Obstructive sleep apnoea-related respiratory events and desaturation severity are associated with the cardiac response

Obstructive sleep apnoea (OSA) causes, among other things, intermittent blood oxygen desaturations, increasing the sympathetic tone. Yet the effect of desaturations on heart rate variability (HRV), a simple and noninvasive method for assessing sympathovagal balance, has not been comprehensively studied. We aimed to study whether desaturation severity affects the immediate HRV.MethodsWe retrospectively analysed the electrocardiography signals in 5-min segments (n=39 132) recorded during clinical polysomnographies of 642 patients with suspected OSA. HRV parameters were calculated for each segment. The segments were pooled into severity groups based on the desaturation severity (i.e.the integrated area under the blood oxygen saturation curve) and the respiratory event rate within the segment. Covariate-adjusted regression analyses were performed to investigate possible confounding effects.ResultsWith increasing respiratory event rate, the normalised high-frequency band power (HFNU) decreased from 0.517 to 0.364 (p<0.01), the normalised low-frequency band power (LFNU) increased from 0.483 to 0.636 (p<0.01) and the mean RR interval decreased from 915 to 869 ms (p<0.01). Similarly, with increasing desaturation severity, the HFNUdecreased from 0.499 to 0.364 (p<0.01), the LFNUincreased from 0.501 to 0.636 (p<0.01) and the mean RR interval decreased from 952 to 854 ms (p<0.01). Desaturation severity-related findings were confirmed by considering the confounding factors in the regression analyses.ConclusionThe short-term HRV response differs based on the desaturation severity and the respiratory event rate in patients with suspected OSA. Therefore, a more detailed analysis of HRV and desaturation characteristics could enhance OSA severity estimation

Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation

Copyright © 2006 Company of BiologistsOocytes regulate follicle growth by secreting paracrine growth factors that act on neighbouring granulosa cells (GCs). Those factors identified to date are mainly members of the transforming growth factor-ß (TGFß) superfamily, but little is known about which specific receptor/signalling system(s) they employ. This study was conducted to determine the requisite pathways utilised by oocytes to promote GC proliferation. We used an established oocyte-secreted mitogen bioassay, where denuded mouse oocytes are co-cultured with mural GCs. Oocytes, growth differentiation factor-9 (GDF9), TGFß1 and activin-A all promoted GC DNA synthesis, but bone-morphogenetic protein 6 (BMP6) did not. Subsequently, we tested the capacity of various TGFß superfamily receptor ectodomains (ECD) to neutralise oocyte- or specific growth factor-stimulated GC proliferation. The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFß1 and activin-A bioactivity, demonstrating its specificity. The TGFßR-II, activinR-IIA and activinR-IIB ECDs all failed to neutralise oocyte- or GDF9-stimulated GC DNA synthesis, whereas they did antagonise the activity of their respective native ligands. An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner. Consistent with these findings, oocytes, GDF9 and TGFß1 all activated SMAD2/3 reporter constructs in transfected GC, and led to phosphorylation of SMAD2 proteins in treated cells. Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did. This study indicates that oocyte paracrine factors primarily utilise a similar signalling pathway first identified for GDF9 that employs an unusual combination of TGFß superfamily receptors, the BMPR-II and a SMAD2/3 stimulatory ALK (4, 5 or 7), for transmitting their mitogenic actions in GC. This cell-signalling pathway may also have relevance in the hypothalamic-pituitary axis and in germ-somatic cell interactions in the testis.Robert B. Gilchrist, Lesley J. Ritter, Samu Myllymaa, Noora Kaivo-Oja, Rebecca A. Dragovic, Theresa E. Hickey, Olli Ritvos and David G. Mottershea

Increased nocturnal arterial pulsation frequencies of obstructive sleep apnoea patients is associated with an increased number of lapses in a psychomotor vigilance task.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObjectives: Besides hypoxaemia severity, heart rate variability has been linked to cognitive decline in obstructive sleep apnoea (OSA) patients. Thus, our aim was to examine whether the frequency domain features of a nocturnal photoplethysmogram (PPG) can be linked to poor performance in the psychomotor vigilance task (PVT). Methods: PPG signals from 567 suspected OSA patients, extracted from Type 1 diagnostic polysomnography, and corresponding results of PVT were retrospectively examined. The frequency content of complete PPGs was determined, and analyses were conducted separately for men (n=327) and women (n=240). Patients were grouped into PVT performance quartiles based on the number of lapses (reaction times ≥500 ms) and within-test variation in reaction times. The best-performing (Q1) and worst-performing (Q4) quartiles were compared due the lack of clinical thresholds in PVT. Results: We found that the increase in arterial pulsation frequency (APF) in both men and women was associated with a higher number of lapses. Higher APF was also associated with higher within-test variation in men, but not in women. Median APF (β=0.27, p=0.01), time spent under 90% saturation (β=0.05, p<0.01), female sex (β=1.29, p<0.01), older age (β=0.03, p<0.01) and subjective sleepiness (β=0.07, p<0.01) were significant predictors of belonging to Q4 based on lapses. Only female sex (β=0.75, p<0.01) and depression (β=0.91, p<0.02) were significant predictors of belonging to Q4 based on the within-test variation. Conclusions: In conclusion, increased APF in PPG provides a possible polysomnography indicator for deteriorated vigilance especially in male OSA patients. This finding highlights the connection between cardiorespiratory regulation, vigilance and OSA. However, our results indicate substantial sex-dependent differences that warrant further prospective studies.Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding Academy of Finland Seinajoki Central Hospital Competitive State Research Financing of Expert Responsibility Area of Tampere University Hospital VTR3242 Business Finland Paulo Foundation Paivikki & Sakari Sohlberg Foundation Research Foundation of the Pulmonary Diseases Finnish Cultural Foundation Alfred Kordelin Foundation Tampere Tuberculosis Foundation Respiratory Foundation of Kuopio Regio

Transforming Growth Factor β Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function

The transforming growth factor β (TGFβ) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGFβ type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGFβ ligands. Tgfbr1 null mice die embryonically, precluding functional characterization of TGFBR1 postnatally. To study TGFBR1–mediated signaling in female reproduction, we generated a mouse model with conditional knockout (cKO) of Tgfbr1 in the female reproductive tract using anti-Müllerian hormone receptor type 2 promoter-driven Cre recombinase. We found that Tgfbr1 cKO females are sterile. However, unlike its role in growth differentiation factor 9 (GDF9) signaling in vitro, TGFBR1 seems to be dispensable for GDF9 signaling in vivo. Strikingly, we discovered that the Tgfbr1 cKO females develop oviductal diverticula, which impair embryo development and transit of embryos to the uterus. Molecular analysis further demonstrated the dysregulation of several cell differentiation and migration genes (e.g., Krt12, Ace2, and MyoR) that are potentially associated with female reproductive tract development. Moreover, defective smooth muscle development was also revealed in the uteri of the Tgfbr1 cKO mice. Thus, TGFBR1 is required for female reproductive tract integrity and function, and disruption of TGFBR1–mediated signaling leads to catastrophic structural and functional consequences in the oviduct and uterus

Enhancement of silicon using micro-patterned surfaces of thin films

Micro-textured biomaterials might enhance cytocompatibility of silicon-based micro-electro-mechanical system (bio-MEMS) dummies. Photolithography-physical vapour deposition was used to produce diamond-like carbon (DLC) or Ti squares and circles on silicon, and also their inverse replicas; then DLC and Ti were compared for their guiding potential, using a SaOS-2 cell model. Scanning electron microscopy at 48 hours indicated cells were well-spread on large-sized patterns (several cells on one pattern) and assumed the geometrical architecture of underlying features. Medium-sized patterns (slightly smaller than solitary indicator cells) were inhabited by singular cells, which stretched from one island to another, assuming longitudinal or branching morphologies. On small-sized patterns (much smaller than individual cells) cells covered large micro-textured areas, but cellular filopodia bypassed the bare silicon. Immunofluorescence and confocal laser scanning microscopy indicated that the actin cytoskeleton and vinculin-containing adhesion junctions were present on the patterned areas, but not on the bare silicon. Cell density/coverage disclosed a 3.4-3.7-fold preference for the biomaterial patterns over silicon substrate (p < 0.001). Differences in the cellular response between materials were lost at 120 hours when cells were confluent. The working hypothesis was proven; enhancement by micro-patterning depends on the pattern size, shape and material and can be used to improve biocompatibility during the initial integration phase of the device