Evaluation of nanoparticles loaded with benzopsoralen in rat peritoneal exudate cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

EVALUATION OF PERITONEAL-FLUID IN HORSES WITH EXPERIMENTAL ENDOTOXEMIA

Clinical parameters and biochemical and cellular changes in the plasma and peritoneal fluid were evaluated in horses after i.v. injection of a sub-lethal dose (50 ng/kg) of E. coli endotoxin. A significant decrease in the number of neutrophils and lymphocytes occurred in the blood 1h 15 min and 3 hours after injection of endotoxin; body temperature was increased significantly at the 3rd hour. No changes were detected in the total number of white blood cells in the peritoneal fluid. No significant differences in biochemical values were detected in either plasma or peritoneal fluid. Endotoxemia caused an alteration in blood cellularity, without effecting the peritoneal cellular population.

Purine nucleoside phosphorylase: A potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell and Apicomplexan parasites-mediated diseases.

Predictors of incorrectness in antimicrobial prescription in the Bauru State Hospital (Bauru city, São Paulo State, Brazil)

The inappropriate use of antimicrobials in hospitals presents a negative impact on patient outcome and is associated with the emergence and spread of multidrug-resistant microorganisms. Antimicrobial stewardship programs (ASPs) have been instituted in order to improve the quality of prescriptions in hospitals. In this setting, the identification of patterns of inappropriate antimicrobial prescription is a valuable tool that allows ASPs to identify priorities for directing educative/restrictive policies. With this purpose, a study was conducted in the Bauru State Hospital, a teaching hospital with 285 beds affiliated to the Botucatu Medical School, São Paulo State University. The hospital maintains an active ASP since it was opened, in 2002. We selected 25% of the requests for parenteral antimicrobials (RPAs) from 2005 for analysis. Prescriptions for prophylactic purposes were excluded. All other RPAs were classified according to a modified Kunin and Jones categories. Univariate and multivariable analyses were performed to identify predictors of general inappropriateness and of specific prescription errors. Prescriptions classified as "appropriate'' or "probably appropriate" were selected as controls in all stages of the study. Among 963 RPAs included in our study, 34.6% were inappropriate. General predictors of inappropriateness were: prescription on weekends/holidays (OR = 1.67, 95% CI = 1.20-2.28, p = 0.002), patient from intensive care unit (OR = 1.57, 95% CI = 1.11-2.23, p = 0.01), peritoneal (OR = 2.15, 95% CI = 1.27-3.65, p = 0.004) or urinary tract infection (OR = 1.89, 95% CI = 1.25-2.87, p = 0.002), combined therapy with two or more antimicrobials (OR = 1.72, 95% CI = 1.15-2.57, p = 0.008) and prescriptions including penicillin (OR = 2.12, 95% CI = 1.39-3.25, p = 0.001) or first-generation cephalosporins (OR = 1.74, 95% CI = 1.01-3.00, p = 0.048). Previous consultation with an infectious diseases (ID) specialist had a protective effect against inappropriate prescription (OR = 0.34, 95% CI = 0.24-0.50, p < 0.001). Factors independently associated with specific prescription errors varied. However, consultation with an ID specialist was protective against both unnecessary antimicrobial use (OR = 0.04, 95% CI = 0.01-0.26, p = 0.001) and requests for agents with insufficient spectrum (OR = 0.14, 95% CI = 0.03-0.30, p = 0.01). In conclusion, the analysis of factors predictive of inappropriateness in antimicrobial prescription allowed us to identify issues requiring intervention. Also, it provided a positive feedback of the ASP efficacy, demonstrating the importance of previous consultation with an ID specialist to assure the quality of antimicrobial prescriptions.