Evidence of Aquaporin 4 Regulation by Thyroid Hormone During Mouse Brain Development and in Cultured Human Glioblastoma Multiforme Cells.

Accumulating evidence indicates that thyroid function and the thyroid hormones L-thyroxine (T4) and L-triiodothyronine (T3) are important factors contributing to the improvement of various pathologies of the central nervous system, including stroke, and various types of cancer, including glioblastoma multiforme (GBM). Low levels of T3 are correlated with the poorest outcome of post-stroke brain function, as well as an increased migration and proliferation of GBM tumor cells. Thyroid hormones are known to stimulate maturation and brain development. Aquaporin 4 (AQP4) is a key factor mediating the cell swelling and edema that occurs during ischemic stroke, and plays a potential role in the migration and proliferation of GBM tumor cells. In this study, as a possible therapeutic target for GBM, we investigated the potential role of T3 in the expression of AQP4 during different stages of mouse brain development. Pregnant mice at gestational day 18, or young animals at postnatal days 27 and 57, received injection of T3 (1 µg/g) or NaOH (0.02 N vehicle). The brains of mice sacrificed on postnatal days 0, 30, and 60 were perfused with 4% paraformaldehyde and sections were prepared for immunohistochemistry of AQP4. AQP4 immunofluorescence was measured in the mouse brains and human GBM cell lines. We found that distribution of AQP4 was localized in astrocytes of the periventricular, subpial, and cerebral parenchyma. Newborn mice treated with T3 showed a significant decrease in AQP4 immunoreactivity followed by an increased expression at P30 and a subsequent stabilization of aquaporin levels in adulthood. All GBM cell lines examined exhibited significantly lower AQP4 expression than cultured astrocytes. T3 treatment significantly downregulated AQP4 in GBM-95 cells but did not influence the rate of GBM cell migration measured 24 h after treatment initiation. Collectively, our results showed that AQP4 expression is developmentally regulated by T3 in astrocytes of the cerebral cortex of newborn and young mice, and is discretely downregulated in GBM cells. These findings indicate that higher concentrations of T3 thyroid hormone would be more suitable for reducing AQP4 in GBM tumorigenic cells, thereby resulting in better outcomes regarding the reduction of brain tumor cell migration and proliferation.

Potential underdiagnosis of obstructive sleep apnoea in the cardiology outpatient setting.

INTRODUCTION: Consistent evidence suggests that obstructive sleep apnoea (OSA) is associated with increased cardiovascular risk. However, it is unclear whether OSA is underdiagnosed in the cardiology outpatient setting. In the present study, we prospectively evaluated the potential underdiagnosis of OSA in several subspecialties from a tertiary cardiology university hospital. METHODS: Consecutive outpatients from five subspecialties (hypertension, coronary, arrhythmia, heart failure (HF), valvular heart disease) were studied. We performed anthropometric measurements, assessed the risk of OSA using the Berlin Questionnaire and evaluated the prior diagnosis and treatment for OSA. In a subset of patients randomly selected, we performed portable sleep monitoring to objectively evaluate the presence of OSA (defined by an apnoea-hypopnoea index ≥15 events/h of sleep). RESULTS: We evaluated 500 patients (100 from each subspecialty). The mean age and body mass index (BMI) were 59±13 years and 28.2±5.3 kg/m(2), respectively. We found that 51.6% (258 patients) had a high risk for OSA (Berlin Questionnaire). However, only 13 (3.1%) of these patients had a previous diagnosis of OSA. Of those, only six patients were receiving specific OSA treatment. Fifty patients (10 from each specialty) participated in sleep studies. No differences were found in patients who underwent sleep monitoring and those who did not. We found a high frequency of OSA (66%), varying from 50% (hypertension group) to 80% (HF group). CONCLUSIONS: Despite significant scientific evidence pointing to OSA as an emerging cardiovascular risk factor, OSA is still underdiagnosed in several cardiology subspecialties.