AIM:To investigate the renal function and pathological changes in Npc1 mutant ( Npc1-/-) mice. METHODS:Different genotypes of Niemann-Pick disease type C1 (Npc1) mice were identified by PCR.Subsequently, the renal function of Npc1-/-and Npc1 +/+mice at postnatal day 60 ( P60) was evaluated by measuring the activity and con-tent of important indicators in the serum including ALT , AST, LDH, urea, UA and Cr.Furthermore,β-galactosidase stai-ning and Masson staining were performed to examine the aging and fibrosis of the renal tissues , respectively .RESULTS:Compared with the Npc1 +/+mice, the body weight and kidney weight had a significant reduction ( P<0.01) in the Npc1-/-mice.The results of hepatic and renal functions showed that the activities of ALT , AST and LDH, and contents of urea, UA and Cr had marked increases (P<0.05) in the Npc1-/-mice.Moreover, the results of senescence-associatedβ-galacto-sidase staining in the renal tissues demonstrated accelerated aging in the Npc1-/-mice (P<0.01), and these results were confirmed by Masson staining, which clearly showed the formation of collagen fibers (P<0.01).CONCLUSION:Muta-tion of the Npc1 gene results in abnormal lipid metabolism , which accelerates kidney senescence by promoting fibrosis in the renal tissue and subsequently causes reduction in renal function .

Objective To explore the value of plasma C-peptide levels in early prediction of type 2 diabetes mellitus with peripheral sensory neuropathy.Methods The vibration perception threshold,pain,temperature sensation,touch-pressure sensation,ankle reflex was detected in 500 eases of type 2 diabetes mellitus,and the patients were divided into 4 groups according to peripheral sensory nerve test results:normal group (159 cases),mildly abnormal group (120 cases),moderately abnormal group (121 cases) and severely abnormal group (100 cases).Fasting and 2-hour postprandial C-peptide levels were determined and analysed with peripheral sensory nerve changes.The receiver-operating characteristic (ROC) curve was used to find the best critical point for diagnosis of diabetic peripheral sensory neuropathy.Results The fasting C-peptide among 4 groups had no significant difference (F =1.632,P ＞0.05).Two-hour postprandial C-peptide from normal group to mildly abnormal group and then moderately abnormal group gradually increased [(1.110 ± 0.526),(1.324 ± 0.490),(1.573 ± 0.716) μ g/L],while 2-hour postprandial C-peptide in severely abnormal group was significantly decreased and lower than that in normal group,and there were significant differences (P＜ 0.05).The max Youden Index was 0.366 when 2-hour postprandial C-peptide was 1.173 μ g/L.Conclusions The fasting C-peptide might be not related to early diabetic peripheral sensory neuropathy,but 2-hour postprandial C-peptide might be closely related to early diabetic peripheral sensory neuropathy.It is helpful to detect the early diabetic peripheral sensory neuropathy if we can take a dynamical observation of 2-hour postprandial C-peptide.

AIM:To investigate the effect of insulin and gliclazide therapies on the liver fat accumulation in type 2 diabetic rats .METHODS:A high-fat diet plus low-dose streptozotocin was implemented to establish a type 2 dia-betic rat model, and the rats were randomly divided into diabetes mellitus (DM) group, diabetic rats treated with insulin ( INS) group, diabetic rats treated with gliclazide per os ( PO) group, and normal control ( NC) group.The diabetic rats in INS group and PO group were given insulin and gliclazide for 3 weeks, respectively.The changes of the liver fatty were evaluated with oil red O staining .Fasting plasma adiponectin concentration was measured by ELISA .The expression of adi-ponectin receptor 1 ( AdipoR1 ) was detected by real-time PCR.The protein levels of AMP-activated protein kinase (AMPK), phosphorylated AMPK on threonine 172 ( Thr172p-AMPK), sterol regulatory element-binding protein 1c (SREBP-1c), phosphorylated SREBP-1c on serine 372 (Ser372p-SREBP-1c), acetyl-CoA carboxylase (ACC), phospho-rylated ACC on serine79 (Ser79p-ACC) and immunoglobulin-binding protein (BiP) in the liver homogenate were deter-mined by Western blotting .RESULTS:Compared with the normal rats , in DM group, the presence of cytoplasmic lipid deposits was confirmed by oil red O staining .In INS group, these changes were significantly lower than those in DM group . Similar results were obtained in PO group .Insulin therapy significantly increased the plasma concentration of diponectin and liver tissue levels of AdipoR1 compared with DM group.At the same time, these 2 indicators returned to normal levels after gliclazide therapy .Thr172p-AMPK/AMPK, Ser372p-SREBP-1c/SREBP-1c and Ser79p-ACC/ACC expression ratios were significantly reduced in DM group compared with control values .The expression of BiP was increased on the contrary . After insulin therapy, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c were significantly increased, and Ser79p-ACC/ACC and BiP returned to the normal levels .After gliclazide treatment, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c returned to the normal levels , the expression ratio of Ser79p-ACC/ACC had no significant improve-ment compared with DM group , and the expression of BiP significantly declined .CONCLUSION: Both the insulin and gliclazide therapies reduce the lipid deposition in the liver of rats with type 2 diabetes by activating AMPK , but the extent and mechanism are not the same.In insulin therapy, AMPK restrains the expression of SREBP-1c directly, increases the phosphorylation of SREBP-1c, and affects SREBP-1c by inhibiting the endoplasmic reticulum stress .Gliclazide treatment, which has no effect on the lipid oxidation , reduces lipid deposition in the liver only through the phosphorylation of SREBP-1c and the suppression of the endoplasmic reticulum stress .

ovel GCK-E339K mutation might be linked to this MODY2 pedigree.

Antibodies, Monoclonal ; metabolism ; CD79 Antigens ; metabolism ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunoglobulin G ; metabolism ; Male ; Middle Aged ; Nose Neoplasms ; metabolism ; pathology ; therapy ; virology ; Paranasal Sinus Neoplasms ; metabolism ; pathology ; therapy ; virology ; Plasmacytoma ; metabolism ; pathology ; therapy ; virology

No abstract available.
Asian Continental Ancestry Group* ; Humans ; Mutation, Missense* ; Piebaldism*

OBJECTIVETo establish a rabbit model of juvenile nonalcoholic steatohepatitis (NASH) for further study.

METHODSTwenty-eight New Zealand rabbit pups were fed with a high-fat diet (standard diet+10 % lard+2 % cholesterol) for 8 or 12 weeks as the two model groups, and 10 rabbits were fed with standard diet as the controls. Liver tissue samples were collected for Heamatoxylin-Eosin staining and pathological examination.

RESULTTypical histological hepatic lesions of NASH were observed in both model groups. Compared with control group, model groups showed a significant increase in serum ALT, AST, TG, TC levels (P <0.01), and decrease in serum adiponectin, IL-10 levels (P <0.05), meanwhile there was no significant difference between two model groups. TC and the degree of liver fatty infiltration were independent determinants of serum adiponectin level by stepwise multiple regression, beta=-1.33, P=0.006 and beta=-0.97, P=0.038, respectively, R square equal to 0.294.

CONCLUSIONThe juvenile steatohepatitis rabbit model has been established and the level of adiponectin can partly reflect the severity of liver steatosis.

Adiponectin ; blood ; Animals ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Fatty Liver ; blood ; metabolism ; pathology ; Female ; Interleukin-10 ; blood ; Male ; Rabbits ; Random Allocation

OBJECTIVETo study the simple infection and super/co-infection of HAV-HEV, HGV in patients with viral hepatitis.

METHODSUsing EIA method to detect anti-HAV IgM, HBV serum markers, anti-HCV IgM, anti-HDV IgM, anti-HEV IgM, anti-HGV IgM in viral hepatitis patients with different clinical types.

RESULTSSeventy-three percent patients (154/210) had HBV infection markers, twenty-nine percent patients (61/210) had HAV infection marker, eight percent patients (17/210) had HCV, HDV infection markers, ten percent patients (21/210) had HEV infection and seven percent patients (15/210) had HGV infection. Only nine percent patients (20/210) had viral hepatitis serum markers negative. In all clinical types, sixty-one percent patients had only one type hepatitis virus infection, thirty-two percent patients had two types of hepatitis virus super/co-infection, six percent patients had three types of hepatitis virus super/co-infection. Super/co-infection often occurred in patients who had cirrhosis or hepatic failure.

CONCLUSIONHBV and HAV infection is very common in viral hepatitis patients, whereas HCV, HDV, HEV and HGV infection is relatively low; double super/co-infection of HAV-HEV, HGV frequently occurs in severe patients with viral hepatitis.

Antibodies, Viral ; blood ; China ; epidemiology ; Female ; GB virus C ; isolation & purification ; Hepatitis A ; epidemiology ; virology ; Hepatitis A virus ; isolation & purification ; Hepatitis E ; epidemiology ; virology ; Hepatitis E virus ; isolation & purification ; Hepatitis Viruses ; isolation & purification ; Hepatitis, Viral, Human ; epidemiology ; virology ; Humans ; Male ; Superinfection

Adiponectin ; blood ; Animals ; Fatty Liver ; pathology ; Rabbits

Animals ; Chlorine Compounds ; toxicity ; Dose-Response Relationship, Drug ; Female ; Lung ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; biosynthesis ; genetics ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics