Sequestration of total and methyl mercury in different subcellular pools in marine caged fish

Mercury contamination is an important issue in marine fish, and can cause toxicity to human by fish consumption. Many studies have measured the mercury concentrations in fish and estimated the threshold levels of its risk to human, but the mercury sequestration in different subcellular pools of fish is unclear. In this study, we investigated the concentration and distribution of total mercury (THg) and methylmercury (MeHg) in different subcellular fractions in the farmed red seabream, red drum, and black seabream from Fujian marine fish farms, China. We found that both THg and MeHg were dominantly bound with the cellular debris, followed by metallothionein-like protein > metal-rich granule > heat-denatured protein > organelles pools. In general, Hg bound with the metal-sensitive fraction was small, indicating that Hg may have little toxicity to the fish (muscle). For the first time we showed that MTLP fraction had the highest % of total Hg as MeHg (88-91%) among all the subcellular fractions. Furthermore, the mercury concentration and subcellular distribution in the black seabream were both dependent on the fish size. Subcellular study may shed light on the detoxification of marine fish to Hg exposure and the potential bioavailability to humans due to fish consumption. © 2011 Elsevier B.V

Efficacy and motor complications of original and generic levodopa in Parkinson's disease treatment

Narongrit Kasemsap,1 Satrirat Onsanit,2 Piyawan Chiewthanakul,3 Kannikar Kongbunkiat,1 Chonthicha Tanking,1 Nisa Vorasoot,1 Kittisak Sawanyawisuth,1,4 Somsak Tiamkao1,5 1Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 2Department of Medicine, Udonthani Hospital, Udonthani, 3Department of Medicine, Khon Kaen Hospital, 4Research Center in Back, Neck, Other Joint Pain and Human Performance (BNOJPH), 5Neuroscience Research and Development Group (NRDG), Khon Kaen University, Khon Kaen, Thailand Background: In general, a generic drug is considered interchangeable with the original formulated drug. In Parkinson’s disease (PD), generic drug use remains debated. This study was aimed to investigate whether the generic drug was as effective as the original in improving the symptoms of PD and the prevalence of motor complications.Methods: This study was a multicenter cohort study of patients with PD enrolled from three northeast hospitals in Thailand between February 2013 and February 2014. The patients were categorized into original and generic levodopa groups. The clinical characteristics, efficacy, and motor complications were compared between the groups.Results: There were 400 eligible patients. Of these, 327 patients (81.75%) met the study criteria and were classified as the original levodopa group (200 patients, 61.16%) and the generic levodopa group (127 patients, 38.84%). The average age of all patients with PD was 65 years. The duration of PD and the modified Hoehn–Yahr stages were not different between the groups. The total doses of original and generic levodopa-equivalent doses were significantly different (199.97±127.08 versus 305.58±138.27 mg; P-value <0.001) and the actual doses were 198.10±117.92 versus 308.85±139.40 mg (P-value <0.001). Approximately 80% of patients with PD in both groups had good responses (P-value >0.999), but the development of motor complications was significantly greater in the original than in the generic group.Conclusion: Generic levodopa was effective in improving the symptoms of PD. The prevalence of motor complications in the original compound group, at a lower dose of levodopa equivalent, was higher than in the generic group. Keywords: Parkinson’s disease, original, generic, levodopa, efficacy, motor complicatio

Adjunctive dexamethasone in HIV-associated cryptococcal meningitis

Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis.In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole.The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites.Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. (Funded by the United Kingdom Department for International Development and others through the Joint Global Health Trials program; Current Controlled Trials number, ISRCTN59144167.)