Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Neighbourhood characteristics, lifestyle factors, and child development: Secondary analysis of the All our families cohort study.

Background: Neighbourhood characteristics have been found to influence child development, but little is known about lifestyle factors that may moderate this relationship, which can provide modifiable targets for policies and programing. This study investigated the association between neighbourhood characteristics (e.g., deprivation, disorder) during pregnancy and child development at age 5 in relation to various lifestyle factors (e.g., physical activity, parent-child reading, community resource use) during early childhood. Methods: A secondary analysis was conducted using multilevel modeling of data from the All Our Families cohort, recruited in Canada from 2008 to 2010. Participants self-reported on demographics during pregnancy, lifestyle factors at 3 years, and child development at 5 years using the Ages and Stages Questionnaire (ASQ-3). Neighbourhood deprivation was evaluated using the Vancouver Area Deprivation Index (VANDIX), while disorder was measured using police services' community crime reports. Results: Geocoded information was available for 2,444 participants. After adjusting for covariates, multilevel modeling indicated a significant negative association between neighbourhood deprivation and overall child development (b = -.726, 95% CI: -1.344, -.120). Parent-child reading was found to be a significant moderator of the effect of neighbourhood disorder (b = .005, 95% CI: .001, .009). There were no statistically significant moderation effects for physical activity or community resource use. Conclusion: Neighbourhood deprivation during pregnancy is associated with early child development. Parent-child reading may function as a protective factor in the presence of higher neighbourhood disorder. Overall, neighbourhood-level effects should be considered in policies and community programs that promote family and child well-being.

Characteristics of a "rebound" in smoking after a tobacco price increase.

SETTING: In Korea, the price of a pack of cigarettes increased 80% from US$2.2 to US$4 in 2015. The smoking rate decreased in 2015. However, it rebounded in the following year.OBJECTIVE: To evaluate the characteristics associated with this rebound in smoking rate following the price increase.DESIGN: We analysed the KNHANES (Korean National Health and Nutrition Examination Survey) data of 44 015 participants to evaluate current smoking rate and the proportion of smokers planning to quit within 6 months from 2010 to 2016. We also performed focused analysis of 18 303 participants between 2014 and 2016 KNHANES to determine the current smoking rate according to their demographic and socio-economic characteristics.RESULTS: Individuals who were older, female, unemployed, had a low household income or a shorter total smoking period, or smoked less per day were more likely to stop or reduce smoking after the price increase. The current smoking rate increased to 18.8% in 2016 from 17.7% in 2015; this difference was significant in men, those in the lower-middle quartile of household income, those with a middle-school or college education, and those who were employed.CONCLUSION: The rebound in smoking after the price increase was significantly related to the individual's sex, income, education and employment status.

Poor nutritional intake is a dominant factor for weight loss in chronic obstructive pulmonary disease.

Increase in energy expenditure and/or decrease in nutritional intake leads to low body mass index (BMI). The balance between energy expenditure and nutritional intake has rarely been evaluated in a large population of patients with chronic obstructive pulmonary disease (COPD). To evaluate BMI, nutritional intake and physical activity and the association of these factors with the severity of airflow obstruction in COPD patients. We analysed the Korean National Health and Nutrition Examination Survey (KNHANES) data set from 2012 to 2015. Among the 9682 individuals (1601 with COPD and 8081 without COPD) recruited, BMI was lower in COPD patients than in non-COPD participants (males, 23.86 ± 2.76 vs. 24.28 ± 2.80, P < 0.001; females, 23.63 ± 2.94 vs. 23.98 ± 3.10, P < 0.05). As the stage of COPD advanced, BMI, intake of nutrients (food, water and carbohydrates) and total energy levels declined in COPD patients. Total time spent walking in the preceding week decreased with advancing COPD stage in male patients with COPD. COPD severity was an important risk factor for the limitation of physical activity due to respiratory problems (OR 3.92, 95%CI 2.77∼5.34, P < 0.001). Patients with COPD had a low nutritional intake with little physical activity, which worsened with advancing COPD stage. In late-stage COPD, impaired nutritional intake outweighed the decrease in physical activity, resulting in weight loss. .

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

An 8-week face-split study to evaluate the efficacy of cosmeceuticals using non-invasive bioengineering devices.

BACKGROUND/AIMS: Even with the increasing demand for functional cosmeceuticals in the recent years, objective standard criteria for assessing their efficacy are currently incomplete at best. In this 8-week face-split study, in which we topically applied high-priced cosmeceuticals on one side and more affordable cosmeceuticals on the other side of the face, we compared the efficacy of these two products using non-invasive bioengineering technology. METHODS: We assessed the efficacy of a skin-whitening and an anti-wrinkle cosmeceutical product on 25 and 19 healthy female volunteers, respectively. In a single blind split setting, each participant received an 8-week topical application of high-priced cosmeceuticals to the left side of the face, and cheaper cosmeceuticals to the right side. Then, the subjects' biophysical parameters were measured for an objective evaluation of the results. This was followed by a questionnaire to obtain a subjective assessment. RESULTS: There was no significant difference in the change between the high-priced cosmeceuticals and the more affordable cosmeceuticals. At each measured site, there were variable changes including skin improvement and aggravation at the end of study. The subjective questionnaire demonstrated also that the participants perceived no difference in the efficacy between the two products. CONCLUSIONS: Our results showed that there were no significant differences in the skin biophysical parameters following the application with high-priced functional cosmeceuticals or less expensive cosmeceuticals. The subject failed to differentiate between the two products. The development of objective standard criteria for assessing its efficacy is essential.

Fast microtomography using bright monochromatic x-rays.

A fast microtomography system for high-resolution high-speed imaging has been developed using bright monochromatic x-rays at the BL29XU beamline of SPring-8. The shortest scan time for microtomography we attained was 0.25 s in 1.25 µm effective pixel size by combining the bright monochromatic x-rays, a fast rotating sample stage, and a high performance x-ray imaging detector. The feasibility of the tomography system was successfully demonstrated by visualization of rising bubbles in a viscous liquid, an interesting issue in multiphase flow physics. This system also provides a high spatial (a measurable feature size of 300 nm) or a very high temporal (9.8 µs) resolution in radiographs.

A comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis.

BACKGROUND: Plaque-type psoriasis manifests with various morphological phenotypes and different clinical activity over time in the same individual or from one patient to another. Circulating cytokines, especially T-helper (Th) 1- and Th17-related, have been suggested to reflect the inflammatory nature of psoriasis. However, studies regarding cytokine profile according to morphological phenotypes are quite scarce. OBJECTIVES: We sought to analyse the circulating Th1 and Th17 cytokines according to clinical phenotype and investigated the correlation between disease severity [Psoriasis Area and Severity Index (PASI)] and the serum level of inflammatory cytokines. METHODS: Seventy-one patients with psoriasis were divided into two groups according to clinical phenotype: chronic stable (CS) and eruptive inflammatory (EI). Th1- and Th17-derived cytokines were measured using multiplex cytokine assay. RESULTS: It was noted that interleukin (IL)-1 receptor antagonist and IL-17A were elevated in the EI group compared with the CS group. We also noticed that the PASI is relatively well correlated with serum cytokine level in the CS state but not as well in the EI counterpart. CONCLUSIONS: The level of serum inflammatory cytokines differs according to morphological phenotype. Also, the PASI does not seem to be a suitable tool to assess disease severity in patients with psoriasis with EI characteristics.

Incidence and management of postoperative abdominal bleeding after liver transplantation.

PURPOSE: To assess the incidence and management of postoperative abdominal bleeding after orthotopic liver transplantation (OLT) and to identify risk factors for abdominal bleeding. METHODS: We retrospectively reviewed the medical records of 1039 patients who underwent OLT at our institution from January 2008 to December 2010 seeking to identify subjects with posttransplantation abdominal bleeding, defined as any hemorrhage requiring radiologic intervention or laparotomy within the first month. RESULTS: Among the 1039 patients, 94 (9%) showed abdominal bleeding, occurring at a mean of 6.1 days (range, day 1 to 21 days). Active bleeding was controlled by endovascular interventional techniques (n = 37; 39%), by surgical ligation or vascular reconstruction (n = 43; 46%), or by sequential combinations of endovascular intervention and surgery (n = 14; 15%). The most frequent bleeding sites for radiologic intervention were the right inferior phrenic artery (n = 14), right and left epigastric arteries (n = 7), intercostal artery (n = 5) and right renal capsular artery (n = 4). The most frequent bleeding sites requiring laparotomy were the hepatic artery (n = 9), diaphragm (n = 8), inferior vena cava (n = 5), abdominal drain insertion site (n = 4), portal vein anastomosis site (n = 4), abdominal wall (n = 3), liver graft cut surface (n = 3), hilar plate (n = 3), and greater omentum (n = 3). Bleeding episodes were associated with greater patient age and increased intraoperative blood loss. CONCLUSIONS: The risk of bleeding from coagulopathy and iatrogenic injury is high during the early posttransplantation period. This risk of bleeding can be minimized by meticulous surgical dissection and bleeding control.

Homologous expression and quantitative analysis of T3SS-dependent secretion of TAP-tagged XoAvrBs2 in Xanthomonas oryzae pv. oryzae induced by rice leaf extract.

Xanthomonas oryzae pv. oryzae (Xoo) produces a putative effector, XoAvrBs2. We expressed XoAvrBs2 homologously in Xoo with a TAP-tag at the C-terminus to enable quantitative analysis of protein expression and secretion. Addition of rice leaf extracts from both Xoo-sensitive and Xoo-resistant rice cultivars to the Xoo cells induced expression of the XoAvrBs2 gene at the transcriptional and translational levels, and also stimulated a remarkable amount of XoAvrBs2 secretion into the medium. In a T3SS-defective Xoo mutant strain, secretion of the TAPtagged XoAvrBs2 was blocked. Thus, we elucidated the transcriptional and translational expressions of the XoAvrBs2 gene in Xoo was induced in vitro by the interaction with rice and the induced secretion of XoAvrBs2 was T3SSdependent. It is the first report to measure the homologous expression and secretion of XoAvrBs2 in vitro by rice leaf extract. Our system for the quantitative analysis of effector protein expression and secretion could be generally used for the study of host-pathogen interactions.

Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism.

INTRODUCTION: Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation. METHODS: C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks. RESULTS: Daidzein supplementation (≥ 0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor ß and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid ß-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor α and ghrelin. CONCLUSIONS: These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.

Genistein and daidzein repress adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via Wnt/ß-catenin signalling or lipolysis.

OBJECTIVES: One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/ß-catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti-adipogenic Wnt/ß-catenin signalling. MATERIALS AND METHODS: Adipose tissue-derived (AD) MSCs were exposed continuously to genistein and daidzein (0.01-100 µm) during adipogenic differentiation (21 days). An oestrogen antagonist, ICI 182,780, was used to determine whether or not the isoflavones activated Wnt signalling via oestrogen receptors (ERs). RESULTS: Genistein and daidzein suppressed adipogenic differentiation of AD-MSCs in a dose-dependent manner and inhibited expression of adipogenic markers, PPARγ, SREBP-1c and Glut 4, from mid-phase differentiation. Microarrays showed that anti-adipogenic effects of genistein were principally attributable to activation of Wnt signalling via ERs-dependent pathway, such as Erk/JNK signalling and LEF/TCF4 co-activators. These findings were supported by evidence that the effects of genistein were offset by ICI182,780. Unlike genistein, daidzein inhibited adipogenesis through stimulation of lipolysis, with for example, PKA-mediated hormone sensitive lipase. This is consistent with the increase in glycerol released from AD-MSCs. In conclusion, understanding that different sets of mechanisms of the two isoflavones on adipogenesis will help the design of novel strategies to prevent observed current epidemic levels of obesity, using isoflavones.

DNER modulates adipogenesis of human adipose tissue-derived mesenchymal stem cells via regulation of cell proliferation.

OBJECTIVES: In recent years, obesity has become a global epidemic, highlighting the necessity for basic research into mechanisms underlying growth of adipose tissue and differentiation of stem cells into adipocytes, in humans. For better understanding of cell signalling in adipogenesis, the role of DNER (delta/Notch-like EGF-related receptor) in adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSC) was investigated. MATERIALS AND METHODS: To assess the role of DNER in hAMSC adipogenesis, hAMSCs were transfected with DNER small interfering RNA (siDNER). Real-time quantitative reverse transcriptase polymerase chain reactions to assess expression levels of adipogenesis-related genes regulated by siDNER, cell cycle and immunoblot analyses were performed. RESULTS: First, it was determined that DNER mRNA was profoundly expressed in hAMSCs and reduced during adipogenic differentiation. Knockdown of DNER altered cell morphology, inhibited proliferation and increased frequency and efficiency of adipogenesis in hAMSC. Expression of CCAAT/enhancer-binding protein delta increased and proportion of cells in S phase decreased by knockdown of DNER, using specific siRNA. Moreover, adipocyte-specific genes including peroxisome proliferator-activated receptor gamma, fatty acid binding protein 4 and perilipin were up-regulated in siDNER compared to the siControl group during adipogenesis in hAMSC. CONCLUSIONS: These results indicate that DNER knockdown in hAMSC accelerated onset of adipogenic differentiation by bypassing mitotic clonal expansion during the early stages of adipogenesis.

Histone deacetylase inhibitors decrease proliferation potential and multilineage differentiation capability of human mesenchymal stem cells.

OBJECTIVES: Histone deacetylase (HDAC) is an important therapeutic target in cancer. Two of the main anticancer mechanisms of HDAC inhibitors are induction of terminal differentiation and inhibition of cell proliferation. To investigate the role of HDAC in maintenance of self-renewal and cell proliferation, we treated mesenchymal stem cells (MSCs) that originated from adipose tissue or umbilical cord blood with valproic acid (VPA) and sodium butyrate (NaBu). MATERIALS AND METHODS: Human MSCs were isolated from mammary fat tissue and cord blood. We performed MTT assay and flow cytometry-based cell cycle analysis to assess self-renewal of MSCs. In vitro differentiation assays into osteogenic, adipogenic, neurogenic and chondrogenic lineages were conducted to investigate MSC multipotency. Immunocytochemistry, Western blot and reverse transcription-polymerase chain reaction were used to interrogate molecular pathways. RESULTS: VPA and NaBu flattened the morphology of MSCs and inhibited their growth. VPA and NaBu activated the transcription of p21(CIP1/WAF1) by increasing the acetylation of histone H3 and H4 and eventually blocked the cell cycle at G2/M phase. The expression level of p16(INK4A), a cdk inhibitor that is closely related to cellular senescence, was not changed by HDAC inhibitor treatment. We performed controlled differentiation into bone, fat, cartilage and nervous tissue to elucidate the role of HDAC in the pluripotency of MSC to differentiate into functional tissues. VPA and NaBu decreased the efficiency of adipogenic, chondrogenic, and neurogenic differentiation as visualized by specific staining and reverse transcription-polymerase chain reaction. In contrast, osteogenic differentiation was elevated by HDAC inhibitor treatment. CONCLUSION: HDAC activity is essential for maintaining the self-renewal and pluripotency of MSCs.

The roles of Wnt antagonists Dkk1 and sFRP4 during adipogenesis of human adipose tissue-derived mesenchymal stem cells.

OBJECTIVES: The canonical Wnt signalling pathway performs an important function in the control of adipogenesis. However, the mechanisms and mediators underlying these interactions have yet to be defined in detail. Thus, this study was performed in order to elucidate the roles of the Wnt family during adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs). MATERIALS AND METHODS: We assessed several members of the Frizzled (FZD) family, the receptors of Wnts, inhibitors including the secreted frizzled-related protein (sFRP) family and Dickkopfs (Dkks), and the downstream factor, beta-catenin. Expressional levels of adipogenic markers regulated by the small interfering RNA of Dkk1 (siDkk1) and sFRP4 (sisFRP4) were assessed using real-time quantitative PCR and Western blot analysis. RESULTS: The mRNA level of Dkk1 was expressed abundantly in the early stages of adipogenesis and decreased rapidly during the late stages of adipogenesis. However, sFRP4 mRNA was up-regulated gradually during adipogenic differentiation in hAMSCs. Expression of FZD1, FZD7 and beta-catenin were reduced during adipogenic differentiation. Transfection of hAMSCs with siDkk1 or sisFRP4 partially inhibited differentiation of hAMSCs into adipocytes and restored levels of beta-catenin. CONCLUSIONS: We determined that Dkk1 was up-regulated transiently in the early stages of adipogenesis, and that sFRP4 levels increased gradually during adipogeneis via inhibition of Wnt signalling. Collectively, these results show that Dkk1 and sFRP4 perform an important function in adipogenesis in hAMSCs.

Combination drug therapy using edaravone and Daio-Orengedoku-to after transient focal ischemia in rats.

In this study, we investigated the effect of Daio-Orengedoku-to (DOT) on ischemic brain damage in a rat model of focal ischemia-reperfusion and attempted to identify synergistic effects for the combination of edaravone and DOT against ischemic insult. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion followed for 22 h. To determine the neuroprotective effect of DOT, it was administered orally just before reperfusion and then 2 h after reperfusion. To examine the effects of combination therapy on survival, rats were divided into groups treated with edaravone, DOT, and edaravone and DOT. Microglial activation, neutrophil infiltration and brain-derived neurotrophic factor (BDNF) expression were examined in surviving animals. Infarct volume was significantly reduced by DOT (100, 200 and 400 mg/kg; P < 0.05), and edaravone plus DOT markedly improved the survival rate after transient ischemia (P = 0.0133). Microglial activation was reduced by edaravone and DOT and their combination (P < 0.05), and neutrophil infiltration was lowered in these groups (P < 0.05). BDNF-positive cells were increased in the combination edaravone and DOT group (P < 0.05). It appears that the neuroprotective mechanisms of combined therapy involve inhibition of microglial activation, reduction of invading neutrophils and enhancement of BDNF expression.

Metalloproteinase-9 is increased after toluene diisocyanate exposure in the induced sputum from patients with toluene diisocyanate-induced asthma.

BACKGROUND AND OBJECTIVE: Persistent asthma symptoms are associated with airway inflammation and remodeling, which may be mediated through metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP). The aim of this study was to evaluate MMPs and TIMP involvement in toluene diisocyanate (TDI)-induced asthma. MATERIALS AND METHOD: Induced sputum was collected in eight newly diagnosed TDI-induced asthma subjects (group I) before and 7 h after the TDI and placebo challenges and in 12 subjects with TDI-induced occupational asthma diagnosed 5 years previously with persistent asthma symptoms (group II). Sera was collected in group I at diagnosis, and in group II, they were collected at the time of the study. 12 nonasthmatic healthy subjects were enrolled as controls. MMP-9, MMP-2 and TIMP-1 levels in both sputum and serum were measured by enzyme-linked immunosorbent assay (ELISA). Gelatinase activity in the sputum was confirmed by zymographic analysis. RESULTS: The serum TIMP-1 level was significantly higher in asthma patients than in healthy controls (P = 0.01), while MMP-9 level was significantly lower in asthmatic patients (P = 0.03). There was no significant difference in MMP-2 level (P = 0.27). MMP-9 level in the sputum was significantly increased after the TDI challenges (P = 0.01). TIMP-1 level in sputum tended to increase after TDI challenges, but no statistical significance was noted (P = 0.09). MMP-9 and MMP-9/TIMP-1 levels in the sputum were significantly higher in group II than in group I (P = 0.04, P = 0.02) with no significant difference in TIMP-1 level. Minimal amount of MMP-2 was found in sputum. Zymography demonstrated that MMP-9 level increased and active form of MMP-9 was generated after the TDI bronchoprovocation test. CONCLUSION: TDI exposure leads to overproduction of MMP-9, which may induce airway inflammation and remodeling, and then contribute to persistent asthmatic symptoms in TDI-induced asthma.

High prevalence of current asthma and active smoking effect among the elderly.

BACKGROUND: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. OBJECTIVE: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. METHODS: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. RESULTS: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). CONCLUSION: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

IgE binding components in Tetranychus urticae and Panonychus ulmi-derived crude extracts and their cross-reactivity with domestic mites.

BACKGROUND: Recent investigation has revealed that spider mites such as Tetranychus urticae and Panonychus ulmi are important allergens in the development of occupational asthma among apple farmers. OBJECTIVE: To evaluate IgE binding components in T. urticae and P. ulmi-derived crude extracts and their cross-reactivity with Panonychus citri, Tyrophagus putrescentiae and Dermatophagoides pteronyssinus in apple cultivating farmers. METHODS: Thirty-one apple farmers with positive skin responses to T. urticae or P. ulmi were randomly recruited, and specific IgE levels in their sera were measured using ELISA. Cross-reactivity was evaluated by ELISA inhibition. IgE binding components were evaluated by IgE immunoblotting. RESULTS: A total of 11 IgE binding components in T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa, 37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41 kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T. urticae-specific IgE binding was completely inhibited by 100 microg/mL of T. urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi-specific IgE binding was completely inhibited by additions of P. citri (92.3%) and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%). CONCLUSION: There were seven dominant allergens found in T. urticae and three in P. ulmi. T. urticae- and P. ulmi-specific IgE bindings were partially inhibited by crude extracts derived from D. pteronyssinus and T. putrescentiae.

Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins.

In the present study, we examined whether the bone morphogenetic proteins (BMPs), which are important in the developmental specification of transmitter type in certain classes of neurons, might also play a role in signaling the differentiation of a dopaminergic (DA) phenotype. We found that BMP-2, -4 and -6 were each capable of inducing, in a dose and time dependent manner, moderate levels of the DA enzyme tyrosine hydroxylase (TH) in cultured neurons from the mouse embryonic striatum. In contradistinction to other TH-inducing agents, BMPs initiated de novo TH expression without the required synergy of exogenous growth factors or co-activating substances and in neurons presumably aged (E16) beyond the critical period for induction. However, the appearance of TH in induced cells was short-lived (24 h) and could not be prolonged by repeated supplementation with the BMPs. Inhibitors of the mitogen-activated protein kinase (MAPK/ERK) signaling pathway, PD98059 and apigenin, did not prevent TH induction by BMP-4, as they did other TH inducing agents, indicating that the MAPK/ERK pathway does not mediate BMPs effects on TH expression. We conclude that BMP-2, -4 and -6 can be added to the expanding inventory of agents capable of inducing TH, making them potentially important in the specification of a DA phenotype in stem/precursor cells for the treatment of Parkinson's disease.