[Feasibility study of telemedicine model for diagnosis and treatment of patients with obstructive sleep apnea hypopnea syndrome in China].

Objective: To explore the feasibility of applying telemedicine model in disease management for patients with obstructive sleep apnea hypopnea syndrome (OSAHS) in China. Methods: A total of 24 patients were enrolled with suspected OSAHS who were admitted to the Sleep Center of Peking University People's Hospital from October 2015 to September 2016. Patients were diagnosed by electronic questionnaire assessment and home sleep apnea monitoring (HSAT) and were treated with remote automatic positive airway pressure (APAP). After 1 week, 1 month and 3 months of treatment, the patients were followed up by video. The follow-up questionnaire was completed by the patients through an independent data management platform. The APAP treatment data and compliance data were obtained through a built-in digital card of the APAP device. Linear regression model was used to explore the factors related to patient compliance. One-way repeated-measure analysis of variance was used to compare the changes of APAP duration and apnea hypopnea index (AHI) among patients at different treatment time points. Paired t-test was used to compare the EPWORTH scale (ESS) scores before and after treatment. Results: A total of 22 patients were diagnosed with OSAHS, including 20 males (90.9%), aged (45.6±10.2) years and AHI before treatment was (46.9±20.4) times/h. A total of 20 OSAHS patients received APAP treatment, and the proportion of patients with good compliance after 1 week, 1 month and 3 months of treatment were 15/19, 10/19 and 8/18, respectively. The severity of sleepiness before treatment affected compliance. Each 1-point increase in ESS score was associated with a 6.16% (95%CI: 3.01%, 9.31%) increase in compliance. Age, body mass index and AHI before treatment had no effect on compliance (all P values>0.05). The AHI of the patients who had been treated for 1 week, 1 month and 3 months were (2.5±2.1), (2.2±1.6) and (1.9±1.0) times/h, respectively. (P=0.195). After 3 months of treatment, the ESS score was (7.0±3.3), lower than that before treatment (10.6±3.1) (P=0.079). Conclusion: Telemedicine mode of diagnosis and treatment of OSAHS patients has good therapeutic effect and patient compliance, which is practical and feasible.

Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide.

Protein tyrosine kinase (PTK) inhibitors have been proposed to reduce lung injury and lethal toxicity. The mechanisms responsible for the effects of PTK inhibitors remain obscure. The purpose of the present study was to examine whether genistein, a specific inhibitor of PTK, inhibits nuclear factor-kappa B (NF-kappaB) activation during acute lung injury induced by lipopolysaccharide (LPS) and, if so, to enumerate the effects of inhibition of NF-kappaB activation on LPS-induced proinflammatory gene products, such as cytokine-inducible neutrophil chemoattractant (CINC) and matrix metalloproteinase-9 (MMP-9), as well as neutrophil influx into the lungs. Intratracheal treatment of rats with LPS (6 mg/kg) resulted in increases in total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid and activated DNA-binding activity of NF-kappaB in alveolar macrophages and lung tissue. A 2-h pretreatment with genistein (50 mg/kg, intraperitoneally) inhibited the LPS-induced changes in lung injury parameters and the induction of NF-kappaB activation. Furthermore, these inhibitory effects of genistein correlated with a depression of LPS-induced protein tyrosine phosphorylation (approximately molecular masses of 46, 48, and 54 kD) and phosphorylation of Jun N-terminal kinase (JNK) in lung tissue. Genistein also substantially reduced the LPS-induced CINC production and MMP-9 activity and suppressed neutrophil recruitment. These results suggest that genistein attenuates LPS-induced acute lung responses through inhibition of NF-kappaB activation. In addition, NF-kappaB activation appears to be an important mechanism mediating LPS-induced CINC production and MMP-9 activity and resulting neutrophil recruitment associated with acute lung inflammation and injury.

Iron tetrakis (n-methyl-4'-pyridyl) porphyrinato (FeTMPyP) is a potent scavenging antioxidant and an inhibitor of stimulant-induced NF-kappaB activation of raw 264.7 macrophages.

Metalloporphyrins have been shown to be protective in oxidative stress models. However, the molecular basis for the antioxidative and antiinflammatory activities of iron tetrakis (N-methyl-4'-pyridyl) porphyrinato (FeTMPyP) is not known. The objective of this study was to determine whether FeTMPyP exhibited the ability to (1) scavenge reactive oxygen species (ROS), (2) inhibit the activation of nuclear factor kappa B (NF-kappaB), or (3) block the production of interleukin 1 (IL-1) in RAW 264.7 cultured macrophages. The results indicate that FeTMPyP is a potent scavenger of hydroxyl radicals and superoxide anion radicals, and an effective inhibitor of stimulant-induced NF-kappaB activation and IL-1 production by RAW 264.7 cells. Therefore, FeTMPyP may be a useful tool to investigate the molecular mechanisms involved in stimulant-induced signal pathways, and may possess therapeutic utility in diseases associated with overproduction of ROS.

Inhaled nitric oxide down-regulates intrapulmonary nitric oxide production in lipopolysaccharide-induced acute lung injury.

OBJECTIVE: To examine whether inhaled nitric oxide (NO) affected the intrapulmonary production of NO, reactive oxygen species, and nuclear factor-kappaB in a lipopolysaccharide (LPS)-induced model of acute lung injury. DESIGN: Prospective, randomized, laboratory study. SETTING: Experimental laboratory at a biomedical institute. SUBJECTS: Twenty male rabbits weighing 2.5-3.5 kg. INTERVENTIONS: Saline or LPS (5 mg/kg of body weight) was administered intravenously with or without NO inhalation (10 ppm) in each group of five rabbits. MEASUREMENTS AND MAIN RESULTS: LPS increased the lung leak index, the neutrophils and NO levels in bronchoalveolar lavage fluid, and NO levels produced by resting and stimulated alveolar macrophages. Inhaled NO decreased the lung leak index, the neutrophils and NO levels as measured by nitrite levels in the lavage fluid, and NO produced by the resting and stimulated alveolar macrophages. Inhaled NO also blocked the activities of reactive oxygen species and nuclear factor-kappaB binding to DNA in lavage cells and in alveolar macrophages. CONCLUSION: Inhaled NO attenuates LPS-induced acute lung injury, possibly by decreasing NO production in the lungs. The mechanism of reducing NO production resulting from inhaled NO may involve, in part, the activities of reactive oxygen species and/or nuclear factor-kappaB.

Zinc tetrakis(N-methyl-4'-pyridyl) porphyrinato is an effective inhibitor of stimulant-induced activation of RAW 264.7 cells.

One proposed mechanism for the development of silica-induced fibrosis is prolonged pulmonary inflammation and lung damage resulting from the secretion of reactive mediators from alveolar macrophages. Metalloporphyrins have antioxidative and antiinflammatory activities. However, the molecular basis for the antiinflammatory action of zinc tetrakis(N-methyl-4'-pyridyl) porphyrinato (ZnTMPyP) has not been elucidated. The objective of this study was to determine whether ZnTMPyP exhibited the ability to inhibit the production of reactive oxygen species (ROS), the activation of NF-kappaB, or the secretion of IL-1 in RAW 264.7 cells, and whether such inhibitory activity was related to the ROS-scavenging ability of ZnTMPyP. The results indicate that, although ZnTMPyP is not cytotoxic to RAW 264.7 cells, it is a potent inhibitor in ROS production by RAW 264.7 cells in response to various stimulants, such as silica, zymosan, or phorbol myristate acetate. ZnTMPyP is also effective in reducing stimulant-induced DNA-binding activity of NF-kappaB and silica-induced tyrosine phosphorylation of IkappaB-alpha. ZnTMPyP also inhibits LPS-induced IL-1 production. However, ZnTMPyP exhibits relatively weak ability to directly scavenge hyroxyl or superoxide radicals. On the basis of effective concentrations of ZnTMPyP, these results suggest that ZnTMPyP directly acts as an inhibitor of cellular activation in addition to exhibiting an antioxidant effect. Therefore, it is suggested that further studies concerning the effects of ZnTMPyP using in vivo oxidative stress models or its effects on the cytotoxic process of human diseases associated with lung inflammation and injury are warranted. In addition, ZnTMPyP may be a useful tool to investigate the molecular mechanisms involved in stimulant-induced signal pathways.

Enhancement of nuclear factor-kappaB activation and protein tyrosine phosphorylation by a tyrosine phosphatase inhibitor, pervanadate, involves reactive oxygen species in silica-stimulated macrophages.

Reactive oxygen species (ROS) and phosphorylation events mediated by tyrosine kinase are involved in silica-induced nuclear factor-kappa B (NF-kappaB) activation. Protein tyrosine phosphatase (PTPase) acts to limit protein tyrosine phosphorylation. In the present study, we investigated the role of PTPase in NF-kappaB activation and tyrosine phosphorylation in silica-stimulated macrophages, and the involvement of ROS in these responses. Treatment of mouse peritoneal macrophages (RAW264.7 cells) with a PTPase inhibitor, pervanadate, markedly enhanced the DNA-binding activity of NF-kappaB in the presence or absence of silica. The stimulatory effect of pervanadate on NF-kappaB activation was also demonstrated in LPS-stimulated macrophages. A specific inhibitor of protein tyrosine kinase (PTK), genistein, prevented the NF-kappaB activation induced by pervanadate in the presence of silica while inhibitors of protein kinase A or C, such as staurosporine or H7, had no inhibitory effect on NF-kappaB activation. A variety of antioxidants, such as catalase, superoxide dismutase, N-acetyl cysteine (NAC), and pyrrolidine dithiocarbamate, inhibited NF-kappaB activation induced by pervanadate in the presence of silica. Furthermore, pervanadate markedly enhanced silica- or LPS-induced protein tyrosine phosphorylation in cells. Treatment of macrophages with NAC abolished the increase in tyrosine phosphorylation in cells stimulated with the combination of pervanadate and either silica or LPS or with silica alone. The results suggest that PTPase may play a crucial role in the negative regulation of silica-signaling pathways leading to NF-kappaB activation in macrophages. Furthermore, ROS appear to be involved in downstream signaling between PTPase inhibition and NF-kappaB activation.

Silica induces nuclear factor-kappa B activation through tyrosine phosphorylation of I kappa B-alpha in RAW264.7 macrophages.

It was previously reported that protein tyrosine kinase (PTK) but not protein kinase C or A plays an important role in silica-induced activation of NF-kappa B in macrophages. The question is raised whether PTK stimulation and NF-kappa B activation in silica-stimulated macrophages are directly connected through tyrosine phosphorylation of I kappa B-alpha. Results indicate that stimulation of macrophages with silica led to NF-kappaB activation through tyrosine phosphorylation without serine phosphorylation. Specific inhibitors of protein tyrosine kinase, such as genistein and tyrophostin AG126, prevented tyrosine phosphorylation of I kappa B-alpha in response to silica. I kappa B-alpha protein levels remained relatively unchanged for up to 60 min after silica stimulation. Moreover, inhibition of proteasome proteolytic activity did not affect NF-kappa B activation by silica. Antioxidants, such as superoxide dismutase (SOD), N-acetylcysteine (NAC), and pyrrolidine dithiocarbamate (PDTC), blocked tyrosine phosphorylation of I kappa B-alpha induced by silica, suggesting reactive oxygen species (ROS) may be important regulatory molecules in NF-kappa B activation through tyrosine phosphorylation of I kappa B-alpha. The results suggest that tyrosine phosphorylation of I kappa B-alpha represents a proteasome proteolytic activity-independent mechanism for NF-kappa B activation that directly couples NF-kappa B to cellular tyrosine kinase in silica-stimulated macrophages. This proposed mechanism of NF-kappa B activation induced by silica could be used as a target for development of antiinflammatory and antifibrosis drugs.

[Relationship between pseudocroup and air pollutant burden of the inhaled air and weather]. / Zusammenhang zwischen Auftreten von Pseudokrupp und Schadstoff-belastung der Atemluft und Wetter.

An epidemiological study is presented to demonstrate, in addition to the viral aetiology, the influence of airpollution and various weather conditions to the incidence of croup. By means of a special statistic tool (baseline data curves) we could demonstrate that rapid changes in airpollutants (especially NO and NO2) are followed by increased occurrence of croup. In addition, the quotient NO2/NO seems to correlate directly to the O3 concentration. The noticeable influence of airpollution as well as changing climatic conditions demonstrate the multiform aetiology of croup.