Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used for treatment of arthritis. However, their long-term use has been associated with considerable morbidity, limiting their application. Thus, there remains a need to develop new drugs for the effective and safe relief of chronic inflammatory pain. In this context, the present study was designed to evaluate the antinociceptive and antiedematogenic effects of the 5-trifluoromethyl-4,5-dihydro-1H-pyrazole derivatives EPFCA3 and MPFCA4 after acute (1-1000 micromol/kg) and chronic (100 micromol/kg for 15 days) administration in rats submitted to a model of adjuvant-induced arthritis. We also analyzed some biochemical indicators of toxicity (alanine aminotransferase, aspartate aminotransferase, urea and creatinine levels) after prolonged administration of these compounds. We found that acute and chronic subcutaneuous administration of EPFCA3 and MPFCA4 produces an antinociceptive, but not antiedematogenic, effect on the arthritis animal model induced by complete Freund's adjuvant (CFA). No signs of toxicity were observed in the animals chronically treated with EPFCA3 or MPFCA4. Dipyrone (1-1000 micromol/kg) was used as the positive control and its effect was similar to that of the novel pyrazoles. The activity of tissue myeloperoxidase, the tissue TNF-alpha level and the serum haptoglobin level was increased by intraplantar CFA injection. However, chronic administration of EPFCA3, MPFCA4 or dipyrone was not able to alter the relation between these parameters and inflammation. Our results suggest that EPFCA3 and MPFCA4 are good candidates for the development of new drugs for pain treatment.
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PMID:Effect of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles on chronic inflammatory pain model in rats. 1954 Feb 23

Benign acute childhood myositis (BACM) is characterised by sudden calf pain and inability to walk. We analyzed the characteristics of seven boys and two girls with BACM treated in the Pediatric Department from April 2005 to March 2009. The mean age at onset of symptoms was 7 +/- 2 years. Two boys were hospitalized twice for BACM. All cases occurred in winter or spring. 7 out of all admissions were clustered together in one week long periods. Patients demonstrated prodromal symptoms of flu-like illness followed by the sudden onset of difficulty in walking. One girl additionally complained of a painful right hip. Four patients received inosine pranobex for prodromal viral infection before the clinical onset of myositis. In all cases, creatine phosphokinase (CPK; the highest value at 8988 U/l) and aspartate aminotransferase (AST; the highest value at 329 U/l) values were elevated. The serum concentration of myoglobin was elevated in five out of six tested patients (the highest value at 2172 microg/l). The following haematological abnormalities were detected: leucocytopenia (the lowest WBC 1.35 x 10(3)/microl), neutropenia, and trombocytopenia. All patients made a rapid recovery within 1 to 5 days. Pediatricians and emergency medicine specialists must be aware that BACM is a self-limiting disorder with the acute onset of inability to walk, elevated CPK and AST levels, and transient haematological abnormalities. There is no sufficient data from clinical reports on immunostimulant use before the onset of BACM.
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PMID:[Benign acute childhood myositis (BACM)--cases report]. 1985 79

Accidents caused by lionfish (Pterios volitans) envenomation are characterized by edema, intense pain, and necrosis at the site of sting. The mode of action and biochemistry of venoms are obviously complex and require a better knowledge and investigation to explore the toxic action and resulting biochemical changes. In the present study the LD(50) value of lionfish venom was found to be 42.5 mug/kg body weight (intraperitoneal injection) in Albino Swiss mice and was associated with reduced motor activity and asphyxiation followed by respiratory failure. The effect on vital organs revealed spongiosis in brain, vascular congestion in liver, cloudy swelling of renal tubules, congested blood vessels in renal tubules, and degeneration of myofibrils in heart. Whereas, the 10% of LD(50) (was 4.25 mug/kg b.w.), the sublethal dose showed reversible changes in the hematological (blood cell count, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and platelet count) parameters, serum enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and creatinine phosphokinase), blood sugar, urea, creatinine, triglycerides, cholesterol, and total protein in mouse in vivo. The in vitro analysis of lionfish venom on mouse brain acetyl cholinesterase and Na(+), K(+), ATPase showed significant increased activity in a dose-dependent manner (10 to 40 mug). Moreover, the lionfish venom was observed to have a protease with a molecular weight of 45 kDa. Hence, the present study suggests the presence of bioactive proteins and peptides with excellent target specificity, which could be trapped for drug development in near future.
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PMID:In vivo and in vitro characterization of the biochemical and pathological changes induced by lionfish (pterios volitans) venom in mice. 2002 Sep 95

The aim of this study was to evaluate the canine blood and urinary profiles after envenomation by Tityus serrulatus venom. Twelve dogs were randomly distributed into two equal groups. Control group animals received 0.5 mL phosphate buffered saline (PBS) injected subcutaneously into the internal portion of the left thigh, whilst dogs in the envenomed group were injected with scorpion venom (250 microg/kg in 0.5 mL PBS). No significant alterations were detected in the urine of envenomed dogs. Levels of plasma glucose and serum urea, creatinine, total protein, potassium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and amylase were determined. Semi-quantitative analysis of serum cardiac troponin I (cTnI) was performed using an immunochromatographic test. The concentrations of cortisol and insulin were determined using commercial radioimmunoassay kits. Increases in serum cortisol levels in experimental group animals coincided with hyperglycaemia and was probably a response to pain. Increased insulin levels were observed during the hyperglycaemic peaks. Envenomed dogs presented discreet increases in ALT, AST and CK, but no alterations in LDH, amylase, cTnI, urea, creatinine and potassium levels were observed. It was concluded that the venom of T. serrulatus induces blood and urinary biochemical changes in dogs.
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PMID:Biochemical profile of dogs experimentally envenomed with Tityus serrulatus scorpion venom. 2006 Apr 4

The long-term use of non-steroidal anti-inflammatory agents in geriatric dogs with osteoarthritis has not been well studied in veterinary medicine. This study evaluated the effects of firocoxib administered to dogs over 7 years of age for 90 days. Pain and lameness scores were evaluated by the owner weekly for the 1st month and then biweekly through to the end of the study, the veterinarian evaluated the dogs monthly. Serum chemistry, including urea, creatinine, alanine transferase, aspartate transaminase, bile acids and bilirubin, urine specific gravity and a urine dipstick, were performed at monthly intervals. Forty-five dogs were enrolled into the treatment group and 9 into the control group. A total of 33 dogs completed the trial in the treatment group and 8 in the control group. Lameness and pain scores were found to be significantly lower in the treated group from day 30 for most parameters evaluated. Bile acids (although not comparable to controls, with higher mean value and a high standard deviation in the control group; in addition the control group had increased bile acids at day 0) and urea (within normal reference range provided (WNL)) were significantly different in the treatment group between days 0 and 90. Urea (WNL) on days 30 and 90 and creatinine (WNL) on day 90 were significantly different between the control group and the treatment group. The most common adverse events reported were diarrhoea, vomition, dark faeces and anorexia. This study showed that firocoxib was effective in managing pain associated with osteoarthritis for 90 days. Despite the geriatric high-risk population used for this study, minimal biochemical changes were seen and adverse drug events seen were in agreement with those previously reported.
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PMID:The effects of firocoxib (Previcox) in geriatric dogs over a period of 90 days. 2016 52

A 52-year-old Indian woman with underlying diabetes mellitus, hyperlipidemia and undiagnosed hypothyroidism presented with generalized musculoskeletal pain and oliguria for three days. The patient was taking 80 mg of simvastatin (initiated 20 days before) after cardiac catheterization for an inferior myocardial infarction. Laboratory evaluation revealed the following serum levels: creatine kinase, 81,660 U/L; aspartate aminotransferase, 2,497 U/L; alanine aminotransferase, 1,304 U/L; blood urea nitrogen, 88 mg/dL; creatinine, 5.1 mg/dL; free thyroxine (FT(4)), 12.6 Pmol/L and thyroid stimulating hormone, 22.7 uIU/L. Simvastatin was discontinued and the patient was administered forced alkaline diuresis. Her hypothyroidism was treated with thyroxine, which was continued after discharge. Her renal function recovered within two months. This case report discusses the higher incidence of rhabdomyolysis in patients with undiagnosed hypothyroidism receiving large doses of simvastatin.
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PMID:Severe rhabdomyolysis and acute renal failure secondary to the use of simvastatin in undiagnosed hypothyroidism. 2036 19

Acetaminophen, a pain-reliever, is one of the most widely used medications in the world. Acetaminophen with normal dosage is considered a nontoxic drug for therapeutic applications, but when taken at overdose levels it produces liver damage in human and various animal species. By a high energy mechanically activated method, we produced acetaminophen in a nanometer crystalline size (24 nm). Forty-eight hours after injection of crystalline particles with normal and reduced size of our drug, the effect of liver toxicity was compared by determination of liver transferase enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase (ALT). These enzymes were examined by routine colorimetric methods using commercial kits and pathologic investigations. Statistical analysis and pathological figures indicated that ALT delivery and toxicity in reduced size acetaminophen was significantly reduced when compared with normal size acetaminophen. Pathology figures exhibited reduced necrosis effects, especially the confluent necrosis, in the central part of the lobule in the reduced size acetaminophen samples when compared with the normal samples.
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PMID:The effect of acetaminophen nanoparticles on liver toxicity in a rat model. 2046 35

Bee venom (BV) has a long tradition of use for the control of pain and inflammation in various chronic diseases. Carbon tetrachloride (CCl4) is known to induce hepatotoxicity after being metabolized to the highly reactive trichloromethyl free radical and its peroxy radical. The purpose of the current study was to examine whether BV regulates the pro-inflammation and fibrosis related genes against a mouse model of hepatic fibrosis induced by CCl4 and ethanol-treated hepatocytes (ETH). Test mice were administered with CCl4 (2 ml/mg) and hepatocytes were treated with 25 mM ethanol. BV was added to the final concentration of 0.05-0.5 mg/kg and 1-100 ng/ml for in vivo and in vitro testing, respectively. Fibrotic livers and ETH were used for the measurement of hepatocyte necrosis, pro-inflammatory cytokines and fibrogenic genes. BV suppressed CCl4-induced hepatocyte necrosis markers of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the secretion of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Moreover, BV inhibited CCl4-induced expression of transforming growth factor (TGF)-beta1, alpha-smooth muscle actin (SMA) and fibronectin. Similarly, ETH exhibited significant suppression of IL-1beta, TNF-alpha, TGF-beta1 and fibronectin when cultured with BV. These results suggest that BV possesses anti-fibrogenic properties that are mediated by the suppression of pro-inflammatory cytokines and fibrogenic gene expression. BV has substantial therapeutic potential for the treatment of fibrotic diseases.
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PMID:Bee venom inhibits hepatic fibrosis through suppression of pro-fibrogenic cytokine expression. 2082 23

BACKGROUND: Although granulocyte colony stimulating factor (G-CSF) mobilization is generally well tolerated by healthy donors, there is also a wide spectrum of adverse events associated with it. Among these events, rhabdomyolysis in peripheral blood stem cell (PBSC) donors is very rare. In this paper, we present a first case of rhabdomyolysis after administration of filgrastim for PBSC mobilization. CASE REPORT: A 6-year-old donor received 10 mug/kg/day filgrastim subcutaneously for 5 days. On the 3rd day of filgrastim, the donor complained of bone pain; a single dose of paracetamol (250 mg) was given to relieve pain. On the 4th day, she complained of bone pain, myalgia, and vomiting. On laboratory analysis, serum creatine phosphokinase was 1,095 U/l (40-226 U/l), LDH 312 U/l (100-190 U/l), aspartate aminotransferase 85 U/l (0-40 U/l), potassium 3.3 mmol/l (3.6-5.1 mmol/l). Urine myoglobin was 110 ng/ml (<5 ng/ml). Rhabdomyolysis was suspected on clinical and laboratory findings. Clinical manifestations regressed and the laboratory results returned to normal within three days after intravenously forced diuresis and potassium replacement. Stem cells were successfully harvested from peripheral blood on the 5th day of G-CSF therapy. CONCLUSION: Rhabdomyolysis is a rare but important adverse effect of G-CSF. Allogeneic PBSC donors should be closely monitored with regard to rhabdomyolysis after G-CSF administration in the mobilization setting.
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PMID:Rhabdomyolysis in a Healthy Peripheral Blood Stem Cell Donor following Mobilization with Filgrastim. 2082 94

Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation in the United States and Europe. Recurrence of HCV is universal in all liver graft recipients, but the natural history of the disease is variable with some patients displaying slowly progressive liver injury, while approximately 30% become cirrhotic within five yr of surgery. Currently, liver biopsy is the reference standard to assess liver injury in the post-transplant setting. But biopsy is associated with complications such as bleeding and pain, as well as the risk of sampling error and discordance in reporting between histopathologists. Thus, as in the pre-transplant setting, there is increasing attention being drawn to the use of non-invasive tests of liver fibrosis. This review examines the role of non-invasive assessment of hepatic fibrosis in the post-transplant setting including simple tests such as aspartate aminotransferase-to-platelet ratio index, the Benlloch formula, London Transplant Centre score, and finally transient elastography. The authors assess the respective advantages and disadvantages of the tests and consider how non-invasive tests of liver fibrosis can be utilized in the future management of post-transplant HCV infection.
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PMID:Non-invasive assessment of fibrosis in liver grafts due to hepatitis C virus recurrence. 2151 74


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