Novel Approach to Simulate Sleep Apnea Patients for Evaluating Positive Pressure Therapy Devices

Bench testing is a useful method to characterize the response of different automatic positive airway pressure (APAP) devices under well-controlled conditions. However, previous models did not consider the diversity of obstructive sleep apnea (OSA) patients’ characteristics and phenotypes. The objective of this proof-of-concept study was to design a new bench test for realistically simulating an OSA patient’s night, and to implement a one-night example of a typical female phenotype for comparing responses to several currently-available APAP devices. We developed a novel approach aimed at replicating a typical night of sleep which includes different disturbed breathing events, disease severities, sleep/wake phases, body postures and respiratory artefacts. The simulated female OSA patient example that we implemented included periods of wake, light sleep and deep sleep with positional changes and was connected to ten different APAP devices. Flow and pressure readings were recorded; each device was tested twice. The new approach for simulating female OSA patients effectively combined a wide variety of disturbed breathing patterns to mimic the response of a predefined patient type. There were marked differences in response between devices; only three were able to overcome flow limitation to normalize breathing, and only five devices were associated with a residual apnea-hypopnea index of <5/h. In conclusion, bench tests can be designed to simulate specific patient characteristics, and typical stages of sleep, body position, and wake. Each APAP device behaved differently when exposed to this controlled model of a female OSA patient, and should lead to further understanding of OSA treatment.     

Protein binding and stability of norepinephrine in human blood plasma. Involvement of prealbumin, alpha 1-acid glycoprotein and albumin

The binding of norepinephrine (NE) to plasma proteins of fresh human blood obtained from healthy volunteers was studied by ultrafiltration at different NE concentrations and incubation times at 37 degrees C. At 1.7 nM L-[3H]-NE binding was approximately 25%. The binding was rapid and was not influenced by the incubation time. [3H]-NE could be dissociated from its binding sites by acid precipitation and, after HPLC, showed to be unchanged NE. No difference in NE binding was found between plasma collected in EGTA-GSH or heparin solution. There was no degradation of NE when incubated in plasma at 37 degrees C for 10 h, even without the addition of antioxidants. Therefore, in the present study, binding represented interaction of unchanged NE with plasma proteins. The whole plasma binding was saturable over the range of 0.66 nM to 0.59 mM of NE. Scatchard plot of specific binding revealed high-affinity sites with a Kd of 5.4 nM and a Bmax of 3.9 fmoles.mg-1 protein, and low-affinity sites with a Kd of 2.7 microM and a Bmax of 3.3 pmoles.mg-1 protein. Electrophoretic characterization of NE-binding proteins showed that about 60% of bound NE was associated to albumin, and 20% to prealbumin. NE binding to pure human plasma proteins was also studied using ultrafiltration. Scatchard analyses revealed a single class of very high-affinity binding sites for prealbumin (Kd 4.9 nM), a single class of binding sites for alpha 1-acid glycoprotein (Kd 54 microM) and two classes of binding sites for albumin with high (Kd 1.7 microM) and low (Kd 0.8 mM) affinities respectively. The main results obtained in this study - a) reversibility of NE binding, b) stability of free and bound NE in plasma, c) involvement of the prealbumin as a specific binding protein - point out to a specific transport for NE in human blood plasma.     

Isolation and purification of the extracellular ribonuclease from Physarum polycephalum

Summary The myxomycete Physarum polycephalum has been reported to produce an extracellular ribonuclease. A quick procedure is described for the isolation and purification of the ribonuclease from the culture supernatant. It involves an initial concentration of the culture supernatant by slow freezing, followed by ammonium sulfate precipitation. The enzyme was adsorbed onto DEAE-cellulose and eluted with a sodium chloride gradient.     

Distribution of alcohol dehydrogenase mRNA in the rat central nervous system. Consequences for brain ethanol and retinoid metabolism.

The localization of alcohol dehydrogenase (ADH) in brain regions would demonstrate active ethanol metabolism in brain during alcohol consumption, which would be a new basis to explain the effects of ethanol in the central nervous system. Tissue sections from several regions of adult rat brain were examined by in situ hybridization to detect the expression of genes encoding ADH1 and ADH4, enzymes highly active with ethanol and retinol. ADH1 mRNA was found in the granular and Purkinje cell layers of cerebellum, in the pyramidal and granule cells of the hippocampal formation and in some cell types of cerebral cortex. ADH4 expression was detected in the Purkinje cells, in the pyramidal and granule cells of the hippocampal formation and in the pyramidal cells of cerebral cortex. High levels of ADH1 and ADH4 mRNAs were detected in the CNS epithelial and vascular tissues: leptomeninges, choroid plexus, ependymocytes of ventricle walls, and endothelium of brain vessels. Histochemical methods detected ADH activity in rodent cerebellar slices, while Western-blot analysis showed ADH4 protein in homogenates from several brain regions. In consequence, small but significant levels of ethanol metabolism can take place in distinct areas of the CNS following alcohol consumption, which could be related to brain damage caused by a local accumulation of acetaldehyde. Moreover, the involvement of ADH in the synthesis of retinoic acid suggests a role for the enzyme in the regulation of adult brain functions. The impairment of retinol oxidation by competitive inhibition of ADH in the presence of ethanol may be an additional origin of CNS abnormalities caused by ethanol.     

Phototherapy and dithranol treatment of psoriasis: new lamps for old.

The response of psoriasis to ultraviolet radiation and dithranol was compared with the response to dithranol alone in 24 patients. The difference in rate of response, measured as change in plaque thickness, and the difference in time to complete clearance of psoriasis between irradiated and non-irradiated forearm lesions was significantly greater for patients treated using fluorescent lamps with negligible ultraviolet C emission (Wolff Helarium) than for those patients treated with a medium pressure mercury arc lamp (p less than 0.01) or an array of fluorescent sunlamps (p less than 0.05). The difference in therapeutic response shows that ultraviolet B phototherapy is effective when used in combination with dithranol. Nevertheless, radiation sources with substantial ultraviolet C emission, such as the medium pressure mercury arc lamp most commonly used to treat psoriasis in the United Kingdom, have little effect because delivery of therapeutic doses of ultraviolet B is limited by erythema induced by ultraviolet C.     

The convergent trajectories of bird communities along ecological successions in european forests

Summary There is much more variation in the composition of bird communities in the earlier open and semi-open seral stages of ecological successions in forested landscapes of Europe than later on in preforested and forested climactic stages. The demonstration of this trend is achieved from the study of four habitat gradients, two in the mediterranean region (Provence and Corsica) and two in central Europe (Burgundy, France and Poland). A multivariate analysis has been used to illustrate the dynamics of communities along these succession. Displays of the results in bivariate space as well as an illustration of the distributional profiles of some of the most characteristic species show that: i) there is a discrimination between the two mediterranean gradients and the two medioeuropean ones and ii) each succession starts with a very distinct set of species and then the four gradients regularly converge in the last climactic stage where there is almost no discrimination between communities. These results are discussed in the light of the history of European biotas during the Pleistocene. The reason why there is more variation in species composition in the earlier seral stages than in the later forested stages are discussed according to current theories on the role of habitat selection on speciation processes.     

Compensatory payments and vasectomy acceptance in urban Sri Lanka

The effects of different levels of compensatory payment for vasectomy on sterilization acceptance were examined in 496 vasectomized men in urban Sri Lanka. The results indicate that compensatory payments significantly enhanced the participation of economically poor men in vasectomy programs, especially those who had already achieved a large family size. The proportion of poor acceptors (those with a monthly income of Rs 1000 or less) increased with higher levels of payment; the acceptor's level of education was negatively correlated with the compensation amount, and the mean age of the youngest child was higher among those who received higher payments. 60% of vasectomy acceptors reported using contraception immediately before the vasectomy, suggesting a high level of motivation not to have another child. Respondents cited high effectiveness, no extra expense, and no side effects for their wives as the main reasons for selecting vasectomy over other means of contraception, regardless of the amount of payment received. Only 5% said cash payment was an important reason for choosing vasectomy, and this response did not vary significantly by level of payment. There was no influence of payment level on postoperative complications or satisfaction. While compensatory payments significantly enhanced the participation of poor men in vasectomy programs, they were not effective in attracting poorer men with few children or those whose last child was relatively young. Overall, this study's findings suggest that the decision to provide compensatory payments and how much to provide should be based on economic and political factors, not on the grounds that higher compensatory payments have led to the recruitment of ineligible men or that the promotion of vasectomy has been at the expense of a loss in the quality of services provided.     

Selective binding of Dolichos biflorus agglutinin to L3T4-, Lyt-2- thymocytes. Expression of terminal alpha-linked N-acetyl-D-galactosamine residues defines a subpopulation of fetal and adult murine thymocytes

Using histochemical and immunocytochemical techniques, a lectin with nominal specificity for alpha-linked N-acetyl-D-galactosamine, Dolichos biflorus agglutinin (DBA), was found to preferentially label thymocytes with an L3T4-, Lyt-2- phenotype from fetal/newborn and adult mice. Through days 14 to 16 of gestation, virtually all thymocytes bound DBA, followed by a dramatic reduction of DBA labeling during the last 4 days of gestation, reaching adult levels of about 2 to 4% of total thymocytes. At later stages of fetal development, the DBA+ cells were confined to the subcapsular area of the thymus. This apparent loss of DBA+ cells was caused by an expansion of the thymocyte population not labeled with this lectin. Affinity purification of thymocyte cell surface components with insolubilized DBA indicated that virtually all of the lectin binding to fetal thymocytes was mediated by a 120-kDa glycoprotein. In addition to thymocytes, DBA also labeled about 5% of bone marrow cells from both normal or nude mice and a small population of spleen cells as well. These results suggest that this lectin may be useful to positively select for LT34-, Lyt-2- thymocytes, and, possibly, other immature populations within the T cell lineage.     

Epithelial heterogeneity in the murine thymus: fucose-specific lectins bind medullary epithelial cells

By means of histochemical techniques, two lectins with nominal specificity for L-fucose, Tetragonolobus purpureas agglutinin (TPA), and Ulex europeus agglutinin (UEA) were found to specifically label the medullary area of murine thymuses. Although the binding of both lectins was restricted to the medullary area of the thymus, each staining pattern was unique. Cells binding UEA formed a reticular network throughout the medulla, whereas cells binding TPA occurred as single cells or small clumps of cells and resembled Hassall's corpuscles. The cells binding either lectin were identified as epithelial on the basis of ultrastructural features (tonofilaments, desmosomes, and keratohyalin bodies) and resembled Ia+ medullary epithelial cells described previously. An age-related decline in UEA binding was observed, whereas labeling with TPA remained unchanged. On the basis of the labeling patterns obtained with UEA and TPA and the reported specificities of these two lectins, it is suggested that the majority of the fucose detected is associated with type 1 carbohydrate chains.     

Effects of ethanol on rat hypothalamic luteinizing hormone releasing hormone. A study utilizing radioimmunoassay

To further understand the mechanism of action by which ethanol (ETOH) decreases plasma luteinizing hormone (LH) levels, the effects of multiple i.p. injections of EOH (1.0--1.5 g/kg) or saline on hypothalamic luteinizing hormone releasing hormone (LHRH) and plasma LH concentrations were evaluated in intact and castrate male rats. After injections, animals were decapitated, brains rapidly removed, and blocks containing the hypothalamus [with median eminence (ME)] were isolated. Hypothalami were subjected to acetic acid extraction and LHRH content quantitated via radioimmunoassay (RIA). Hypothalamic LHRH was found to be inversely correlated with plasma LH. In response to castration, both saline and ETOH-treated rats showed a decrease in hypothalamic LHRH content with a concomitant increase in plasma LH; however, the ETOH-treated animals retained significantly greater concentrations of LHRH and showed significantly lower plasma LH levels when compared to saline-treated controls. Likewise, ETOH-treated intact animals showed significant increases in LHRH content, with LH levels remaining significantly lower than the saline-treated intact controls. Thus, these data from both intact and castrate rats provide evidence to support the hypothesis that alcohol-induced decreases in LH levels are due to a diminished release rate of hypothalamic LHRH.