Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The author has performed in vivo investigations of the methotrexate (MTX) accumulation, kinetics and polyglutamate metabolism in erythrocytes, neutrophils and myeloid bone marrow cells during clinical MTX therapy of patients with acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma and psoriasis. On the basis of these studies the clinical applicability of monitoring erythrocyte MTX concentrations in children with ALL and adult psoriasis patients have been evaluated. To accomplish this task a set of methods has been developed: 1) An automated enzymatic assay adapted for a centrifugal analyzer was used to measure MTX concentrations between 10 and 60 nmol/l in erythrocytes and serum. 2) For the study of MTX kinetics in myeloid cells, age fractionated erythrocytes and HPLC fractionated methotrexate polyglutamates a sequential radioligand binding assay with a range of 1-8 (and 1-16) nmol/l was employed. 3) Discontinuous Percoll gradients of increasing densities were used to separate myeloid cells and erythrocytes of increasing mean cell age. Declining reticulocyte counts and erythrocyte-aspartate aminotransferase activity were taken as parameters of increasing mean erythrocyte age. 4) In order to study MTX polyglutamate metabolism a high performance liquid chromatography (HPLC) procedure was set up using tetrabutylammonium phosphate in acetonitrile in an automatically generated gradient buffer system. The MTX polyglutamates were separated, and the concentrations determined by the radioligand binding assay. The individual polyglutamates were identified by comparisons with the retention times of MTX polyglutamate standards (MTX-glu1+2+3+4+6+7) which were detected spectrophotometrically at 304 nm. During 24 hour infusions MTX was incorporated predominantly in the proliferating myeloid bone marrow cells before appearing in circulating neutrophils about seven days later. Evidence for MTX incorporation in the erythroid precursors of the bone marrow was provided by demonstrating high MTX content in density fractionated reticulocyte enriched erythrocyte populations. During weekly low dose MTX treatment the erythrocyte MTX concentration reached a constant level (steady state ery-MTX) after 4-6 weeks. MTX concentrations in age fractionated red blood cells and the terminal decline of the ery-MTX and its polyglutamate forms after cessation of MTX administration revealed that maintenance of the steady state ery-MTX depended on three conditions: 1) The amount of MTX added to the circulation via MTX containing reticulocytes. 2) The in vivo efflux of MTX from circulating erythrocytes, and 3) The loss of MTX with age dependent destruction of red blood cells. The in vivo efflux of MTX accounted for a loss of MTX which was 3-4 times greater than the amount that was lost with age dependent erythrocyte destruction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo methotrexate kinetics and metabolism in human hematopoietic cells. Clinical significance of methotrexate concentrations in erythrocytes. 217 86

To determine whether liver function tests and clinical and demographic information would predict methotrexate-associated hepatotoxicity, we identified 78 patients who had undergone 147 liver biopsies associated with methotrexate therapy for psoriasis. The joint sensitivity of aspartate aminotransferase, alkaline phosphatase, and total bilirubin values in detecting abnormal results from a biopsy specimen obtained after treatment was .86; the predictive value of negative test results was .93. A logistic regression model significantly predicted the presence of abnormal (grade III or higher) liver biopsy specimen results. The concordance index was .92 (perfect, 1.0). Regression coefficients may be used along with information from a specific patient to calculate the predicted probability of an abnormal result from a liver biopsy specimen after treatment. We conclude that this multivariate risk estimation model significantly predicts the likelihood of positive findings from liver biopsy specimens in this patient population. The clinical use of this model awaits further validation.
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PMID:Detection of hepatotoxicity associated with methotrexate therapy for psoriasis. 277 96

Two children, 19 months of age, were independently treated with a compassionate protocol of etretinate therapy for recalcitrant, debilitating pustular psoriasis. Laboratory test results, roentgenograms of the spine, and bone age were periodically monitored. Over a 31/2-year period of intermittent treatment with a maximum dosage of 1.5 mg/kg/d, both children showed remarkable improvement with no apparent drug effect on growth and development. Side effects included xerosis, skin fragility and transient, minimal elevations of aspartate aminotransferase, lactic dehydrogenase, and triglyceride levels. Etretinate therapy may prove to be a viable treatment option for the child with intractable pustular psoriasis that seriously impairs quality of life.
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PMID:Etretinate therapy for generalized pustular psoriasis in children. 354 86

The activities of glutamic-pyruvic transaminase (GPT) and catalase are increased by 42 to 283% in patients with neurodermatitis, eczema, and psoriasis, whereas the activities of glutamic-oxaloacetic transaminase, alkaline phosphatase, and cholinesterase are unchanged. In women with neurodermatitis and psoriasis the level of GPT is by 24-28% lower than in men. In psoriasis catalase activity in women is by 50% higher than in men. Hence, the activities of some enzymes in disease are related to patients' sex. Blood serum catalase measurements are diagnostically valuable in skin diseases.
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PMID:[Blood enzyme activities in men and women with certain diseases]. 775 54

Thirty patients completed this open-label, multicenter prospective study performed to evaluate the efficacy and safety of terbinafine treatment of onychomycosis of the feet in elderly patients. Inclusion criteria included an age of 60 years or older, a diagnosis of onychomycosis confirmed by positive potassium hydroxide (KOH) preparation at baseline, and toenails capable of regrowth. Patients were excluded from the study if they had received any systemic antifungal therapy within the previous 3 months or topical antifungal therapy within 1 week prior to the start of the study; had psoriasis; had toenail abnormalities interfering with normal toenail appearance; were immunosuppressed or immunodeficient; or had serum hepatic enzyme (serum glutamic-oxaloacetic transaminase, SGOT; serum glutamic-pyruvic transaminase, SGPT) values greater than 1.5 times the upper limit of normal at baseline. Following baseline evaluations, eligible patients received a 12-week supply of oral terbinafine (250 mg/day) for self-administration. Compliance was assessed by tablet counts at each visit and defined as the use of at least 80% of the medication prescribed at the first two visits. Follow-up evaluations were conducted for the next 60 weeks, for a total study period of 72 weeks. These visits occurred at weeks 6, 12, 24, 36, 48, and 72. All follow-up visits included: (i) the reporting of adverse effects; (ii) assessment of efficacy by KOH preparation, mycologic culture, and investigator evaluation; and (iii) physician and patient global assessments of various quality of life parameters (except for the visit at week 36). Safety and tolerance were assessed by physical examination at baseline and week 12, by laboratory evaluations (hematology, blood chemistry, and urinalysis) at baseline, week 6 and week 12, and by reporting and evaluation of adverse events throughout the entire study. Investigators assessed the extent of involvement of the target toenail and recorded global assessments of therapeutic efficacy at all visits. Mycologic evaluation was conducted by KOH preparation and a mycologic culture of the target toenail. Because of discrepancies in KOH results between the investigator sites and the central laboratory in early analyses, we chose to use the mycologic culture results to evaluate efficacy. Because all 30 subjects were treated with terbinafine, the entire group was considered for safety evaluation.
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PMID:Clinical trial: the safety of terbinafine in patients over the age of 60 years: a multicenter trial in onychomycosis of the feet. 1112 52

A 24-year-old man was admitted to our hospital because of liver dysfunction. He had been diagnosed as having psoriasis vulgaris at 18 years of age. Physical examination demonstrated obesity, general erythema, and hepatomegaly. Laboratory data revealed elevated serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and glucose. A histological examination of the liver revealed macrovesicular fatty change and infiltration of inflammatory cells, including lymphocytes and polymorphonuclear cells, within the liver lobules. Pericentral fibrosis and pericellular fibrosis were also recognized. He was diagnosed as having nonalcoholic steatohepatitis (NASH), based on the fact that he had no habit of drinking alcohol, as well as psoriasis vulgaris and diabetes mellitus. We herein report a very rare case of NASH associated with psoriasis vulgaris.
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PMID:Nonalcoholic steatohepatitis associated with psoriasis vulgaris. 1558 Apr 5

A continuing sub-clinical streptococcal infection might be responsible for chronic plaque psoriasis. In this open study, we investigated thirty patients with moderate to severe chronic plaque psoriasis. The majority of the patients had been ill for 5 years or more (21 out of the total 30), and they had taken various treatment modalities for psoriasis with no significant improvement and frequent relapses. Total duration of the study was two years. Initially benzathine penicillin 1.2 million units, was given I.M. AST fortnightly. After 24 weeks benzathine penicillin was reduced to 1.2 million units once a month. Relevant investigations and clinical assessment was done at regular intervals to detect side effects and to observe the progress of disease. Significant improvement in the PASI score was noted from 12 weeks onwards. All patients showed excellent improvement at 2 years. Patients tolerated the therapy well. Controlled studies are needed to further confirm the benefits of long-term use of benzathine penicillin in the treatment of psoriasis.
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PMID:Long-term use of penicillin for the treatment of chronic plaque psoriasis. 1617 45

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor that comprises the primary molecular target for thiazolidinedione (TZD) insulin-sensitizing drugs. Whilst expressed in many tissues in humans, its abundant expression in adipose tissue is believed to be the focal point through which TZDs regulate genes involved in glucose and lipid metabolism and via which these agents ultimately improve the hyperglycemia of type 2 diabetes. However, TZDs exhibit many additional properties, not least an array of effects which suggest a broad attack on the inflammatory process. Thus, TZDs have been shown to reduce plasma levels of the chemokine, monocyte chemotactic protein-1 (MCP-1), the anti-fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1), the endothelial cell adhesion molecules, e-selectin and inter-cellular adhesion molecule-1 (ICAM-1), the leucocyte-activating molecule, CD40L, and the tissue-remodeling enzyme, matrix metalloproteinase-9 (MMP-9). Further tangible evidence of a reduction by TZDs of systemic inflammation in patients with the classical metabolic syndrome stems from falls in the white blood cell count, P-selectin-positive platelets and in the acute-phase inflammatory proteins, C-reactive protein, serum amyloid A and fibrinogen. At the tissue level, TZDs improve vascular endothelial function, and reduce the rate of progression of intimal-medial thickening of the carotid artery and the microalbuminuria of type 2 diabetes. Further, TZDs have been shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis (NASH). In the case of the latter, a broad spectrum of TZD-related properties is visible. Here, these drugs improve insulin sensitivity for glucose metabolism, reduce hyperinsulinemia, hepatic steatosis, inflammation and fibrosis, and lower the circulating levels of liver transaminases (ALT, AST), alkaline phosphatase and gamma glutamyl transferase. These effects in humans are also well-supported by investigative animal and in vitro studies. The ameliorative effects on liver fibrosis are of particular interest since they suggest that TZDs are able to activate a program of corrective tissue-remodeling. The basis for this action may be partly an ability to inhibit matrix protein secretion by hepatic stellate cells. An analogous action has also been seen in kidney mesangial cells. In conclusion, TZDs are important new drugs, presently indicated for the treatment of type 2 diabetes but with a spectrum of properties which suggests their potential for treating a number of degenerative inflammatory diseases, including NASH. However, full-scale, long-term clinical trials are needed with TZDs to test their potential to treat NASH, not least because of the (hepatotoxic) legacy of the prototype TZD, troglitazone, but also in view of the escalating burden of liver disease which is accompanying the increasing global prevalence of clinical obesity and type 2 diabetes.
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PMID:Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection. 1619 19

The authors conducted a prospective, open-label, pilot trial of the effects of the antidiabetic thiazolidinedione (TZD) rosiglitazone in two patients with moderate to severe plaque psoriasis. Case 1: A lean, euglycemic 43-year-old nondiabetic man with a 2-year history of plaque psoriasis presented with lesions involving 10% of his body surface (Figures 1A, 1B, 1C). He had no other chronic or acute medical problems. He had previously been managed sporadically with topical triamcinolone acetonide, an intermediate-strength glucocorticoid, and was off antipsoriatic medication for 5 months. He was started on rosiglitazone p.o., 8 mg q.d. After 10 weeks on rosiglitazone, the lesions developed increased erythema, spreading, and shedding of scale (Figures 2A, 2B, 2C). After an additional 26 weeks, the lesions had largely disappeared (Figures 3A, 3B, 3C). The patient remained euglycemic throughout the study. His liver function enzymes (alanine transferase [ALT] and aspartate transferase [AST]) remained normal throughout the study: ALT, 23 IU/L; AST, 47 IU/L before treatment; ALT, 25 IU/L; AST, 33 IU/L after treatment. There were no adverse events. Case 2: An overweight 68-year-old woman (body mass index, 29 kg/m2; with a 12-year history of type 2 diabetes and 5-year history of psoriasis presented with generalized plaque psoriasis over 20% of her body, including two large, thick, silvery plaques with the texture of leather over the lower part of the back (Figure 4A). She was given rosiglitazone p.o., 4 mg b.i.d. for 24 weeks, which resulted in significant improvement in psoriasis (Figure 4B). After an additional 26 weeks on rosiglitazone, the plaques had cleared on her back (Figure 4C) and over her entire body, including scalp, ears, and posterior forearms (not shown). Her glycemic control improved (hemoglobin A1c decreased from 7.7% to 7.2%) and liver function remained normal throughout the study (ALT, 24 IU/L; AST, 14 IU/L before treatment; and ALT, 26 IU/L; AST, 15 IU/L after treatment). There were no adverse events.
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PMID:Improvement in psoriasis with rosiglitazone in a diabetic and a nondiabetic patient. 1627 61

A 21-year-old woman of Romany origin, in the third trimester of her fourth pregnancy, was admitted to the hospital because of a generalized erythematous and pustular eruption and desquamation involving her face, neck, trunk, and extremities. The skin changes were accompanied by fever (100.4 degrees F [38 degrees C]) and malaise. The patient was convinced that the dermatitis was induced by the consumption of "spoilt" pork sausage (bad smell, changed taste) approximately 24 hours earlier. Clinical examination revealed a woman with phototype III skin, black eyes, and black hair, in good general health. Widespread, symmetrical, moderately intense erythema and isolated or coalescing targetoid lesions studded with discrete, pinhead-sized, nonfollicular pustules in the center or at the periphery were distributed over her face, trunk, groins, and upper and lower extremities (Figures 1). On the neck and abdomen, lamellar desquamation was observed (Figure 2). Palms, soles, scalp, mucous membranes, hair, and nails were not affected. Nikolsky's sign was negative. The patient complained of very slight skin burning and itching. The pregnancy was proceeding without any complications and her obstetric status was normal. The woman had neither any accompanying diseases, nor previous personal or family history of psoriasis, nor any known allergies. She had taken no systemic medication (not even vitamins). She had three pregnancies; two ended with the delivery of healthy babies and one of them was aborted at her will. Laboratory studies revealed leukocytosis (13.2 x 109/L), neutrophilia (8 x 109/L), anemia (hemoglobin, 108 g/L), and an elevated erythrocyte sedimentation rate (68-110 mm/h). The results from the following investigations were normal: urinalysis, renal and hepatic function, serum albumin, Ca, Na, K, aspartate aminotransferase titer, cryoprotein, hepatitis B surface antigen, and serum markers for syphilis. Bacterial and fungal cultures of pustular content were sterile. A skin biopsy specimen of lesional skin revealed subcorneal pustules containing leukocytes and necrotic keratinocytes and a mixed perivascular inflammatory infiltrate with isolated eosinophils in the dermis (Figure 3). The patient was treated with systemic methylprednisolone in gradually reduced doses, fluocinonide cream 0.05%, and emollients. As a result, her fever disappeared and her erythema faded. Frequent obstetric examination and cardiotocography were normal and showed no evidence of placental insufficiency. At 40 weeks' gestation, the patient spontaneously gave birth without any complications to a healthy boy. She was discharged with complete resolution of the skin lesions, preceded by massive desquamation of the epidermis. The 1-year follow-up of the patient revealed no relapses or new pustular eruptions.
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PMID:Food-induced acute generalized exanthematous pustulosis in a pregnant woman. 1685 16


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