The effect of leptin on the ventilatory responseto hyperoxia

Leptin-deficient mice show a blunted response to hypercapnia explained by central nervous system effects. The impact of leptin on peripheral chemoreceptor function is unclear. Therefore, 9 mutant (ob/ob) and 9 wild-type (+/+) mice were exposed to room air or 100% oxygen and respiratory rate (RR) and tidal volume (Vt) were measured. Subsequently, ob/ob mice received either leptin or vehicle and measurements were repeated. Compared to baseline, for +/+ mice, RR decreased significantly by 9.4% +/- 3.0% (means +/- SD), whereas Vt remained unchanged. Transition from normoxia to hyperoxia did not change RR and Vt in untreated ob/ob mice, whereas after leptin treatment, RR and Vt decreased significantly. Leptin deficiency abolishes the response to hyperoxia, which is restored by leptin replacement. Thus, leptin seems to be influential for a competent peripheral chemoreceptor function.     

Effect of Point Sampling Density in Quantifying Mouse Lung Emphysema

In the official joint policy document of the American Thoracic Society and European Respiratory Society (Hsia et al., Am J Respir Crit Care Med 181:394‐418), the need for proper stereologic assessment of lungs was emphasized. In this document it was emphasized that for the quantitative analysis of lung histologic sections, one of the most robust and reliable methods is point and intercept counting (Knudsen et al., J Appl Physiol 108:412‐421). One of the practical aspects of this method is how many points or intercepts are needed. The answer to this question has been considered from a theoretical perspective, and it depends on the relative magnitudes of the methodological and biologic variabilities. Although it is generally accepted that in a normal lung, one needs only 100–200 points to sufficiently lower the methodological variability, given the increased variability often seen in experimental emphysematous lung injury, the requisite number of points of intercepts has not been evaluated. In this study, we examined this question by focusing on some of the relevant sampling levels in mice with extensive elastase‐induced emphysema. Using fixed samples of tissue blocks, we varied the number of sampling points or intercepts from about 25 to 1,000 in control and emphysematous lungs. Our results show that, at the sampling levels investigated, even with the increased heterogeneity in the lung tissue damage caused by elastase, the number of sampling points needed to detect changes is similar to what is needed for control mice. Anat Rec, 298:531–537, 2015. © 2014 Wiley Periodicals, Inc.     

Oral and Written Language in Late Adulthood: Findings From the Nun Study

As a part of the Nun Study, a longitudinal investigation of aging and Alzheimer's disease, oral and written autobiographies from 118 older women were analyzed to examine the relationship between spoken and written language. The written language samples were more complex than the oral samples, both conceptually and grammatically. The relationship between the linguistic measures and participant characteristics was also examined. The results suggest that the grammatical and conceptual characteristics of oral and written language are affected by participant differences in education, cognitive status, and physical function and that written language samples have greater power than oral language samples to differentiate between high- and low-ability older adults.     

Treatment of Thyrotoxic Crisis With Plasmapheresis and Single Pass Albumin Dialysis: A Case Report

Thyrotoxic crisis (thyroid storm) is a life‐threatening condition. Standard therapy is based on thiamazole, prednisolone, and nonselective beta‐blockers. Extracorporeal plasmapheresis is an additional tool for removing circulating thyroxine in patients who do not respond quickly to conventional standard therapy. As thyroxine can be bound by albumin, the aims of the present therapy report were to investigate the potential of extracorporeal single‐pass albumin dialysis (SPAD) to remove thyroid hormones and to compare it with plasmapheresis. A 68‐year‐old female with thyrotoxic crisis refractory to conventional therapy underwent two sessions of plasmapheresis without clinical response. For the treatment dose to be increased, the patient was then treated with a modified continuous veno‐venous hemodialysis with a dialysate containing 4% of human serum albumin (SPAD) intended to bind and remove thyroxines continuously. In total, the patient received three sessions of plasmapheresis and four SPAD treatments. Thyroxine levels were detected in the patient and in exchanged plasma or albumin dialysate, respectively, to calculate the amount removed. The main finding was that SPAD treatments were tolerated well by the patient. Due to continuous approach, SPAD sessions removed more thyroid hormone than plasmapheresis did, resulting in the improvement of the clinical status of the patient (reduction of heart rate and catecholamine dosage), which enabled bridging the patient to thyroidectomy as the ultimate surgical treatment. This is the first clinical report of the use of albumin dialysis in thyroid storm. SPAD represents a safe and efficient alternative to plasmapheresis as it can be performed continuously in this critical condition.     

Animal models of airway inflammation and airway smooth muscle remodelling in asthma

Asthma is a complex disease that involves chronic inflammation and subsequent decline in airway function. The widespread use of animal models has greatly contributed to our understanding of the cellular and molecular pathways underlying human allergic asthma. Animal models of allergic asthma include smaller animal models which offer ‘ease of use’ and availability of reagents, and larger animal models that may be used to address aspects of allergic airways disease not possible in humans or smaller animal models. This review examines the application and suitability of various animal models for studying mechanisms of airway inflammation and tissue remodelling in allergic asthma, with a specific focus on airway smooth muscle.     

Antioxidant bioavailability and rapid immune-modulating effects after consumption of a single acute dose of a high-metabolite yeast immunogen: results of a placebo-controlled double-blinded crossover pilot study

The objective of this pilot study was to investigate the acute effects on circulating lymphocyte subsets, antioxidant status, and cytokine profile after consumption of EpiCor(?) (EP) (Embria Health Sciences, Ankeny, IA, USA), a dried fermentate produced from Saccharomyces cerevisiae, using a placebo-controlled randomized crossover study design with 12 healthy adult human subjects. EP contains high levels of bioavailable antioxidants and strongly activates natural killer (NK) cells in vitro. EP consumption has been shown to increase erythrocyte hematocrit levels, boost mucosal immune protection, reduce cold/flu symptoms, reduce seasonal allergy symptoms and the need for rescue medication, and increase salivary secretory immunoglobulin A levels. This warranted further study on immune effects in humans. A within-subject analysis of data collected before and at 1 and 2 hours after consumption of a single dose of 500 mg of EP versus placebo was performed. A transient reduction in circulating T and NK cell numbers was observed 2 hours post-consumption, suggesting that homing and recirculation of these cells, as part of healthy immune surveillance, were supported by EP. The increased expression of activation markers on the CD3(-) CD56(+) NK cell population was significant for CD69 at 1 hour post-consumption (CD25, P<.07; CD69, P<.05), whereas for CD25 it was significant at 2 hours after consumption (CD25, P<.03; CD69, P<.15). A rapid increase in serum interferon-γ was observed at 1 hour post-consumption (P<.07; after removal of two outlying data sets, P<.05) and may have contributed to the effects seen on NK and T cell subsets. Significant increase in serum antioxidant protection was seen 2 hours after consumption (P<.04). Thus consumption of a single 500 mg dose of EP provides a rapid and transient effect on the trafficking and activation status of specific lymphocyte subsets, as well as increased antioxidant protection.     

Effect of induced oligohydramnios on fetal lung development

To investigate the impact of oligohydramnios on fetal growth, development, and lung function, amniotic fluid was shunted from alternate gestational sacs into the maternal peritoneal cavity at 23 days' gestation in the fetal rabbit. Uninstrumented fetuses served as controls. Oligohydramnios was confirmed at the time of planned cesarean delivery on either day 26 or 28. Fetuses subjected to prolonged oligohydramnios had significantly decreased body weight at 26 (p = 0.002) and 28 days (p = 0.007). Similarly, lung weight was decreased at 26 (p = 0.02) and 28 days (p = 0.005). There was a trend toward decreased maximum lung volume for instrumented fetuses at 28 days (p = 0.07). Deflation limbs of the pressure-volume curves revealed significantly increased air trapping for instrumented fetuses at 28 days. These studies suggest not only a detrimental effect of oligohydramnios on fetal body and lung weight but also a beneficial effect of premature rupture of membranes on fetal lung function. Analysis of phospholipid and histologic changes is currently under way.     

Glucocorticoids and the rhesus fetal lung.

The effects of glucocorticoids on primate fetal lung function have not been clearly delineated. In this prospective study of preterm rhesus fetuses exposed in utero to betamethasone for 72 hours, the most significant alteration was a striking increase in maximum lung volumes. Functionally less significant increases in residual lung volumes were also noted. The lungs of the treated fetuses did not exhibit lower extract surface tensions or increased phospholipid concentrations. These findings suggest that the major effect of betamethasone is on lung connective tissue elements, with minimal effects on alveolar surfactant. Additional evidence of the multisystemic effects of glucocorticoids was obtained in that significant differences in fetal, adrenal, hepatic, and placental weights also were observed.