Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several dideoxynucleosides, including 3'-azido-2',3'-dideoxythymidine (zidovudine, azidothymidine, AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyinosine (ddI), have been shown to be potent inhibitors of human immunodeficiency virus (HIV) replication in human T cells and macrophages. These compounds undergo anabolic phosphorylation within target cells to a 3'-triphosphate moiety; as triphosphates, they act at the level of HIV DNA polymerase (reverse transcriptase). AZT has been shown to reduce the morbidity and mortality of patients with severe HIV infection and to at least temporarily ameliorate certain cases of HIV-induced dementia. In phase 1 studies, ddC and ddI have been shown to induce immunologic and virologic improvements in patients with AIDS or related disorders; phase 2 studies of ddC and ddI are underway. The use of these drugs can be associated with toxicity. AZT can cause bone marrow toxicity or myositis with prolonged use, ddC can cause peripheral neuropathy at high doses, and ddI can cause sporadic pancreatitis and peripheral neuropathy at high doses. For each compound, however, a therapeutic window exists in which an anti-HIV effect can be attained without short-term toxicity in most patients. Dose-intensity appears to be an important determinant of the toxicity of dideoxynucleosides. Studies are underway to explore how the therapeutic profiles of these compounds may be enhanced by attention to scheduling or through the use of combination therapy.
 ...
PMID:Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. 207 27

Nucleoside analogues represent the cornerstones of antiretroviral regimens. A range of drug- or tissue-specific toxicities, such as peripheral neuropathy, myopathy, pancreatitis and lactic acidosis with hepatic steatosis, has been documented with these agents. The fat atrophy seen on long term antiretroviral therapy may also be related to nucleoside analogues. The mechanisms by which nucleoside analogues cause toxicity are not clearly established. In vitro, the triphosphates of these agents are weak to modest substrates for human DNA polymerases, showing the greatest affinity for mitochondrial DNA polymerase gamma. Short term exposure in vitro to some nucleoside analogues has been demonstrated to cause increased lactate production or falls in mitochondrial DNA suggestive of mitochondrial toxicity. However, stavudine and to a lesser extent zidovudine are poor substrates for mitochondrial thymidine kinase type 2, the predominant form in cells that are not actively mitotic such as neurons, myocytes and adipocytes. These are the cell types where the proposed mitochondrial toxicities neuropathy, myopathy and lipoatrophy are observed. Thus, active concentrations of phosphorylated products of stavudine and zidovudine may not be present in mitochondria. The familial mitochondrial diseases do not have identical presentations to nucleoside analogue toxicities. These disorders most commonly involve the CNS, typically with seizures or dementia, and occasionally the kidneys. Although nucleoside analogues are known to penetrate the CNS and are commonly renally excreted unchanged, mitochondrial toxicities at these sites have not been documented. Furthermore, toxicity caused by nucleoside or nucleotide analogues does not always appear to arise through the mitochondrial route. Cidofovir appears to cause renal tubular dysfunction via a toxic intracellular metabolite, and zidovudine-related anaemia appears to be related to decreased globin RNA synthesis. In vitro or animal models suggest that zidovudine myopathy, stavudine-related (but not zalcitabine- or didanosine-related) neuropathy and didanosine-related pancreatitis may all be not related, or not exclusively related, to mitochondrial dysfunction. The integration of nucleoside analogues into nuclear DNA, best documented with zidovudine but likely to occur with other agents, represents an alternative but potentially delayed pathway to cytotoxicity and cell apoptosis. This is the mechanism of cell death during therapy with antineoplastic nucleoside analogues, and may have contributed to the multisystem toxicities observed with the anti-hepatitis B drug fialuridine. New research evaluating the effects of long term exposure of cell lines is required to address the possibility that nuclear genotoxicity plays a role in long term nucleoside analogue toxicity.
 ...
PMID:Toxicity of antiretroviral nucleoside and nucleotide analogues: is mitochondrial toxicity the only mechanism? 1114 57

Pancreatic encephalopathy is a rare complication of acute pancreatitis. Clinical features include focal neurological signs and acute onset of dementia. This picture can fluctuate over time: cyclic progression with remission and relapses has been described. We present the case of a 43-year-old man who, after an acute episode of pancreatitis, experienced five relapses, with alternating focal signs. The patient has improved, but cognitive impairment persists after a 7-year follow-up.
 ...
PMID:Pancreatic encephalopathy: a 7-year follow-up case report and review of the literature. 1253 91

Mitochondriopathies (MCPs) are either due to sporadic or inherited mutations in nuclear or mitochondrial DNA located genes (primary MCPs), or due to exogenous factors (secondary MCPs). MCPs usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Although several proteins with signalling, assembling, transport, enzymatic function can be impaired in MCP, most frequently the activity of the respiratory chain (RC) protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. MCPs represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in MCP are the peripheral nervous system (myopathy, polyneuropathy, lactacidosis), brain (leucencephalopathy, calcifications, stroke-like episodes, atrophy with dementia, epilepsy, upper motor neuron signs, ataxia, extrapyramidal manifestations, fatigue), endocrinium (short stature, hyperhidrosis, diabetes, hyperlipidaemia, hypogonadism, amenorrhoea, delayed puberty), heart (impulse generation or conduction defects, cardiomyopathy, left ventricular non-compaction heart failure), eyes (cataract, glaucoma, pigmentary retinopathy, optic atrophy), ears (deafness, tinnitus, peripheral vertigo), guts (dysphagia, vomiting, diarrhoea, hepatopathy, pseudo-obstruction, pancreatitis, pancreas insufficiency), kidney (renal failure, cysts) and bone marrow (sideroblastic anaemia). Apart from well-recognized syndromes, MCP should be considered in any patient with unexplained progressive multisystem disorder. Although there is actually no specific therapy and cure for MCP, many secondary problems require specific treatment. The rapidly increasing understanding of the pathophysiological background of MCPs may further facilitate the diagnostic approach and open perspectives to future, possibly causative therapies.
 ...
PMID:Mitochondriopathies. 1500 63

The aim of the overview is to show the distribution of common apolipoprotein E (APOE) genotypes in the Croatian population, and to test whether it could serve as a new molecular biomarker in some clinical entities. The study included the following groups: patients with angiographically confirmed coronary artery disease, myocardial infarction, Alzheimer's dementia, vascular dementia, hyperlipidemias, diabetes mellitus, pancreatitis, and healthy subjects. Group comparisons of different clinical entities and control group were performed using Pearson's Chi2-test. There was no difference in APOE genotype frequencies between coronary artery disease neither myocardial infarction and control group. The ApoE genotype frequencies in patients with Alzheimer's disease were significantly different from those in the control group. APOE-4 allele tends to be a risk factor for the development of Alzheimer's disease. The frequencies were only marginally different in vascular dementia. Patients with hypercholesterolemia, those with inherited familial hypercholesterolemia, children with diabetes mellitus, and patients with pancreatitis of different etiology showed distributions of APOE genotypes that differed from the control group. It is concluded that the frequencies of APOE genotypes yielded no statistically significant result to confirm the association between APOE genotypes and any specific disease with the exception of Alzheimer's disease; APO-epsilon4 allell has become one of the important biomarkers in diagnosis of Alzheimer's dementia.
 ...
PMID:[The frequencies of apolipoprotein E genotypes in health and disease in the Croatian population--an overview of expectations and real results]. 1721 95

Strategic lesions of the thalamus interfere with cognitive functions and produce complex neuropsychological symptoms. Bilateral, simultaneous thalamic hemorrhages are unusual causes of thalamic dementia. We present clinical, neuropsychological and structural neuroimaging data of a 12-month follow-up period of a patient with bilateral thalamic hemorrhages. After the operation of pancreatitis acuta hemorrhagico-necroticans, the patient developed coma. Computed tomography (CT) and magnetic resonance (MR) of the brain showed medially situated bithalamic hematomas. During the follow-up period, patient's level of consciousness has improved. Moderate dementia (MMSE 20/30) was found with severe temporal and spatial disorientation. Neuropsychological tests showed that attention and concentration were prominently impaired; there were severe verbal and less prominent, visual memory deficits, with anterograde and retrograde amnesia, accompanied by confabulations. Loss of cognitive flexibility and dysexecutive syndrome were also demonstrated. Dynamic apraxia, visual organization and visual construction deficit and impairment of categorial and phonemic fluency were noted. Language was only moderately impaired (anomia). A year later, neuropsychological profile was similar with moderate improvement of retrograde amnesia, whereas anterograde deficits persisted. Neuropsychological syndrome in our patient with bilateral thalamic hemorrhages was characteristic for subcortico-cortical cognitive deficit and was caused by disruption of the cortico-thalamic circuitry.
 ...
PMID:Neuropsychological deficits after bithalamic hemorrhages. 1739 6

Different types of alcoholic beverages such as wine and beer were used in ancient times for various medicinal purposes. Being the oldest and probably the most widely used drugs, they were known to have some therapeutic value, in addition to the vital part they played in the daily life of people. Ethanol is produced by fermentation of a variety of plants and consumed either in a diluted form or concentrated by distillation to concoct alcoholic beverages. Beer made of fermented barley is an alcoholic drink that was believed to contain a spirit or a god. It is a drink of relatively low alcohol content with supernatural properties. The same was believed for wine. Considered to be divine, these beverages were the long sought elixirs of life and appeared in religious ceremonies, in mythology, and in social meals, such as the Greek symposia. In addition, these alcoholic drinks were considered to be a remedy for practically every disease and, therefore, were a common ingredient in ancient prescriptions. They were used as anaesthetics that dull the pain, as stimulants, as analgesics, as antiseptics to cleanse wounds and relieve pain, as emetics, as digestives, as antidotes for plant poisoning, for bites and stings, and as purifiers. However, we should not overlook the harmful effects of alcohol abuse such as drunkenness, chronic liver disease and, in modern terminology, infirmities that included pancreatitis, cardiomyopathy, peripheral neuropathy, dementia, and central nervous system disorders.
 ...
PMID:Beer and wine in antiquity: beneficial remedy or punishment imposed by the Gods? 2356 Jul 53

To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.
...
PMID:First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia. 2502 35

It has long been known that people with alcohol use disorder (AUD) not only may develop physical dependence but also may experience devastating long-term health problems. The most common and identifiable alcohol-associated health problems include liver cirrhosis, pancreatitis, cardiomyopathies, neuropathies, and dementia. However, the lung also is adversely affected by alcohol abuse, a fact often overlooked by clinicians and the public. Individuals with AUD are more likely to develop pneumonia, tuberculosis (TB), respiratory syncytial virus (RSV) infection, and acute respiratory distress syndrome (ARDS). Increased susceptibility to these and other pulmonary infections is caused by impaired immune responses in people with AUD. The key immune cells involved in combating pulmonary conditions such as pneumonia, TB, RSV infection, and ARDS are neutrophils, lymphocytes, alveolar macrophages, and the cells responsible for innate immune responses. Researchers are only now beginning to understand how alcohol affects these cells and how these effects contribute to the pathophysiology of pulmonary diseases in people with AUD.
...
PMID:Alcohol's Effects on Lung Health and Immunity. 2669 45

Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure-harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.
 ...
PMID:Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research. 2886 38


1 2 Next >>