Angiomatose bacilar: descrição de 13 casos relatados em cinco centros de referência para tratamento de AIDS no Rio de Janeiro, Brasil

The aim of this case series was to describe the clinical, laboratory and epidemiological characteristics and the presentation of bacillary angiomatosis cases (and/or parenchymal bacillary peliosis) that were identified in five public hospitals of Rio de Janeiro state between 1990 and 1997; these cases were compared with those previously described in the medical literature. Thirteen case-patients were enrolled in the study; the median age was 39 years and all patients were male. All patients were human immunodeficiency virus type 1 (HIV-1) infected and they had previous or concomitant HIV-associated opportunistic infections or malignancies diagnosed at the time bacillary angiomatosis was diagnosed. Median T4 helper lymphocyte counts of patients was 96 cells per mm³. Cutaneous involvement was the most common clinical manifestation of bacillary angiomatosis in this study. Clinical remission following appropriate treatment was more common in our case series than that reported in the medical literature, while the incidence of relapse was similar. The frequency of bacillary angiomatosis in HIV patients calculated from two of the hospitals included in our study was 1.42 cases per 1000 patients, similar to the frequencies reported in the medical literature. Bacillary angiomatosis is an unusual opportunistic pathogen in our setting.Esta série de casos foi conduzida com o objetivo de descrever a apresentação clínica, as características epidemiológicas, os exames laboratoriais e a evolução dos casos de angiomatose bacilar (e/ou peliose parenquimatosa bacilar) ocorridos em cinco hospitais públicos do Rio de Janeiro, no período de 1990 a 1997, comparando a casuística encontrada com a relatada na literatura médica. Foram incluídos 13 pacientes com mediana de idade de 39 anos, sendo todos pertencentes ao sexo masculino. Todos os pacientes apresentaram infecções oportunistas e/ou neoplasias associadas ao vírus da imunodeficiência humana (HIV-1) anteriores (ou concomitantes) ao diagnóstico de angiomatose bacilar. A mediana da contagem de linfócitos T Helper encontrada foi de 96 células por mm³. O acometimento cutâneo foi a apresentação clínica de angiomatose bacilar mais freqüente deste estudo. A freqüência de remissão após tratamento específico foi discretamente maior do que a relatada na literatura médica, enquanto a de recidiva foi semelhante. A freqüência de angiomatose bacilar entre indivíduos infectados pelo HIV de dois hospitais do Rio de Janeiro foi de 1,42 casos por 1.000 pacientes, semelhante ao relatado na literatura médica e sugestivo de que a angiomatose bacilar é relativamente incomum em nosso meio

Short-term changes in left and right systolic function following ferric carboxymaltose : a substudy of the Myocardial-IRON trial

Funding: This work was supported in part by an unrestricted grant from Vifor Pharma and Proyectos de Investigación de la Sección de Insuficiencia Cardiaca 2017 from Sociedad Española de Cardiología.The mechanisms underlying the beneficial effect of ferric carboxymaltose (FCM) in patients with heart failure (HF) and iron deficiency (ID) have not been completely characterized. The Myocardial-IRON trial was a double-blind, randomized trial that evaluated myocardial iron repletion following FCM vs. placebo in 53 patients with HF and ID. In this post hoc analysis, we evaluated whether treatment with FCM was associated with cardiac magnetic resonance changes in left and right ventricular function (LVEF and RVEF, respectively) at different points of systolic dysfunction. We included patients from the Myocardial-IRON trial with left and right ventricular systolic dysfunction (LVSD and RVSD, respectively) at enrolment. Linear mixed regression models were used to evaluate changes at 7 and 30 days on LVEF and RVEF at cardiac magnetic resonance. At enrolment, 27 (50.9%) and 38 (71.7%) patients had LVEF < 40% (LVSD) or <45% (LVSD), respectively, and 10 (18.9%) and 17 (32.1%) patients had RVEF < 45% (RVSD) or <51% in women and <52% in men (RVSD, respectively. Treatment with FCM was associated with a significant improvement in LVEF at 30 days (LVSD: Δ2.3%, P < 0.001; LVSD: Δ4.1, P = 0.014). FCM was also associated with a significant and early improvement in RVEF at 7 days (RVSD: Δ6.9%, P = 0.003; RVSD: Δ3.2%, P = 0.003) that persisted at 30 days (RVSD: Δ8.1%, P < 0.001; RVSD: Δ4.7%, P < 0.001). In patients with HF and systolic dysfunction with ID, FCM was associated with short-term improvement in LVEF and, especially, in RVEF

Separación de gases mediante difusión por presión en una tobera curva

La evolución de la concentración de cada especie en una mezcla de gases se puede obtener a través de la ecuación de transporte por difusión, derivada de la teoría cinética de gases. Éste es el problema a resolver en procesos de separación de gases, como son por ejemplo los procesos centrífugos, las toberas curvas y la expansión libre o free-jet. En este trabajo nos enfocamos en la separación de gases que se genera a partir del gradiente de presión obtenido en una tobera curva. Se resolvieron las ecuaciones de Navier-Stokes de flujo compresible utilizando el código FLUENT de volúmenes finitos. Con las soluciones obtenidas se modeló el proceso de difusión de especies a partir de una ecuación constitutiva para los flujos de entrada y salida de los volúmenes finitos, donde se tiene en cuenta el efecto del gradiente de presión. Los resultados se compararon con datos experimentales de concentración de oxígeno en un flujo de aire.Fil: Guouzden, T.. Comisión Nacional de Energía Atómica; ArgentinaFil: Clausse, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Cortizo, E.. Comisión Nacional de Energía Atómica; ArgentinaFil: Fainstein, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Fiol, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Fregenal, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Fuhr, Javier Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Kaul, Enrique Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Knoblauch, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Invap S. E.; ArgentinaFil: Lamagna, Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Maceira, P.. Comisión Nacional de Energía Atómica; ArgentinaFil: Rozas, G.. Comisión Nacional de Energía Atómica; ArgentinaFil: Zarco, Maximiliano Alfredo. Comisión Nacional de Energía Atómica; Argentin

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis

African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.JAGS was funded by the European Union, grant FP7-HEALTH-2007-B-2.3.4-1.223048, NANOTRYP and Ministerio de Economía y Competitividad, Spain Plan Nacional de Investigación grant SAF2011- 30528. JLA was funded by Instituto de Salud Carlos III, Spain, grant FIS. 11/02571. HPdK was supported by a grant from the Medical Research Council (84733)

Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial

This is the peer reviewed version of the following article: Del Canto I, Santas E, Cardells I, Miñana G, Palau P, Llàcer P, Fácila L, López-Vilella R, Almenar L, Bodí V, López-Lereu MP, Monmeneu JV, Sanchis J, Moratal D, Maceira AM, de la Espriella R, Chorro FJ, Bayés-Genís A, Núñez J; Myocardial¿IRON Investigators. Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial. J Am Heart Assoc. 2022 Apr 5;11(7):e022214. doi: 10.1161/JAHA.121.022214, which has been published in final form at https://doi.org/10.1161/jaha.121.022214. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] BACKGROUND: The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial-IRON trial showed short-term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short-term left and right ventricular CMR feature tracking derived strain. METHODS AND RESULTS: This is a post hoc subanalysis of the double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction <50%, and iron deficiency [Myocardial-IRON trial (NCT03398681)]. Three-dimensional left and 2-dimensional right ventricular CMR tracking strain (longitudinal, circumferential, and radial) changes were evaluated before, 7 and 30 days after randomization using linear mixed-effect analysis. The median (interquartile range) age of the sample was 73 years (65-78), and 40 (75.5%) were men. At baseline, there were no significant differences in CMR feature tracking strain parameters across both treatment arms. At 7 days, the only global 3-dimensional left ventricular circumferential strain was significantly higher in the FCM treatment-arm (difference: -1.6%, P=0.001). At 30 days, and compared with placebo, global 3-dimensional left ventricular strain parameters significantly improved in those allocated to FCM treatment-arm [longitudinal (difference: -2.3%, P<0.001), circumferential (difference: -2.5%, P<0.001), and radial (difference: 4.2%, P=0.002)]. Likewise, significant improvements in global right ventricular strain parameters were found in the active arm at 30 days (longitudinal [difference: -3.3%, P=0.010], circumferential [difference: -4.5%, P<0.001], and radial [difference: 4.5%, P=0.027]). CONCLUSIONS: In patients with stable heart failure, left ventricular ejection fraction <50%, and iron deficiency, treatment with FCM was associated with short-term improvements in left and right ventricular function assessed by CMR feature tracking derived strain parameters.This work was supported in part by an unrestricted grant from Vifor Pharma, CIBER Cardiovascular [grant numbers 16/11/00420 and 16/11/00403], Unidad de Investigacion Clinica y Ensayos Clinicos INCLIVA Health Research Institute, Spanish Clinical Research Network (SCReN; PT13/0002/0031 and PT17/0017/0003), cofounded by Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III, and Proyectos de Investigacion de la Seccion de Insuficiencia Cardiaca 2017 from Sociedad Espanola de Cardiologia.Del Canto Serrano, I.; Santas, E.; Cardells, I.; Miñana, G.; Palau, P.; Llàcer, P.; Fácila, L.... (2022). Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial. Journal of the American Heart Association. 11(7):1-19. https://doi.org/10.1161/JAHA.121.02221411911