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.

Cytomegalovirus Infections ; complications ; Female ; Humans ; Infant, Newborn ; Male ; Skin Diseases ; etiology

ADP-ribosyl Cyclase 1 ; immunology ; Biopsy ; Bone Marrow ; immunology ; pathology ; Epoxy Resins ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; immunology ; Plastic Embedding ; Staining and Labeling ; methods

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 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 investigate the safety of different intensity anticoagulation therapy of warfarin in preventing thromboembolism in octogenarian patients with nonvalvular atrial fibrillation (NVAF). Methods The 130 patients with persistent or permanent NVAF were randomly divided into three groups: low-intensity warfarin group (35 cases, international normalized ratio, INR (1.5-2.0), moderate-intensity warfarin group (32 cases, INR 2.1-2.5) and aspirin control group (63 cases). The rate of hemorrhagic events and the effect on renal function were observed. Results The incidence of hemorrhage was the lowest in low-intensity warfarin group compared to the other groups with slight bleeding in one case. life-threatening bleeding in one case, severe bleeding in one case and slight bleeding in four cases occurred in moderate-intensity warfarin group. Life-threatening bleeding in three cases, severe bleeding in two cases and slight bleeding in six cases occurred in aspirin control group. There were significant differences in bleeding incidence among the three groups (χ2=5.13,P＜0.05). The low-intensity warfarin group and moderate-intensity warfarin group were superior to the aspirin control group in the effect on renal function (P＜0.05). Conclusions It is safe that the dose of warfarin is maintained at low anticoagulation intensity between INR 1.5 and 2.0 in octogenarians with NVAF.

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.

Objective To investigate the effects of lipoxin A4 (LXA4) on the inflammatory response to focal cerebral ischemia-reperfusion(I/R) inmy in rats.Methods Fifty-six healthy male SD rats weighing 200-250 g were randomly divided into 3 groups:group Ⅰ sham operation(group S,n=8);group Ⅱ cerebral I/R(n=24)and group Ⅲ lipoxin A4+I/R(group LXA4,n=24).Right mid-cerebral artery was occluded for 2 h by inserting cranially a nylon thread with rounded tip into internal carotid artery.LXA4 0.03 nmol/5 μl was injected into cerebral ventricle at 5 min after cerebral ischemia.Neurological deficit was scored at 24 h of reperfusion.Then four animals in each group were killed and their brains were removed for microscopic examination and expression of MPO at 24 h of reperfusion.Meantime,content of IL-1β,TNF-α,TGF-β1,and IL-10 in the brain tissue were measured at 1,6,12,24 and 48 h of reperfusion by ELISA.Glial cell activity was examined at 24 h of reperfusion by immuno-histochemistry.Results Intra-cerebroventricular administrated LXA4 0.03 nmol/5 μl provided mild neuroprotection against focal cerebral I/R injury,improved neurological deficits,and reduced morphological brain damages and PMN infiltration.LXA4 also decreased the content of TNF-α and IL-1β,and increased the content of IL-10 and TGF-β1.The numbers of activated astroglia and microglia were decreased in group LXA4 compared with group I/R.Conclusion LXA4 protects the brain against I/R injury by inhibiting inflammatory response.

AIM To establish an HPLC-DAD method for the simultaneous content determination of four constituents in Compound Kendir Leaves Tablets Ⅰ (Apocyni veneti Folium,Chrysanthemi indici Flos,Stephaniae tetrandrae Radix,etc.).METHODS The analysis of 50％ methanol extract of this drug was performed on a 35 ℃ thermostatic Shimadzu VP-ODS column (250 mm × 4.6 mm,5 μm),with the mobile phase comprising of methanol-0.5％ phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 260 nm and 325 nm.RESULTS Chlorogenic acid,hydrochlorothiazide,buddleodide and promethazine hydrochloride showed good linear relationships within the ranges of 24.91-498.2 ng (r =0.999 9),286.33-5 726.7 ng (r =0.999 9),10.04-200.9 ng (r =0.999 9) and 154.80-3 096.1 ng (r =0.999 9),whose average recoveries were 98.3％ (RSD =1.3％),99.1％ (RSD =0.6％),98.5％ (RSD =1.0％) and 99.3％ (RSD =1.2％),respectively.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Compound Kendir Leaves Tablets Ⅰ.