No evidence for humoral autoimmunity against cardiomyocytes,adrenergic or muscarinic receptors in patients with Tako-Tsubo cardiomyopathy

Background

An association between Tako-Tsubo cardiomyopathy (TTC) and underlying malignancies has been observed, suggesting that TTC might be the consequence of paraneoplastic phenomena. This study investigates the presence of autoantibodies against cardiomyocytes as well as adrenergic (β₁, β₂) and muscarinic (M2) receptors in patients with TTC.

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

Activation of CD4⁺ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4⁺ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4⁺ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4⁺ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4⁺ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.     

Strategies for the reduction of cerebral microembolism during transmyocardial laser revascularization

BACKGROUND AND OBJECTIVES: During transmyocardial laser revascularization (TMLR), multiple microembolic signals (MES) can be detected in cerebral arteries. We sought to characterize composition and clinical relevance of these MES and to evaluate strategies to reduce cerebral microembolization during TMLR. STUDY DESIGN/MATERIALS AND METHODS: TMLR was performed in pigs. Laser energy was set to 4-10 J (group A) or 80 J (group B). Oxygen concentration was varied between 21 and 100%. MES were recorded in the ophthalmic artery. Brain and spinal cord were investigated histologically after 10 days. RESULTS: More MES could be detected during high- compared to low-energy laser procedures. Ventilation with 100% oxygen reduced the number of MES. No lesions were found on histology. CONCLUSIONS: The number of MES depends on the laser energy. Laser-induces cavitation-effects lead to an additional release of nitrogen bubbles. Thus, the microembolic load can be reduced by ventilation with 100% oxygen and by decreasing the laser energy.     

Ozone and allergen exposure during postnatal development alters the frequency and airway distribution of CD25+ cells in infant rhesus monkeys

The epidemiologic link between air pollutant exposure and asthma has been supported by experimental findings, but the mechanisms are not understood. In this study, we evaluated the impact of combined ozone and house dust mite (HDM) exposure on the immunophenotype of peripheral blood and airway lymphocytes from rhesus macaque monkeys during the postnatal period of development. Starting at 30 days of age, monkeys were exposed to 11 cycles of filtered air, ozone, HDM aerosol, or ozone + HDM aerosol. Each cycle consisted of ozone delivered at 0.5 ppm for 5 days (8 h/day), followed by 9 days of filtered air; animals received HDM aerosol during the last 3 days of each ozone exposure period. Between 2-3 months of age, animals co-exposed to ozone + HDM exhibited a decline in total circulating leukocyte numbers and increased total circulating lymphocyte frequency. At 3 months of age, blood CD4+/CD25+ lymphocytes were increased with ozone + HDM. At 6 months of age, CD4+/CD25+ and CD8+/CD25+ lymphocyte populations increased in both blood and lavage of ozone + HDM animals. Overall volume of CD25+ cells within airway mucosa increased with HDM exposure. Ozone did not have an additive effect on volume of mucosal CD25+ cells in HDM-exposed animals, but did alter the anatomical distribution of this cell type throughout the proximal and distal airways. We conclude that a window of postnatal development is sensitive to air pollutant and allergen exposure, resulting in immunomodulation of peripheral blood and airway lymphocyte frequency and trafficking.     

Evaluation of the Ventricular System in Adults by Transcranial Duplex Sonography

Transcranial duplex color-flow sonography provides visualization of intracranial structures, and measures angle-corrected blood flow velocity in the basal cerebral artenes of adults. In 44 patients with central nervous system disease, the oblique diameters of the third and the middle part of the lateral ventricle were measured by transcranial duplex color-flow sonography using a system with a 2.5-MHz transducer, and compared to computed tomography measurements. The correlation coefficients for the third and lateral ventncle measurements were r = 0.83 (p < 0.0001, N = 38) and 0.73 (p < 0.0001, N = 78), respectively. A second investigation was performed by transcranial duplex to evaluate intraobserver and mterobserver reproducibility. The correlation coefficient representing interobserver reproducibility in 27 patients was r = 0.87 (p < 0.0001, N = 47) for the lateral ventricle and r = 0.9 (p < 0.0001, N = 49) for the third ventricle. The intraobserver reproducibility correlation coefficient was r = 0.93 (p < 0.0001, N = 22) for the lateral ventricle in 12 patients. In 49 healthy volunteers the oblique diameters of the lateral and third ventricles were age dependent measuring 16.7 ± 2.3 mm and 4.8 ± 1.9 mm, respectively, in those younger than 59 years, compared to 19.0 ± 2.9 mm and 7.6 ± 2.1 mm in those 60 years or older. Therefore, transcranial duplex color-flow sonography measures noninvasively the third and the lateral ventncle in adults.     

Ozone exposure, food restriction and protein deficiency: changes in collagen and elastin in rodent lung

Two groups of weanling or young adult rats were fed ad lib casein-based diets containing 4 or 16% protein. Food was restricted in a third group (fed the 16% protein diet) to the amount consumed daily by rats (adult or weanlings) fed the 4% diet. After 3 weeks (weanlings) or 1, 3 or 5 weeks (adults), one-half of the rats in each group were exposed to 0.64 ppm (1.28 mg/m3) of ozone for 7 days (23.5 h each day). Several parameters were then evaluated related to lung connective tissue metabolism including: (1) total lung hydroxyproline, (2) total lung elastin, (3) apparent rates for lung collagen synthesis and elastin accumulation and (4) lung and body weights. In general, the response to protein deficiency and food restriction was more pronounced than to ozone exposure. Protein deficiency and food restriction resulted in decreased lung size and collagen content. However, the ability of lung to respond to ozone (in relative terms) was not altered by changes in diet as assessed by changes in lung weight or the collagen synthetic rate.