Histological and morphometric investigations of changes induced by the RAL strain of Trypanosoma cruzi in the mouse placenta

Camundongos suíços prenhes(Mus musculus)foram inoculados, intraperitonealmente, com 2 x 10(5) tripomastigotas da cepa RAL de Trypanosoma cruzino 7º dia da prenhez e sacrificados no 19º dia da prenhez. Foram realizados cortes histológicos para avaliar as alterações histológicas e morfométricas das placentas. A cepa RAL mostrou intenso tropismo pela placenta, com parasitismo atingindo as três camadas placentárias. Houve envolvimento da parte materna e fetal das placentas, bem como das células gigantes e dos espongioblastos. As placentas dos animais infectados apresentaram escassas áreas de degeneração e necrose, com calcificação distrófica exígua na decídua. O processo inflamatório era constituído de plasmócitos e linfócitos, revelando comprometimento da decídua. O estudo citométrico das células trofoblásticas gigantes mostrou que as placentas do grupo infectado foram bastante afetadas, inclusive no que se refere ao volume celular. As alterações provocadas pela cepa RAL sobre as células trofoblásticas e a diferença de comportamento observado nas populações celulares das diversas regiões placentárias podem afetar o desenvolvimento intra-uterino, provavelmente por uma produção deficiente de hormônios, tais como o lactogênio placentário, que atua como hormônio de crescimento fetal, ou indiretamente, mediante uma invasão decidual deficiente causada por uma vascularização útero-placentária ineficiente, prejudicando desta maneira a nutrição fetal.Pregnant Swiss mice (Mus musculus) were inoculated intraperitoneally with 2 x 10(5) trypomastigotes of the RAL strain of Trypanosoma cruzi on the 7th day of pregnancy and sacrificed on the 19th day of pregnancy. The placenta was sectioned for the assessment of histological and morphometric changes. The RAL strain showed intense tropism for the placenta, with parasitism reaching the three placental layers. There was involvement of the maternal and fetal portions of the placentas, and also of giant cells and spongioblasts. The placentas of infected animals presented sparse areas of degeneration and necrosis, with mild dystrophic calcification of the decidua. The inflammatory process consisted of plasmocytes and lymphocytes, revealing involvement of the decidua. Cytometric study of giant trophoblastic cells showed that the placentas of the infected group were seriously affected, also with respect to cell volume. The changes provoked by the RAL strain in the trophoblastic cells and the difference in behavior observed in the cell population of the various placental regions may affect intrauterine development, probably by a deficient production of hormones such as placental lactogen, which acts as a fetal growth hormone, or indirectly by deficient tissue invasion caused by inefficient utero-placental vascularization, thus impairing fetal nutrition

Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF

Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV

Continuous Cultivation as a Tool Toward the Rational Bioprocess Development With Pichia Pastoris Cell Factory

The methylotrophic yeast Pichia pastoris (Komagataella phaffii) is currently considered one of the most promising hosts for recombinant protein production (RPP) and metabolites due to the availability of several tools to efficiently regulate the recombinant expression, its ability to perform eukaryotic post-translational modifications and to secrete the product in the extracellular media. The challenge of improving the bioprocess efficiency can be faced from two main approaches: the strain engineering, which includes enhancements in the recombinant expression regulation as well as overcoming potential cell capacity bottlenecks; and the bioprocess engineering, focused on the development of rational-based efficient operational strategies. Understanding the effect of strain and operational improvements in bioprocess efficiency requires to attain a robust knowledge about the metabolic and physiological changes triggered into the cells. For this purpose, a number of studies have revealed chemostat cultures to provide a robust tool for accurate, reliable, and reproducible bioprocess characterization. It should involve the determination of key specific rates, productivities, and yields for different C and N sources, as well as optimizing media formulation and operating conditions. Furthermore, studies along the different levels of systems biology are usually performed also in chemostat cultures. Transcriptomic, proteomic and metabolic flux analysis, using different techniques like differential target gene expression, protein description and 13 C-based metabolic flux analysis, are widely described as valued examples in the literature. In this scenario, the main advantage of a continuous operation relies on the quality of the homogeneous samples obtained under steady-state conditions, where both the metabolic and physiological status of the cells remain unaltered in an all-encompassing picture of the cell environment. This contribution aims to provide the state of the art of the different approaches that allow the design of rational strain and bioprocess engineering improvements in Pichia pastoris toward optimizing bioprocesses based on the results obtained in chemostat cultures. Interestingly, continuous cultivation is also currently emerging as an alternative operational mode in industrial biotechnology for implementing continuous process operations

Activity monitoring in professional soccer goalkeepers during training and match play

The purpose of the present study was to quantify the external load of professional soccer goalkeepers. Twenty professional goalkeepers participated in the study. Data were classified according to the number of days before or after the match day (MD) as follows: MD-4, MD-3, MD-2, MD-1 for the sessions before the match, and MD+1 for the session after the match. The total running distance covered (TD), the high metabolic load (HMLD), the number of high metabolic load efforts (HMLE) were progressively reduced from MD-4 to MD-1 but the values of these variables were always inferior to MD (ES: -3.79 to −1.11). There was a tendency for a progressive reduction in the number of high-intensity accelerations (ACC) and decelerations (DEC) from MD-4 to MD-1 although the values of ACC/DEC were superior to MD (ES: 0.19 to 2.05). Overall, MD-2 was the day with the lowest external load. During training sessions, starter goalkeepers performed more TD (ES: 0.36) and more HMLE (ES: 0.29) than non-starters. External load was progressively decreased in the days before match play for goalkeepers which is reflective of appropriate recovery and preparation practices within the cohort analysed. However, habitual goalkeepers training has an excess of accelerations/decelerations and a lack of running actions performed at high metabolic loads

Avaliação do potencial carcinogênico do cadmio no epitélio de revestimento do palato e gengiva de ratos: estudo morfológico e morfométrico

Cadmium (Cd) is a heavy metal that exerts a variety of toxic effects, chronic and acute, in exposed organisms. The aim of this study was to investigate the carcinogenic potential of Cd in the palatal and gingival epithelium of Wistar rats. Two groups of animals were studied: group 1 consisted of 5 rats exposed to cadmium chloride (CdCl2) in drinking water (300 mg/L) for 6 months; group 2 also consisted of 5 rats placed in the same conditions as those of group 1, but kept free of Cd for 6 additional months. Two other groups (C1 and C2) with the same number of animals, but not exposed to CdCl2, were used as a control for groups 1 and 2, respectively. All animals were weighed before and after the experimental period. After animals being killed, tissues of interest were fixed in solution of 10% formalin, processed by standard histologic techniques, stained with HE, and analyzed under light microscopy using karyometric and stereologic parameters. Loss of body weight, atrophy of the gingiva and soft-palate epithelium were the principal findings of this study, and verified only in the group 1 (p < 0.05). In conclusion, at the concentration tested, Cd presented no carcinogenic effect on the oral tissues within the experimental time period.Cádmio (Cd) é um metal pesado que exerce uma variedade de efeitos tóxicos, crônicos e agudos, em organismos expostos. O objetivo deste estudo foi investigar o potencial carcinogênico do Cd no epitélio do palato e da gengiva de ratos Wistar. Dois grupos de animais foram estudados: grupo 1 que consistiu de 5 ratos expostos a cloreto de cádmio (CdCl2) em água de bebedouro (300 mg/L) por um período de 6 meses; grupo 2 que também consistiu de 5 ratos submetidos às mesmas condições dos animais do grupo 1, mas permaneceu livre de Cd por um período adicional de 6 meses. Dois outros grupos (C1 and C2) com o mesmo número de animais, entretanto não expostos ao CdCl2, foram usados como controle para o grupo 1 e 2, respectivamente. Todos os animais foram pesados antes e após o período experimental. Após terem sido sacrificados, os tecidos de interesse para o estudo foram fixados em formalina a 10%, processados por meio de técnica histopatológica padrão, corados em HE, e analisados sob microscopia de luz, utilizando parâmetros cariométricos e estereológicos. Perda de peso, atrofia do epitélio da gengiva e do palato mole foram os principais achados deste estudo, e verificados apenas no grupo 1 (p < 0.05). Em conclusão, Cd não produziu efeito carcinogênico nos tecidos orais, nas condições experimentais empregadas neste estudo

Types and Distribution of Bioactive Polyunsaturated Aldehydes in a Gradient from Mesotrophic to OligotrophicWaters in the Alborán Sea (Western Mediterranean)

Polyunsaturated aldehydes (PUAs) are bioactive molecules suggested as chemical defenses and infochemicals. In marine coastal habitats, diatoms reach high PUA production levels during bloom episodes. Two fractions of PUA can usually be analyzed: pPUA obtained via artificial breakage of collected phytoplankton cells and dissolved PUA already released to the environment (dPUA). In nature, resource supply arises as a main environmental controlling factor of PUA production. In this work, we monitored the vertical distribution and daily variation of pPUA associated with large-size phytoplankton and dPUA, at three sites located in the Alboran Sea from mesotrophic to oligotrophic waters. The results corroborate the presence of large-size PUA producers in oligotrophic and mesotrophic waters with a significant (58%-85%) diatom biomass. In addition to diatoms, significant correlations between pPUA production and dinoflagellate and silicoflagellate abundance were observed. 2E,4E/Z-Heptadienal was the most abundant aldehyde at the three sites with higher values (17.1 fg center dot cell(-1)) at the most oligotrophic site. 2E,4E/Z-Decadienal was the least abundant aldehyde, decreasing toward the oligotrophic site. For the first time, we describe the daily fluctuation of pPUA attributable to cellular physiological state and not exclusively to taxonomical composition. Our results demonstrate the persistence of threshold levels of dPUA deep in the water column, as well as the different chromatographic profiles of dPUA compared with pPUA. We propose different isomerization processes that alter the chemical structure of the released PUAs with unknown effects on their stability, biological function, and potential bioactivity

Leigh syndrome associated with TRMU gene mutations

tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) deficiency causes an early onset potentially reversible acute liver failure, so far reported in less than 30 patients. We describe two new unrelated patients with an acute liver failure and a neuroimaging compatible with Leigh syndrome (LS) due to TRMU deficiency, a combination not previously reported. Our report enlarges the phenotypical spectrum of TRMU disease

Urinary Tartaric Acid, a Biomarker of Wine Intake, Correlates with Lower Total and LDL Cholesterol

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60-80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartaric acid was analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Correlations between tartaric acid and the study variables were adjusted for age, education level, smoking status, physical activity, BMI, cholesterol-lowering, antihypertensive, and insulin treatment, total energy intake, and consumption of fruits, vegetables, and raisins. A strong association was observed between wine consumption and urinary tartaric acid (0.01 μg/mg (95% confidence interval (CI): 0.01, 0.01), p-value < 0.001). Total and low-density lipoprotein (LDL) cholesterol were inversely correlated with urinary tartaric acid (-3.13 μg/mg (-5.54, -0.71), p-value = 0.016 and -3.03 μg/mg (-5.62, -0.42), p-value = 0.027, respectively), whereas other biochemical and anthropometric variables were unrelated. The results suggest that wine consumption may have a positive effect on cardiovascular health in postmenopausal women, underpinning its nutraceutical properties

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice: CEIPC 2008 Spanish adaptation

Basado en el Documento del Cuarto Grupo de Trabajo Conjunto de la Sociedad Europea de Cardiología y otras sociedades científicas: Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al et al. European guidelines on cardiovascular disease prevention in clinical practice: fourth joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2007; 28: 2375 2414.We present the Spanish adaptation from the CEIPC of the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice 2008. This guide recommends the SCORE model for risk evaluation. The aim is to prevent premature mortality and morbidity due to CVD by means of dealing with its related risk factors in clinical practice. The guide focuses on primary prevention and emphasizes the role of the nurses and primary care medical doctors in promoting a healthy life style, based on increasing physical activity, change dietary habits, and non smoking. The therapeutic goal is to achieve a Blood Pressure <140/90 mmHg, but among patients with diabetes, chronic kidney disease, or definite CVD, the objective is <130/80 mmHg. Serum cholesterol should be <200 mg/dl and cLDL <130 mg/dl, although among patients with CVD or diabetes, the objective is <100 mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2 diabetes and those with metabolic syndrome must lose weight and increase their physical activity, and drugs must be administered whenever applicable, with the objective guided by BMI -body mass index- and waist circumference. In diabetic type 2 patients, the objective is glycated haemoglobin <7%. Allowing people to know the guides and developing implementation programs, identifying barriers and seeking solutions for them, are priorities for the CEIPC in order to put the recommendations into practice.S