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)

New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.
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PMID:Gemtuzumab ozogamicin-induced sinusoidal obstructive syndrome treated with defibrotide: a case report. 1688 10

The present study examined the acute toxicity and antinociceptive effects of diphenyl diselenide (PhSe)2, given orally (p.o.), in chemical and thermical models of pain in mice. Diphenyl diselenide (7.8-312 mg/kg, p.o.) did not cause mortality. This compound did not change plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels in mice after 72 h of exposure. Diphenyl diselenide (1-100 mg/kg, p.o.) inhibited acetic acid-, capsaicin-, glutamate-, bradykinin(BK)- and phorbol myristate acetate (PMA)-induced pain. Diphenyl diselenide also reduced glutamate-, bradykinin-, PMA-induced paw oedema formation. Moreover, diphenyl diselenide caused a significant increase in tail-immersion response latency time. Diphenyl diselenide co-injected subplantarly in association with glutamate-induced a significant reduction of the licking and in the paw oedema formation induced by glutamate. The local pre-treatment of mice with l-arginine, intraplantarly, restored antinociception caused by diphenyl diselenide or N(G)-nitro-L-arginine methyl ester (L-NAME) when analyzed against glutamate-induced nociception. The pre-treatment of mice with dithiothreitol (DTT) intraplantarly restored local antinociception caused by diphenyl diselenide or 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) when analyzed against glutamate-induced nociception. These results indicate that diphenyl diselenide produced antinociception in several models of pain through mechanisms that involve an interaction with not only nitrergic system but also via interaction with redox modulatory sites of glutamate receptors.
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PMID:Antinociceptive properties of diphenyl diselenide: evidences for the mechanism of action. 1712 7

A total of 100 patients who underwent elective lobar donor hepatectomy from 2000 to 2002 at the University of Rochester Medical Center were reviewed. Assessed clinical data were estimated blood loss, intraoperative central venous pressure (CVP), blood product and fluid administration, perioperative arterial blood gas tension and acid-base state, metabolic status, perioperative serum levels of aspartate aminotransferase, alanine aminotransferase, prothrombin time, albumin, and lactate, procedure duration, and perioperative complications. All patients survived surgery, and the average duration of surgery (from skin incision to skin closure) was 615 +/- 99.6 minutes. Mean blood loss was 549 +/- 391 mL (range, 80-2,500 mL), and only 4 patients required homologous blood transfusion. The intraoperative blood loss did not correlate with CVP values. A total of 72 patients received isotonic sodium bicarbonate solution, and their metabolic variables were superior to those of normal saline group patients (arterial pH, 7.35 +/- 0.03 vs. 7.29 +/- 0.07; base excess, -4.3 +/- 2.4 vs. 7.3 +/- 3.4; and serum bicarbonate level, 20.6 +/- 2.2 vs. 18.6 +/- 2.9). However, the better control of metabolic acidosis was not associated with serum lactate levels or other outcome measures. Maintaining the CVP < 5 mmHg was not associated with blood loss. Clinically significant anesthetic complications were severe metabolic acidosis, pneumothorax and respiratory insufficiency immediately following extubation in the operating room. In conclusion, placement of a thoracic epidural catheter delivering a local anesthetic in addition to intravenous (IV) patient-controlled analgesia with opiates provided safe and effective pain control in most patients. Further prospective studies should shed a light on the optimal care of patients undergoing liver donor hepatic resection.
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PMID:Anesthesia care for adult live donor hepatectomy: our experiences with 100 cases. 1739 51

Transient potential vanilloid 1 (TRPV1) receptor is an ion channel receptor primarily localized on sensory nerves and activated by specific stimuli to initiate and amplify pain and inflammation, as typified by murine models of scald and arthritis. Little is known of the role of TRPV1 in sepsis, an infective disease associated with inflammation. Through use of a sublethal murine model of lipopolysaccharide-induced peritoneal sepsis, we provide novel evidence that genetic deletion of TRPV1 leads to an enhanced onset of various pathological components of systemic endotoxemia. Paired studies of TRPV1 knockout (KO) and wild-type mice demonstrate significantly enhanced hypotension (56+/-2% vs. 38+/-6% decrease in blood pressure, n=12), hypothermia (13+/-3% vs. 7+/-1% decrease in core temperature, n=6), and peritoneal exudate mediator levels (TNF-alpha, 0.78+/-0.2 vs. 0.38+/-0.1 ng/ml; nitrite, for NO, 35+/-10 vs. 15+/-3 microM; n=8) in TRPV1 KO mice, indicating loss of protective effect. Findings correlated with liver edema and raised plasma levels of aspartate aminotransferase in TRPV1 KO mice. These data suggest that TRPV1 may play an important regulatory role in sepsis independent of the major sensory neuropeptide substance P. The findings are relevant to developing strategies that increase the beneficial, and reduce the harmful, components of sepsis to prevent and treat this often fatal condition.
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PMID:The transient receptor potential vanilloid 1 (TRPV1) receptor protects against the onset of sepsis after endotoxin. 1760 84

Acetaminophen (APAP) is one of the most commonly used drugs for the safe and effective treatment of fever and pain. However, it is a well-established hepatotoxin. The objective of this study was to identify alternation in various genes in liver of mice after administration of low and high doses of APAP. Male C57BL/6J mice received APAP (30 or 300 mg/kg, i.p.). They were sacrificed after 6 hr and 24 hr for assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total RNA isolation, cDNA microarray analysis and histopathological analysis of liver injury. Low dose of APAP did not cause hepatotoxicity in mice. However, it was toxic at a high dose. Using microarray technology, we selected changed genes more than 1.5 fold. Gene expression changes were recorded even at a low dose treatment with APAP. Six (6) hr after APAP treatment at low dose, 6 genes were up-regulated and 25 genes were down-regulated. However, 24 hr after treatment at low dose 8 genes were up-regulated and 34 genes were down-regulated. 6 hr after of high dose treatment 29 genes were down-regulated and none was up-regulated. A 24 hr treatment with high dose up-regulated 6 genes and down-regulated 18 genes. These expression patterns provide information on high versus low dose mechanisms of APAP toxicity. Gene expression signatures recorded after a nontoxic dose of APAP strongly support the validity of gene expression changes as meaningful markers of hepatotoxicity.
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PMID:Effects of acetaminophen on hepatic gene expression in mice. 1847 68

The aetiology of muscle fatigue has yet not been clearly established. Administration of two nucleotides, cytosine monophosphate (CMP) and uridine monophosphate (UMP), has been prescribed for the treatment of neuromuscular affections in humans. Patients treated with CMP/UMP recover from altered neurological functions and experience pain relief, thus the interest to investigate the possible effect of the drug on exhausting exercise. With such aim, we have determined, in exercised rats treated with CMP/UMP, exercise endurance, levels of lactate, glucose and glycogen, and the activity of several metabolic enzymes such as, creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Our results show that rats treated with CMP/UMP are able to endure longer periods of exercise (treadmill-run). Before exercise, muscle glucose level is significantly higher in treated rats, suggesting that the administration of CMP/UMP favours the entry of glucose in the muscle. Liver glycogen levels remains unaltered during exercise, suggesting that CMP/UMP may be implicated in maintaining the level of hepatic glycogen constant during exercise. Lactate dehydrogenase and aspartate aminotransferase activity is significantly lower in the liver of treated rats. These results suggest that administration of CMP/UMP enable rats to endure exercise by altering some metabolic parameters.
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PMID:Effect of the nucleotides CMP and UMP on exhaustion in exercise rats. 1866 91

Acute rhabdomyolysis is a syndrome characterized by the lesion of skeletal muscle resulting in subsequent release of intracellular contents into the circulatory system, which can cause potentially lethal complications. These contents include myoglobin, creatine phosphokinase, potassium, aldolase, lactate dehydrogenase and glutamic-oxaloacetic transaminase. There are numerous causes that can lead to acute rhabdomyolysis and many of patients present with multiple causes. The most common potentially lethal complication of rhabdomyoloysis is acute renal failure. In this article we present a case of a patient that developed clinical signs of acute rhabdomyolysis after consumption of heroin and alcohol. After approximately nine hours of alcohol and heroin induced coma he had acute compartment syndrome of the right arm, and clinical and laboratory signs of acute rhabdomyolysis with acute renal failure as a complication of rhabdomyolysis. Acute rhabdomyolysis developed in the patient as the result of acute compartment syndrome, with direct toxic activity of alcohol and diamorphine. During the period of coma, due to lying in particular position over a long period of time, pressure upon the certain part of the body caused muscle compression and capillary occlusion in fascial compartments, which led to ischemia. Upon pressure relief and beginning of tissue recovery, post ischemic compartment syndrome occurred with subsequent rhabdomyolysis. Getting out of coma the patient started to complain of severe pain in the right arm, which clinically worsened on passive stretching of the limb, with the loss of sensation and weakness. Laboratory findings showed high levels of creatine phosphokinase as the most sensitive marker of muscular damage. The peak of creatine phosphokinase level can be predictive for the development of acute renal failure because myoglobin level may return to normal within 6 hours after muscle injury. The peak of creatine phosphokinase (186.080 U/L; normal range 0-177) was recorded at 12 hours of admission. Other pertinent laboratory results such as urea, creatinine, prothrombin time, alanine aminotransferase and aspartate aminotransferase were also changed significantly. The peak of potassium level before dialysis was 6.8 mmol/L. Emergency fasciotomy of the anterior and posterior compartment syndrome was performed by a team of physicians after clinical examination. The second look debridement was performed at 48 and 72 hours. The plastic surgical procedure was performed 4 weeks later. On admission the patient also had oliguria with dark brown pigment in his urine. Arterial blood gases revealed metabolic and respiratory acidosis. The patient was hypovolemic and IV rehydratation with crystalloids, sodium bicarbonate and mannitol started immediately upon admission. Despite therapy his urine output decreased. Hemodialysis was initiated at serum potassium level of 6.8 mm/L and continued until his urine output returned to normal in three weeks. The patient was discharged from the hospital after six weeks, with normal urine output, without functional abnormality in his upper right limb. Acute rhabdomyolysis should be considered as a possibility in any patient with prolonged imobilization while in coma as well as in any intoxicated patient. Of course, creatine phosphokinase is the most sensitive indicator of muscle injury and the degree of creatine phosphokinase elevation correlates with the amount of muscle injury and disease severity. Other laboratory findings can help identify common complications of rhabdomyolysis such as acute renal failure, metabolic derangements and disseminated intravascular coagulopathy.
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PMID:[Acute rhabdomyolysis: a case report and literature review]. 1884 54

Revision surgery for loosened hip prostheses is a heavy burden for elderly patients with comorbidity. As an alternative to surgery we performed a study to stabilize the prosthesis by percutaneous cement injection after removing inflammatory tissue with an intraarticular virus-directed enzyme prodrug approach. Twelve elderly patients with debilitating pain from a loosened hip prosthesis were included in a phase 1 dose-escalating clinical study. The patients were admitted to the hospital for 10 days for an intraarticular vector and prodrug injection, and subsequently for a percutaneous bone cement injection. This paper reports the adverse and serious adverse events of the study. After prodrug injection 9 of 12 patients had gastrointestinal adverse events (nausea, vomiting, and diarrhea), and 8 patients had hepatic adverse events (rise in aspartate aminotransferase and alanine aminotransferase). Five patients developed anemia (World Health Organization grade 1 or 2) from hematomas after cement injection. There were four serious adverse events in the first 6 months after vector injection, but these were not related to gene therapy as judged by an independent safety committee. There was no dose-limiting toxicity. However, the extensive comorbidity in these patients makes it difficult to fully establish the safety of the approach in this small and heterogeneous patient population.
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PMID:Gene therapy for the treatment of hip prosthesis loosening: adverse events in a phase 1 clinical study. 1895 51

A 52-year-old Indian woman with underlying diabetes mellitus and hyperlipidemia, presented with generalized musculoskeletal pain and oliguria for three days. The patient was taking 80 mg of simvastatin initiated 20 days earlier after cardiac catheterization for an inferior myocardial infarction. Laboratory investigations revealed the following serum levels: creatine kinase 81,620 U/L, aspartate aminotransferase 2497 U/L, alanine aminotransferase 1304 U/L, blood urea nitrogen 21.7 mmol/L, creatinine 447 micromol/L, Free T4 12.6 pmol/L, and thyroid stimulating hormone (TSH) 22.7 microIU/L. Simvastatin was discontinued and the patient received forced alkaline diuresis. Her hypothyroidism was treated with thyroxin, which was continued upon discharge, and her renal function recovered within two months. This case report discusses the incidence of rhabdomyolysis in a patient with primary hypothyroidism receiving large doses of simvastatin.
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PMID:Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in undiagnosed hypothyroidism. 1911 32

CASE DESCRIPTION - A 6-year-old castrated male Llewelyn Setter was evaluated because of an acute onset of myalgia and respiratory distress. CLINICAL FINDINGS - Physical examination revealed a stiff stilted gait, swollen muscles that appeared to cause signs of pain, panting, and ptyalism. The dog had a decrease in palpebral reflexes bilaterally and a decrease in myotatic reflexes in all 4 limbs. The panniculus reflex was considered normal, and all other cranial nerve reflexes were intact. Serum biochemical analysis revealed markedly high cardiac troponin-I concentration and creatine kinase and aspartate aminotransferase activities. Urinalysis revealed myoglobinuria. Results for thoracic and abdominal radiography, blood pressure measurement, and an ECG were within anticipated limits. Echocardiographic findings were consistent with secondary systolic myocardial failure. Arterial blood gas analysis confirmed hypoxemia and hypoventilation. The dog had negative results when tested for infectious diseases. Examination of skeletal muscle biopsy specimens identified necrotizing myopathy. TREATMENT AND OUTCOME - Treatment included ventilatory support; IV administration of an electrolyte solution supplemented with potassium chloride; administration of dantrolene; vasopressor administration; parenteral administration of nutrients; use of multimodal analgesics; administration of clindamycin, furosemide, mannitol, and enrofloxacin; and dietary supplementation with L-carnitine and coenzyme Q(10). Other medical interventions were not required, and the dog made a rapid and complete recovery. CLINICAL RELEVANCE - Necrotizing myopathy resulting in rhabdomyolysis and myoglobinuria can lead to life-threatening physical and biochemical abnormalities. Making a correct diagnosis is essential, and patients require intensive supportive care. The prognosis can be excellent for recovery, provided there is no secondary organ dysfunction.
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PMID:Successful management of a dog that had severe rhabdomyolysis with myocardial and respiratory failure. 1936 38


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