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Ischemic preconditioning (IP) reduces brain damage after subsequent ischemic strokes by activating endogenous protective mechanisms in rodents. Transient ischemic attack (TIA) induces tolerance in the human brain after ischemic strokes; defining mechanisms of IP effects may provide therapeutic targets to improve recovery of patients with ischemic strokes. Iron transported across the blood-brain barrier (BBB) is required for brain functions, including myelination, and its levels should be finely regulated to avoid harmful effects. This study aimed to determine whether IP enhances repair processes by modulating iron metabolism during the post-stroke chronic phase. Male mice were divided into sham and IP groups, and IP was induced 24 h before a transient focal ischemic stroke. Sensorimotor recovery was observed over 8 weeks after the stroke, and brain volumes and levels of proteins related to repair processes and iron metabolism in the ischemic brains were examined 8 weeks after the stroke. There was significantly less ischemic brain atrophy in the IP group than in the sham group, with no differences in sensorimotor recovery between the groups. Levels of tight junction proteins of BBB, neurites outgrowth markers, and myelin sheath proteins and markers for mature oligodendrocytes were significantly increased in the IP group. Iron import proteins, transferrin receptor 1 and DMT1, were also increased in the IP group. selleck chemical These results indicate that IP increases brain repair processes and iron uptake during the chronic phase after an ischemic stroke, and provide new insights to understand the molecular mechanisms of TIA effects on post-stroke recovery.
Drinking cold water evokes decreases in spirometric indices of lung function. We studied whether this could be explained by changes in exhaled-breath temperature (EBT), airflow dynamics, and spirometer measurement sensitivity.
In a randomized/crossover design, 10 healthy adults consumed 1000 mL refrigerated water (2.1 ± 0.64 °C) or water at room temperature (19.4 ± 0.5 °C), with EBT assessed at baseline and at 5, 10, 15 and 30-min post-ingestion. The influence of EBT on pneumotachograph measurement characteristics was modelled using computational fluid dynamics (CFD).
At 5-min post-ingestion, EBT was lower (p < 0.001) following the ingestion of cold water versus water at room-temperature (31.7 ± 1.1 vs. 33.0 ± 0.9 °C), and remained lower until 30-min post-ingestion. At a flow of 8 L s
, a decrease in EBT of 2.1 °C (as observed following cold-water ingestion) was modelled to underpredict lung volume by 0.7%.
Cold water reduces EBT below baseline but effects pneumotachograph measurements only negligibly. Therefore, decreased lung function following cold-water ingestion likely has a physiological explanation which warrants further study.
Cold water reduces EBT below baseline but effects pneumotachograph measurements only negligibly. Therefore, decreased lung function following cold-water ingestion likely has a physiological explanation which warrants further study.Aberrant androgen metabolism is a characteristic feature of polycystic ovary syndrome (PCOS). Various androgens as well as their precursors and metabolites can accumulate in the blood of PCOS patients. Although these steroids include neuroactive steroids, such as allopregnanolone and androstenedione (Δ4A), it remains unknown whether altered blood steroid levels contribute to the high risk of mood disorders in PCOS. In this study, we measured blood levels of 11 steroids in 25 PCOS patients using liquid chromatography-tandem mass spectrometry and chemiluminescent enzyme immunoassay, and assessed the psychological status of these patients using the Hospital Anxiety and Depression Scale (HADS) questionnaire. We also examined age and the degree of metabolic abnormalities of each patient. Steroid values of the patients were compared to our previous data from 31 eumenorrheic women. As a result, 20 patients exhibited aberrant blood levels of one or more of the 11 tested steroids. In most cases, Δ4A and allopregnanolone levels were within or close to the reference ranges. Levels of four steroids were negatively correlated with patients' age, while no correlation was observed between steroid values and metabolic conditions. Seven patients showed high HADS scores. HADS scores were correlated with blood Δ4A levels even after stratifying by body mass indexes, but not with the levels of other steroids or clinical data. These results indicate that the high frequency of anxiety and depression in PCOS patients cannot be ascribed to altered blood levels of a specific steroid, although there may be a weak association between circulating Δ4A levels and psychological conditions of the patients.The progression of cardiovascular research is often impeded by the lack of reliable disease models that fully recapitulate the pathogenesis in humans. These limitations apply to both in vitro models such as cell-based cultures and in vivo animal models which invariably are limited to simulate the complexity of cardiovascular disease in humans. Implementing human heart tissue in cardiovascular research complements our research strategy using preclinical models. We established the Human Explanted Heart Program (HELP) which integrates clinical, tissue and molecular phenotyping thereby providing a comprehensive evaluation into human heart disease. Our collection and storage of biospecimens allow them to retain key pathogenic findings while providing novel insights into human heart failure. The use of human non-failing control explanted hearts provides a valuable comparison group for the diseased explanted hearts. Using HELP we have been able to create a tissue repository which have been used for genetic, molecular, cellular, and histological studies. This review describes the process of collection and use of explanted human heart specimens encompassing a spectrum of pediatric and adult heart diseases, while highlighting the role of these invaluable specimens in translational research. Furthermore, we highlight the efficient procurement and bio-preservation approaches ensuring analytical quality of heart specimens acquired in the context of heart donation and transplantation.
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