Synthesis and evaluation of tumor cell growth inhibition of Methyl 3-Amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates: structure-activity relationships, effects on the cell cycle and apoptosis

The methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate, recently reported by some of us, was reacted in Sonogashira couplings with several (hetero)arylacetylenes. The growth inhibitory activity of the novel methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates obtained was evaluated on three human tumor cell lines (MCF-7, NCI-H460, A375-C5). The para-methoxyphenyl and the ortho and para-aminophenyl derivatives were the most promising compounds, and their effects were further studied regarding alterations in the normal cell cycle distribution and induction of apoptosis in the NCI-H460 cell line. All three compounds altered cell cycle distribution and the ortho-aminophenyl derivative was further shown to induce apoptosis in the same cell line.Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher EducationFundação para a Ciência e a Tecnologia (FCT) - (Bruker Avance III 400) REDE/1517/RMN/2005, PTDC/QUI-QUI/111060/2009, SFRH/BD/29274/2006, SFRH/BPD/29112/2006European Social Fund

Flow of red blood cells in microchannel networks: in vitro studies

Human blood is a multiphase biofluid primarily composed by the deformable red blood cells (RBCs) suspended in plasma. Because the complex structure of RBCs, blood exhibits unique flow characteristics on micro-scale level, due to their complex biochemical mechanisms and their response to both shear and extensional flow, which influence the rheological properties and flow behaviour of blood [1,2]. In the past years in vitro blood studies have been extensively performed and some important physiological phenomena, such as Fahraeus and Fahraeus-Lindqvist effect, were revealed [1,3]. This pioneer studies performed by Fahraeus and Fahraeus-Lindqvist in straight glass microchannels [4] revealed that for narrow tubes (diameter<300 μm), the apparent viscosity of blood declines with decreasing diameter. More recently, due to the developments in microscopy, computers and image analysis techniques, several researchers have used new measuring methods to obtain deeper quantitative understanding of the blood flow dynamics, in vitro [5-8] and in vivo experiments [9-10]. The increasing interest by the microfluidic and biomedical communities has also played a key role in several recent developments of lab-on-chip devices for blood sampling, analysis and cell culturing, aimed in a near future, the development of blood diagnostic devices, as an alternative tool to the traditional diagnostic strategies. However, the blood flow in microvascular networks phenomena remains incompletely understood. Thus, it is important to investigate in detail the behaviour of RBCs flow occurring in a microchannel network, such as, with divergent and convergent bifurcations, which mimics the irregular vessel segments linked by numerous diverging and converging bifurcations. Previously, we made in vitro studies in microchannels with a simple divergent and convergent bifurcation, that showed a pronounced cell-free layer (CFL) immediately downstream of the apex of the convergent bifurcation [1,4]. This interesting result led us to the present work, where the CFL in a microchannel network is investigated by using a high-speed video microscopy system in order to further understand the blood flow behaviour in microvessels networks

Encapsulation of a new antitumoral fluorescent 6-(benzo[d]thiazo-2-ylamino)thieno[3,2-b]pyridine derivative in nanoliposomes

Publicado no suplemento da Revista Portuguesa de Farmácia, Vol. 50, nº 4This work was funded by FCT-Portugal through CFUM, CQ/UM, Project PTDC/QUI/81238/2006 cofinanced by FCT and program FEDER/COMPETE (FCOMP-01-0124-FEDER-007467) and by FCT grants of R. C. Calhelha (SFRH/BD/29274/2006) and L. Vale-Silva (SFRH/BPD/29112/2006)

Sacral Fractures and Associated Injuries.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management

Studies on the interaction of the carbohydrate binding module 3 from the Clostridium thermocellum CipA scaffolding protein with cellulose and paper fibres

The adsorption of a carbohydrate binding module (CBM3) from the Clostridium thermocellum scaffolding protein (CipA) to cellulose was analysed in this work. The effect of CBM-PEG on the drainability of E. globulus and P. sylvestris pulps and on the physical properties of the respective papersheets was also studied. The CBM binding to cellulose is often described as “irreversible”, but this classification does not fully characterize this interaction. Indeed, the results obtained demonstrate that, although the adsorption on cellulose is rather stable, CBM inter-fibre mobility may be observed. The results also showed that the CBM-PEG conjugate improves the drainability of E. globulus and P. sylvestris pulps without affecting the physical properties of the papersheets.This research was supported by Fundacao para a Ciencia e a Tecnologia under grant POCTI/BIO/45356/2002

Left ventricular systolic dysfunction in Marfan syndrome is related to aortic distensibility

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2019.Background: The cardiovascular involvement in Marfan syndrome (MS) is characterized mainly by dilatation and reduced distensibility of the ascending aorta. Left ventricular (LV) dysfunction has been detected in MS and a primary cardiomyopathy has been suggested but the pathophysiology is unclear. The purpose of this study was to evaluate the LV function in patients with MS and to assess the relationship with the aortic distensibility, as possible underlying mechanism. Methods: We studied 53 patients with MS (27.0 ± 11 years, 29 men) without valvular or hypertensive heart disease and a control group of 26 healthy subjects (29 ± 9 years, 17 men). All underwent echocardiography and cardiac magnetic resonance (CMR) and the following indexes were analyzed: a) Echo: mitral flow velocities E/A ratio and deceleration of mitral E; E’ velocity obtained from the medial and lateral mitral ring; E/E’ ratio b) CMR: LV volumes indexed to BSA and ejection fraction (EF); global longitudinal strain (GLS, Circle cvI42); maximal size and distensibility of proximal ascending aorta. Distensibility was calculated from maximal (systolic) and minimum (diastolic) area of maximal proximal ascending aorta (cross-sectional images from SSFP sequence) using the formula=(maximum area-minimum area)/[ minimum area x (systolic BP-diastolic BP)]. Results: 17 from 53 patients with MS had increased LV end-diastolic volume, 14 decreased EF (<50%) and 22 decreased GLS. Compared with the control group, patients with MS showed increased LV end-diastolic volume (85.0 ± 5.2vs 80.1 ± 5.3ml/m2, p = 0.04), lower GLS (17.1 ± 1.9 vs 18.9 ± 2.2, p = 0.01) lower LVEF (53.0 ± 7.1% vs 56.0 ± 5.4%, p = 0.03) and higher E/E’ value (9.2 ± 1.3 vs. 6.2 ± 0.8, p = 0.01) as well as larger dimensions of proximal aorta (39 ± 2.2cm vs 32 ± 0.8,p = 0.010) and lower aortic distensibility (3.4 ± 1.9 vs. 4.4 ± 1.7 dynes cm-1, p = 0.03). In the group of patients, a correlation was found between the aortic distensibility and the LVEF (r = 0.47, p = 0.045) and GLS (r = 0.65, p = 0.02), but not with the other variables. Aortic distensibility was an independent predictor of LV dysfunction using a cutoff of 50% for LVEF and 19% for GLS. Conclusion: In our population of patients with MS, we found changes in the LV function, which were related with aortic distensibility, possibly sharing a common pathway. The prognostic significance of these findings is under evaluation.info:eu-repo/semantics/publishedVersio

The Role of a Medical Intermediate Care Unit in the Management of Budd-Chiari Syndrome: Case Series

Budd-Chiari syndrome (BCS) has a wide spectrum of presentations, from an asymptomatic status to acute liver failure (ALF). The therapeutic approach depends on disease severity and related etiology with patients with severe forms of presentation classically managed in intensive care units (ICUs). Here, we report a series of five BCS patients managed in a medical intermediate care unit (IntCU), with three of them presenting with acute liver injury. Progression to ALF was seen in three patients, two of whom died, with one being successfully submitted to liver transplantation. IntCUs allow a 24-h patient surveillance and a prompt management of BCS, with less economic impact when compared to ICUs. Mortality was related to the presence of associated comorbidities that limited therapeutic approach.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

BiLaWO6: Er3+/Tm3+/Yb3+ phosphor: study of multiple fluorescence intensity ratiometric thermometry at cryogenic temperatures

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Analytical results for coupled map lattices with long-range interactions

We obtain exact analytical results for lattices of maps with couplings that decay with distance as $r^{-\alpha}$. We analyze the effect of the coupling range on the system dynamics through the Lyapunov spectrum. For lattices whose elements are piecewise linear maps, we get an algebraic expression for the Lyapunov spectrum. When the local dynamics is given by a nonlinear map, the Lyapunov spectrum for a completely synchronized state is analytically obtained. The critical lines characterizing the synchronization transition are determined from the expression for the largest transversal Lyapunov exponent. In particular, it is shown that in the thermodynamical limit, such transition is only possible for sufficiently long-range interactions, namely, for $\alpha\le alpha_c<d$, where $d$ is the lattice dimension.Comment: 4 pages, 2 figures, corrections included. Phys. Rev. E 68, 045202(R) (2003); correction in pres

Antioxidant activity of aminodiarylamines in the thieno[3,2-b]pyridine series: radical scavenging activity, lipid peroxidation inhibition and redox profile

The antioxidant activity of the aminodi(hetero)arylamines, prepared by C-N coupling of the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with bromonitrobenzenes and further reduction of the obtained nitro compounds, was evaluated by chemical, biochemical and electrochemical assays. The aminodi(hetero)arylamine with the amino group ortho to the NH and a methoxy group in para, was the most efficient in radical scavenging activity (RSA, 63 µM) and reducing power (RP, 33 µM), while the aminodiarylamine with the amino group in para to the NH, gave the best results in β-carotene-linoleate system (41 µM) and inhibition of formation of thiobarbituric acid reactive substances in porcine brain cells homogenates (7 µM), with EC50 values even lower than those obtained for the standard trolox. This diarylamine also presented the lowest oxidation potential, lower than the one of trolox, and the highest antioxidant power in the electrochemical assays. The para substitution with an amino group enables higher antioxidant potential.The authors are grateful to FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoral grant attributed to R.C.C. (SFRH/BPD/68344/2010)