Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

MDGC-MS analysis of essential oils from Protium heptaphyllum (Aubl. ) and their antifungal activity against Candida specie / Análise MDGC-MS de óleos essenciais de Protium heptaphyllum (Aubl. ) e sua atividade antifúngica contra espécies de Candida

ABSTRACT Protium heptaphyllum is found in the Amazon region, and in various Brazilian states and South American countries. Also Known as almecega, it produces an oil resin used in traditional medicine as analgesic, anti-inflammatory, cicatrizant and expectorant, it is rich in pentacyclic triterpenes and essential oil. The main objective of this study was to analyze the chemical composition of P. heptaphyllumresin (OEPh) over different extraction times and to evaluate their antifungal activity against Candida species, obtained from gardeners with onychomycosis, using the disk diffusion method. The OEPh was obtained by hydrodistillation and analyzed by Multidimensional Gas Chromatography coupled with Mass Spectrometry (MDGC / MS). Candida species were obtained from lesions on the nails of horticulturist from a community garden in the city of Teresina, Piauí, Brazil. The antifungal activity in concentrations of 1000 µg/L, 500 µg/L and 250 µg/L, PROTOCOL M44-A2 (CLSI 2009) OEPh was tested. The main constituents identified were: l-limonene, α-terpineol, p-cineol, o-cymene and α-phellandrene, however, its composition varies significantly with extraction time. All species, except C. rugosa, were inhibited with halo (≥ 14 mm) at 1000 μg / L. C. krusei is naturally resistant to the drug fluconazole, but when tested with OEPh the clinical species (case 9) demonstrated sensitivity in three dilutions (halo ≤ 10 ≥ 14) and the standard strain was inhibited at concentration of 1000 μg/Lg / L (halo 14mm). A similar situation also occurred with the standard strain of C. parapsilosis (halo ≥ 11mm). OEPh has considerable antifungal activity, which merits further investigation for alternative clinical applications, since this species is widely distributed in our community, and it presents good yields, and also has important therapeutic applications.

RESUMO Protium heptaphyllum é encontrada na região amazônica, em vários estados do Brasil e países da América do Sul. Conhecida como almecega produz uma resina oleosa usada na medicina popular como analgésica, antiinflamatória, cicatrizante e expectorante, é rica em triterpenos pentaciclicos e óleo essencial. O objetivo principal do presente trabalho foi analisar a composição química do óleo essencial da resina P. heptaphyllum (OEPh) em diferentes tempo de extração e avaliarsuaatividade antifúngica contra espécies de Candida, isoladas de horticultores com onicomicoses, por método de disco-difusão. O OEPh foi obtido por hidrodestilação, analisado por Cromatografia Gasosa Multidimensinal Acoplada a Espectrometria de Massas (MDGC/MS). As espécies de Candida foram obtidas de lesões nas unhas de horticultores de uma horta comunitária na cidade de Teresina, Piauí, Brasil. Testou-se a atividade antifúngica do OEPhnas concentrações de 1000 μg/L, 500 μg/L e 250 μg/L, protocolo M44-A2 (CLSI 2009). Os principais constituintes identificados foram l- limoneno, α-terpineol, p-cineol, o-cimeno e α-felandreno, entretanto, sua composição varia significativamente em decorrência do tempo de extração. Todas as espécies, exceto a C. rugosa, foram inibidas com halo ( Χ ≥ 14 mm) na concentração de 1000 μg/L. C. krusei é naturalmente resistente ao fármaco fluconazol, mas quando testado com OEPh,a espécie clínico (caso 9) demonstrou sensibilidade nas três diluições (halo Χ ≤ 10 ≥ 14) e a cepa padrão foi inibida na concentração de 1000 μg/L (halo Χ 14mm). Fato semelhante também ocorreu com a cepa padrão de C. parapsilosis (halo Χ ≥ 11mm). O OEPh possui atividade antifúngica considerável, merecendo uma investigação mais aprofundada para aplicações clínicas alternativas, uma vez que esta espécie é amplamente distribuída em nossa comunidade, apresenta bom rendimento e, ainda, aplicações terapêuticas importantes.

First isolation of cryptococcus neoformans genotype VNI MAT-alpha from wood hollow trunks of hymenaea courbaril

Cryptococcal infection is transmitted by the inhalation of Cryptococcus spp. propagules. Information about the Cryptococcus species inhabiting plants might be clinically relevant due to the epidemiological role of these habitats as possible sources of human infection. The aim of this study was to increase the knowledge about the environmental occurrence of cryptococcosis agents. Hollow tree vegetal debris of nine plant species was sampled quarterly over a 12-month period. Melanized colonies were screened for Cryptococcus neoformans and C. gattii by biochemical tests, followed by URA5-RFLP molecular analysis, M13 fingerprinting assays, and mating-typing with the specific a and α primers. The susceptibility to fluconazole of all of the confirmed species colonies was determined using the AFST-EUCAST broth dilution method. We found that the typical Brazilian flora tree Hymenaea courbaril yielded a high cryptococcal burden (median, 10(2) CFU/g) during the summer, autumn and winter seasons. C. neoformans VNI molecular type MAT alpha was identified in all of the samples. The fingerprinting analyses showed great molecular variability with no correlation with the susceptibility profile to fluconazole (MIC range 4 to ≥64 mg/l). To our knowledge, this study is the first describing the association between C. neoformans and Hymenaea courbaril. These observations extend the known geographic distribution of and substantiate a new urban environmental niche for C. neoformans and also emphasize the genetic diversity of the environmental C. neoformans VNI molecular type isolates.

Efeito de fungos micorrízicos arbusculares na bioprodução de fenóis totais e no crescimento de Passiflora alata Curtis / Total phenols in Passiflora alata Curtis inoculated with mycorrhizal fungi

Os compostos fenólicos encontrados no extrato das folhas de maracujazeiro doce (Passiflora alata Curtis) são os principais responsáveis pelos efeitos terapêuticos, incluindo a atividade ansiolítica. O presente trabalho avaliou o efeito de diferentes espécies de fungo micorrízicos arbusculares (FMAs) e doses de fósforo sobre a bioprodução de fenóis totais, bem como, o crescimento vegetal e os conteúdos de nitrogênio, fósforo e potássio na massa da matéria seca da parte aérea do maracujazeiro doce. O experimento, fatorial 4x2, foi conduzido em um telado com quatro tratamentos microbiológicos: Glomus etunicatum, Glomus intraradices, inóculo misto (Glomus clarum e Gigaspora margarita) e o controle sem fungo, e duas doses de fósforo: 0 e 50 mg kg-1 de solo. O delineamento experimental foi de blocos casualizados com quatro repetições. As plantas foram colhidas 90 dias após a semeadura. Na ausência da adubação fosfatada, o conteúdo de fenóis totais, a massa da matéria seca da parte aérea e o número de folhas foram maiores nos tratamentos inoculados com FMAs, quando comparados ao tratamento sem fungo. Plantas com inóculo misto apresentaram maior altura com ou sem adubação fosfatada. Os tratamentos inoculados com FMAs, tanto na dose 0 quanto na dose 50 mg kg-1 de P incrementaram os conteúdos de N, P e K na parte aérea do maracujazeiro doce, evidenciando a capacidade dos FMAs em promover o melhor estado nutricional das plantas.

The phenolic compounds found in extracts from leaves of sweet passion fruit (Passiflora alata) are mainly responsible for its therapeutic effects, such as the anxiolytic activity. This study evaluated the effects of different species of mycorrhizal fungi (AMF) and phosphorus levels on the bioproduction of total phenols, as well as plant growth and the contents of nitrogen, phosphorus and potassium in the dry mass of shoots of sweet passion fruit. The experiment was conducted in a greenhouse. The factors were arranged in a :[(microbiological treatments: Glomus etunicatum, Glomus intraradices, mixed inoculum (Glomus clarum and Gigaspora margarita) and without fungus] x 2 (doses of phosphorus: 0 and 50 mg kg-1 soil) factorial arrangement, in a randomized block experimental design with four replications. The plants were harvested 90 days after seeding. In the absence of phosphate fertilization, the total phenol content, dry mass of shoot and leaf number were greater in treatments inoculated with AMF compared to the treatments without fungus. Mixed inoculum plants had higher plant height with or without phosphate fertilization. Treatments inoculated with AMF in both the 0 and 50 mg kg-1 doses of P increased the content of N, P and K in the shoots of sweet passion fruit, demonstrating the ability of AMF to promote better nutritional statusfin plants.

Ectoparasitic flies (Diptera, Streblidae) of bats (Chiroptera, Phyllostomidae) in an Atlantic Forest area, southeastern Brazil / Moscas ectoparasitas (Diptera, Streblidae) de morcegos (Chiroptera, Phyllostomidae) numa área de Mata Atlântica, sudeste do Brasil

We studied infestation rates and parasite-host associations between streblid flies and phyllostomid bats in an Atlantic Forest area of Rio de Janeiro state, southeastern Brazil. We captured 301 individuals from seven Phyllostomidae bat species. Out of that total, 69 bats had been parasitised by nine Streblidae species; the most frequent species were Trichobius joblingi and Trichobius tiptoni. The species Paraeuctenodes longipes, associated with Anoura geoffroyi, was the most frequent species. The highest mean intensity was observed for Paraeuctenodes longipes, associated with A. geoffroyi, and Paratrichobius longicrus associated with Artibeus lituratus, both ectoparasite species with a mean intensity of five individuals per bat. Trichobius joblingi exhibited the highest mean abundance, which was over three on its host species. Streblid richness in the study area was similar to the richness found in other studies carried out in the Atlantic Forest. We observed that streblid richness in this biome depends more on inherent characteristics of each physiognomy and on the host-species than on the sampling effort.

Estudou-se as taxas de infestação e as associações parasita-hospedeiros de dípteros estreblídeos ectoparasitas de morcegos filostomídeos, em um fragmento de Mata Atlântica, no estado do Rio de Janeiro. Foram capturados 301 indivíduos de sete espécies de morcegos da família Phyllostomidae. Desse total, 69 morcegos encontravam-se parasitados com nove espécies de Streblidae, sendo Trichobius joblingi e Trichobius tiptoni as espécies mais freqüentes do total de estreblídeos coletados. Paraeuctenodes longipes, associada à Anoura geoffroyi foi a espécie mais prevalente. A maior intensidade média foi encontrada para Paraeuctenodes longipes, associada à A. geoffroyi e Paratrichobius longicrus associada à Artibeus lituratus, ambos com cinco ectoparasitas em média por morcego infestado. Trichobius joblingi apresentou a maior abundância média de infestação, que foi superior a três nas espécies de hospedeiros em que foi encontrada. A riqueza de estreblídeos da área de estudo é similar àquela obtida em outros estudos realizados na Mata Atlântica, e verificou-se que a riqueza de estreblídeos nesse bioma depende mais de outras características inerentes a cada fitofisionomia e à espécie hospedeira do que do esforço amostral de coleta.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (9.2 ± 0.9; 13.8 ± 1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (2.8 ± 1.1; 4.4 ± 1.1) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.

Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5 percent Tween 80 in 0.9 percent NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82 percent, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42 percent reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.

Fatores associados com os tipos de heparina usados no tratamento da angina instável em um hospital brasileiro / Factors Associated with the Types of Heparin used in the Treatment of Unstable Angina at a Brazilian Hospital

Unfractionated heparin (UFH) and low-molecularweight heparins (LMWHs) are widely used in curative and preventive treatments of thromboembolic disorders. The aim of the study was to investigate factors associated with the choice of these types of heparin to treat patients with unstable angina under real conditions of hospital use. A cross-sectional study was performed in a private general hospital in Belo Horizonte, Brazil, from January 1st to December 31th, 2001. Data were collected from the hospital electronic database. Inpatients with angina who received enoxaparin or UFH were included in the survey. Data for 555 patients were recorded, including 401 treated with enoxaparin and 154 with UFH. Univariate analysis showed that male and elderly people predominated in both groups, with no statistical difference in the proportions (p>0.05). Multivariate analysis showed 4 factors associated with the use of enoxaparin: cardiac revascularization surgery (OR=0.434), arrhythmias (OR=9.343), risk factors for coronary artery disease (OR=1.333) and private health insurance (OR=0.297). Thus, clinical and organizational factors were associated with the type of heparin used by patients with unstable angina at this hospital. Further drug utilization studies are necessary to expand and improve the data available on the use of heparins in the hospital setting.

A heparina não-fracionada (HNF) e heparinas de baixo peso molecular (HBPM) são amplamente utilizadas em tratamentos curativos e preventivos de tromboembolismo. O objetivo do estudo foi investigar os fatores associados com a escolha desses tipos de heparinas para tratar pacientes com angina instável sob as condições reais de uso hospitalar. Trata-se de um estudo transversal realizado em hospital geral privado, na cidade de Belo Horizonte,MG Brasil, no período de Janeiro a Dezembro de 2001. Para a coleta de dados, utilizou-se o banco de dados informatizado do referido hospital. Pacientes internados com angina que receberam enoxaparina ou HNF foram incluídos no estudo. Registrou-se dados de 555 pacientes, incluindo 401 tratados com enoxaparina e 154 com HNF. Na análise univariada, observouse que o gênero masculino e pacientes idosos foram predominantes em ambos os grupos, sem diferença estatística entre as proporções (p>0,05). A análise multivariada revelou quatro fatores associados ao uso de enoxaparina: cirurgia de revascularização cardíaca (OR=0,434), arritmias (OR=9,343), fatores de risco para doença coronariana (OR=1,333) e atendimento por plano de saúde (OR=0,297). Assim, fatores clínicos e organizacionais estão associados com o tipo de heparina usado por pacientes com angina instável, neste hospital. A realização de mais estudos de utilização de medicamentos é necessária para aprimorar o conhecimento sobre o uso de heparinas, em hospitais.

Rehabilitation of exacerbated case of oral mucositis associated with renal failure following bone marrow transplantation.

Inflammation of oral mucosa induced by anti neoplastic drugs is an important, dose limiting and costly side effect of cancer therapy. Here is presented an exacerbated case of oral mucositis associated with renal failure in a patient who underwent bone marrow transplantation. The clinical aspects and an integrated rehabilitation program are discussed below.

Effects of exercise training on atrophy gene expression in skeletal muscle of mice with chronic allergic lung inflammation

We evaluated the effects of chronic allergic airway inflammation and of treadmill training (12 weeks) of low and moderate intensity on muscle fiber cross-sectional area and mRNA levels of atrogin-1 and MuRF1 in the mouse tibialis anterior muscle. Six 4-month-old male BALB/c mice (28.5 ± 0.8 g) per group were examined: 1) control, non-sensitized and non-trained (C); 2) ovalbumin sensitized (OA, 20 µg per mouse); 3) non-sensitized and trained at 50 percent maximum speed _ low intensity (PT50 percent); 4) non-sensitized and trained at 75 percent maximum speed _ moderate intensity (PT75 percent); 5) OA-sensitized and trained at 50 percent (OA+PT50 percent), 6) OA-sensitized and trained at 75 percent (OA+PT75 percent). There was no difference in muscle fiber cross-sectional area among groups and no difference in atrogin-1 and MuRF1 expression between C and OA groups. All exercised groups showed significantly decreased expression of atrogin-1 compared to C (1.01 ± 0.2-fold): PT50 percent = 0.71 ± 0.12-fold; OA+PT50 percent = 0.74 ± 0.03-fold; PT75 percent = 0.71 ± 0.09-fold; OA+PT75 percent = 0.74 ± 0.09-fold. Similarly significant results were obtained regarding MuRF1 gene expression compared to C (1.01 ± 0.23-fold): PT50 percent = 0.53 ± 0.20-fold; OA+PT50 percent = 0.55 ± 0.11-fold; PT75 percent = 0.35 ± 0.15-fold; OA+PT75 percent = 0.37 ± 0.08-fold. A short period of OA did not induce skeletal muscle atrophy in the mouse tibialis anterior muscle and aerobic training at low and moderate intensity negatively regulates the atrophy pathway in skeletal muscle of healthy mice or mice with allergic lung inflammation.

13CO2 recovery fraction in expired air of septic patients under mechanical ventilation

The continuous intravenous administration of isotopic bicarbonate (NaH13CO2) has been used for the determination of the retention of the 13CO2 fraction or the 13CO2 recovered in expired air. This determination is important for the calculation of substrate oxidation. The aim of the present study was to evaluate, in critically ill patients with sepsis under mechanical ventilation, the 13CO2 recovery fraction in expired air after continuous intravenous infusion of NaH13CO2 (3.8 µmol/kg diluted in 0.9 percent saline in ddH2O). A prospective study was conducted on 10 patients with septic shock between the second and fifth day of sepsis evolution (APACHE II, 25.9 ± 7.4). Initially, baseline CO2 was collected and indirect calorimetry was also performed. A primer of 5 mL NaH13CO2 was administered followed by continuous infusion of 5 mL/h for 6 h. Six CO2 production (VCO2) measurements (30 min each) were made with a portable metabolic cart connected to a respirator and hourly samples of expired air were obtained using a 750-mL gas collecting bag attached to the outlet of the respirator. 13CO2 enrichment in expired air was determined with a mass spectrometer. The patients presented a mean value of VCO2 of 182 ± 52 mL/min during the steady-state phase. The mean recovery fraction was 0.68 ± 0.06 percent, which is less than that reported in the literature (0.82 ± 0.03 percent). This suggests that the 13CO2 recovery fraction in septic patients following enteral feeding is incomplete, indicating retention of 13CO2 in the organism. The severity of septic shock in terms of the prognostic index APACHE II and the sepsis score was not associated with the 13CO2 recovery fraction in expired air.

Efeito de um programa de condicionamento físico aeróbio nos aspectos psicossociais, na qualidade de vida, nos sintomas e no óxido nítrico exalado de portadores de asma persistente moderada ou grave / Effects of an aerobic physical training program on psychosocial characteristics, quality-of-life, symptoms and exhaled nitric oxide in individuals with moderate or severe persistent asthma

OBJETIVO: Avaliar o papel de um programa de condicionamento físico aeróbio nos aspectos psicossociais, qualidade de vida, sintomas e óxido nítrico exalado (NOe) de adultos com asma persistente moderada ou grave. MATERIAIS E MÉTODOS: Vinte pacientes foram divididos aleatoriamente em Grupo Controle (GC, n= 10; programa de educação e exercícios respiratórios) e Grupo Treinado (GT, n= 10; programa de educação e exercícios respiratórios mais condicionamento aeróbio, 70 por cento potência máxima obtida). A intervenção aconteceu duas vezes por semana durante três meses. Antes e após, foram avaliados a capacidade aeróbia máxima, a função pulmonar, a dispnéia ao esforço, os níveis de ansiedade e depressão e a qualidade de vida. Mensalmente, eram avaliados o NOe em repouso e o número de dias livres de sintomas. RESULTADOS: Apenas o GT apresentou redução dos sintomas (GT 24,8 [IC95 por cento= 23-27] versus GC 15,7 [IC95 por cento= 9-21] dias livres de sintomas, p< 0,05), dos níveis de NOe (GT 25,8 [IC95 por cento= 15,3-44] versus GC 44,3 [IC95 por cento= 24-60] ppb, p< 0,05), da ansiedade (GT 39,3 [IC95 por cento= 37-50] versus GC 40,9 [IC95 por cento= 37-50] escore, p< 0,001) e da depressão (GT 6,6 [IC95 por cento= 1-21] versus GC 9 [IC95 por cento= 1-20] escore, p< 0,001), melhora da qualidade de vida (GT 42,8 [IC95 por cento= 34,3-71,7] versus GC 69,7 [IC95 por cento= 45,1-87,9] por cento, p< 0,001), e incremento da aptidão aeróbia (GT 25,7 [IC95 por cento= 16,2-31,3] versus GC 20,5 [IC95 por cento= 17,3-24,1] mL/kg/min, p< 0,001). CONCLUSÕES: Os resultados sugerem que o treinamento físico reduz o NOe, os sintomas e melhora a qualidade de vida e os aspectos psicossociais de adultos com asma persistente moderada ou grave.

OBJECTIVE: To evaluate the role of an aerobic physical training program on psychosocial characteristics, quality of life, symptoms and exhaled nitric oxide of adults with moderate or severe persistent asthma. METHODS: Twenty patients were randomly assigned to a Control Group (CG, n= 10, education program and respiratory exercises) and a Trained Group (TG, n= 10, education program and respiratory exercises plus aerobic training at 70 percent of the maximum power obtained). The intervention took place twice a week for three months. Maximum aerobic capacity, pulmonary function, effort dyspnea, anxiety levels, depression levels and quality of life were assessed before and after the treatment. Exhaled nitric oxide at rest and the number of days without asthma symptoms were evaluated every month. RESULTS: The TG presented increased numbers of symptom-free days (TG 24.8 days [95 percentCI= 23-27] versus CG 15.7 days [95 percentCI= 9-21]; p< 0.05), decreased exhaled nitric oxide levels (TG 25.8 ppb [95 percentCI= 15.3-44.0] versus CG 44.3 ppb [95 percentCI= 24-60]; p< 0.05), decreased anxiety scores (TG 39.3 [95 percentCI= 37-50] versus CG 40.9 [95 percentCI= 37-50]; p< 0.001), decreased depression scores (TG 6.6 [95 percentCI= 1-21] versus CG 9 [95 percentCI= 1-20]; p< 0.001), improved quality of life (TG 42.8 percent [95 percentCI= 34.3-71.7] versus CG 69.6 percent [95 percentCI= 45.1-87.9]; p< 0.001) and improved aerobic aptitude (TG 25.7 mL/kg/min [95 percentCI= 6.2-31.3] versus CG 20.5 mL/kg/min [95 percentCI= 17.3-24.1]; p< 0.001). CONCLUSIONS: Our results suggest that physical training reduces exhaled nitric oxide and symptoms and improves the quality of life and psychosocial characteristics of adults with moderate or severe persistent asthma.

Oral Candida spp. colonization in human immunodeficiency virus-infected individuals: [review]

Several yeast species of Candida genus can colonize the skin as well as the mucous membrane of the vagina and the digestive tract for short or long periods. Depending on the host's immunological state and the yeast's virulence, colonization can become an infection, invading the colonized tissues and also disseminating. AIDS is characterized by the host's intensive and progressive immunodepression which manifests as diverse symptoms, mainly lesions in the mouth. Oral candidiasis is the most prevalent opportunistic infection in individuals infected with human immunodeficiency virus (HIV) and is an important indicator of the disease progress and the immunosuppression increase. The factors involved in the equilibrium between Candida spp. and HIV-infected subjects are sometimes contradictory and were evaluated in the present study specially for colonization.

Avaliação das atividades de vida diária de idosos com diferentes níveis de demência / Evaluation of the activities of daily living of elderly people with different levels of dementia

OBJETIVOS: Comparar o desempenho de idosos com diferentes níveis de gravidade de demência em questionários de atividades básicas de vida diária (ABVDs) e atividades instrumentais de vida diária (AIVDs). Verificar se existe correlação entre os questionários de AIVDs aplicados. METODOLOGIA: Foram aleatorizados 90 idosos (75,46 ± 7,66 anos) atendidos no Centro de Referência do Idoso-MG, com diagnóstico clínico de demência (DSM-IV/APA) e classificados quanto ao nível de gravidade da demência (Clinical Dementia Rating). As ABVDs foram avaliadas pelo índice de Katz, e as AIVDs, pelo índice de Lawton-Brody e de Pfeffer. Os testes de Kruskal-Wallis e de Mann-Whitney foram utilizados para verificar o desempenho dos idosos nas ABVDs, e a correlação de Spearman, para investigar a relação entre os instrumentos de AIVDs (alfa< 0,05). RESULTADOS: Foram encontradas diferenças estatisticamente significativas entre o desempenho dos idosos com diferentes níveis de gravidade de demência avaliados pelos instrumentos de ABVDs e AIVDs (p< 0,001). Os questionários de AIVDs apresentaram correlação significativa na amostra total (p< 0,0001; r= -0,818), nos grupos com demência leve (p= 0,007; r= -0,530) e grave (p< 0,0001; r= -0,723). CONCLUSÃO: A gravidade do processo demencial interferiu no desempenho dos idosos nas atividades básicas e instrumentais de vida diária. As AIVDs foram mais comprometidas nos estágios iniciais das demências, e as ABVDs, nos estágios mais avançados. Os questionários de AIVDs utilizados, apesar de sua particularidade estrutural, parecem medir um construto comum. A variabilidade do quadro clínico nos indivíduos com demência moderada pode explicar a ausência de correlação dos questionários usados nesse grupo específico.

OBJECTIVE: To compare the performance of elderly people with different levels of severity of dementia using questionnaires on basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). Also, to verify whether there were any association between the IADL questionnaires applied. METHOD: Ninety elderly people, aged 75.46 ± 7.66 years with a clinical diagnosis of dementia (DSM-IV/APA) who were seen at the Minas Gerais Reference Center for the Elderly, were randomized selected and classified according to the level of severity of their dementia (Clinical Dementia Rating). Their BADLs were assessed using the Katz Index and their IADLs by the Lawton-Brody and Pfeffer indexes. The Kruskal-Wallis and Mann-Whitney tests were used in order to investigate the elderly people's performance regarding BADLs, while the Spearman correlation was used to investigate the relationships among the IADL (alpha< 0.05). RESULTS: Statistically significant differences in performance were found between the elderly people with different levels of severity of dementia, as assessed by the BADL and IADL questionnaires (p< 0.001). The IADL questionnaires presented significant correlation for the total sample (p< 0.0001; r = -0.818) as well as for the groups with mild dementia (p= 0.007; r = -0.530) and severe dementia (p< 0.0001; r = -0.723). CONCLUSION: The severity of the dementia process interfered with the elderly people's performance of the elderly in BADLs and IADLs. The IADLs were more affected in the early stages of dementia whereas the BADLs were more affected in the more advanced stages. Despite structural particularities, the IADL questionnaires utilized seemed to be measuring a common construct. The variability in the clinical condition of the individuals with moderate dementia may be an explanation for the lack of correlation between the questionnaires in this specific group.

A pyrazolyl-thiazole derivative causes antinociception in mice

The present study investigates the antinociceptive effect of the pyrazolyl-thiazole derivative 2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1 H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole (B50) in mice. Male albino Swiss mice (30-40 g) were used in the acetic acid-induced abdominal writhes and tail-immersion tests. B50 caused dose-dependent antinociception (8, 23 and 80 µmol/kg, sc) in the acetic acid writhing assay (number of writhes: vehicle: 27.69 ± 6.15; B50 (8 µmol/kg): 16.92 ± 3.84; B50 (23 µmol/kg): 13.85 ± 3.84; B50 (80 µmol/kg): 9.54 ± 3.08; data are reported as means ± SEM for 9 animals per group). On the other hand, B50 did not cause antinociception in the tail immersion assay. Naloxone (2.75 µmol/kg, sc) prevented B50-induced antinociception (number of writhes: vehicle-saline: 31.11 ± 3.15; vehicle-naloxone: 27.41 ± 3.70; B50 (80 µmol/kg)-saline: 8.70 ± 3.33; B50 (80 µmol/kg)-naloxone: 31.84 ± 4.26; morphine-saline: 2.04 ± 3.52; morphine-naloxone: 21.11 ± 4.26; 8-9 animals per group). The removal of the methyl group of the thiazole ring of B50 or substitution of the bromo substituent with the methyl at position 4 of the phenyl group, which is attached to the thiazole ring of B50, resulted in loss of activity, suggesting that these substituents are important for antinociceptive activity. B50 had no effect on spontaneous locomotion or rotarod performance, indicating that the antinociceptive effect of B50 is not related to nonspecific motor effects. The antinociceptive profile of B50 seems to be closer to nonsteroidal anti-inflammatory drugs than to classic opioid agents, since it had no analgesic effect in a thermally motivated test.

Effect of salbutamol on pulmonary responsiveness in chronic pulmonary allergic inflammation in guinea pigs

Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 ± 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergen-specific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG1-specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of ß2-agonists results in a loss of some of their protective effects against the allergen.

Thymus involution in alloxan diabetes: analysis of mast cells

We previously reported that alloxan-induced diabetes results in reduction in the number and reactivity of mast cells at different body sites. In this study, the influence of diabetes on thymic mast cells was investigated. Thymuses from diabetic rats showed marked alterations including shrinkage, thymocyte depletion, and increase in the extracellular matrix network, as compared to those profiles seen in normal animals. Nevertheless, we noted that the number and reactivity of mast cells remained unchanged. These findings indicate that although diabetes leads to critical alterations in the thymus, the local mast cell population is refractory to its effect. This suggests that thymic mast cells are under a different regulation as compared to those located in other tissues.

A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics

It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP) test) to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51°C and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 æg/paw) and mice (125-500 æg/paw) with carrageenan led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, ip) inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 æg/paw) also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals.

Inflamação do parênquima pulmonar na asma e sua relação com as vias aéreas / Pulmonary parenchyma inflammation in asthma

A inflamação da asma não está limitada às vias aéreas e pode comprometer também o parênquima pulmonar periférico, no entanto, não há estudos na literatura que enfoquem a participação do parênquima pulmonar na asma. Objetivo: Caracterizar o infiltrado inflamatótrio do parênquima peribronquiolar e distal em vítimas de asma fatal, comparando-o ao de outras regiões de vias aéreas e a de tecido pulmonar de não asmáticos. Fragementos de tecido pulmonar obtidos de 20 pacientes com asma fatal e 10 controles, necropsiados no Serviço de verificacão de óbito da capital - São Paulo, foram submetidos a estudo de imuno-histoquímica e marcados com anticorpos anti-proteína básica principal (eosinófilos), anti-triptase (mastócitos), anti-elastase neutrofílica (neutrófilos) e anti-marcadores de superfície de linfócitos (CD3, CD$, CD* e CD20). Foram determinadas as densidades celulares no parênquima pulmonar periférico peribronquiolar e distal e nas áreas interna e externa das vias aéreas de grande e de pequeno calibre. Resultados: A densidade de eosinófilos foi significativamente maior nas duas regiões do parênquima pulmonar de asmáticos comparados aos controles, bem como as vias aéreas (p<0,02). Nos pacientes asmáticos a densidade eosinófilica se mostrou menos no parênquima distal em relação à da área interna da via aérea grande apenas (p<0,01). A densidade dos mastócitos foi maior no parênquima peribronquiolar bem como na área externa das vias aéreas de grande e de pequeno calibre de asmáticos comparados aos controles (p<0.04). Diferenças significativas quanto à densidade de linfócitos se restringiram às vias aéreas de asmáticos comparadas as de controles. Maior densidade de neutrófilos foi observada apenas no parênquima pulmonar de asmáticos (p=0.029). Conclusões: O parênquima pulmonar participa do processo inflamatório na asma fatal com aumento de células efetoras (mastócitos, neutrófilos e eosinófilos). A área externa da via aérea foi a região que melhor diferenciou o asmáticodo controle e com o maior número de diferenças significativas. A inflamação do parênquima peribronquiolar, associado ao da área externa da via áerea pequena, reforça o papel do pulmão distal na patofisiologia da asma.