nuclei, the hippocampus, the habenular nuclei and around the blood vessels. Ir-TNF alpha was detected in round cells identified as ameboid microglia and/or infiltrated macrophages. A marked activation of microglial and astroglial cells was observed mainly in the hypothalamus, the thalamus and hippocampus and around the blood vessels, at day 4 p.i. and later, revealing a high central inflammatory reaction in brains of rabies virus infected rats. These results showed that IL-1 beta and TNF alpha are produced in the brain both by local microglial cells and infiltrating macrophages during rabies infection. Thus, these cytokines may play an important role in coordinating the dramatic inflammatory response associated with the rabies-encephalopathy as well as in the neural modification and alteration of brain functions.
 ...
PMID:Induction of immunoreactive interleukin-1 beta and tumor necrosis factor-alpha in the brains of rabies virus infected rats. 878 59

Both in vitro and in vivo studies have implicated a role for tumor necrosis factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related encephalopathy. To investigate whether intravitreal TNF alpha can induce optic nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively) and studied at varying time intervals for up to 24 weeks post-injection, using light and electron microscopy. Control optic nerves (no injection or diluent injection only) had normal myelinated axons and glia; the myelinated regions, neural retina, retinal glia and vasculature of control retinas were normal. In TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF alpha-exposed optic nerves, and activated macrophages or microglia were not obvious. Axonal degeneration was visible among the more superficial myelinated fibers in TNF alpha-exposed retinas however the neural retina glia were unaffected. These observations suggest that the axonal degeneration induced in TNF alpha-exposed rabbit optic nerves over a 24 week period was most likely related to direct effects of TNF alpha on optic nerve axons, and not primarily due to anterograde degeneration from retinal lesions. In-so-far as neurological pathology in general, and optic nerve degeneration in particular, has been described in AIDS, and TNF alpha levels may be elevated in this disease, it is of great clinical significance that TNF alpha has the capacity to mediate neuronal or axonal injury. If so, strategies to block or inhibit TNF alpha can be pursued for treatment for the neurological symptoms of AIDS.
 ...
PMID:Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits. 916 75

In order to explore the allelic polymorphism of HLA-DR and TNF B loci and susceptibility to systemic lupus erythematosus (SLE) in the Han nationality of northern China with the aid of methods of polymerase chain reaction/sequence specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. The findings from a case-control study on 151 blood samples (45 from the cases and 106 from the controls) indicated that there were significantly higher frequency of DR2 (P < 0.05, RR = 1.56) and DR3 (P < 0.01, RR = 2.69), which represent candidate susceptible genes or useful markers for SLE. The DR5 allele in the samples (P < 0.05, RR = 0.43) might be an antagonistic or protective allele, or a marker for such allele. The frequency of TNF B * 1 and TNF B * 2 alleles was investigated in 45 SLE patients and 80 healthy controls and it was found that the frequency of TNF B * 2 allele was significantly higher in the patient group (P < 0.05, RR = 1.84). It might also be a suspicious susceptible allele or a marker for such allele. The frequency of HLA polymorphisms in various clinical/immunological subsets of our patient population was also determined. Clinical findings used include plasma SC5b-9 level, SSA, SSB, Sm, RNP, ANA antibodies, and SLE complications (SLE nephritis, pneumonia & encephalopathy). It turned out that there was a positive association between HLA-DR2 allele and SLE nephritis (P < 0.05, RR = 1.32).
 ...
PMID:[Study on some susceptible genes of systemic lupus erythematosus in Han nationality of China]. 927 40

The central nervous system (CNS) is often affected by HIV-1 infection. Over 40% of AIDS cases present with neurological symptoms and CNS lesion are detected by anatomical and pathological studies in 80 to 90% of AIDS cases. There may be infections and tumors secondary to the immunodeficiency and pathologies may occur directly due to the neurotropism of the virus. Neurological problems associated with HIV-infection include encephalopathies, myelopathies, neuropathies and myopathies. HIV-1-induced encephalopathy may develop at any stages of HIV-1 infection and affects all risk groups equally. Its frequency worldwide is between 4 and 65% among individuals seropositive for HIV-1. The frequencies reported differ between studies due to differences in sampling methods, geographical factors, diagnostic criteria and investigative methods used. The pathogenesis of HIV-1-associated encephalopathy is not understood, but there are several hypotheses. The involvement of HIV-1 infected macrophages and microglial cells has been demonstrated. Indirect mechanisms such as release of lymphokines (tumor necrosis factor-TNF alpha- and interleukin-1) and neurotoxicity of the HIV envelope protein, gp 120, have also been suggested. This disorder is known as HIV-1-associated cognitive and motor syndrome. It presents clinically as a form of sub-cortical dementia with cognitive problems, motor deficits and behavioral disorders depending on the type and stage of HIV infection. The diagnosis can only be made after all other infections and tumors common in HIV-1 patients have been ruled out by appropriate investigations such as cerebrospinal fluid analysis, cerebral scan and magnetic resonance imaging. Electrophysiological studies, such as evoked responses and electroencephalograms, are particularly useful in its diagnosis. Anatomical examination shows diffuse paleness of the white matter, multi-nucleated giant cells and microglial nodes. Neuropsychological studies could be of value in diagnosis and in assessing the response to anti-retroviral treatment. There is currently no specific therapy for HIV-1-associated cognitive and motor syndrome. The use of new nucleoside analogue drugs in combination with existing drugs may provide new approaches to managing these patients.
 ...
PMID:[HIV-1 cognitive and motor syndrome]. 929 10

The neuropathology associated with HIV (Human Immunodeficiency Virus) infection is one of the major complications of this disease. The virological and cellular mechanisms by which HIV infection induces motor and cognitive disorders remain unknown. This lack of understanding of the pathophysiology is partly due to the difficulty of experimental analysis in man because only post-mortem samples from terminal phases of the disease and cerebrospinal fluid samples are available. Two animal models, very closely resembling human HIV infection, are available: the cat model infected by FIV (Feline Immunodeficiency Virus) and the macaque model infected by the SIVmac (Simian Immunodeficiency Virus) which have enabled us to conduct a longitudinal study of encephalopathy during primo-infection and the asymptomatic and pre-AIDS (Acquired Immune Deficiency Syndrome) phases. In the cat-FIV model, which presents the advantage of being non-infectious to man, and therefore easier to manipulate, it was shown that infected cats develop behavioural abnormalities and a neuropathology which resemble HIV dementia. Central nervous system lesions induced by FIV are similar to those of HIV infection apart from the absence of multinucleated giant cells. This model was used to analyse the relationship between CNS lesions and the viral load of the brain and showed that the severity of the lesions contrasted with a low viral load. The pathophysiology of SIVmac infection in the rhesus macaque is almost identical to human infection with a more rapid course, since the duration of the asymptomatic phase is 6 months to 5 years, depending on the animal. We studied the relationship between lesions, viral load and cytokine production (IL-1 beta, IL-2, IL-6, TNF alpha, INF gamma, TGF-beta 1) within the CNS. Our results show early, low-grade and constant infection of the brain. The dissociation between the viral load and the lesions observed is our favour of an indirect mechanism for the pathogenesis of these lesions. The relationship between lesions and the cytokine profile studied shows the importance of glial cells in the pathogenesis of the lesions.
 ...
PMID:[Contribution of animal models in the understanding of AIDS encephalopathy]. 938 13


1 2 3 4 5 6 7 8 9 Next >>