Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

[Chemical constituents from Barringtonia racemosa].

To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3ß-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3ß, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3ß-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3ß, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterol（12） by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC50>50 mg•L⁻¹).

[Comparison of efficacy between continuous positive airway pressure and renal artery sympathetic denervation by radiofrequency ablation in obstructive sleep apnea syndrome patients with hypertension].

OBJECTIVE: To compare the efficacy of renal arterial sympathetic denervation (RSD) and continuous positive airway pressure (CPAP) in patients with coexisting moderate-to-severe obstructive sleep apnea syndrome (OSAS) and hypertension. METHODS: Retrospective analysis was conducted for patients with coexisting moderate to severe OSAS and hypertension for the efficacy of RSD (RSD group, n = 15) and CPAP (CPAP group, n = 16). Comparison was made for polysomnographic parameters and 24 hours ambulatory blood pressure (Bp) between two groups. RESULTS: There was no significant difference in age, gender, body mass index, nocturnal apnea hypopnea index (AHI), mean and minimal pulse oxygen saturation (mean SpO2 and mini SpO2) between two groups. Compared with those at pre-treatment, the following changes were observed at Day 30 post-treatment: in RSD group, the nocturnal AHI and T90 statistically decreased (27 ± 14 vs 32 ± 12, 8.7% ± 7.8% vs 13.8% ± 13.1%, all P < 0.05) with a significant increase in mean SpO2 (94.3% ± 2.2% vs 93.9% ± 2.0%, P < 0.05) while mini SpO2 showed no significant difference (80.1% ± 6.2% vs 79.5% ± 4.7%, P > 0.05); in CPAP group during treatment, nocturnal AHI and the ratio of duration SpO2 < 90% to total sleep time (T90) were all significantly reduced (5 ± 3 vs 35 ± 12, 1.5% ± 1.2% vs 12.9% ± 6.3%, all P < 0.05) while mean SpO2 and mini SpO2 became significantly elevated (95.6% ± 1.4% vs 93.6% ± 1.7%, 89.2% ± 2.7% vs 79.1% ± 4.0%, all P < 0.05). Compared with RSD group, there was a significantly lower AHI (P = 0.000) but higher mean SpO2 and mini SpO2 (all P < 0.05) at Day 30 in CPAP group. At Day 30 in RSD and CPAP groups, the mean systolic blood pressure (MSBp) were (122 ± 9) and (130 ± 12) mm Hg (1 mm Hg = 0.133 kPa) respectively while the mean diastolic blood pressure (MDBp) (80 ± 8) and (83 ± 7) mm Hg respectively. All these were significantly lower than those at pre-treatment with MSBp (134 ± 20) mm Hg and MDBp (88 ± 14) mm Hg in RSD group and MSBp (136 ± 14) mm Hg and MDBp (87 ± 7) mm Hg in CPAP group. The extent of decrease in MSBp post-treatment was more remarkable in RSD group than that in CPAP group (P < 0.05). CONCLUSIONS: In moderate-to-severe OSAS patients with hypertension, both RSD and CPAP may improve sleep respiratory parameters and blood pressure to varying degrees. There is a more significant improvement of nocturnal AHI and SpO2 in CPAP group and more lower MSBp in RSD group.

Epworth Sleepiness Scale may be an indicator for blood pressure profile and prevalence of coronary artery disease and cerebrovascular disease in patients with obstructive sleep apnea.

OBJECTIVE: This study seeks to determine whether scores of a short questionnaire assessing subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]) are associated with blood pressure (BP) level, BP profile, and prevalence of related coronary artery disease (CAD) and cerebrovascular disease (CVD) in obstructive sleep apnea (OSA) patients diagnosed by polysomnography (PSG). METHODS: Twenty university hospital sleep centers in China mainland were organized by the Chinese Medical Association to participate in this study. Between January 2004 and April 2006, 2,297 consecutive patients (aged 18-85 years; 1,981 males and 316 females) referred to these centers were recruited. BP assessments were evaluated at four time points (daytime, evening, nighttime, and morning) under standardized conditions. Anthropometric measurements, medical history of hypertension, CAD, and CVD were collected. ESS score was calculated for each participant and at the night of BP assessment, nocturnal PSG was performed and subjects were classified into four groups based on the apnea-hypopnea index (AHI) from PSG as follows: control group (control, n = 213) with AHI < 5; mild sleep apnea (mild, n = 420) with AHI ≥ 5 and <15; moderate sleep apnea (moderate, n = 460) with AHI ≥ 15 and <30; and severe sleep apnea (severe, n = 1,204) with AHI ≥ 30. SPSS 11.5 software package was used for the relationships between ESS and BP profile and prevalence of CAD and CVD. RESULTS: ESS is correlated positively with average daytime, nighttime, evening, and morning BP before and even after controlling for confounding effects of age, sex, BMI, AHI, and nadir nocturnal oxygen saturation (before--r = 0.182, 0.326, 0.245, and 0.329, respectively, all P values < 0.001; after--r = 0.069, 0.212, 0.137, and 0.208, respectively, all P values < 0.001). In the severe group, nighttime, evening, morning average BPs (ABPs), the ratio of nighttime/daytime average BP (ratio of nighttime average BP to daytime average BP), and prevalence of hypertension, drug-resistant hypertension (R-HTN), isolated nighttime hypertension (IN-HTN), CAD, and CVD in excessive daytime sleepiness (EDS, ESS ≥ 11) subjects are higher than those in non-EDS (ESS 0-10; t/χ(2) = -8.388, -6.207, -8.607, -5.901, 12.742, 38.980, 16.343, 59.113, and 67.113, respectively; all P values < 0.05). For EDS subjects in the moderate group but not in the control and mild group, nighttime ABP and the ratio of nighttime/daytime average BP are higher (t = -2.086 and -3.815, respectively, all P values < 0.05). Linear fitting with ESS and the ratio of nighttime/daytime average BP shows a positive correlation (r(2) = 0.049, P < 0.001). CONCLUSIONS: In severe OSA patients with comparable AHI, EDS may identify a subset of individuals with OSA at higher risk of hypertension, R-HTN, IN-HTN, CAD, and CVD. Overall, nighttime ABP seems to be more sensitive to be influenced by EDS than other ABP parameters. Future studies should investigate the potential dose-effect relationship between EDS and hypertension and the possibility that diagnosis and treatment of EDS could aid in BP reduction and ultimately in decreased morbidity and mortality from cardiovascular and cerebrovascular complications (TMUIRB20010002 at www.clinicaltrials.gov ).

[Evaluation of carotid artery elasticity in patients with obstructive sleep apnea syndrome using quantitative arterial stiffness technique].

OBJECTIVE: To explore the changes and clinical value of carotid elasticity index in patients with obstructive sleep apnea syndrome (OSAS) by quantitative arterial stiffness (QAS) technique. METHODS: Seventy-two OSAS patients were divided into 2 groups according to whether there was coexisting hypertension. Of them, there were 37 OSAS patients without hypertension (OSAS1 group) and 35 OSAS patients with hypertension (OSAS2 group). In addition, forty healthy volunteers were recruited as the normal control group. We measured the arterial elastic parameters including vascular expansibility (VE), compliance coefficient (CC), stiffness index (ß) and pulse wave velocity (PWV) through QAS analysis technique. The difference of the parameters among the groups was analyzed. In the OSAS group, polysomnograph (PSG) data were recorded and analyzed including apnea-hypopnea index (AHI), minimal pulse oxyhemoglobin saturation (miniSpO(2)), time spent below oxygen saturation of 90% (Ts90%) and oxygen desaturation index (ODI). Correlations and regression were calculated between indices of oxygen saturation and PWV. RESULTS: Compared with normal control group, in OSAS1 and OSAS2 groups, VE and CC were significantly lower, but ß and PWV was significantly higher (P < 0.05). Compared with OSAS1 group, CC in OSAS2 group decreased but ß and PWV increased significantly (P < 0.05). In the OSAS group, PWV was correlated positively with systolic blood pressure, AHI, ODI and age (r = 0.285 - 0.542, all P < 0.05). Through stepwise multiple linear regression analysis, age and ODI were the significant variables to determine PWV. CONCLUSION: The decreases in arterial elasticity are present in OSAS patients. These changes are more evident in OSAS patients with hypertension. QAS technique plays an important role in analyzing the arterial elasticity accurately and could be used as a quantitative mean to evaluate early atherosclerosis.

[Clinical significance and intervention study of serum interleukin 18 in preeclampsia patients with coexisting obstructive sleep apnea].

OBJECTIVE: To investigate the role of IL-18 in the obstructive sleep apnea syndrome (OSAS)-induced preeclampsia (PE), by comparison of the changes of serum IL-18 levels among different groups as well as before and after continuous positive airway pressure (CPAP) treatment in pregnant women with both OSAS and PE. METHODS: In control group there were 18 normal pregnant women with apnea hypopnea index (AHI) < 5. In simple PE group 18 pregnant PE patients with an AHI < 5 were recruited. In PE plus OSAS group 16 PE patients with coexisting OSAS were collected. CPAP treatment was performed for 1 week in 6 patients with AHI > 15 from PE plus OSAS group.Serum IL-18 levels were measured with ELISA. RESULT: There was a significant difference in serum IL-18 levels among control group [(261 ± 95) ng/L], simple PE group [(382 ± 121) ng/L], and PE plus OSAS group [(601 ± 89) ng/L, all P < 0.001]. Following CPAP treatment, there was a significant decrease in AHI, systolic blood pressures, and serum IL-18 levels, but a significant increase in minimal SpO2 (P < 0.01). CONCLUSION: Our study demonstrated that serum IL-18 levels in PE patients with OSAS were significantly elevated, which suggested that OSAS might increase the incidence of PE by enhancing inflammatory response, while CPAP treatment could effectively improve the pathological process.

[Effect of Bi-level positive airway pressure ventilator on the heart function and vascular endothelial function of patients with the overlap syndrome].

OBJECTIVE: To study the mechanism of Bi-level positive airway pressure (BIPAP) on the heart function and the vascular endothelial function of the overlap syndrome (OS). METHODS: There were 87 males and 33 females (mean age 48 ± 4, range 40 - 53 years) admitted to the Affiliated Jiangning Hospital respiratory department of Nanjing Medical University. Subjects tested with PSG were allocated to normal, OSAHS, COPD and OS groups by the result of pulmonary function testing. All persons were tested with pulmonary function (FEV(1)% of predicted, FEV(1)/FVC%, PEF%), heart function (Tei index, BNP), vascular endothelial function (ET-1, NO, AT-III) and PSG (AHI, LSaO2, the time of SaO2 < 90%). The measurements were repeated in patients with OS after BiPAP treatment and 1 month after follow-up. One-way ANOVA was used for comparison between 2 groups. Post-hoc multiple comparisons of means were performed by using LSD. Paired-samples t Test was used for comparison of data between baseline and post-treatment. RESULTS: The FEV(1)% of predicted, FEV(1)/FVC%, and PEF% in the OS group were significantly lower than the those in the other groups (F = 215.47 - 681.65, P < 0.05). The vascular endothelial function was impaired more severely than the other groups (F = 46.60 - 259.12, P < 0.05). The heart function, pulmonary function, and vascular endothelial function were significantly improved after BiPAP treatment (t = -17.13 - 42.06, P < 0.05). CONCLUSION: The vascular endothelial dysfunction is associated with OS. Treatment by BiPAP can improve hypoxia and vascular endothelial function, and therefore may be useful in prevention of cardiovascular disease in OS.

[Effect of chronic intermittent hypoxia on mitochondrial function of rat genioglossus cells and intervention role of adiponectin].

OBJECTIVE: To investigate the effect of chronic intermittent hypoxia (CIH) on mitochondrial function in genioglossus cells of rats and intervention role of adiponectin (Ad). METHODS: Thirty-nine healthy male Wistar rats were randomly divided into 3 groups, normal control (NC) group, CIH group and CIH + Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH + Ad groups experienced the same CIH environment (CIH 8 h/day for successive 5 weeks). However, rats in CIH + Ad group was given intravenous Ad supplement at the dosage of 10 µg, twice a week for successive 5 weeks. At the end of experiment (day 35), the levels of plasma adiponectin, mitochondrial membrane potential activities of respiratory chain complexes I and IV in mitochondrion of genioglossus cells were compared among different groups. RESULTS: Serum Ad level was significantly lower in CIH group than that in NC group [(1108 ± 112) ng/ml vs (2241 ± 121) ng/ml, P < 0.01]. Serum Ad level in CIH + Ad group [(1889 ± 119) ng/ml] was significantly higher than that in NC group but lower than that in CIH group (all P < 0.01). Mitochondrial membrane potential was significantly lower in CIH group than that in NC group [(1.82 ± 0.11) vs (2.09 ± 0.14), P < 0.01]. Mitochondrial membrane potential in CIH + Ad group (1.98 ± 0.09) was higher than that in CIH group but lower than that in NC group (all P < 0.05). The concentrations of mitochondrial respiratory chain complexes I and IV in CIH group (35.68 ± 1.73) µmol×min(-1)×mg(-1) and (2.37 ± 0.11) nmol×min(-1)×mg(-1), respectively) were the lowest but became higher from CIH + Ad group [(37.18 ± 1.95) µmol×min(-1)×mg(-1) and (2.49 ± 0.09) nmol×min(-1)×mg(-1), respectively] to NC group (39.02 ± 1.38) µmol×min(-1)×mg(-1) and (2.81 ± 0.12) nmol×min(-1)×mg(-1), respectively), with a significant difference between NC and CIH groups (P < 0.01), between CIH + Ad and CIH groups (P < 0.05), as well as between CIH + Ad and NC groups (P < 0.05). CONCLUSION: CIH could lead to hypoadiponectinemia and impaired mitochondrial function in genioglossus cells of rats. Since such changes could be partially improved by supplement of adiponectin, it was suggested that hypoadiponectinemia might be involved in CIH-induced impairment of genioglossus energy metabolism.

[Twenty years follow-up: the correlation between sleep apnea syndrome and cerebrovascular disease].

OBJECTIVE: To explore the correlation between obstructive sleep apnea syndrome (OSAS) and cerebrovascular disease (CVD). METHODS: A cohort of 1868 people was screened for OSAS, and followed from November 1989 to November 2009. Annual medical examinations including blood pressure, blood fat, serum glucose, electrocardiogram and chest x-ray were performed. Computer tomography was carried out when CVD, the endpoint of the study, was manifested. RESULTS: Among the 1868 elderly people, 598 (32.0%) were confirmed to have OSAS, including 496 (82.9%) males and 102 (17.1%) females. Compared with the non-OSAS group, patients with OSAS had more symptoms including daytime somnolence, headache, decreased ability of memory, aphronesia and allolalia (P < 0.05). CVD occurred in 276 (46.2%) patients of the OSAS group, but in 150 (11.8%, P < 0.01) subjects of the non-OSAS group. During the 20-year follow-up, 817 people died, 66.2% (396/598) in the OSAS group, but 33.1% (421/1270) in the non-OSAS group (P < 0.01). CONCLUSION: Patients with OSAS are more likely to suffer from CVD. OSAS may be an independent risk factor for CVD.

Beta(2)-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population.

Association and linkage studies of beta2-adrenergic receptor (beta2AR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. This study was designed to analyze the relationship of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of the beta2AR gene with bronchial asthma, bronchodilator response, and total IgE. By direct DNA sequencing, five SNPs (in positions -47, -20, 46, 79, and 252) of beta2AR gene were determined and combined with haplotypes in 201 asthmatic patients and 276 normal controls recruited from the Chinese Han population. Significantly higher bronchodilator response was observed in patients with homozygotic genotype 46A/A (13.40 ± 3.48%), compared with those with homo-46G/G (7.25 ± 3.11%) and heterozygotes 46A/G (7.39 ± 3.14%), respectively (p < 0.0001). There was also a significant difference in bronchodilator response when beta2AR haplotypes were analyzed (p = 0.003). From two common SNPs at positions 46A/G and 79C/G, we had determined three haplotypes that constructed six haplotype pairs. Comparison of the mean delta forced expiratory volume in 1 second (FEV1) values for the six haplotype pairs showed significant difference. Subjects homozygous for 46A/79C (Arg16/Gln27) had the highest deltaFEV1 (13.40 ± 3.48%) and those with 46G/79C (Gly16/Gln27) homozygote had the lowest (6.43 ± 0.55%). The two SNP haplotype pairs were significantly associated with delta FEV1 (p < 0.0001). Significantly higher total IgE levels were found in patients with homozygotic carriers of 79C genotypes (p = 0.022) and homozygotic haplotype -47 T/-20 T/46 A/79 C/252 G (p < 0.0001). These results indicate that the manifestation of asthma might be affected by either an individual beta2AR SNPs or beta2AR haplotype.

Inhibition of CD8+ T lymphocytes attenuates respiratory syncytial virus-enhanced allergic inflammation.

BACKGROUND: CD8+ T cells have an important role in the pathogenesis of respiratory virus-induced asthma exacerbations. However, the cellular mechanism of CD8+ T cells, linking viral respiratory infections to the development of airway inflammation, is not well defined. OBJECTIVES: To clarify the role of CD8+ T cells in the development of respiratory virus-induced asthma exacerbations. METHODS: Using a murine model of prior ovalbumin exposure and subsequent respiratory syncytial virus infection, the airway responsiveness was assessed by barometric whole-body plethysmography. Airway eosinophils, lymphocytes, neutrophils as well as IFN-gamma, IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were measured by Diff-Quick staining and ELISA. The frequency of cytokine-producing CD8+ T lymphocytes in peribronchial lymph nodes was detected using 2-color immunofluorescence analysis. Histological examinations were carried out using hematoxylin and eosin and immunohistochemistry. RESULTS: Anti-CD8 monoclonal antibody (1 mg/kg) clearly inhibited increases in airway responsiveness to acetylcholine and markedly reduced the number of eosinophils, neutrophils, lymphocytes as well as IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid. Furthermore, the antibody also attenuated airway inflammation and CD8+ T lymphocyte infiltration in lung tissue. CONCLUSIONS: These findings suggest that CD8+ T lymphocytes play a critical role for the development of respiratory syncytial virus-induced airway inflammation and airway hyperresponsiveness.

[Efficacy of continuous positive airway pressure therapy upon resistant hypertension in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the efficacy and possible mechanism of continuous positive airway pressure (CPAP) therapy upon blood pressure in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and resistant hypertension (RH). METHODS: Thirteen OSAHS patients with RH were recruited. Before and after 3-month CPAP therapy, their blood pressures at 10:00 PM, 2:00 AM and 6:00 AM were measured and their morning plasma concentrations of aldosterone (ALD) and plasma renin activity (PRA) tested at supine position with radioimmunoassay. RESULTS: Compared with blood pressure parameters at pre-CPAP therapy, there was a significant decrease in blood pressure before sleep at the end of 3-month CPAP therapy [(135.5 +/- 2.8)/(84.2 +/- 4.6) vs (152.2 +/- 19.2)/(98.9 +/- 15.6) mm Hg, P < 0.01], at night during sleep [ (133.1 +/- 2.4)/(81.5 +/- 4.6) vs (156.6 +/- 19.4)/(102.8 +/- 16.6) mm Hg, P < 0.01] and in the early morning [(151.5 +/- 3.0)/(81.2 +/- 3.2) vs (172.1 +/- 23.7)/(98.1 +/- 6.5) mm Hg, P < 0.01]. Comparison of plasma concentrations of ALD and PRA before and after 3-month CPAP therapy indicated that there was a significant difference in ALD [(538 +/- 42) vs (408 +/- 53) pmol/L, P < 0.01] but not significantly different in PRA [(0.27 +/- 0.14) microg x L(-1) x h(-1) vs (0.20 +/- 0.12), P = 0.221]. CONCLUSIONS: CPAP therapy could significantly improve RH and plasma ALD concentration. Elevated plasma ALD concentration is possibly involved in the pathogenesis of RH in OSAHS patients.

[A preliminary study on the early diagnosis of sinus dysfunction in patients with obstructive sleep apnea syndrome].

OBJECTIVES: To observe the characteristics of sinus dysfunction (SD) in patients with obstructive sleep apnea syndrome (OSAHS) and to explore the method for early detection of SD in these patients. METHODS: From January 2007 to June 2008, 119 snorers were recruited. All of them underwent polysomnography (PSG) examination and received atropine test under ultramicroelectrocardiogram (UMECG). Based on the results of atropine test, they were divided into 2 groups: the UMECG group (n = 78) including subjects diagnosed as having SD by a positive result of atropine test with UMECG, and the non-UMECG group (n = 41) including subjects with a negative result of atropine test. Comparison was made for the incidence of OSAHS between the 2 groups and the diagnostic sensitivities for SD between UMECG and PSG electrocardiogram (SD(PSG)). The association was also observed between PSG parameters and SD(PSG). RESULTS: The incidence of OSAHS in the non-UMECG group was significantly higher than that in the UMECG group (31% vs 55%, P < 0.05). SD(PSG) was not detected in the non-UMECG group. In the UMECG group, SD(PSG)/UMECG was 26/43 (60%) in the OSAHS subjects and 29/35 (83%) in the non-OSAHS subjects (P < 0.05). Of the OSAHS subjects in the UMECG group, SD(PSG)/UMECG was 10/20 (50%) in the mild to moderate OSAHS subjects and 16/23 (70%) in the severe OSAHS subjects (P < 0.05). Compared with the OSAHS subjects with UMECG but without SD(PSG), the average duration of apnea events as well as the longest apnea event were prolonged while the minimal SaO2 was lower in those OSAHS patients with SD(PSG). Among all of the 17 OSAHS subjects with SD(UMECG) but with out SD(PSG), there were 13 subjects (76%) with a fastest sinus heart rate slower than 90 beats/min even though they also had hypoxemia during sleep. CONCLUSIONS: SD was associated with OSAHS. The actual incidence of SD may be underestimated by PSG only, especially in those with mild to moderate OSAHS. SD should be suspected in OSAHS patients whose fastest sinus rate is lower than 90 beats/min in spite of hypoxemia. UMECG was more sensitive for early detection of SD.

High-sensitivity C-reactive protein: a predicative marker in severe asthma.

BACKGROUND AND OBJECTIVE: Serum levels of high-sensitivity CRP (hs-CRP) are associated with asthma but the relationship between higher levels of hs-CRP and the degree of asthma severity remains unclear. This study investigated whether hs-CRP is associated with asthma severity as well as with other clinical indices of asthma activity (pulmonary function, total serum IgE, and peripheral blood eosinophil counts). METHODS: Levels of hs-CRP and clinical indices of asthma were determined among 177 control subjects and 281 asthmatic patients (84 intermittent, 30 mild, 63 moderate and 104 severe). RESULTS: The level of hs-CRP was examined as both a continuous variable and by quartiles (<0.23, 0.23-0.51, 0.51-1.42 and >or=1.42 mg/L) in the five groups. Compared with the first quartile of hs-CRP, patients with higher levels were at increased risk of severe asthma independently of other clinical indices (adjusted OR 3.49, 95% CI: 1.51-8.12 for the third quartile; adjusted OR 6.46, 95% CI: 2.85-16.62 for fourth quartile, respectively). CONCLUSIONS: These findings suggest that hs-CRP might be a sensitive marker for severe asthma.

Increased RhoGDI2 and peroxiredoxin 5 levels in asthmatic murine model of beta2-adrenoceptor desensitization: a proteomics approach.

BACKGROUND: Beta(2)-adrenoceptor (beta(2)AR) desensitization is a common problem in clinical practice. beta(2)AR desensitization proceeds by at least such three mechanisms as heterologous desensitization, homologous desensitization and a kind of agonist-induced rapid phosphorylation by a variety of serine/threonine kinases. It is not clear whether there are other mechanisms. This study aimed to investigate potential mechanisms of beta(2)AR desensitization. METHODS: Twenty-four BALB/c (6-8 weeks old) mice were divided into three groups, which is, group A, phosphate buffered saline (PBS)-treated; group B, ovalbumin (OVA)-induced; and group C, salbutamol-treated. Inflammatory cell counts, cytokine concentrations of bronchoalveolar lavage fluid (BALF), pathological sections, total serum IgE, airway responsiveness, membrane receptor numbers and total amount of beta(2)AR were observed. Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were established. Groups B and C were selected for two-dimensional gel electrophoresis (2DE) analysis so as to find key protein spots related to beta(2)AR desensitization. RESULTS: Asthmatic mouse model and beta(2)AR desensitization asthmatic mouse model were verified by inflammatory cell count, cytokine concentration of BALF, serum IgE level, airway hyperreactivity measurement, radioligand receptor binding assay, Western blot analysis, and pathologic examination. Then the two groups (groups B and C) were subjected to 2DE. Two key protein spots associated with beta(2)AR desensitization, Rho GDP-dissociation inhibitor 2 (RhoGDI(2)) and peroxiredoxin 5, were found by comparative proteomics (2DE and mass spectrum analysis). CONCLUSION: Oxidative stress and small G protein regulators may play an important role in the process of beta(2)AR desensitization.

Expression of surface markers on peripheral CD4+CD25high T cells in patients with atopic asthma: role of inhaled corticosteroid.

BACKGROUND: CD4(+)CD25(+) regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules, particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), and transforming growth factor beta (TGF-beta), but little is known about the exact role of Tregs in the pathogenesis of asthma. This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects, and to investigate the effect of inhaled corticosteroid on them. METHODS: The expression of surface molecules on CD4(+)CD25(high) Tregs was detected by flow cytometry. The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro. Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay, respectively. RESULTS: Equivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects. Tregs preferentially expressed CTLA-4, GITR, toll-like receptor 4 (TLR4), latency-associated peptide (LAP/TGF-beta1), and forkhead box P3 (FOXP3). Patients with acute asthma had decreased numbers of CD4(+)CD25(high)LAP(+) T cells compared to healthy subjects and stable asthmatics. Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently. Furthermore, the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma, but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma. CONCLUSIONS: The results suggest that membrane-bound TGF-beta1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of asthma. Strategies targeting Tregs on their surface markers, especially TGF-beta1, are promising for future therapy of asthma.

[Association between residual sleepiness and central sleep apnea events in patients with obstructive sleep apnea syndrome].

OBJECTIVE: To investigate the possible association between residual sleepiness (RS) and central sleep apnea events in patients with obstructive sleep apnea syndrome (OSAS) following continuous positive airway pressure (CPAP) treatment, as well as the effects of adaptive servo-ventilation (ASV) on RS. METHODS: Following correct application of CPAP treatment and exclusion of other sleepiness-associated disorders, 50 patients with moderate-to-severe OSAS were recruited, including 26 patients with RS (RS group) and 24 patients without RS (control group). The treatment of one month's auto-CPAP (AutoCPAP) followed by one week ASV with autoCS2 ventilator was performed. Comparisons were made separately before treatment, on AutoCPAP and ASV treatments in both groups of the following parameters: polysomnographic parameters including central sleep apnea index (CSAI), micro-arousal index (MAI), etc; daytime Epworth sleepiness score (ESS), and possibly sleepiness-associated factor, i.e., plasma tumor necrosis factor-alpha (TNF-alpha). Plasma TNF-alpha levels were measured by enzyme linked immunosorbent assay (ELISA). t test and single factor analysis of variances were used for comparison between two groups and within group respectively. q test was used for couple comparison within group at 3 different stages. Pearson correlation test was performed for correlation analysis between 2 variables. RESULTS: Before treatment there was no significant difference between two groups in apnea hypopnea index (AHI), MAI, minimal pulse oxygen saturation (minSpO2), ESS and plasma TNF-alpha levels (t: 0.630, 1.223, 0.691, 0.764 and 0.19 2, all P > 0.05). However, the CSAI in RS group was significantly higher than that in the control group [(7.19 +/- 1.75) times/h vs (3.37 +/- 1.04) times/h, t = 4.097, P < 0.05)]. After 1 month's AutoCPAP treatment there was a significant decrease in AHI, CSAI, MAI and ESS in both groups (q: 0.87-112.55, all P < 0.05), but CSAI, MAI and ESS in the RS group than those in the control group [CSAI: (7.19 +/- 1.75) times/h vs (3.37 +/- 1.04) times/h, t = 9.473, P < 0.05; MAI: (9.00 +/- 1.95) times/h vs (2.36 +/- 0.66) times/h, t = 14.385, P < 0.05; ESS: 9.54 +/- 0.51 vs 5.42 +/- 1.32, t = 2.857, P < 0.05). On one weeks' ASV treatment there was such a further significant decrease in CSAI, MAI and daytime ESS in the RS group and the control group. In addition, compared with the plasma TNF-alpha level before treatment in the RS group, there was no statistical difference on AutoCPAP treatment but a significant decrease on ASV treatment. Plasma TNF-alpha levels were positively correlated with ESS (r = 0.503, P < 0.01) and MAI (r = 0.545, P < 0.01). CONCLUSIONS: RS in OSAS patients following CPAP treatment was associated with their CSAI before and during treatment. By effectively eliminating CSA events with ASV, RS was significantly improved, which suggested that ASV was effective in treatment of RS. The elevation of plasma TNF-alpha level was correlated with the severity of sleepiness and may be involved in the pathogenesis of RS.

[Treatment of Knee Osteoarthritis with Acupuncture plus Intra-articular Injection of Sodium Hyaluronate].

OBJECTIVE: To examine the clinical benefits of acupuncture combined with intra-articular injection of sodium hyaluronate for knee osteoarthritis (KOA) patients. METHODS: A total of 150 KOA patients were randomized into simple medication and acupuncture plus medication (combined treatment) groups (n＝75 in each). For all the patients, intra-articular injection of sodium hyaluronate (2 mL) was performed once a week for 5 weeks, and for patients of the combined treatment group, filiform needles were separately inserted into unilateral or bilateral Zusanli (ST 36), Liangqiu (ST 34), Yanglingquan (GB 34), Yinlingquan (SP 9), Xiyangguan (GB 33), Dubi (ST 35), Neixiyan (EX-LE 4) and Xuehai (SP 10) according to the focus, and manipulated with the uniform reinforcing and reducing technique, followed by retaining the needles for 30 min. The acupuncture treatment was given once every day or every other day, 5 weeks in total. The visual analog scale (VAS) was used to assess the pain severity of knee-joint, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) employed to assess the 1) pain severity during various positions or movements (20 points), 2) severity of joint stiffness (8 points), and 3) difficulty in performing daily functional activities (68 points). The therapeutic effect was evaluated according to the decreased level of WOMAC subscale scores and improvement of daily activities. RESULTS: After the treatment, the VAS scores of both medication and combined treatment groups were decreased significantly in comparison with their own pre-treatment in each group (P<0.05), and that of the combined treatment group was significantly lower than that of the medication group (P<0.05). WOMAC and daily activity fin-dings showed that of the two 75 KOA patients in the medication and combined treatment groups, 16 (21.33%) and 32 (42.67%) experienced marked improvement, 46 (61.33%) and 38 (50.67%) were improved, and 13 (17.33%) and 5 (6.67%) ineffective, with the total effective rates being 82.67% and 93.33%, respectively. The therapeutic effect of the combined treatment group was apparently superior to that of the simple medication group (P<0.05). CONCLUSION: Acupuncture combined with intra-articular injection of sodium hyaluronate is effective in improving KOA patients' pain severity and other symptoms as well as functional activities.

Effect of continuous positive airway pressure treatment on serum adiponectin level and mean arterial pressure in male patients with obstructive sleep apnea syndrome.

BACKGROUND: Recent research suggested that obstructive sleep apnea syndrome (OSAS) might be independently associated with hypoadiponectinemia, which was linked to some complications of OSAS, such as hypertension, diabetes, etc. This study was conducted to investigate the effect of continuous positive airway pressure (CPAP) treatment on changes of both serum adiponectin levels and mean arterial pressure and their possible links in male OSAS patients. METHODS: Twenty-three adult male patients with moderate-to-severe OSAS but without obesity, coronary heart disease and diabetes were recruited. Their blood samples were collected and morning mean arterial pressure (MAP) was measured before CPAP treatment and on day 3, 7, 14 of CPAP treatment respectively. The serum adiponectin concentration was tested with radioimmunoassay. RESULTS: Compared with the serum adiponectin level before CPAP treatment, no significant change was found in OSAS patients on day 3 and day 7 of CPAP treatment (P > 0.05). It was not until day 14 of CPAP treatment did a significant elevation in serum adiponectin level occur (P < 0.01). Meanwhile, the MAP showed no statistically significant difference among its levels before CPAP, on day 3 and day 7 of CPAP treatment (P > 0.05). However, on day 14 of CPAP treatment, a significantly lower MAP than that obtained before treatment was observed (P < 0.05). CONCLUSIONS: CPAP treatment can gradually reverse hypoadiponectinemia and reduce MAP in OSAS patients. Hypoadiponectinemia might be involved in the pathogenesis of OSAS-mediated hypertension.