Direct spectrofluorimetric methods as alternatives to compendial ones used for the quality control of biopharmaceuticals: development, validation and application

Abstract A simple, rapid, precise, accurate and sustainable spectrofluorimetric method (SFM) was developed, validated and applied for the determination of 4-aminobenzoic acid and aromatic amino acids (phenylalanine, tryptophan and tyrosine). These compounds are used in biopharmaceutical formulations and therefore must be analyzed by quality control laboratories to meet the criteria established in pharmacopoeias. In general, potentiometric titration (PT) is described in the compendia as the official analytical technique. However, this method showed low sensitivity and selectivity, and moreover was performed with a non-aqueous solvent (acetic acid), which led to higher consumption of reagents and consequently to the formation of residues. Therefore, the SFM was developed in aqueous medium at pH 7.2 using phosphate buffer. It was successfully validated according to the ICH guidelines and showed good linearity range (r>0.999), specificity, accuracy and precision (within and between days) and robustness. The test results were compared between the SFM and PT using raw material samples, while according to the F- and t-tests at 95% confidence level, no statistical difference was found between the methods.

Prevention of bone infection after open fracture using a chitosan with ciprofloxacin implant in animal model

Abstract Purpose To evaluate different concentrations of ciprofloxacin to prevent infection after open fracture contaminated with S. aureus in rats using absorbable local delivery system. Methods Fifty-two Wistar rats were assigned to six groups. After 4 weeks, all animals underwent 99mTc-ceftizoxima scintigraphy evaluation, callus formation measurement and histological analysis. ANOVA, t-Student and Kruskal Wallis were used for quantitative variables statistical analysis, whereas qui square and exact Fisher were used for qualitative variables. Results Treatment using 25% and 50% of ciprofloxacin incorporated at the fracture fixation device were effective in preventing bone infection compared to control group (p<0.05). Chitosan were not effective in preventing bone infection when used alone compared to control group (p>0.05). Histological findings demonstrated bone-healing delay with 50% of ciprofloxacin. No difference in callus formation were observed (p>0.05). Conclusion Local delivery treatment for contaminated open fracture using chitosan with ciprofloxacin is effective above 25%.

Serological evidence of exposure to Toxoplasma gondii and Neospora caninum in free-ranging Orinoco goose (Neochen jubata) in Brazil / Evidência sorológica de exposição à Toxoplasma gondii e Neospora caninum em Ganso-do-Orinoco (Neochen jubata) de vida livre no Brasil

Abstract Toxoplasma gondii and Neospora caninum are Apicomplexan intracellular protozoan parasites that affect numerous animal species, thus leading to severe diseases and economic losses, depending on the vertebrate species involved. The role of the avian species in maintaining and transmission of these coccidia has been studied for several years as they tend to serve as a potential source of infection for mammals and humans. The present study aimed to assess the serological exposure of Orinoco goose (Neochen jubata) to T. gondii and N. caninum. Between 2010 and 2013, 41 free-ranging Orinoco geese were captured in the Araguaia River, Brazil. The presence and titration of IgY antibodies to both coccidia were assayed via indirect immunofluorescent antibody test (IFAT). While IgY antibodies for N. caninum were present in 5 animals, with titers of 20, the antibodies for T. gondii were found in 35 animals, with titers ranging from 20 to 640. Considering that the Orinoco goose's meat is consumed by the local population in the studied area, it may represent an important source of T. gondii infection for humans. Due to its migratory behavior, this goose may play a pivotal role in the natural dispersion of both parasites. Furthermore, molecular studies are required for genotyping the isolates of T. gondii that occurs in this avian species.

Resumo Toxoplasma gondii e Neospora caninum são parasitas protozoários intracelulares do philo Aplicomplexa que afetam uma vasta gama de espécies animais, causando sérias doenças e levando a perdas econômicas, dependendo da espécie envolvida. O papel das aves na manutenção e transmissão destes coccídios tem sido estudado por anos, já que eles são potenciais fontes de infecção para outros animais e humanos. O objetivo deste estudo foi avaliar a exposição do Ganso-do-Orinoco (Neochen jubata) a T. gondii e N. caninum por meio de técnicas sorológicas. Entre os anos de 2010 e 2013, 41 Gansos-do-Orinoco de vida livre foram capturados no Vale do Rio Araguaia, Brasil. A presença e titulação de anticorpos IgY para ambos os coccídios foi obtida utilizando-se a Reação de Imunofluorescência Indireta (RIFI). Enquanto a presença de anticorpos IgY para N. caninum foi detectada em 5 aves, com titulação 20, anticorpos para T. gondii foram encontrados em 35 aves, com títulos variando de 20 a 640. Considerando que a carne do Ganso-do-Orinoco é uma fonte de alimento para a população da área estudada, a ave pode representar uma importante fonte de infecção de T. gondii para humanos. Devido ao seu comportamento migratório, esta espécie assume grande importância na dispersão de ambos os parasitas. Estudos moleculares são necessários a fim de caracterizar genotipicamente os isolados de T. gondii que ocorrem nesta espécie de ave.

Frequency of antibodies and risk factors associated with Toxoplasma gondii infection in backyard pig production in the city of Mossoró, state of Rio Grande do Norte, Brazil / Frequência de anticorpos e fatores de risco associados à infecção por Toxoplasma gondii em criações de suínos em Mossoró, Rio Grande do Norte

Abstract Toxoplasmosis is an important zoonosis for pregnant women and immunosuppressed people. The pig population also becomes infected by this pathogen, and undercooked or raw meat is an important source of infection for humans. The aims of the present study were to evaluate the rate of exposure of pigs to T. gondii in the municipality of Mossoró, Rio Grande do Norte and seek to identify associations with possible risk factors. Blood samples were collected from 412 pigs and were analyzed using the immunofluorescence assay. Among these 412 serum samples, 40.7% were seropositive for T. gondii. The IgG antibody titers were 64 (56 specimens), 128 (32), 256 (37), 512 (23), 1024 (14), 2048 (5) and 4046 (1). Seropositivity for T. gondii was found to be related (p-value < 0.05) to the following factors: female gender, semi-confined rearing system, use of well water, dewormed animals, presence of cats, goats, sheep, mice and vultures on the farm and carcasses left on the ground. In contrast, seropositivity was not related (p-value < 0.05) to the age of the pigs, type of facility or feeding with human food remains. Preventive measures need to be adopted on the farms studied here, with the aim of decreasing the animals' intake of sporulated oocysts.

Resumo A toxoplasmose é uma importante zoonose para mulheres grávidas e pessoas imunossuprimidas. Os suínos também são infectados por este patógeno; e a carne crua ou malcozida é uma importante fonte de infecção para o ser humano. O objetivo do presente trabalho foi avaliar a taxa de exposição suína à T. gondii no município de Mossoró, Rio Grande do Norte e identificar associações com possíveis fatores de risco. Amostras de sangue foram coletadas em tubos sem anticoagulante e o soro foi separado de 412 porcos e analisadas pelo ensaio de imunofluorescência. Dentre as 412 amostras de soro, 40,7% foram positivas para T. gondii. Os títulos para o anticorpo IgG foram 64 (56 amostras); 128 (32); 256 (37); 512 (23); 1024 (14); 2048 (5) e 4046 (1). A soropotividade para T. gondii foi relacionada (p-valor < 0,05) aos seguintes fatores: gênero feminino, sistema de criação de semi-confinamento, uso de água de poço, animais vermifugados, presença de gatos, cabras, ovelhas, ratos e urubus na fazenda e carcaças deixadas à céu aberto. Em contrapartida, a soropositividade não foi relacionada (p-valor < 0,05) à idade dos suínos, tipo de instalações ou alimentação com restos de comida humana. As adoções de medidas preventivas são necessárias na propriedade estudada, objetivando diminuir a ingestão de oocistos esporulados pelos animais.

Phylogeography of msp4 genotypes of Anaplasma marginale in beef cattle from the Brazilian Pantanal / Filogeografia de genótipos msp4 de Anaplasma marginale em gado de corte no Pantanal brasileiro

Abstract The msp4 gene of A. marginale is unicodon, stable and mostly homogeneous, being considered as a useful marker for phylogeographic characterization of this bacterium. The objective of this work was to analyze the phylogeography of A. marginale based on the msp4 gene in beef cattle from the Brazilian Pantanal, compared to those found in other regions worldwide. The blood samples investigated were collected from 400 animals (200 cows and 200 calves) reared in five extensive breeding farms in this region. The results indicated that of the evaluated samples, 56.75% (227/400) were positive for A. marginale based on the msp1β gene by quantitatitve PCR (qPCR), while 8.37% (19/227) were positive for the msp4 gene in the conventional PCR. In the Network distance analysis, 14 sequences from the Brazilian Pantanal were grouped into a single group with those from Thailand, India, Spain, Colombia, Parana (Brazil), Mexico, Portugal, Argentina, China, Venezuela, Australia, Italy and Minas Gerais (Brazil). Among 68 sequences from Brazil and the world, 15 genotypes were present while genotype number one (#1) was the most distributed worldwide. Both Splitstree and network analyses showed that the A. marginale msp4 sequences detected in beef cattle from the Brazilian Pantanal showed low polymorphism, with the formation of one genogroup phylogenetically related to those found in ruminants from South and Central America, Europe, and Asia.

Resumo O gene msp4 de A. marginale é unicodon, estável e pouco heterogêneo, sendo considerado como um marcador útil para caracterização filogeográfica desta bactéria. Este trabalho teve como objetivo analisar a filogeografia de A. marginale com base no gene msp4 em bovinos de corte do Pantanal Brasileiro, comparativamente a outra regiões do mundo. Alíquotas de sangue foram colhidas de 400 bovinos (200 vacas e 200 bezerros) em cinco propriedades de cria e recria extensiva. Como resultado, 56,75% (227/400) mostraram-se positivas para A. marginale pela qPCR para o gene msp1β e destas, 8,37% (19/227) amostras foram positivas na PCR convencional para o gene msp4. Na análise de distância Network, 14 sequências do Pantanal brasileiro foram agrupadas em um único grupo com as da Thailândia, Índia, Espanha, Colômbia, Paraná (Brasil), México, Portugal, Argentina, China, Venezuela, Austrália, Italia e Minas Gerais (Brasil). Dentre 68 sequências do Brasil e do mundo, constatou-se a presença de 15 genótipos, sendo o genótipo número um (#1) o mais distribuído. As sequências msp4 de A. marginale detectadas em bovinos de corte no Pantanal brasileiro apresentaram baixo polimorfismo com formação de dois genogrupos filogeneticamente relacionados àqueles encontrados em ruminantes de países das América do Sul e Central, Europa e Ásia.

Molecular detection of Anaplasmataceae agents in Dasyprocta azarae in northeastern Brazil / Detecção molecular de agentes Anaplasmataceae em Dasyprocta azarae no nordeste do Brasil

Abstract Recently, the importance of wild-living rodents for maintenance of pathogens of the family Anaplasmataceae in the environment was investigated. These mammals play a role as reservoirs for these pathogens and act as hosts for the immature stages of tick vectors. The aim of the present study was to investigate the prevalence of Ehrlichia sp. and Anaplasma sp. in 24 specimens of Azara's agouti (Dasyprocta azarae) that had been trapped in the Itapiracó Environmental Reserve, in São Luís, Maranhão, northeastern Brazil, using molecular methods. Four animals (16.7%) were positive for Ehrlichia spp. in nested PCR assays based on the 16S rRNA gene. In a phylogenetic analysis based on the 16S rRNA gene, using the maximum likelihood method and the GTRGAMMA+I evolutionary model, Ehrlichia sp. genotypes detected in Azara's agoutis were found to be closely related to E. canis and to genotypes relating to E. canis that had previously been detected in free-living animals in Brazil. The present work showed the first molecular detection of Ehrlichia sp. in Azara's agoutis in Brazil.

Resumo Recentemente, a importância de roedores selvagens na manutenção de agentes Anaplasmataceae no ambiente tem sido investigada, haja visto o papel que tais mamíferos podem desempenhar como reservatórios para os patógenos e como hospedeiros para estágios imaturos dos carrapatos vetores. O presente estudo objetivou investigar a ocorrência de Ehrlichia sp. e Anaplasma sp. em 24 cotias (Dasyprocta azarae) capturadas na Reserva Ambiental de Itapiracó, em São Luís, Maranhão, nordeste do Brazil, utilizando métodos moleculares. Quatro animais (16,7%) mostraram-se positivos nos ensaios de nested PCR para Ehrlichia spp. baseados no gene 16S rRNA gene. Na análise filogenética baseda no gene 16S rRNA e utilizando o método de Máxima Verossimilhança e modelo evolutivo GTRGAMMA+I, os genótipos de Ehrlichia sp. detectados em cotias mostraram-se filogeneticamente relacionados às sequências de E. canis e outros genótipos relacionados a E. canis detectados previamente em animais selvagens no Brasil. O presente trabalho mostrou a primeira detecção molecular de Ehrlichia sp. em cotias no Brasil.

Mammary artery Doppler ultrasonography of Brazilian Bergamasca dairy ewe lambs under the influence of two different feeding plans / Avaliação ultrassonográfica por Doppler da artéria mamária de cordeiras da raça Bergamácia Brasileira sob a influência de dois planos de alimentação diferentes

Blood supply of mammary gland is extremely important, since it is a crucial factor in the mammary tissue development. The objective of this study was to describe and assess main mammary artery hemodynamic characteristics of lambs with two growth rates, using Doppler ultrasound. Two experimental groups, A and B, (n=10) of female Brazilian Bergamasca lambs were kept under the same management conditions and facilities. There were two phases: Phase 1, from 90 days of age until onset of puberty; Phase 2, from puberty until 1 year of age. During phase 1, a specific diet was formulated to each experimental group to obtain two different average daily gains: 150g, for treatment A, and 250g, for treatment B. During phase 2, there was no difference on the diet offered to both groups. Every 14 days, all animals were weighed and their body condition score was evaluated. Every 60 days, ultrasound exams (Doppler) of mammary artery were performed to obtain resistance and pulsatility indexes. Treatment B lambs showed higher weight gain and higher body condition score (P<0.05). However, for resistance and pulsatility indexes, there was no difference between treatments (P>0.05). Hemodynamic values remained constant, independent of diet or body development presented by the animals. Obtained data is valuable information on Bergamasca ewe lambs development.(AU)

O suprimento sanguíneo da glândula mamária é extremamente importante, uma vez que é um fator crucial para o desenvolvimento do tecido mamário. Assim, a necessidade de registro dos parâmetros de fluxo sanguíneo arterial é evidente. O objetivo do estudo foi descrever e avaliar as principais características hemodinâmicas da artéria mamária de cordeiras submetidas a diferentes taxas de crescimento, usando o ultrassom Doppler. Dois grupos experimentais, A e B, (n=10) de cordeiras da raça Bergamácia brasileira foram mantidas sob as mesmas condições de manejo e instalações. O estudo foi dividido em diferentes fases, sendo: Fase 1, de 90 dias de idade até o início da puberdade; Fase 2, desde a puberdade até 1 ano de idade. Durante a fase 1, dietas específicas foram formuladas para cada grupo experimental, a fim de obter duas médias diferentes de ganho de peso diário: 150g, para o tratamento A, e 250g, para o tratamento B. Durante a Fase 2, não houve diferença na dieta oferecida para os dois grupos. A cada 14 dias, todos os animais foram pesados e determinado o escore de condição corporal. A cada 60 dias, exames de ultrassom (Doppler) da artéria mamária foram realizados a fim de calcular os índices de resistência e pulsatilidade. As cordeiras do tratamento B registrou maior ganho de peso e escore de condição corporal (P<0,05). No entanto, não houve diferença para os índices de resistência e pulsatilidade entre os tratamentos (P>0,05). Os valores hemodinâmicos permaneceram constantes, independente da dieta ou o desenvolvimento do corpo apresentada pelos animais. Assim, os dados obtidos são informações valiosas sobre o desenvolvimento da raça a que se refere.(AU)

Associação entre privação do sono e obesidade em trabalhadores / Association between sleep deprivation and obesity in workers

OBJETIVOS: estudar a associação entre privação de sono e obesidade em trabalhadores. MÉTODOS: Foi conduzido um estudo transversal com trabalhadores de uma manufatura de cadernos no sul do Brasil, que possui três setores de trabalho (linha de produção, setor administrativo e logística), sendo que o setor de produção trabalha 24 horas por dia. Características demográficas, socioeconômicas, ocupacionais e comportamentais foram obtidas através de um questionário autopreenchível, padronizado e pré-testado. As medidas de peso e altura foram autorreferidas e o índice de massa corporal calculado. O ponto de corte para obesidade foi de ≥30 kg/m². A duração do sono foi categorizada em no mínimo seis horas por dia e menos de seis horas por dia (privação do sono). Para análise bivariada, foi utilizado o teste do Qui-quadrado e o teste de tendência linear. As razões de prevalência brutas e ajustadas foram calculadas pela Regressão de Poisson. RESULTADOS: A amostra final contou com 193 trabalhadores, com média de idade de 34±11 anos, sendo 99 (51%) mulheres. A prevalência de obesidade foi de 27 (13,98%), e a prevalência de privação do sono foi de 40 (20,7%). A privação de sono foi associada ao setor de produção (p=0,011), ao turno noturno (p<0,001) e à inatividade física (p=0,003). A presença de obesidade foi associada à privação do sono (p=0,006). Após o controle para possíveis fatores de confusão, a probabilidade de ser obeso foi de 2,37 (IC 95% 1,08-5,21) vezes maior entre trabalhadores em privação de sono. CONCLUSÕES: Os resultados demostraram associação entre privação de sono e obesidade. Além disso, a privação de sono foi associada ao trabalho no turno noturno.

AIMS: To study the association between sleep deprivation and obesity among workers. METHODS: We conducted a cross-sectional study of workers at a notebooks manufacturing in southern Brazil, which has three sectors of work (production line, back office and logistics), and the production sector works 24 hours a day. Demographic, socioeconomic, occupational and behavioral characteristics were obtained by a self-completion questionnaire, standardized and pre-tested. Weight and height measurements were self-reported and body mass index calculated. The cutoff point for obesity was ≥30 kg/m². Sleep duration was categorized into at least six hours a day and less than six hours a day (sleep deprivation). For bivariate analysis, chi-square test and test for linear trend were used. The crude and adjusted odds ratios were calculated using Poisson regression. RESULTS: The final sample consisted of 193 workers, with a mean age of 34±11 years, 99 (51%) women. The prevalence of obesity was 27 (13.98%), and the prevalence of sleep deprivation was 40 (20.7%). Sleep deprivation has been associated with the production sector (p=0.011), the night shift (p<0.001) and physical inactivity (p=0.003). The presence of obesity was associated with sleep deprivation (p=0.006). After controlling for potential confounding factors, the likelihood of being obese was 2.37 (95% CI 1.08 to 5.21) times higher among workers in sleep deprivation. CONCLUSIONS: The results showed an association between sleep deprivation and obesity. In addition, sleep deprivation was associated with work on the night shift.

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Background Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol.L−1 (S. aureus) and 10.10 μmol.L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.(AU)

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 mol.L1 (S. aureus) and 10.10 mol.L1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 g of LyeTx I-K-HYNIC; 250 g of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Suicide risk in cocaine addicts with a current depressive episode: feelings and experiences / Risco de suicídio em dependentes de cocaína com episódio depressivo atual: sentimentos e vivências / Riesgo de suicidio en dependientes de cocaína con episodio depresivo actual: sentimientos y vivencias

Death by suicide is now the third most frequent cause of death in the population 15-44 years old. This self-inflicted death has meaning that requires understanding and attention. The objective of this study was to understand the experiences and feelings of cocaine users within the relationship of addiction and suicide. This is a qualitative study conducted from August 2012 to February 2013. The 18 individuals who met criteria for a depressive episode responded to the semi-structured interview for suicide risk, the Mini International Neuropsychiatric Interview. During the analysis of the narrated content, there were three categories established: previous history, previous suicide attempts, and depression. The results were evaluated seeking to reflect and understand the experiences exposed by users. This study helps to understand the meaning of the experiences and feelings of crack/cocaine users who are at the risk for suicide...

Clonal profile, virulence and resistance of Staphylococcus aureus isolated from sheep milk

The objective of this study was to characterize the clonal profile, virulence factors and antimicrobial resistance, particularly oxacillin resistance, of Staphylococcus aureus isolated from sheep milk. Milk samples were collected from all teats for the California Mastitis Test (CMT), somatic cell count, identification of S. aureus, investigation in these strains of genes encoding toxins (sea, seb, sec, sed, tst), biofilm (icaA, icaC, icaD, bap), leukocidin (luk-PV) oxacillin resistance by mecA gene detection and susceptibility testing (12 antibiotics). Messenger RNA expression was evaluated by RT-PCR in isolates carrying toxin and biofilm genes. Biofilm formation was also evaluated phenotypically by adherence to polystyrene plates. The clonal profile of S. aureus was investigated by pulsed-field gel electrophoresis. A total of 473 milk samples were collected from 242 animals on three farms and 20 S. aureus strains were isolated and none carried the mecA gene. The two sec gene-positive isolates and the isolates carrying the tst and luk-PV genes were positive by RT-PCR. Staphylococcus aureus isolated from the three flocks studied showed high susceptibility to the drugs tested and none was biofilm producer, indicating that biofilm formation was not a virulence factor causing infection by these strains. The typing of 17 S. aureus isolates revealed the presence of a common clone on the three farms studied, and the presence and expression of the sec and tst genes in one strain of this clone suggest the possible acquisition of virulence genes by this clone, a fact that is important for animal health and food hygiene.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

Os benefícios obtidos com a parada do uso de drogas por usuários de um serviço de teleatendimento / The benefits obtained with the stop of drug use users of a call center service

Este artigo se propõe a entender se há relação entre os benefícios relatados pelos ex-usuários de drogas atendidos em um serviço de teleatendimento sobre dependência química após a parada do uso de substâncias com o perfil sociodemográfico destes. Trata-se de uma pesquisa fundamentada no método de análise de conteúdo, em que foram agrupados os benefícios em parar com o uso da substância em categorias, que serão descritas detalhadamente ao longo do trabalho. A partir dos dados obtidos, foi observado que as categorias denominadas, apoio social e sentimentos positivos foram os mais relatados entre os ex-usuários, abrindo possibilidades de pensar modelos de tratamento, visando ao fortalecimento desses fatores no indivíduo.

This article aims to understand whether there is a relation between the benefits reported by ex-drug users attending a telephone service about addiction after stopping the use of substances with the demographic profile of these. It is one based on the method of content analysis where the benefits stop substance use into categories, which will be described in detail throughout the work. From the data obtained it was observed that the categories namely, social support and positive feelings were the most common among former users, opening up possibilities of thinking treatment models aimed at strengthening these factors.

Non-adherence to telemedicine interventions for drug users: systematic review / Não adesão em intervenções por telemedicina para usuários de drogas: revisão sistemática

OBJECTIVE To estimate rates of non-adherence to telemedicine strategies aimed at treating drug addiction. METHODS A systematic review was conducted of randomized controlled trials investigating different telemedicine treatment methods for drug addiction. The following databases were consulted between May 18, 2012 and June 21, 2012: PubMed, PsycINFO, SciELO, Wiley (The Cochrane Library), Embase, Clinical trials and Google Scholar. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of the studies. The criteria evaluated were: appropriate sequence of data generation, allocation concealment, blinding, description of losses and exclusions and analysis by intention to treat. There were 274 studies selected, of which 20 were analyzed. RESULTS Non-adherence rates varied between 15.0% and 70.0%. The interventions evaluated were of at least three months duration and, although they all used telemedicine as support, treatment methods differed. Regarding the quality of the studies, the values also varied from very poor to high quality. High quality studies showed better adherence rates, as did those using more than one technique of intervention and a limited treatment time. Mono-user studies showed better adherence rates than poly-user studies. CONCLUSIONS Rates of non-adherence to treatment involving telemedicine on the part of users of psycho-active substances differed considerably, depending on the country, the intervention method, follow-up time and substances used. Using more than one technique of intervention, short duration of treatment and the type of substance used by patients appear to facilitate adherence. .

OBJETIVO Estimar taxas de não adesão em intervenções com estratégias de telemedicina para tratamento de dependência química. MÉTODOS Foi realizada revisão sistemática de ensaios clínicos randomizados com diferentes métodos terapêuticos de dependência química que incluíam telemedicina. Foram consultadas as bases de dados PubMed, PsycINFO, SciELO, Wiley (The Cochrane Library), Embase e Clinical Trials e a plataforma Google Scholar no período de 18/4/2012 a 21/6/2012. Para avaliar a qualidade dos estudos, utilizou-se a escala Grading of Recommendations Assessment, Development and Evaluation . Os critérios avaliados foram: adequada sequência da geração de dados, ocultação da alocação, cegamento, descrição das perdas e exclusões e análises por intenção de tratar. Foram selecionados 274 estudos, dos quais 20 foram analisados. RESULTADOS As taxas de não adesão variaram entre 15,0% e 70,0%. As intervenções avaliadas possuíam no mínimo três meses de intervenção e, embora todos utilizassem a telemedicina como apoio, os métodos de tratamentos foram diferentes. Em relação à qualidade dos estudos, os valores também variaram entre muito baixa qualidade e alta qualidade. Os estudos com qualidade alta demonstraram maiores taxas de adesão, bem como aqueles que utilizaram mais de uma técnica de intervenção e tempo limitado de tratamento. Estudos com monousuários apontaram maiores taxas de adesão que estudos com poliusuários. CONCLUSÕES As taxas de não adesão a tratamentos para usuários de substâncias psicoativas por meio de telemedicina apresentaram consideráveis diferenças, dependendo do país, método da intervenção, tempo de seguimento ...

Efficacy of the telephone-based Brief Motivational Intervention for alcohol problems in Brazil

Background: The Brief Motivational Intervention (BMI) is an effective treatment for alcohol misuse but has not been adequately tested for use in helplines for alcoholics. The main objective of this study was to evaluate the efficacy of a telephone-based BMI for Brazilians seeking help with alcohol use cessation. Methods: A randomized, controlled trial was performed with Brazilian subjects. Participants were randomly assigned to either the minimal intervention group (i.e., given reference materials) or the BMI group. Alcohol abstinence was evaluated in a 6-month follow-up telephone counseling session. The analysis was based on the intention to treat (ITT). Results: Of the 5,896 drug users who called the helpline, 700 (12%) used alcohol, 637 of whom enrolled in this study. At 6-month follow-up, 70% of the BMI group had stopped consuming alcohol compared to 41% in the control group (odds ratio = 1.5; 95% confidence interval = 1.2-1.9; p = 0.001). Conclusions: A helpline-based BMI helps alcohol users achieve abstinence. .

Quality of life of users of psychoactive substances, relatives, and non-users assessed using the WHOQOL-BREF / Qualidade de vida em usuários de substâncias psicoativas, familiares e não usuários por meio do WHOQOL-BREF

Quality of life is related to one of the basic human desires, which is to live well and feel good. The scope of this study was to evaluate the quality of life of psychoactive substance users and relatives, compared to non-users, analyzed by socioeconomic strata. A cross-sectional study with users of psychoactive substances, relatives, and other individuals who called the Information and Orientation Service regarding drug abuse. Data collection took place between November 2009 and December 2010. Data was collected from users, relatives, and non-users, including socioeconomic characteristics and data regarding substance consumption when appropriate. In addition to this the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was given to 347 individuals. Among the 138 users (70%) used alcohol, 76 (39%), marijuana, 111 (57%) tobacco, 78 (40%) cocaine and 70 (36%) crack. Control subjects had higher, scores than the relatives of users and users in all areas of the questionnaire (p < 0.05). Psychoactive substance users scored lower in almost all domains and overall score in the WHOQOL-BREF questionnaire in comparison with the sample of non-drug users. These findings reflect poor quality of life of patients and their relatives.

Qualidade de vida está relacionada a um dos desejos humanos básicos, que é viver bem e se sentir bem. O objetivo deste estudo foi avaliar a qualidade de vida dos usuários de substâncias psicoativas e familiares, em comparação aos não-usuários, analisados por estratos socioeconômicos. Foi realizado um estudo transversal com usuários de substâncias psicoativas, parentes e outras pessoas que chamaram o Serviço de Informação e Orientação sobre o abuso de drogas (VIVAVOZ). A coleta de dados ocorreu entre novembro de 2009 e dezembro de 2010. Foram coletados dados de usuários, parentes e não-usuários, incluindo as características socioeconômicas e dados sobre consumo de substâncias, quando apropriado, além disso, foi administrado o questionário WHOQOL-BREF. Responderam ao WHOQOL-Bref 347 pessoas, 138 (70%) usuários de álcool , 76 (39%) maconha, 111 (57%) tabaco, 78 (40%) de cocaína e 70 (36%) crack. Os controles tiveram escores maiores de qualidade de vida, que os familiares de usuários e usuários em todas as áreas do questionário (p < 0,05). Usuários de substâncias psicoativas tiveram escores mais baixos em quase todos os domínios e escore geral do WHOQOL-Bref em comparação com a amostra de não usuários de drogas. Estes resultados refletem baixa qualidade de vida dos pacientes e seus familiares.

A judicialização do acesso aos medicamentos em Santa Catarina: um desafio para gestão do sistema de saúde / The judicialization of access to medicines in Santa Catarina State: a challenge for the management of the health system

O objetivo deste estudo foi analisar os mandados judiciais para fornecimento de medicamentos impetrados contra o Estado de Santa Catarina entre 2000 e 2006. As informações foram levantadas junto ao Programa de Medicamentos Judiciais (Mejud) da Secretaria Estadual de Saúde. Foi calculada a distribuição dos solicitantes por sexo, descritas as séries históricas do total de ações,o volume de recursos gastos pela Secretaria no período de 2000 a 2006 e se os medicamentos e/ou correlatos solicitados estavam padronizados no SUS. Também se calcularam as taxas de ações judiciais dos municípios por habitante a fim de testar a sua associação com indicadores socioeconômicos. No ano 2000 houve apenas uma ação deferida; em 2006 foram 1.661; de sete medicamentos solicitados em 2000, o total saltou para 3.542 em 2006.Destes, 29 por cento eram padronizados pelo SUS. Os medicamentos mais solicitados destinavam-se ao tratamento do sistema nervoso e os que acarretaram maior custo foram os antineoplásicos. Municípios com melhores condições socioeconômicas apresentaram maior número de ações deferidas por habitante. Verificou-se necessidade de melhor articulação entre Executivo e Judiciário garantindo efetivação dos direitos constitucionais e uso racional dos medicamentos.

Manejo do paciente obeso pediátricona atenção primária: proposta de uma abordagem terapêutica prática / Obese pediatric patient management inprimary care: a proposal for a practicaltherapeutic approach

Inúmeros são os desafios do Sistema Único de Saúde (SUS) em atender de forma adequada na infância a maior epidemia em Saúde Pública do mundo: a obesidade. Por isso, os cuidados clínicos pediátricos na prevenção, identificação e tratamento da obesidade infantil são de fundamental importância na atenção primária à saúde. O presente artigo tem por objetivo descrever e apresentar uma abordagem terapêutica prática no manejo do paciente obeso pediátrico, baseada na experiência no atendimento do ambulatório de Obesidade Infanto-juvenil do Serviço de Nutrologia do Hospital de Clínicas de Porto Alegre (1). No tratamento da obesidade infantil não há estratégias milagrosas. No entanto, as ações clássicas, educação nutricional e adesão familiar, ao longo do tempo, conferem um potencial benefício, podendo ser realizadas pela maioria dos profissionais de saúde e prestadores de cuidados primários de saúde.

The Unified Health System (SUS) faces countless challenges in providing adequate effective assistance in childhood to the largest epidemic in Public Health in the world: obesity. Therefore, pediatric clinical care in prevention, identification and treatment of childhood obesity is of paramount importance in primary health care. The objective of this article is to describe and present a practical therapeutic approach in the management of the pediatric obese patient, based on the experience at the juvenile obesity outpatient clinic of the Nutrition Service at Hospital de Clínicas de Porto Alegre (HCPA). The treatment for childhood obesity provides no miraculous strategy. However, the classical approaches, nutrition education and family support, offer potential benefit throughout time, and may be adopted by most health care professionals and primary health care providers.

Diagnóstico de um grupo de familiares em risco para o câncer de mama: contribuição para a assistência de enfermagem / A family group on risk of breast cancer diagnosis: contribution for nursing assistance

Devido a sua alta incidência, mortalidade e custos elevados, o câncer de mama feminino é considerado um problema de saúde pública no Brasil. Sua etiologia envolve uma interação de diversos fatores denominados de risco os quais podem ser ambientais e genéticos. A história familiar positiva para câncer de mama é um importante fator de risco para o desenvolvimento dessa patologia. Conhecer esses fatores e as medidas de proteção permite que mulheres com risco elevado possam criar estratégias pessoais que venham minimizar os danos causados pela doença. Diante do exposto, o presente estudo tem como objetivos avaliar o nível de conhecimento de mulheres acerca do risco de desenvolverem câncer de mama em decorrência do vínculo familiar com a população portadora desta neoplasia matriculada no Hospital do Câncer III, unidade do Instituto Nacional de Câncer (INCA) especializada no tratamento e controle do câncer de mama, localizada no município do Rio de Janeiro, Brasil; descrever as características sociodemográficas das mulheres familiares de pacientes portadoras de câncer de mama e descrever a história reprodutiva e hormonal, bem como seus hábitos de cuidado com a saúde. Metodologia: trata-se de um estudo exploratório sob a perspectiva quantitativa, transversal e descritiva com 52 mulheres que acompanhavam suas familiares internadas em unidade clínica e cirúrgica do Hospital do Câncer III. A coleta de dados ocorreu no período entre julho e agosto de 2011. A técnica de amostragem adotada foi a não probabilística, intencional Para o cálculo amostral aplicou-se a fórmula de população infinita. Foram selecionadas as seguintes variáveis para compor o estudo: aspectos sociodemográficos, aspectos da vida reprodutiva e hormonal, aspectos de cuidados com a saúde e aspectos de esclarecimento relacionados à patologia/doença. Realizou-se entrevista estruturada com utilização de um formulário composto por 63 questões...

Due to the incidence, mortality and high costs, female breast cancer is considered a Health Care issue in Brazil. Its etiology binds an interaction of various risk factors which can be environmental and genetic ones. A positive family history for breast cancer is an important risk factor for the development of this pathology. Knowing the factors and protection measures allow the women with high risk create personal strategies that minimize the damage caused by the disease. Objectives: evaluate the level of knowledge of the women regarding the risk of breast cancer development related to family history with population which carries this neoplasia assisted by the Hospital do Câncer III, Cancer National Institute (INCA) branch specialized on breast cancer treatment and control, located at the city of Rio de Janeiro, Brazil; describe the social demographical characters of the women whose relatives are breast cancer patients and report their hormonal and reproductive history as well as their health care habits. Methodology: It consists of an exploratory study under a quantitative perspective in a descriptive and transversal way with 52 women that accompanied their hospitalized relatives in a clinic and surgery unity of Hospital do Câncer III. The data collection was performed between July and August 2011. The sampling technique adopted was intentionally the non-probabilistic. The applied sample size calculation was infinite population. The selected variables to compose the study were the following: social demographical aspects, reproductive and hormonal life aspects, health care aspects and awareness concerning the pathology/disease. The structured interview counted with a form of 63 questions...