The EBI Enzyme Portal.

The EBI enzyme portal.

Filed under: Drug and Alcohol Rehabilitation

Nucleic Acids Res. 2012 Nov 21;
Alcántara R, Onwubiko J, Cao H, Matos PD, Cham JA, Jacobsen J, Holliday GL, Fischer JD, Rahman SA, Jassal B, Goujon M, Rowland F, Velankar S, López R, Overington JP, Kleywegt GJ, Hermjakob H, O’Donovan C, Martín MJ, Thornton JM, Steinbeck C

The availability of comprehensive information about enzymes plays an important role in answering questions relevant to interdisciplinary fields such as biochemistry, enzymology, biofuels, bioengineering and drug discovery. At the EMBL European Bioinformatics Institute, we have developed an enzyme portal (http://www.ebi.ac.uk/enzymeportal) to provide this wealth of information on enzymes from multiple in-house resources addressing particular data classes: protein sequence and structure, reactions, pathways and small molecules. The fact that these data reside in separate databases makes information discovery cumbersome. The main goal of the portal is to simplify this process for end users.
HubMed – drug

 

Enzymatic synthesis of N-Acylethanolamines: Direct method for the aminolysis of esters.

Filed under: Drug and Alcohol Rehabilitation

Tetrahedron Lett. 2012 Oct 24; 53(43): 5753-5755
Whitten KM, Makriyannis A, Vadivel SK

Immobilized Candida antarctica (Novozyme 435) catalyzed synthesis of N-acylethanolamines is described. Treatment of methyl esters with lipase and amines yielded the desired amides within 2-24 hrs with yields ranging from 41-98%.
HubMed – drug

 

The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South Sumatra, Western Indonesia: an open label randomized controlled trial.

Filed under: Drug and Alcohol Rehabilitation

Clin Infect Dis. 2012 Nov 21;
Sutanto I, Suprijanto S, Kosasih A, Dahlan MS, Sjafruddin D, Kusriastuti R, Hawley WA, Lobo NF, Ter Kuile FO

Background.?Artemisinin-based combination therapy (ACT) is very effective in clearing asexual stages of malaria and reduces gametocytemia, but may not affect mature gametocytes. Primaquine is the only commercially available drug that eliminates mature gametocytes.Methods and objectives.?We conducted a two-arm open-label randomized controlled trial to evaluate the efficacy of single dose primaquine (0.75 mg/kg) following treatment with dihydroartemisinin-piperaquine on P. falciparum’s gametocytemia, in Indonesia. Patients with symptomatic uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase (G6PD) enzyme levels, aged ?5 years and hemoglobin levels ?8 g/dL were assigned by computerized-generating sequence to receive either a standard 3-day course dihydroartemisinin-piperaquine alone (n=178) or combined with a single dose of primaquine on Day-3 (n=171). Patients were seen on days 1, 2, 3, 7 and then weekly for 42 days to assess the presence of gametocytes and asexual parasites by microscopy. Survival analysis was stratified by the presence of gametocytes on Day-3.Results.?DHP prevented development of gametocytes in 277 patients without gametocytes on Day-3. In the gametocytemic patients (n=72), primaquine was associated with faster clearance of gametocytes (HR=2.42, 95% CI 1.39- 4.19, P= 0.002) and reduced gametocyte densities (geometric mean area-under-the-curve 157 vs 330, P= 0.018). The Day-42 cure rate of asexual stages in the DHP-PQ and DHP-alone arms were: PCR-unadjusted: 98.7% vs 99.4% respectively; PCR-adjusted:100% for both. Primaquine was well tolerated.Conclusion.?Addition of a single dose of primaquine shortens the infectivity period of DHP treated patients with acute uncomplicated malaria and should be considered in low transmission regions that aim to control and ultimately eliminate falciparum malaria.Clinical Trial Registration.?NCT01392014.
HubMed – drug

 

Effect of high dose or split dose artesunate on parasite clearance in artemisinin resistant falciparum malaria.

Filed under: Drug and Alcohol Rehabilitation

Clin Infect Dis. 2012 Nov 21;
Das D, Tripura R, Phyo AP, Lwin KM, Tarning J, Lee SJ, Hanpithakpong W, Stepniewska K, Menard D, Ringwald P, Silamut K, Imwong M, Chotivanich K, Yi P, Day NP, Lindegardh N, Socheat D, Nguon C, White NJ, Nosten F, Dondorp AM

Background.?The emergence of Plasmodium falciparum resistance to artemisinins on the Cambodian and Myanmar-Thai borders poses severe threats to malaria control. We investigated whether increasing or splitting the dose of the short half-life drug artesunate improves parasite clearance in falciparum malaria in the two regions.Methods.?In Pailin, Western Cambodia (from 2008 to 2010) and Wang Pha, North-western Thailand (2009-2010), patients with uncomplicated falciparum malaria were randomized to oral artesunate 6 mg/kg/day as single or twice-daily dose for 7 days, or artesunate 8 mg/kg/day as single or twice daily dose for 3 days, followed by mefloquine. Parasite clearance and recrudescence up to 63-days follow-up were assessed. Trial registration: ISRCTN15351875.Results.?A total of 159 patients were enrolled. Overall median (IQR) parasitaemia half-life (half-life) was 6.03 (4.89-7.28) hours in Pailin versus 3.42 (2.20-4.85) hours in Wang Pha (p=0.0001). Splitting or increasing the artesunate dose did not shorten half-life in either site. Pharmacokinetic profiles of artesunate and dihydroartemisinin were similar between sites and did not correlate with half-life. Recrudescent infections occurred in 4 out of 79 patients in Pailin and 5/80 in Wang Pha and was not different between treatment arms (p=0.68). High dose artesunate was associated with transient reticulocytopenia and in one patient with transient neutropenia (0.78 x 10(3)/?L) at day 14.Conclusions.?Increasing the artesunate treatment dose up to 8 mg/kg/day or splitting the dose does not improve parasite clearance in either artemisinin resistant or more sensitive infections with P. falciparum.
HubMed – drug

 


 

First Century Foundations: Season 5 Episode 1.mov – This week Joe Amaral is on location in Jerusalem. He is given a personal tour of one of the most recent archaeological discoveries in Israel, in the ancient and historic City of David! Joe talks about a personal experience as he teaches about Jesus as the Fourth Day Messiah! Our Israel Ministry segment introduces a drug and alcohol rehabilitation center in Jerusalem. Watch the entire episode and be blessed!

 

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