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The helminth fauna of juvenile green sea turtles (Chelonia mydas Linnaeus, 1758) is still poorly known. Herein, we study the gastrointestinal helminths of 28 juvenile green sea turtles found stranded on the north coast of Rio de Janeiro state, Brazil. All turtles were infected showing a rich helminth fauna. In total, 14802 trematodes belonging to 30 species and 5 families including Micros-caphidiidae, Plagiorchiidae, Pronocephalidae, Hapalotrematidae, and Telorchiidae were recovered. An unidentified nematode specimens was also found. The mean intensity was 536 (95% CI = 362 - 853) (range: 1 - 2831), and the species richness was 7.86 (95% CI = 6.46 - 9.21) (range: 1 - 17). The coast of Rio de Janeiro state represents new locality records for Angiodictyum posterovitellatum, Microscaphidium aberrans, M. warui, Octangium hyphalum, O. sagitta, Enodiotrema reductum and Pleurogonius laterouterus. This study confirms that the green sea turtle harbors the richest helminth fauna among sea turtle species and provides useful information on the gastrointestinal helminths of a poorly known stage in the life cycle of this endangered chelonian.
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Introducción La quimioterapia neoadyuvante (QTn) es una herramienta de uso cada vez más frecuente en el tratamiento del cáncer de mama. su repercusión es objetivada a partir de parámetros clínicos (examen físico y estudios por imagen) y parámetros anatomo-patológicos sobre la pieza quirúrgica. Existe variabilidad en el impacto de la Qt según el subtipo molecular. Este estudio evalúa el grado de respuesta (clínica y patológica) a la QTn de las pacientes con cáncer de mama subtipo luminal y la tasa de cirugías conservadoras en este subgrupo. Objetivo Describir la tasa de respuesta clínica y patológica obtenida en el subgrupo de pacientes luminales y evaluar la tasa de conversión a cirugía conservadora luego del tratamiento neoadyuvante. Material y método Se analizaron 220 historias clínicas pertenecientes a pacientes que realizaron neoadyuvancia en el periodo 2014-2017 en el Servicio de Patología Mamaria del Hospital Oncológico Marie Curie. Se incluyeron 78 pacientes con diagnóstico de carcinoma invasor subtipo luminal A y B, Her 2 negativas. Se evaluó la tasa de respuesta clínica, patológica y la tasa de cirugía conservadora. Resultados Se clasificaron como Luminal A el 26.9% (n=21) de las 78 pacientes, y Luminal B el 73.1% (n=57). La distribución por tamaño tumoral fue: T1 en el 1.25% (n= 1); T2 en 46.1% (n= 36); T3 en 37.2% (n=29) y T4 en el 15.4% (n=12) de los casos. No presentaban compromiso axilar (N0) el 24.3% de las pacientes (n=19), y se vio afectación ganglionar el 75.5 % (n= 59). El Estadio clínico más frecuente fue el III A (32% = 25 pacientes). El 60.3% (47 pacientes) de los casos tenía indicación de mastectomía de inicio y el 39.7% (41 pacientes) eran candidatas a cirugía conservadora. Posterior a la quimioterapia, se indicaron cirugías conservadoras en el 52.6 % (n=41) y mastectomía en el 47.4% (n=37), con una tasa de conversión a cirugía conservadora del 24.4%. La respuesta clínica completa fue del 28.2% (n=22) y la respuesta patológica completa del 16.6%. Conclusión Se observó una respuesta clínica y patológica acorde a la experiencia de otros centros, sobre todo en el subtipo luminal B, con una alta tasa de conversión a cirugía conservadora del 24.4%. Esto nos permite considerar la quimioterapia neoadyuvante como una opción de tratamiento válida para aquellas pacientes con cáncer de mama subtipo luminal B- Her 2 negativa.
Introduction Neoadjuvant chemotherapy (QTn) is a tool that is increasingly used in the treatment of breast cancer. its repercussion is objectified based on clinical parameters (physical examination and imaging studies) and anatomo-pathological parameters on the surgical specimen. There is variability in the impact of Qt according to the molecular subtype. This study evaluates the degree of response (clinical and pathological) to the QTn of patients with luminal subtype breast cancer and the rate of conservative surgeries in this subgroup. Objective To describe the clinical and pathological response rate in the subgroup of luminous patients and to evaluate the conversion rate in a conservative surgery after neoadjuvant treatment. Material and method We will analyze 220 clinical records belonging to patients that developed during the 2014-2017 period in the Breast Pathology Service of the Marie Curie Oncology Hospital. We included 78 patients with a diagnosis of invasive carcinoma luminal subtype A and B, their 2 negative. The clinical and pathological response rate and the rate of conservative surgery in each group were evaluated. Results Luminal A was classified as 26.9% (n = 21) of the 78 patients, and Luminal B was 73.1% (n = 57). The distribution by tumor size was: T1 at 1.25% (n = 1); T2 at 46.1% (n = 36); T3 in 37.2% (n = 29) and T4 in 15.4% (n = 12) of the cases. There is no axillary involvement (N0) in 24.3% of the patients (n = 19), and the ganglion was affected 75.5% (n = 59). The most frequent clinical stage was III A (32% = 25 patients). Sixty-three percent (47 patients) of the cases had an initial mastectomy indication and 39.7% (41 patients) were candidates for conservative surgery. After chemotherapy, conservative surgeries were indicated in 52.6% (n = 41) and mastectomy in 47.4% (n = 37), with a conversion rate to conservative surgery of 24.4%. The complete clinical response was 28.2% (n = 22) and the complete pathological response was 16.6%. Conclusion A clinical and pathological response was observed according to the experience of other centers, especially in luminal subtype B, with a high conversion rate to conservative surgery of 24.4%. This allows us to consider neoadjuvant chemotherapy as a valid treatment option for those patients with luminal B-Her 2 negative breast cancer.
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Humanos , Feminino , Neoplasias da Mama , Terapia Neoadjuvante , Tratamento FarmacológicoRESUMO
The probabilities of locating peaks with a high relative peak-area uncertainty were determined empirically with nine types of peak-location software used in laboratories engaged in gamma-ray spectrometry measurements. It was found that it is not possible to locate peaks with a probability of 0.95, when they have a relative peak-area uncertainty in excess of 50%. Locating peaks at these relatively high peak-area uncertainties with a probability greater than 0.95 is only possible in the library-driven mode, where the peak positions are supposed a-priori. The deficiencies of the library-driven mode and the possibilities to improve the probabilities of locating peaks are briefly discussed.
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CONTEXT: Bothrops snakes are the most frequent agents of snakebites in South and Central America. Acute kidney injury (AKI) is one of its complications and has multifactorial origin. Thrombotic microangiopathy (TMA)-induced AKI in snakebites is uncommon and is not described in Bothrops envenomation. CASE DETAILS: We report two cases of patients bitten by young Bothrops jararaca who developed AKI induced by TMA. Both patients evolved with mild envenomation and received the specific antivenom within 4 h after the snakebite. None of them had hypotension or shock, bleeding or secondary infection. Patient 1 (P1) was diabetic and using oral hypoglycemic drugs, and patient 2 (P2) was hypertensive without regular use of medication. On admission, both patients had levels of fibrinogen lower than 35 mg/dL, D-dimer higher than 10,000 ng/mL. They evolved with AKI, thrombocytopenia, normal coagulation assays, anemia, lactate dehydrogenase (LDH) elevation, low haptoglobin levels, negative direct antiglobulin test, and presence of schizocytes in peripheral blood. Only P1 required renal replacement therapy, and plasmapheresis was not required. Both patients were discharged and did not require outpatient dialysis, and subsequently had normal creatinine levels. DISCUSSION: TMA may occur in Bothrops jararaca envenomation, even in mild cases that received early specific antivenom
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Animais , Mordeduras de Serpentes , Bothrops , Insuficiência Renal , Microangiopatias TrombóticasRESUMO
CONTEXT: Bothrops snakes are the most frequent agents of snakebites in South and Central America. Acute kidney injury (AKI) is one of its complications and has multifactorial origin. Thrombotic microangiopathy (TMA)-induced AKI in snakebites is uncommon and is not described in Bothrops envenomation. CASE DETAILS: We report two cases of patients bitten by young Bothrops jararaca who developed AKI induced by TMA. Both patients evolved with mild envenomation and received the specific antivenom within 4 h after the snakebite. None of them had hypotension or shock, bleeding or secondary infection. Patient 1 (P1) was diabetic and using oral hypoglycemic drugs, and patient 2 (P2) was hypertensive without regular use of medication. On admission, both patients had levels of fibrinogen lower than 35 mg/dL, D-dimer higher than 10,000 ng/mL. They evolved with AKI, thrombocytopenia, normal coagulation assays, anemia, lactate dehydrogenase (LDH) elevation, low haptoglobin levels, negative direct antiglobulin test, and presence of schizocytes in peripheral blood. Only P1 required renal replacement therapy, and plasmapheresis was not required. Both patients were discharged and did not require outpatient dialysis, and subsequently had normal creatinine levels. DISCUSSION: TMA may occur in Bothrops jararaca envenomation, even in mild cases that received early specific antivenom.
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Injúria Renal Aguda/etiologia , Bothrops , Mordeduras de Serpentes/complicações , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/etiologia , Injúria Renal Aguda/terapia , Idoso , Animais , Antivenenos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/complicações , Mordeduras de Serpentes/terapiaRESUMO
Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP-schizophrenia spectrum (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73). We also verified whether gene expression was correlated to severity of psychotic, manic, depressive symptoms and/or functional impairment. All participants were antipsychotic-naive. After the psychiatric interview, blood samples were collected and the expression of 12 psychotic-disorder-related genes was evaluated by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients compared with that in SCZ patients and healthy controls, suggesting that expression of these genes is associated more specifically to manic features. Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients than in healthy controls, indicating that these genes are psychosis related (independent of diagnosis). No correlation was found between gene expression and severity of symptoms or functional impairment. Our findings suggest that genes related to neurodevelopment are altered in psychotic disorders, and some might support the differential diagnosis between schizophrenia and bipolar disorder, with a potential impact on the treatment of these disorders.
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Transtorno Bipolar/genética , Regulação da Expressão Gênica/genética , Transtornos Psicóticos/genética , Esquizofrenia/genética , Psicologia do Esquizofrênico , Adulto , Proteínas de Transporte/genética , Estudos de Casos e Controles , RNA Helicases DEAD-box/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Proteína Básica da Mielina/genética , Proteínas Proto-Oncogênicas c-akt/genética , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Valores de Referência , Ribonuclease III/genética , Esquizofrenia/diagnóstico , Estatística como Assunto , Adulto JovemRESUMO
Socio-economic and environmental changes are well known causes of demographic collapse of agrarian cultures. The collapse of human societies is a complex phenomenon where historical and cultural dimensions play a key role, and they may interact with the environmental context. However, the importance of the interaction between socio-economic and climatic factors in explaining possible breakdowns in Native American societies has been poorly explored. The aim of this study is to test the role of socio-economic causes and rainfall variability in the collapse suffered by the Aymara people of the semiarid Andean region of Tarapacá during the period 1820-1970. Our motivation is to demonstrate that simple population dynamic models can be helpful in understanding the causes and relative importance of population changes in Andean agro-pastoral societies in responses to socio-environmental variability. Simple logistic models that combine the effects of external socio-economic causes and past rainfall variability (inferred from Gross Domestic Product [GDP] and tree-rings, respectively) were quite accurate in predicting the sustained population decline of the Aymara people. Our results suggest that the depopulation in the semiarid Tarapacá province was caused by the interaction among external socio-economic pressures given by the economic growth of the lowlands and demands for labor coupled with a persistent decline in rainfall. This study constitutes an example of how applied ecological knowledge, in particular the application of the logistic equation and theories pertaining to nonlinear population dynamics and exogenous perturbations, can be used to better understand major demographic changes in human societies.
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Meio Ambiente , Indígenas Sul-Americanos/história , Indígenas Sul-Americanos/estatística & dados numéricos , Fatores Socioeconômicos , Agricultura/história , Agricultura/métodos , Agricultura/tendências , Chile , História do Século XIX , História do Século XX , Humanos , Densidade Demográfica , Dinâmica Populacional , População Rural/história , População Rural/estatística & dados numéricos , População Rural/tendências , Mudança Social/históriaRESUMO
Loxosceles gaucho spider venom induces in vitro platelet activation and marked thrombocytopenia in rabbits. Herein, we investigated the involvement of platelets in the development of the dermonecrosis induced by L. gaucho venom, using thrombocytopenic rabbits as a model. L. gaucho venom evoked a drop in platelet and neutrophil counts 4 h after venom injection. Ecchymotic areas at the site of venom inoculation were noticed as soon as 4 h in thrombocytopenic animals but not in animals with initial normal platelet counts. After 5 days, areas of scars in thrombocytopenic animals were also larger, evidencing the marked development of lesions in the condition of thrombocytopenia. Histologically, local hemorrhage, collagen fiber disorganization, and edema were more severe in thrombocytopenic animals. Leukocyte infiltration, predominantly due to polymorphonuclears, was observed in the presence or not of thrombocytopenia. Thrombus formation was demonstrated by immunohistochemistry at the microvasculature, and it occurred even under marked thrombocytopenia. Taken together, platelets have an important role in minimizing not only the hemorrhagic phenomena but also the inflammatory and wound-healing processes, suggesting that cutaneous loxoscelism may be aggravated under thrombocytopenic conditions.
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Plaquetas/fisiologia , Endotélio Vascular/efeitos dos fármacos , Diester Fosfórico Hidrolases/toxicidade , Dermatopatias/sangue , Dermatopatias/patologia , Pele/efeitos dos fármacos , Venenos de Aranha/toxicidade , Animais , Contagem de Células Sanguíneas , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Necrose , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Tempo de Protrombina , Coelhos , Pele/irrigação sanguínea , Pele/patologia , Dermatopatias/induzido quimicamente , Trombocitopenia/sangue , Fator de von Willebrand/análiseRESUMO
Plant growth-promoting rhizobacteria (PGPR) affect growth of host plants through various direct and indirect mechanisms. Three native PGPR (Pseudomonas putida) strains isolated from rhizospheric soil of a Mentha piperita (peppermint) crop field near Córdoba, Argentina, were characterised and screened in vitro for plant growth-promoting characteristics, such as indole-3-acetic acid (IAA) production, phosphate solubilisation and siderophore production, effects of direct inoculation on plant growth parameters (shoot fresh weight, root dry weight, leaf number, node number) and accumulation and composition of essential oils. Each of the three native strains was capable of phosphate solubilisation and IAA production. Only strain SJ04 produced siderophores. Plants directly inoculated with the native PGPR strains showed increased shoot fresh weight, glandular trichome number, ramification number and root dry weight in comparison with controls. The inoculated plants had increased essential oil yield (without alteration of essential oil composition) and biosynthesis of major essential oil components. Native strains of P. putida and other PGPR have clear potential as bio-inoculants for improving productivity of aromatic crop plants. There have been no comparative studies on the role of inoculation with native strains on plant growth and secondary metabolite production (specially monoterpenes). Native bacterial isolates are generally preferable for inoculation of crop plants because they are already adapted to the environment and have a competitive advantage over non-native strains.
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Endófitos , Mentha piperita/crescimento & desenvolvimento , Óleos Voláteis/metabolismo , Estruturas Vegetais/crescimento & desenvolvimento , Pseudomonas , Microbiologia do Solo , Argentina , Endófitos/metabolismo , Ácidos Indolacéticos/metabolismo , Mentha piperita/metabolismo , Monoterpenos/metabolismo , Fosfatos/metabolismo , Desenvolvimento Vegetal , Estruturas Vegetais/metabolismo , Pseudomonas/metabolismo , Rizosfera , Sideróforos/metabolismo , Solo , Especificidade da EspécieRESUMO
Introducción: La educación médica debería garantizar la formación de profesionales competentes que posean los conocimientos, las destrezas y las actitudes planificados en la capacitación. En general, los programas no tienen en cuenta a la urgencia, que no figura como materia específica en los programas de grado. Objetivos: Cuantificar las competencias adquiridas por los internos en el Departamento de Urgencias y en Terapia Intensiva, estableciendo el grado de cumplimiento entre lo planificado y lo logrado; desglosar el grado de cumplimiento según las diferentes áreas de la competencia clínica. Materiales y Métodos: Diseño prospectivo, de observación, longitudinal, analítico. Se incluyeron 93 alumnos del ciclo clínico que realizaron el internado rotatorio (2000-2009). Se valoró el cumplimiento de 37 competencias que se clasificaron por área: actitudes, conocimientos y destrezas, en números de 9, 5 y 23, respectivamente. Resultados: El cumplimiento global de las competencias en el área de emergentología y terapia intensiva es del 61,18% (IC95% 59,20-63,13). Al desglosar por área de la competencia clínica, se halla que las actitudes fueron del 66,26%; los conocimientos, del 63,28% y las destrezas, del 58,15%. Clasificándolas según el grado de cumplimiento, se establece una escala con cumplimiento alto (76-100%), medio (51-75%) y bajo (<51%). Conclusiones: Los aspectos actitudinales y cognitivos de las competencias tuvieron un cumplimiento medio. La mitad de las competencias vinculadas a destrezas tuvo un cumplimiento medio-alto.(AU)
Introduction: Medical education should guarantee the formation of competent professionals with the knowledge, skills and attitudes planned in training. Generally programs do not bear in mind the urgency, which does not appear as a specific subject in the university. Objectives: To quantify the competitions acquired by the boarders in the Emergency Department and the Intensive Care Unit, establishing the degree of fulfillment between what was planned and what was achieved; to perceive the degree of fulfillment according to the different areas of clinical competition. Materials and Methods: Prospective, observational, longitudinal and analytical study. We included 93 students from the clinical cycle who performed rotating boarding school (2000-2009). Fulfillment of 37 competitions classified by area: attitudes, knowledge and skills, in numbers of 9, 5 and 23, respectively, was evaluated. Results: The global fulfillment of the competitions was 61.18% (CI95%: 59.20-63.13). Specifically, in each area of the clinical competition, we found that the attitudes were 66.26%, knowledge 63.28% and skills 58.15%. Classifying them according to the degree of fulfillment, a scale is established: high (76-100%), medium (51-75%) and low (<51%). Conclusions: Attitude and cognitive aspects of the competitions had average fulfillment. Half of the competitions linked to skills had average-high fulfillment.(AU)
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Humanos , Estudantes , Competência Clínica , Cuidados Críticos , EmergênciasRESUMO
The consistency of the published values for fission averaged cross-sections of threshold reactions induced in a nuclear reactor is analyzed. The influence of the literature data involved in the determination of these cross-sections is discussed. Renormalizations based on cross-sections value for the standard reactions, isotopic abundances of the precursors and radiation emission probabilities of the radionuclide under study and the monitor, are applied to the evaluation of the cross-sections for the reactions: (46)Ti(n,p)(46)Sc; (47)Ti(n,p)(47)Sc; (48)Ti(n,p)(48)Sc; and (64)Zn(n,p)(64)Cu.
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Radioisótopos de Cobre/química , Nêutrons , Fissão Nuclear , Radiometria/métodos , Escândio/química , Titânio/química , Radioisótopos de Zinco/química , Radioisótopos de Cobre/efeitos da radiação , Isótopos/química , Isótopos/efeitos da radiação , Doses de Radiação , Escândio/efeitos da radiação , Titânio/efeitos da radiação , Radioisótopos de Zinco/efeitos da radiaçãoRESUMO
Estudou-se o perfil de proteínas totais (PLB) e proteínas ligadoras de heparina (PLH) do plasma seminal de touros da raça Gir e suas associações com parâmetros andrológicos e fertilidade in vitro. A concentração da PLB variou de 4,1 a 167,9 mg/mL e da PLH entre 0,02096 e 0,19025 (%). O perfil cromatográfico apresentou nove picos de afinidade para PLB e cinco picos para PLH. As associações significativas foram: PLB x taxa de blastocistos, PLH do pico 1 x taxa de blastocistos, PLH do pico 5 x taxa de clivagem e blastocistos. Nenhuma proteína estudada apresentou associação com parâmetros andrológicos. (AU)
It was studied the seminal plasma total protein (TP) and heparin binding protein (PLH) profiles of Gyr bulls and their associations with andrological parameters and in vitro fertility. Total protein concentration varied between 4,1 a 167,9 mg/ml and heparin binding protein 0,02096 to 0,19025 (%). Chromatographic profile of TP presented nine peaks. PLH presented five affinity peaks. Associations were for: total proteins x blastocysts rate, peak 1 heparin binding proteins x blastocysts rate, peak 5 heparin binding protein x cleavage rate and blastocysts rate. However no protein showed association with andrological parameters. (AU)
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Animais , Masculino , Bovinos , Sêmen/enzimologia , Proteínas/análise , Heparina/química , Fertilização in vitro , Espermatozoides/enzimologia , Blastocisto , Preservação do SêmenRESUMO
Estudou-se o perfil de proteínas totais (PLB) e proteínas ligadoras de heparina (PLH) do plasma seminal de touros da raça Gir e suas associações com parâmetros andrológicos e fertilidade in vitro. A concentração da PLB variou de 4,1 a 167,9 mg/mL e da PLH entre 0,02096 e 0,19025 (%). O perfil cromatográfico apresentou nove picos de afinidade para PLB e cinco picos para PLH. As associações significativas foram: PLB x taxa de blastocistos, PLH do pico 1 x taxa de blastocistos, PLH do pico 5 x taxa de clivagem e blastocistos. Nenhuma proteína estudada apresentou associação com parâmetros andrológicos.
It was studied the seminal plasma total protein (TP) and heparin binding protein (PLH) profiles of Gyr bulls and their associations with andrological parameters and in vitro fertility. Total protein concentration varied between 4,1 a 167,9 mg/ml and heparin binding protein 0,02096 to 0,19025 (%). Chromatographic profile of TP presented nine peaks. PLH presented five affinity peaks. Associations were for: total proteins x blastocysts rate, peak 1 heparin binding proteins x blastocysts rate, peak 5 heparin binding protein x cleavage rate and blastocysts rate. However no protein showed association with andrological parameters.
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Masculino , Animais , Bovinos , Espermatozoides/enzimologia , Fertilização in vitro , Heparina/química , Proteínas/análise , Sêmen/enzimologia , Blastocisto , Preservação do SêmenRESUMO
A new fibrinogenolytic metalloproteinase (Bmoo FIBMP-I) was purified from Bothrops moojeni snake venom. This enzyme was isolated through a combination of three chromatographic steps (ion-exchange, molecular exclusion, and affinity chromatography). Analyses by reverse phase chromatography, followed by mass spectrometry, showed the presence of enzyme isoforms with average molecular mass of 22.8 kDa. The SDS-PAGE analyses showed a single chain of 27.6 kDa, in the presence and absence of reducing agent. The protein has a blocked N-terminal. One of the peptides obtained by enzymatic digestion of a reduced and S-alkylated isoform was completely sequenced by mass spectrometry (MS/MS). Bmoo FIBMP-I showed similarity with hemorrhagic factor and several metalloproteinases (MP). This enzyme degraded Aα-chain faster than the Bß-chain and did not affect the γ-chain of bovine fibrinogen. The absence of proteolytic activity after treatment with EDTA, together with the observed molecular mass, led us to suggest that Bmoo FIBMP-I is a member of the P-I class of the snake venom MP family. Bmoo FIBMP-I showed pH-dependent proteolytic activity on azocasein, but was devoid of coagulant, defibrinating, or hemorrhagic activities. The kinetic parameters of proteolytic activity in azocasein were determined (V max = 0.4596 Uh(-1)nmol(-1) ± 0.1031 and K m = 14.59 mg/mL ± 4.610).
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MOTIVATION: Protein-protein interfaces contain important information about molecular recognition. The discovery of conserved patterns is essential for understanding how substrates and inhibitors are bound and for predicting molecular binding. When an inhibitor binds to different enzymes (e.g. dissimilar sequences, structures or mechanisms what we call cross-inhibition), identification of invariants is a difficult task for which traditional methods may fail. RESULTS: To clarify how cross-inhibition happens, we model the problem, propose and evaluate a methodology called HydroPaCe to detect conserved patterns. Interfaces are modeled as graphs of atomic apolar interactions and hydrophobic patches are computed and summarized by centroids (HP-centroids), and their conservation is detected. Despite sequence and structure dissimilarity, our method achieves an appropriate level of abstraction to obtain invariant properties in cross-inhibition. We show examples in which HP-centroids successfully predicted enzymes that could be inhibited by the studied inhibitors according to BRENDA database. AVAILABILITY: www.dcc.ufmg.br/~raquelcm/hydropace CONTACT: valdetemg@ufmg.br; raquelcm@dcc.ufmg.br; santoro@icb.ufmg.br SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Serina Proteases/química , Serina Proteases/metabolismo , Software , Animais , Interações Hidrofóbicas e Hidrofílicas , Modelos Biológicos , Ovomucina/farmacologia , Proteínas/farmacologia , PerusRESUMO
An analytical method based on capillary electrophoresis (CE) with a partially aqueous electrolyte system was developed to enable the free fatty acids of Brazil nut oil to be identified in cosmetic formulations. In this study, a gel cream formulation was developed and its oil phase was extracted with a mixture of chloroform-methanol-water (1:2:0.8 v/v/v). The chloroform layer was saponified with a methanolic solution of NaOH (0.5 mol L-1) at 75-80 °C for 25 minutes. Experiments were carried out on a Beckman PACE/MDQ CE system (Fullerton, CA, USA) equipped with an on-column, diode-array detection system set at 254 nm and at 25ºC. The electrolyte consisted of 12.5 mmol L-1 sodium tetraborate buffer pH 7.0, 12.5 mmol L-1 polyoxyethylene 23-lauryl ether, 7.5 mmol L-1 sodium dodecylbenzenesulfonate (used as chromophore for indirect UV detection) and acetonitrile (35% v/v). The proposed method allowed the separation and identification of the fatty acids of Brazil nut oil in a cosmetic gel cream, as well as enabling possible interference by the oily phase components in the formulation to be identified.
Um método de análise por eletroforese capilar com sistema de eletrólito parcialmente aquoso foi desenvolvido para identificar os ácidos graxos livres do óleo de Castanha do Brasil em formulações cosméticas. No presente trabalho foi desenvolvida uma formulação cosmética (gel creme) cuja fase oleosa foi extraída com uma mistura de clorofórmio-metanol-água (1:2:0.8 v/v/v). A camada de clorofórmio, foi saponificada com solução de NaOH em metanol (0,5 mol L-1) a 75-80 °C durante 25 minutos. Os experimentos foram realizados em sistema de eletroforese capilar Beckman PACE/MDQ (Fullerton, CA, USA), com detecção de arranjo de diodos a 254 nm e a 25 ºC. O eletrólito utilizado foi 12,5 mmol L-1 de tetraborato de sódio tampão a pH 7,0, 12,5 mmol L-1 de éter de polioxietileno 23-lauril, 7,5 mmol L-1 de dodecilbenzenosulfonato de sódio (utilizado como agente cromóforo para detecção UV indireta) e acetonitrila (35% v/v). O método proposto permitiu a separação e a identificação dos ácidos graxos do óleo de Castanha do Brasil em formulações cosméticas, bem como possibilitou a identificação de interferências presentes na fase oleosa da formulação.
Assuntos
Cosméticos , Eletroforese Capilar , Ácidos GraxosRESUMO
BACKGROUND: The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents. OBJECTIVE: To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan. METHODS: Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia. RESULTS: Platelet counts were markedly diminished in rats administered with either ARPI (± 88%) or busulfan (± 96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase. CONCLUSIONS: Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.
Assuntos
Plaquetas/citologia , Bothrops , Carragenina/farmacologia , Venenos de Crotalídeos/farmacologia , Hiperalgesia/induzido quimicamente , Animais , Aspirina/farmacologia , Plaquetas/enzimologia , Bussulfano/toxicidade , Clopidogrel , Ciclo-Oxigenase 1/efeitos dos fármacos , Hiperalgesia/prevenção & controle , Masculino , Ratos , Ratos Wistar , Trombocitopenia/induzido quimicamente , Ticlopidina/análogos & derivados , Ticlopidina/farmacologiaRESUMO
Background:The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents. Objective:To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan. Methods:Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia. Results:Platelet counts were markedly diminished in rats administered with either ARPI (±88%) or busulfan (±96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase. Conclusions:Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.
Assuntos
Animais , Ratos , Bothrops , Serpentes/classificação , Venenos de Serpentes , Hemorragia , InflamaçãoRESUMO
Despite the clinical relevance of anti-factor VIII (FVIII) antibodies (anti-FVIII inhibitors) impairing haemostatic activity of haemophilia A (HA) patients, the immunological mechanisms underlying their production are unknown. Aiming to understand more clearly the immune response in patients with [HAα-FVIII(+)] and without [HAα-FVIII(-)] anti-FVIII inhibitors, we have characterized the cytokine pattern of peripheral blood leucocytes, using an in vitro stimulation of whole blood samples with plasma-derived (pFVIII) or recombinant FVIII (rFVIII). The results highlighted decreased levels of tumour necrosis factor (TNF)-α(+) neutrophils with higher interleukin (IL)-5/TNF-α ratio in HAα-FVIII(+). All HA samples displayed decreased levels of IL-10(+) monocytes when compared to the blood donor (BD) samples. HAα-FVIII(+) showed lower levels of TNF-α(+) monocytes and increased IL-10/TNF-α ratio. Analysis of adaptive immunity revealed increased levels of interferon (IFN)-γ(+) , TNF-α(+) and IL-4(+) T-cells, from both CD4(+) and CD8(+) T cells, in HAα-FVIII(-) when compared to BD. Moreover, increased frequency of IL-10(+) B cells and higher levels of α-FVIII IgG1 were observed in HAα-FVIII(-). Basal levels of cytokine(+) B-cells, similar to BD, and higher levels of α-FVIII IgG4 are major features in HAα-FVIII(+). The global cytokine profile demonstrated a major anti-inflammatory/regulatory pattern in HAα-FVIII(+), confirmed by the in vitro stimuli with pFVIII or rFVIII. The polarized anti-inflammatory/regulatory immune response in HAα-FVIII(+) and the mixed pattern with a bias towards an inflammatory cytokine profile, modulated by IL-4 in HAα-FVIII(-), may be the key element to drive the development of distinct subclasses of anti-FVIII antibodies. These finding have implications for the design of safe and effective therapeutic protocols to control inhibitors synthesis in HA patients.
Assuntos
Citocinas/metabolismo , Fator VIII/metabolismo , Hemofilia A/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Formação de Anticorpos/genética , Autoanticorpos/genética , Autoanticorpos/metabolismo , Células Cultivadas , Criança , Citocinas/genética , Citocinas/imunologia , Fator VIII/genética , Fator VIII/imunologia , Feminino , Hemofilia A/sangue , Hemofilia A/genética , Hemofilia A/terapia , Humanos , Imunidade Inata , Ativação Linfocitária , Masculino , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Equilíbrio Th1-Th2RESUMO
Microscopy has been used in the routine evaluation of sperm metabolism. Nevertheless, it has limited capacity to preview male fertility. As calorimetry may be used to evaluate directly the metabolic activity of a biological system, the aim of this study was to use microcalorimetry as an additive method for sperm metabolism evaluation of cooled equine semen. Two ejaculates of four stallions were collected and motility, viability (eosin 3%) and membrane functional integrity (hyposmotic swelling test) of spermatozoa were evaluated. Sperm samples were processed following different protocols and the metabolism of these samples was accessed by calorimetry. Centrifugation is part of some of these processing protocols and although this procedure has been deleterious for sperm viability and plasma membrane integrity, no decrease in sperm motility was observed. Microcalorimetry was capable of detecting the positive effect of re-suspending the sperm pellet with Kenney extender. Thus, the use of microcalorimetry offered additional information for equine sperm metabolism evaluation and was efficient in detecting important information from sperm cell metabolism.