Albendazole metabolism in patients with neurocysticercosis: antipyrine as a multifunctional marker drug of cytochrome P450

The present study investigates the isoform(s) of cytochrome P450 (CYP) involved in the metabolism of albendazole sulfoxide (ASOX) to albendazole sulfone (ASON) in patients with neurocysticercosis using antipyrine as a multifunctional marker drug. The study was conducted on 11 patients with neurocysticercosis treated with a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h). On the 5th day of albendazole treatment, 500 mg antipyrine was administered po. Blood and urine samples were collected up to 72 h after antipyrine administration. Plasma concentrations of (+)-ASOX, (-)-ASOX and ASON were determined by HPLC using a chiral phase column and detection by fluorescence. The apparent clearance (CL/f) of ASON and of the (+) and (-)-ASOX enantiomers were calculated and compared to total antipyrine clearance (CL T) and the clearance for the production of the three major antipyrine metabolites (CLm). A correlation (P<=0.05) was obtained only between the CL T of antipyrine and the CL/f of ASON (r = 0.67). The existence of a correlation suggests the involvement of CYP isoforms common to the metabolism of antipyrine and of ASOX to ASON. Since the CL T of antipyrine is a general measure of CYP enzymes but with a slight to moderate weight toward CYP1A2, we suggest the involvement of this enzyme in ASOX to ASON metabolism in man. The study supports the establishment of a specific marker drug of CYP1A2 in the study of the in vivo metabolism of ASOX to ASON.

Participation of the endoplasmic reticulum protein chaperone thio-oxidoreductase in gonadotropin-releasing hormone receptor expression at the plasma membrane

Chaperone members of the protein disulfide isomerase family can catalyze the thiol-disulfide exchange reaction with pairs of cysteines. There are 14 protein disulfide isomerase family members, but the ability to catalyze a thiol disulfide exchange reaction has not been demonstrated for all of them. Human endoplasmic reticulum protein chaperone thio-oxidoreductase (ERp18) shows partial oxidative activity as a protein disulfide isomerase. The aim of the present study was to evaluate the participation of ERp18 in gonadotropin-releasing hormone receptor (GnRHR) expression at the plasma membrane. Cos-7 cells were cultured, plated, and transfected with 25 ng (unless indicated) wild-type human GnRHR (hGnRHR) or mutant GnRHR (Cys14Ala and Cys200Ala) and pcDNA3.1 without insert (empty vector) or ERp18 cDNA (75 ng/well), pre-loaded for 18 h with 1 µCi myo-[2-3H(N)]-inositol in 0.25 mL DMEM and treated for 2 h with buserelin. We observed a decrease in maximal inositol phosphate (IP) production in response to buserelin in the cells co-transfected with hGnRHR, and a decrease from 20 to 75 ng of ERp18 compared with cells co-transfected with hGnRHR and empty vector. The decrease in maximal IP was proportional to the amount of ERp18 DNA over the range examined. Mutants (Cys14Ala and Cys200Ala) that could not form the Cys14-Cys200 bridge essential for plasma membrane routing of the hGnRHR did not modify maximal IP production when they were co-transfected with ERp18. These results suggest that ERp18 has a reduction role on disulfide bonds in wild-type hGnRHR folding.

De artificio, quo in nutriendo fetu humano utitur natura

Arkit: 1 arkintunnukseton lehti, A-C4 D3.

Effects of sciatic nerve transection on ultrastructure, NADPH-diaphorase reaction and serotonin-, tyrosine hydroxylase-, c-Fos-, glucose transporter 1- and 3-like immunoreactivities in frog dorsal root ganglion

Frogs have been used as an alternative model to study pain mechanisms. Since we did not find any reports on the effects of sciatic nerve transection (SNT) on the ultrastructure and pattern of metabolic substances in frog dorsal root ganglion (DRG) cells, in the present study, 18 adult male frogs (Rana catesbeiana) were divided into three experimental groups: naive (frogs not subjected to surgical manipulation), sham (frogs in which all surgical procedures to expose the sciatic nerve were used except transection of the nerve), and SNT (frogs in which the sciatic nerve was exposed and transected). After 3 days, the bilateral DRG of the sciatic nerve was collected and used for transmission electron microscopy. Immunohistochemistry was used to detect reactivity for glucose transporter (Glut) types 1 and 3, tyrosine hydroxylase, serotonin and c-Fos, as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase). SNT induced more mitochondria with vacuolation in neurons, satellite glial cells (SGCs) with more cytoplasmic extensions emerging from cell bodies, as well as more ribosomes, rough endoplasmic reticulum, intermediate filaments and mitochondria. c-Fos immunoreactivity was found in neuronal nuclei. More neurons and SGCs surrounded by tyrosine hydroxylase-like immunoreactivity were found. No change occurred in serotonin- and Glut1- and Glut3-like immunoreactivity. NADPH-diaphorase occurred in more neurons and SGCs. No sign of SGC proliferation was observed. Since the changes of frog DRG in response to nerve injury are similar to those of mammals, frogs should be a valid experimental model for the study of the effects of SNT, a condition that still has many unanswered questions.

De arcto musices cum ingenio humano nexu, ejusque ad hoc excolendum momento 1

Invokaatio: Q.F.S.F.Q.

De monstro humano bicipite & bicorpore, truncis ad anteriora coalitis artubusque duplicatis

Painovuosi nimekkeestä.

Uso da acidez titulável no controle de qualidade do leite humano ordenhado

O perfil físico-químico do leite humano ordenhado cru (LHOc) com acidez titulável acima de 7ºD após 15 dias de congelamento, teores de creme, gordura total e valor energético, foram avaliados. Na etapa controle, os valores absolutos de creme, gordura total e valor energético (n=3887) foram determinados pelo método do crematócrito e a acidez titulável (n=4204) do LHOc por um método titulimétrico adaptado de leite de vaca. Na etapa teste, determinou-se o teor de creme, gordura total e valor energético de amostras (n=66) com acidez acima de 7ºD armazenadas entre -10º e -18ºC por 15 dias. A acidez titulável variou de 0,5 a 21ºD (3,52 ± 2,45ºD) e os teores de creme, gordura total e valor energético foram, respectivamente, 4,90 ± 0,25 %, 4,49 ± 0,26 % e 617,47 ± 17,37 Kcal/Litro. Houve redução significante nos teores de creme (6,45 ± 2,28% para 5,79 ± 2,57%), gordura total (4,0 ± 1,81% para 3,49 ± 1,76%) e valor energético (716,27 ± 176,59 Kcal/Litro para 666,82 ± 171,90 Kcal/Litro), com p<0,05. O uso do teste da acidez titulável constitui uma ferramenta importante no controle de qualidade do LHOc.

O caminho intermediário: alguns limites do conhecimento intelectual humano, segundo Tomás de Aquino

O presente trabalho tem a intenção de apresentar o alcance e os limites do conhecimento intelectual humano de acordo com Tomás de Aquino, tendo como base sobretudo as questões 84 e 85 da primeira parte de sua Suma de Teologia.

Sucedâneos à ética clássica: reflexões sobre o agir humano e o além do homem nietzscheano

Baseado nas reflexões de Nietzsche sobre a ação humana e o além-do-homem, este artigo discute sua crítica demolidora à ética clássica à luz do contexto mais amplo do século XIX de desconstrução dos valores éticos enraizados até então. Duas questões são enfatizadas: A suspeita lançada por Nietzsche sobre a ética clássica desencadeou um vazio ético? A efetivação histórico-social da Unwertung seria apenas uma utopia?

A alternativa como categoria em Lukács: a captura das mediações humano-genéricas

Entre os desafios postos para as pesquisas em ciências humanas e sociais está a compreensão do cotidiano como espaço para a captura das formas de apropriação da realidade objetiva por parte dos sujeitos e, ao mesmo tempo, a identificação das respostas dos sujeitos diante das condições postas. Como categoria analítica, destacamos as reflexões de Lukács acerca da categoria alternativa, tomando-a como mediação entre teleologia e reflexo, no processo de objetivação da teleologia em causalidade posta.

A dimensão teleológica e ordenada do agir humano em Santo Agostinho

A busca da vida feliz e o caminho que nos leva até ela, sempre se colocou como um dos grandes pilares das reflexões de Santo Agostinho. O presente trabalho tem a intenção de apresentar alguns aspectos da ética agostiniana, principalmente a noção de ordo amoris.

Planifica el talento humano al crear tu empresa

Bogotá Emprende

Desarrollo humano y organizacional, primer semestre 2011 - 2012

Banco del conocimiento

Planifica el talento humano al crear tu empresa

Bogotá Emprende

Planifica el talento humano al crear tu empresa

Bogotá Emprende