Bothropic and crotalic venoms: main aspects and derivative products for therapeutic and diagnostic purposes - a brief approach / Venenos botrópicos e crotálicos: principais aspectos e produtos derivados para fins terapêuticos e diagnósticos - uma breve abordagem

 Ophidian accidents, mainly by snakes of the Bothrops and Crotalus genera, are an important public health problem, especially in tropical countries due to the high rate of occurrence and lethality, being considered as a neglected disease and with challenging treatment. Thus, more knowledge that can minimize the devastating effects of snakebites is required.  This brief review addressed aspects related to snakebite accidents belonging to the Bothrops and Crotalus genera, with regard to their epidemiology, some biochemical characteristics of the respective venoms and the development of pharmaceutical products from snake venoms for therapeutic and diagnostic purposes

roteiro para a gestão dos fluxos gerados na atividade agropecuária

A grande dimensão dos custos económicos e ambientais decorrente da intensificação dos sistemas agrícolas, pecuários e agroindustriais, torna imperiosa a procura de soluções que valorizem os seus efluentes e coprodutos, visando tanto a redução da sua toxicidade como o desenvolvimento sustentável de novos processos e de novos produtos. No Âmbito do Programa de Desenvolvimento Rural 2020, Medida 1. Promoção para a Inovação, Ação 1.1. Inovação por Grupos Operacionais, foi financiado o GoEfluentes - Efluentes de pecuária: abordagem estratégica à valorização agronómica/energética dos fluxos gerados na atividade agropecuária (PDR2020-1.0.1-FEADER-031831). (https://projects.iniav.pt/goefluentes), apoio que confirma a importância com que se revestem as preocupações ambientais do sector

Efeito do ácido acetilsalicílico na ativação plaquetária e perfil oxidativo em pacientes com Diabetes Mellitus tipo 2

Exportado OPUSMade available in DSpace on 2019-08-13T20:58:52Z (GMT). No. of bitstreams: 1 disserta__o_final_rita_carolina_2dez2012.__doc_1_.pdf: 1938860 bytes, checksum: d78b700faf6efdf8022d66492bd8f76c (MD5) Previous issue date: 22O diabetes mellitus tipo 2 (DM2) é uma doença metabólica associada a complicações macro e microvasculares, onde se observa hiperativação de plaquetas e consequente aumento na formação das micropartículas de plaquetas (MP). O estresse oxidativo também está relacionado às complicações macrovasculares do diabetes, sendo que as plaquetas ativadas produzem espécies reativas do oxigênio (ROS) que são pró-trombóticas e, além disso, as ROS estão relacionadas com a propagação da ativação plaquetária. O Ácido Acetilsalicílico (AAS) é um agente antiplaquetário utilizado na prevenção de eventos aterotrombóticos por bloquear a formação de tromboxano A2, via inibição da ciclooxigenase-1 plaquetária. O efeito do AAS pode ser determinado pelos níveis de 2,3-dinor-tromboxano B2 (2,3-dinor-TXB2) e do 11-dhidro-tromboxano B2 (11-dhTXB2). Para avaliar a resposta ao tratamento com AAS, por meio da ativação plaquetária e do perfil oxidativo, foram coletadas amostras de sangue e urina de 81 pacientes com DM2 em dois momentos distintos, a saber: imediatamente antes do início do tratamento e aos 15 dias de uso diário de 100 mg deste medicamento. Foram quantificados os níveis urinários do 11 dhTXB2 e plasmáticos do 2,3 dinorTXB2 e das MP. Ademais, foram determinados os níveis de espécies reativas ao ácido tiobarbitúrico (TBARS) e do 3-(4,5-dimetiltiazol-2yl)-2,5-difenil brometo de tetrazolina (MTT), para avaliação da peroxidação lipídica e da capacidade antioxidante do soro, respectivamente. Foi observada uma diminuição significativa dos níveis de 2,3 dinorTXB2 (p < 0,001) e de 11 dhTXB2 (p =0,00) aos 15 dias de uso do AAS, porém a maioria dos pacientes apresentou uma redução dos níveis destes marcadores de, no máximo, 90%. Por outro lado, a comparação dos níveis de MP, TBARS e MTT antes e durante o uso de AAS não apresentou diferença significativa. Estes resultados analisados em conjunto, evidenciam que o uso do AAS não modificou os perfis de micropartículas e oxidativo, e que os pacientes não apresentaram uma resposta equânime e satisfatória ao uso deste medicamento. Tal achado está em consonância com relatos prévios da literatura de que os pacientes com DM2 não se beneficiam de forma igual com o uso do AAS para prevenção primária de eventos aterotrombóticos.Type 2 diabetes mellitus (DM2) is a metabolic disorder associated with cardiovascular complications, hyperactivation of platelets and consequent increased formation of platelet microparticles (MP). Oxidative stress is also related to macrovascular and microvascular complications of the diabetes, and the activated platelets produce reactive oxygen species (ROS) which are prothrombotic and moreover, ROS are related to the propagation of platelet activation. Acetylsalicylic acid (ASA) is an antiplatelet agent used in the prevention of atherothrombotic events by blocking the formation of thromboxane A2 via inhibition of platelet cyclooxygenase-1. The effect of ASA can be determined by the levels of 2,3-dinor-thromboxane B2 (2,3-dinor-TXB2), and 11-dehydro-thromboxane B2 (11-dhTXB2). In order to evaluate the response to ASA by means platelet activation and oxidative profile, we collected samples of blood and urine of 81 patients with DM2 in two distinct moments, the first immediately prior to initiation of treatment with ASA and the second, at the fifteenth day of treatment with 100 mg of this medication daily. These samples were analyzed to determine the urinary 11-dhTXB2 and plasma levels of 2.3 dinorTXB2 and MPs. Furthermore, were measured levels of thiobarbituric acid reactive species (TBARS) and 3 - (4,5-dimethylthiazol-2yl) -2,5-diphenyltetrazolium bromide (MTT) for evaluation of lipid peroxidation and antioxidant status of serum, respectively. It was observed a significant decrease in the levels of 2.3 dinorTXB2 (p <0.001) and 11-dhTXB2 (p = 0.00), however most of the patients showed a reduction in levels of these markers, at the maximum, 90%. On the other side, no significant difference was found between the levels of MP, TBARS and MTT before and after use of AAS. These results analysed together indicate that ASA did not change the MP and oxidative profiles and that patients did not show an equal and satisfactory response to this drug. This finding is consistent with previous reports in the literature that patients with DM2 do not benefit in an equal way from the use of aspirin for primary prevention of atherothrombotic events

Thrombin generation assays for global evaluation of the hemostatic system: perspectives and limitations

Abstract The existing techniques to evaluate hemostasis in clinical laboratories are not sensitive enough to detect hypercoagulable and mild hypocoagulable states. Under different experimental conditions, the thrombin generation test may meet these requirements. This technique evaluates the overall balance between procoagulant and anticoagulant forces and has provided new insights in our understanding of the coagulation cascade, as well as of the diagnosis of hypocoagulability and hypercoagulability conditions. Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. The calibrated automated thrombogram method is an open system, in which different antibodies, proteins, enzymes and peptides can be introduced to answer specific questions regarding hemostatic processes. The thrombin generation test has great clinical potential, such as in monitoring patients taking anticoagulants and antiplatelet drugs, screening for genetic or acquired thrombotic disorders, and evaluating bleeding risk control in patients with hemophilia using bypass agents or replacement therapy. Different to conventional coagulation tests, the thrombin generation test can be used for an overall evaluation of hemostasis, the results of which can then be used to evaluate specific characteristics of hemostasis, such as prothrombin time, activated partial thromboplastin time, and levels of fibrinogen and other coagulation factors. The introduction of this method will contribute to a better understanding and evaluation of overall hemostatic processes; however, this method still requires standardization and clinical validation

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter

Chronic Lymphocytic Leukemia (CLL): evaluation of AKT protein kinase and microRNA gene expression related to disease pathogenesis

The present study evaluated 56 patients diagnosed with Chronic Lymphocytic Leukemia (CLL) and a control group of 44 clinically healthy subjects with no previous history of leukemia. Genetic expressions of AKT and microRNAs were evaluated by quantitative PCR (qPCR). A significant increase in AKT gene expression in patients when compared to controls was observed (p&nbsp;= 0.017). When the patients were stratified according to Binet subgroups, a significant difference was observed between the subgroups, with this protein kinase appearing more expressed in the B+C subgroup (p&nbsp;= 0.013). Regarding miRNA expression, miR-let-7b and miR-26a were reduced in CLL patients, when compared to controls. However, no significant differences were observed in these microRNA expressions between the Binet subgroups (A versus B+C). By contrast, miR-21 to miR-27a oncogenes showed no expression difference between CLL patients and controls. AKT protein kinase is involved in the signaling cascade that occurs with BCR receptor activation, leading to increased lymphocyte survival and protection against the induction of cell death in CLL. Thus, increased AKT protein kinase expression and the reduction of miR-let-7b and miR-26a, both tumor suppressors, may explain increased lymphocyte survival in CLL patients and may be promising markers for the prognostic evaluation of this disease

Circulating microparticles and thrombin generation in patients with Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia (CLL) has shown great biological heterogeneity, with a variable prognosis, and a short survival in some patients. In this light, the present study focused on the prognostic utility of circulating microparticles (MPs) and a Thrombin Generation (TG) Profile for thrombotic risk and disease progression in CLL patients. Circulating microparticles and TG were evaluated in 35 patients with CLL and 35 healthy individuals. For circulating microparticles, significant differences were observed among the following groups: MPs derived from endothelial cells (p&nbsp;= 0.002), B lymphocytes (p&nbsp;&lt; 0.001), platelets (p&nbsp;= 0.003), and Tissue Factor MPs in monocytes (p&nbsp;&lt; 0.001). In all cases, MP values were higher for the CLL group. When compared to the controls, CLL patients presented a decrease in TG, characterized by a reduced endogen thrombin potential (ETP) (p&nbsp;= 0.031). When the results were analyzed according to the Binet stage, as compared to the controls, the Binet B+C group also presented lower ETP values (p&nbsp;= 0.009). No significant differences were observed between the control and the Binet A groups or between the Binet A and the Binet B + C groups. Although hemostatic alterations may occur in patients with CLL, these parameters do not seem to be useful to indicate disease progression

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved