56 resultados para Comparative drug forgiveness index

em Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho"


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In recent years, many researchers in the field of biomedical sciences have made successful use of mathematical models to study, in a quantitative way, a multitude of phenomena such as those found in disease dynamics, control of physiological systems, optimization of drug therapy, economics of the preventive medicine and many other applications. The availability of good dynamic models have been providing means for simulation and design of novel control strategies in the context of biological events. This work concerns a particular model related to HIV infection dynamics which is used to allow a comparative evaluation of schemes for treatment of AIDS patients. The mathematical model adopted in this work was proposed by Nowak & Bangham, 1996 and describes the dynamics of viral concentration in terms of interaction with CD4 cells and the cytotoxic T lymphocytes, which are responsible for the defense of the organism. Two conceptually distinct techniques for drug therapy are analyzed: Open Loop Treatment, where a priori fixed dosage is prescribed and Closed Loop Treatment, where the doses are adjusted according to results obtained by laboratory analysis. Simulation results show that the Closed Loop Scheme can achieve improved quality of the treatment in terms of reduction in the viral load and quantity of administered drugs, but with the inconvenience related to the necessity of frequent and periodic laboratory analysis.

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Antifungal activity of natural products has been tested by adapting methods designed for synthetic drugs. In this study, two methods for the determination of antifungal activity of natural products, agar diffusion and broth microdilution, the CLSI reference methods for synthetic drugs, are compared and discussed. The microdilution method was more sensitive. The minimal inhibitory concentrations (MIC) of crude extracts, fractions and pure substances from different species of the plant families Piperaceae, Rubiaceae, Clusiaceae, Fabaceae and Lauraceae, from the Biota project, were determined. Antifungal activities against Candida albicans, C.krusei, C.parapsilosis and Cryptococcus neoformans were produced by several samples.

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Lycopene is a natural carotenoid, free radical scavenger, and presents protective effects by inhibiting oxidative DNA damage. The objective of the current study was to investigate the cytogenetic effects of a single acute and four daily gavage administrations of lycopene, and to examine possible protective effects on chromosomal damage induced by the antitumor drug cisplatin (cDDP) in rat bone marrow cells. The animals were divided into treatment groups, with three lycopene doses in the acute treatment (2, 4, and 6 mg/kg b.w.), three lycopene doses in the subacute treatment (0.5, 1.0, and 1.5 mg/kg b.w.) with and without cDDP (5 mg/kg b.w. i.p.), and respective controls. The results indicated that lycopene is neither cytotoxic nor clastogenic when compared with the negative controls (P > 0.01). cDDP-treated animals submitted to acute and subacute treatments with different lycopene doses showed a significant reduction (p < 0.01) in the number of abnormal metaphases when compared with the animals treated only with cDDP. The protective effects of lycopene on cDDP-induced chromosomal damage may be attributed to its antioxidant activity. These results suggest that this carotenoid may prove useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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An analysis of scientific bibliographic productivity using the Hirsch h-index, information from the Institute of Scientific Information database and the Curriculum Lattes (CNPq, Brazil) was performed at the Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo (FFCLRP-USP) that has four departments in natural, biological and social sciences. Bibliometric evaluations of undergraduate programs showed a better performance of the departments of Chemistry (P < 0.001) and Biology (P < 0.001) when compared to the departments of Physics and Mathematics and Psychology and Education. We also analyzed the scientific output of the six graduate programs of FFCLRP: Psychology, Psychobiology, Chemistry, Physics Applied to Medicine and Biology, Comparative Biology, and Entomology. The graduate program in Psychology presented a lower h-index (P < 0.001) and had fewer papers indexed by the ISI web of science (P < 0.001) when compared to the other graduate programs. The poorer performance of the Psychology program may be associated with the limited coverage by the Thompson Institute of Scientific Information database.

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

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The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer's (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed. in the stomach for intramucosal gastric CO2 (Pgco(2)) determination and for the calculation of intramucosal. pH (pHi):[pHi = pHa - log(Pgco(2)/Paco(2))].The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40-50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL / kg; HSD (n = 12), 6 mL / kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous Po-2 and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.

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Aim. Extrinsic compression of the popliteal artery and absence of surrounding anatomical abnormalities characterize the functional popliteal artery entrapment syndrome (PAES). The diagnosis is confirmed to individuals who have typical symptoms of popliteal entrapment and occlusion or important stenosis of the popliteal artery with color duplex sonography (CDS), magnetic resonance imaging (MRI) or arteriography during active plantar flexion-extension maneuvers. However, variable result findings in normal asymptomatic subjects have raised doubts as to the validity of these tests. The purpose of this study was to compare the frequency of popliteal artery compression in 2 groups of asymptomatic subjects, athletes and non-athletes.Methods. Forty-two individuals were studied. Twenty-one subjects were indoor soccer players, and 21 were sedentary individuals. Physical activity was evaluated through questionnaires, anthropometric measurements, and cardiopulmonary exercise test. Evaluation of popliteal artery compression was performed in lower limbs with CDS, ankle-brachial index (ABI) measurements and continuous wave Doppler of the posterior tibial artery.Results. The athletes studied fulfilled the criteria of high level of physical activity whereas sedentary subjects met the criteria of low level of activity. Popliteal artery compression was observed with CDS in 6 (14.2%) studied subjects; 2 of whom (4.7%) were athletes and 4 (9.5%) were non-athletes. This difference was not statistically significant (p=0.21). Doppler of the tibial arteries and ABI measurements gave good specificity and sensibility in the identification of popliteal artery compression.Conclusion. The frequency of popliteal artery compression during maneuvers in normal subjects was 14.2% irrespective of whether or not they performed regular physical activities. Both Doppler and ABI showed good agreement with CDS and should be considered in screening popliteal arteries in individuals suspected of PAES.

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OBJETIVO: Comparar duas técnicas de infusão de propofol em cadelas submetidas à ovariohisterectomia, estudando a eficácia da dose alvo de propofol, avaliando os atributos cardiorrespiratórios, hemogasométricos e escala do índice bispectral, (BIS) bem como as características do período de recuperação. MÉTODOS: Foram anestesiadas 20 cadelas, distribuídos em dois grupos (GI e GII). em GI, os animais foram pré-tratados com levomepromazina e anestesiados com propofol por infusão alvo controlada, através de bomba de infusão Harvard pump, associado com remifentanila, através de bomba de seringa. em GII, os animais receberam o mesmo tratamento de GI, só que ao invés de receberem o propofol por infusão alvo controlada, receberam o propofol em infusão contínua de velocidade fixa. RESULTADOS: Bradicardia e discreta hipotensão, estabilidade hemogasométrica e respiratória, além de um bom miorrelaxamento, mais evidente na infusão contínua e boa hipnose. CONCLUSÕES: As doses de propofol utilizadas em ambas as técnicas, após o pré-tratamento de levomepromazina e associadas ao opióide, foram eficazes para a realização cirúrgica. A técnica de anestesia alvo controlada obteve um menor consumo de anestésico (propofol) com períodos mais rápidos de recuperação.

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Objectives: To investigate the occurrence and severity of lymphoedema of the lower extremities (LLE), quality of life (QoL), and urinary and sexual dysfunction in women with vulvar cancer submitted to surgical treatment.Study design: Twenty-eight patients with vulvar cancer submitted to vulvectomy and inguinofemoral lymphadenectomy and 28 healthy, age-matched women (control group) were evaluated. The occurrence and severity of LLE were determined by Miller's Clinical Evaluation. QoL, urinary function and sexual function were assessed by the EORTC QLQ-C30, SF-ICIQ and FSFI questionnaires, respectively. The differences between groups and correlations were assessed using Student's r-test, Chi-squared test, Mann-Whitney U-test and Spearman's rho test.Results: The groups were similar in terms of marital status, educational status, menopausal status, hormone therapy and height. The occurrence and severity of LLE were higher in women with vulvar cancer compared with the control group (p < 0.001 and p = 0.003, respectively). A significant association was found between the severity of LLE and advanced age (p = 0.04), and the severity of LLE and higher body mass index (BMI; p = 0.04) in patients with vulvar cancer. In the patients with vulvar cancer, there was a significant correlation between the severity of LLE and worse QoL in the following domains: physical, cognitive, emotional, social, fatigue, pain, sleep and financial questions (p < 0.05). There was no difference in urinary function between the two groups (p = 0.113). Age and number of deliveries were the only variables associated with the occurrence of urinary incontinence (p = 0.01). Urinary incontinence was present in women with a mean age of 74.9 +/- 4.6 years and a mean of 7.3 +/- 1.3 normal deliveries. There was no difference between the groups in terms of the sexual function. Multivariate analysis showed an association between sexual function and age (p = 0.01), and sexual function and being in a stable relationship (p = 0.02).Conclusion: Patients submitted to vulvectomy or inguinofemoral lymphadenectomy for vulvar cancer are at higher risk of developing LLE compared with healthy, age-matched women. This has a negative effect on QoL, but does not interfere with urinary or sexual function. (C) 2012 Elsevier B.V. All rights reserved.

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

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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