Dose-Response Relationship, Drug ; Enzymes ; adverse effects ; Humans ; Hypersensitivity ; Occupational Diseases ; chemically induced ; Occupational Exposure ; adverse effects

Aged ; Anthracosis ; physiopathology ; Autonomic Nervous System ; physiopathology ; Death, Sudden ; Humans ; Male ; Middle Aged

Child, Preschool ; Coronary Aneurysm ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; pathology

OBJECTIVETo establish a new rat model of chronic cyclosporine A nephrotoxicity and explore its features.

METHODSTotally 24 male SD rats were equally randomized divided into 3 groups: sham-adrenalectomized (sham-ADX) group, ADX group and ADX plus cyclosporine A (CsA) group. Rats in ADX and CsA group first underwent adrenalectomy, followed by the administration of placebo or dexamethasone, respectively. Rats in sham-ADX group received sham adrenalectomy and distilled water as control. Six weeks later, all rats were sacrificed and the following indicators were evaluated: urine protein excretion, creatinine clearance, aldosterone level in serum and urine, aldosterone level and its synthase CYP11B2 gene expression in kidney, serum natrium and potassium, urine natrium and potassium excretion, and tubulointerstitial fibrosis by masson trichrome stain.

RESULTSIn ADX and CsA group, serum and urine aldosterone were undetectable on the second post-operative day, with other observations including natriuresis, hyponatremia, decreased urine potassium excretion, and hyperpotassemia, suggesting that adrenals were removed intact and the adrenalectomy was successful. Rats in CsA group showed increased urine protein, decreased creatinine clearance and tubulointerstitial fibrosis, suggesting that a model of chronic CsA nephrotoxicity was successfully established. At the endpoint, serum potassium, serum aldosterone, urine potassium and urine aldosterone excretion partially retrieved. Natrium in serum and urine was not significant different between ADX group/CsA group and sham-ADX group. Local renal aldosterone and its gene expression were remarkably upregulated.

CONCLUSIONSWe successfully established a new rat model of chronic CsA nephrotoxicity by adrenalectomy without low sodium diet. After adrenalectomy, local renal aldosterone in kidney may compensate for circulatory aldosterone deficit to maintain electrolyte balance.

Acute Kidney Injury ; chemically induced ; Adrenalectomy ; Aldosterone ; metabolism ; Animals ; Cyclosporine ; toxicity ; Disease Models, Animal ; Immunosuppressive Agents ; toxicity ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

Objective To observe the expression of I-Ab/I-E on circulating,lung and splenic dendritic cells (DC) in acute lung injury (ALI) mice.Methods Twenty-four C57BL/6 mice were randomly divided into four groups:control group,ALI 6 h,ALI 12 h and ALI 24 h group.Blood,lungs and spleens were harvested after lipopolysaccharide or phosphate butter solution administration.The expression of I-Ab/I-E on DC was assessed by flow cytometry (FCM).IL-6 level in the lung was measured by enzymelinked immunosorbent assay (ELISA).Lung wet weight/body weight (LW/BW) was recorded to assess lung injury.Meanwhile,pathological changes were examined under optical microscope.Results (1) lipopolysac charide-induced ALI mice resulted in a significant increase in lung LW/BW ratio.(2) Histologically,widespread alveolar wall thickening caused by edema,marked and diffuse interstitial infiltration with inflammatory cells,and severe hemorrhage in the interstitium and alveolus were observed in the ALI groups.(3) The level of IL-6 in lung tissue was significantly enhanced in ALI mice.(4) FCM analysis showed that I-Ab/I-E expressions on lung DC [(73 ±9)％],and splenic DC [(81 ±8)％] were significantly higher than that on circulating DC [(24 ± 7) ％ ; P ＜ 0.05] in control mice.(5) In ALI mice,the expressions of I-Ab/I-E on peripheral blood DC were (34 ± 17)％ at 6 h,(51 ± 16)％ at 12 h,(50 ± 17)％ at24 h respectively; I-Ab/I-E expressions on lung DC were (82 ± 14)％ at 6 h,(88 ±6)％ at 12 h,(90 ±10)％ at 24 h respectively; the expressions of I-Ab/I-E on splenic DC were (88 ± 8)％ at 6 h,(89 ± 4)％ at 12 h,(93 ± 9)％ at 24 h respectively,which were also significantly higher than those on the peripheral blood DC (P ＜ 0.05).(6) The I-Ab/I-E expressions on circulating DC in ALl mice at 12 h and 24 h was significantly higher than that on circulating DC in control mice (P ＜ 0.05).(7) The I-Ab/I-Eexpressions on lung DC and splenic DC in ALI mice at 24 h were significantly higher than those on lung DC and splenic DC in control mice (P ＜ 0.05).(8) There was a significant correlation of I-Ab/I-E expression on respiratory DC with the IL-6 level and lung injury score in LPS-induced ALI group (P ＜ 0.05).Conclusions There is a dynamic characteristic in the expression I-Ab/I-E on circulating,lung and splenic DC populations in ALI mice.I-Ab/I-E on pulmonary DC seems to play an important role in the pathogenesis of ALI.

ObjectiveTo investigate the relationship between HLA-DRB1 alleles and chronic urticaria with positive autologous serum skin test (ASST) in Guangxi Zhuang Autonomous Region.MethodsASST was conducted in 144 patients with chronic urticaria,who were subsequently divided into two groups according to the test result:positive group (n =62) and negative group (n =82).PCR amplification with sequence-specific primers was used to determine the genotypes of HLA-DRB1 alleles in the patients and 199 normal human controls.Chi-square test was performed to analyse the difference in the frequency of HLA-DRB1 alleles between the 3 groups by using the SPSS 13.0 statistical software package.ResultsThere were significant differences in the frequency of HLA-DRB1*01,*1401 and *16 alleles among the patients with positive and negative ASST and the controls (x2 =10.92,Pc =0.032;x2 =35.34,Pc ＜ 0.01 ;x2 =12.69,Pc =0.032).Paired comparison revealed significant differences in the frequency of HLA-DRB1*1401 allele between the patients with positive ASST and controls(RR =17.09,Pc ＜ 0.01 ) as well as between the patients with positive and negative ASST (RR =7.20,Pc ＜ 0.01).ConclusionHLA-DRB1*1401 allele may be,or be linked to,the predisposing gene of chronic urticaria with positive ASST in Guangxi Zhuang Autonomous Region.

Objective To study the change and the significance of T-lymphocyte immune function in peripheral blood in population living in arsenic-contaminated area. Methods Fifty-three cases of patients with arsenism symptoms were selected into experimental group, inhabitants who had no chronic arsenism symptoms into control group in the endemic area of Shuocheng District, Shuozhou City, Shanxi Province in 2006. Vein blood samples were taken and analyzed with SAP assay to measure the percentage of CD3+ ,CD4+ and CD8+ T-cells. Results It was found that the percentage of CD3+, CD4+, and CD4+/CD8+ [(41.89 ± 11.58)%, (25.60 ± 9.05)% and 1.02 ± 0.41] in the experimental group was lower than that in the control group [(68.38 ± 7.23)%, (39.17± 4.28)% ,1.69 ± 0.56, t = 13.61,18.72,14.79, all P < 0.05], while there was no statistical differences of CD8+ [(25.30 ± 6.85)%] compared to the control group[(23.54 ± 8.35)%,t = 3.07,P > 0.05]. The gender-related effect of arsenic on CD4+ and CD8+ was found by multiple linear step regression analysis(t = - 3.05, - 4.30, all P < 0.05). In case group, there were no statistical differences in CD3+, CD4+, CD8+ and CD4+/CD8+[(40.65±10.06)%, (24.48 ± 6.29)%, (24.52 ± 8.16)%,0.98 ± 0.25] between males and females [(43.07±12.96)%, (26.77±3.12)%, (26.50 ±9.32)%, 1.07 ±0.41, t = - 0.76,3.05,0.30,2.10, all P > 0.05]. Conclusions The immune function of T-lymphocytes of patients with chronic arsenism has been suppressed. It is of active significance to detect T-lymphocyte subpopulation in peripheral vein in patients with chronic arsenism aiming at estimating the function of cell immune and providing early diagnosis index.

Objective To investigate the immunoregulatory effect and compare the different regula- tions of bone marrow mescnchymal stem cells(MSCs)derived from both lupus(NZBWF1/J)and normal(BALB/ c)mice on T lymphocytes in vitro.Methods MSCs from NZBWF1/J and BALB/c mice bone marrow were iso- lated and expanded,and identified by the surface phenotypes.CD3~+ T lymphocytes isolated by nylon wool columns were stimulated by phorbol myristate acetate(PMA)and co-cultured with or without the two strains of MSCs for 24 h.Intracellular eytokines of T cell,such as interferon(IFN)-?,interleukin(IL)-4,IL-12,IL-6, were analyzed by flow cytometry and quantification of transcription factors T-box expressed in T cells(T-bet) and GATA-binding protein 3(GATA-3)were detected by reverse transcriptase PCR(RT-PCR).T cell apop- tosis was assessed by flow cytometry using rhodamine123.Results The results showed that a decrease of CD3~+ T cell apoptosis was seen when NZBWF1/J MSCs or BALB/c MSCs were added to T cells stimulated by PMA(P＜0.05),and an increase of TH2 cytokines by NZBWF1/J MSCs and TH1 eytokines by BALB/c MSCs were observed in the CD3~+ T cells eo-cuhured with MSCs(P＜0.05).Conclusion It is suggested that the al- teration of T subsets caused by MSCs may interfere with the systemic lupus erythematosus(SLE)development and normal MSCs may be effective in the improvement of SLE.NZBWF1/J MSCs have defective immunoregula- tory function when compared with MSCs from healthy mouse strains.

Objective To clarify the role of FLT3 signaling-dependent pulmonary conventional dendritic cells (cDCs) in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI),and as well as the modulation effects of cDCs in vivo on the inflammatory responses to acute lung injury.Methods Thirty C57BL/6 male mice were divided into normal control group,LPS group,FLT3L pretreatment group,lestaurtinib,(a high efficient and specific blocker in FLT3 signal pathway) pretreatment group and vehicle (DMSD) control group.FLT3L and lestaurtinib were administrated subcutaneously for 5 days.Murine model of ALI was subsequently established by intra-tracheal application of LPS and lung specimens were harvested 6 h or 24 h later.The accumulation and maturation of pulmonary cDCs were assessed by flow cytometry.IL-6 and TNF-α were quantified to evaluate lung inflammation.Lung injury was estimated by lung wet weight/body weight ratio (LWW/BW) and histopathological assessment.Lung myeloperoxidase (MPO) activity was measured to evaluate neutrophil infiltration.Transcription factors Tbet/GATA-3 mRNA ratio was determined to estimate balance of Th1/Th2 response.IFN-γ and IL-4 were quantified to evaluate Th1-specific and Th2-specific cytokine production respectively.Results The accumulation and maturation of pulmonary cDCs peaked at 6h after LPS challenge.FLT3L pretreatment significantly stimulated the accumulation and maturation of pulmonary cDCs (P ＜ 0.05),leading to markedly deterioration of LWW/BW and lung histopathological changes.Meanwhile lung MPO activity and T-bet/GATA-3 mRNA ratio were elevated (P ＜ 0.05).Furthermore,the production of IL-6,TNF-α and IFN-γwas markedly increased by FLT3L pretreatment (P ＜ 0.05).In contrast,lestaurtinib pretreatment markedly inhibited the accumulation and maturation of pulmonary cDCs (P ＜ 0.05),leading to significant improvement of LWW/BW and lung histopathological changes.Meanwhile lung MPO activity and T-bet/ GATA-3 mRNA ratio were decreased (P ＜ 0.05).Furthermore lestaurtinib efficiently suppressed the production of IL-6,TNF-α and IFN-γ (P ＜ 0.05).Conclusion This study thus demonstrated that FLT3 signaling-dependent pulmonary cDCs could control the initiation of acute lung inflammation response to LPS-induced ALI through the regulation of neutrophil infiltration and balance of Thl/Th2 response.

Objective To explore the effect of carbon nanoparticles-epirubicin suspension on proliferation and apoptosis in human breast cancer MCF-7 cells.Methods MCF-7 cells were cultured with different concentrations of CNP-EPI in vitro.CCK-8 assay was used for determinate inhibition effect of CNP-EPI on the proliferation of MCF-7 cells at different concentration and different time.According to the determination of IC90,5 μg/ml CNP-EPI was selected,and cell morphology and cell apoptosis rates were observed after 24 h.Results The inhibition effect of the CNP-EPI was stronger significantly in CNP-EPI group than in normal control group within 24 h,48 h,72 h when the concentration was from 1 μg/ml to 200 μg/ml (P＜0.01).The inhibition of CNP-EPI on the proliferation of MCF-7 cells was gradually strengthened in a dose-dependent relation within the same time,and the inhibition effect is reduced in the same concentration of drugs with the time extension,but it still has a strong inhibitory effect in 72 h,and the inhibition effect of different concentration of CNP was not obvious on MCF-7 cells.Obvious changes of cell morphology were observed under inverted microscope such as:a lot of dead cells,cell adherent growth poor,cell morphology became round and karyopycnosis etc,in 5 μg/ml CNP-EPI group after 24 h.However,no obvious abnormity of cell norphology was observed in normal control group and corresponding CNP group.Late apoptosis rate was (14.57±2.41) ％,the mortality rate could reach (78.63±-20.55)％ in 5 μg/ml CNP-EPI group after 24 h.The mortality rate and apoptosis rate of cells was higher significantly in CNP-EPI group than in CNP group and normal control group (P＜0.05).Conclusion CNP-EPI can obviously inhibit the proliferation or kill human breast cancer MCF-7cells,and the inhibition effect of CNP-EPI on proliferation of breast cancer cells might be the result of delayed releasing of EPI.