Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection

Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease

Parathyroid Cyst: Differential Diagnosis

Parathyroid cysts are rare lesions of the cervical region and less frequently of the mediastinum. They occur mostly in women and are usually asymptomatic. They generally occur in the fourth and fifth decades of life and mainly are non-functioning. They commonly present as a neck mass that is found incidentally during surgery or in imaging test. Its importance lies in the difficulty in diagnosis, often confusing itself with thyroid pathology. The diagnosis is usually made intraoperatively, confirmed by histopathological examination.The aim of this paper is to report a case of parathyroid cyst that mimics a thyroid nodule.info:eu-repo/semantics/publishedVersio

Studies of charmless three-body b-hadron decays at LHCb

Studies of charmless three-body decays of either B0(s) mesons or beauty baryons with a K0 meson in the final state are presented in this thesis. The analyses are performed using the 2011 and 2012 LHCb dataset, corresponding to an integrated luminosity of 1.0 fb−1 and 2.0 fb−1 recorded at a centre-of-mass energy of 7 TeV and 8 TeV, respectively. The decays B0s->K 0K±⇡⌥ and B0s -> K0⇡+⇡− are observed for the first time, and the decay mode B0 -> K 0K±⇡⌥, previously observed by the BaBar experiment, is confirmed. Moreover, the ⇤0b -> K0p⇡− channel is also observed for the first time and its phase-space integrated CP asymmetry measured, which shows no significant deviation from zero. No significant signals are seen for ⇤0b -> K0pK− decays, ⌅0 b decays to both the K0 S p⇡− and K0 SpK− final states, and the ⇤0b ! D−s (K0 SK−)p decay, and upper limits on their branching fractions are reported. Finally, the first untagged decay-time-integrated amplitude analysis of B0s -> K0 SK±⇡⌥ decays has been performed. All branching fraction results obtained from this analysis are either the most precise to date or are first measurements

Sisal : recomendações técnicas

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Protective role of new nitrogen compounds on ROS/RNS-mediated damage to PC12 cells

Reactive oxygen (ROS) and nitrogen (RNS) species are known to be involved in many degenerative diseases. This study reports four new nitrogen compounds from organic synthesis, identified as FMA4, FMA7, FMA762 and FMA796, which differ mainly by the number of hydroxyl groups within their phenolic unit. Their potential role as antioxidants was evaluated in PC12 cells by assessing their protection against oxidative and nitrosative insults. The four compounds, and particularly FMA762 and FMA796, were able to protect cells against lipid peroxidation and intracellular ROS/RNS formation to a great extent. Their protective effects were likely mediated by their free radicals scavenging ability, as they appeared to be involved neither in the induction of natural antioxidant enzymes like GSH-PX and SOD, nor in the inhibition of NOS. Nevertheless, these results suggest a promising potential for these compounds as ROS/RNS scavengers in pathologies where oxidative/ nitrosative stress are involved.Fundação para a Ciência e Tecnologia (FCT

Danger signals, inflammasomes, and the intricate intracellular lives of chlamydiae

Chlamydiae are obligate intracellular bacterial pathogens, and as such are sensitive to alterations in the cellular physiology of their hosts. Chlamydial infections often cause pathologic consequences due to prolonged localized inflammation. Considerable advances have been made in the last few years regarding our understanding of how two key inflammation-associated signaling pathways influence the biology o

Oxidative stress protection by newly synthesized nitrogen compounds with pharmacological potential

In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds. The results obtained with cellular models (L929 and PC12) show that they are not toxic and really protect from membrane lipid peroxidation induced by the ascorbate-iron oxidant pair. The level of protection correlates with the drugs lipophilic profile and is sometimes superior to trolox and equivalent to that observed for a-tocopherol. The compounds FMA4 and FMA7 presented also a high protection from cell death evaluated in the presence of a staurosporine apoptotic stimulus. That protection results in a significant reduction of caspase-3 activity induced by staurosporine which by its turn seems to result from a protection observed in the membrane receptor pathway (caspase-8) together with a protection observed in the mitochondrial pathway (caspase-9). Taken together the results obtained with the new compounds, with linear chains, open up perspectives for their use as therapeutical agents, namely as antioxidants and protectors of apoptotic pathways. On the other hand the slight pro-oxidant profile obtained with the cyclic structures suggests a different therapeutic potential that is under current investigation.Fundação para a Ciência e a Tecnologia (FCT) - POCTI and/or FEDER programmes, SFRH/BD/17174/2004, SFRH/BD/3185/2000

Nitrogen fertilization management in no-tillage maize with different witer crops.

The nitrogen (N) utilization by maize grown in a no-tillage system is dependent on the quality of the preceding crop residues, which may promote differences in N fertilization efficiency with respect to time. Thus, the purpose of this study was to evaluate the nutritional state, dry matter production and grain yield of maize grown in a clayey soil (Typic Acrustox) under a no-tillage system. The split-plot experimental design was set up in randomized complete blocks with three replications, in which the main plot was treated with different N application strategies and the split-plots were planted with winter crops (soybean and maize). The fertilizer strategies (rate: 120 kg ha-1 of N) used were as follows: (0 ? 0), (20 ? 100), (60 ? 60), (120 ? 0) and (0 ? 120), with the first number corresponding to the rate of N (kg ha-1) applied before planting and the second number corresponding to the top dressing rate (V4-5 stage). Nitrogen fertilization raised the N content (in shoots and leaves) and maize yield (in the shoot dry matter and grain). The maize grown after soybean had both greater N concentrations and production (dry matter and grain) relative to the maize grown after maize. Applying 120 kg ha-1 N did not significantly affect the evaluated variables, regardless of the winter crop

Office Hysteroscopy After Ultrasonographic Diagnosis of Thickened Endometrium in Postmenopausal Patients

The aim of our study was to access office hysteroscopy results in postmenopausal patients with thickened endometrium. A retrospective descriptive study was carried out on 245 postmenopausal patients submitted to office hysteroscopy after sonographic diagnosis of thickened endometriumin 20 consecutive months.Women were evaluated for age, hormonal therapy, hysteroscopic findings, procedure duration, complications and associated pain, and histological diagnosis. Patients with and without uterine bleeding were considered separately. Symptomatic patients were older and had longer procedure duration. The most frequent hysteroscopic finding was endometrial polyp in both groups. Pain was subjectively assessed in a numeric scale from 0 to 10 and median value was 4. There were no complications reported. Global neoplasia rate was 2.9% for asymptomatic patients and 16.4% for symptomatic ones (p<0.05). Thickened endometrium with postmenopausal metrorrhagia gave patients a significantly higher risk for neoplasia and hyperplasia