Regulation of kidney mitochondrial function by caloric restriction.

Caloric restriction (CR) prevents obesity and increases resilience against pathological stimuli in laboratory rodents. At the mitochondrial level, protection promoted by CR in the brain and liver is related to higher Ca2+ uptake rates and capacities, avoiding Ca2+-induced mitochondrial permeability transition. Dietary restriction has also been shown to increase kidney resistance against damaging stimuli; if these effects are related to similar mitochondrial adaptations has not been uncovered. Here, we characterized changes in mitochondrial function in response to 6 mo of CR in rats and measured bioenergetic parameters, redox balance, and Ca2+ homeostasis. CR promoted an increase in succinate-supported mitochondrial oxygen consumption rates. Although CR prevents mitochondrial reactive oxygen species production in many tissues, in kidney, we found that mitochondrial H2O2 release was enhanced in a succinate-dependent manner. Surprisingly, and opposite to the effects observed in the brain and liver, mitochondria from CR animals were more prone to Ca2+-induced mitochondrial permeability transition, in a manner reversed by the antioxidant dithiothreitol. CR mitochondria also displayed higher Ca2+ uptake rates, which were not accompanied by changes in Ca2+ efflux rates or related to altered inner mitochondrial membrane potentials or amounts of the mitochondrial Ca2+ uniporter. Instead, increased mitochondrial Ca2+ uptake rates in CR kidneys correlated with loss of mitochondrial Ca2+ uptake protein 2 (MICU2), a mitochondrial Ca2+ uniporter modulator. Interestingly, MICU2 is also modulated by CR in the liver, suggesting that it has a broader diet-sensitive regulatory role controlling mitochondrial Ca2+ homeostasis. Together, our results highlight the organ-specific bioenergetic, redox, and ionic transport results of CR, with some unexpected deleterious effects in the kidney.NEW & NOTEWORTHY Prevention of obesity through caloric restriction (CR) is well known to protect many tissues but has been poorly studied in kidneys. Here, we determined the effects of long-term CR in rat kidney mitochondria, which are central players in energy metabolism and aging. Surprisingly, we found that the diet increased mitochondrial reactive oxygen production and permeability transition. This suggests that the kidneys respond differently to restricted diets and may be more susceptible under CR.

Melatonin regulates maternal pancreatic remodeling and B-cell function during pregnancy and lactation.

The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well-known the role of melatonin in the maintenance of the endocrine pancreas and its tropism. Studies indicate increasing nocturnal serum concentrations of maternal melatonin during pregnancy in both humans and rodents. The present study investigated the role of melatonin on energy metabolism and in pancreatic function and remodeling during pregnancy and early lactation in rats. The results confirm that the absence of melatonin during pregnancy impairs glucose metabolism. In addition, there is a dysregulation in insulin secretion at various stages of the development of pregnancy and an apparent failure in the glucose-stimulated insulin secretion during the lactation period, evidencing the role of melatonin on the regulation of insulin secretion. This mechanism seems not to be dependent on the antioxidant effect of melatonin and probably dependent on MT2 receptors. We also observed changes in the mechanisms of death and cell proliferation at the end of pregnancy and beginning of lactation, crucial periods for pancreatic remodeling. The present observations strongly suggest that both functionality and remodeling of the endocrine pancreas are impaired in the absence of melatonin and its adequate replacement, mimicking the physiological increase seen during pregnancy, is able to reverse some of the damage observed. Thus, we conclude that pineal melatonin is important to metabolic adaptation to pregnancy and both the functionality of the beta cells and the remodeling of the pancreas during pregnancy and early lactation, ensuring the return to nonpregnancy conditions.

Remarks on Eimeria spp. (Apicomplexa: Eimeriidae) from Kobus spp. (Bovidae: Reduncini), with supplementary morphological data of Eimeria congolensis Ricci-Bitti et al., 1973 from a new host subspecies, the common waterbuck Kobus ellipsiprymnus ellipsiprymnus (Ogilbyi, 1833).

Reduncin bovids of Kobus spp. (Bovidae: Reduncini) are natively distributed in sub-Saharan Africa, although some populations have been introduced into parks and zoos around the world. The majority of the species has declining populations, being categorized as threatened by the International Union for Conservation of Nature and Natural Resources; therefore, protective measures for the conservation of Kobus spp. are necessary, including the study of their parasites, such as the eimeriid coccidians (Apicomplexa: Eimeriidae). In this context, the aim of the current study was to brings together the taxonomic data from the descriptions and reports of Eimeria spp. from reduncin bovids, based on the detailed morphological identification of Eimeria congolensis Ricci-Bitti, Pampiglione & Kabala, 1973 from a new host subspecies, the common waterbuck Kobus ellipsiprymnus ellipsiprymnus (Ogilbyi, 1833), in a safari park of Portugal. Five Eimeria spp. are recorded from reduncin bovids, in addition to six more reports identified generically as Eimeria sp., which were compared and taxonomically rearranged. The oocysts identified as E. congolensis in the current study were compatible with the original description and were supplemented for some taxonomic characters not originally included, such as: Stieda body flattened to nipplelike, sub-Stieda body rounded to trapezoidal, sporocyst residuum granular and membrane-bound, in addition to greater details of the micropyle, among others. Finally, the current study highlights the importance of studying the coccidians of reduncin bovids for the conservation of Kobus spp. due to the possibility of these Eimeria spp. are extra-intestinal parasites, which can potentially cause severe coccidiosis associated with increased morbidity and mortality in certain threatened populations of Kobus spp.

Evaluation of the Influence of Geodimensional and Histological Parameters on the Need for Margin Widening in Breast Lesions Marked With Magnetic Seeds.

Objective: Breast cancer is an important topic worldwide, posing morbidity and mortality to women. Considerable efforts have been put in the early recognition of malignancy through different screening methods, such as mammography and ultrasound. The precise localization of infraclinical malignant lesions is key in surgical management and magnetic seeds gather particular interest for this purpose. As with other systems, a need for reintervention may be needed to obtain adequate surgical margins. This work evaluated the relation between the need for surgical reintervention in order to obtain negative margins and geodimensional and histological parameters. The main objective was the identification of parameters significantly associated with reintervention for margin widening. Materials and Methods: A retrospective analysis of 198 patients from a single centre was performed. The association between pre-defined geodimensional and histological parameters and the need for margin widening in infraclinical lesions marked with magnetic seed was evaluated. Results: Results showed that reintervention to widen margins was significantly higher in patients with ductal carcinoma in situ (DCIS) in the pre-operative biopsy when compared with invasive carcinoma (p = 0.03) in the bivariate analysis. No statistically significant differences were observed between the need for reintervention and lesion size (p = 0.197), breast quadrant location (p = 0.626) and distance of skin to lesion (p = 0.356). Conclusion: This work suggests that a more invasive margin clearance in lesions with a pre-operative DCIS diagnosis might obviate the need for reintervention to obtain negative margins. On the other hand, it is not necessary to be surgically more invasive in larger lesions, deeply located or that are present in a certain quadrant, since there are no significant differences regarding the need for reintervention.

Perforated duodenal ulcer after Roux-en-Y gastric bypass: an unusual complication.

Summary: Bariatric surgery is increasingly being accepted as a viable treatment for managing the growing obesity epidemic. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures. Perforated duodenal ulcer following RYGB is a rare condition with a low incidence. We report a case of a patient with a perforated duodenal ulcer post RYGB, and the surgical approach. A 66-year-old man with hypertension and a history of laparoscopic RYGB for class III obesity was admitted to the emergency department with severe epigastric pain radiating to the right side of his abdomen and right shoulder, associated with nausea and vomiting. Computed tomography (CT) showed intraperitoneal free fluid, a thickened wall of the duodenum and free air, duodenal perforation was suspected. The patient underwent exploratory laparoscopy that revealed a perforated duodenal ulcer that was closed with an absorbable barbed suture and omental patch. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis, and clinicians should be aware of and have a low threshold for diagnostic laparoscopy. Learning points: Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures in bariatric surgery. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis. The pathophysiology of this perforation is not clear, but several mechanisms have been proposed. Helicobacter pylori has been implicated. Clinicians should be aware and have a low threshold for diagnostic laparoscopy for a patient who has acute abdominal pain after RYGB, despite negative diagnostic measures.

Adiponectin reverses ß-Cell damage and impaired insulin secretion induced by obesity.

Obesity significantly decreases life expectancy and increases the incidence of age-related dysfunctions, including ß-cell dysregulation leading to inadequate insulin secretion. Here, we show that diluted plasma from obese human donors acutely impairs ß-cell integrity and insulin secretion relative to plasma from lean subjects. Similar results were observed with diluted sera from obese rats fed ad libitum, when compared to sera from lean, calorically restricted, animals. The damaging effects of obese circulating factors on ß-cells occurs in the absence of nutrient overload, and mechanistically involves mitochondrial dysfunction, limiting glucose-supported oxidative phosphorylation and ATP production. We demonstrate that increased levels of adiponectin, as found in lean plasma, are the protective characteristic preserving ß-cell function; indeed, sera from adiponectin knockout mice limits ß-cell metabolic fluxes relative to controls. Furthermore, oxidative phosphorylation and glucose-sensitive insulin secretion, which are completely abrogated in the absence of this hormone, are restored by the presence of adiponectin alone, surprisingly even in the absence of other serological components, for both the insulin-secreting INS1 cell line and primary islets. The addition of adiponectin to cells treated with plasma from obese donors completely restored ß-cell functional integrity, indicating the lack of this hormone was causative of the dysfunction. Overall, our results demonstrate that low circulating adiponectin is a key damaging element for ß-cells, and suggest strong therapeutic potential for the modulation of the adiponectin signaling pathway in the prevention of age-related ß-cell dysfunction.

Calorie restriction changes muscle satellite cell proliferation in a manner independent of metabolic modulation.

Calorie restriction is known to promote healthy aging, which includes prevention of muscle loss. We investigated the effect of rodent calorie restriction on mitochondrial respiration and clonogenic capacity of muscle satellite stem cells, since metabolic alterations are known to regulate stem cell activity. Surprisingly, short or long-term calorie restriction do not change mitochondrial or glycolytic function. Nevertheless, both short- and long-term calorie restriction enhance myogenic colony formation. Overall, our results show that not all changes in satellite stem cell function are accompanied by metabolic remodeling.

Intermittent Fasting for Twelve Weeks Leads to Increases in Fat Mass and Hyperinsulinemia in Young Female Wistar Rats.

Fasting is known to cause physiological changes in the endocrine pancreas, including decreased insulin secretion and increased reactive oxygen species (ROS) production. However, there is no consensus about the long-term effects of intermittent fasting (IF), which can involve up to 24 hours of fasting interspersed with normal feeding days. In the present study, we analyzed the effects of alternate-day IF for 12 weeks in a developing and healthy organism. Female 30-day-old Wistar rats were randomly divided into two groups: control, with free access to standard rodent chow; and IF, subjected to 24-hour fasts intercalated with 24-hours of free access to the same chow. Alternate-day IF decreased weight gain and food intake. Surprisingly, IF also elevated plasma insulin concentrations, both at baseline and after glucose administration collected during oGTT. After 12 weeks of dietary intervention, pancreatic islets displayed increased ROS production and apoptosis. Despite their lower body weight, IF animals had increased fat reserves and decreased muscle mass. Taken together, these findings suggest that alternate-day IF promote ß -cell dysfunction, especially in developing animals. More long-term research is necessary to define the best IF protocol to reduce side effects.

The insulin resistance is reversed by exogenous 3,5,3'triiodothyronine in type 2 diabetic Goto-Kakizaki rats by an inflammatory-independent pathway.

PURPOSE: Diabetes mellitus (DM) has a multifactorial etiology that imparts a particular challenge to effective pharmacotherapy. Thyroid hormone actions have demonstrated beneficial effects in diabetic as well as obese rats. In both conditions, inflammation status plays a crucial role in the development of insulin resistance. Taking this into consideration, the present study aimed to demonstrate another possible pathway of thyroid hormone action on insulin sensitivity in a spontaneous type 2 diabetic rat model: the Goto-Kakizaki (GK) rats. GK animals present all typical hallmarks of type 2 DM (T2DM), except the usual peripheric inflammatory condition, observed in the other T2DM animal models. METHODS: GK rats were treated or not with 3,5,3'triiodothyronine (T3). Insulin sensitivity, glucose tolerance, and proteins related to glucose uptake and utilization were evaluated in the skeletal muscle, white adipose tissue, and liver. RESULTS: GK rats T3-treated presented enhanced insulin sensitivity, increased GLUT-4 content in the white adipose tissue and skeletal muscle, and increased hexokinase and citrate synthase content in skeletal muscle. Both non-treated and T3-treated GK rats did not present alterations in cytokine content in white adipose tissue, skeletal muscle, liver, and serum. CONCLUSIONS: These results indicate that T3 improves insulin sensitivity in diabetic rats by a novel inflammatory-independent mechanism.

Liderança no exercício docente no ensino superior: um olhar psicodinâmico / Leadership in teaching in higher education: a psychodynamic perspective / Liderazgo en la enseñanza en la educación superior: una perspectiva psicodinámica

O trabalho docente representa um campo fundamental na sociedade, dada sua importância na formação de futuros profissionais e, especialmente, cidadãos. Dessa forma, a intenção do presente artigo consiste em levantar as questões oriundas do exercício de liderança na atribuição docente e refletir acerca desta liderança no Ensino Superior no que tange à sua importância para o processo formativo, bem como a inspiração que esse ofício pode proporcionar aos educandos, partindo da ideia de que a docência é um exercício de liderança. A proposta metodológica com que analisamos tal exercício, consiste na perspectiva qualitativa de caráter descritivo-analítico. Dois professores foram entrevistados por meio de um roteiro semi-dirigido com vistas a levantar e compreender as experimentações oriundas de suas trajetórias de vida que culminaram no trabalho docente que atualmente exercem. Como fundamentação teórica e metodológica de análise, utilizou-se a Psicodinâmica do Trabalho, por seu olhar quanto aos modos de ser dos sujeitos provocados pelo encontro com o trabalho e as exigências pertinentes aos processos deste. Como resultado, a amostra revelou significativa concordância com os aspectos de liderança na prática docente que exercem, embora reiterassem que existem consideráveis dificuldades nesse ofício. Essa clareza requer uma mobilização por parte dos professores líderes que por vezes se sentem sobrecarregados e redescobrindo meios de não adoecerem. Tais resultados têm potência para que novos estudos sejam elaborados no sentido de ampliar a discussão e contribuir para ações docentes, mas, sobretudo, humanas, melhores e mais afetivas.(AU)

Teaching work represents a fundamental field in society, given its importance in the training of future professionals and, especially, citizens. In this way, the intention of this article is to raise the matters arising from the exercise of leadership in teaching assignments and to reflect on this leadership in Higher Education in terms of its importance for the training process, as well as the inspiration that this craft can provide to students, based on the idea that teaching is an exercise in leadership. The methodological proposal with which we analyze this exercise consists of a qualitative perspective of a descriptive-analytical nature. Two teachers were interviewed through a semi-guided script which intended to raise and understand the experiences arising from their life trajectories that culminated in the teaching work they currently perform. As a theoretical and methodological basis for the analysis, the Psychodynamics of Work was used, due to its view on the subjects' ways of being, provoked by the encounter with work and the demands pertinent to its processes. As a result, the sample revealed significant agreement with the aspects of leadership in their teaching practice, although they reiterated that there are considerable difficulties in this job. This clarity requires mobi-lization on the part of leading teachers who sometimes feel overwhelmed and rediscover ways not to get sick. Such results have the power for new studies to be developed in order to broaden the discussion and contribute to teaching actions, but, above all, human, better and more affective actions. (AU)

El trabajo docente representa un campo fundamental en la sociedad, dada su importancia en la formación de los futuros profesionales y, en especial, de los ciudadanos. De esta forma, la intención de este artículo es plantear las cues-tiones derivadas del ejercicio del liderazgo en la tarea docente y reflexionar sobre este liderazgo en la Educación Superior en cuanto a su importancia para el proceso formativo, así como la inspiración que este oficio puede brindar a los estudiantes, partiendo de la idea de que enseñar es un ejercicio de liderazgo. La propuesta metodológica con la que analizamos este ejercicio consiste en una perspectiva cualitativa de carácter descriptivo-analítico. Se entrevistó a dos docentes a través de un guion semidirigido con miras a plantear y comprender las experiencias surgidas de sus trayectorias de vida que culminaron en la labor docente que desempeñan actualmente. Como base teórica y metodológica para el análisis, se utilizó la Psicodinámica del Trabajo, por su mirada sobre las formas de los sujetos de ser provocados por el encuentro con el trabajo y las exigencias propias de sus procesos. Como resultado, la muestra reveló un acuerdo significativo con los aspectos de liderazgo en su práctica docente, aunque reiteraron que existen dificultades considerables en este trabajo. Esta claridad requiere movilización por parte de los docentes líderes que a veces se sienten abrumados y redescubriendo formas de no enfermarse. Tales resul-tados tienen el poder de que se desarrollen nuevos estudios para ampliar la discusión y contribuir a la acción docente, pero, principalmente, a la acción humana, mejor y más afectiva. (AU)

Immediate and residual effects of low-dose nandrolone decanoate and treadmill training on adipose and reproductive tissues of male Wistar rats.

CONTEXT: Residual effects after nandrolone decanoate (ND) treatment are not reported. OBJECTIVE: Immediate and residual effects of low-dose ND and treadmill training were investigated. MATERIALS AND METHODS: Male rats were trained and/or ND-treated for four weeks and the assessments were made after this period or four weeks later. RESULTS: The groups did not differ in final plasma glucose or AUC of the ivGTT, but hyperinsulinemia was noticed in some trained/treated groups. Training with ND increased muscle mass and ND decreased the reproductive structures. Decreased fat with training was reversed by detraining. DISCUSSION: The anabolic action of ND on skeletal muscle was enhanced by training. Fat and lipid changes were more linked to training/detraining, but the effects of ND on the reproductive structures persisted after treatment. CONCLUSIONS: The effects of training on fat and muscle were not maintained after detraining, but low-dose ND had persistent effects on the reproductive structures.

Control of Insulin Secretion by Production of Reactive Oxygen Species: Study Performed in Pancreatic Islets from Fed and 48-Hour Fasted Wistar Rats.

Mitochondria and NADPH oxidase are important sources of reactive oxygen species in particular the superoxide radical (ROS) in pancreatic islets. These molecules derived from molecular oxygen are involved in pancreatic ß-cells signaling and control of insulin secretion. We examined the involvement of ROS produced through NADPH oxidase in the leucine- and/or glucose-induced insulin secretion by pancreatic islets from fed or 48-hour fasted rats. Glucose-stimulated insulin secretion (GSIS) in isolated islets was evaluated at low (2.8 mM) or high (16.7 mM) glucose concentrations in the presence or absence of leucine (20 mM) and/or NADPH oxidase inhibitors (VAS2870-20 µM or diphenylene iodonium-DPI-5 µM). ROS production was determined in islets treated with dihydroethidium (DHE) or MitoSOX Red reagent for 20 min and dispersed for fluorescence measurement by flow cytometry. NADPH content variation was examined in INS-1E cells (an insulin secreting cell line) after incubation in the presence of glucose (2.8 or 16.7 mM) and leucine (20 mM). At 2.8 mM glucose, VAS2870 and DPI reduced net ROS production (by 30%) and increased GSIS (by 70%) in a negative correlation manner (r = -0.93). At 16.7 mM glucose or 20 mM leucine, both NADPH oxidase inhibitors did not alter insulin secretion neither net ROS production. Pentose phosphate pathway inhibition by treatment with DHEA (75 µM) at low glucose led to an increase in net ROS production in pancreatic islets from fed rats (by 40%) and induced a marked increase (by 144%) in islets from 48-hour fasted rats. The NADPH/NADP+ ratio was increased when INS-1E cells were exposed to high glucose (by 4.3-fold) or leucine (by 3-fold). In conclusion, increased ROS production through NADPH oxidase prevents the occurrence of hypoglycemia in fasting conditions, however, in the presence of high glucose or high leucine levels, the increased production of NADPH and the consequent enhancement of the activity of the antioxidant defenses mitigate the excess of ROS production and allow the secretory process of insulin to take place.

Melatonin modifies basal and stimulated insulin secretion via NADPH oxidase.

Melatonin is a hormone synthesized in the pineal gland, which modulates several functions within the organism, including the synchronization of glucose metabolism and glucose-stimulated insulin secretion (GSIS). Melatonin can mediate different signaling pathways in pancreatic islets through two membrane receptors and via antioxidant or pro-oxidant enzymes modulation. NADPH oxidase (NOX) is a pro-oxidant enzyme responsible for the production of the reactive oxygen specie (ROS) superoxide, generated from molecular oxygen. In pancreatic islets, NOX-derived ROS can modulate glucose metabolism and regulate insulin secretion. Considering the roles of both melatonin and NOX in islets, the aim of this study was to evaluate the association of NOX and ROS production on glucose metabolism, basal and GSIS in pinealectomized rats (PINX) and in melatonin-treated isolated pancreatic islets. Our results showed that ROS content derived from NOX activity was increased in PINX at baseline (2.8 mM glucose), which was followed by a reduction in glucose metabolism and basal insulin secretion in this group. Under 16.7 mM glucose, an increase in both glucose metabolism and GSIS was observed in PINX islets, without changes in ROS content. In isolated pancreatic islets from control animals incubated with 2.8 mM glucose, melatonin treatment reduced ROS content, whereas in 16.7 mM glucose, melatonin reduced ROS and GSIS. In conclusion, our results demonstrate that both basal and stimulated insulin secretion can be regulated by melatonin through the maintenance of ROS homeostasis in pancreatic islets.

Evidências para a avaliação dos pés da pessoa com diabetes mellitus / Evidence for the evaluation of the feet of people with diabetes mellitus

Objetivo: identificar os critérios de avaliação dos pés da pessoa com Diabetes Mellitus. Método: revisão integrativa com busca nas bases de dados MEDLINE, LILACS, Cochrane, SCOPUS e biblioteca virtual SciELO, com delimitação temporal entre 2011 e 2017 e amostra final de 16 artigos categorizados em anamnese, avaliação da pele e anexos, avaliação neurológica, avaliação vascular, avaliação anatômica dos pés e autocuidado. Resultados: a maioria dos artigos foi de 2013, com nível de evidência II. A categoria anamnese compreendeu questões sociodemográficas e clínicas e a categoria avaliação da pele e anexos contemplou as afecções de pele, unhas, pelos e espaços interdigitais. Na categoria avaliação neurológica, predominou o teste com monofilamento Semmes-Weinstein 10g para a avaliação da sensibilidade tátil. Na avaliação vascular, destacou-se a palpação dos pulsos pediosos e tibiaisposteriores. Na categoria avaliação anatômica dos pés, apenas dois artigos retrataram o tipo de deformidade pesquisada e em quatro estudos foram realizadas orientações de autocuidado. Conclusão: Em síntese, o estudo permitiu extrair indicadores importantes para a avaliação dos pés e observou-se consonância entre as pesquisas analisadas com o que é recomendado.(AU)

Artrite psoriásica associada com hiperprolactinemia: relato de caso / Psoriatic arthritis in association with hyperprolactinemia: report of a case

Relatamos um caso raro de paciente do sexo feminino, 32 anos com diagnóstico de Artrite Psoriásica que na evoluçäo apresentou Hiperprolactinemia e conseqüente galactorréia e amenorréia. Esta associaçäo mostrou um caso raro na literatura médica nos últimos dez anos

Manifestaçöes otorrinolaringológicas em pacientes com síndrome de imunodeficiência adquirida (Sida) / Otolaryngologic manifestations in patients with acquired immunodeficiency syndrome (AIDS)

Os sintomas, diagnósticos e tratamentos das manifestaçoes otorrinolaringológicas de 25 pacientes com Sida, foram retrospectivamente estudados. Oitenta e sete sintomas diferentes foram relatados, 51 diagnósticos e 17 intervençoes cirúrgicas foram realizadas. A maioria dos pacientes apresentou mais de uma manifestaçao. A grande variedade de patologias e a alta incidência de afecçoes otorrinolaringológicas na Sida foram também discutidas.