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Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A2A receptors (A2ARs) have been considered as key elements in signaling pathways mediating neurodegenerative diseases such as Huntington's and Alzheimer's, as well as cognitive function regulation. Herein, we investigated A2AR role in cognitive impairment induced by chronic intermittent hypoxia (CIH). Mice were exposed to CIH 7 h every day for 4 weeks, and intraperitoneally injected with A2AR agonist CGS21680 or A2AR antagonist SCH58261 half an hour before IH exposure daily. The 8-arm radial arm maze was utilized to assess spatial memory after CIH exposures.To validate findings using pharmacology, the impact of intermittent hypoxia was investigated in A2AR knockout mice. CIH-induced memory dysfunction was manifested by increased error rates in the radial arm maze test. The behavioral changes were associated with hippocampal pathology, neuronal apoptosis, and synaptic plasticity impairment. The stimulation of adenosine A2AR exacerbated memory impairment with more serious neuropathological damage, attenuated long-term potentiation (LTP), syntaxin down-regulation, and increased BDNF protein. Moreover, apoptosis-promoting protein cleaved caspase-3 was upregulated while anti-apoptotic protein Bcl-2 was downregulated. Consistent with these findings, A2AR inhibition with SCH58261 and A2AR deletion exhibited the opposite result. Overall, these findings suggest that A2AR plays a critical role in CIH-induced impairment of learning and memory by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity. Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice.

Objective To exam the relationship between snoring and morbidities of multiple systems in children. Study design Children with snoring were enrolled and divided into primary snorer (PS) group and obstructive sleep apnea hypopnea syndrome (OSAHS) group based on polysomnography. The healthy children served as the control group. The growth parameters, maxillofacial malformations, blood chemistry, electrocardiogram, and echocardiogram were recorded and intelligence testing was performed in the enrolled children who were ≥6 years old. Results The weight and height were similar in the control group (n = 60) and the PS group (n = 63), but lower in the OSAHS group (n = 89; P

The aim of the study was to test whether calcium citrate combined with rhBMP-2 was able to enhance bone regeneration compared with a matrix containing only rhBMP-2. In each of experimental mice, one cylinder of calcium citrate–rhBMP-2 or rhBMP-2 alone was implanted into the thigh muscle pouches of the mouse. The following two treatment modalities were randomly allocated: (1) empty control with rhBMP-2 alone in a gelatin matrix and (2) a gelatin matrix including both calcium citrate and BMP-2. After several weeks, bone granules were obtained by histological analysis. Histomorphometric analysis showed the greatest amount of newly formed bone was observed in the group that contained 10.0 mg calcium citrate with 2.0 mg rhBMP-2 (p

Obstructive sleep apnea hypopnea syndrome (OSAHS) in children is associated with multiple system morbidities. Cognitive dysfunction as a result of central nervous system complication has been reported in children with OSAHS. However, the underlying mechanisms are poorly understood. Endoplasmic reticulum stress (ERS)-related apoptosis plays an important role in various diseases of the central nervous system, but very little is known about the role of ERS in mediating pathophysiological reactions to cognitive dysfunction in OSAHS. Chronic intermittent hypoxia (CIH) exposures, modeling OSAHS, across 2 and 4 weeks in growing rats made more reference memory errors, working memory errors and total memory errors in the 8-Arm radial maze task, increased significantly TUNEL positive cells, upregulated the unfolded protein response in the hippocampus and prefrontal cortex as evidenced by increased phosphorylation of PKR-like endoplasmic reticulum kinase, inositol-requiring enzyme l and some downstream products. A selective inhibitor of eukaryotic initiation factor-2a dephosphorylation, salubrinal, prevented C/EBP-homologous protein activation in the hippocampus and prefrontal cortex throughout hypoxia/reoxygenation exposure. Our findings suggest that ERS mediated cell apoptosis may be one of the underlying mechanisms of cognitive dysfunction in OSAHS children. Further, a specific ERS inhibitor Salubrinal should be tested for neuroprotection against CIH-induced injury.

To observe proliferation and differentiation of osteoblasts cultured in the plane on appropriate electrical stimulation, to specify whether it promote the proliferation, and observe expression of BMP-2 on electrical stimulation.Osteoblasts were extracted from the skull of rabbit offspring and cultured. Cells after the 2nd generations were cultured. In experimental group, cells had electrical stimulation, and same stimulation time and intensity were given. In control group cells had not electrical stimulation. The proliferation and differentiation were detected at different time, and BMP-2 protein expression was analyzed.The cell morphology of experimental group in 8 days under the light microscope was observed and showed a lot of proliferation of osteoblasts, pleomorphic changes, in 6 to 8 days a small amount of Calcified spots was also observed; while in the control group, proliferation was slower. Differentiation of the experimental group was significantly, alkaline phosphatase staining and calcium nodules were positive, quantitative analysis of alkaline phosphatase increaseed significantly. Experimental group showed that BMP-2 was gradually increased by immunohistochemistry analysis.Electrical stimulation can promote the proliferation and differentiation of osteoblasts and achieved the increasement the number of cells in short-term, intracellular staining by immunohistochemistry showed the increasement in expression of BMP-2.

To explore the role of endoplasmic reticulum stress in brain injury following chronic intermittent hypoxia (CIH) in weanling rats.A total of 48 male healthy Sprague-Dawley rats (3-4-week-old, 80-100 g) were randomly divided into 4 groups: 2-week-CIH (2IH) group, 4-week-CIH (4IH) group, 2-week-control (2C) group and 4-week-control (4C) group. The morphologic changes were observed by hematoxylin-eosin (HE) staining and cell apoptosis detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Then hippocampus and prefrontal cortices were collected for transcription and expression analysis of glucose regulated protein 78 (GRP78) by reverse transcription (RT)-PCR and Western blotting respectively. And the expressions of Caspase-12 mRNA and Caspase-12 protein in prefrontal cortex were analyzed by RT-PCR and immunohistochemistry.The neuronal apoptosis in hippocampus and prefrontal cortices in CIH exposed groups were more pronounced than those of the control groups (all P0.01), especially in the 4IH group (hippocampus: 8.78% ± 0.71% vs 3.26% ± 0.45%, cortices: 6.02% ± 0.32% vs 2.91% ± 0.29%). The expression levels of GRP78 mRNA (hippocampus: 0.424 ± 0.033 vs 0.326 ± 0.013 and 0.444 ± 0.028 vs 0.310 ± 0.015, cortices: 0.514 ± 0.038 vs 0.430 ± 0.017 and 0.524 ± 0.038 vs 0.439 ± 0.033) and GRP78 protein in hippocampus and prefrontal cortices (hippocampus: 0.221 ± 0.032 vs 0.178 ± 0.014 and 0.241 ± 0.019 vs 0.170 ± 0.013, cortices: 0.307 ± 0.012 vs 0.226 ± 0.022 and 0.311 ± 0.023 vs 0.225 ± 0.025), and the expression levels of Caspase-12 mRNA (0.396 ± 0.004 vs 0.323 ± 0.014, 0.417 ± 0.011 vs 0.313 ± 0.011) and Caspase-12 protein (0.334 ± 0.035 vs 0.197 ± 0.023, 0.368 ± 0.079 vs 0.215 ± 0.024) in prefrontal cortex in the IH groups all were more than those in the 2C and 4C groups (all P0.05).Chronic intermittent hypoxia can up-regulate the GRP78 transcription and expression in brain regions associated with learning and memory. This may induce the endoplasmic reticulum stress and activate the Caspase-12 mediated apoptosis signaling pathway. In the end, neuronal apoptosis occurs. All these factors may play an important role in the impairment of learning memory during the exposure of growing rats to chronic intermittent hypoxia.

The sleep disorder in pregnant women remains unfamiliar to perinatal care providers, resulting in lack of appropriate care. This study was designed to investigate the prevalence of sleep disorder-related symptoms in pregnant women and to identify the associated risk factors.Married pregnant women were enrolled from their first trimester and followed up until delivery. Nonpregnant married healthy women were selected as controls. A survey questionnaire was administered to each of them.We successfully performed a survey to 1,993 pregnant women and 598 nonpregnant women. The overall prevalence of sleep disorder-related symptoms in pregnant women was significantly higher than the controls (56.1 vs. 29.9 %, P0.05). There was higher prevalence of snoring (30.2 %), observed sleep apnea (1.1 %), mouth breathing (23.7 %), nocturnal arousal (46.5 %), insomnia (35.1 %), and daytime sleepiness (52.6 %) in pregnant women. There were no significant differences of the prevalence of bruxism (7.0 vs. 6.7 %), sleep talking (8.1 vs. 7.2 %), and sleep walking (0.4 vs. 0.2 %) between the two groups (P0.05). Nocturnal sleep time (8.0 ± 1.3 h) was less in the third trimester compared with the nonpregnant women (8.2 ± 1.1 h) (P0.05). Smoking (OR = 3.39), drinking (OR = 2.40), allergic rhinitis/asthma (OR = 1.71), an obvious difference in neck circumference (OR = 1.11), and waistline (OR = 1.07) changes between the first and third trimesters were the risk factors for sleep disorder-related problems.There is a high prevalence of sleep disorder-related symptoms in pregnant women. Our data may provide a baseline for prevention and treatment of sleep disturbances in pregnant women.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) may cause serious morbidities, such as systemic hypertension, diabetes, and cor pulmonale. However, currently no many reports on study of OSAHS in children are available. This study aimed to explore the effects of OSAHS on children's multiple systems.A total of 89 cases of children who came to the Sleep Treatment Center in the authors' hospital from March 2009 to December 2010 with snoring were tested with overnight polysomnography (PSG). They were classified into mild OSAHS group (n = 59, mean age of 5.71, SD = 2.46) and moderate to severe group (n = 30, mean age of 5.30, SD = 2.73) based on the PSG results, and 100 healthy children were selected as the control group (n = 100, mean age of 6 years, SD = 2.98). Data including height, weight, body mass index and blood pressure, peripheral blood routine, blood lipids, glucose and insulin, electrocardiogram and echocardiography were collected. Patients' adenoid face and abnormal occlusion were also recorded. Comparisons of the data were made among those groups.Mild OSAHS and moderate to severe group had significantly higher prevalence of adenoid face (23.7%, 26.7%), and abnormal occlusion (74.6%, 60.0%) than that in control group (0, 40%) (P0.05). There were no significant differences in terms of BMI between the OSAHS group and the control group, but the weight (kg) and height (cm) in the mild OSAHS group (23.3 ± 10.1, 114.9 ± 16.2) and moderate to severe group (21.9 ± 8.4, 110.8 ± 13.3) were lower than those of the control group (31.8 ± 10.1, 136.1 ± 15.1) (all P0.05). Compared with the control group, the level of HDL-C (mmol/L)and insulin (mU/L) in moderate and severe group decreased [(1.20 ± 0.30) vs. (1.40 ± 0.27), 2.79 (0.84 - 16.16) vs. 4.92 (0.76 - 16.80), P0.05], while the LDL-C (mmol/L) increased [(2.61 ± 0.75) vs. (2.32 ± 0.62), P0.05]. The red blood cell counts (× 10(12)/L) and the blood platelet counts (× 10(9)/L) in the mild OSAHS (4.93 ± 0.37, 292.92 ± 75.64) and moderate and severe OSAHS group (5.23 ± 0.22, 292.50 ± 63.05) were significantly higher in contrast to the control group (4.70 ± 0.31, 255.60 ± 69.12) (all P0.05), systolic blood pressure (mmHg) in mild group (98.54 ± 10.44) and moderate to severe group (99.13 ± 19.13) was significantly higher compared to control group (87.88 ± 11.37), and the heart rate (beats/min) in moderate to severe group (94.43 ± 10.64) was higher than those in control group (87.12 ± 16.20) (all P0.05). The mild OSAHS and moderate and severe OSAHS group had decreased right ventricular internal diameter [(14.24 ± 1.64) mm, (13.17 ± 2.07) mm ], increased main pulmonary artery diameter [(17.05 ± 3.33) mm, (16.33 ± 3.14) mm] and the thickness of right ventricular wall [(3.43 ± 0.26) mm, (3.57 ± 0.20) mm] compared to control group [ (16.10 ± 2.96) mm, (14.11 ± 2.52) mm, (3.32 ± 0.25) mm] (all P0.05).OSAHS in children may be associated with craniofacial malformations, and may contribute to slow growth and development, elevated blood viscosity and blood pressure, metabolic abnormalities, and change cardiac structure.

Objective To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period. Results The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week. Conclusions Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects.

To investigate the distribution characteristics of the single nucleotide polymorphisms (SNPs) in the promoter region of the toll-like receptor 9 gene (TLR9) in Chinese Han children from Zhejiang province, and their associations with asthma susceptibility and phenotypes.A case-control study was conducted. A total of 312 asthmatic children aged between 1.9 and 11.6 and 339 age matched healthy controls were enrolled in this study from April 2007 to November 2008. The -1486 C/T in rs187084 and -1237 C/T in rs5743836 loci of the TLR9 gene were genotyped by direct DNA sequencing of the PCR products. Serum levels of IFN gamma, IL-12 and IL-4 were detected by enzyme linked immunosorbent assay.Serum levels of total IgE were detected by chemiluminescence, and serum levels of antigen specific IgE antibodies were detected by fluoroenzymeimmunoassay.(1) The -1486 C/T polymorphism was identified in both groups. The genotype frequencies of TT, TC and CC at -1486 C/T were 41.0%, 44.3%, 14.7% in the healthy controls, and 38.8%, 48.4%, 12.8% in the asthmatic children. The -1237 C/T polymorphism was not detected in the population. (2) There were no statistically significant differences in the allele and genotype frequencies at the -1486 C/T locus between the two groups (P;0.05). (3) Serum levels of IFN gamma and IL-4 differed significantly among the three genotypes at the -1486 C/T locus in asthmatic children (P0.01). The CC genotype had the lowest levels of serum IFN gamma and the highest levels of serum IL-4 among the three genotypes. There were no significant differences in these cytokines among the healthy controls (P0.05). No statistical differences of serum IL-12 were found among the three genotypes in the two groups (P0.05). (4) There were no significant differences of total IgE (log-transformed) among the three genotypes in the asthmatic children (P0.05).The -1237 C/T polymorphism of TLR9 gene was not detected in Chinese Han children in this study. The -1486 C/T polymorphism was associated with the levels of serum IFN gamma and IL-4 in children with asthma. However, there were no correlations between the -1486C/T polymorphism and serum IL-12 levels, total IgE levels or asthmatic susceptibility.