The state of the youth: prisons, drugs and car crashes

By virtue of the volume and nature of their attributions, including secondary school as well as problem-areas such as security and traffic, the Brazilian states are the ultimate responsible entities for young people. This study argues in favour of granting greater freedom for the states to define their own public policy parameters to deal with local features and to increase the degree of learning about such actions at the national level. In empirical terms, the study assesses the impacts of new laws, such as the new traffic code (from the joint work with Leandro Kume, EPGE/FGV doctor’s degree student) and traces the statistics for specific questions like drugs, violence and car accidents. The findings show that these questions produce different results for young men and women.The main characters in these dramas are young single males, suggesting the need for more distinguished public policies according not only to age, but also by gender. The study also reveals that the magnitude of these problems changes according to the youth’s social class. Prisons concern poorer men (except for the functional illiterate) while fatal car accidents and the confessed use of drugs concern upper-class boys.

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Isolation of Pseudomonas aeruginosa strains from dental office environments and units in Barretos, state of São Paulo, Brazil, and analysis of their susceptibility to antimicrobial drugs

Uma ampla variedade de patógenos oportunistas tem sido detectadas nos tubos de alimentação de água dos equipos odontológicos, particularmente no biofilme formado na superfície do tubo. Entre os patógenos oportunistas encontrados nos tubos de água, Pseudomonas aeruginosa é reconhecida como uma das principais causadoras de infecções nosocomiais. Foram coletadas 160 amostras de água e 200 amostras de fomites em quarenta clinicas odontológicas na cidade de Barretos, São Paulo, Brasil, durante o período de Janeiro a Julho de 2005. Setenta e seis cepas de P. aeruginosa, isoladas a partir dos fomites (5 cepas) e das amostras de água (71 cepas), foram analisadas quanto à susceptibilidade à seis drogas antimicrobianas freqüentemente utilizadas para o tratamento de infecções provocadas por P. aeruginosa. As principais suscetibilidades observadas foram para a ciprofloxacina, seguida pelo meropenem. A necessidade de um mecanismo efetivo para reduzir a contaminação bacteriana dentro dos tubos de alimentação de água dos equipos odontológicos foi enfatizada, e o risco da exposição ocupacional e infecção cruzada na prática odontológica, em especial quando causada por patógenos oportunistas como a P. aeruginosa foi realçado.

Lipodystrophy in HIV/AIDS patients with different levels of physical activity while on antiretroviral therapy

INTRODUÇÃO: A lipodistrofia relacionada ao uso de terapia antirretroviral (TARV) pode causar estigma estético e elevar o risco de doenças cardiovasculares. A atividade física pode ser uma alternativa válida para o tratamento e prevenção da lipodistrofia. Entretanto, poucos estudos tratam dessa temática. O objetivo deste estudo foi verificar a ocorrência de lipodistrofia relacionada ao uso de TARV em portadores de HIV/AIDS, com diferentes hábitos de atividades físicas. MÉTODOS: A casuística foi formada por 42 portadores de HIV em uso de TARV, do Centro de Testagem e Aconselhamento de Presidente Prudente. Para obtenção do nível de atividade física aplicou-se o Questionário Internacional de Atividade Física (IPAQ); a lipodistrofia foi diagnosticada pelo autorrelato do paciente e a confirmação médica. O percentual de gordura de tronco foi estimado pela absortometria por raio-X de dupla energia (DEXA). Foram coletados também dados referentes a sexo, idade, tempo de uso de TARV, valores de CD4 e carga viral. RESULTADOS: Verificou-se maior ocorrência de lipodistrofia no grupo sedentário quando comparado ao ativo, além de fator protetor da prática da atividade física em relação à ocorrência da lipodistrofia. O grupo com valores mais elevados de CD4 também apresentou maior proporção de sujeitos com lipodistrofia, além de maior proporção de ativos e de indivíduos com menor faixa etária. Os acometidos pela lipodistrofia apresentaram maiores valores de percentual de gordura de tronco, bem como, os sedentários em relação aos ativos. CONCLUSÕES: O estilo de vida fisicamente ativa resultou em efeito protetor para ocorrência da lipodistrofia relacionada ao uso da TARV.

Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

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

Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

The release of reactive oxygen specie (ROS) by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM), indomethacin (12 µM), naproxen (160 µM), piroxicam (13 µM), and tenoxicam (30 µM) were incubated at 37ºC in PBS (10 mM), pH 7.4, for 30 min with rat neutrophils (1 x 10(6) cells/ml) stimulated by phorbol-12-myristate-13-acetate (100 nM). The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6). For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6). Using the myeloperoxidase (MPO)/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%), indomethacin (97 ± 2, 100 ± 1%), naproxen (56 ± 8, 76 ± 3%), piroxicam (77 ± 5, 99 ± 1%), and tenoxicam (90 ± 2, 100 ± 1%), respectively (N = 3). These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

A broad study of two new promising antimycobacterial drugs: Ag(I) and Au(I) complexes with 2-(2-thienyl)benzothiazole

Synthesis, characterization, DFT simulation and biological assays of two new metal complexes of 2-(2-thienyl)benzothiazole - BTT are reported. The complexes [Ag(BTT)(2)NO3] - AgBTT2 and [Au(BTT)Cl]center dot 1/2H(2)O - AuBTT were obtained by mixing the ligand with silver (I) nitrate or gold(I) chloride in methanolic solution. Characterization of the complexes were based on elemental (C, H, N and S), thermal (TG-DTA) analysis, C-13 and H-1 NMR, FT-IR and UV-Vis spectroscopic measurements, as well as the X-ray structure determination for AgBTT2. Spectroscopic data predicted by DFT calculations were in agreement with the experimental data for both complexes. The ligand BTT was synthesized by the condensation of 2-thiophenecarboxaldehyde and 2-aminothiophenol in a microwave furnace. AgBTT2 has a monomeric structure. Both complexes show a good activity against Mycobacterium tuberculosis. Free BIT shows low antitubercular activity. (C) 2012 Elsevier Ltd. All rights reserved.

Preparation of polymeric micelles for use as carriers of tuberculostatic drugs

Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger antimycobacterial activity than the original drugs.Conclusion: the results demonstrate that polymeric micelles can be used as efficient carriers for drugs, which alone, exhibit undesired pharmacokinetics, poor solubility, and low stability. The synthesized micelle-forming tuberculostatic prodrugs opens a perspective of alternative prodrugs that prolong action and decrease the toxicity of the tuberculostatic drugs of choice.

Influence of phosphated cross-linked high amylose on in vitro release of different drugs

The influence of structural characteristics of high amylose cross-linked at different degrees on the release of drugs with important molecular differences, namely sodium diclophenac (SD) and nicotinamide (NI), was assessed in vitro from non-compacted systems. The release profiles were related with classical kinetic mathematical models for better understanding of the release mechanism. An increase in polymer cross-linking degree resulted in longer release time for both drugs, although SD generally was released slower than NI. SD release from samples cross-linked at 2% of basis was driven mainly by Fickian diffusion, while from samples cross-linked at 4% of basis follows anomalous mechanism. Inversely, anomalous mechanism was responsible for NI release from 2% samples and Fickian diffusion from 4% samples. Results suggest that the performance of cross-linked high amylose as excipient for controlled drug release not only depends on cross-linking degree but also is highly influenced by structural characteristics of the drug. (C) 2009 Elsevier Ltd. All rights reserved.

Comparison of resazurin microtiter assay performance and BACTEC MGIT 960 in the susceptibility testing of Brazilian clinical isolates of Mycobacterium tuberculosis to four first-line drugs

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

Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis with drugs

Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing which involves excision of introns and union of exons in two independent transcripts. For the first time, we present the standardization of Trypanosoma cruzi permeable cells (Y strain) as a model for trans-splicing study of mRNAs in trypanosomes, following by RNase protection reaction, which localizes the SL exon and intron. This trans-splicing reaction in vitro was also used to analyze the influence of NFOH-121, a nitrofurazone-derivative, on this mechanism. The results suggested that the prodrug affects the RNA processing in these parasites, but the trans-splicing reaction still occurred.

Skin reactions to drugs

OBJECTIVE - To assess drug reactions and report the drugs involved and the most frequent types of skin reactions.METHODS - A retrospective and descriptive study. Data of inpatients at the Dermatology Ward with initial diagnosis of adverse drug reactions were evaluated from January 1999 to June 2004. Patients with confirmed diagnosis were included in the study based on clinical and histopathological criteria, after analysis of medical charts.RESULTS - Initial diagnosis of adverse drug reactions was confirmed in 121 patients. Forty-three patients were included in the study; 51.2% were females and 86% were caucasians. A total of 48,8% were on one drug only. Antibiotics were the most commonly used drug (20%) and accounted for 33% of the drug eruptions. The second group comprised anti-inflammatory drugs (16 7%), followed by anticonvulsants (13%), analgesic/antipyretic (13%.) agents. Skin eruption manifested as maculopapular exanthema in 41.9% patients, erythrodermia in 25.6%, and urticaria in 23.3%.CONCLUSION - Maculopapular exanthema was the main type of skin reaction triggered by use of drugs, and these reactions were most frequently caused by antibiotics.

Acquired immunodeficiency syndrome in Brazil

Aim. To describe the acquired immunodeficiency syndrome (AIDS) epidemic in Brazil and analyze the impact of federal government measures addressing the problem since its onset.Method. Retrospective review of AIDS epidemic data from its onset in 1980 up to the last published data in June 2001.Results. AIDS was first reported in Brazil in 1980. By 1988, all 27 Brazilian states had diagnosed cases, and until June 2000 more than half of Brazilian municipalities had recorded at least one case of the disease. The AIDS incidence reached its peak between 1996 and 1997 (14.7 per 100,000 population), and then declined between 1998 and 2000 to 9 per 100,000 population. In the last two decades, the proportion of deaths has been also significantly reduced. These were not random events, but reflected the efficiency of the program implemented by the Brazilian Health Ministry's Coordination on Sexually Transmitted Diseases and AIDS. The program includes an epidemiological surveillance modeling system, which records cases from several regular epidemiological bulletins; national network of diagnosis and monitoring of HIV-infected individuals (ill or not); highly active antiretroviral therapy available free to all patients; mother-infant protection program; educational programs on condom use; the introduction of the female condom; development of AIDS studies in different areas to provide practical solutions; constant preoccupation about drug costs accounting for the patent breaking; and national production of many drugs currently in use.Conclusion. Well-planned and implemented national program against AIDS can significantly reduce the burden of this disease to the population.

Occurrence of pneumocystis pneumonia in HIV-infected patients and the interference of the highly active antiretroviral therapy

From the beginning of the AIDS epidemic, pneumocystis pneumonia ( PCP) has been distinguished as one of the most frequent opportunistic diseases with high morbid-mortality. As from 1996, the advent of the highly active antiretroviral therapy ( HAART) has changed the characteristics of such epidemic by reducing its related diseases and, as a result, AIDS-related mortality. With the purpose to estimate PCP occurrence and HAART interference, 376 HIV-infected or AIDS patients were studied from January 1992 to December 2002. Among them, 58 ( 15.5%) PCP cases were found. There was a higher occurrence of PCP in the group of patients in which HAART was not used, with 40 ( 69.0%) of the episodes. As regards the studied period, a tendency to a linear reduction in annual PCP incidence was observed. The mean of T CD4+ lymphocytes in the patients with PCP ( 117 cells/mm(3)) was significantly lower when compared to that of the other individuals ( 325 cells/mm(3)). Therefore, this study suggests a temporal reduction in PCP occurrence related to HAART use with higher T CD4+ lymphocyte counts. Nevertheless, this opportunistic infection still shows significant incidence in AIDS patients. ( NCT00516581).