Associations of Cough Prevalence with Ambient Polycyclic Aromatic Hydrocarbons, Nitrogen and Sulphur Dioxide: A Longitudinal Study.

Information on potential cough triggers including environmental irritants is vital for successful management of chronic cough in patients. We investigated the relationship between ambient levels of particulate polycyclic aromatic hydrocarbons (PAH), nitrogen dioxide (NO2) and sulphur dioxide (SO2) exposures with cough prevalence. Eighty-three adult patients, who had been physician diagnosed with at least asthma, cough variant asthma and/or atopic cough, were divided into asthma and non-asthma groups. They recorded daily cough symptoms during 4 January-30 June 2011 study period while daily samples of total suspended particles were simultaneously collected by use of glass fiber filters and the particulate PAH content determined by high performance liquid chromatography coupled with a fluorescence detector. Ambient concentrations of NO2 and SO2 were obtained from a local monitoring site. Logistic regression models using generalized estimating equations were used to determine population-averaged estimates of association between cough prevalence and ambient pollutant exposures for the two groups. Fully adjusted odds ratios from single pollutant models were 1.083 (95% confidence interval (CI): 1.029, 1.140) and 1.097 (95% CI: 1.016, 1.185) per 0.57 ng/m³ for lag2 PAH exposure, while only for asthma group had significant associations with NO2 and SO2 exposures for both lag2 and lag02. Similar associations were observed in multipollutant models. This finding suggests that ambient PAH, NO2, and SO2 exposure even at low levels is related to cough prevalence in adult chronic cough patients and may be considered as aggravating factor during clinical management of the condition.

Effects of substituent branching and chirality on the physical properties of ionic liquids based on cationic ruthenium sandwich complexes.

An appropriate understanding of how substituents affect the physical properties of ionic liquids is important for the molecular design of ionic liquids. Toward this end, we investigated how the branching and chirality of substituents affect the physical properties of organometallic ionic liquids. We synthesized a series of ionic liquids bearing a branched or linear alkoxy group with the same number of carbons: [Ru(C5H5)(η(6)-C6H5OR)]X (rac-[1]X: R = -CH(C2H5)(C6H13), [2]X: R = -CH(C4H9)2, [3]X: R = -C9H19), where X = PF6(-), (SO2F)2N(-), and (SO2CF3)2N(-). rac-[1]X are racemic salts. Salts with less symmetrical substituents tend to maintain the liquid state due to suppression of crystallization; crystallization is completely suppressed in most of the rac-[1]X salts and in some of the [2]X salts, whereas not in [3]X salts. The glass-transition temperatures and viscosities of the salts with branched substituents are greater than those with linear substituents. Chiral resolution of rac-[1][PF6] was performed by chiral chromatography. The melting point of rac-[1][PF6] is much lower than that of the enantiopure salt (chiral-[1][PF6]), which we ascribe to the formation of a conglomerate in the solid state. X-ray structure analysis revealed that the solid salts form layered structures.

A Longitudinal Study of Association between Heavy Metals and Itchy Eyes, Coughing in Chronic Cough Patients: Related with Non-Immunoglobulin E Mediated Mechanism.

The association between heavy metals exposure and respiratory diseases or allergic sensitization showing high serum immunoglobulin E (IgE) has been suggested. However, previous findings have been inconsistent and the mechanisms responsible remain unclear. We evaluated heavy metal exposure and its association with coughing, itchy eyes in chronic cough patients with different IgE levels. Ninety outpatients in Kanazawa University Hospital were recruited between January-June 2011. Subjects whose total IgE measured by radioimmunosorbent test were asked to record their daily symptoms. We collected daily total suspended particles (TSP) from which concentrations of calcium (Ca), cadmium (Cd), chromium (Cr), iron (Fe), manganese (Mn), nickel (Ni), and lead (Pb) were determined then divided into high and low level groups. Generalized estimating equations were applied to compute the relationship between concentrations of these metals and symptoms. All metals at high levels were significantly associated with itchy eyes compared with low levels, with exception of Ca, the six others were significant in patients with IgE < 250 IU/mL. Cd, Fe, Mn had association with coughing (odds ratio-OR (95% confidence interval-CI): 1.13 (1.03, 1.24), 1.22 (1.05, 1.42), and 1.13 (1.01, 1.27), respectively), this relationship remained significant for Cd (OR (95% CI): 1.14 (1.03, 1.27)) and Mn (OR (95% CI): 1.15 (1.00, 1.31)) in patients with lower IgE. Our findings demonstrate the relationship between aerial heavy metals and itchy eyes, coughing in chronic cough patients, suggesting these symptoms may be due to a non-IgE mediated mechanism.

Factors associated with tuberculosis cases in Semarang District, Indonesia: case-control study performed in the area where case detection rate was extremely low.

OBJECTIVES: Indonesia is ranked as the 4th highest contributor to tuberculosis (TB) in the world. Semarang District in Central Java displays extremely low case detection rate (CDR), possibly contributing to the local prevalence of TB. METHODS: A case-control study was performed to explore the factors that cause such low CDR. We recruited 129 TB cases and 83 controls that visited the same centers and were not diagnosed with TB. RESULTS: The cases had 7.5 ± 2.3 symptoms/person on average, indicating the delay in diagnosis because the controls only displayed 1.0 ± 1.7. The multiple logistic regression analysis comparing the cases/controls extracted following factors as a risk to have TB: farmer, close contact with TB patients, ignorance of whether Bacillus Calmette-Guérin (BCG) was accepted or no, smoking, low income, a lot of people living in the same room, irregular hand wash before meals, not wash hands after blow, soil floor, and no sunlight and no ventilation in the house. CONCLUSIONS: Neither the cases nor the controls knew the symptoms and how to avoid TB infection, which probably caused the delay in diagnosis. It is difficult to change the current living conditions. Thus, the amendment of the community-based education program of TB seems to be required.

Aberrant glycogen synthase kinase 3ß is involved in pancreatic cancer cell invasion and resistance to therapy.

BACKGROUND AND PURPOSE: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3ß (GSK3ß) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3ß in the invasive and treatment resistant phenotype of pancreatic cancer. METHODS: Pancreatic cancer cells were examined for GSK3ß expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3ß inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3ß inhibition on cancer cell xenografts were also examined. RESULTS: Pancreatic cancer cells showed higher expression and activity of GSK3ß than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3ß significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3ß also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3ß inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. CONCLUSION: The targeting of GSK3ß represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.

Phylogenetic analysis of atmospheric halotolerant bacterial communities at high altitude in an Asian dust (KOSA) arrival region, Suzu City.

The microbial communities transported by Asian desert dust (KOSA) events have attracted much attention as bioaerosols because the transported microorganisms are thought to influence the downwind ecosystems in Korea and Japan. However, the atmospheric microbial community has not been investigated at high altitude in the KOSA arrival area. In this study, to estimate the viability and diversity of atmospheric halotolerant bacteria, which are expected to resist to various environmental stresses as well as high salinities, bioaerosol samples were collected at 10 and 600 m above the ground within the KOSA arrival area, Suzu City, Japan, during KOSA events. During the sampling period, the particle numbers at 600 m were higher than those at 10 m, suggesting that large particles of aerosol fall from the high altitude of 600 m to the ground surface. The microorganisms in bioaerosol samples grew in media containing up to 15% NaCl concentrations demonstrating the viability of the halotolerant bacteria in bioaerosol samples. The PCR-DGGE analysis using 16S rDNA revealed that the bacterial species in NaCl-amended cultures were similar to the bacteria detected from the genomic DNA directly extracted from the bioaerosol samples. The 16S rDNA sequences of bacterial communities in bioaerosol samples were classified into 4 phylotypes belonging to the Bacilluscereus or Bacillussubtilis group. The bioaerosol samples collected at 600 m included 2 phylotypes belonging to B. subtilis, and one phylotype among all 4 phylotypes was identical between the samples at 10 and 600 m. In the atmosphere at 600 m, the halotolerant bacterial community was expected to remain viable, and the species composition was expected to include a few species of the genus Bacillus. During this investigation period, these atmospheric bacteria may have been vertically transported to the ground surface, where the long-range KOSA particle transport from China is frequently observed.

Purpurin is a key molecule for cell differentiation during the early development of zebrafish retina.

Recently, we cloned purpurin cDNA as an upregulated gene in the axotomized fish retina. The retina-specific protein was secreted from photoreceptors to ganglion cell layer during an early stage of optic nerve regeneration in zebrafish retina. The purpurin worked as a trigger molecule for axonal regrowth in adult injured fish retina. During zebrafish development, purpurin mRNA first appeared in ventral retina at 2 days post-fertilization (dpf) and spread out to the outer nuclear layer at 3 dpf. Here, we investigated the role of purpurin for zebrafish retinal development using morpholino gene knockdown technique. Injection of purpurin morpholino into the 1-2 cell stage of embryos significantly inhibited the transcriptional and translational expression of purpurin at 3 dpf. In the purpurin morphant, the eyeball was significantly smaller and retinal lamination of nuclear and plexiform layers was not formed at 3 dpf. Retinal cells of purpurin morphants were still proliferative and undifferentiated at 3 dpf. The visual function of purpurin morphant estimated by optomotor response was also suppressed at 5 dpf. By contrast, the control morphants with random sequence morpholino showed retinal lamination with distinct layers and differentiated cells at 3 dpf. These results strongly suggest that purpurin is a key molecule for not only optic nerve regeneration in adult but also cell differentiation during early development in embryo.

Effects of cruciferous allyl nitrile on phase 2 antioxidant and detoxification enzymes.

BACKGROUND: High intake of cruciferous vegetables has been associated with lower risk of various cancers, and the cancer preventive effect of the vegetables has been associated with their high levels of glucosinolates. The hydrolysis of glucosinolates results in the generation of bioactive compounds, including allyl nitrile which we previously found to be an active inducer of some phase 2 enzymes. In this study, we further explored the inductive ability of this nitrile in light of increasing evidence that antioxidants delay or prevent the development of cancer. MATERIAL/METHODS: Groups of 6 mice were administered subtoxic doses of allyl nitrile (5, 50, 100 or 200 micromol/kg) or vehicle-distilled water daily for 5 days by gastric intubation. On the sixth day, the animals were sacrificed for examination of enzyme activities in their tissues. Enzymes tested were thioredoxin reductase (TR), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase. RESULTS: Allyl nitrile increased the activity of TR in the liver, kidneys and rectum at doses of 100-200 micromol/kg/day, and GPx in the kidneys and small intestine at 50 to 200 micromol/kg/day, while in the colon, alone, it decreased the activities of GR and catalase at doses of 200 and 100-200 micromol/kg/day, respectively not. CONCLUSIONS: The present results suggest an involvement of allyl nitrile in antioxidant defense in the body, except for the colon.

Purpurin expression in the zebrafish retina during early development and after optic nerve lesion in adults.

Purpurin, a retina-specific protein, is known to play a role in cell adhesion during development of the chicken retina. Although purpurin has been significantly detected in adult chicken retina, its function in the matured retina is not well understood. Therefore, to determine the expression pattern of purpurin in the retina, we simultaneously investigated expression patterns of purpurin in the zebrafish retina during development in larvae and optic nerve regeneration after nerve transection in adults. In early development, levels of purpurin suddenly increased in the zebrafish retina 3 to 5 days after fertilization, and purpurin-positive immunoreactivity was diffusely located in all retinal layers. In contrast, levels of purpurin mRNA rapidly increased in the adult retina 1-3 days after optic nerve transection, and rapidly declined by 10 days after injury. Signal for purpurin mRNA was seen only in photoreceptors. Immunohistochemistry showed that levels of purpurin protein were also increased in the retina 1-3 days after nerve injury, but positive staining was located in photoreceptors and ganglion cells, and the staining in ganglion cells was stronger than that in photoreceptors. Thus, the transient expression of purpurin protein was greatly different during development and optic nerve regeneration. In the former, purpurin may be required in all retinal layers, whereas in the latter, purpurin may be required for injured ganglion cells.

Novel functional single nucleotide polymorphisms in the latent transforming growth factor-beta binding protein-1L promoter: effect on latent transforming growth factor-beta binding protein-1L expression level and possible prognostic significance in ovarian cancer.

Latent transforming growth factor (TGF)-beta binding proteins (LTBPs) play important roles in the secretion and activation of TGF-beta. We previously reported that LTBP-1L is overexpressed in some patients with ovarian cancer. To clarify the molecular mechanism of LTBP-1L regulation, we analyzed DNA sequences in the promoter region of LTBP-1L and identified two novel single nucleotide polymorphisms, -202G/C and +20A/C. While the alleles with -202C and +20C were initially reported, our data demonstrated that -202G and +20A are common in both ovarian cancer patients and healthy patients in the Japanese population. Luciferase reporter assays revealed that the G-A haplotype induced transcriptional activation in a Sp1-dependent manner. Electrophoretic mobility shift assays showed that increased binding affinity of Sp1 to the promoter with -202G and +20A. Interestingly, ovarian cancer patients (n = 42) with G-A/G-A homozygous genotype had increased expression of LTBP-1 and apparently poorer survival than those with other genotypes (P = 0.02). These findings suggest that the single nucleotide polymorphisms -202G/C and +20A/C on the LTBP-1L promoter may affect the clinical outcome of ovarian cancer patients, probably via up-regulating protein expression. Further studies using a larger number of samples will definitively determine the correlation between LTBP-1 haplotype and clinical behavior of ovarian cancer.

Induction of detoxication enzymes in mice by naturally occurring allyl nitrile.

Little is known about whether glucosinolate-derived nitriles have the ability to increase phase 2 detoxication enzymes and glutathione (GSH) in vivo. In this study, the ability of allyl nitrile, a hydrolysis product of the glucosinolate sinigrin, to increase tissue levels of the phase 2 detoxication enzymes glutathione S-transferase and quinone reductase and GSH in a variety of mouse tissues was examined. At the lowest dose level (11.8 mg/kg/day), allyl nitrile showed inductive ability in the stomach and lungs. At 23.6 mg/kg/day, the inductive effect was observed in the stomach, rectum, urinary bladder, and lungs, whereas at 47.2 mg/kg/day, it was recorded in the stomach, rectum, urinary bladder, kidneys, and lungs. These results show that allyl nitrile displays its maximum potency in the stomach and lungs, which is of interest in light of epidemiological studies demonstrating an inverse association between crucifer intake and the incidence of stomach and lung cancers.