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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deferiprone, also known as L1, is an orally active iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of agranulocytosis in association with deferiprone and the highly variable frequency of other possible side effects such as arthralgia have created uncertainty about the true incidence of deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of deferiprone. Using the Apotex formulation of deferiprone, 187 patients with thalassemia who were unable or unwilling to use deferoxamine were enrolled in four centers; 162 patients completed one year of therapy. Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by infection and resolved following treatment with G-CSF. Nine other subjects developed less severe neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The neutropenia in these patients developed after 1-50 weeks of therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than neutropenia for discontinuing use of deferiprone included nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed ANC (1), protocol violation (1) fatigue (1), and depression (1). Mean ALT levels rose within three months of therapy and stabilized thereafter. Arthralgia and nausea and/or vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of agranulocytosis was 0.58 per 100 patient-years, and the frequency of agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of deferiprone, using the careful monitoring system employed in this trial.
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PMID:A multi-center safety trial of the oral iron chelator deferiprone. 966 43

Itraconazole, an oral antifungal agent, was evaluated for the clinical efficacy and safety in patients documented or suspected of systemic fungal infection (SFI) complicated with hematological malignancies. The data was also evaluated according to serological tests and fungal culture. Out of a total of 79 patients, the clinical efficacy of itraconazole was evaluated in 52 patients, comprising 4 patients with proven SFI, 33 with clinical SFI, and 15 with suspected SFI. The overall efficacy was 67.3% (35/52), in which 25.0% in the established SFI group (1/4), 78.8% in the clinical SFI group (26.33), and 53.3% in the suspected SFI (8/15). When assessed according to the severity of SFI, the effectiveness rates were 75.0% in the mild group (15/20), 76.2% in the moderate group (16/21), and 36.4% in the severe group (4/11), resulting in significantly higher rates in the mild and the moderate groups than in the severe group (p = 0.0479). Out of the 10 patients who were switched from the previous antifungals, 7 patients were judged as showing marked or good responses. All of these patients were switched from intravenous fluconazole therapy. With respect to the safety of itraconazole, among 79 patients eligible for safety evaluation, adverse events such as hepatic dysfunction, increase in GOT and/or GPT, nausea and vomiting, and chest pain were observed in 6 patients (7.6%), and itraconazole may have been associated with them. As a conclusion, itraconazole proved to be effective and safe on SFI developed in patients with various hematological malignancies.
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PMID:[Clinical study of itraconazole for systemic fungal infections complicated with hematological malignancies--multicenter cooperative study. West-Japan Systemic Fungal Infection Study Group]. 988 8

2-Amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)-quinazoline dihydrochloride (nolatrexed dihydrochloride, Thymitaq, AG337), a specific inhibitor of thymidylate synthase, was developed using protein structure-based drug design. Intravenously administered nolatrexed is active clinically. As oral bioavailability is high (70-100%), nolatrexed was administered orally, 6 hourly for 10 days, at 3-week intervals, and dose escalated from 80 to 572 mg m(-2) day(-1) in 23 patients. Common toxicity criteria (CTC) grade 3 toxicities included nausea, vomiting, stomatitis and liver function test (LFT) abnormalities. Thrombocytopenia (grade 1 or 2) occurred at doses > or = 318 mg m(-2) day(-1) and neutropenia (grade 2) at 429 and 572 mg m(-2) day(-1). An erythematous maculopapular rash occurred at dosages > or = 318 mg m(-2) day(-1) (7 out of 19 patients). LFT abnormalities occurred in two out of six patients (grade 3 or 4 bilirubin and grade 3 alanine transaminase) at 572 mg m(-2) day(-1). Nolatrexed plasma concentrations 1 h after dosing were 6-16 microg ml(-1), and trough 3-8 microg ml(-1), at 572 mg m(-2) day(-1). Inhibition of thymidylate synthase was demonstrated by elevation of plasma deoxyuridine. Six-hourly oral nolatrexed for 10 days was associated with antiproliferative effects, but nausea and vomiting was dose limiting at 572 mg m(-2) day(-1). Nine patients were treated at 429 mg m(-2) day(-1); three out of nine experienced grade 3 nausea, but 17 out of 22 treatment courses were completed (with the co-administration of prophylactic antiemetics) and this dose level could be considered for phase II testing.
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PMID:A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. 1007 Aug 90

In this phase II study, the efficacy and tolerability of gemcitabine were studied in 42 patients with locally advanced or metastatic breast cancer who had received up to one prior chemotherapy regimen in an adjuvant setting. Ten patients had received adjuvant chemotherapy. Twenty-eight patients (67%) had visceral disease spread at entry. Gemcitabine (1000 mg/m2) was administered weekly on days 1, 8 and 15 of a 28-day cycle. The mean number of completed cycles was 3.9 and the mean dose delivered was 942.2 mg/m2. Ninety-seven percent of injections were administered as assigned. No complete responses were observed, but there were six partial responses and 24 patients with stable disease lasting 2-9 months. The overall response rate was 14.3% (95% CI 5.4-28.5%). The median survival for all patients was 15.2 months. Maximum WHO grade 3 and 4 toxicities were observed in five patients for nausea and vomiting, one patient for diarrhea, one patient for pain, seven patients for alanine transaminase, and eight patients for segmented neutrophils. There were no grade 3 and 4 toxicities for alopecia. These data confirm modest single-agent gemcitabine activity in advanced or metastatic breast cancer. Gemcitabine's favorable toxicity profile makes it an ideal candidate for combination chemotherapy.
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PMID:Phase II study of gemcitabine as first-line chemotherapy in patients with advanced or metastatic breast cancer. 1021 45

This study was undertaken to determine the prognosis value of laboratory and clinical findings in the progression of preeclampsia to eclampsia. Nausea and vomiting and glucose level > 105 mg/dL, serum creatinine level > 1.0 mg/dL, aspartate aminotransferase level > 35 IU/L, alanine aminotransferase level > 40 IU/L and lactate deshiydrogenase level > 450 IU/L can be used to estimate the risk for the advancement to eclampsia. This information could be helpful to the clinician for management purposes.
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PMID:[Prognosis factors associated with the progression of preeclampsia to eclampsia]. 1100 47

The anti-emetic effect and safety in patients receiving ondansetron hydrochloride (OND group) and concurrent use of ondansetron and dexamethasone (DEX group) in cases of acute and delayed onset emesis induced by a single high dose of cisplatin, given as a chemotherapy to lung cancer patients, were comparatively studied. The study subjects were 78 lung cancer patients. The OND group received 4 mg of ondansetron via slow intravenous injection on Day 1, 30 minutes prior to cisplatin, and for Days 2 to 5, the subjects orally received 4 mg ondansetron tablet each day. The DEX group received the same dose regimen of ondansetron as the OND group for Days 1-5, but in addition the subjects received dexamethasone injection in doses of 8 mg twice daily on Day 1 and 4 mg (1 mg QID) daily for Days 2-5. An anti-emetic effect against acute nausea and vomiting was achieved in 83.8% of the OND group and in a higher rate of 94.6% of the DEX group. Significantly better efficacy was seen in the DEX group as to the complete suppression rate of nausea and vomiting and the improvement of food intake. The group also achieved better efficacy in delayed onset of emesis. Two cases of adverse reactions (hiccups and elevation of ALT and BUN) were observed in the DEX group; however, since the symptoms were all mild, we did not consider there was any problem in safety. We conclude from the above findings that concurrent administration of ondansetron hydrochloride and dexamethasone is a clinically useful treatment for acute and delayed onset emesis induced by a single high dose of cisplatin given to lung cancer patients.
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PMID:[Examination on efficacy and safety of concurrent use of ondansetron hydrochloride and steroid in lung cancer patients on cisplatin]. 1147 44

We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.
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PMID:[Clinical usefulness of ondansetron hydrochloride for nausea and vomiting during repeated courses of chemotherapy for malignant lymphoma--impact of prognosis announcement on anti-emetic effect and evaluation of patient perception of chemotherapy-associated adverse events]. 1186 34

We carried out a 1-year trial to evaluate the efficacy and tolerability of lamivudine, an oral nucleoside analogue, in a small group of children with vertically acquired chronic hepatitis B. Patients were assessed for serum alanine aminotransferase (ALT) and serum hepatitis B virus (HBV) DNA at baseline and every 4 weeks thereafter, and for hepatitis B s antigen, hepatitis B e antigen and their antibodies every 12 weeks. Analysis of HBV mutation was undertaken at entry and on the occasion of the last positive control of HBV DNA. Lamivudine suppressed serum HBV DNA to undetectable levels in all treated patients within 24 weeks. Serum ALT levels returned to normal values within 36 weeks. Therapy was well tolerated, and although nausea and vomiting were reported in one child, it was not necessary to stop treatment. A new observation was that, contrary to previous data, seroconversion appeared to occur earlier in children with lower ALT levels at baseline.
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PMID:A 1-year trial of lamivudine for chronic hepatitis B in children. 1202 29

SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC). It is administered via the hepatic artery, using a carrier, lipiodol, that consists of ethyl esters of iodized poppy seed oil. We have performed a phase I clinical trial of an SM-11355-lipiodol formulation in 11 HCC patients, in order to investigate the maximum allowable dose and to maximize the efficacy and safety of the drug in the treatment of HCC. The SM-11355 arterial infusion suspension was administered at doses of 6, 12 and 20 mg ml(-1) in a maximum lipiodol volume of 6 ml. An antitumour efficacy rating of complete response was achieved for one patient and a partial response rating was achieved for a second patient, giving an overall response rate of 18.2%. Anorexia, nausea and vomiting, pyrexia, thrombocytopenia and increases in AST, ALT and total bilirubin were observed as adverse effects, but each was transient and each patient had recovered completely by 4 weeks after drug administration. Hence, we concluded that the maximum allowable dose was not reached in this study. Overall, our results suggest that SM-11355 is effective in treating HCC and we suggest that the dose for early phase II trials should be 20 mg ml(-1).
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PMID:Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in patients with hepatocellular carcinoma refractory to cisplatin/lipiodol. 1458 58

The plant Mentha piperita, or peppermint, is commonly used in the treatment of loss of appetite, common cold, bronchitis, sinusitis, fever, nausea and vomiting, and indigestion as a herbal agent. In this study, we aimed to investigate biochemical and histological effects of M. piperita Labiatae, growing in the Yenisar Bademli town of Isparta city, and Mentha spicata Labiatae, growing in the Anamas high plateau of the Yenisar Bademli town, on the rat liver tissue. Forty-eight male Wistar albino rats weighing 200-250 g were used for this study. Rats were divided into four groups of 12 animals: Group I received no herbal tea (control group); Group II received 20 g/L M. piperita tea; Group III received 20 g/L M. spicata tea; and Group IV received 40 g/L M. spicata tea. Herbal teas were prepared daily and provided at all times to the rats during 30 days as drinking water. Liver function tests, including aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) activities were measured. To evaluate liver antioxidant defences, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid reactive substance (TBARS) activities were determined in the homogenates of liver tissue. In addition, liver tissues were submitted for histopathologic examination. AST and ALT activities were increased in Group II, Group III and Group IV gradually when compared with the control group. The difference between Group II and the control group was not statistically significant (P > 0.016). Increases in AST and ALT activities of Group III and Group IV were statistically significant when compared with the control group. SOD, GSH-Px and CAT activities were increased in Group II when compared with the control group but the difference was not statistically significant (P > 0.016). However, SOD, GSH-Px activities and the TBARS level were significantly increased, and CAT activity was significantly decreased in Group III when compared with the control group. In Group IV, while SOD, GSH-Px and CAT activities were decreased, the TBARS level was increased as compared with the control group (P < 0.0016). Histopathological evaluation of experimental groups revealed a mild to severe degree of hepatic damage when compared to the control group. In Group II, there was only minimal hepatocytes degeneration. In Groups III and IV, there were granular or ballooning hepatocyte degeneration and necrosis, sinusoidal and central vein dilatation. It was concluded that lipid peroxidation and hepatic damage occurs after M. piperita and M. spicata administration in rat liver and the damage seems to be dose dependent.
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PMID:Investigation of biochemical and histopathological effects of Mentha piperita Labiatae and Mentha spicata Labiatae on liver tissue in rats. 1502 12


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