L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats

Dapsone use is frequently associated to hematological side effects such as methemoglobinemia and hemolytic anemia, which are related to N-hydroxylation mediated by the P450 enzyme system. The aim of the present study was to evaluate the influence of L-arginine supplementation, a precursor for the synthesis of nitric oxide, as single or multiple dose regimens on dapsone-induced methemoglobinemia. Male Wistar rats were treated with L-arginine at 5, 15, 30, 60 and 180 mg/kg doses (p.o., gavage) in single or multiple dose regimens 2 hours prior to dapsone administration (40 mg/kg, i.p.). The effect of the nitric oxide synthase inhibitor L-NAME was investigated by treatment with multiple doses of 30 mg/kg (p.o., gavage) 2 hours before dapsone administration. Blood samples were collected 2 hours after dapsone administration. Erythrocytic methemoglobin levels were assayed by spectrophotometry. The results showed that multiple dose supplementations with 5 and 15 mg/kg L-arginine reduced dapsone-induced methemoglobin levels. This effect is mediated by nitric oxide formation, since the reduction in methemoglobin levels by L-arginine is blocked by simultaneous administration with L-NAME, a nitric oxide synthase inhibitor.

Comparative morphology of the gas bladder in driftwood catfishes (Siluriformes: Auchenipteridae)

The gross morphology of the gas bladder is described and illustrated for representatives of most species and all valid genera of the Auchenipteridae (Siluriformes). Although, a simple cordiform gas bladder is present in some species of the family, others are characterized by their distinctive gas-bladder shape and diverticula disposition. An acute posterior end of the gas bladder characterizes Centromochlus heckelii and C. macracanthus, and is variably present in specimens of Auchenipterus. Tocantinsia piresi and Asterophysus batrachus have distinctive gas bladders differing in number of diverticula (two or many). The two species of Trachycorystes are diagnosed based on their gas bladder morphology: T. menezesi has a simple cordiform bladder, whereas T. trachycorystes has a pair of lateral diverticulum and, usually, a well-developed terminal diverticulum. Species of Auchenipterichthys are characterized by having a secondary bladder with simple chamber. Short or elongate and divergent terminal diverticula are exclusive to most cis-andine species of Trachelyopterus. Tetranematichthys and trans-andine species of Trachelyopterus share a well-developed secondary chamber or terminal diverticula ventrally or dorsally connected to the posterior chambers. The small-sized species of Ageneiosus have well-developed gas bladders with a pair of posterior diverticula, whereas large-sized species have a reduced gas bladder with tunica externa varying from non-, partially, or completely ossified. Eight phylogenetic characters are proposed based on the morphology of the gas bladder and associated structures in species of Auchenipteridae, and the evolution of those characters in the family discussed. J. Morphol., 2012. (C) 2012 Wiley Periodicals, Inc.

Extensor indicis brevis Muscle: an Unusual Muscular Variant

Knowledge of anatomical variations of the musculoskeletal system is important for interpreting unusual clinical presentations. We observed the presence of an abnormal extensor indicis muscle in the left hand of an adult male cadaver. In this case, the muscle comes from the ligament and over the scaphoideum and trapezoideum bones and continues after the short muscle belly; it is attached to the dorsal aponeurosis of the indicis. This muscular disposition was described in other studies which demonstrated approximately 1.0% of incidence. Clinically, this anatomical variation may be associated with pain and swelling at the back of the hand. In these cases symptoms tend to increase due to mechanical stress and can be confused with the presence of a dorsal synovial cyst. This report will help clinicians, surgeons, occupational and physical therapists formulate better clinical or surgical decisions when presented with a rare anatomical variation.

Influence of Genomic Ancestry on the Distribution of SLCO1B1, SLCO1B3 and ABCB1 Gene Polymorphisms among Brazilians

The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations.

Analysis of carvedilol enantiomers in human plasma using chiral stationary phase column and liquid chromatography with tandem mass spectrometry

Carvedilol is an antihypertensive drug available as a racemic mixture. (-)-(S)-carvedilol is responsible for the nonselective beta-blocker activity but both enantiomers present similar activity on a1-adrenergic receptor. To our knowledge, this is the first study of carvedilol enantiomers in human plasma using a chiral stationary phase column and liquid chromatography with tandem mass spectrometry. The method involves plasma extraction with diisopropyl ether using metoprolol as internal standard and direct separation of the carvedilol enantiomers on a Chirobiotic T (R) (Teicoplanin) column. Protonated ions [M + H]+ and their respective ion products were monitored at transitions of 407 > 100 for the carvedilol enantiomers and 268 > 116 for the internal standard. The quantification limit was 0.2 ng ml-1 for both enantiomers in plasma. The method was applied to study enantioselectivity in the pharmacokinetics of carvedilol administered as a single dose of 25 mg to a hypertensive patient. The results showed a higher plasma concentration of (+)-(R)-carvedilol (AUC08 205.52 vs. 82.61 (ng h) ml-1), with an enantiomer ratio of 2.48. Chirality, 2012. (C) 2012 Wiley Periodicals, Inc.

SENSITIVE METHOD FOR DETERMINATION OF PIPLARTINE, AN ALKALOID AMIDE FROM Piper SPECIES, IN RAT PLASMA SAMPLES BY LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

Piplartine (PPTN) is an alkaloid amide found in Piper species that presents different activities. PPTN determination in rat plasma is necessary to better understand its biological effects. The aim of this study was to develop a sensitive LC-MS/MS method for the determination of PPTN in rat plasma. The performance criteria for linearity, sensitivity, precision, accuracy, recovery, and stability have been assessed and were within the recommended guidelines. The validated method proved to be suitable in a pilot study of PPTN kinetic disposition in rat plasma after a single intraperitoneal dose, and represents an appropriate tool to further pharmacokinetic studies.

Designing piezoresistive plate-based sensors with distribution of piezoresistive material using topology optimization

Piezoresistive sensors are commonly made of a piezoresistive membrane attached to a flexible substrate, a plate. They have been widely studied and used in several applications. It has been found that the size, position and geometry of the piezoresistive membrane may affect the performance of the sensors. Based on this remark, in this work, a topology optimization methodology for the design of piezoresistive plate-based sensors, for which both the piezoresistive membrane and the flexible substrate disposition can be optimized, is evaluated. Perfect coupling conditions between the substrate and the membrane based on the `layerwise' theory for laminated plates, and a material model for the piezoresistive membrane based on the solid isotropic material with penalization model, are employed. The design goal is to obtain the configuration of material that maximizes the sensor sensitivity to external loading, as well as the stiffness of the sensor to particular loads, which depend on the case (application) studied. The proposed approach is evaluated by studying two distinct examples: the optimization of an atomic force microscope probe and a pressure sensor. The results suggest that the performance of the sensors can be improved by using the proposed approach.

Effect of pH, mucin and bovine serum on rifampicin permeability through Caco-2 cells

Rifampicin, a poorly soluble drug, has great importance in therapeutics as it is the main drug used to treat tuberculosis. The characterization of its permeability and the factors that influence it represent an important tool for predicting its bioavailability. Caco-2 cell monolayers were used as models of the intestinal mucosa to assess the uptake and transport of rifampicin and the effects of various experimental conditions were investigated, in order to establish the influence of these variables on rifampicin permeability. Different pHs (5.8, 6.8 and 7.4) in the apical medium, the presence or absence of mucin (3.0% w/v) in the donor site and the presence or absence of bovine serum albumin (4.0% v/v) in the receptor chamber were the evaluated conditions. The quantification of rifampicin in the apical or basolateral chambers was performed by a validated HPLC-UV method. The change in the donor chamber pH showed that permeability values were greater at pH 6.8, although this increase does not result in an alteration of the qualitative classification of rifampicin, which has high permeability. Mucin and bovine serum showed no effects on the permeability of rifampicin at the concentration tested. Overall, the current study suggests that pH, artificial mucin and bovine serum proteins have no influence on rifampicin permeability. Copyright (c) 2012 John Wiley & Sons, Ltd.

Sistema em Leibniz e Descartes

Descartes concebe que a verdadeira ordem científica é a ordem das razões, na qual se parte das verdades mais fáceis e evidentes em direção às mais difíceis e complexas. Assim, estabelece-se uma ordem única, progressiva e irreversível, onde cada membro da cadeia depende daqueles que o antecederam, de modo que cada tese possui um lugar não-intercambiável dentro da doutrina. Leibniz, ao contrário, defende que "[...] uma mesma verdade pode ter vários lugares, conforme as diferentes relações que pode possuir" (Novos Ensaios, IV, XXI, § 4). A fim de evitar as repetições, reunindo-se o máximo de verdades no mínimo de volumes, o autor propõe que a melhor ordem científica é a disposição sistemática das matérias, que consiste em uma organização do saber na qual cada lugar reenvia a outros, tornando clara a conexão entre os conhecimentos. Em contraposição ao modelo de sistema cartesiano, no modelo leibniziano, as teses se fundamentam mutuamente e a ordem das verdades estabelecidas é reversível. Ora, é devido a essas diferenças na concepção de sistema que Leibniz, ao contrário de Descartes, pode pretender tomar o que há de melhor nos sistemas legados pela tradição para constituir o seu próprio sistema, já que para ele há uma certa maleabilidade na constituição do sistema filosófico.

Sensitive method for determination of piplartine, an alkaloid amide from Piper species, in rat plasma samples by liquid chromatography-tandem mass spectrometry

Piplartine (PPTN) is an alkaloid amide found in Piper species that presents different activities. PPTN determination in rat plasma is necessary to better understand its biological effects. The aim of this study was to develop a sensitive LC-MS/MS method for the determination of PPTN in rat plasma. The performance criteria for linearity, sensitivity, precision, accuracy, recovery, and stability have been assessed and were within the recommended guidelines. The validated method proved to be suitable in a pilot study of PPTN kinetic disposition in rat plasma after a single intraperitoneal dose, and represents an appropriate tool to further pharmacokinetic studies.

Morfologia do funículo espermático em caprinos da raça Bhuj Brasileira

Estudamos em 40 caprinos adultos da raça Bhuj Brasileira os aspectos histológicos do funículo espermático. Observamos que este se acha envolvido por uma cápsula de tecido conjuntivo fibroelástico denso, de espessura variável, pregueada em alguns pontos, e revestida por mesotélio que circunda todo o conjunto vásculo-nervoso, e projeta-se para formar o mesoducto deferente. Em posição subcapsular, verifica- se uma camada de tecido conjuntivo fibroelástico frouxo, de espessura variável, que circunda parcialmente o funículo espermático, isolando nas regiões deferencial e abdeferencial, conjuntos vásculo-nervosos, responsáveis pela nutrição do epidídimo. Na região do mesoducto deferente, o tecido subcapsular acompanhado de tecido adiposo constitui a camada interna deste meso, formando a sua adventícia e abrigando vasos e nervos deferenciais. Na região abdeferencial, pequenos acúmulos de tecido adiposo são vistos de permeio aos vasos e nervos desta região. Entre as artérias, veias e nervos testiculares, bem como entre os vasos das regiões deferencial e abdeferencial, observa-se o tecido conjuntivo denso, intervascular, rico em fibras elásticas, que constitui as adventícias contínuas destes vasos. O arranjo vascular mostra que o segmento da artéria testicular, contido no funículo espermático, apresenta trajeto sinuoso. Estando envolvido pelo plexo venoso pampiniforme, formado por veias testiculares desprovidas de válvulas de calibres variados, apresentando amplas comunicações entre si. As veias responsáveis pela drenagem do epidídimo e ducto deferente estão localizadas em posição subcapsular deferencial e abdeferencial e mostram-se providas de válvulas. O trato das artérias testiculares no funículo espermático apresenta como média e desvio padrão 134,6±38,1cm à direita, e 137,0±33,9cm à esquerda, não existindo diferenças estatisticamente significantes ao nível de 5%, quando comparamos a média do segmento da artéria testicular contida no funículo espermático direito em relação ao esquerdo.