Objective To investigate the effects of chloroquine on metabolism of insulin,glucose,lipids and expression of insulinase gene (EIG) in patients with type 2 diabetes mellitus.Methods Fasting plasma insulin (FINS),fasting plasma glucose (FPG),glycoslated hemoglobin (HbA1c),plasma lipids and lipoprotein,insulinase activity of erythrocytes (EIA) and EIG were determined in 30 patients with type 2 diabetes mellitus laking chloroquine for 14 day in dosage of 250mg twice daily,27 diabetic patients laking placebo and 20 normal subjects.Insulin sensitive index (ISI) were also calculated.Results Chloroquine caused a decrease in total plasma cholesterol,low density lipoprotein,EIA and EIG,and an increase in ISI,plasma high density lipoprotein and subclass 2.No change of these indices was observed in diabetic patients with placebo.Conclusion Chloroquine can ameliorate the dyslipidemia and insulin sensitivity of patients with type 2 diabetes mellitus.This may be due to a decrease in EIG,which may result in lowered degradation of insulin.

BACKGROUND: Impaired glucose tolerance(IGT) is mainly related to genetic factors and environmental factors including excessive calorie intake and obesity. Insulin resistance(IR) plays a major role in the onset of IGT.OBJECTIVE: To investigate the relationship between erythrocyte insulinase activity(EIA) and IR in patients with IGT soas to provide theoretic basis for improving IR in patients with IGT by exercise.DESIGN: Observational and comparative study based on IGT patients as the subjects and adults with normal glucose tolerance as controls.SETTING: Department of endocrinology of a hospital affiliated to a military medical university.SUBJECTS: The study was conducted in the Department of Endocrinology of Nanfang Hospital, First Military Medical University of Chinese PLA, from January 2001 to April 2003. A total of 50 inpatients and outpatients with IGT, 26 males and 24 females aged(52 ± 7) years, were randomly selected. Inclusion criteria: those whose diagnosis met the WHO 1999 for criteria oral glucose tolerance test (OGTT) and whose heart, liver and kidney functions and blood test were within the normal range without taking any antidiabetics. Exclusion criteria: those who had liver and kidney diseases, infection, malignant tumor, coronary heart disease, cerebrovascular disorder and connective tissue disease. The patients with IGT were divided into 2 subgroups according to the presence of abnormal fasting plasma glucose (FPG).Subgroup A consisted of 20 patients (9 males and 11 females) with IGT accompanied with impaired FPG. Subgroup B was composed of 30 IGT patients (17 males and 13 females) with normal FPG. Twenty adults with normal glucose tolerance were set as control group(20 females and 10 males) with the age of(48 ± 12)years.METHODS: EIA was measured with the method of radioenzymatic assay in all subjects. Blood sugar, serum insulin and glycosylated hemoglobin were also measured, and homeostasis model analysis-insulin resistance (HOMA-IR) index was calculated for estimation of insulin sensitivity.MAIN OUTCOME MEASURES: The differences and correlation between EIA and HOMA-IR in IGT patients of each group.RESULTS: EIA, serum fasting insulin and HOMA-IR indexes of the patients with IGT were significantly higher than those of the controls ( P < 0.01 or P < 0.05) . EIA and HOMA-IR of the patients in subgroup A was significantly higher than those in subgroup B ( P < 0. 01 ). Linear regression analysis showed that EIA had significant positive correlation with serum fasting insulin, glycosylated hemoglobin and HOMA-IR indexes( r = 0.51, 0.44,0.49, P <0.01).CONCLUSION: The degradation rate of erythrocyte insulinase in patients with IGT tolerance is significantly higher than that of normal persons, and is closely related to the onset and development of insulin resistance.

OBJECTIVE: To investigate the effects of Liuwei Dihuang Pills (LWDHP) on expressions of apoptosis-related genes bcl-2 and Bax in pancreas of OLETF rats. METHODS: Forty male OLETF rats were randomly divided into LWDHP-treated group and untreated group. Another ten male LETO rats were included in normal control group. OLETF rats in the LWDHP-treated group were given LWDHP (2.4 g.kg(-1).d(-1)) orally since the age of 8 weeks and the rats in the other two groups were given distilled water orally. Body weights of rats were recorded weekly and blood glucose concentration was determined by oral glucose tolerance test (OGTT). Pancreas weights were recorded after rats were killed and the expression levels of bcl-2 mRNA and Bax mRNA were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In the LWDHP-treated group, the expression of bcl-2 mRNA in the pancreas of rats at the age of 40 weeks (1.25+/-0.07) was much higher than that in the untreated group (1.01+/-0.16), P<0.01. Bax mRNA level in the LWDHP-treated group (0.57+/-0.11) was obviously lower than that in the untreated group (1.18+/-0.28), P<0.01. There was no significant difference of pancreas-to-body weight ratios between the LWDHP-treated group and the untreated group. The ability of glucose tolerance was improved in the LWDHP-treated group. CONCLUSION: LWDHP can up-regulate the expression of bcl-2 and down-regulate the expression of Bax at transcription level, which maybe contribute to the anti-apoptosis effects of LWDHP.

Objective To observe the effect of the optimized formulas of extracts of Radix Astragali and Radix Angelicae Sinensis on the survival status of the idiopathic pulmonary fibrosis (IPF) mice,and on the expression levels of transforming growth factor-β (TGF-β) and vascular endothelial growth factor(VEGF),so as to optimize the therapeutic regimen and to explore the therapeutic mechanism.Methods One hundred and five SPF ICR male mice were randomly divided into normal group,model group and 5 Chinese medicine treatment groups (group 1,2,3,4,5 of the optimized formula of Radix Astragali and Radix Angelicae Sinensis extracts).The mice in the model group and the 5 treatment groups were intratracheally injected with bleomycin (5 mg/kg) to induce the pulmonary fibrosis model.On day 21,the lung tissues were taken out for the test.Hydroxyproline content was detected by alkaline hydrolysis method,and morphological changes of lung tissues were observed by hematoxylineosin (HE) staining and Mallory's staining methods.The expression levels of TGF-β and VEGF were detected by polymerase chain reaction (PCR).Results The HE staining and Mallory's staining results showed that the pulmonary fibrosis in the 5 treatment groups was relieved as compared with that in the model group,especially in the group 1,and the alveolar structure recovered better.The 21-day overall death rate in the treatment groups were lower than those in the model group,and group 1 and group 5 had the lowest rates,the difference being statistically significant (P＜ 0.05).Compared with the model group,the content of hydroxyproline in the lung tissues of the treatment groups were decreased to some degrees,and there was significant difference (P ＜ 0.05 or P ＜ 0.01).The expression levels of TGF-β and VEGF in model group were higher than those in normal group,but were deceased in the treatment groups to some degrees,except TGF-β expression in group 5,and the difference was significant(P ＜ 0.05 or P ＜ 0.01).Conclusion When the contents of Radix Astragali water-extract and Radix Angelicae Sinensis alcohol-extract were predominated,the extract formula exerts certain effects on decreasing hydroxyproline content in the lung tissues,inhibiting the expression levels of TGF-β and VEGF,and relieving the degree of pulmonary fibrosis in IPF mice.

OBJECTIVETo investigate the protective effects of exendin-4 on vascular endothelial cells and explore the possible mechanism.

METHODSHuman umbilical vascular endothelial cells (HUVECs) were cultured in the presence of high glucose and tumor necrosis factor-α (TNF-α, 10 ng/ml) with or without exendin-4. The level of nitric oxide (NO) in the cell culture supernatant was measured using a nitrate reductase method. The expression of intercellular adhesion molecule-1 (ICAM-1) mRNA was measured by real-time PCR, and nuclear factor-κB (NF-κB) p65 translocation was detected using immunofluorescence assay. Western blotting was employed to measure the expression of p38 MAPK protein in the treated cells.

RESULTSIn the presence of high glucose and TNF-α, treatment of cells with exendin-4 did not obviously affect the cellular synthesis of NO, but significantly down-regulated the expression of ICAM-1 mRNA (P<0.01). The nuclear fluorescence intensity of NF-κB p65 and the expression level of p38 MAPK protein in the cells were significantly lowered by exendin-4 treatment (P<0.01).

CONCLUSIONExendin-4 ameliorates high glucose- and TNF-α-induced HUVEC-12 cell damage by inhibiting the expression of p38 MAPK protein and translocation of NF-κB p65.

Cell Line ; Culture Media ; chemistry ; Glucose ; adverse effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Peptides ; pharmacology ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; adverse effects ; Venoms ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To investigate the quantitative value of the signal intensity ratio of extraocular muscle and ipsilateral white matter measured by MRI for the evaluation of activity in thyroid-associated ophthalmopathy. Methods A total of 129 patients and 245 eyeballs with thyroid-associated ophthalmopathy were enrolled in this study and this 245 eyeballs were set as thyroid-associated ophthalmopathy group(TAO group). There were 10 patients with newly diagnosed Graves'disease and in the same period and these 20 eyeballs were set as graves'disease group(GD group). 32 normal people from annual physical test excluded thyroid and eye diseases and their 64 eyes were selected randomly for the normal control group(NC group). The signal intensity of the extraocular muscle and the ipsilateral white matter on the MRI images were measured, while did exophthalmos and the width of the inner fat of eyeballs (FWs)measurements in the same time. Results SIR,FWs,and exophthalmos of TAO group were higher than those of the other 2 groups[SIRs:1.71(1.40,2.10)vs 1.26(1.22,1.34)and 1.23(1.14,1.32);FWs:8.04(6.70, 8.71)mm vs 6.16(4.86,7.08)mm and 6.93(6.41,7.65)mm,exophthalmos:20.10(18.56,22.15)mm vs 15.40(14.87,16.60)mm and 14.73(13.40,16.07)mm,all P<0.05]. The reference value of SIR establishing based on SIRs of NC group is less than 1.37. In total 129 TAO patients,55 patients(with 106 eyeballs)have a clinical activity score(CAS). Then,these eyeballs were grouped to activity and non-activity(grouped by CAS≥3),and the baseline group difference of these 2 groups was not statistically significant. The SIRs and exophthalmos of activity group were higher than the non-activity group[SIRs:1.70(1.45,2.33)vs 1.41(1.25,1.75); exophthalmos:(20.38 ± 2.40)mm vs(19.05 ± 3.70)mm,all P<0.05]. But the difference of FWs of these two groups was not statistically significant(P>0.05). The SIRs and CAS had a positive correlation(r=0.580,P=0.000),through the receiver operating characteristic curve(ROC)we get the best diagnostic performance of TAO activity when the SIR≥1.56(sensibility=65.6%,specificity=89.1%,AUC=0.815,P=0.000). Conclusion The signal intensity ratio of extraocular muscle and ipsilateral white matter may discriminate the activity of TAO early as a quantitative indicator, reflecting its efficacy,and is worth clinically generalizing.

UV photolithography and hydrofluoric acid wet etching were used to produce silicon master molds and polydimethylsiloxane (PMDS)-based soft lithography was adopted to fabricate three-dimensional poly(lactic-co-glycolic acid) (PLGA) and PDMS microwell patterns with high aspect ratio and channel connection. Nine microwell patterns were thus obtained with different structural dimensions. Patterns were treated with oxygen plasma etching and polylysine coating to enhance hydrophilicity and cell compatibility for subsequent culture of C17. 2 neural stem cells. With proliferation during the culture, C17. 2 cells gradually distributed within the microwells, showing an obviously three-dimensional (3-D) growth behavior. The presence of channel structures greatly favored the 3-D growth of C17. 2 neural stem cells on the microwell patterns. Multi-layered scanning with confocal microscopy and 3-D rendering after carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) staining showed that most C17. 2 cells grew within a range of 30 to 90 microm from the microwell bottom. Immunofluorescence staining indicated that C17. 2 cells within 3-D microwell patterns were uniformly nestin-positive on day 2 after cell plating. It could well be concluded that the microwell patterns thus fabricated were suitable for the 3-D culture and subsequent differentiation of C17. 2 neural stem cells. And the cells can be maintained with uniform stemness properties while cultured in these microwell patterns.
Cell Culture Techniques ; methods ; Dimethylpolysiloxanes ; chemistry ; Imaging, Three-Dimensional ; Intermediate Filament Proteins ; metabolism ; Lactic Acid ; chemistry ; Microscopy, Confocal ; Nerve Tissue Proteins ; metabolism ; Nestin ; Neural Stem Cells ; cytology ; Polyglycolic Acid ; chemistry

Humans ; Acupuncture Points ; Deglutition Disorders ; Electroacupuncture