Prediabetes is an abnormal condition between normal glucose metabolism and diabetes mellitus. Impaired glucose tolerance (IGT) is an indicator of high-risk state of prediabetes. Positive interventions of IGT, including life style changes and pharmacological intervention, can effectively postpone and reduce the development of prediabetes into type 2 diabetes mellitus, suggesting that IGT is a key point of diabetes prevention. Currently, pharmacological intervention for prediabetes is still at early stage. In this review, we summarizes recent clinical and preclinical studies on pharmacological intervention for prediabetes, and studies in the development of animal models with IGT and the application of new techniques. We also discuss the prospects of drugs for diabetes prevention, especially with the traditional Chinese medicine.
Animals ; Diabetes Mellitus, Type 2 ; prevention & control ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Glucose Intolerance ; Humans ; Prediabetic State ; drug therapy

OBJECTIVETo investigate the effects of α3 neuronal nicotinic acetylcholine receptor (nAChR) on apoptosis and p38 signal transduction pathway in SH-SY5Y cells and to assess the roles of α3 nAChR in the pathogenesis of Alzheimer's disease (AD).

METHODSThe levels of α3 nAChR mRNA and protein were measured by real-time PCR and Western blot, respectively, in SH-SY5Y cells transfected with α3 nAChR siRNA. The mRNA level of bcl-2 and bax was measured by the real-time PCR. The siRNA transfected SH-SY5Y cells and control were then treated with 10 µmol/L Aβ25-35 for another 48 h, and the change in apoptotic rate and the levels of p-p38 and p38 were measured by flow cytometry and Western blot. Subsequently these SH-SY5Y cells were exposed to a blocker of p38 protein, and the apoptotic rate was measured again.

RESULTSCompared to the controls, the expression of α3 nAChR at mRNA and protein levels in the SH-SY5Y cells transfected with α3 nAChR siRNA decreased by 95% and 86%, respectively; the mRNA levels of bax increased 2.11 times and that for bcl-2 decreased 0.53 times. The apoptotic rate was unaffected (3.40% ± 0.20%); but it increased after Aβ25-35 treatment (24.52% ± 1.59%); the level of p-p38 protein also increased by 178% in the α3 nAChR inhibited cells treated with Aβ25-35. Compared to controls, the Aβ25-35-treated SH-SY5Y cells and the Aβ25-35-treated and siRNA-transfected cells both showed a reduction in apoptosis after treatment with p38 blocker, especially in the former.

CONCLUSIONThe siRNA silencing of α3 nAChR mRNA may enhance the effect of Aβ25-35 on the cell apoptosis by increasing the levels of p38 protein and bax mRNA and decreasing the level of bcl-2 mRNA, which may play a role in the pathogenesis of AD.

Alzheimer Disease ; etiology ; Amyloid beta-Peptides ; metabolism ; Apoptosis ; Cell Line, Tumor ; Gene Silencing ; Humans ; Neuroblastoma ; metabolism ; pathology ; Peptide Fragments ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Nicotinic ; genetics ; metabolism ; Signal Transduction ; Transfection ; bcl-2-Associated X Protein ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo study the influence of beta-amyloid protein (Abeta) and cholesterol on the pathological changes of Alzheimer's disease (AD) and on the expression of nicotinic acetylcholine receptor (nAChR) subunits in the brains of rats.

METHODThe rats were treated by intracerebroventricular injection of Abeta1-42 and fed with a diet containing 5% cholesterol to establish animal model of AD. The pathological changes, learning and memory, and expression of nAChRs of rats were analyzed by Bieoschowsky staining, immunohistochemistry, water-labyrinth, Western blot, and RT-PCR.

RESULTSAbeta intracerebroventricular injection induced Abeta deposition in rat brains and high-cholesterol diet resulted in hypercholesterolemia in the animals. Injection of Abeta caused a reduction of learning and memory of rats and modifications of the expression of nAChRs. Cholesterol enhanced these effects of Abeta on neuropathology and expression of nAChRs.

CONCLUSIONSAbeta can induce marked neuropathological changes, influence the learning and study ability, and modify the expression of nAChRs. Cholesterol can enhance the neurotoxicity of Abeta.

Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; Amyloid beta-Peptides ; metabolism ; Animals ; Cerebral Cortex ; metabolism ; pathology ; Cholesterol ; blood ; Drug Synergism ; Female ; Hypercholesterolemia ; blood ; Learning ; drug effects ; Male ; Peptide Fragments ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Nicotinic ; biosynthesis ; genetics

Application of Rogerson Spatial Pattern Surveillance Method was discussed in real-time surveillance and early monitoring for infectious diseases. Theory of Rogerson Spatial Pattern Surveillance Method was introduced in detail. Data from the program on 'Monitoring epidemic cerebrospinal meningitis with Rogerson Spatial Pattern Surveillance Method' by the Chinese Center for Disease Control and Prevention provided evidence as how to choose crucial parameters such as K, H, n0 and tau, how to simulate surveillance process and how to interpret results. Rogerson Spatial Pattern Surveillance Method seemed to be able to continuously monitor the changes of infectious diseases. New cases could be added to this model at any moment and this model could provide early warning information in time when the excess of cases occurred. Simultaneously it could provide the time and site of the extra cases. Rogerson Spatial Pattern Surveillance Method could implement dynamic and real-time surveillance for infectious diseases. Simultaneously it could avoid the problem of multiple tests that causing large type I error. It greatly helped in providing reliable information for controlling infectious diseases in early epidemic period. Hence,it had important value of application in early warning on infectious diseases.
Communicable Diseases ; epidemiology ; Computer Simulation ; Data Interpretation, Statistical ; Humans ; Population Surveillance ; methods

OBJECTIVETo assess the association between G894T (Glu298Asp) mutation in exon 7 of the endothelial nitric oxide synthase gene and premature coronary heart disease (P-CHD).

METHODSHospital-based case-control study was conducted. Newly-diagnosed CHD patients were recruited as study subjects. 132 CHD patients diagnosed at/before age 55 for males and 65 for females were assigned to P-CHD case group with other 172 CHD patients as the control group. Polymerase chain reaction with Ban II restriction enzyme digestion was performed to detect the G894T mutation.

RESULTSG894T mutant genotypes in P-CHD group (TT, GT and GG frequencies were 6.06%, 20.45% and 73.48%, respectively) were significant higher than those in control group (TT, GT and GG frequencies were 1.74%, 11.63% and 86.63%, respectively) (P = 0.01). Mutant T allele frequency in P-CHD group was also significantly higher than that in control group (16.29% versus 7.56%, P = 0.001, OR = 2.38, 95% CI: 1.38 - 4.16). Stepwise multiple logistic regression analysis at 0.05 significant level with sex, smoking, alcohol drinking, and overweight covariates indicated that G894T mutation also having significant effect on P-CHD (P = 0.01, OR = 2.25, 95% CI: 1.19 - 4.26).

CONCLUSIONThis study suggested that G894T mutation in endothelial nitric oxide synthase gene might serve as a major risk factor to the pathogenesis of P-CHD in this study population.

Age Factors ; Case-Control Studies ; Coronary Disease ; enzymology ; genetics ; Exons ; genetics ; Female ; Gene Frequency ; Humans ; Male ; Middle Aged ; Nitric Oxide Synthase Type III ; genetics ; Point Mutation ; Risk Factors

OBJECTIVETo analyze the differential proteomics in human umbilical cord mesenchymal stem cells (MSC) induced by chemical hypoxia-mimetic agent cobalt chloride (CoCl(2)) by two-dimensional gel electrophoresis (2-DE) and mass-spectrometry.

METHODS2-DE was performed to separate proteins from treated and untreated human umbilical cord MSC with CoCl(2). 2-DE images were analyzed by ImageMaster 2D Platinum software 6.0. The differential expressed proteins was identified by MALDI-TOF-MS. The differential proteins were classified based on their functions.

RESULTS2-DE reference patterns of CoCl(2) treated human umbilical cord MSC were established. A total of twenty-six differential proteins were identified, of them eleven proteins were up-regulated and fifteen down-regulated. Their biological functions involved in carbohydrate metabolism, protein metabolism and modification, lipid metabolism, coenzyme and prosthetic group metabolism, cell cycle, immunity and defense, cell structure and motility, signal transduction, protein targeting and localization, neuronal activities, muscle contraction, etc. Peroxiredoxin1 (Prdx) was down-regulated, whereas alpha-enolase (ENO1) and vesicle amine transport protein 1 homolog (VAT1) up-regulated.

CONCLUSIONThe effects of hypoxia on human umbilical cord MSC were participated by multiple proteins and involved in multiple functional pathways.

Cobalt ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; Proteome ; analysis ; Proteomics ; Umbilical Cord ; cytology ; drug effects

OBJECTIVEApplication of Knox method was discussed in exploring temporal-spatial cluster for infectious diseases.

METHODSThe theory of Knox method was introduced in detail. As an example, the temporal-spatial cluster of epidemic cerebrospinal meningitis cases from April to May in 2005 was explored in Beijing and the statistical process of Knox method was clearly demonstrated with related results well interpreted.

RESULTSOnly when time and distance threshold values were set as 13 days and 29.67 km, potential temporal-spatial cluster could be detected in epidemic cerebrospinal meningitis cases.

CONCLUSIONAccording to the characteristics of the epidemics, under Knox method, if appropriate threshold values of time and distance were chosen, information on temporal-spatial cluster of infectious diseases could be obtained. According to the records of different time and distance threshold values, the nature of an infectious disease might be explored. Thus Knox method could help us to strengthen the early warning system on infectious disease control strategy.

China ; epidemiology ; Cluster Analysis ; Communicable Diseases ; epidemiology ; Disease Outbreaks ; Humans ; Meningitis ; epidemiology ; Time Factors

Objective To explore the dosage and injection method of concanavalin A(Con A) for inducing Wistar rats into the acute hepatic injury model. Methods (1)According to the dosage of Con A, 42 Wistar rats were randomly divided into groups A, B, C, D, E, N, 7 rats in each group. Group N was given tail intravenous injection of normal saline as normal control group. Groups A, B, C, D, E were given intravenous injection of 4, 8, 16, 30, 40 mg/kg of Con A respectively. At the 8th hour after modeling, the levels of alanine transaminase(ALT), aspartate aminotransferase(AST), albumin(ALB), interleukin(IL)-2 , IL-10, interferon (IFN)-γ, and tumor necrosis factor(TNF)-αwere detected. And HE staining was used to observe the pathological feature of hepatic tissue. (2)According to the injection method of Con A, 21 Wistar rats were randomly divided into normal control group, intraperitoneal injection group and tail intravenous injection group, 7 rats in each group. The dosage of Con A for the rats in intraperitoneal injection group and tail intravenous injection group was 16 mg/kg. At the 8th hour after modeling, the levels of serum ALT, AST, and ALB were determined. Results The number of abnormal deaths in various dose Con A groups at the end of each experiment was 0 in groups A, B, C, and 2 in group D, and 7 in group E. A small amount of spotty necrosis, inflammatory cell infiltration, and hepatic lobule with almost integrity of structure were found in groups A, B, while obvious bridging-like necrosis was seen in groups C, D. Serum ALT, AST, and ALB levels in intraperitoneal injection group had no statistically significant difference as compared with the normal control group. Conclusion Tail intravenous injection of 16 mg/kg of Con A can be used to induce an acute immunological liver injury rat model successfully.

OBJECTIVETo examine the temporal and spatial expression of vascular endothelial growth factor (VEGF) and angiopoietins (Ang) in rat brain after cerebral ischemia, and to elucidate the roles they played in angiogenesis and vascular permeability.

METHODSRats were subjected to either middle cerebral artery occlusion (MCAO) or sham operation. Reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry were used to detect the expression of VEGF, Ang-1 and Ang-2 at different time points after ischemia. CD31 was used to label endothelial cells after MCAO. Vascular permeability was determined by Evans blue.

RESULTSVEGF was markedly increased at 2 h, had an initial peak at 12 h (0.7249 ± 0.1933, P < 0.01), and a second peak at 7 days (0.5264 ± 0.1519, P < 0.01). Ang-2 mRNA and protein significantly increased after MCAO, both of them peaked at 12 h (0.6747 ± 0.2416, P < 0.01; 1.1197 ± 0.1780, P < 0.01). In contrast, Ang-1 mRNA and protein gradually decreased after MCAO, respectively reaching a minimum at 3 d (0.3220 ± 0.1427, P < 0.01) and 1 d (0.1298 ± 0.0293, P < 0.01). Changes in the expression of these factors correlated with the progress of angiogenesis and vascular permeability. Evans blue test revealed that the vascular permeability gradually increased, and peaked at day 1 after ischemia [(6.219 ± 0.887) µg/g, P < 0.01].

CONCLUSIONDynamic temporal changes in VEGF, Ang-1 and Ang-2 expression stimulate the cerebral angiogenesis after focal cerebral ischemia.

Angiopoietin-1 ; genetics ; metabolism ; Angiopoietin-2 ; genetics ; metabolism ; Animals ; Blotting, Western ; Capillary Permeability ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; physiopathology ; Male ; Neovascularization, Physiologic ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

China ; epidemiology ; Disease Outbreaks ; Humans