Características genotípicas e fenotípicas de Candida Albicans isoladas da cavidade bucal de pacientes transplantados renais com ênfase na ação do extrato bruto de Eugenia uniflora em fatores de virulência

Candida albicans is a diploid yeast that in some circumstances may cause oral or oropharyngeal infections. The investigation of natural products is mandatory for the discovery of new targets for antifungal drugs development. This study aimed to determine the genotypes of 48 clinical isolates of C. albicans obtained from the oral cavity of kidney transplant patients from two distinct geographic regions of Brazil. In addition, we investigated three virulence factors in vitro: phospholipase activity, morphogenesis and the ability to evade from polymorphonuclear neutrophils. The expression of these virulence factors in vitro was also investigated in the presence of the crude extract of Eugenia uniflora. The genotype A was the most prevalent (30 isolates; 62.5%), followed by genotype C (15 isolates; 31.5%) and genotype B (3 isolates; 6.25%). When microsatellite technique with primer M13 was applied, 80% of the isolates from the South were placed within the same cluster. All Genotype C strains were grouped together within two different clusters. Genotype C was considered more resistant to PMNs attack than genotypes A and B. Strains isolated from the South of Brazil showed higher ability to combat PMNs phagocytosis. We found a high rate of genotype C strains isolated from the oral cavity of this group of patients. The crude extract of E. uniflora inhibited proper hypha formation and phagocytosis by PMNs, but had no significant effect on phospholipase activity. This study characterized oral C. albicans strains isolated from kidney transplant recipients and will contribute for the better understanding of the pathogenesis and alternative therapeutics for oral candidiasis

Triagem antifúngica de extratos obtidos de espécies vegetais do nordeste brasileiro

The increase in the incidence of fungal infections due to the drug-resistance or to the number of patients with immune alterations such as AIDS, chemotherapy or organ transplantation, has done the research necesseray for new antifungal drugs. The species from Northeastern Brazil may become an important source of innovative natural molecules. To evaluate the antifungal activity of 10 medicinal plants from Northeastern Brazil, traditionally used as antimicrobial agents, 30 crude extracts (CE) were tested in vitro against four standard species of Candida spp. The CE most promising of these plants were evaluated against yeasts of the oral cavity of kidney transplant patients and through a bioassay-guided fractionation. The extracts form leaves of E. uniflora, the stem bark of L. ferrea and leaves of P. guajava showed significant activity against all yeasts evaluated, with MIC values between 15.62 and 62.5 μg/mL. E. uniflora also showed fungicidal properties against all yeasts, especially against Candida dubliniensis. In patients with immune systems compromised, such as transplanted, oral candidiasis manifests mainly due to immunosuppressive therapy, and resistance to conventional antifungals. The CE of E. uniflora presented range of MIC values between 1.95 to 1000 μg/mL, and lower MIC50 and MIC90 values were observed against C. non-albicans. Due the better results, the CE of E. uniflora was elected to performe the bioassay-guided fractionation. Thus it was possible to obtain enriched fractions, which showed good inhibitory ability against ATCC strains of Candida spp. It was also possible to perform experiments to verify the production of biofilm in two strains of C. dubliniensis and action of extracts and fractions on the same. With this, we observed a behavior between the yeast ATCC and clinical isolate. In addition, CE, fractions and subfractions of E. uniflora inhibit planktonic cells to preventing the growth of biofilm. The preliminary chemical characterization of the fractions obtained revealed the presence of polyphenols (especially flavonoids and tannins). Finally, the results suggests that among the plant species studied, E. uniflora showed a pattern very promising as regards the antifungal, requiring further study of purification and structural elucidation of compounds in order to verify that the antifungal effect found can be attributed to a specific compound or some mechanism depends on synergistic the mixture of polyphenols

Novo sistema de aplicação de drogas em cirurgias oftalmológicas

The topical corneal application of antimitotic mitomycin-C (MMC) during refractive surgery is still characterized by a lack of standardization and considerable empirism. For this reason the creation of a system capable of reliable drug delivery represents a beneficial innovation for patients submitted to these procedures. Objective: Elaborate a new MMC delivery system during the transoperatory period of photorefractive keratectomy (PRK) followed by patent application. Methods: The project consists of an in vitro experimental study to create an MMC (0.02%) release system. The drug was impregnated in sterile Whatman® 41 paper filter discs with a diameter of 8 mm. After drying, the discs were applied to antibiogram plates seeded with Staphylococcus epidermidis (American Type Culture Collection ATCC 12228), followed by the addition of a drop of sterile water. At the end of 1 minute, the discs were removed and the plates incubated for 48 hours at 35oC. Mean drop volume in the collyrium flasks was measured using analytical balance weighing. The inhibition halo (mm) was correlated with the MMC impregnated into the disc. After completion of the invention design a patent application was lodged at the National Institute of Industrial Property. Results: The correspondence between MMC-produced inhibition halos indicated that a dose of 16μg was ideal for impregnating into the discs. The mean drop volume obtained from the collyrium flasks was 37.7 μL. A minute after the application of one drop of balanced saline solution, the system released an adequate concentration for PRK surgery. Conclusion: A new MMC delivery system was created for transoperatory application in photorefractive keratectomy (PRK). Publication of the patent application (number PI 0704739-8) gives the authors exclusive intellectual property rights. The study was sponsored by Ophthalmos Indústria e Comércio de Produtos Farmacêuticos S.A. (São Paulo-SP, Brazil) and received the indispensable scientific contribution of researchers from the fields of Pharmacy, Medicine, Biology, Statistics and Law, characterizing the work as multidisciplinary, in accordance with norms established by the Postgraduate Health Sciences Program of the Federal University of Rio Grande do Norte (UFRN)

Guerra contra as drogas: uma análise sob a perspectiva do princípio da proporcionalidade

As substâncias entorpecentes acompanham a humanidade desde o início da civilização. No entanto, várias delas foram consideradas proscritas ao longo do tempo. Seu combate foi inaugurado na comunidade internacional a partir do começo do século XX. No início, tinha o condão eminentemente moral, porquanto a proibição encerrava, por princípio, a proteção da ética ameaçada pelo padrão desviado do consumo de estupefacientes. Na década de 1970, a guerra contra as drogas, expressão cunhada nesse período, evoluiu para se tornar o meio pelo qual o consumo seria mitigado. Dez anos mais tarde, ante à impossibilidade de sucumbir o narcotráfico, passou a ser um fim em si mesma o novo argumento para os esforços militares dos Estados Unidos da América. A criminalização das substâncias entorpecentes consideradas ilícitas é fundamento jurídico da guerra contra as drogas. Esse modelo proibicionista encontra argumento no direito penal do inimigo, segundo o qual o Estado pode, em situações que exponham a coletividade a grave perigo, negar à determinada categoria de criminosos (os inimigos) as garantias inerentes ao direito penal, cabendo-lhes apenas a coação estatal. Mesmo tendo consumido trilhões de dólares, encarcerado aos milhões e custado a vida de milhares de pessoas, pode-se dizer que a guerra contra as drogas não reduziu a oferta e o consumo de substâncias entorpecentes consideradas ilícitas, nem mitigou os danos delas decorrentes pelo contrário, tornou-se um problema de segurança pública. Assim, impõe-se a verificação da constitucionalidade da norma penal que fundamenta a guerra contra as drogas, sob ponderação do princípio da proporcionalidade. Referido postulado cobra que a norma seja adequada, cumprindo a finalidade pretendida, necessária, não havendo meio menos gravoso à obtenção do mesmo fim, e proporcional, estrito senso, que a sanção imposta ao indivíduo seja equivalente ao dano que se quis prevenir. Em matéria penal há de se incluir um outro elemento, a ponderar se as consequências da proibição em matéria penal, por si só, são mais graves que os consectários dos fatos que se pretendem proibir - exige-se que a lei seja socialmente menos ofensiva. A norma penal que fundamenta a guerra contra as drogas não se mostrou hábil a mitigar os danos sociais delas decorrentes sendo, por isso, inadequada. Existem meios alternativos à criminalização mais eficientes à esse objetivo, pelo que se faz desnecessária. Na medida em que estupefacientes mais nocivos à coletividade são considerados lícitos, a criminalização de drogas menos danosas se mostra desproporcional. E, uma vez que dela resultam graves danos à sociedade, não atende ao critério da menor ofensividade social. É, portanto, inconstitucional

Efeito do tratamento com as drogas antipsicóticas haloperidol e clozapina sobre a infecção de toxoplasma gondii em cultura de células retinianas embrionárias

T. gondii is an obligate intracellular protozoan and the main cause of retinochoroiditis in humans. The aim of this study was to evaluate the effect of the antipsychotic drugs haloperidol and clozapine on the course of infection by T. gondii of cultured embryonic retinal cells. Embryo retinas of Gallus gallus domesticus (E12) were used for the preparation of mixed monolayer cultures of retinal cells. Cultures were maintained on plates of 96 and 24 wells by 37°C in DMEM medium supplemented with 5% fetal bovine serum for 2 days. After this period, cultures were simultaneously infected with tachyzoites of T. gondii and treated with the antipsychotics haloperidol and clozapine for 48 hours. Treatment effects were determined by both assessing cell viability with the MTT method and evaluating infection outcomes in slides stained with Giemsa. The treatment with haloperidol and clozapine cells infected with T. gondii resulted in higher viability of these cells, suggesting a possible prevention of neuronal degeneration induced by T. gondii. Additionally, intracellular replication of this protozoan in cells treated with haloperidol and clozapine were significantly reduced, possibly by modulation of the parasite s intracellular calcium concentration

A redução de danos no atendimento especializado em álcool e outras drogas

The harm reduction HR is the official policy of Ministry of Public Health to deal with problem derived from alcohol consumption and other drugs AD. The HR refers to policies and support programs whose purpose is to reduce the risks related to the use of AD, without necessarily decrease individual consumption. This research aim was to analyze the HR conceptions and practices at two specialized institutions for AD users: 1) Psychosocial Care Center Alcohol and Drugs III (CAPSad III); 2) Therapeutic Community Fazenda da Esperança (FE) Dom Bosco. This is a qualitative research that used the following methodological tools: semi-structured interview with 21 professionals; socio demographic file and rounds of conversation with 63 participants users; participant observation and field journal. The interviews with professionals have characterized HR as a less complex and cheap treatment. At FE the HR proposal does not make part of their actions, being considered ―against the human being dignity‖. At CAPSad III is understood as an ―inevitable‖ guideline to service, once users do not remain abstinent. The users understand RD as an improvement in healthy conditions, social relations and work that occurs with the decreasing consumption of AD. They use the HR when they avoid situations that facilitate AD consumption, share relapse prevention strategies and, exclusively at CAPSad III, decrease psychotropic consumption. Stands out as an analyzer the HR comprehension as a less efficient treatment that opposes to the objective of both institutions, which is abstinence. The HR is not operationalize in daily routine by professionals and users as a healthy promotion strategy, however, the users are more affected to HR and produce strategies to face the difficulties arising from the AD consumption

Suporte ao uso de álcool e drogas na atenção primária: um estudo com equipes de Natal/RN

National surveys indicate that 6.8 % of the brazilian population is dependent on alcohol and 1 % dependent on illicit drugs, representing a significant portion of the population affected by this issue . Primary Care becomes instrumental in expanding the coverage of this demand and in reducing unnecessary referrals for specialized care. This study aimed to investigate the responsiveness and institutional support of Primary Care Teams in relation to the demands of alcohol and drugs users. The research was conducted in a Family Health Unit in West Sanitary District of Natal City. With quantitative and qualitative nature, our study consisted of two stages. At first, we performed a mapping of alcohol and other drugs abusive use in a sample of the population assisted by Family Heath Teams, using sociodemographic questionnaire and ASSIST (Alcohol, Smoking and Substance Involvement Screening Test). 406 questionnaires were completed. Of these questionnaires, 27.8% are men and 72.2% women, of which 56% are between 20 and 39 years-old, they are housewives, have a stable relationship and are consumers of tobacco (37.6%), marijuana (13%) and especially alcohol (57%). In second stage, two Conversation Circles with Family Health Teams and the referential Family Health Support Center were formed to discuss the data of the mapping realized in the previous phase. The circles, which had participation of 20 of the 37 professional teams from Family Health and 2 from Family Health Support Center, showed a lack of professional training in the subject; inability of the healthcare network in the user embracement; belief of professionals that nothing can be done when matter is alcohol and drugs; and referencing as the only care action performed by teams. Thus we point out the need to support an approach on issues of alcohol and drugs which consider gender issues, investing in Harm Reduction Policy as a possibility of working in this context for recognizing each user in their uniqueness and strategizing with them to promote health in a broad and contextualized way

Tratamento do Centro de Atenção Psicossocial para usuários de álcool e outras drogas CAPSad II Leste Natal/RN : uma avaliação da efetividade

The treatment for abusive users of alcohol and other drugs suffered significant modifications until arriving to the psychosocial model that is used by Centro de Atenção Psicossocial CAPSad II Eastern Natal/RN (Psychosocial Support Center). That model appears starting from Brazilian sanitary and psychiatric reforms which are expressed in the principles and propositions of Sistema Único de Saúde SUS (Unique System of Health). The Psychiatric Reform meant a rupture with the mental hospital and hospital centered treatment pattern which was destined to the abusive users of alcohol and other drugs. The new proposal offers the universalization, democratization, regionalization and completeness of the actions in the field of mental health. It gathers a strictly interdisciplinary health staff. The purpose of this study is to evaluate the effectiveness of the treatment for abusive users of alcohol and other drugs offered by CAPSad II Eastern Natal/RN. The evaluation used, as priority, the qualitative social research through an evaluating study starting from the non-experimental model. The methodological process used different instruments of data collection: bibliographical and documental researches, systematic observations at CAPSad II Eastern Natal/RN and, mainly, the semistructured interviews (21) that were accomplished with the professionals, users and relatives of CAPSad II Eastern Natal/RN. The investigation showed the effectiveness of the service and, therefore, CAPSad II Eastern Natal/RN constitute itself as the main confronting strategy to the mental hospital and hospital centered treatment pattern of caring the abusive users of alcohol and other drugs

Frequência e significado clínico da expressão da glicoproteína P e da proteína relacionada a resistência a múltiplas drogas na leucemia mielóide aguda

Despite the advances in the cure rate for acute myeloid leukemia, a considerable number of patients die from their disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) confer resistance to the treatment these leukemias. OBJECTIVE: To analyze the expression of the Gpp and MRP1 in patients with AML by flow cytometry (FC) and to determine the correlation between expression and demographic and also clinical and laboratorial variables. METHODS: Bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by FC. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in adolescents, observing also a high incidence in patients with refractory disease, recurrence and secondary in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed a higher correlation statistically significant between the expression of Pgp and MRP1 in AML CD34+ and FAB AML M7, M5A and M2 and lower the M3 subtype, not observed statistically significant correlation between the phenotype MDR and other laboratory data such with hemoglobin, leukocyte count, platelet count, aberrant expression of lymphoid antigens (CD2, CD7 and CD19) and clinical signs related to the disease. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis independent patients diagnosed with AML.

Criminalização do porte de drogas para consumo pessoal: uma perspectiva jurídico-constitucional

This dissertation has the main objective to assess the legal and constitutional legitimacy of the legislative state act that criminalizes the conduct of carrying drugs for own consumption - in the case of Brazil, art. 28 of the Federal Law n.º 11.343 of August 23rd, 2006. Therefore, it is done, initially, a contextualization, pointing the main regulatory frameworks, internal and external, of what is conventionally called prohibition in the matter of drugs, as well as the different species of liberalizing initiatives today on an upward trend in the international scenario. Then analyzes the state intervention in question in the light of references of human dignity, freedom and privacy, emphasizing, in the point, among other contributions, the various precedents of foreign constitutional jurisdiction over the theme. Immediately thereafter, confronts the policy in screen with what is perhaps, these days, the main control mechanism of the restrictive measures of fundamental rights, namely the proportionality test, here represented by classical elements of appropriateness, necessity and proportionality in the strict sense. After that, it examines the criminalization on the agenda before the parameter of equality and the general interests of health and public safety. Based on theory and empirical enrolled in the development, it is concluded, finally, the unconstitutionality of the option of the ordinary legislature to impose criminal penalties on users - problematic or not - of substances or products capable of causing physical or psychological dependence.