Effects of diethylpropion treatment and withdrawal on aorta reactivity, endothelial factors and rat behavior

Diethylpropion (DEP) is an amphetamine-like compound used as a coadjutant in the treatment of obesity and which presents toxicological importance as a drug of abuse. This drug causes important behavioral and cardiovascular complications; however, the vascular and behavioral alterations during DEP treatment and withdrawal, have not been determined. We evaluated the effects of DEP treatment and withdrawal on the rat aorta reactivity to noradrenaline, focusing on the endothelium, and the rat behavior during DEP treatment and withdrawal. DEP treatment caused a hyporreactivity to noradrenaline in aorta, reversible after 2 days of withdrawal and abolished by both the endothelium removal and the presence of L-NAME, but not by the presence of indomethacin. Furthermore, DEP treatment increased the general activity of rats. Contrarily, DEP withdrawal caused a decrease in the locomotor activity and an increase in grooming behavior, on the 2nd and 7th days after the interruption of the treatment, respectively. DEP treatment also caused an adaptive vascular response to noradrenaline that seems to be dependent on the increase in the endothelial nitric oxide system activity, but independent of prostaglandins synthesis. The data evidenced chronological differences in the adaptive responses of the vascular and central nervous systems induced by DEP treatment. Finally, a reversion of the adaptive response to DEP was observed in the vascular system during withdrawal, whereas a neuroadaptive process was still present in the central nervous system post-DEP. These findings advance on the understanding of the vascular and behavioral pathophysiological processes involved in the therapeutic and abusive uses of DEP. (C) 2003 Elsevier B.V. (USA). All rights reserved.

Exposure to acute restraint stress reinstates nicotine-induced place preference in rats

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

Fatores prognósticos para o abandono precoce do tratamento da dependência do álcool, crack e outras drogas em uma comunidade terapêutica

Pós-graduação em Saúde Coletiva - FMB

Animal models of alcohol and drug dependence

Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overview of the preclinical procedures used to study drug abuse and dependence and describe recent progress that has been made in studying more specific aspects of addictive behavior in animals.

Incorporation of Ag nanoparticles into membrane mimetic systems composed by phospholipid layer-by-layer (LbL) films to achieve surface-enhanced Raman scattering as a tool in drug interaction studies

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

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Improvement of the oral praziquantel anthelmintic effect by cyclodextrin complexation

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

Computational analysis and physico-chemical characterization of an inclusion compound between praziquantel and methyl-beta-cyclodextrin for use as an alternative in the treatment of schistosomiasis

Schistosomiasis is still an endemic disease in many regions, with 250 million people infected with Schistosoma and about 500,000 deaths per year. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, however it is classified as Class II in the Biopharmaceutics Classification System, as its low solubility hinders its performance in biological systems. The use of cyclodextrins is a useful tool to increase the solubility and bioavailability of drugs. The aim of this work was to prepare an inclusion compound of PZQ and methyl-beta-cyclodextrin (MeCD), perform its physico-chemical characterization, and explore its in vitro cytotoxicity. SEM showed a change of the morphological characteristics of PZQ:MeCD crystals, and IR data supported this finding, with changes after interaction with MeCD including effects on the C-H of the aromatic ring, observed at 758 cm(-1). Differential scanning calorimetry measurements revealed that complexation occurred in a 1:1 molar ratio, as evidenced by the lack of a PZQ transition temperature after inclusion into the MeCD cavity. In solution, the PZQ UV spectrum profile in the presence of MeCD was comparable to the PZQ spectrum in a hydrophobic solvent. Phase solubility diagrams showed that there was a 5.5-fold increase in PZQ solubility, and were indicative of a type A(L) isotherm, that was used to determine an association constant (K(a)) of 140.8 M(-1). No cytotoxicity of the PZQ:MeCD inclusion compound was observed in tests using 3T3 cells. The results suggest that the association of PZQ with MeCD could be a good alternative for the treatment of schistosomiasis.

Synthesis, ex Vivo and in Vitro Hydrolysis Study of an Indoline Derivative Designed as an Anti-Inflammatory with Reduced Gastric Ulceration Properties

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cocaine-induced behavioral sensitization in adolescent rats endures until adulthood: Lack of association with GluR1 and NR1 glutamate receptor subunits and tyrosine hydroxylase

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

Influence of Steroidal Anti-Inflammatory Drugs on Viability and Fertility of Equine Semen

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

Evalution of methods for the detection of MRSA in patients of Botucatu Medical School Hospital, São Paulo, Brazil

Oxacillin is the main drug of choice for the treatment of S. aureus infections. However, S. aureus resistance to oxacillin has become a major problem in the recent decades. The study aimed assess the rates of oxacillin resistance in S. aureus samples obtained at the Botucatu Medical School Hospital, UNESP, and to compare phenotypic techniques for the detection of MRSA against the gold standard method (mecA gene detection) in these samples. A total of 102 samples, previously isolated between 2002 and 2006, and kept at the Culture Collection of the Department of Microbiology and Immunology, in the Botucatu Biosciences Institute, UNESP, were included. Oxacillin resistance was assessed by oxacillin and cefoxitin disk diffusion and agar dilution tests, screening tests using Mueller-Hinton agar with 6 mu g/mL of oxacillin and 4% NaCl, E-test, and mecA gene detection. of the samples analyzed, 46 (45.1%) were mecA-positive. Oxacillin disk sensitivity and specificity were 86.9% and 91.1%, respectively. Cefoxitin disk sensitivity and specificity were respectively 91.3% and 91.1%. The screening test with the cefoxitin disk showed almost the same level of sensitivity (91.3%) and specificity (91.1%). With E-test strips, sensitivity was higher (97.8%) and specificity was comparable to that found with the other methods (91.1%). Ninety-three percent of the samples produced beta-lactamase and five of them were mecA-negative. There was a gradual increase in the number of oxacillin-resistant S. aureus samples between 2002 and 2004. However, from 2004 to 2006, the number of resistant samples dropped from 55% of MRSA in 2004, to 45% in 2005 and 34.6% in 2006. The data obtained reveal that, among phenotypic methods, the E-test yielded the best results, with higher sensitivity levels when compared to the other methods. The decreased resistance rate observed over the most recent years may be explained by the rational use of antimicrobial agents associated with good practices in the control of hospital infection, or may be related to the diminished use of oxacillin as a treatment option.

Loading of praziquantel in the crystal lattice of solid lipid nanoparticles Studies by DSC and SAXS

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

Alternatives for the Treatment of Schistosomiasis: Physico-Chemical Characterization of an Inclusion Complex Between Praziquantel and Hydroxypropyl-beta-Cyclodextrin

"Alternatives for the Treatment of Schistosomiasis: Physico-Chemical Characterization of an Inclusion Complex Between Praziquantel and Hydroxypropyl-beta-Cyclodextrin". Praziquantel (PZQ) is the drug of choice commonly used for the treatment of shistosomiasis. However, it has low aqueous solubility, which could limit its bioavailability in the body. To circumvent these features, an inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was prepared. Thus, the objective of this work was to prepare and characterize the PZQ/HP-beta-CD inclusion complex. Morphological, spectroscopic, and calorimetric analysis showed the first signs of the guest/host interaction. The complexation kinetic analysis was used to determine the kinetic constant and, besides that, it was possible to establish the time consumed to reach equilibrium. Using the solubility isotherm, it was observed that the interaction with HP-beta-CD increased 2.4 fold the aqueous solubility of plain PZQ. In vitro cytotoxicity tests, using fibroblast cells, evidenced no toxicity for these cells at the concentrations tested. These results demonstrated that there is a potential use of PZQ in formulations with HP-beta-CD.