Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty subjects with acute uncomplicated falciparum malaria were treated orally with a new micronized formulation of halofantrine. The dose given corresponded to one-half the normal dose for the standard formulation. Parasitemia cleared in all subjects within 78 h. There was recrudescence of falciparum malaria in seven subjects after day 14. The mean +/- standard deviation clearance times of parasitemia and fever were 49.0 +/- 14.2 and 24.3 +/- 13.2 h, respectively. Other clinical symptoms related to malaria cleared within the first 3 days. Pruritus occurred in two subjects, back pain occurred in one subject, and diarrhea occurred in one subject; all of these symptoms were mild. Hematological and biochemical indices were not adversely affected by treatment except in five subjects in whom minor and transitory increases in aspartate aminotransferase and alanine aminotransferase were observed. Micronized halofantrine appears to be a safe, well-tolerated, and effective treatment for acute falciparum malaria in semiimmune patients.
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PMID:Efficacy of micronized halofantrine in semi-immune patients with acute uncomplicated falciparum malaria in Cameroon. 823 11

A 2-year-old, male, red-necked (Bennett's) wallaby (Macropus rufogriseus) from a zoological facility was presented for peracute onset of severe depression, unresponsiveness, ataxia, and loose feces. Serum biochemical abnormalities included azotemia, hypoalbuminemia, increased alanine aminotransferase activity, hyperbilirubinemia, hyperphosphatemia, and hyperkalemia, consistent with multi-organ system failure. Severe thrombocytopenia suggested possible disseminated intravascular coagulation. Peripheral blood smear examination revealed numerous ovoid, protozoal inclusions within monocytes and occasionally within neutrophils. Despite aggressive supportive therapy, the patent died within 5 hours of presentation. Gross necropsy and histopathologic findings included severe multifocal necrotizing lesions in multiple organs. Numerous intralesional protozoal organisms were observed and were identified as Toxoplasma gondii by immunohistochemistry. Macropods (wallabies and kangaroos) are known to be highly susceptible to toxoplasmosis, with high mortality rates; diagnosis most often is obtained at necropsy. Detection of protozoal organisms in peripheral blood leukocytes is reported rarely and has not been documented previously in a macropod. Parasitemia in this case was attributed to severe, disseminated disease. Careful examination of peripheral blood smears in macropods suspected of toxoplasmosis may be warranted.
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PMID:Toxoplasma gondii inclusions in peripheral blood leukocytes of a red-necked wallaby (Macropus rufogriseus). 1731 Dec 3

Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator. After a 2:1 randomization (block size three, equating to N = 12 for each ferroquine dose and N = 6 for each of four amodiaquine comparator groups) patients received daily for three consecutive days, either ferroquine + AS (200 mg/day) or amodiaquine (612 mg/day) + AS (200 mg/day). Safety, electrocardiograms, parasite clearance times, efficacy, and pharmacokinetics were assessed to day 28. Seventy-two patients were randomized. Ferroquine + AS showed generally mild increases (Grade 1 toxicity) in alanine aminotransferase (ALT) levels with a dose trend starting at 400 mg. There were two Grade 2 ALT events: one patient receiving 200 mg (3.8 upper limit of normal [ULN], day 7) and one receiving 600 mg (3.3 ULN, day 14), both without increased bilirubin. One ferroquine 100 mg + AS patient after one dose was withdrawn after developing a QTcF interval prolongation > 60 milliseconds over baseline. Parasitemias in all patients cleared quickly, with no recurrence through day 28. Hepatic, as well as cardiac, profiles should be monitored closely in future trials. (ClinicalTrials.gov: NCT00563914).
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PMID:Phase 2a, Open-Label, 4-Escalating-Dose, Randomized Multicenter Study Evaluating the Safety and Activity of Ferroquine (SSR97193) Plus Artesunate, versus Amodiaquine Plus Artesunate, in African Adult Men with Uncomplicated Plasmodium falciparum Malaria. 2882 27