Norepinephrine responses in rat renal and femoral veins are reinforced by vasoconstrictor prostanoids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metabolomic analysis characterizes tissue specific indomethacin-induced metabolic perturbations of rats

In this study, the promising metabolomic approach integrating with ingenuity pathway analysis (IPA) was applied to characterize the tissue specific metabolic perturbation of rats that was induced by indomethacin. The selective pattern recognition analyses were applied to analyze global metabolic profiling of urine of rats treated by indomethacin at an acute dosage of reference that has been proven to induce tissue disorders in rats, evaluated throughout the time-course of -24-72 h. The results preliminarily revealed that modifications of amino acid metabolism, fatty acid metabolism and energetically associated metabolic pathways accounted for metabolic perturbation of the rats that was induced by indomethacin. Furthermore, IPA was applied to deeply analyze the biomarkers and their relations with the metabolic perturbations evidenced by pattern recognition analyses. Specific biochemical functions affected by indomethacin suggested that there is an important correlation of its effects in kidney and liver metabolism, based on the determined metabolites and their pathway-based analysis. The IPA correlation of the three major biomarkers, identified as creatinine, prostaglandin E2 and guanosine, suggested that the administration of indomethacin induced certain levels of toxicity in the kidneys and liver. The changes in the levels of biomarker metabolites allowed the phenotypical determination of the metabolic perturbations induced by indomethacin in a time-dependent manner.

Stereochemistry of Peptides Containing 1-AminocyclopentanecarboxylicA cid ( Am5): Solution and Solid-state Conformations of Boc-Acc '-Acc'-NHMe

The conformational analysis of a protected homodipeptide of 1-aminocyclopentanecarboxylic acid (Acc5) has been carried out. 1H-nmr studies establish a -turn conformation for Boc-Acc5-Acc5-NHMe in chloroform and dimethylsulfoxide solutions involving the methylamide NH in an intramolecular hydrogen bond. Supportive evidence for the formation of an intramolecular hydrogen bond is obtained from ir studies. X-ray diffraction studies reveal a type III -turn conformation in the solid state stabilized by a 4 1 hydrogen bond between the Boc CO and methylamide NH groups. The , values for both Acc5 residues are close to those expected for an ideal 310-helical conformation ( ± 60°, ±30°).

A utilização da fitoterapia e de plantas medicinais em unidades básicas de saúde nos municípios de Cascavel e Foz do Iguaçu Paraná: a visão dos profissionais de saúde

A fitoterapia e o uso de plantas medicinais fazem parte da prática da medicina popular, que diminuiu frente ao processo de industrialização nas décadas de 1940 e 1950, aumentando a busca, pela população, por terapias menos agressivas destinadas ao atendimento primário à saúde. Essa complementa o tratamento usualmente empregado para a população de menor renda. O objetivo deste trabalho foi analisar o conhecimento dos gestores e profissionais de saúde que atuam na atenção primária, sobre fitoterapia e uso de plantas medicinais, nos municípios de Cascavel e Foz do Iguaçu - Paraná. Para tanto, no período de fevereiro a julho de 2009, foi realizado estudo exploratório, descritivo, qualitativo, empregando como instrumentos de pesquisa entrevistas semiestruturadas e um questionário estruturado, auto aplicado, com perguntas fechadas, a fim de contemplar os seguintes aspectos: perfil dos profissionais; aceitabilidade quanto à implantação da fitoterapia na atenção básica; confiança nos tratamentos com fitoterápicos; capacitação e formação profissional relacionadas à fitoterapia, entre outros itens. Um dos gestores considerou recente o programa de fitoterapia. Indicadores de satisfação da população quanto ao uso dos fitoterápicos ou plantas medicinais ainda não existem. O gestor do município de Cascavel relatou interesse na implantação do programa. Os demais profissionais entrevistados, de maneira geral, relataram não haver recebido formação sobre o tema durante a graduação, nem mesmo dentro das UBS onde trabalham. Entre os profissionais entrevistados seis (60%) relataram o acesso às informações sobre fitoterapia através do conhecimento popular, uma (10%) formação na UBS, dois (20%) através de periódicos, quatro (40%) através de meio de comunicação, sendo que quatro citaram mais que uma das opções. Em Foz do Iguaçu, nas UBS onde a terapêutica está implantada, os profissionais relataram não terem sido consultados antes de sua implantação, e a avaliação das plantas utilizadas pelos pacientes atendidos ocorre somente através de avaliação objetiva e subjetiva do tratamento Para implantação da fitoterapia nas UBS desses dois municípios, é necessário capacitar os profissionais quanto ao tema, desde o cultivo até a prescrição, melhorando o uso racional desses medicamentos.

Screening and Structural Characterization of alpha-Glucosidase Inhibitors from Hawthorn Leaf Flavonoids Extract by Ultrafiltration LC-DAD-MSn and SORI-CID FTICR MS

In vitro a-glucosidase inhibition assays and ultrafiltration liquid chromatography with photodiode array detection coupled to electrospray ionization tandem mass spectrometry (ultrafiltration LC-DAD-ESI-MSn) were combined to screen a-glucosidase inhibitors from hawthorn leaf flavonoids extract (HLFE). As a result, four compounds were identified as alpha-glucosidase inhibitors in the HLFE, and their structures were confirmed to be quercetin-3-O-rha-(1-4)-glc-rha and C-glycosylflavones (vitexin-2 ''-O-glucoside, vitexin-2 ''-O-rhamnoside and vitexin) by high-resolution sustained off resonance irradiation collision-induced dissociation (SORI-CID) data obtained by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS).

A study of isomeric diglycosyl flavonoids by SORI CID of Fourier transform ion cyclotron mass Spectrometry in negative ion mode

High-resolution Sustained off resonance irradiation (SORI) CID was employed to distinguish four pairs of isomeric diglycosyl flavonoids in the negative mode using the electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS). All of these isomers can be distinguished via MS/MS data. For these diglycosyl flavones and flavanones, the deprotonated alpha 1-->6 linkage diglycosyl flavonoids produce fewer fragments than the alpha 1-->2 linkage type compounds and the Retro-Diels-Alder (RDA) reaction in MS/MS only takes place when the aglycone is a flavanone and glycosylated with an alpha 1-->2 intersaccharide linkage disaccharide. The deprotonation sites after collisional activation are discussed according to the high mass accuracy and high-resolution data of tandem spectrometry. Some of these high-resolution SORI CID product ions from alpha 1-->2 linkage diglycosyl flavonoids involve multibond cleavages; the possible mechanism is discussed based on the computer modeling using Gaussian 03 program package at the B3LYP/6-31G level of theory. Unambiguous elementary composition data provides fragmentation information that has not been reported previously.

ICP-AES-CID二维光谱的频率特性研究

本文对电感耦合等离子体原子发射光谱分析 (ICP AES)中电荷注入检测器 (CID)得到的二维光谱的频率特性作了研究。测量光谱经过傅里叶变换得到其光谱的频域分布。结果表明 ,测量光谱在频域中的信号可被分为两部分 :即低频信号和高频信号。前者代表有用的分析信号而后者代表背景和噪声。然而 ,不能采用简单滤除高频信号的方法来去除噪声 ,因为这样虽然高频信号没有明显改变但会使背景变形。

A STUDY ON CH5O+ IONS IN GAS PHASE CID EYPERIMENT AND QUANTUM CHEMISTRY CALCULATION

The structures of CH5O+ from two different reactions which are protonation of CH3OH from the above two pathways possess the same structures, CH3OH2+. The value of kinetic energy release for the metastable decomposition CH2OH3+-> CH2OH+ + H-2 determined from the experiment is in good agreement with that from theoretical calculations. The transition state of above reaction were disscussed.

Steady state pharmacokinetic profile of indomethacin in elderly patients and young volunteers

The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20-34 y) and in 12 elderly subjects (7 m, 5 f; 70-88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, Tmax and AUC (0-12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (micrograms.ml-1.h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.