Avaliação a longo prazo do tratamento etiológico da doença de Chagas com benznidazol

O objetivo deste artigo é verificar o resultado da terapêutica específica com o benznidazol na doença de Chagas aguda e crônica, após prazo longo de seguimento dos pacientes, tomando como base do critério de cura a reversão pós-terapêutica definitiva à negatividade das reações sorológicas convencionais quantitativas. Foram avaliados 21 pacientes agudos e 113 crônicos, em uma ou outra das diferentes formas clínicas, selecionados por terem sido tratados somente com o benznidazol e acompanhados por longo tempo, de 13 a 21 anos os agudos e de seis a 18 anos os crônicos. Expôs-se o esquema terapêutico, dando ênfase à estreita correlação entre os efeitos colaterais e a dose total de 18 g, aproximadamente, limite obrigatório porque com essa dose surge a polineurite, se já não estiver presente. Foram relacionadas algumas precauções para a segurança do tratamento. Anotou-se a duração da doença, tanto aguda como crônica, circunstância que influi no resultado do tratamento. As reações sorológicas usadas foram a de fixação do complemento, a de imunofluorescência indireta, a de hemaglutinação indireta, e, ocasionalmente, a da ELISA. Verificou-se a cura em 76 por cento dos pacientes agudos e de apenas 8 por cento dos crônicos. Tendo em mente esses resultados, discutiram-se pontos duvidosos da terapêutica etiológica da doença de Chagas, como critério de cura, o papel da imunossupressão para o conhecimento da patogenia da doença e as reações adversas ao medicamento. A hipótese do autor é que na doença crônica de longa duração o T. cruzi persiste nos tecidos, após o tratamento, na grande maioria dos doentes tratados, escapando à ação do medicamento e mantendo positivos os testes sorológicos. Relacionam-se razões que justificam o tratamento na doença crônica. Com relação ao ciclo vital do Trypanosoma cruzi no hospedeiro vertebrado, há ainda pontos obscuros e controvertidos. Embora não haja prova da existência de formas resistentes ou latentes, a descoberta, ao longo dos últimos 15 anos, de que a imunossupressão desencadeia a doença aguda nos pacientes crônicos de longa duração, justifica revisão do assunto.The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of chronic patients

Small but long koch fractal monopole

A small but long wire fractal antenna based on the Koch curve is presented. Experimental and numerical results show that the antenna improves the features of a common linear monopole. The radiation resistance is increased and the Q is reduced at each fractal iteration, approaching the fundamental limit on small antennas.Peer ReviewedPostprint (published version

Evaluation of strengthening techniques of traditional masonry buildings: case study of a four-building aggregate

Increasing appraisal of the durability, conservation state, and changeable use and function of old buildings in urban centers relies a great deal on the structural safety evaluation of vertical load capacity and the ability to resist horizontal forces. The need to assess seismic vulnerability, particularly of traditional masonry buildings, is a key issue. Evaluation of the seismic vulnerability of old buildings is essential in the definition of strengthening needs and minimization of damage from seismic actions in the safeguarding of built heritage. A three-dimensional model was developed for an aggregate of four traditional masonry buildings located in the old city center of Coimbra, in Portugal. The finite element modeling of these buildings has aimed to identify structural fragility, understand the damages detected, and evaluate the global structural safety of these types of buildings. The primary results obtained in this case study helped to interpret the structural damage and stress distribution, and verified global stability and its consequences. Different strengthening techniques to improve the global behavior of these buildings were modeled and analyzed. A comparison of the efficiencies of strengthening strategies is also discussed. DOI: 10.1061/(ASCE)CF.1943-5509.0000164. (C) 2011 American Society of Civil Engineers

Diet of Common buzzard (Buteo buteo) (Linnaeus, 1758) in an area of Northwestern Spain as assessed by direct observation from blinds

Accuracy of raptor diet assessments can vary depending on the technique employed. In the available studies in Spain, the Common buzzard (Buteo buteo) shows a diverse and non-specialized diet, reflecting local and seasonal variation in the prey availability. This study reports information on the diet of the Common buzzard in an area of Northwestern Spain, on the basis of direct observation during 308 h. of four nests from blinds. The delivery prey rate to the nest was of 0.49 ± 0.04 items per hour. From a total of 145 prey delivered to the nests, 64.7% could be determined to the taxonomic level of class, 34.5% to the levels of species, genus or suborder and a 34.5% were undetermined prey items. Mammals and reptiles were the most frequent preys in their diet, while amphibians and birds were much less frequent. These results obtained are in agreement with those from previous studies carried out in the North of Spain based on other assessments raptor diet techniques

Adjuvants : an essential component of neisseria vaccines

Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop "universal" antigens (e.g. proteins, peptides and plasmid DNA) for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases

Multiport Multiband Decoupling Optimization for Miniature Antennas

Multiband multiport antennas are increasingly used for wireless communications and sensing miniature devices. The equations governing the multiport multiband antennas are analyzed in this paper with the objective of drawing the design guidelines for low coupling small antennas. Those guidelines have been applied in the design and optimization of a two-port dual band small antenna of size around λ0/13 x λ0/13 at the lowest frequency. Certain coupling conditions are applied to the port loads achieving a coupling reduction of 8 dB when having a simple two-element real load. A reduction of 27 dB can be obtained when having ideal loads composed by a higher number of elements. The antenna geometry is shown together with coupling minimization results

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.Uma pesquisa clínica compreendendo 80 pacientes de ambos os sexos, de 15 a 55 anos de idade, portadores de esquistossomose mansônica crônica, formas intestinal ou hepatintestinal, foi efetivada para avaliar a eficácia do praziquantel em diferentes esquemas posológicos. Os pacientes foram distribuídos aleatoriamente em quatro grupos, com igual número de casos, sendo tratados com uma das seguintes dosagens: 60 mg/kg em um dia, 60 mg/kg diários por dois dias, 60 mg/kg diários por três dias e 30 mg/kg diários por seis dias. A avaliação da cura parasitológica baseou-se na técnica do oograma quantitativo mediante biópsias da mucosa retal, realizadas antes, bem como um, dois, quatro e seis meses após o tratamento. Concomitantemente, efetuaram se exames de fezes segundo os métodos qualitativo de Hoffman, Pons & Janer e quantitativo de Kato-Katz. A melhor tolerabilidade foi verificada com 30 mg/kg diários durante seis dias, enquanto a maior incidência de efeitos colaterais, em especial tontura e náusea, ocorreu com 60 mg/kg diários durante três dias. Nenhuma reação adversa grave foi observada com o medicamento. Alcançaram se os seguintes índices de cura: 25% com 60 mg/kg em um dia; 60% com 60 mg/kg diários por dois dias; 89,5% com 60 mg/kg diários por três dias e 90% com 30 mg/kg diários por seis dias. Paralelamente houve uma queda de, respectivamente, 64%, 73%, 87% e84% no número mediano de ovos viáveis de S. mansoni por grama de tecido. Assim, constatou se uma correlação direta entre dose e efeito. Os correspondentes índices de cura, segundo os exames de fezes, foram 39%, 80%, 100% e 95% com o método de Hoffman, Pons & Janer e com o de Kato-Katz 89%, 100%, 100% e 100%. A discrepância encontrada nos resultados entre os três métodos parasitológicos decorre da desigualdade na precisão dos mesmos. Quando o número de ovos viáveis por grama de tecido caiu abaixo de 5000, a diferença no percentual de achados falso-negativos entre Hoffmann, Pons & Janer (28%) e Kato-Katz (80%) tornou-se significativa. Quando esse número baixou para menos de 2000, a percentagem de resultados falso-negativos encontrada com Hoffman, Pons & Janer (49%) também passou a ser significativa em relação ao oograma. Em conclusão, ficou provado que o praziquantel é altamente eficaz na infecção pelo S. mansoni. Administrado na dose total de 180 mg/kg, dividida em três ou seis dias, o praziquantel proporcionou 90% de cura. Provavelmente, poderia atingir 100% se a dose total fosse aumentada para 240 mg/kg. Ademais, confirmou-se que o oograma quantitativo consiste no método mais fidedigno para avaliar a eficácia terapêutica de novas drogas na esquistossomose mansônica