Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate reports of abnormal levels of free amino acids (AA) in patients with amyotrophic lateral sclerosis (ALS), we studied serum, cerebrospinal fluid, and urine AA in 12 patients with ALS and 12 controls matched for age, sex, and severity of disability. ALS patients had statistically significant elevations in serum levels of tyrosine, total aromatic AA, and total basic AA. ALS patients also had statistically significant elevations in cerebrospinal fluid of total basic AA, lysine, essential AA, and leucine. The severity of ALS correlated inversely with acidic AA (glutamate and aspartate) and O-phosphoserine in cerebrospinal fluid. Activity of ALS correlated directly with serum aspartate and cerebrospinal fluid alanine. We conclude that subtle abnormalities of AA levels are present in ALS and that these are not due to age, sex, or disability. The pattern of distribution of AA levels differs from that in hepatic or renal disease and suggests defective membrane transport or poor cellular utilization of basic and essential AA in the central nervous system.
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PMID:Free amino acid levels in amyotrophic lateral sclerosis. 66 70

The role of free radicals (FR) in the pathogenesis and in the progression of many diseases has been often discussed, but not widely investigated. However, the total antioxidant capacity in the serum seems to be of great evidence. Total antioxidant capacity was determined using oxygen absorbance capacity assay (ORAC) in serum of patients suffering from depression, schizophrenia, Alzheimer's disease (AD), anorexia nervosa, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Aids-encephalopathy, diabetic polyneuropathy (PNP), cardiomyopathy (CM), renal disease, and healthy individuals as controls (C). The results showed that the total antioxidant capacity in serum decreased significantly (p < 0.01) by 24, 20, 13, and 17% for anorexia nervosa, Aids-encephalopathy, PNP and CM respectively. In serum of patients with renal disease significantly elevated antioxidant capacity was found. The data indicated that increased oxidative stress can be involved in the pathogenesis or in the progression of PNP and CM. Decrease of serum antioxidant capacity in patients with anorexia nervosa and Aids-encephalopathy are probably due primarily to malnutrition and secondly to insufficient antioxidant and immune system. In renal disease, the accumulation of urea in serum seems to be responsible for high antioxidant capacity. In contrast, there were no changes in PD, AD, depression syndrome and schizophrenia.
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PMID:Serum antioxidant capacity in neurological, psychiatric, renal diseases and cardiomyopathy. 1211 62

Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia). In this paper the goal is evaluation of cell therapy in treatment of Parkinson's disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.
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PMID:Stem cell therapy in treatment of different diseases. 2235 76

Enormous strides have been made in the last 100 years to extend human life expectancy and to combat the major infectious diseases. Today, the major challenges for medical science are age-related diseases, including cancer, heart disease, lung disease, renal disease, and late-onset neurodegenerative disease. Of these, only the neurodegenerative diseases represent a class of disease so poorly understood that no general strategies for prevention or treatment exist. These diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, the transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis (ALS), are generally fatal and incurable. The first section of this review summarizes the diversity and common features of the late-onset neurodegenerative diseases, with a particular focus on protein misfolding and aggregation-a recurring theme in the molecular pathology. The second section focuses on the particular case of ALS, a late-onset neurodegenerative disease characterized by the death of central nervous system motor neurons, leading to paralysis and patient death. Of the 10% of ALS cases that show familial inheritance (familial ALS), the largest subset is caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). The unusual kinetic stability of SOD1 has provided a unique opportunity for detailed structural characterization of conformational states potentially involved in SOD1-associated ALS. This review discusses past studies exploring the stability, folding, and misfolding behavior of SOD1, as well as the therapeutic possibilities of using detailed knowledge of misfolding pathways to target the molecular mechanisms underlying ALS and other neurodegenerative diseases.
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PMID:Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis. 2350 86

Allisartan isoproxil (ALS-3) is a selective, nonpeptide blocker of the angiotensin II type 1 receptor. It is a new antihypertensive drug under development with a novel chemical structure. The aim of this study was to evaluate the potential toxicity of ALS-3 in Sprague-Dawley rats. Animals were orally administered either vehicle or ALS-3 at doses of 20, 80 and 320 mg/kg once-daily for 26 weeks, followed by a 6-week recovery period. Toxicity was assessed by mortality, clinical signs, body weight, food consumption, hematology, coagulation, serum chemistry, gross necropsy, organ weights and microscopic examination. Decreased body-weight gain was noted at 320 mg/kg/day in both sexes as well as at the 80-mg/kg/day dose in females. Food consumption was decreased at all doses in males and at 80- and 320-mg/kg/day doses in females. Decreased erythrocyte parameters (erythrocyte count, hemoglobin and hematocrit) were observed in males receiving 320 mg/kg/day. Elevated urea nitrogen (BUN), increased kidney weight, decreased heart weight and exacerbation of chronic progressive nephropathy (CPN) severity were all observed in males at 80 and 320 mg/kg/day. However, only an exacerbated incidence of CPN was observed in females at 320 mg/kg/day. All changes were reversed after the 6-week recovery period, except BUN and CPN. Based on these results, we concluded that a dose of 20 mg/kg/day was the no observed adverse effect level. The toxicity target organ was the kidney. Males were more affected than females.
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PMID:A 26-week repeated-dose toxicity study of allisartan isoproxil in Sprague-Dawley rats. 2353 54

Chronic neurologic diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as various forms of chronic renal disease and systolic congestive heart failure, are among the most common progressive degenerative disorders encountered in medicine. Each disease follows a nearly relentless course, albeit at varying rates, driven by progressive cell dysfunction and drop-out. The neurologic diseases are characterized by the progressive spread of disease-causing proteins (prion-like proteins) from cell to cell. Recent evidence indicates that cell autonomous renin angiotensin systems operate in heart and kidney, and it is known that functional intracrine proteins can also spread between cells. This then suggests that certain progressive degenerative cardiovascular disorders such as forms of chronic renal insufficiency and systolic congestive heart failure result from dysfunctional renin angiotensin system intracrine action spreading in kidney or myocardium.
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PMID:A possible mechanism for the progression of chronic renal disease and congestive heart failure. 2553 96

Ralstonia species are Gram-negative bacilli that have increasingly been recognized as emerging nosocomial pathogens, particularly in immunocompromised hosts. Ralstonia pickettii is the most clinically important pathogen from the Ralstonia genus. Nosocomial outbreaks of Ralstonia pickettii infections brought about by the use of contaminated medical solutions, including saline, sterile water, as well as disinfectants, have been reported. There have been case reports of invasive infections with variable presentations. Here, we describe three cases of Ralstonia pickettii bacteremia during a period of one year in a tertiary care hospital in Karachi, Pakistan. The first case was a 76-year-old male, known case of type 2 diabetes mellitus (DM), hypertension, and amyotrophic lateral sclerosis, who presented with complaints of burning micturition, hematuria, and fever. The patient had a history of multiple hospital admissions in the recent past. His blood culture was found to be positive for Ralstonia pickettii. A computed tomography scan of the kidneys, ureter, and bladder (CT KUB) was suggestive of pyelonephritis. The patient improved on intravenous meropenem. The second case was a 47-year-old man, who was admitted with a gunshot injury to the neck, resulting in complete cervical cord resection and mild hydrocephalus with intraventricular hemorrhage. The patient had a prolonged intensive care unit (ICU) stay, which was complicated by ventilator-associated pneumonia with Acinetobacter and central line-associated bloodstream infection (CLABSI) with Ralstonia pickettii. He was treated with meropenem and colistin but continued to deteriorate and expired. The third case was a 46-year-old lady, known case of end-stage renal disease (ESRD), who was admitted with prosthetic valve endocarditis. She had a prolonged hospital stay complicated by CLABSI with Ralstonia pickettii, improved on meropenem, but later died due to fungemia. Ralstonia pickettii is an emerging cause of nosocomial infection in patients, particularly those with a prolonged hospital stay, and can cause invasive and severe infections.
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PMID:Ralstonia pickettii Bacteremia: An Emerging Infection in a Tertiary Care Hospital Setting. 3151 93

Good health depends on the maintenance of metabolic flexibility, which in turn is dependent on the maintenance of regulatory flexibility of a large number of regulatory enzymes, but especially the pyruvate dehydrogenase complex (PDC), because of its central role in carbohydrate metabolism. Flexibility in regulation of PDC is dependent on rapid changes in the phosphorylation state of PDC determined by the relative activities of the pyruvate dehydrogenase kinases (PDKs) and the pyruvate dehydrogenase phosphatases. Inactivation of the PDC by overexpression of PDK4 contributes to hyperglycemia, and therefore the serious health problems associated with diabetes. Loss of regulatory flexibility of PDC occurs in other disease states and pathological conditions that have received less attention than diabetes. These include cancers, non-alcoholic fatty liver disease, cancer-induced cachexia, diabetes-induced nephropathy, sepsis and amyotrophic lateral sclerosis. Overexpression of PDK4, and in some situations, the other PDKs, as well as under expression of the pyruvate dehydrogenase phosphatases, leads to inactivation of the PDC, mitochondrial dysfunction and deleterious effects with health consequences. The possible basis for this phenomenon, along with evidence that overexpression of PDK4 results in phosphorylation of "off-target" proteins and promotes excessive transport of Ca2+ into mitochondria through mitochondria-associated endoplasmic reticulum membranes are discussed. Recent efforts to find small molecule PDK inhibitors with therapeutic potential are also reviewed.
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PMID:Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases. 3262 51