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Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance, reverse pulmonary vascular remodeling, and thereby improving right ventricular function. Iptakalim, a lipophilic para-amino compound with a low molecular weight, has been demonstrated to be a new selective ATP-sensitive potassium (K(ATP)) channel opener via pharmacological, electrophysiological, biochemical studies, and receptor binding tests. In hypoxia-induced animal models, iptakalim decreases the elevated mean pressure in pulmonary arteries, and attenuates remodeling in the right ventricle, pulmonary arteries and airways. Furthermore, iptakalim has selective antihypertensive effects, selective vasorelaxation effects on smaller arteries, and protective effects on endothelial cells, but no effects on the central nervous, respiratory, digestive or endocrine systems at therapeutic dose. Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1, reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells. Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials, it can be a potential candidate of HPH in the future.

Summary form only given. Pulsed discharges in hydrogen and its isotopes play critical roles in several applications1, 2: pre-ionization plasmas in field reversed configuration, plasma lens for focusing heavy-ion beams, and gas-puff Z-pinches. However, the initial phase of these discharges is still poor understood.

To observe the effect of noradrenalin (NE) on human pulmonary arterial smooth muscle cells (PASMC) by using a proteomic approach.Human PASMC were cultured primarily in vitro. Experiments were performed in the 3(rd) to 5(th) passages of the cells. The human PASMC were cultured in serum-free medium for 24 h prior to treatment with either NE (10(-5) mol/L, the test group) or completed-serum culture medium (the control group) for 24 h. And then analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was performed to display the different protein profiles of whole cell protein from cultures of the control and the NE-treatment group. Real-time RT-PCR and Western blot analysis were used to confirm the proteomic analysis.The purity of the primary culture cells was about 99%. When the human PASMC were treated by NE, the expression of different groups of cellular proteins was changed, including cell cytoskeleton-associated proteins, cell signal-associated proteins, and glycolytic and metabolism-associated proteins. The results were confirmed using real-time RT-PCR and Western blot. NE enhanced the proliferation of human PASMC partly by affecting the expression of α-enolase.The data suggest that a wide range of signaling pathways may be involved in NE-induced proliferation of human PASMC, and α-enolase associated pathway may be an important one.

to study the association between interleukin-4 receptor α chain (IL-4RA) Q576R polymorphisms and bronchial asthma susceptibility by Meta-analysis.four medical databases, including Pubmed, Embase, CNKI and Wanfang, were searched for the case-control studies about the IL-4RA polymorphisms and bronchial asthma susceptibility. Odds ratios (OR) of IL-4RA Q576R genotype distributions in asthma patients against healthy controls were analyzed in both RR vs QR + QQ model and QR + RR vs QQ model. Analyses were performed for asthma in general and for subgroups based on the atopy status of the asthma population. The sensitivity analysis and the publication bias tests were conducted.fifteen case-control studies, with 2675 asthma cases, 1202 atopic asthma cases and 331 nonatopic asthma cases respectively, were identified and all control group genotype frequencies were consistent with Hardy-Weinberg equilibrium. In genotype RR vs QR + QQ model no heterogeneity among the studies was found, while in genotype QR + RR vs QQ model, heterogeneity among these studies was found. These studies were analyzed by fixed-effect model (RR vs QR + QQ model) or random-effect model (QR + RR vs QQ model). The pooled odds ratio of IL-RA Q576R genotype RR vs QR + QQ was 2.02 (95%CI: 1.53 - 2.66), and the pooled odds ratio in this model in the atopic asthma subgroup was 2.26 (95%CI: 1.47 - 3.49), while the pooled odds ratio (QR + RR vs QQ model) was 1.02 (95%CI: 1.06 - 1.53).a meta-analysis of results from case-control studies strongly supports the conclusion that IL-4RA Q576R polymorphisms impart a modest yet significant risk for asthma.

To investigate whether pulmonary vascular remodeling in hypoxic pulmonary hypertensive rats could be prevented by treatment with a selective K(ATP)CO, iptkalim (Ipt).Rats were fed in hypoxic and normobaric environment (10% +/- 0.5% O2, 8 h/day and 6 day/week) and divided into control group, hypoxia group (hypoxic rat treated with ig NS 5.0 ml x kg(-1) x d(-1)), treated group I (hypoxic rat treated with ig Ipt 0.75 mg x kg(-1) x d(-1)), treated group II (hypoxic rat treated with ig Ipt 1.5 mg x kg(-1) x d(-1)). After 4 wk, the mean pulmonary arterial pressure (mPAP), right ventricle/left ventricle and septum [RV/(LV + S)] were measured, and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in four groups.The level of mPAP and RV/(LV+ S) was significantly higher in the hypoxic group than those in control group (P0.01). Morphometric analysis revealed that the ratio of vascular medial wall thickness to external diameter (MT%) and the ratio of vascular medial cross-sectional area to total arterial cross-sectional area (MA%) were also significantly increased in the hypoxic group than those in control group (P0.01) and the ratio of vessel lumen cross-sectional area to total arterial cross-sectional area (VA%) was significantly lower in the hypoxic group than those in control group (P0.01). Ipt 0.75 mg x kg(-1) x d(-1) or 1.5 mg x kg(-1) x d(-1) decreased the level of mPAP(mmHg), RV/(LV+ S), and inhibited the small pulmonary arterial remodeling significantly. Ipt 1.5 mg x kg(-1) x d(-1) reversed all pathological indices.K(ATP)CO iptkalim can be a very promising candidate for the treatment of hypoxic pulmonary hypertension.

The degradation of azo dye wastewater, containing MX-5B, was investigated by using high frequency ultrasonic irradiation. The effect of different factors like the initial pH of solution, sonolysis parameters, air-blowing, Fe2+ concentration were studied, the synergistic action of complex frequency and the mechanism of degradation was explored primarily. The results show that MX-5B in aqueous solution can be degraded efficiently by ultrasonic irradiation, when the pH 3.5, ultrasonic frequency 418.3 kHz, ultrasonic power 69 W, color removal rate up to 100% in 180 min. Adding of Fe2+ and blowing air had some effects. The results also indicated that radical-oxidation controlled the ultrasonic decompose of MX-5B and MX-5B ultrasonic removal was observed to behave as pseudo-first-order kinetics under different experimental conditions tested in the present work. Comparison of UV-Vis absorption spectrums before and after treatment showed that all of the conjugate structure and part of aromatic structure were destroyed after being ultrasonic irradiation.

To improve the understanding of the clinical manifestations of pulmonary coccidioidomycosis.A case of pulmonary coccidioidomycosis was reported, and the literature was reviewed. The epidemiologic, clinical and diagnostic aspects of coccidioidomycosis were discussed.A 74 year old male was admitted to the hospital because of physical examination revealing lung space occupying lesions for 9 months and cough for 2 weeks. Lung puncture biopsy was carried out and the diagnosis of cryptococcosis was established in another hospital. After 6 months' therapy with fluconazole, the chest CT showed no change. After being hospitalized, thoracoscopic wedge resection of lung was performed and the final diagnosis was pulmonary coccidioidomycosis. After the surgery, he was immediately started on voriconazole 200 mg daily for 1 month. Then oral fluconazole was prescribed for 5 months. A follow-up chest CT performed 6 months after surgery was normal.Coccidioidomycosis is uncommon. It's pathological appearance is similar to cryptococcus. With the extensive using of immune suppressive drugs, we should improve the recognition of coccidioidomycosis.

The study of an explosive pulsed power source based on inductive energy storage technology is presented in this paper. The power source consists of a capacitor bank used as the primary energy source, an explosive magnetic flux compression generator (MFCG), and an inductive energy storage power conditioning system with a low resistor load. A pulse voltage of over 400 kV with more than 200 ns duration and less than 50 ns rising time is obtained on a 10 load in experiment

To investigate the effects of adenoviral gene transfer of IkappaBalpha mutant (IkappaBalphaM), a novel inhibitor of nuclear factor kappaB (NF-kappaB), on apoptosis, phenotype and function of human monocyte-derived dendritic cells (DC).Monocytes, cocultured with granulocyte/macrophage colony-stimulating factor (GM-CSF; 900 ng/mL) and interleukin (IL)-4 (300 ng/mL) for 5 d, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 2 d differentiated into mature DC. Monocytes were either left untransfected or were transfected with AdIkappaBalphaM or AdLacZ. The transcription and expression of the IkappaBalphaM gene, and the inhibitory effect of IkappaBalphaM on tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation in mature DC were detected by polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and electrophoretic mobility shift assays, respectively. The phenotype, apoptosis, IL-12 secretion level of DC, and ability to stimulate the proliferation of T cells were determined by flow cytometry, enzyme-linked immunosorbent assay and mixed leukocyte reaction.PCR and RT-PCR were used to detect a unique 801 bp band in AdIkappaBalphaM-transfected mature DC, and also a dose- and time-dependent expression of the IkappaBalphaM gene, which peaked at a multiplicity of infection of 100 pfu/cell and at 48 h. Furthermore, AdIkappaBalphaM significantly suppressed the TNF-alpha-induced NF-kappaB activation, augmented apoptosis, downregulated CD80, CD83, and CD86 surface molecules, IL-12 secretion levels and the ability to stimulate the proliferation of T cells in mature DC.AdIkappaBalphaM effectively transfected and potently inhibited NF-kappaB activation in monocyte-derived mature DC. Overexpression of the IkappaBalphaM gene in mature DC may contribute to T-cell immunosuppression through induction of DC apoptosis and downregulation of B7 molecules, providing a potential strategy for future DC-based immunotherapy of asthma.

Nuclear factor kappaB (NF-kappaB) overactivation, requiring phosphorylation and degradation of its inhibitor IkappaBalpha, is the basis for chronicity of airway inflammation in asthma. Based on our previous plasmid pShuttle-IkappaBalpha, carrying an IkappaBalpha gene from human placenta, we optimized a novel IkappaBalpha mutant (IkappaBalphaM) gene, constructed and characterized its replication-deficient recombinant adenovirus (AdIkappaBalphaM), and tested whether AdIkappaBalphaM-mediated overexpression of IkappaBalphaM could inhibit the NF-kappaB activation in endothelial cells.IkappaBalphaM gene (203 - 1003 bp) encoding 267 amino acids, acquired by site-directed deleting N-terminal phosphorylation sites of serine 32/36, was subcloned into the pShuttle and pGEM-T vectors for further polymerase chain reaction (PCR), restriction digestion, deoxyribonucleic acid (DNA) sequencing and homology analyses. Subsequent to inserting the expression unit of pShuttle-IkappaBalphaM, containing cytomegalovirus (CMV) promoter, IkappaBalphaM complementary DNA (cDNA) and polyadenylic acid (PolyA) signals, into the type 5 adenovirus (Ad5) vector, the resultant AdIkappaBalphaM was packaged in human embryonic kidney (HEK) 293 cells by cotransfection with lipofectamine. Western blot analysis and electrophoretic mobility shift assay were utilized to detect the AdIkappaBalphaM-mediated overexpression of IkappaBalphaM in HEK293 cells and its suppressive effect on phorbol 12-myristate 13-acetate (PMA)-induced NF-kappaB activation in human umbilical vein endothelial (ECV304) cells, respectively.The relevant nucleotides and deduced amino acids of 801 bp IkappaBalphaM gene were consistent with those of IkappaBalpha gene (GenBank accession number: M69043). The titer of the prepared AdIkappaBalphaM was 4.0 x 10 (12) plaque-forming units (pfu)/L. Moreover, the IkappaBalphaM gene was overexpressed in HEK293 cells, and potently inhibited the PMA-induced NF-kappaB activation in ECV304 cells dose-dependently.AdIkappaBalphaM is a novel vector for both efficient transfer and specific overexpression of IkappaBalphaM gene, as well as potent inhibition of NF-kappaB activity, providing a promising strategy for gene therapy of asthma.

To explore the effects of iptakalim on the proliferation of rabbit pulmonary arterial smooth muscle cell(PASMC) induced by endothelin-1(ET-1) in vitro.The experimental models of proliferation of rabbit PASMC induced by ET-1 in vitro were established and [(3)H]-thymidine ([(3)H]-TdR) incorporation and flow cytometric analysis(FCA) were used.The value of [(3)H]-TdR incorporation in ET-1 group was increased 1.468 times higher than that in control group. Iptakalim at the concentrations of 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L lowered [(3)H]-TdR incorporation by (19.8 +/- 4.6)%,(41.2 +/- 9.5)%, (54.7 +/- 10.1)%, declined the total of the DNA synthesis (S) and the mitotic phase (G(2)/M) ratios by (36.6 +/- 5.7)%, (42.6 +/- 4.9)%, (66.3 +/- 4.7)%, and increased the static phase (G(0)/G(1)) ratio by (14.4 +/- 3.0)%, (17.9 +/- 2.6)%, (27.9 +/- 3.2)%, respectively, compared with the value of the cells treated with ET-1 only (P0.01). Glibenclimide abolished the effect of iptakalim on [(3)H]-TdR incorporation.Iptakalim has an inhibitory effect on PASMC proliferation induced by ET-1 through activating ATP sensitive potassium (K(ATP)) channels.

The hydrothermal reaction of rare earth nitrates, CuCN, 1H-1,2,3-triazole-4,5-dicarboxylic acid (H3tda), and isonicotinic acid (Hina) resulted in the formation of a new series of 3d–4f heterometallic coordination polymers [LnCu(tda)(ina)2(H2O)]·3H2O (Ln = Eu (1), Tb (2), Gd (3), Dy (4), Ho (5)], H3tda = 1H-1,2,3-triazole-4,5-dicarboxylic acid, Hina = isonicotinic acid). Complexes 1–5 are isostructural and structurally characterized by elemental analysis, FT-IR spectroscopy, thermogravimetric analysis (TGA), and single-crystal powder X-ray diffraction (PXRD). Single-crystal X-ray diffraction analysis reveals that the metal cations in these compounds are firstly interconnected by H3tda ligands to produce a carpet-shaped heterometallic ring [Ln2(tda)2Cu4], and then pillared by bridging Hina molecules to form the 3D layer-pillared porous Ln(III)–Cu(II) heterometallic coordination polymers. In addition, the magnetic properties of 1–5 were also investigated in detail.

To explore the influence of different carboxylate ligands on the structures of metal–organic frameworks (MOFs), five novel Zn(II) coordination polymer compounds, namely, {[Zn(atz)(bia)]}n (1), {[Zn3(atz)3(tpa)3/2]}n (2), {[Zn2(atz)2(pda)]}n (3), {[Zn4(atz)2(btc)]·4H2O}n (4) and {[Zn2(atz)2(btec)]·H2O}n (5) have been successfully obtained by introducing various secondary auxiliary ligands in Zn(II)–L systems, characterized by elemental analysis, FT-IR, thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction (Hatz = 3-amino-1,2,4-triazolate, Hbia = benzoic acid, H2tpa = 1,4-terephthalic acid, H2pda = 1,4-benzenediacetic acid, H3btc = 1,3,5-benzenetricarboxylate, H4btec = 1,2,4,5-benzenetetracarboxylic). Compound 1 features a 2D layer with (4.82) topology, which is further stabilized by hydrogen bonds between the uncoordinated amino groups and uncoordinated oxygen atoms from bia ligands. Compound 2 exhibits a 3D 3,4-connected framework with {4.82.103}{4.82} topology, constructed from Zn(II) ions and μ3-atz ligand. Compound 3 displays a 3D 3,4-connected network with {4.6.8}{4.62.83} topology. Compound 4 possesses a 3D 9-nodal network with a point symbol of {4.8.9}2{4.82}{4.83.9.10}{5.8.9}4{5.82}. Compound 5 shows a 3D 3,4,4-connected framework with {4.82}4{42.83.10}2{84.102} topology. The diverse structures of these five complexes demonstrate that the skeleton of carboxylate ligands have a significant impact on the construction of MOFs. Moreover, the luminescence properties of complexes 1–5 were investigated in the solid state.