Long-term Survival Following Heart Transplantation for Chagas Versus Non-Chagas Cardiomyopathy: A Single-center Experience in Northeastern Brazil Over 2 Decades.

Data on post-heart transplant (HT) survival of patients with Chagas cardiomyopathy (CC) are scarce. We sought to evaluate post-HT survival in patients with CC as compared with other causes of heart failure across different eras of HT. Methods: We conducted a retrospective, cohort study of 376 adult HT recipients between October 1997 and November 2019. Participants were classified according to the etiology of heart failure as CC (N = 66), nonischemic cardiomyopathy (N = 214), and ischemic cardiomyopathy (N = 96), and according to the era of HT as early (1997-2009), recent (2010-2014), and current era (2015-2019). Results: After a mean follow-up of 5.0 y (0-20.5 y), post-HT survival rates at 1, 5, and 10 y were comparable between groups. One-y survival improved from 70% in the early eras to 80% in the current era (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.97; P = 0.034). After adjustment for sex, age, and mechanical circulatory support, time-related improvement in survival was observed only in patients without CC (HR, 0.54; 95% CI, 0.32-0.91; P = 0.019) but not in those with CC (HR, 0.99; 95% CI, 0.36-2.73; P = 0.98). Causes of death were similar between patients with CC and the other etiological subgroups. Conclusions: Posttransplant survival is comparable between patients with CC, nonischemic cardiomyopathy, and ischemic cardiomyopathy. Although survival has improved significantly over years for most HT recipients, it has remained unchanged for those with Chagas disease. These trends underscore the importance of scientific research, policy discussions and a collaborative registry of heart transplantation in Chagas cardiomyopathy.

The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects.

Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2 saturation and PMNs RLU (R = -0.62, P = 0.02), and with LF/HF (R = -0.79, P = 0.02) post-HPX6. In addition, an association was found between PMNs RLU and PR post-HPX6 (R = 0.58, P = 0.04). Conclusion: Acute exposure to intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may lead to an impairment in peripheral vascular resistance.

Occurrence and removal of estrogens in Brazilian wastewater treatment plants.

This paper evaluated the occurrence and removal efficiency of four estrogenic hormones in five biological wastewater treatment plants (WWTPs), located in the State of Ceará, Brazil. The five WWTPs comprised: two systems consisted of one facultative pond followed by two maturation ponds, one facultative pond, one activated sludge (AS) system followed by a chlorination step, and one upflow anaerobic sludge blanket (UASB) reactor followed by a chlorination step. Estrogen occurrence showed a wide variation among the analyzed influent and effluent samples. Estrone (E1) showed the highest occurrence in the influent (76%), whereas both 17ß-estradiol (E2) and 17α-ethynylestradiol (EE2) presented a 52% occurrence, and the compound 17ß-estradiol 17-acetate (E2-17A), a 32% one. The occurrence in the effluent samples was 48% for E1, 28% for E2, 12% for E2-17A, and 40% for EE2. The highest concentrations of E1 and EE2 hormones in the influent were 3050 and 3180 ng L(-1), respectively, whereas E2 and E2-17A had maximum concentrations of 776 and 2300 ng L(-1), respectively. The lowest efficiencies for the removal of estrogenic hormones were found in WWTP consisted of waste stabilization ponds, ranging from 54 to 79.9%. The high-rate systems (AS and UASB), which have chlorination as post-treatment, presented removal efficiencies of approximately 95%.

Rodlet cells development in the intestine of sea bass (Dicentrarchus labrax).

The enigmatic rodlet cells (RCs) are characterized by conspicuous inclusions named "rodlets". They were discovered over 100 years ago and were considered as parasites but shortly afterward interpreted as endogenous cells. The RCs have been described in different tissues of marine and freshwater teleosts, but their origin and function remain unknown. This work was designed to an ultrastructural study on RCs development and distribution in intestinal epithelium of Dicentrarchus labrax. Three different stages of RCs development from early precursor cells to mature phase were observed, as well as a migration and finally an extrusion of their contents. In this study, the immature cells were found near the basal epithelium membrane. They were mainly identified by a rough endoplasmic reticulum with dilated cisternae, by developing rodlets and a thin fibrillar coat. The maturing RCs, localized in the middle zone of the epithelium, appeared to be undergoing a reorganization of the cell organelles. The mature RCs, placed near the free surface, showed a thick subplasmalemmar fibrillar coat. Most of the organelles were aggregated at the cell apex with a basally located nucleus. A cellular polarity was more evident. One of the most conspicuous features was the occurrence of mature rodlets club-sac in shape orientated toward the cell apex. Adhesive junctions between surface epithelial cells and RCs, while discharging their contents, were seen. We have connected morphological figures and distribution to different stages of development in RCs, supporting the hypothesis of their secretory function.

Presença de corantes e lactose em medicamentos: avaliação de 181 produtos / Oyes and lactose in drugs: evaluation of 181 products

Corantes e lactose são frequentemente utilizados como excipientes em medicações pediátricas e podem causar reações adversas em crianças, inclusive com manifestações clínicas graves. Objetivo: Descrever a presença de corantes e de lactose em medicamentos habitualmente utilizados em prescrições pediátricas no Brasil. Método: Para descrição dos aditivos (corante e lactose) presentes nas medicações foram utilizados para consulta bulas, bulários e registros na entidade nacional regulatória (Agência Nacional de Vigilância Sanitária). Resultados: Foram analisados 181 diferentes apresentações de 42 medicamentos sendo que para apenas quatro drogas não constavam as informações requeridas nas fontes pesquisadas. Os medicamentos foram classificados como analgésicos/antipiréticos, antiinflamatórios não esteróides, antibióticos, anti-histamínicos, antieméticos, corticóides orais, corticóides inalatórios, broilcodilatadores de ação prolongada, corticosteróides inalatórios associados a broncodilatadores, antileucotrienos e estabilizadores da membrana de mastócitos. Das 181 apresentações, 28% contêm lactose e 26% contêm algum corante. Dentre estes os mais citados foram tartrazina, amarelo crepúsculo e vermelho 40. Conclusão: A maioria dos medicamentos analisados descreve adequadamente seus excipientes em alguma das fontes pesquisadas. O conhecimento dos excipientes contidos nas formulações farmacêuticas permite a melhor adequação das prescrições pediátricas, especialmente para aqueles pacientes que já apresentaram antecedente de reação adversa medicamentosa.

Dyes and lactose are frequently used as excipients in pediatric medications and can cause adverse reactions to children, moreover severe clinicai manifestations. Objective: To describe the presence of dyes and lactose in drugs usually used in pediatric prescriptions in Brazil. Method: For description of the excipients (dyes and lactose) presented in the medications, it was performed a survey on drug labels, bulls and registrations in the National Agency of Sanitary Surveillance. Results: 181 different presentations of 42 medicines were analysed. Excipient's information was not found in the researched sources for four drugs. The medicines were c1assified as analgesic/antipyretic, non-steroidal anti-inflammatories, antibiotics, antihistamines, antiemetics, oral corticosteroids, inhaled corticosteroids, long-acting beta-agonists, inhaled corticosteroids associated with long-acting beta-agonists, antileukotrienes and mast cell stabilizers. Of the 181 presentations, 28% contain lactose and 26% contain any dye. Among these, the more frequently mentioned were tartrazine yellow, sunset yellow and red#40. Conclusion: Most of the analyzed drugs described their excipients appropriately in the researched sources. The knowledge of the excipients contained in the pharmaceutical formulations allows the best adaptation of the pediatric prescriptions, especially for those patients that have already presented any adverse drug reaction.

Differential distribution of S100 protein and calretinin in mechanosensory and chemosensory cells of adult zebrafish (Danio rerio).

Calcium-binding proteins play a critical role in vertebrate sensory cells, and some of them have been detected in mechanosensory and chemosensory cells of bony and cartilaginous fishes. In this study immunohistochemistry and Western blot were used to investigate the occurrence and the distribution of S100 protein and calretinin in mechanosensory (neuromasts of the lateral line system; maculae and cristae ampullaris of the inner ear) as well as chemosensory (superficial and oral taste buds; olfactory epithelium) cells in adult zebrafish (Danio rerio). Specific protein bands with an estimated molecular weight of around 10 kDa and 30 kDa were detected by Western blot and were identified with S100 protein and calretinin, respectively. S100 protein and calretinin were observed segregated in mechanosensory and chemosensory cells, and the presence of S100 protein in a cell excluded that of calretinin, and vice versa. As a rule, the mechanosensory cells were S100 protein positive, whereas the chemosensory ones displayed calretinin immunoreactivity. Calretinin was also detected in nerve fibers supplying some of the investigated organs. In the olfactory epithelium, S100 protein immunoreactivity was present in the crypt olfactory sensory neurons, whereas calretinin immunoreactivity was widespread in olfactory sensory neurons and probably other olfactory cells. In this localization the co-expression of S100 protein and calretinin cannot be excluded. These results demonstrate the cell segregation of two specific calcium-binding proteins, and they enable to selectively label these cells by using easily reproducible immunohistochemical techniques associated to well-known antibodies.

Beta-catenin localization and timing of early development of bovine embryos obtained from oocytes matured in the presence of follicle stimulating hormone.

In mammalian species, embryos which grow more rapidly are believed to be more competent and viable than they are slower developing counterparts. Although the most important decrease in development occurs between the zygote and blastocyst stages, there is a growing amount of evidence to suggest that maturation conditions and oocyte quality have a profound influence on the developmental potential of early mammalian embryos. Gene transcripts and polypeptides stored in the oocytes, such as junctional proteins, sustain the initial development of embryos. In the present study we demonstrated a relationship between the timing of the development of in vitro-produced bovine embryos and the distribution and localization of the junctional protein beta-catenin. We further demonstrated that the presence of FSH during IVM supports cleavage and the blastocyst rate, and also has a positive effect on the speed of development, since embryos obtained from oocytes matured with the gonadotropin and observed on days 4, 5 and 6 post-insemination (p.i.) grew faster than those matured in a medium supplemented with BSA. Moreover, the majority of embryos which developed past the 16-cell stage showed a proper distribution of beta-catenin just beneath the membrane surfaces of all blastomeres and an appropriate morphology, as confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analysis. In conclusion, our data suggest that supplementing FSH during in vitro maturation aids the development of bovine embryos and promotes the correct expression of beta-catenin, increasing the likelihood that embryos will develop to the blastocyst stage.

Human immunodeficiency virus type 1 (HIV-1) and Mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic profiles in a Brazilian cohort.

Co-infections with human immunodeficiency virus (HIV) and Mycobacterium leprae represent unique opportunities to investigate the interaction of both pathogens. We determined the immunologic, virologic, and histopathologic characteristics of 22 co-infected Brazilian patients (median age = 38 years, 81.8% males, 72.2% with paucibacillary leprosy, and 95.4% with acquired immunodeficiency syndrome). The HIV-1 subtypes B and BF predominated in envelope and gag heteroduplex mobility analysis. Borderline tuberculoid (BT), tuberculoid, lepromatous, and indeterminate morphology with CD3+, CD8+, and CD68+ cell distributions compatible with leprosy patients not infected with HIV were observed. Histologic evidence of nerve damage was observed in BT lesions. IgM antibody to M. leprae-specific phenolic glycolipid I was not detected. Two of six co-infected patients monitored during highly active antiretroviral therapy (HAART) developed a leprosy type 1 reaction after an increase in CD4+ cells, suggesting an immune restoration phenomenon. Clinical, immunologic, histopathologic, and virologic features among these HIV-leprosy co-infected patients indicate that each disease progressed as in single infection. However, HAART immune reconstitution may trigger potential adverse effects, such as leprosy acute inflammatory episodes.

Absence of Meissner corpuscles in the digital pads of mice lacking functional TrkB.

The TrkB-expressing sensory neurons seem to be involved in touch and other discriminative sensibilities. Thus, several slowly and rapidly adapting cutaneous mechanoreceptors, as well as muscle spindles, are reduced or absent in the territory of the trigeminal nerve in functionally TrkB-deficient mice. Whether this also occurs in the cutaneous or muscular territories of dorsal root ganglia has not been analyzed. Here we used immunohistochemistry and transmission-electron microscopy to analyze the impact of a mutation in the gene coding for TrkB on Meissner and Pacinian corpuscles, and muscle spindles. The animals were studied at the post-natal days 15 and 25, because at this time all the mechanoreceptors examined are fully developed. Typical Meissner's corpuscles, displaying S-100 protein immunoreactivity, were found in the digital pads of wild-type and TrkB+/- mice whereas they were absent in the TrkB-/- animals. Regarding Pacinian corpuscles, the mutation in the trkB gene does not alter either the immunohistochemical or the ultrastructural characteristics. Finally, in muscle spindles the arrangement of the intrafusal muscle fibers and nerve fibers was unchanged in the mutated animals. Nevertheless, about 10% of muscle spindles showed increased number of the intrafusal cells (between 6 and 12) and were supplied by more than one large myelinic nerve fiber. The present results strongly suggest that TrkB-expressing sensory neurons in dorsal root ganglia, like those of the trigeminal ganglion, are responsible for the development and maintenance of several rapidly adapting cutaneous mechanoreceptors, i.e. Meissner's corpuscles.

Insulin-like growth factor 1-receptor (IGF-1R) in developing and adult human dorsal root ganglia / El factor de crecimiento tipo insulina receptor-1 (IGF-1R) en los ganglios de la raíz dorsal humana en desarrollo y adulta

Insulin-like growth factors (IGFs) promote neurite outgrowth in cultured sensory neurons that binding to IGF type 1 receptor (IGF-1R) and seem to be involved in the pathogenesis of some metabolic and toxic peripheral neuropathies coursing with altered sensitivity. However, the distribution of IGF-1R in the human sensory peripheral nervous system is unknown. In this study, we used light immunohistochemistry to analyse the occurrence and localization of IGF-1R in developing (6 to 22 weeks of estimated gestational age, e.g.a.) and adult (age range 25-41 years) human dorsal root ganglia (DRG). In human embryos (6-8 weeks e.g.a.) and young foetuses (9 weeks e.g.a.), most neurons (84%, 92%, and 83%, respectively) displayed IGF-1R immunoreactivity (IR). In older foetuses (12 and 22 weeks e.g.a.), the number of immunoreactive neurons decreased progressively (78 and 68%, respectively) reaching values similar to those observed in adults (64%). The subpopulation of adult primary sensory neurons showing IGF-1R IR covered the entire size range, but the neurons were mainly small. Furthermore, in adults all satellite glial cells and Schwann cells were immunoreactive. The present results suggest a role for IGF-1R in the differentiation and maturation of primary sensory neurons, and in the maintenance of a subset of them in adulthood, as well as in the control of peripheral glial cells (Schwann and satellite glial cells). These findings might serve as a basis for future studies in pathologic DRG, in which IGF-1R or its ligands may be involved (AU)

Los factores de crecimiento tipo insulina (IGFs) promueven el crecimiento de neuritas en neuronas sensitivas en cultivo que se unen al IGF receptor tipo 1 (IGF-1R) y parecen estar implicados en la patogénesis de algunas neuropatías periféricas metabólicas y tóxicas cursando con alteraciones de la sensibilidad. Sin embargo, se desconoce la distribución de IGF-1R en el sistema nervioso periférico sensitivo humano. En este estudio, usamos inmunohistoquímica a microscopía óptica para analizar la existencia y localización de IGF-1R en los ganglios de la raíz dorsal humana (DRG) en desarrollo (6 a 22 semanas de edad estimada de gestación, e.g.a.) y adulta (rango de edad de 25-41 años). En embriones humanos (6-8 semanas e.g.a.) y fetos jóvenes (9 semanas e.g.a.), la mayoría de las neuronas (84 por ciento, 92 por ciento, y 83 por ciento, respectivamente) mostraron inmunorreactividad (IR) a IGF-1R. En fetos de más edad (12 y 22 semanas e.g.a.), el número de neuronas inmunorreactivas disminuyó progresivamente (78 y 68 por ciento, respectivamente), alcanzando valores similares a los observados en los adultos (64 por ciento). La subpoblación de neuronas sensitivas primarias adultas que mostraron IGF-1R IR cubrieron un rango completo de tamaños, pero las neuronas fueron principalmente pequeñas. Además, en adultos todas las células satélites gliales y las células de Schwann fueron inmunorreactivas. Los presentes resultados sugieren un papel para IGF-1R en la diferenciación y maduración de las neuronas sensitivas primarias, y en el mantenimiento de una subpoblación de ellas en el estado adulto, así como en el control de las células gliales periféricas (Schwann y células satélites gliales). Estos hallazgos podrían servir como base para futuros estudios de los ganglios de la raíz dorsal patológicos, en los que el IGF-1R o sus ligandos pueden estar implicados (AU)