Antibodies as Snakebite Antivenoms: Past and Future.

Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab')2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.

Pathophysiology of COVID-19: Critical Role of Hemostasis.

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.

Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses.

A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.

Design, synthesis, and evaluation of Bothrops venom serine protease peptidic inhibitors.

BACKGROUND: In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation. METHODS: In order to search for tools to improve the antivenom's, 6-mer peptides were designed based on a specific substrate for Bothrops jararaca venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes. RESULTS: Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on B. jararaca venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity. CONCLUSION: Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving Bothrops spp. envenomation treatment.

Design of bioactive peptides derived from CART sequence isolated from the toadfish Thalassophryne nattereri.

The emergence of bacterial resistance due to the indiscriminate use of antibiotics warrants the need for developing new bioactive agents. In this context, antimicrobial peptides are highly useful for managing resistant microbial strains. In this study, we report the isolation and characterization of peptides obtained from the venom of the toadfish Thalassophryne nattereri. These peptides were active against Gram-positive and Gram-negative bacteria and fungi. The primary amino acid sequences showed similarity to Cocaine and Amphetamine Regulated Transcript peptides, and two peptide analogs-Tn CRT2 and Tn CRT3-were designed using the AMPA algorithm based on these sequences. The analogs were subjected to physicochemical analysis and antimicrobial screening and were biologically active at concentrations ranging from 2.1 to 13 µM. Zeta potential analysis showed that the peptide analogs increased the positive charge on the cell surface of Gram-positive and Gram-negative bacteria. The toxicity of Tn CRT2 and Tn CRT3 were analyzed in vitro using a hemolytic assay and tetrazolium salt reduction in fibroblasts and was found to be significant only at high concentrations (up to 40 µM). These results suggest that this methodological approach is appropriate to design novel antimicrobial peptides to fight bacterial infections and represents a new and promising discovery in fish venom.

Leptospira interrogans Bat proteins impair host hemostasis by fibrinogen cleavage and platelet aggregation inhibition.

Leptospirosis is a worldwide spread zoonosis, caused by pathogenic Leptospira. Evidences suggest that compromised hemostasis might be involved in the leptospirosis pathophysiology. In the genome of L. interrogans serovar Copenhageni, we found two genes coding for proteins which comprise von Willebrand factor (VWF) A domains (BatA and BatB). As VWF A domains exhibit multiple binding sites which contributes to human VWF hemostatic functions, we hypothesized that the L. interrogans BatA and BatB proteins could be involved in the hemostatic impairment during leptospirosis. We have cloned, expressed in Escherichia coli, and purified recombinant BatA and BatB. The influence of recombinant BatA and BatB on different in vitro hemostatic assays evaluating the enzymatic activity, platelet aggregation and fibrinogen integrity was investigated. We describe BatB as a new serine protease which is able to cleave thrombin chromogenic substrate, fibrin, fibrinogen, gelatin and casein; while BatA is active only towards fibrinogen. BatA and BatB interfere with the platelet aggregation induced by VWF/ristocetin and thrombin. Our results suggest an important role of the L. interrogans serovar Copenhageni Bat proteins in the hemostasis dysfunction observed during leptospirosis and contribute to the understanding of the leptospirosis pathophysiological mechanisms.

Fatores emocionais associados ao hábito de fumar em usuários de um programa antitabagismo / Emotional factors associated with smoking in individuals enrolled in a tobacco cessation program / Factores emocionales asociados con el hábito de fumar de usuarios de un programa de cesación de tabaquismo

Objetivo: Caracterizar a população atendida por um programa de tratamento do tabagismo e identificar os fatores emocionais associados ao hábito de fumar. Métodos: Estudo transversal, realizado em 2016, com dados secundários extraídos dos registros do programa de tratamento do fumante do município de Água Clara, Mato Grosso do Sul, Brasil. Os dados analisados referem-se a 173 participantes que realizaram a entrevista inicial do programa, de janeiro de 2012 a setembro de 2015. Foram estudadas as variáveis: sexo, idade, história tabagística, grau de dependência da nicotina, fatores emocionais e outras condições de saúde-doença. Analisaram-se os dados por meio de estatística descritiva, e a associação do grau de dependência aos fatores emocionais foi analisada pelo teste exato de Fisher. Resultados: Verificou-se a predominância do sexo feminino (63,6%, n=110); com idade média de 45,99 anos; média de idade de início do hábito de fumar de 14,38 anos; e média de tempo de uso do cigarro de 31,62 anos. Dos sintomas apresentados, predominaram os transtornos emocionais (75,1%, n=130), com confirmação de 38,2% (66) para depressão. Com relação ao grau de dependência da nicotina, 68,2% (118) apresentaram grau "elevado ou muito elevado", sendo observada associação entre nível "elevado e muito elevado" de dependência e fatores emocionais, como ansiedade e depressão (p<0,05). Conclusão: Os participantes do programa são mulheres em idade adulta, com tempo prolongado de uso do cigarro e decorrente presença de comprometimentos na saúde. Foi observada associação entre fatores emocionais como ansiedade e depressão e o maior grau de dependência da nicotina.

Objective: To characterize the population enrolled in a smoking treatment program and to identify the emotional factors associated with smoking. Methods: Cross-sectional study carried out in 2016 using secondary data extracted from the records of a smoking treatment program in the municipality of Água Clara, Mato Grosso do Sul, Brazil. The data analyzed refer to 173 participants who had undergone the initial interview of the program from January 2012 to September 2015. The following variables were studied: gender, age, smoking history, degree of nicotine dependence, emotional factors and other health-disease conditions. The data were analyzed using descriptive statistics, and the association between the degree of dependence and emotional factors was analyzed using Fisher's exact test. Results: There was a predominance of women (63.6%, n=110), with a mean age of 45.99 years, mean age of onset of smoking of 14.38 years and mean time of cigarette use of 31.62 years. Of the symptoms presented, emotional disorders were predominant (75.1%, n=130), with a 38.2% (66) rate of depression. Regarding the degree of nicotine dependence, 68.2% of the participants presented high or very high levels, with an association between high and very high levels of dependence and emotional factors such as anxiety and depression (p<0.05). Conclusion: The program participants are adult women with a long time of cigarette use and consequently compromised health. There was an association between emotional factors and a greater degree of nicotine dependence.

Objetivo: Caracterizar la población asistida por un programa para tratamiento del tabaquismo e identificar los factores emocionales asociados al hábito de fumar. Métodos: Estudio transversal realizado en 2016 con los datos secundarios de registros del programa de tratamiento para fumadores del municipio de Agua Clara, Mato Grosso do Sul, Brasil. Los datos analizados son de 173 participantes que realizaron la entrevista inicial del programa entre enero de 2012 y septiembre de 2015. Se estudiaron las variables sexo, edad, historia de tabaco, grado de dependencia de nicotina, factores emocionales y otras condiciones de salud-enfermedad. Se analizaron los datos a través de la estadística descriptiva. La asociación del grado de dependencia y los factores emocionales ha sido analizada por el test exacto de Fisher. Resultados: Se verificó la predominancia del sexo femenino (63,6%, n=110) con la media de edad de 45,99 años; la media de edad del inicio del hábito de fumar de 14,38 años; y la media del tiempo de consumo de cigarro de 31,62 años. Entre los síntomas presentados hubo predominancia para los trastornos emocionales (75,1%, n=130) y la confirmación del 38,2% (66) de depresión. Respecto el grado de dependencia de nicotina el 68,2% (118) presentaron grado "elevado o muy elevado" con asociación entre el nivel "elevado y muy elevado" de dependencia y los factores emocionales como la ansiedad y la depresión (p<0,05). Conclusión: Los participantes del programa son mujeres en edad adulta con largo uso del cigarro y la presencia de problemas de salud. Se observó la asociación entre los factores emocionales y el mayor grado de dependencia de nicotina.

Leptospira Infection Interferes with the Prothrombinase Complex Assembly during Experimental Leptospirosis.

Leptospirosis is a worldwide zoonotic and neglected infectious disease of human and veterinary concern, caused by pathogenic Leptospira species. Although bleeding is a common symptom of severe leptospirosis, the cause of hemorrhage is not completely understood. In severe infections, modulation of hemostasis by pathogens is an important virulence mechanism, and hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. Here, we analyze the coagulation status of experimentally infected hamsters in an attempt to determine coagulation interferences and the origin of leptospirosis hemorrhagic symptomatology. Hamsters were experimentally infected with L. interrogans. The lungs, kidneys, and livers were collected for culture, histopathology, and coagulation assays. L. interrogans infection disturbs normal coagulation in the organs of animals. Our results suggest the presence of a thrombin-like factor or FX activator, which is able to activate FII in the leptospirosis organ extracts. The activity of those factors is accelerated in the prothrombinase complex. Additionally, we show for the first time that live leptospires act as a surface for the prothrombinase complex assembly. Our results contribute to the understanding of leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments in the severe manifestations of the disease.

[Antituberculosis-drug resistance in the border of Brazil with Paraguay and Bolivia]. / Resistência às drogas antituberculose na fronteira do Brasil com Paraguai e Bolívia.

OBJECTIVE: To estimate the rate of drug resistance among pulmonary tuberculosis (PTB) cases in the state of Mato Grosso do Sul, Brazil, and specifically in the border areas with Paraguay and Bolivia, as well as to identify associated risk factors. METHOD: The present cross-sectional, epidemiological study focused on PTB cases recorded between January 2007 and December 2010 in the State Reportable Disease Information System with results of susceptibility tests to rifampicin, isoniazid, ethambutol, and streptomycin. Dependent variables were development of resistance to a single drug or any combination of drugs. Independent variables were being a new or treated case, living in border areas, presence/absence of diabetes, and history of alcoholism. RESULTS: There were 789 TBP cases with susceptibility testing. The following characteristics were associated with resistance: treated case (P = 0.0001), border region (P = 0.0142), alcoholism (P = 0.0451), and diabetes (P = 0.0708). The rates of combined, primary, and acquired resistance for the state were 16.3%, 10.6%, and 39.0%, vs. 22.3%, 19.2%, and 37.5% for the border region. The rates of combined, primary, and acquired multidrug resistance for the state were 1.8%, 0.6%, and 6.3%, vs. 3.1%, 1.2%, and 12.5% for the border region. CONCLUSIONS: In the border region, the state should investigate drug resistance in all patients with respiratory symptoms, determine the pattern of resistance in confirmed cases, adopt directly observed treatment for cases of PTB, and develop health actions together with neighboring countries. Across the state, the levels of acquired resistance should be monitored, with investigation of resistance in all treated cases and implementation of directly observed treatment especially among patients with diabetes or alcoholism.

Resistência às drogas antituberculose na fronteira do Brasil com Paraguai e Bolívia / Antituberculosis-drug resistance in the border of Brazil with Paraguay and Bolivia

RESUMO Objetivo Estimar as taxas de resistência às drogas entre casos de tuberculose pulmonar (TBP) para o estado de Mato Grosso do Sul, Brasil, e especificamente para a região da fronteira com Paraguai e Bolívia, além de identificar fatores de risco associados. Métodos O presente estudo epidemiológico, transversal, enfocou os casos de TBP registrados de janeiro de 2007 a dezembro de 2010 no Sistema de Informação de Agravos de Notificação da Secretaria de Estado de Saúde com resultados do teste de suscetibilidade a rifampicina, isoniazida, etambutol e estreptomicina. Definiram-se como variáveis dependentes o desenvolvimento de resistência a uma única droga e a qualquer combinação de drogas. As variáveis independentes foram ser caso novo ou tratado, residência em região de fronteira ou outra região, presença ou ausência de diabetes e história de alcoolismo. Resultados Foram identificados 789 casos de TBP com teste de suscetibilidade. As características associadas à resistência foram: caso tratado (P=0,0001), região de fronteira (P=0,0142), alcoolismo (P=0,0451) e diabetes (P=0,0708). As taxas de resistência combinada, primária e adquirida no estado foram de 16,3%, 10,6% e 39,0%, e na fronteira, de 22,3%, 19,2% e 37,5%. As taxas de resistência a múltiplas drogas combinada, primária e adquirida no estado foram de 1,8%, 0,6% e 6,3%, e na fronteira, de 3,1%, 1,2% e 12,5%. Conclusões O estado deve, na região de fronteira, realizar cultura em todos os sintomáticos respiratórios, investigar o padrão de resistência nos casos confirmados, adotar o tratamento diretamente observado nos casos de TBP e desencadear ações de saúde conjuntas com os países fronteiriços. Em todo o estado, é necessário monitorar os níveis de resistência adquirida, ampliar a investigação de resistência para todos os casos tratados e adotar o tratamento diretamente observado prioritariamente entre pacientes com alcoolismo e diabetes.

ABSTRACT Objective To estimate the rate of drug resistance among pulmonary tuberculosis (PTB) cases in the state of Mato Grosso do Sul, Brazil, and specifically in the border areas with Paraguay and Bolivia, as well as to identify associated risk factors. Method The present cross-sectional, epidemiological study focused on PTB cases recorded between January 2007 and December 2010 in the State Reportable Disease Information System with results of susceptibility tests to rifampicin, isoniazid, ethambutol, and streptomycin. Dependent variables were development of resistance to a single drug or any combination of drugs. Independent variables were being a new or treated case, living in border areas, presence/absence of diabetes, and history of alcoholism. Results There were 789 TBP cases with susceptibility testing. The following characteristics were associated with resistance: treated case (P = 0.0001), border region (P = 0.0142), alcoholism (P = 0.0451), and diabetes (P = 0.0708). The rates of combined, primary, and acquired resistance for the state were 16.3%, 10.6%, and 39.0%, vs. 22.3%, 19.2%, and 37.5% for the border region. The rates of combined, primary, and acquired multidrug resistance for the state were 1.8%, 0.6%, and 6.3%, vs. 3.1%, 1.2%, and 12.5% for the border region. Conclusions In the border region, the state should investigate drug resistance in all patients with respiratory symptoms, determine the pattern of resistance in confirmed cases, adopt directly observed treatment for cases of PTB, and develop health actions together with neighboring countries. Across the state, the levels of acquired resistance should be monitored, with investigation of resistance in all treated cases and implementation of directly observed treatment especially among patients with diabetes or alcoholism.

Exploring the in vivo wound healing effects of a recombinant hemolin from the caterpillar Lonomia obliqua.

BACKGROUND: Hemolin proteins are cell adhesion molecules from lepidopterans involved in a wide range of cell interactions concerning their adhesion properties. However, hemolin's roles in cell proliferation and wound healing are not fully elucidated. It has been recently reported that rLosac, a recombinant hemolin from the caterpillar Lonomia obliqua, presents antiapoptotic activity and is capable of improving in vitro wound healing. Therefore, this study aimed to explore rLosac's in vivo effects using a skin wound healing model in rats. METHODS: Circular full-thickness wounds in the rat dorsum skin were treated either with rLosac, or with saline (control), allowing healing by keeping the wounds occluded and moist. During the wound healing, the following tissue regeneration parameters were evaluated: wound closure and collagen content. Furthermore, tissue sections were subjected to histological and immunohistochemical analyses. RESULTS: The rLosac treatment has demonstrated its capacity to improve wound healing, as reflected in findings of a larger number of activated fibroblasts, proliferation of epithelial cells, increase of collagen type 1, and decrease of inflammatory infiltrate. CONCLUSION: The findings have indicated the rLosac protein as a very promising molecule for the development of new wound-healing formulations.

Amblyomin-X having a Kunitz-type homologous domain, is a noncompetitive inhibitor of FXa and induces anticoagulation in vitro and in vivo.

BACKGROUND: Cancer has long been associated with thrombosis and many of the standard chemotherapeutics used to treat cancer are pro-thrombotic. Thus, the identification of novel selective anticancer drugs that also have antithrombotic properties is of enormous significance. Amblyomin-X is an anticancer protein derived from the salivary glands of the Amblyomma cajennense tick. METHODS: In this work, we determined the inhibition profile of Amblyomin-X and its effect on activated partial thromboplastin time (aPTT) and prothrombin time (PT), using various approaches such as, kinetic analyses, amidolytic assays, SDS-PAGE, and mass spectrometry. RESULTS: Amblyomin-X inhibited factor Xa, prothrombinase and tenase activities. It was hydrolyzed by trypsin and plasmin. MS/MS data of tryptic hydrolysate of Amblyomin-X suggested the presence of Cys(8)-Cys(59) and Cys(19)-Cys(42) but not Cys(34)-Cys(55) disulfide bond. Instead of Cys(34)-Cys(55), two noncanonical Cys(34)-Cys(74) and Cys(55)-Cys(74) disulfide bonds were identified. Furthermore, when Amblyomin-X (1mg/kg) injected in rabbits, it prolonged aPTT and PT. CONCLUSION: Amblyomin-X is a noncompetitive inhibitor (Ki=3.9µM) of factor Xa. It is a substrate for plasmin and trypsin, but not for factor Xa and thrombin. The disulfide Cys(34)-Cys(55) bond probably scrambles with interchain seventh free cysteine residues (Cys(74)) of Amblyomin-X. The prolongation of PT and aPTT is reversible. GENERAL SIGNIFICANCE: In term of anticoagulant property, this is structural and functional characterization of Amblyomin-X. All together, these results and previous findings suggest that Amblyomin-X has a potential to become an anticancer drug with antithrombotic property.

Leprosy in Brazilian counties bordering Paraguay: Mato Grosso do Sul State, 2001-2011.

BACKGROUND: In Mato Grosso do Sul state, Brazil, the dry border shared with Paraguay is a territory marked by facilities in the flow of goods, services and people, bringing difficulties for surveillance of communicable diseases. PURPOSE: The purpose of this study is to characterise leprosy epidemiologically in dry border municipalities of Mato Grosso do Sul in Brazil with contiguous urban areas with neighbouring Paraguayan counties, in the period 2001-2011. METHODS: This is an exploratory descriptive investigation that includes the four dry border municipalities of Mato Grosso do Sul (Coronel Sapucaia, Paranhos, Ponta Porã, and Sete Quedas) in Brazil whose urban areas are contiguous with Paraguay. Data comprised the period 2001-2011. RESULTS: The rates of leprosy detection and prevalence oscillated along the study period, increasing in the last 2 years investigated. The detection rate was 3.3/10,000 in 2011, up from 1.7/10,000 in 2009. Prevalence was 5.3/10,000 in 2011, up from 2.5/10,000 in 2009. The Virchowian disease form was predominant in 8 of the 11 years investigated. Most patients were male, with limited formal education (44.2% with less than 4 years of study). CONCLUSION: In the border of Brazil, most (greater than 70%) of the cases detected were classified as multibacillary. The higher coefficient found in Brazilian municipalities was the Virchowian clinical form, which can influence the operational classification in multibacillary. The predominance of the Virchowian clinical form, larger number of patients in rural areas and children under 15 years of age provides new information on the manifestations of the disease in the border territories. The study revealed that municipalities with contiguous cross-border urban areas with Paraguay have unique epidemiological features that need to be addressed by policies focusing leprosy as a public health priority.

Spatial distribution and environmental factors associated to phlebotomine fauna in a border area of transmission of visceral leishmaniasis in Mato Grosso do Sul, Brazil.

BACKGROUND: Mato Grosso do Sul has been undergoing a process of urbanization which results in loss of native vegetation. This withdrawal makes vectors of man and domestic animals closer, causing changes in the epidemiology of diseases such as American Visceral Leishmaniasis. The aim of the study was to evaluate the phlebotomine fauna and environmental issues related to the transmission of AVL in Ponta Porã, Mato Grosso do Sul, between 2009 and 2010. METHODS: Vegetation of the urban area was evaluated by Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI) and Soil Adjusted Vegetation Index (SAVI). RESULTS: The results showed that the phlebotomine fauna of the city consists of five species, especially Lutzomyia longipalpis (Lutz and Neiva, 1912), the vector of Leishmania (Leishmania) infantum. Predominance of males was observed. The insects were captured in greater quantity in the intradomicile. Lu. longipalpis was the most frequent and abundant species, present throughout the year, with a peak population after the rainy season. Vectors can be found in high amounts in forest and disturbed environments. CONCLUSIONS: The finding of Lu. longipalpis in regions with little vegetation and humidity suggests that the species is adapted to different sorts of environmental conditions, demonstrating its close association with man and the environment it inhabits. The tourist feature of Ponta Porã reinforces its epidemiological importance as a vulnerable city. The geographical location, bordering Paraguay through dry border, makes possible the existence of a corridor of vectors and infected dogs between the two countries.

Hepatitis B virus infection in a population exposed to occupational hazards: firefighters of a metropolitan region in central Brazil.

INTRODUCTION: By the nature of their activities, firefighters are exposed to a high risk of contracting hepatitis B virus (HBV) as most of the Fire Brigade occurrences in Campo Grande, State of Mato Grosso do Sul (MS), Brazil, are related to the rescue of victims of traffic accidents and the transportation of clinical and psychiatric emergencies. The aim of this study was to investigate the seroepidemiological profile of HBV infection in firefighters from the City of Campo Grande, central Brazil. METHODS: The research involved 308 firefighters. After giving written consent, they were interviewed and blood was collected for the detection of HBsAg, anti-HBs and total anti-HBc of enzyme-linked immunosorbent assays (ELISA). RESULTS: The participants had an average of 36.4 years of age (SD ± 6.5), being 89.9% male. Blood tests revealed 6.5% of seropositivity for hepatitis B (HB) infection (n=20), and 1% for HbsAg. Isolated anti-HBs markers, indicative of vaccine immunity, were found in 66.9% of the participants and 28.2% were susceptible to infection. With regard to risk factors for HB infection, multivariate regression analysis showed a statistically significant association with length of service; and prevalence was higher in individuals with over 20 years of service. CONCLUSIONS: The prevalence of HB found among the firefighters was low and length of time in the profession was found to be a risk factor. Non-occupational risk factors did not influence the occurrence of HB infection in the population studied.

Analysis of working conditions focusing on biological risk: firefighters in Campo Grande, MS, Brazil.

UNLABELLED: Firefighters are exposed to a wide range of risks, among them, biological risk. The objective was to analyze working conditions of firefighters in the city of Campo Grande, MS, Brazil, focusing on risk conditions of exposure to biological material. Three hundred and seven (307) firefighters were interviewed for data collection and observed for ergonomic job analysis (AET). RESULTS: 63.5% of the firefighters suffered some kind of job related accident with blood or body fluids. Statistically significant association was found between having suffered accidents at work and incomplete use of personal protective equipment (PPE). About AET regarding the biological risks, 57.1% of all patients had blood or secretions, which corresponds in average to 16.0% of the total work time, based on a working day of 24 h. Besides biological risks, other stressing factors were identified: emergency and complexity of decision, high responsibility regarding patients and environment, and conflicts. Health promotion and accident prevention actions must be emphasized as measures to minimize these risks.

Maternal decision on obtaining prenatal care: a study in Brazil.

OBJECTIVE: to address the social aspects of pregnancy and the views of pregnant women regarding prenatal assistance in Brazil. DESIGN: this qualitative study was focused on describing the Social Representations of prenatal care held by pregnant women. The discourse of the collective subject (DCS) framework was used to analyse the data collected, within the theoretical background of social representations, as proposed and developed by Serge Moscovici. PARTICIPANTS AND SETTING: 21 pregnant women who were users of the publicly funded Brazilian unified health-care system and resided in the area served by its family health programme in a low- to middle-income neighbourhood on the outskirts of Campo Grande, the capital of the state of Mato Grosso do Sul, in southwestern Brazil. Data were collected by conducting in-depth, face-to-face interviews from January to October 2006. FINDINGS: all participants were married. Formal education of the participants was less than five years in four cases, between five and eight years in six cases, and greater than 11 years in 10 cases. Nine participants had informal jobs and earned up to US$ 200 per month, four participants had administrative jobs and earned over US$ 500 per month, and eight participants did not work. No specific racial/ethnic background predominated. Lack of adherence to prenatal care allowed for the identification of two DCS themes: 'organisation of prenatal care services' and 'lifestyle features'. KEY CONCLUSIONS: the respondents were found to have negative feelings about pregnancy which manifest as many fears, including the fear of harming their children's health, of being punished during labour, and of being reprimanded by health-care professionals for overlooking their prenatal care, in addition to the insecurity felt towards the infant and self. IMPLICATIONS FOR PRACTICE: the findings reveal that communication between pregnant women and health-care professionals has been ineffective and that prenatal care has not been effective for the group interviewed--features that are likely to be found among other low- to middle-income groups living elsewhere in Brazil.

[Social representations of nurses on the integral care available to women through Brazil's basic healthcare network]. / Representações sociais das enfermeiras sobre a integralidade na assistência à saúde da mulher na rede básica.

Brazil's Basic Healthcare Act establishes the principle of integral care in terms of networking between services and professional practices, to which we add a dimension: the configuration of public policies. Nurses were selected for this survey as they handle the initial contacts with women and also because we believe they are endowed with an across-the-board view of integral care during the various phases in the lives of this population. This paper examines the social representations of nurses on the scope of the integral care available to women through Brazil's Basic Healthcare Network, explored through qualitative interviews with ten nurses in Mato Grosso do Sul State. These data were analyzed through the Collective Subject Discourse (CSD) approach, based on the Theory of Social Representations. The findings are presented in seven Collective Subject Discourses that describe the main ideas identified during the interviews. This leads to the conclusion that nurses have a fragmented view of women's healthcare, still guided by physical complaints; they cannot define integral care, repeating the discourse of the holistic approach without understanding what this really means; they work on an individualized basis, feeling that this area is not structured to offer integral care.

[Vulnerability of men who have sex with men in the context of AIDS]. / Vulnerabilidade de homens que fazem sexo com homens no contexto da AIDS.

The number of AIDS cases in men who have sex with men (MSM) decreased in the initial years of the epidemic, but the percentage of cases in this group has remained unaltered in the last five years. This study, aimed to improve knowledge on the impact of AIDS in the daily lives of MSM, was conducted in Campo Grande, Mato Grosso do Sul State, Brazil, using a questionnaire and interviews. The results show that MSM perceive their vulnerability to HIV infection, referring to inconsistent condom use and multiple sex partners, given that 65% of homosexuals, 75% of bisexuals, and 33% of transvestites reported up to 5 partners in the previous month and emphasizing that 59% of the group reported more than 11 partners during the same period. The susceptibility of certain groups and the identification and understanding of their specificities pose a major challenge in any geographic context where such conditions are present.

Structural insights into the catalytic mechanism of sphingomyelinases D and evolutionary relationship to glycerophosphodiester phosphodiesterases.

Spider venom sphingomyelinases D catalyze the hydrolysis of sphingomyelin via an Mg(2+) ion-dependent acid-base catalytic mechanism which involves two histidines. In the crystal structure of the sulfate free enzyme determined at 1.85A resolution, the metal ion is tetrahedrally coordinated instead of the trigonal-bipyramidal coordination observed in the sulfate bound form. The observed hyperpolarized state of His47 requires a revision of the previously suggested catalytic mechanism. Molecular modeling indicates that the fundamental structural features important for catalysis are fully conserved in both classes of SMases D and that the Class II SMases D contain an additional intra-chain disulphide bridge (Cys53-Cys201). Structural analysis suggests that the highly homologous enzyme from Loxosceles bonetti is unable to hydrolyze sphingomyelin due to the 95Gly-->Asn and 134Pro-->Glu mutations that modify the local charge and hydrophobicity of the interfacial face. Structural and sequence comparisons confirm the evolutionary relationship between sphingomyelinases D and the glicerophosphodiester phosphoesterases which utilize a similar catalytic mechanism.