Silent Patent Ductus Arteriosus Aneurysm

Ductus arteriosus aneurysm, a rare and potentially fatal condition, has been reported as a complication after surgical ductus arteriosus closure. Its spontaneous appearance as a septic complication, which was common in the presurgical and preantibiotic era, has been rarely reported in the contemporary literature. Persistence of silent ductus arteriosus in healthy children and adults is a frequent condition that currently has an increasing diagnostic possibility due to the availability of more accurate investigative methods, especially echocardiography. We report the case of a 1-year-old child, in whom no previous heart disease was known, who developed a giant aneurysm of the ductus arteriosus during a staphylococcal infection. This complication appeared after craniotomy for emptying an accidental subdural hematoma. This report associates the persistence of ductus arteriosus with a complication considered rare, which has a rapidly fatal evolution.

Differences in the patent management in Brazilian companies with and without plants abroad

This paper compares the procedures of local Brazilian companies (those which have plants in Brazil only) with those of international Brazilian companies (which have plants in at least two countries) regarding the patent management. Although there are a lot more variables to consider when examining the issue of patents in companies, this study presents and analyzes the results of a qualitative research on the decision to patent innovations, the choice of countries where to patent and the strategic significance of patents to the company.

Panorama de propriedade intelectual, transferência de tecnologia e inovação da química brasileira e a comparação com os países do BRIC

Based on Science, Technology & Innovation (ST&I) indicators, Brazil is a competitive and interesting country from the point of view of technological foreign investment. However, it is still incipient with regard to national investments, production of technological knowledge, inbound mobility of scientists and technology transfer to the productive sector. Among many other factors, global patent production is considered as an important indicator of innovation. Likewise, the balance between revenue and expenses obtained through royalties and licensing fees of technologies is also critical in mapping the diffusion and absorption of knowledge. The understanding of intellectual property and its strategic management brings a significant advantage to the economic and technological development of nations, especially in the field of chemistry, which greatly contributes to biotechnology, new materials and microelectronics - three fundamental areas for innovation in developed countries. Therefore, this article aims to map out competencies in chemistry in Brazil and evaluate science, technology and innovation indicators in the country, comparing this dynamic to the one of other BRIC members (Russia, India and China). Chemistry is the fourth biggest field of interest in Brazil based on the number of researchers registered at the governmental platform for researchers, Plataforma Lattes/CNPq, and is preceded by education, medicine and agronomy. The majority of research groups are registered in the area of materials, followed by macromolecules and polymers, pharmaceutical products and basic materials chemistry. These groups represent approximately 77% of research groups analyzed, therefore, indicating a tendency in the country. The analyses of patents in different sub-areas of chemistry reveal that non-residents file most deposits in the country, a probable reflection of the low internal intellectual property culture. Pharmaceutics and Fine Chemistry are prominent areas in the country, in line with the global trend. Among BRIC countries, China has the highest number of patents and of requests for protection in international offices. On the other hand, Brazil has the lowest number of chemical patents published at USPTO, EPO and JPO. An analysis of the transfer of technology data indicates an increase in this activity in various sub-areas of chemistry in the country. Despite the great efforts made by the country to consolidate its national innovation system, more needs to be done to put Brazil in a competitive position. In a globalized world dominated by large players, Brazil needs a lot of progress on ownership and generation of chemistry technologies to strengthen its national sovereignty. It is essential to strengthen chemical research at all levels, from elementary school to university, as an inexhaustible source of knowledge and technology that, when properly protected, may generate real public achievement and social return.

Strategies for price reduction of HIV medicines under a monopoly situation in Brazil

ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

Synanthropic rodent reservoirs of Trypanosoma (Schizotrypanum) cruzi in the valley of Caracas, Venezuela

Direct blood examination and xenodiagnosis of 47 synanthropic rodents (Rattus rattus, R. norvegicus, Mus musculus) captured in the valley of Caracas, Venezuela, revealed trypanosomal infections in 12 R. rattus, 10 with T. lewisi and 2 with T. cruzi. Of the latter the course of parasitemia, the pleomorphism of the bloodstream trypomastigotes, tissue tropism in naturally and experimentally infected rats and mice, host mortality, morphology of fecal parasites in Rhodnius prolixus used for xenodiagnosis, and infectivity of the bug feces for NMRI mice, were all characteristic of Trypanosoma (Schizotrypanum) cruzi. One rat, with a patent parasitemia, had numerous nests of amastigotes in cardiac muscle and moderate parasitism of the smooth muscle of the duodenum and of skeletal muscle. Mice inoculated with fecal flagellates from the bugs had moderate tissue tropism in the same organs and also in the colon and pancreas. The possible role of R. rattus in the establishment of foci of Chagas’ disease in Caracas is discussed

Does Cleome droserifolia have anti-schistosomiasis mansoni activity?

The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46%) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.

Biological implications of the phenotypic plasticity in the Schistosoma mansoni - Nectomys squamipes model

The water-rat Nectomys squamipes is mostly important non-human host in schistosomiasis mansoni transmission in Brazil, due to its susceptibility, high abundance and water-contact pattern. During experimental infection of N. squamipes with Schistosoma mansoni, adult worms show phenotypic plasticity. This finding led us to investigate whether biological behavior is also affected. This was assessed comparing the biological characteristics of four S. mansoni strains: BE (State of Belém do Pará), CE (State of Pernambuco), CMO (State of Rio Grande do Norte) and SJ (State of São Paulo) using laboratory-bred N. squamipes. The infection was monitored by determination of the pre-patent period, fecal egg output, egg viability, intestinal egg count and, infectivity rate. No biological modification was observed in these parameters. Overall results highlight that N. squamipes was susceptible to several S. mansoni strains, suggesting that it might contribute to the maintenance of schistosomiasis mansoni in Brazil.

The effects of the experimental infection from a focus of transmission of Schistosoma mansoni in a population of Biomphalaria tenagophila (D'Orbigny, 1835) in the region of "Vale do Ribeira de Iguape", Brazil

To observe the effects of the parasitic infection on the biology of B. tenagophila, field and laboratory populations of this mollusk from Itariri, in Vale do Ribeira, Brazil, were experimentally infected. Each mollusk received 10 miracidia of Schistosoma mansoni (SJ lineage) and was observed throughout the parasite's development. The biological variables were compared according to the criteria "group" and "infectious phase". The main damage caused by the parasitic infection manifested itself in reproduction, longevity and lesions on the shell of the mollusks in the patent phase. An infection rate of 58.8% was observed. Microanatomical study of the mollusk's digestive gland and ovotestis revealed the presence of evolving larval forms and cercariae. It was concluded that the effects of the parasitic infection on both populations were moderate, despite the low survival rate of the infected mollusks, the damage did not prevent either reproduction or the elimination of cercariae, which continued for a long time.

Estudos sobre a persistência da infectividade do Trypanosoma cruzi: I. Efeito da temperatura sobre a infectividade de flagelados da amostra Peru de T. cruzi obtidos de fezes de triatomíneos

An investigation was made about the influence of environment temperature on the infectivity of flagellate of T. cruzi Peru sample in triatomine feces by periconjuntival instilation in albino mice. The results demonstrate that infection, measured by patent parasitemia decreases when fecal suspension is maintained at 30ºC. The possible implication of these findings in relation to transmission of T. cruzi to human, in field, is briefty discussed.

Trypanosoma cruzi in marsupial didelphids (Philander frenata and Didelhis marsupialis): differences in the humoral immune response in natural and experimental infections

Philander frenata and Didelphis marsupialis harbor parasitism by Trypanosoma cruzi without developing any apparent disease and on the contrary to D. marsupialis, P. frenata maintains parasitism by T. cruzi II subpopulations. Here we compared the humoral immune response of the two didelphids naturally and experimentally infected with T. cruzi II group, employing SDS-PAGE/Western blot techniques and by an Indirect immunofluorescence assay. We also studied the histopathological pattern of naturally and experimentally infected P. frenata with T. cruzi. P. frenata sera recognized more antigens than D. marsupialis, and the recognition pattern did not show any change over the course of the follow up of both didelphid species. Polypeptides of 66 and 90kDa were the most prominent antigens recognized by both species in the soluble and enriched membrane fractions. P. frenata recognized intensely also a 45kDa antigen. Our findings indicate that: 1) there were no quantitative or qualitative differences in the patent or subpatent phases in the recognition pattern of P. frenata; 2) the significant differences in the recognition pattern of parasitic antigens by P. frenata and D. marsupialis sera suggest that they probably "learned" to live in harmony with T. cruzi by different strategies; 3) although P. frenata do not display apparent disease, tissular lesions tended to be more severe than has been described in D. marsupialis; and 4) Both didelphids probably acquired infection by T. cruzi after their evolutionary divergence.

Molecular characterization of Trypanosoma cruzi Mexican strains and their behavior in the mouse experimental model

INTRODUCTION: For a long time, the importance of Chagas disease in Mexico, where many regarded it as an exotic malady, was questioned. Considering the great genetic diversity among isolates of Trypanosoma cruzi, the importance of this biological characterization, and the paucity of information on the clinical and biological aspects of Chagas disease in Mexico, this study aimed to identify the molecular and biological characterization of Trypanosoma cruzi isolates from different endemic areas of this country, especially of the State of Jalisco. METHODS: Eight Mexican Trypanosoma cruzi strains were biologically and genetically characterized (PCR specific for Trypanosoma cruzi, multiplex-PCR, amplification of space no transcript of the genes of the mini-exon, amplification of polymorphic regions of the mini-exon, classification by amplification of intergenic regions of the spliced leader genes, RAPD - (random amplified polymorphic DNA). RESULTS: Two profiles of parasitaemia were observed, patent (peak parasitaemia of 4.6×10(6) to 10(7) parasites/mL) and subpatent. In addition, all isolates were able to infect 100% of the animals. The isolates mainly displayed tropism for striated (cardiac and skeletal) muscle. PCR amplification of the mini-exon gene classified the eight strains as TcI. The RAPD technique revealed intraspecies variation among isolates, distinguishing strains isolated from humans and triatomines and according to geographic origin. CONCLUSIONS: The Mexican T. cruzi strains are myotrophic and belong to group TcI.

Biological behavior of Trypanosoma cruzi stocks obtained from the state of Amazonas, Western Brazilian Amazon, in mice

INTRODUCTION: The biological diversity of circulating Trypanosoma cruzi stocks in the Amazon region most likely plays an important role in the peculiar clinic-epidemiological features of Chagas disease in this area. METHODS: Seven stocks of T. cruzi were recently isolated in the State of Amazonas, Brazil, from humans, wild mammals, and triatomines. They belonged to the TcI and Z3 genotypes and were biologically characterized in Swiss mice. Parasitological and histopathological parameters were determined. RESULTS: Four stocks did not promote patent parasitemia in mice. Three stocks produced low parasitemia, long pre-patent periods, and a patent period of 1 day or oscillating parasitemia. Maximum parasitemia ranged from 1,400 to 2,800 trypomastigotes/0.1mL blood. Mice inoculated with the T. cruzi stocks studied showed low positivity during fresh blood examinations, ranging from 0% to 28.6%. In hemoculture, positivity ranged from 0% to 100%. Heart tissue parasitism was observed in mice inoculated with stocks AM49 and AM61. Stock AM49 triggered a moderate inflammatory process in heart tissue. A mild inflammatory process was observed in heart tissue for stocks AM28, AM38, AM61, and AM69. An inflammatory process was frequently observed in skeletal muscle. Examinations of brain tissue revealed inflammatory foci and gliosis in mice inoculated with stock AM49. CONCLUSIONS: Biological and histopathological characterization allowed us to demonstrate the low infectivity and virulence of T. cruzi stocks isolated from the State of Amazonas.

Molecular and biological characterization of Trypanosoma cruzi strains isolated from children from Jequitinhonha Valley, State of Minas Gerais, Brazil

Introduction The biological diversity of Trypanosoma cruzi strains plays an important role in the clinical and epidemiological features of Chagas disease. Methods Eight T. cruzi strains isolated from children living in a Chagas disease vector-controlled area of Jequitinhonha Valley, State of Minas Gerais, Brazil, were genetically and biologically characterized. Results The characterizations demonstrated that all of the strains belonged to T. cruzi II, and showed high infectivity and a variable mean maximum peak of parasitemia. Six strains displayed low parasitemia, and two displayed moderate parasitemia. Later peaks of parasitemia and a predominance of intermediate and large trypomastigotes in all T. cruzi strains were observed. The mean pre-patent period was relatively short (4.2±0.25 to 13.7±3.08 days), whereas the patent period ranged from 3.3±1.08 to 34.5±3.52 days. Mortality was observed only in animals infected with strain 806 (62.5%). Histopathological analysis of the heart showed that strains 501 and 806 caused inflammation, but fibrosis was observed only in animals infected with strain 806. Conclusions The results indicate the presence of an association between the biological behavior in mice and the genetic characteristics of the parasites. The study also confirmed general data from Brazil where T. cruzi II lineage is the most prevalent in the domiciliary cycle and generally has low virulence, with some strains capable of inducing inflammatory processes and fibrosis.

Aortofemoral thromboendarterectomy

PURPOSE: To study whether endarterectomy is feasible in all patients with aortofemoral atherosclerotic obstruction, considering early and late results. METHODS: A clinical, prospective, and descriptive study carried out in a university hospital. Inclusion criteria were atherosclerotic aortofemoral obstructive disease, clinical status compatible with major surgery, and absence of prior restorative procedure. Exclusion criteria were aneurysm, inflammatory arterial disease, and prior restorative procedure found during surgery. Eighty patients entered the protocol, but 9 were excluded (11.2%). Seventy-one patients, mean age of 57.3 years, underwent endarterectomy. Operative indications were intermittent claudication and critical ischemia. A ring-stripper endarterectomy technique was employed in all patients. Results were related to age, gender, symptoms, presence of diabetes mellitus, extension of endarterectomy, and extent of obstructive disease. Chi square or Fisher exact tests were used when appropriate, and the Wilkoxon (Gehan) test was used to compare survival curves. RESULTS: Sixty-eight (100%) endarterectomies were patent at discharge. The mortality rate was 4.2%. The amputation rate (4.3%) was higher in diabetic patients and when there was associated femoropopliteal obstruction. The 5-year survival rate was 83.3%, and late deaths were mostly cardiovascular. Diabetes mellitus, age above 65 years, and associated femoropopliteal obstruction lowered the survival rate. The 5-year patency rate was 87.0%. Critical ischemia and less extensive endarterectomies were associated with a lower patency rate. There were no anastomotic aneurysms or deep infections. CONCLUSIONS: Aortofemoral thromboendarterectomy is feasible in 90% of patients, early mortality rate is low, diabetic patients and those with associated femoropopliteal obstructive disease have a higher mortality rate, amputation rate is low, late deaths are mostly cardiovascular, and late patency rate is high, and even higher in the intermittent claudication group.