Effect of Fe3+ on Na,K-ATPase: Unexpected activation of ATP hydrolysis.

Iron is a key element in cell function; however, its excess in iron overload conditions can be harmful through the generation of reactive oxygen species (ROS) and cell oxidative stress. Activity of Na,K-ATPase has been shown to be implicated in cellular iron uptake and iron modulates the Na,K-ATPase function from different tissues. In this study, we determined the effect of iron overload on Na,K-ATPase activity and established the role that isoforms and conformational states of this enzyme has on this effect. Total blood and membrane preparations from erythrocytes (ghost cells), as well as pig kidney and rat brain cortex, and enterocytes cells (Caco-2) were used. In E1-related subconformations, an enzyme activation effect by iron was observed, and in the E2-related subconformations enzyme inhibition was observed. The enzyme's kinetic parameters were significantly changed only in the Na+ curve in ghost cells. In contrast to Na,K-ATPase α2 and α3 isoforms, activation was not observed for the α1 isoform. In Caco-2 cells, which only contain Na,K-ATPase α1 isoform, the FeCl3 increased the intracellular storage of iron, catalase activity, the production of H2O2 and the expression levels of the α1 isoform. In contrast, iron did not affect lipid peroxidation, GSH content, superoxide dismutase and Na,K-ATPase activities. These results suggest that iron itself modulates Na,K-ATPase and that one or more E1-related subconformations seems to be determinant for the sensitivity of iron modulation through a mechanism in which the involvement of the Na, K-ATPase α3 isoform needs to be further investigated.

Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats.

Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH1-24 on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH1-24 (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH1-24 dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100ß, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH1-24. ACTH1-24 could be further evaluated to determine its suitability for preclinical models of PVH in premature infants.

Iron overload: Effects on cellular biochemistry.

Iron is an essential element for human life. However, it is a pro-oxidant agent capable of reacting with hydrogen peroxide. An iron overload can cause cellular changes, such as damage to the plasma membrane leading to cell death. Effects of iron overload in cellular biochemical processes include modulating membrane enzymes, such as the Na, K-ATPase, impairing the ionic transport and inducing irreversible damage to cellular homeostasis. To avoid such damage, cells have an antioxidant system that acts in an integrated manner to prevent oxidative stress. In addition, the cells contain proteins responsible for iron transport and storage, preventing its reaction with other substances during absorption. Moreover, iron is associated with cellular events coordinated by iron-responsive proteins (IRPs) that regulate several cellular functions, including a process of cell death called ferroptosis. This review will address the biochemical aspects of iron overload at the cellular level and its effects on important cellular structures.

Importância da eletrocardiografia como um exame pré-cirúrgico em cães / Importance of electrocardiography as a pre-operative examination in dogs

Foi analisado o perfil eletrocardiográfico pré-cirúrgico de 124 cães submetidos a diferentes intervenções cirúrgicas com objetivo de relacionar as variáveis idade, sexo, porte, ausência ou presença de alterações cardiovasculares detectadas durante o exame físico e afecção cirúrgica com os achados eletrocardiográficos. Não foi observada associação entre essas variáveis e as alterações eletrocardiográficas. Um total de 79 animais (63,7%) apresentou algum tipo de alteração no eletrocardiograma. Assim, este estudo sugere que o exame eletrocardiográfico pré-cirúrgico é de grande valia, independente do sexo, idade, peso, histórico ou sinais clínicos associados a doença cardíaca.(AU)

An analysis of the pre-surgical electrocardiographic profile was made of 124 dogs submitted to different surgical interventions to correlate the variables age, sex, size, absence or presence of cardiovascular abnormalities detected during physical examination and of the surgical cases with electrocardiographic findings. No association between these variables and electrocardiographic changes were observed. A total of 79 cães (63.7%) showed some type of change in the electrocardiogram. The study suggests that pre-surgical electrocardiographic examination is of great importance, regardless of sex, age, weight, historic or clinical signs associated with heart disease.(AU)

Ventilatory and muscular assessment in healthy subjects during an activity of daily living with unsupported arm elevation.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) report dyspnea when performing activities of daily living (ADLs) with elevated upper limbs. To elucidate the determinants of dyspnea, it is important to study the changes in the respiratory pattern of these patients and the electromyographic activity of their accessory muscles of respiration during ADLs. In the literature, there are no reports of a normative parameter, therefore it is necessary to study how these variables behave in healthy subjects. OBJECTIVES: To verify, in healthy subjects, the existence of changes in the respiratory pattern and activation of the sternocleidomastoid (SCM) muscle during an ADL with unsupported arm elevation. METHODS: Thirteen male subjects, 60.57 (± 6.42) years old, with normal spirometry values for age and sex, were evaluated using surface electromyography (EMG) and respiratory inductive plethysmography (RIP) collected at rest and during the activity of combing their hair with elevated and unsupported upper limbs. The data distribution was assessed using Shapiro-Wilk's test. ANOVA was used to compare the phases, and when the difference was significant (p<0.05), Tukey's test was applied. RESULTS: The RIP during the ADL showed a significant increase in tidal volume, minute ventilation, respiratory frequency and mean inspiratory flow. Thoracoabdominal asynchrony was identified in percentage of asynchrony in inspiration, expiration, and Phase Angle (p<0.05). The EMG showed an increase in SMC muscle recruitment (p<0.05). CONCLUSIONS: Healthy subjects increased their SCM muscle activation and changed their breathing pattern when performing the ADL with unsupported arm elevation, resulting in thoracoabdominal asynchrony.

Ventilatory and muscular assessment in healthy subjects during an activity of daily living with unsupported arm elevation / Avaliação ventilatória e muscular de indivíduos saudáveis durante atividade de vida diária com os braços elevados e sem apoio

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) report dyspnea when performing activities of daily living (ADLs) with elevated upper limbs. To elucidate the determinants of dyspnea, it is important to study the changes in the respiratory pattern of these patients and the electromyographic activity of their accessory muscles of respiration during ADLs. In the literature, there are no reports of a normative parameter, therefore it is necessary to study how these variables behave in healthy subjects. OBJECTIVES: To verify, in healthy subjects, the existence of changes in the respiratory pattern and activation of the sternocleidomastoid (SCM) muscle during an ADL with unsupported arm elevation. METHODS: Thirteen male subjects, 60.57 (±6.42) years old, with normal spirometry values for age and sex, were evaluated using surface electromyography (EMG) and respiratory inductive plethysmography (RIP) collected at rest and during the activity of combing their hair with elevated and unsupported upper limbs. The data distribution was assessed using Shapiro-Wilk's test. ANOVA was used to compare the phases, and when the difference was significant (p<0.05), Tukey's test was applied. RESULTS: The RIP during the ADL showed a significant increase in tidal volume, minute ventilation, respiratory frequency and mean inspiratory flow. Thoracoabdominal asynchrony was identified in percentage of asynchrony in inspiration, expiration, and Phase Angle (p<0.05). The EMG showed an increase in SMC muscle recruitment (p<0.05). CONCLUSIONS: Healthy subjects increased their SCM muscle activation and changed their breathing pattern when performing the ADL with unsupported arm elevation, resulting in thoracoabdominal asynchrony.

INTRODUÇÃO: Pacientes com doença pulmonar obstrutiva crônica (DPOC) relatam dispneia quando realizam atividades da vida diária (AVD) com membros superiores (MMSS) elevados. Estudar as alterações do padrão respiratório e a atividade eletromiográfica dos músculos acessórios da respiração desses pacientes nas AVD pode contribuir para esclarecer os determinantes de dispneia. Entretanto, não se encontrou, na literatura, um padrão de normalidade, fazendo-se necessário estudar, primeiramente, o comportamento dessas variáveis em saudáveis. OBJETIVOS: Verificar, em indivíduos saudáveis, a existência de mudanças no padrão respiratório e na ativação do músculo esternocleidomastoideo (ECM) durante a realização de uma AVD com os MMSS elevados e sem apoio. MÉTODOS: Treze voluntários masculinos, com média de idade 60,57 (6,42) anos, com valores espirométricos normais para idade e sexo foram avaliados com eletromiografia (EMG) de superfície e pletismografia respiratória por indutância (PRI), coletadas durante o repouso e na atividade de pentear cabelos com MMSS elevados sem apoio. A distribuição dos dados foi analisada pelo teste Shapiro-Wilk. Para a comparação entre as fases avaliadas, utilizou-se ANOVA e, quando a diferença foi considerada significativa (p<0,05), aplicou-se o teste de Tuckey. RESULTADOS: A PRI, durante a AVD, mostrou aumentos significativos do volume corrente, do volume minuto, da frequência respiratória e do fluxo inspiratório médio. Observou-se assincronia toracoabdominal tanto em porcentagem de assincronia na inspiração e na expiração quanto na análise do Ângulo de Fase (p<0,05). A EMG mostrou aumento no recrutamento do ECM (p<0,05). CONCLUSÕES: Indivíduos saudáveis apresentam maior ativação do músculo ECM e modificam o padrão respiratório durante AVD com MMSS elevados sem apoio, gerando assincronia toracoabdominal.