Objective To observe the changes in OLETF kideys at different stage and the beneficial influences by modulating serum lipids. Methods OLETF rats aged 8 wks were randomly divided into treated group and untreated group,and LETO rats served as normal control.Fenofibrate 20 mg/kg was given daily to the treated group.OGTT was performed at the age of 8,16 and 24 wks.Blood glucose,serum lipids and 24 h urine albumin excretion(UA) were investigated.The rats were killed at 16 and 24 wks of age,and the kidney sections were stained with PAS.Transforming growth factor-?_1(TGF?_1),vascular endothelial growth factor(VEGF) and fibronectin(FN) were investigated by immunohistochemistry assay.The electron microscope(EM) sections were made to measure GBM width and to observe the mesangial matrix.Results(1) Blood glucose had no significant difference between untreated and treated groups at 16 and 24 wks of age;(2) Fenofibrate decreased serum TG, increased HDL-C markedly but had no influence on LDL-C;(3) As aging,24hrs UA increased in untreated group,and reduced significantly in fenofibrate group at 24 wks of age;(4) TGF-?_1,VEGF and FN expressions were all higher in untreated group than in treated group at 24 wks of age.(5) EM revealed GBM obviously thickened and mesangial matrix widened in untreated group.Fenofibrate attenuated the kidney lesion greatly in EM picture.Conclusions (1) Dyslipidemia occurs prior to glucose metabolism abnormity in OLETF rats;(2) As aging,dyslipidemia progresses accompanying markedly the increased UA,enlarged glomeruli,thickened GBM and widened masangial matrix;(3) Modulating lipids early couldn′t improve glucose metabolism,but corrects dyslipidemia and reveals beneficial influence on kidneys;(4) The possible mechanism is that modulating lipids decreases TGF-?_1 and VEGF expressions.

Objective To investigate the effects and anti-atherosclerotic mechanism of rosiglitazone on the expression of ATP-binding cassette transporter A1 (ABCA1) and reverse cholesterol transport (RCT) in atherosclerotic rabbits. Methods Twelve rabbits were randomly divided into two groups (6 each): control group (only high cholesterol diet for 6 weeks), rosiglitazone group [high cholesterol diet plus rosiglitazone 0.5mg/(kg?d) for 6 weeks]. ABCA1 expression and [3H] cholesterol efflux rates were evaluated by flow cytometry and liquid scintillation spectrometry, respectively. Enzymatic methods were used to assay serum lipids levels and cholesterol contents in tissues, and the atherosclerotic area of aorta was calculated by professional image analysis software. Results For the rabbits of both control and rosiglitazone group, the serum levels of high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (NHDL-C) and apolipoprotein A1 (apoA1) significantly went up when they took their cholesterol rich diet for 6 weeks (P0.05). Compared with control group, the ABCA1 expressions in monocytes, peritoneal macrophages, adipocytes and hepatocytes, as well as the cholesterol efflux rates in peritoneal macrophages, adipocytes and hepatocytes increased significantly (P

Objective To explore the expression and the role of Toll-like receptor(TLR3 and TLR4) in rats with nephrotic syndrome induced by respiratory syncytial virus(RSV).Methods SD rats were inoculated intranasally and intraperitoneally with 6?106 plaque for-ming unit(PFU) RSV to construct RSV-induced nephropathy in rat model.Rats were anesthetized and blood was withdrawn from cardiac on day 4,14,30,60 after inoculation.The normal ones without intervention were set as control group.The renal histology was observed by light microscope and electron microscope.The urinary protein collected in 24 hours were measured.Meanwhile,the expressions of TLR3 and TLR4 were detected by indirect immunofluorescence staining and flow cytometry in peripheral blood mononuclear cells of rats.The results were analyzed by SPSS 13.0 softwore.Results After inoculation,the proteinuria increased and under the electron microscope the foot processes of glomerular epithelial cells were fused which resembled human minimal change nephrotic syndrome.Proteinuria reached the peak and the fusion of foot processes were most extensive in rats of RSV at 60 d.The expressions of TLR3 and TLR4 in each group of RSV-induced nephropathy in rat models were significantly higher than those in normal control group(Pa0.05).Conclusions TLR3 and TLR4 in peripheral blood mononuclear cells of RSV-induced nephropathy rat mo-dels had being significantly activated until 60 d after RSV inoculation.TLR signaling pathway may play an important role in nephrotic syndrome of rats induced by RSV.

Objective To investigate the effect of fusidic acid cream on inflammatory reaction caused by skin barrier damage.Methods Eight male SKH-1 hairless mice were included in this study.The back of each of these mice were equally divided into six regions measuring 1 cm × 2 cm in size,which were then assigned into six groups:blank control group remaining untreated,barrier-impaired group,barrier-impaired and fusidic acid-treated group,barrier-impaired and vehicle-treated group,barrier-unimpaired and fusidic acid-treated group,barrierunimpaired and vehicle-treated group.Stratum corneum was removed by adhesive tape stripping to establish an animal model of acute skin barrier damage in the corresponding skin regions of these mice,and fusidic acid cream or vehicle was topically applied to the corresponding regions once.Twelve hours later,skin surface swab samples were collected from the back of these mice followed by bacterial culture and colony counting.Mice were then sacrificed,and skin tissue specimens were resected from these mice,and subjected to real-time fluorescence-based quantitative PCR for the measurement of the mRNA expressions of myeloid differentiation factor 88 (MyD88),interleukin-1α (IL-1α),IL-6,epidermal antibacterial peptides S100a8 and S100a9.Statistical analysis was carried out by repeated-measures analysis of variance (ANOVA) and least significant difference (LSD) test.Results The mRNA expressions of MyD88,IL-1α,IL-6,S100a8 and S100a9 were all significantly higher in the barrier-impaired group than in the blank control group (all P ＜ 0.05).Specifically,the mRNA expression level of MyD88 in the barrier-impaired group was 8 times that in the blank control group (8.3 ± 3.0 vs.0.8 ± 0.4).Compared with the barrier-impaired group,the barrier-impaired and fusidic acid-treated group showed a significant decrease in the mRNA expressions of IL-1α (2.8 ± 0.3 vs.20.1 ± 10.0,F =47.11,P ＜ 0.01),IL-6 (1.6 ± 2.3 vs.9.4 ± 4.0,F =16.18,P＜ 0.01),S100a8 (1.5 ± 1.4 vs.5.0 ± 1.6,F=59.71,P＜ 0.05) and S100a9 (1.2 ± 0.7 vs.3.4 ± 1.6,F=21.94,P ＜ 0.05).Conlusions Fusidic acid cream could attenuate the inflammatory reaction caused by acute skin barrier damage,which might partly explain its action mechanism in the treatment of inflammatory skin diseases.

Objective To evaluate the inhibitory effect of butyl flufenamate (BT) on ultraviolet (UV)-induced acute skin phototoxic reaction,and to investigate its possible mechanisms.Methods Eight SKH-1 hairless mice were included in this study.The back of each SKH-1 hairless mouse was divided into six regions,which were then randomly classified into six groups:blank group receiving no treatment,UV group receiving UV radiation only,BT + UV group and vehicle + UV group topically treated with BT ointment and vehicle respectively followed by UV radiation,UV + BT group and UV + vehicle group topically treated with BT ointment and vehicle respectively after UV radiation.Skin samples were obtained from these mice at 24 hours after treatment.Subsequently,hematoxylin-eosin (HE) staining was performed,real-time PCR was carried out to detect mRNA expressions of caspase-3,p53,COX-2,PGER1,interleukin (IL)-1β,IL-6,and an immunofluorescence assay was conducted to observe the expression of caspase-3.Statistical analysis was carried out by repeated-measures analysis of variance (ANOVA).Results Compared with the UV group,both BT + UV group and UV + BT group showed a decrease in the degree of skin edema and number of apoptotic cells at 24 hours after UV radiation.Real-time PCR showed that the mRNA expressions of caspase-3,p53,COX-2,PGER1,IL-l β and IL-6 were significantly higher in the UV group than in the blank group (all P ＜ 0.05),but significantly lower in the BT + UV group than in the UV group (all P ＜ 0.05),and only the expressions of caspase-3 and p53 mRNAs were significantly decreased in the UV + BT group compared with the UV group (both P ＜ 0.05).The immunofluorescence assay revealed that the expression of caspase-3 increased in the UV group compared with the blank group,but decreased in both BT + UV group and UV + BT group compared with the UV group.Conclusion BT could partially inhibit UV-induced acute skin phototoxicity in SKH-1 hairless mice.

Objective To study dIe ESBLs and plasmid-mediated AmpC enzymes in E.Coli and Klebsiella spp. with CLSI ESBL-screening test positive,confirmation test negative but cefepime susceptible.Methods Antimierobial susceptibility testing were performed by Kirby-Bauer(K-B)method.The genes encoding ESBLs and plasmid-mediated AmpC enzymes were detected by PCR Transfer of ESBLs or plagmid-mediated AmpC resistance was studied by conjugation experiments.The homology of donor (E.coli),recipient(E.coli J53)and their transconjugants were analyzed by ERIC-PCR DNA fingerprints of E.coli and Klebsiella pneumoniae were analyzed by PFGE as recommended bv PulseNet protocoL Results Of 18 isolates from Huashan Hospital,11 were E.coli.6 were Klebsiella pneumoniae and 1 was Klebsiella oxytoca.Antimicrobial susceptibility testing indicated all of 18 isolates were positive on the CLSI ESBL screening test but negative on the confirmation test.and all of isolates were susceptible to cefepime(a zoneof-inhibition diameter of≥18 mm wag considered to indicate susceptible).PCR results indicated that 9 of the 11 E.coli isolates predued CMY-2 AmpC enzyme.TEM,SHV,CTX-M,PER,VEB or SFO type β-lactamages were not identified.Of 6 Klebsiella pneumoniae isolates.5 were DHA-1 AmpC-producing strains.4 of the 5 DHA-1 AmpC-producing strains were coexistence of broad-speetrumβ-lactamaae or extended-spectrumβ-lactamase.including two producing SHV-11 and two producing CTX-M-14 and SHV-62 type ESBL respectively.One Klebsiella oxytoca wag also DHA-1 AmpC producing strain.Conjugation experiments indicated that both ESBLs and AmpC enzymes could be transfefred from donor to recipient.PFGE indicated that the DNA fingerprints of K.pneumoniae were difierent but seven CMY-2 AmpC-producing E.coli isolates from general surgieal ward were similar.Concluslons The main mechanism of antibiotic resistance in CLSI ESBLs-screening test-positive but eefepime.susceptible E.coli and KIebsiellaspp.is production of plagmid-mediated AmpC enzymes.Some strains produce both AmpC enzyme and ESBLs.Such strains should be reported as resistant to cefepime.The results suggest that laboratories should routinely conduct research on the ESBLs and plnsmid.mediated AmpC enzymes in Enterobacteriaceae in order to report antimicrobial susceptibility testing results more correcdy.

Objective To evaluate the effects of dexmedetomidine on the oxidative stress responses during global cerebral ischemia-reperfusion (I/R) in rats.Methods Thirty-six male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg).In group D,dexmedetomidine was infused at a rate of 3 μg · kg-1 · h-1until 2 h of reperfusion after a loading dose of dexmedetomidine 3 μg/kg was intravenously injected immediately after onset of reperfusion.The neurological deficit score (NDS) was assessed at 24 h of reperfusion,the rats were then sacrificed,and their brains were immediately removed for determination of cell apoptosis and levels of malondialdehyde (MDA),superoxide dismutase (SOD) and catalase (CAT).Apoptotic rate was calculated.Results Compared with group S,NDS,apoptotic rate and MDA level were significantly increased,and SOD and CAT levels were decreased in I/R and D groups.Compared with group I/R,NDS,apoptotic rate and MDA level were significantly decreased,and SOD and CAT levels were increased in group D.Conclusion Dexmedetomidine attenuates global cerebral I/R injury through inhibiting the oxidative stress responses.

Objective To evaluate the effects of dexmedetomidine on the permeability of blood-brain barrier in rats subjected to global cerebral ischemia-reperfusion (I/R).Methods Thirty-six male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each):sham operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP was maintained at 35-45 mm Hg) in anesthetized rats.In group D,dexmedetomidine was infused at a rate of 3μg· kg-1 · h-1 until 2 h of reperfusion after a loading dose of dexmedetomidine 3 μg/kg was injected intravenously immediately after onset of I/R.The rats were sacrificed at 24 h of reperfusion and their brains were immediately removed for microscopic examination of hippocampal CA1 region and for determination of the cell apoptosis,brain water content,Evans blue content and aquaporin 4 (AQP4) expression.Results The number of apoptotic cells was significantly larger,and brain water content,Evans blue content and AQP4 expression were higher in groups I/R and D than in group S (P ＜ 0.05 or 0.01).The number of apoptotic cells was significantly smaller,and brain water content,and Evans blue content and AQP4 expression were lower in group D than in group I/R (P ＜ 0.05 or 0.01).Global cerebral I/R-induced pathological changes were significantly attenuated in group D.Conclusion Dexmedetomidine can decrease the permeability of blood-brain barrier and attenuate global cerebral I/R injury in rats,and down-regulation of AQP4 expression may be involved in the mechanism.

Objective To observe the suppressing effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on ultraviolet ray (UV)-induced erythema.Methods A solar simulator and an UV phototherapy device were used as light sources,respectively.Erythema reaction was induced on the back skin of 30 healthy volunteers by 1,2 and 3 minimal erythema doses (MED) of irradiation.Five preparations including butyl flufenamate 2.5％ ointment,butyl flufenamate 5％ ointment,the base of butyl flufenamate ointment,halometasone ointment,and diclofenac 1％ ointment,were applied to the irradiation sites respectively half an hour before or immediately after the irradiation.One irradiation site remained untreated and served as the control.The degree of erythema was evaluated by a chromameter at 4,24,and 48 hours after the irradiation.Intragroup and intergroup comparisons were done by t test and analysis of variance,respectively.Results When applied half an hour before solar-simulated irradiation,both 2.5％ and 5％ butyl flufenamate ointment totally suppressed the erythema reaction induced by 1-3 MED of UV irradiation,with no significant increase in erythema index at all the three time points after irradiation (all P ＞ 0.05); diclofenac 1％ only inhibited the erythema induced by 1 MED of UV irradiation at 4 and 48 hours,with no difference observed in erythema index between the baseline and these time points after irradiation; however,halometasone significantly aggravated the erythema reaction (P ＜ 0.05).Neither NSAIDs nor corticosteroids applied immediately after solar-simulated irradiation showed statistical effect on the degree of UV-induced erythema.When applied immediately after irradiation using the phototherapy device,butyl flufenamate 2.5％ ointment,butyl flufenamate 5％ ointment and halometasone ointment all induced a significant reduction in erythema reaction at 4 hours after 1 MED of irradiation (all P ＜ 0.05),and diclofenac caused a statistical decrease in erythema reaction at all the time points after 1-3 MED of irradiation (all P ＜0.05).Conclusions Topical use of butyl flufenamate before UV irradiation can effectively inhibit erythema reaction induced by 1-3 MED of irradiation.When applied immediately after irradiation,diclofenac shows the strongest erythema-suppressive effect,followed sequentially by butyl flufenamate and halometasone.

Objective To investigate the effects of dexmedetomidine on global cerebral ischemia-reperfusion (I/R) injury in rats.Methods Fifty-four adult male SD rats weighing 200-250 g were randomly divided into 3 groups (n =18 each): shame operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral I/R was produced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mm Hg).In group D dexmedetomidine 3 μg/kg was injected iv immediately after I/R,followed by infusion of dexmedetomidine at a rate of 3 μg· kg- 1 · h- 1 until 2 h of reperfusion.The neurological deficit score (NDS) was assessed (0 =normal,100 =brain death) at 6 h (T1),24 h (T2)and 72 h (T3) of reperfusion.Then six rats were sacrificed in each group and brain tissues were removed for microscopic examination of hippocampus CA1 region and determination of activity of myeloperoxidase (MPO),contents of TNF-α and IL-1β and expression of glial fibrillary acidic protein ( GFAP).Results Compared with group S,NDS,MPO activity and the contents of TNF-α and IL-1β at T1-3 were significantly increased,the expression of GFAP was up-regulated at T2,3 in groups I/R and D ( P ＜ 0.05 or 0.01).Compared with group I/R,NDS,MPO activity and TNF-α concent were significantly decreased at T1-3,IL-1β concent was decreased at T1,2,the expression of GFAP was down-regulated at T2,3 in group D (P ＜ 0.05 or 0.01 ).The pathologic changes were significantly attenuated in group D as compared with group I/R.Conclusion Dexmedetomidine can attenuate global cerebral I/R injury in rats,and the inhibition of inflammatory response may be involved in the mechanism.