BackgroundThe genetic variation underlying atorvastatin (ATV) pharmacokinetics was evaluated in a Mexican population. Aims of this study were: 1) to reveal the frequency of 87 polymorphisms in 36 genes related to drug metabolism in healthy Mexican volunteers, 2) to evaluate the impact of these polymorphisms on ATV pharmacokinetics, 3) to classify the ATV metabolic phenotypes of healthy volunteers, and 4) to investigate a possible association between genotypes and metabolizer phenotypes.MethodsA pharmacokinetic study of ATV (single 80-mg dose) was conducted in 60 healthy male volunteers. ATV plasma concentrations were measured by high-performance liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated by the non-compartmental method. The polymorphisms were determined with the PHARMAchip® microarray and the TaqMan® probes genotyping assay.ResultsThree metabolic phenotypes were found in our population: slow, normal, and rapid. Six gene polymorphisms were found to have a significant effect on ATV pharmacokinetics: MTHFR (rs1801133), DRD3 (rs6280), GSTM3 (rs1799735), TNFα (rs1800629), MDR1 (rs1045642), and SLCO1B1 (rs4149056). The combination of MTHFR, DRD3 and MDR1 polymorphisms associated with a slow ATV metabolizer phenotype.ConclusionFurther studies using a genetic preselection method and a larger population are needed to confirm these polymorphisms as predictive biomarkers for ATV slow metabolizers.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12614000851662, date registered: August 8, 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2062-2) contains supplementary material, which is available to authorized users.
cDNA encoding mature human placental variant growth hormone (HGH-V) was synthesized by retro-transcription polymerase chain reaction (RT-PCR) from total RNA recovered from human term-placenta and cloned in pBluescript plasmid (pBS) in Escherichia coli. cDNA was subcloned into pPIC9, fusing it to the flanking regulatory sequences of the Pichia pastoris alcohol oxidase 1 gene (AOX1) and finally introduced into the genome of this yeast by homologous recombination. The resulting new recombinant strain produced and secreted, towards the culture medium, mature HGH-V, whose activity was demonstrated in cell culture by the Nb2 proliferation assay.
We report for the first time the design and expression of the recombinant E. histolytica LC3 protein fused to PEΔIII and KDEL3, with potential application as an immunogen.
Mycetoma is a chronic human infectious disease that produces severe deformation frequently in the lower extremities. Etiological agents include fungi (eumycetoma) and bacteria (actinomycetoma) that produce similar clinical and microscopic changes. The clinical appearance includes swelling, abscesses, ulcers, scars, and sinuses that drain purulent material with microbe microcolonies. The pathogenesis of actinomycetoma has been studied mainly in rodents. Using this approach, it was found that Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A. Nitric oxide (NO) is a molecule with biological activities depending on its local concentration. Its effect on killing intracellular bacteria such as Mycobacterium tuberculosis has been known for decades. NO plays an important role in innate and adaptive immunity. It can promote or suppress some biological activities despite its short half-ife. NO is produced by three different nitric oxide synthases (NOS). We used the genetic blockade of eNOS in C57BL/6 mice to demonstrate the role of NO in actinomycetoma development. Inflammation and actinomycetoma were prevented in genetically modified mice infected with Nocardia brasiliensis. T cell proliferation was increased in these rodents, and antibody production, IL-6, and IL-10 expression were similar and TNF-α was lower.
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