Polyaromatic Bis(indolyl)methane Derivatives with Antiproliferative and Antiparasitic Activity.

Bis(indolyl)methanes (BIMs) are a class of compounds that have been recognized as an important core in the design of drugs with important pharmacological properties, such as promising anticancer and antiparasitic activities. Here, we explored the biological activity of the BIM core functionalized with different (hetero)aromatic moieties. We synthesized substituted BIM derivatives with triphenylamine, N,N-dimethyl-1-naphthylamine and 8-hydroxylquinolyl groups, studied their photophysical properties and evaluated their in vitro antiproliferative and antiparasitic activities. The triphenylamine BIM derivative 2a displayed an IC50 of 3.21, 3.30 and 3.93 µM against Trypanosoma brucei, Leishmania major and HT-29 cancer cell line, respectively. The selectivity index demonstrated that compound 2a was up to eight-fold more active against the parasites and HT-29 than against the healthy cell line MRC-5. Fluorescence microscopy studies with MRC-5 cells and T. brucei parasites incubated with derivative 2a indicate that the compound seems to accumulate in the cell's mitochondria and in the parasite's nucleus. In conclusion, the BIM scaffold functionalized with the triphenylamine moiety proved to be the most promising antiparasitic and anticancer agent of this series.

Colorimetric Chemosensor for Cu2+ and Fe3+ Based on a meso-Triphenylamine-BODIPY Derivative.

Optical chemosensors are a practical tool for the detection and quantification of important analytes in biological and environmental fields, such as Cu2+ and Fe3+. To the best of our knowledge, a BODIPY derivative capable of detecting Cu2+ and Fe3+ simultaneously through a colorimetric response has not yet been described in the literature. In this work, a meso-triphenylamine-BODIPY derivative is reported for the highly selective detection of Cu2+ and Fe3+. In the preliminary chemosensing study, this compound showed a significant color change from yellow to blue-green in the presence of Cu2+ and Fe3+. With only one equivalent of cation, a change in the absorption band of the compound and the appearance of a new band around 700 nm were observed. Furthermore, only 10 equivalents of Cu2+/Fe3+ were needed to reach the absorption plateau in the UV-visible titrations. Compound 1 showed excellent sensitivity toward Cu2+ and Fe3+ detection, with LODs of 0.63 µM and 1.06 µM, respectively. The binding constant calculation indicated a strong complexation between compound 1 and Cu2+/Fe3+ ions. The 1H and 19F NMR titrations showed that an increasing concentration of cations induced a broadening and shifting of the aromatic region peaks, as well as the disappearance of the original fluorine peaks of the BODIPY core, which suggests that the ligand-metal (1:2) interaction may occur through the triphenylamino group and the BODIPY core.

Bioimaging of Lysosomes with a BODIPY pH-Dependent Fluorescent Probe.

Fluorescence-based probes represent a powerful tool for noninvasive imaging of living systems in real time and with a high temporal and spatial resolution. Amongst several known fluorophores, 3-difluoroborodipyrromethene (BODIPY) derivatives have become a cornerstone for innovative fluorescent labelling applications, mainly due to their advantageous features including their facile synthesis, structural versatility and exceptional photophysical properties. In this context, we report a BODIPY-based fluorescent probe for imaging of lysosomes in living cells. The BODIPY derivative displayed a remarkable fluorescence enhancement at low pH values with a pKa* of 3.1. In vitro studies by confocal microscopy in HeLa cells demonstrated that the compound was able to permeate cell membrane and selectively label lysosome whilst remaining innocuous to the cell culture at the maximum concentration tested. Herein, the BODIPY derivative holds the promise of investigating lysosomal dynamics and function in living cells through fluorescence imaging.

All-Aqueous Freeform Fabrication of Perfusable Self-Standing Soft Compartments.

Compartmentalized structures obtained in all-aqueous settings have shown promising properties as cell encapsulation devices, as well as reactors for trans-membrane chemical reactions. While most approaches focus on the preparation of spherical devices, advances on the production of complex architectures have been enabled by the interfacial stability conferred by emulsion systems, namely mild aqueous two-phase systems (ATPS), or non-equilibrated analogues. However, the application of non-spherical structures has mostly been reported while keeping the fabricated materials at a stable interface, limiting the free-standing character, mobility and transposition of the obtained structures to different setups. Here, the fabrication of self-standing, malleable and perfusable tubular systems through all-aqueous interfacial assembly is shown, culminating in the preparation of independent objects with stability and homogeneity after disruption of the polymer-based aqueous separating system. Those hollow structures can be fabricated with a variety of widths, and rapidly printed as long structures at flow rates of 15 mm s-1 . The materials are used as compartments for cell culture, showcasing high cytocompatibility, and can be tailored to promote cell adhesion. Such structures may find application in fields that benefit from freeform tubular structures, including the biomedical field with, for example, cell encapsulation, and benchtop preparation of microfluidic devices.

Strategies for re-vascularization and promotion of angiogenesis in trauma and disease.

The maintenance of a healthy vascular system is essential to ensure the proper function of all organs of the human body. While macrovessels have the main role of blood transportation from the heart to all tissues, microvessels, in particular capillaries, are responsible for maintaining tissues' functionality by providing oxygen, nutrients and waste exchanges. Occlusion of blood vessels due to atherosclerotic plaque accumulation remains the leading cause of mortality across the world. Autologous vein and artery grafts bypassing are the current gold standard surgical procedures to substitute primarily obstructed vascular structures. Ischemic scenarios that condition blood supply in downstream tissues may arise from blockage phenomena, as well as from other disease or events leading to trauma. The (i) great demand for new vascular substitutes, arising from both the limited availability of healthy autologous vessels, as well as the shortcomings associated with small-diameter synthetic vascular grafts, and (ii) the challenging induction of the formation of adequate and stable microvasculature are current driving forces for the growing interest in the development of bioinspired strategies to ensure the proper function of vasculature in all its dimensional scales. Here, a critical review of well-established technologies and recent biotechnological advances to substitute or regenerate the vascular system is provided.

Desenvolvimento de um modelo experimental de hemodiálise em cães / Development of a dog model of hemodialysis

To develop a model of hemodialysis (HD), 18 healthy dogs, without a defined breed, males, weighing 7-14 kg, were studied. A double lumen catheter was inserted into the jugular vein for vascular access. HD sessions, totalizing 5 for each dog, were performed with a proportional HD machine, controlled isovolemic ultrafiltration, standard dialysis solution and bicarbonate buffer. Sodium profile and sodium heparin were used. During HD sessions the dogs were kept anesthetized (levomepromazine and propofol). Hematological and biochemistry data, blood gas analysis, systemic arterial blood pressure, and activated clotting time were evaluated. Serum biochemistry e blood gas analysis showed, respectively, sodium and SO2 maintenance. Systemic blood pressure kept sustained during HD sessions. It could be concluded that it was possible to develop a HD dog model that is a safe and viable technique to be used in chronic renal failure patients.

Com o objetivo de desenvolver um modelo de hemodiálise (HD) em cães, foram estudados 18 animais, sem raça definida, machos, clinicamente sadios, com peso corporal variando entre sete e 14 kg. O acesso vascular foi obtido através de implantação do cateter de duplo lúmen em veia jugular externa. As sessões de HD, em número de cinco por animal, com até três horas de duração, foram realizadas em hemodialisadora de sistema proporcional com ultrafiltração (UF) controlada, com solução dialisante padrão e tampão bicarbonato. A UF foi ajustada para HD isovolêmica, utilizou-se perfil de sódio, e para anticoagulação heparina sódica. Os animais foram mantidos anestesiados com cloridrato de levomepromazina e propofol. Foram avaliados dados hematológicos, bioquímicos, hemogasometria, pressão arterial sistêmica e tempo de coagulação ativado. Foi observada diminuição do número global de hemácias, volume globular, hemoglobina e leucócitos. Em relação aos exames bioquímicos, houve manutenção nos níveis de sódio sérico, e quanto à hemogasometria, a manutenção da SO2. A pressão arterial sistêmica manteve-se constante. Os resultados obtidos no presente trabalho permitiram concluir que foi possível o desenvolvimento do modelo proposto e mostrou que a HD em cães é um método viável e seguro, que poderá contribuir para o tratamento clínico da insuficiência renal nesta espécie.

Effects of aerobic training on psychosocial morbidity and symptoms in patients with asthma: a randomized clinical trial.

BACKGROUND: Asthma symptoms reduce patients' daily activities, impair their health-related quality of life (HRQoL), and increase their reports of anxiety and depression, all of which seem to be related to a decrease in asthma control. Aerobic exercise training is known to improve aerobic fitness and reduce dyspnea in asthmatics; however, its effect in reducing psychologic distress and symptoms remains poorly understood. We evaluated the role of an aerobic training program in improving HRQoL (primary aim) and reducing psychologic distress and asthma symptoms (secondary aims) for patients with moderate or severe persistent asthma. METHODS: A total of 101 patients were randomly assigned to either a control group or an aerobic training group and studied during the period between medical consultations. Control group patients (educational program plus breathing exercises) (n = 51) and training group patients (educational program plus breathing exercises plus aerobic training) (n = 50) were followed twice a week during a 3-month period. HRQoL and levels of anxiety and depression were quantified before and after treatment. Asthma symptoms were evaluated monthly. RESULTS: At 3 months, the domains (physical limitations, frequency of symptoms, and psychosocial) and total scores of HRQoL significantly improved only in the training group patients (P < .001); the number of asthma-symptom-free days and anxiety and depression levels also significantly improved in this group (P < .001). In addition, a linear relationship between improvement in aerobic capacity and the days without asthma symptoms was observed (r = 0.47; P < .01). CONCLUSIONS: Our results suggest that aerobic training can play an important role in the clinical management of patients with persistent asthma. Further, they may be especially useful for patients with higher degrees of psychosocial distress. TRIAL REGISTRATION: clinicaltrials.gov; Identifier: NCT-00989365.

Assessment of muscle shortening and static posture in children with persistent asthma.

Asthmatic patients experience an increase in airway resistance that overburdens both respiratory and non-respiratory muscles. The objective of the present study was to determine whether children with persistent asthma present muscle shortening and postural changes. The 60 boys evaluated, aged 7-12 (pubertal ages up to Tanner stage G2) were divided into three age- and BMI-matched groups of equal number: CON (no history of asthma or allergy); MPA (mild persistent asthma); SPA (severe persistent asthma). Pulmonary function, muscle shortening and static posture were evaluated. The SPA group presented higher protraction of the head and shoulder compared with the CON group [9.5 (6.0-12.0) degrees vs 5.5 (0.0-12.0) degrees, P < 0.05; 0.89 (0.80-0.94) anterior/posterior ratio vs 0.94 (0.87-1.1) anterior/posterior ratio, P < 0.01)]. Severe asthmatic patients also presented shortening of arm flexor and posterior muscle of the thigh compared with the CON group [18.0 (10.0-24.0) degrees vs 12.0 (6.0-16.0) degrees, P < 0.05; and 16.5 (10.0-38.5) cm vs 8.0 (0.0-21.0) cm, respectively, P < 0.05]. Chest expansion at axillar and xiphoid levels were limited in SPA subjects compared with CON subjects [3.7 (1.5-6.5) cm vs 5.5 (2.0-8.0) cm and 4.7 (1.5-6.5) vs 6.0 (3.5-8.0) cm, respectively, P < 0.01]. SPA subjects also presented a higher incidence of lumbar spine straightening compared with CON and MPA subjects. Moderate asthmatic subjects presented intermediate values compared with severe and control subjects in five out nine evaluated outcomes. Our data suggest that severe asthmatic children present postural adaptations and muscle shortening that seem to be related to disease severity.

Avaliação dos critérios médicos para o encaminhamento de pacientes com disfunções neurológicas para atendimento fisioterapêutico / Assessment of medical criteria for referring neurological patients to physical therapy treatment

Este estudo objetivou investigar critérios utilizados por neurologistas para o encaminhamento de pacientes para o atendimento fisioterapêutico. Foram convidados os 44 neurologistas de um hospital universitário que atuam em todos os níveis do atendimento terciário à saúde...

The aim of the present study was to investigate the criteria used by neurologists to refer patients to physical therapy treatement. All (44) neurologists from a university hospital were contacted, Thirthy physicians answered a questionnaire composed by 12 multiple choice and four open ones, in view of assessing both their referral criteria...