Summary of best evidence for the management of thirst in ICU patients / 中国实用护理杂志

Objective:To summarize the best evidence of thirst management in ICU patients and provide evidence-based basis for dinical practice.Method:According to the "6S" evidence pyramid model, the literature on thirst management of ICU patients was systematically retrieved from relevant guidelines websites, evidence-based databases, association websites and original literature databases at home and abroad. The retrieval time was from the establishment of the database to June 31, 2022. Two researchers with evidence-based nursing training independently completed literature quality evaluation. To extract and summarize the evidence of the literature that meets the quality standard.Results:A total of 17 articles were included, including 8 randomized controlled trials, 5 quasi-experimental studies and 4 cross-sectional studies. The 18 pieces of best evidence were formed, including 5 aspects: basic requirements of thirst management, intervention evaluation, intervention methods, matters needing attention and health education.Conclusions:This study summarized the best evidence of thirst management in ICU patients. Nurses should translate and apply the best evidence in combination with the clinical situation and specific policies of the department to relieve the thirst symptoms of ICU patients.

Identification and analysis of the R2R3-MYB transcription factor based on a transcriptome database in Morinda officinalis / 药学学报

In order to explore MYB transcription factors related to developmental processes and secondary metabolism in Morinda officinalis, we analyzed MoMYB expression based on transcriptome data from three tissues (root, stem and leaf). We used this analysis to provide a theoretical foundation for regulating the metabolism of M. officinalis. RNA-seq data along with the five databases including PFAM and plantTFDB and others were used to screen and classify MoMYB, including GO functional annotation and classification, subcellular localization, signal peptide prediction, conserved motif discovery, and comparative phylogenetic analysis. RT-qPCR was carried out to detect tissue-specific expression differences of MoMYB genes. According to transcriptome data, 109 MoMYB sequences were identified and divided into four classes, containing 51 sequences related to R2R3-MYB. Subcellular localization analysis indicated that a majority of sequences were located in nucleus. Blast2GO analysis showed that 109 MoMYB sequences were classified into three major functional ontologies including molecular function (112), biological processes (76) and cellular components (239). The R2-MYB conserved motif of 51 R2R3-MYB sequences possessed three significantly conserved tryptophan residues, whereas a phenylalanine replaced the first tryptophan in R3-MYB. The results of multiple sequence alignment and phylogenetic analysis revealed that the R2R3-MYB was distributed in all subgroups, apart from the S10, S19 and S21 subgroups. RT-qPCR indicated that several R2R3-MYB genes were differentially expressed among the three tissues, and this finding was consistent with transcriptome data. The 109 MoMYB sequences were annotated and divided into different classes, which lays the foundation for further study on MYB transcriptional factors in M. officinalis.

Cloning and analysis of the DXR gene and its promoter in Morinda officinalis / 药学学报

The objective of this research was to clone 1-deoxy-D-xylulose 5-phosphate reductoisomerase gene (MoDXR) and its promoter sequence from Morinda officinalis and carry out bioinformatic analysis, cis-acting elements analysis, and prokaryotic expression. On the basis of the MoDXR gene sequence obtained from the M. officinalis transcriptome and with NCBI-ORFfinder analysis, a pair of specific primers were designed, and used for RT-PCR amplification. The promoter region sequence at the 5′ end of MoDXR gene was isolated by the genome walking technique. Localization of MoDXR was carried out by subcellular analysis. The prokaryotic expression plasmid pET-28a-MoDXR was constructed and transfected into Escherichia coli BL21(DE3) chemically-competent cells; the recombiant plasmid expressed fusion protein after the induction by IPTG. The full-length cDNA of MoDXR was 2 015 bp,and open reading frame (ORF) size was 1 425 bp, and it encoded 474 amino acid residues and had a molecular mass of 51.27 kD. Sequence comparison with BlastP to the NCBI database revealed that MoDXR had high sequence similarity with many other DXRs, such as Coffea arabica DXR (CaDXR) and Rauvolfia verticillata DXR (RvDXR). A phylogenetic tree revealed that MoDXR had its closest relationship with DXR from Coffea arabica and Gardenia jasminoides. The subcellular localization revealed that MoDXR protein was located on the chloroplast. Plantcare analysis indicated that the promoter region sequence of MoDXR was 1 493 bp, covering multiple light, stress, and hormone-responsive cis-regulatory elements; protein electrophoresis showed that the expressed protein was the anticipated size. This research lays the foundation for further purification and structural and functional characterization of the MoDXR protein.

Nasality Changes With Age in Normal Korean-Speaking Adults

OBJECTIVES: This study was performed to investigate the effects of aging on nasality and the influence of age-related changes in nasal cavity volume and nasal patency on nasality. METHODS: A total of 180 healthy Korean-speaking adult volunteers, who had no nasal or voice-related complaints, were enrolled in this study. Nasometry, acoustic rhinometry, and rhinomanometry were performed to obtain the nasalance score, nasal cavity volume, and nasal resistance, respectively. Changes in these parameters with age were analyzed. RESULTS: Nasal cavity volume increased significantly, and nasal resistance decreased significantly, with age. The nasalance scores for the nasal passage and oronasal passage decreased significantly with age, while there were no age-related changes in nasalance scores for the oral passage. CONCLUSION: Nasalance scores for the passages containing nasal consonants decreased with age although significant increases were observed in nasal cavity volume and nasal patency with age. Therefore, the age-related decreases in nasalance scores may result from factors other than changes in the nasal cavity.

Effect and mechanism of human dental pulp stem cells-derived exosomes on lipopolysaccharide induced acute lung injury / 军事医学

Objective To investigate the protective role and underlying mechanism of human dental pulp stem cells (DPSCs)-derived exosomes against lipopolysaccharide ( LPS) induced acute lung injury ( ALI) in pulmonary alveolar macrophage(PAM) cells of rats.Methods DPSCs were cultured in the complete culture medium , and their supernatants at passage 6 were collected after serum-free medium treatment for 24 hours.Exosomes were extracted and purified with ultracentrifugation .Rat PAM NR8383 was cultured in 12-well plate and treated with LPS of 1μg/ml alone or together with exosomes.The supernatants were then collected at 0, 6, 12 and 24 h respectively after treatment .Inflammatory cytokine levels of tumor necrosis factor-α(TNF-α)and interleukins (IL-1βand IL-6) in the supernatant were measured by ELISA assay and the expression and phosphorylation level of MAPK (p44/42), NF-κB and IκBαin cell lysates were detected with Western-blotting.Results Compared with control group , the content of TNF-α,IL-1βand IL-6 increased significantly in LPS group (P<0.05), which indicated that the inflammatory cell model was induced successfully .The levels of TNF-αand IL-1βwere obviously attenuated after a high doses of exosomes treatment (P<0.05), and the expression of IL-6 was markedly suppressed after low and high doses of exosomes treatment (P<0.05), compared with the group of LPS treatment alone.The phosphorylation of NF-κB, IκBαand p44/42 was significantly inhibited after treatment with the DPSCs-derived exosomes.Conclusion DPSCs-derived exosomes may have a potential protective effect on LPS-induced ALI, and the underlying mechanism is that the activity of MAPK (p44/42) and NF-κB/IκBαpathways are eliminated by DPSCs-derived exosomes.

Construction of full-length cDNA library of Sarcandra glabra and sequences analysis on EST / 中草药

Objective: Sarcandra glabra was recognized as an important research material attributing to its high medicinal value and economic value. However, little information was known about its genomics and regulatory pathway participating in reproductive development. For the first step to understand the molecular basis and further explore genes which related to metabolism and resistance in S. glabra. Methods: A SMART full-length complementary DNA library from the leaves tissue was constructed and characterized to providing the experimental basis for discovery of functional genes of S. glabra. The assembly expressed sequence tag (EST) data were completed by ABI3730 DNA program. A high quality full-length cDNA library was constructed successfully from S. glabra leaves. Results: The titer of library was 1.14×107 pfu/mL and the average length of inserted fragments was 1 000 bp. A total of 221 clones were sequenced from the cDNA library and obtained 177 EST sequences. The EST sequences were assembled into 151 unigenes including 12 contigs and 119 singletons (79%). EST exhibited significant similarity with known putative functional nucleotide sequences in the GenBank database. These genes were mostly involved in cell development, signal transduction, protein synthesis, transcription, stress tolerance response, energy metabolism based on molecular function of GO annotation. Conclusion: This report constructs a full-length-cDNA library and analyzes the bioinformatics of the related EST sequences, and then offers a reference to genomic research of S. glabra.

Two Different Total Hip Arthroplasties for Hartofilakidis Type C1 Developmental Dysplasia of Hip in Adults / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH) is more complex than the normal hip, with large replacement risks and many complications. Although nonosteotomy THA is convenient to perform, femoral osteotomy shortening can avoid blood vessel and nerve traction injuries. This study aimed to compare osteotomy THA with nonosteotomy to determine reasonable options for operative management of DDH.</p><p><b>METHODS</b>Data on 48 DDH patients who underwent THA were analyzed retrospectively. The patients were divided into two groups: Group A 29 cases (nonosteotomy), and group B 19 cases (osteotomy). Harris and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, limb length discrepancy (LLD), radiological data on the hip, and claudication were evaluated. Data were analyzed by using paired-sample Student's t-test, independent-sample Student's t-test, and Pearson's Chi-square test; the test level was α =0.05.</p><p><b>RESULTS</b>Postoperative Harris (90.7 ± 5.1) and WOMAC scores (88.0 ± 10.6) were significantly improved compared with preoperative Harris (44.8 ± 5.7) and WOMAC scores (42.0 ± 5.3) in group A (P < 0.05). Postoperative Harris (90.4 ± 2.8) and WOMAC scores (88.2 ± 5.9) were significantly improved compared with preoperative Harris (44.4 ± 4.2) and WOMAC scores (43.2 ± 4.3) in group B (P < 0.05). One case of dislocation occurred in group A; after closed reduction, dislocation did not recur. In group A, 2 patients developed cutaneous branch injury of the femoral nerve, which spontaneously recovered without treatment. Postoperative LLD >2 cm was seen in one case in group A and five cases in group B. Postoperative claudication showed no significant difference between the two groups (P > 0.05). No patients developed infection; postoperative X-rays showed that the location of the prosthesis was satisfactory, and the surrounding bone was not dissolved.</p><p><b>CONCLUSIONS</b>THA is effective and safe for DDH. For unilateral high dislocation DDH patients with limb lengthening ≤4 cm and good tissue conditions, THA without femoral osteotomy may be considered.</p>

HIS-based analysis of clinical characteristics and combined treatment of Chinese and western medicine in diabetes deaths / 中国中药杂志

To understand the clinical characteristics and distribution of combined treatment of Chinese and western medicine in diabetes deaths, the hospitalization information of diabetes deaths from HIS system of 20 national 3A-grade general hospitals. Then the frequency statistics and association rules analysis were used to analyze the general information, complications, combined treatment, death time and other information of the patients died from diabetes. The results showed that most of the diabetes deaths were of middle aged and elderly people, more often in males than females. The complications with higher incidence included hypertension, pulmonary infection, coronary heart disease, cerebral infarction and renal inadequacy. In combined treatment rules, western medicines insulin, cefuroxime, furosemide, dopamine, nikethamide and sodium bicarbonate were used in combination at highest frequencies, followed by the combinations of traditional Chinese medicines panax notoginseng, radix bupleuri and western medicines, and the combinations between Chinese medicines had the lowest use frequency. Most of the diabetes deaths were of middle aged and elderly people, more often in males than females. They mainly died from 3 pm to 5 pm and from 5 pm to 7 pm. Therefore, the diabetes deaths often had complications of cardiovascular and cerebrovascular diseases, and early prevention shall be noted in clinics; the clinical treatment plan was basically in accordance with the guidelines for clinical treatment of diabetes; the drugs with promoting blood circulation to remove blood stasis and soothing liver-qi stagnation effects were the common Chinese medicines in treatment of diabetes.

Lower-limb valgus deformity associated with developmental hip dysplasia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treating developmental dysplasia of the hip is often challenging. The difficulties include not only the hip surgery itself but also the treatment of the associated lower-limb valgus deformity. However, there have been very few studies on such deformity in patients with developmental hip dysplasia. In this study, we investigated the prevalence and severity of lower-limb valgus deformity, along with the relationship between the severity of valgus deformity and mechanical alterations of the hip or the ipsilateral knee.</p><p><b>METHODS</b>Two hundred and six affected lower limbs of 116 adult patients with untreated developmental dysplasia of the hip were included in the study, grouped according to the severity of hip dysplasia. Each study participant's radiographs were measured to quantitatively evaluate the mechanical axis deviation of the lower limb, and further to evaluate the prevalence and severity of the lower-limb valgus deformity. Some mechanical alterations of the hip and the ipsilateral knee were also measured on the radiographs.</p><p><b>RESULTS</b>Of the affected lower limbs, 14.1% had valgus deformities. Study participants with Crowe type III hip dysplasia had the most severe deformity and the highest prevalence of deformity. Severity of valgus deformity had a strong positive correlation with the lateral migration of the femoral head but not with the superior migration. A decreased lateral distal femoral angle contributed to the lower-limb valgus deformity, and the lateral distal femoral angle had a strong negative correlation with the severity of valgus deformity.</p><p><b>CONCLUSIONS</b>Hip dysplasia is commonly associated with lower-limb valgus deformity, and the severity of the lower-limb valgus deformity is mostly affected by lateral migration but not superior migration of the femoral head. The valgus deformity may originate mainly in the distal femur, in addition to the hip joint itself. These findings can be taken into account when planning to treat the patients with hip dysplasia.</p>

Study of cognitive function in patients with lacunar infarction associated with leukoaraiosis / 中国脑血管病杂志

Objective: To investigate the effect of different degrees of ischemic white matter lesions on the cognitive function in patients with lacunar infarction. Method: One hundred twelve consecutive patients with lacunar infarction were collected. Age-related white matter changes rating scale (ARWMCRs) was used, and according to the results of ARWMCRs scores, the patients were divided into mild (n = 34, 0-3 scores), moderate (n = 43, 4-7 scores), and severe (n = 35, 8-24 scores) groups. The national health institutes of stroke scale (NIHSS) and the modified Rankin scale (mRS) scores were used to assess the degree of neurological deficit. The mini-mental status scale (MMSE) and the Montreal Cognitive Assessment (MoCA) were used for neuropsychological tests, and event-related potential two-tone sequence auditory P300 (2t-P300) wave was used for neural electrophysiological examination. The cognitive function was evaluated. The cognitive function among all groups was compared. Results: Circled digit oneThere were significant differences in comparison of the MoCA scores among the three groups. Only the mRS score and the MMSE score in the severe group were lower than those in the mild and moderate groups. There were significant differences (P < 0.05). Circled digit twoThe latency of P300 wave in the severe group was higher than that in the moderate and mild groups, and the latency of P300 wave in the moderate group was higher than that in the mild group. There was significant difference (P <0.05). The amplitude of P300 wave in the severe group was lower than that in the moderate group and mild group. There were significant differences (P < 0.05). Circled digit threeThe ARWMCRs score in patients with white matter lesions was negatively correlated with the MMSE score, MoCA score, and amplitude of P300 wave. It was positively correlated with the latency of P300 wave and mRS score. Conclusion: White matter lesions impact the cognitive function in patients with lacunar infarction. The more severe the white matter lesions, the more significant decline in cognitive function.

Human mesenchymal stem cells modified by hepatocyte growth factor gene promote chicken embryonic angiogenesis / 中国实验血液学杂志

This study was purposed to investigate the angiogenesis-promoting activities of human mesenchymal stem cells (hMSCs) modified by hepatocyte growth factor (HGF) and the underlying mechanisms. The hMSCs were transfected by recombinant adenoviral vector carrying human HGF gene and seeded onto the chicken chorioallantoic membrane. Three days later, the number of blood vessels was counted and their angiogenic response was compared with those of hMSCs of same generation, recombinant basic fibroblast growth factor (bFGF) and alpha-MEM as control. The expression levels of bFGF, VEGF, angiopoietin-1 and angiopoietin-2 were evaluated by RT-PCR assay. The results showed that gene-modified hMSCs exhibited greatest activity to promote angiogenesis while the angiogenic response was nearly same between groups treated by hMSCs and bFGF, all of which were significantly higher than that observed in control (p < 0.01). RT-PCR analysis revealed that hMSCs constitutively expressed multiple angiogenesis-associated growth factors and their levels seemed up-regulated by HGF gene transfer. It is concluded that HGF gene-modified hMSCs show a potent angiogenesis-promoting function and may be useful in the treatment of ischemic disorders.

A study of CXCR4/SDF-1 in hepatocellular carcinoma and liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the expressions of stromal cell-derived factor-1 (SDF-1) and CX chemokine receptor-4 (CXCR-4) in patients with hepatocellular carcinoma (HC) and liver cirrhosis.</p><p><b>METHODS</b>Peripheral blood and/or ascites fluid were collected from 39 hepatocellular carcinoma patients, 16 patients with liver cirrhosis, 12 with hepatitis and 12 healthy donors. The SDF-1 expression was assayed by ELISA and CXCR-4 was measured by immunohistochemical methods.</p><p><b>RESULTS</b>The level of SDF-1 expression in the carcinoma patients was higher than that of the liver cirrhosis, hepatitis patients and healthy donors, but there was no significant difference between those of the healthy donors and hepatitis patients or liver cirrhosis patients. The levels of CXCR-4 expression were closely related to the tumor differentiation.</p><p><b>CONCLUSION</b>The expression of SDF-1 in the peripheral blood and the CXCR4 expression in the HCC tissues of the HC patients may be regarded as markers of HC and they may have a positive relationship with the differentiation and metastasis of HC.</p>

Research progress in hirudin fusion protein--review / 中国实验血液学杂志

Natural hirudin extracted from the secretion of medical leech salivary gland is a single-chain peptide containing 65 aminoacid residues with molecular weight of 7000 D, and exists in three isomers of HV1, HV2 and HV3. Hirudin possesses three disulfide bridges forming the structure of core cyclic peptides, which binds to the catalytic site of thrombin so as to inhibit the catalysis of thrombin. Its c-terminus rich in acidic aminoacid residues possesses hydrophilicity, and is free on the molecular surface, and can bind with fibrin recognition site of hirudin. The minimal segment of 12 - 16 C-terminal acidic residues keeps the minimal activity of anti-thrombosis. Thus, hirudin, as a potent and specific inhibitor of thrombin, can be used to protect from and to treat clinically thrombosis. As it has some disadvantages such as short half-life, bleeding side-effect and mono-function, and so on, hirudin has been fused with some other functional proteins in recent years. The obtained fusion proteins can prolong the half life of hirudin, or relieve it bleeding side effect, or bring new functions, such as thrombolysis, inhibiting the platelet aggregation, targeting specifically. The research progress in hirudin fusion protein was summarized in this review.

Transsphenoidal microsurgery of non-adenomas disease intrasellar region:a report of 23 cases / 中华显微外科杂志

Objective To evaluate the overall effect of transsphenoidal microsuegery for 23 patients with non-adenomas disease intrasellar region.Methods A toal of 23 patients with non-adenomas disease in- trasellar region,7 cases of Rathke's cleft cyst,3 cases of craniopharyngiomas,2 cases of meningiomas,2 ca- ses of pituitary tuberculous granuloma,5 cases of pituitary abscess,2 cases of empty sella,2 cases of chord- mas,were treated via sublabio-septo-sphenoidal microsurgery.Results There were among the 23 patients, groos total removal of the disease were achieved in 14 cases,subtotal removal in 7 cases,and partial removal in remain 2 cases.Diminished visual activity and visual field defects were improved in 13 cases.Menstrual disorder in all female cases and sexual disturbance in male were improved.There was no death in group. Conclusion Microsurgical technique via transsphenoidal approach is a safe and effective one for the treatment of patients with non-adenomas disease intrasellar region.

Effects of Repeated Ozone Exposure on Allergic Responses in Mice / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: We Investigated whether repeated ozone exposure has a priming effect on allergic sensitization and whether ozone exposure has an exacerbating effect on allergic responses during allergen challenge in previously sensitized animal. SUBJECTS AND METHOD: Thirty-five female BALB/c mice were divided into the following five groups; controls (I), ovalbumin (OVA)-aerosol exposure group (II), OVA-aerosol/ozone exposure group (III), OVA-systemic sensitization group (IV), and OVA-systemic sensitization/ozone exposure group (V). Mice of group III and V were exposed to 0.3 ppm ozone for 4 hours, three times a week for four weeks. Mice of group II and III were exposed to OVA-aerosol for 20 minutes, five times a week for four weeks. Mice of group IV and V were sensitized by intraperitoneal injections with OVA/Al(OH)3 solution on day 0, 7, and 14. Animals received five consecutive allergen challenges by OVA-aerosol nebulization from day 23 to 27. At 24 hours after the last exposure, nasal lavage fluid (NLF) and blood were obtained. The concentrations of total serum IgE, anti-OVA IgE, and anti-OVA IgG1 were measured by enzyme-linked immunosorbent assay (ELISA). The levels of IL-4, IL-5 and INF-gamma in NLF were measured by ELISA. In addition, Luna staining was performed to identify eosinophils that infiltrated in nasal mucosa. RESULTS: OVA-aerosol exposure alone induced weak allergic response to OVA in nonsensitized mice. In contrast, the combination of OVA-aerosol and ozone resulted in augmented immune responses to OVA as indicated by significant increases in total serum IgE, anti-OVA IgE, and anti-OVA IgG1 antibody titers, as well as significant increases in the levels of Th2 cytokines In NLF and the number of eosinophils infiltrating nasal mucosa. Although the titers of total IgE and anti-OVA IgE of group III were significantly lower than those of group IV, the titers of anti-OVA IgG1, levels of IL-4 and IL-5, and the number of eosinophIls infiltrating nasal mucosa showed no significant differences between group III and group IV. In sensitized mice, ozone exposure durIng OVA challenge enhanced the allergic responses to OVA. CONCLUSION: These results suggest that ozone exposure induces and enhances the allergic responses by augmenting the production of allergen-specific antibody and Th2 cytokines.

Purification of Recombinant Fusion Protein Staphylokinase-Hirudin Expressed by Escherichia coli and Analysis of its Dimer / 中国生物工程杂志

The recombinant fusion protein staphylokinase-hirudin(rSFH) was purified from the high density-fermented engineered E.coli by means of ion-exchange chromatography (IEC) and gel filtration (GF). The purity of rSFH reached to more than 98% determined by RP-HPLC and SDS-PAGE, and the yield was up to 0.7g per liter of fermentation broth. The analysis of homologous dimmer of rSFH appeared during the purification and calculation of the surface hydrophobic area had been carried out by means of hydrophobic chromatography and MALD-TOF. The influence of sodium chloride and temperature on the behavior of rSFH reversible dimerization was analyzed by high performance sized- exclusive chromatography(HPSEC). It is concluded that the hydrophobic interaction played an important role in the reversible dimerization of rSFH.

Design and Functional Investigation of a Novel Anti-coagulative Fusion Protein by Hirudin With a Recognizing Sequence of FXa / 中国生物工程杂志

Hirudin (HV) is known as the most potent and specific inhibitor of thrombin. Although hirudin has many advantages , it has the bleeding side effect and this is the great shortage of hiudin for clinical application. In order to alleviate bleeding side effect of hirudin, fusion protein, named as FHV (fusion hirudin linked with FXa recognition peptide) was designed. The fusion protein gene ( fhv) was cloned into plasmid pPIC9K. FHV engineered Pichia pastoris containing high copies was chosen for fermentation and purification at 30 L fermentor scale, finally, FHV with purity of above 97% was obtained. To investigate the function of FHV in vivo, mouse tail thrombosis model was used. In the mice thrombus tail model induced by carrageenan, FHV decreased the length of tail thrombus significantly, similar to that of HV control, and had no obvious effects on the TT, PT and APTT. In conclusion, FHV is constructed and expressed in yeast. FHV fusion proteins is obtained by fermentation and purification. FHV has antithrombotic effects not influencing IT, PT and APTT after administration immediately in animal models. Therefore, FHV is a promising anticoagulant and antithrombotic drug.

Effects of Ebselen on Ozone-Induced Nasal Mucosal Inflammation in Mice / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Although the mechanism of ozone-induced airway inflammation and hyperresponsiveness is largely unknown, NO and peroxynitrite has been suggested to be associated with it. Ebselen, a seleno-organic compound, is known to inhibit the production of superoxide, iNOS-related NO, and their combined product, peroxynitrite. The purpose of this study is to investigate whether ebselen suppress ozone-induced nasal inflammation and whether ebselen inhibit the production of NO and peroxynitrite in nasal mucosa. SUBJECTS AND METHOD: Thirty-six BALB/c mice were divided into three groups: control group, ozone exposure group, and ozone+ebselen treated group. In the ozone exposure group, mice were exposed to 1 ppm ozone for 8 hours a day for 3 consecutive days. In the ebselen treated group, the ebselen (32.5 mg/kg) solution was injected intraperitoneally 1 hour before and 3 hours after the ozone exposure. At 18 hours of the last ozone exposure, Evans blue was infused via tail vein in 6 animals of each group. Mice were sacrificed five minutes later and nasal mucosa was obtained to measure the amount of extravasated Evans blue dye. From the remaining 6 animals in each group, nasal lavage fluid (NLF) was obtained to measure the concentration of albumin and the number of neutrophils. After lavage fluid was obtained, nasal mucosa was taken for immunohistochemical staining against iNOS and nitrotyrosine usng the ABC method. RESULTS: Extravasation of Evans blue was significantly increased in the ozone exposure group, but it was significantly decreased in the ebselen treated group. Albumin concentration in NLF showed a tendency to increase in the ozone exposure group and a tendency to decrease in the ebselen treated group when compared with the ozone exposure group. The number of neutrophils was significantly increased in the ozone exposure group and was decreased more in the ebselen treated group than in the ozone exposure group. Immunoreactivity to iNOS and nitrotyrosine was strongly expressed in nasal mucosa of the ozone exposure group. However, it was nearly abolished by the treatment with ebselen. CONCLUSIONS: These results may suggest that ebselen can be applied as a useful therapeutic agent for airway diseases by modulating the oxidant-related inflammatory process.

Repeated Ozone Exposure Induces Th2 Immune Responses in Mice

BACKGROUND AND OBJECTIVES: It has been reported that ozone exposure exacerbate allergic rhinitis symptoms and may contribute to increase allergic rhinitis prevalence. However, a causal relationship still remained unsolved. The purpose of this study is to investigate whether prolonged exposure to ozone induce Th2 immune response without allergen. MATERIALS AND METHODS: Fourteen BALB/c mice were divided into two groups: control group and ozone exposure group. Mice were exposed to 0.3 ppm of ozone for 4 hours a day, 3 times per week, for 4 weeks. At 24 hour after the last ozone exposure, nasal lavage fluid (NLF) was obtained to measure the levels of cytokine IL-4, IL-5, and IFN-gamma. After lavage fluid was obtained, blood was obtained via inferior vena cava to measure the amount of total IgE and IgG1. The concentration of cytokines and immunoglobulins was measured using the ELISA method. In addition, Luna staining was performed to identify eosinophils infiltrated in nasal mucosa. RESULTS: The levels of IL-4 and IL-5 in NLF were significantly increased in ozone exposure group compared with control group. But the level of IFN-gamma in NLF shows no significant difference between two groups. Serum total IgE and IgG1 were significantly increased in ozone exposure group compared with control group. On histologic examination, number of eosinophils infiltrating nasal mucosa was significantly increased in ozone exposure group. CONCLUSION: These results suggest that repeated ozone exposure induces Th2 response in the nasal mucosa of mice.

The Inhibitory Effect of Anti-P-Selectin, Anti-PSGL-1 and Anti-CD49d Antibodies on Experimental Allergic Airway Inflammation in Mice

BACKGROUND AND OBJECTIVES: Eosinophil recruitment in allergic inflammation is dependent on the interactions between adhesion molecules. The objective of this study was to determine whether blocking of P-selectin glycoprotein ligand-1 (PSGL-1), P-selectin or CD49d adhesion molecules using monoclonal antibodies can reduce eosinophil recruitment in mice with the airway allergy. MATERIALS AND METHODS: Seven different groups of mice were used. One experimental group of mice (group A) served as naive control and sensitized with phosphate-buffered saline (PBS). Six experimental groups of mice (groups B to G) were sensitized to ovalbumin (OVA). The mice in group B were treated with PBS before OVA aerosol challenge and served as positive controls. The mice in other remaining groups were treated with monoclonal antibodies (mAb) against specific adhesion molecules before OVA challenge; anti-P-selectin mAb (group C), anti-PSGL-1 mAb (group D), anti-CD49d mAb (group E), anti-P-selectin mAb & anti-CD49d mAb (group F), anti PSGL-1 mAb & anti-CD49d mAb (group G). Eosinophils in the nasal mucosa and bronchoalveolar lavage (BAL) fluid in each animal group were measured. RESULTS: Mucosal eosinophilic infiltrations were significantly reduced at the mice in the group C, F or G compared with group B. Eosinophils in BAL fluid were significantly reduced only at the group C mice. CONCLUSION: These results suggest that blockade of P-selectin is superior to blockade of PSGL-1 or CD49d in the inhibitory effect against eosinophil recruitment.