Objective To establish a euglycemic clamp technique in beagle dogs. Methods The euglycemic clamp technique was applied in healthy beagle dogs and the blood glucose, insulin, C-peptide, insulin and glucagon were monitored during the clamp. Results The blood glucose was controlled within the basal level.The coefficient of variation was less than 5% during the clamp. The serum insulin concentration finally reached(40.0±3.8)mIU/L stably and a significant inhibition was shown in endogenous insulin by the determination of C-peptide. But there was no significant increase in serum glucagon compared with basal values.Conclusion Methodology confirmed that the euglycemic clamp technique is successful in beagle dogs and can be applied in the study of pharmacodynamics of insulin preparations.

A combination product is a new model of the medical product that incorporates at least two of the regulated component categories of device, drug, or biological product into one product. It has become a new hot point within the development of devices and drugs, and has brought about a new opportunity for device and drug industries and a new challenge for administration too. In the paper, the properties of combination products are summed up and the impact on device and drug industries are discussed.
Biological Products ; Device Approval ; Drug Industry ; instrumentation ; Drug-Eluting Stents ; Equipment and Supplies

OBJECTIVETo observe the effect of Ningdong Granule (NG) on serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) of children patients with Tourette's syndrome (TS).

METHODSTotally 90 TS children patients were randomly assigned to the NG group, the NG + Tiapride group (abbreviated as the combined treatment group), and the Tiapride group, 30 in each group. Besides,another 30 healthy children were recruited as the healthy control group. Patients in the NG group were treated with NG (consisting of all gastrodia rhizome, Codonopsis pilosula, Ophiopogon japonicus, white peony root, Rhinocerotidae, oyster, earthworm, licorice root, etc.), one dose daily, administered by dissolving it in boiled water, taken in two portions in the morning and in the evening respectively. Patients in the Tiapride group took Tiapride Tablet, 50 -100 mg each time, twice daily. The dosage was adjusted according to individual difference and changes of pathogenic conditions. The maximal dosage was 300 mg per day. Those in the combined treatment group were treated with equal dose of NG and Tiapride Tablet in combination. The treatment course was 3 months for all. Changes of pathogenic condition before and after treatment were assessed by Yale global tic severity scale (YGTSS). Serum levels of IL-12 and TNF-alpha were detected by enzyme-labeled immunosorbent assay (ELISA) before and after treatment.

RESULTS(1) The total effective rate of the NG group, the combined treatment group, and the Tiapride group was 79.3%, 83.3%, and 67.9%, respectively. It was the lowest in the Tiapride group (P < 0.05). It was significantly higher in the combined treatment group than in the NG group (P < 0.05). (2) The post-treatment YGTSS score was obviously lower in each group after treatment than before treatment (P < 0.05). The posttreatment YGTSS score was obviously lower in the NG group and the combined treatment group than in the Tiapride group (P < 0.05), but with no statistical difference between the fromer two groups (P > 0.05).(3) Compared with the healthy control group before treatment, serum levels of IL-12 and TNF-alpha (pg/mL) were 124.95 +/- 22.78 and 209.52 +/- 21.69 in the NG group, 126.14 +/- 25.65 and 208.97 +/- 22.46 in the combined treatment group, 123.00 +/- 24.26 and 205.10 +/- 26.16 in the Tiapride group, being higher than those in the healthy control group (64.56 +/- 27.59 and 78.13 +/- 33.42; P < 0.05). After treatment, serum levels of of IL-12 and TNF-alpha were 104.67 +/- 16.84 and 183.01 +/- 24.95 in the NG group, 109.04 +/- 16.81 and 179.87 +/- 23.45 in the combined treatment group, significantly lower than before treatment (P < 0.05). But there was no statistical difference in serum levels of IL-12 or TNF-alpha in the Tiapride group between before treatment (123.00 +/- 24.26 and 205.10 +/- 26.16) and after treatment (117.75 +/- 16.79 and 199.76 +/- 33.21; P > 0.05).

CONCLUSIONNG could modulate abnormal serum levels of IL-12 and TNF-alpha in TS children patients, which might be one of its pharmacodynamic mechanisms for treating TS.

Adolescent ; Child ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interleukin-12 ; blood ; Male ; Phytotherapy ; Tourette Syndrome ; blood ; drug therapy ; Tumor Necrosis Factor-alpha ; blood

To summarize Professor LIU Feng-bin's clinical experience and theoretical thoughts on chronic atrophic gastritis (CAG), the study group designed a retrospective study on his case series and expert interview. First of all, the data of CAG patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine between 2009 and 2013, e. g. herbs, diseases, syndrome type, prescription amount and number of herbs, was collected and processed. The statistical description and binary logistic regression were used to determined the syndrome type, initial basic remedy and modification. During the statistics, a complete and sub-group analysis was performed simultaneously. After the expert interview, the syndrome type and medication were finalized. As a result, a total of 228 CAG patients aged at (50.30 ± 10.18) were collected, including 151 males (66.23%). Of them, the TCM diagnosis and syndrome type were extracted from the information of 157 patients, including 115 cases with gastric stuffiness, 23 cases with gastric pain, 19 missing cases, 2 cases with spleen-stomach weakness syndrome, 57 cases with spleen deficiency and dampness-heat syndrome, 18 cases with spleen-stomach disharmony syndrome, 23 cases with syndrome of liver depression syndrome, 21 cases with liver qi invading stomach syndrome and 26 qi and yin deficiency syndrome, respectively. All of the 228 patients used totally 104 herbs, while the subgroups with 157 patients used 94 herbs. The most frequently used 15 herbs used in each groups were analyzed to determine the initial basic remedy and modification. Subsequently, based on the information of the sub-groups with 157 patients, with the syndrome type as the dependent variable, the logistic regression analysis was made on the most frequently used 32 herbs, in order to determined the modification in herbs for different syndrome types. After experts reviewed and modified, they believed the main causes of CAG were dietary irregularities, moodiness and weak constitution; the pathogenesis of CAG was spleen deficiency with qi stagnation, heat depression and blood stasis in the stomach meridian. The above six syndrome types and 12 herbs were determined, including Pseudostellariae Radix, Poria, Atractylodismacrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Fritillariae Thunbergii Bulbus, Sepiae Endoconcha, Arecae Pericarpium, Aurantii Fructus, Perillae Caulis, Herba Hedyotis Diffusae, Scutellariae Barbatae Herba, Curcumae Rhizoma. This study summarized Professor LIU Feng-bin's clinical experience and theoretical thoughts of chronic atrophic gastritis based on clinical practice data and expert interview, with a rigorous design and good scientificity and practicability.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chronic Disease ; Female ; Gastritis, Atrophic ; drug therapy ; Humans ; Logistic Models ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Retrospective Studies

Objective To estalish an accurate method for determining the content of astragaloside Ⅳ in Shouqing Granula. Method TLC scanner was selected to detect astragaloside Ⅳ with silica gela thin layer. The sample was separated by using chloroform-methanol-water (13 : 6 : 2) below 10 ℃ overnight with the under layer solution, ?_s=530 nm, ?_R=700 nm. Results The linear ranges of astragaloside Ⅳ was 0.22～ 0.73 ?g, the average recovery was 97.72%, RSD=0.69%. Conclusion The method was simple and accurate, and can be used for the quality control of Shouqing Granula.

Objective: To investigate the effect of taurine on learning and memory impairment, cytokines secretion in rats intrahippocampally injected with ?-amyloid (A?) 1-40. Methods: SD rats were randomly divided into control group, A? injected group, taurine (0.3g/kg?d, 0.6g/kg?d) groups. The rats were fed with taurine for 7 days, and then subjected to bilateral intrahippocampus injection of A?1-40 or vehicle. Two weeks later, all rats performed Morris water maze test. The contents of IL-6, TNF-? were checked by way of radio-immunity assay for hippocampus samples. Results: Compared with A?model group, the escape latency and distance were significantly reduced in taurine (0.6g/kg?d) group; the ratio of swimming distance in the target quadrant to that in the whole pool of the probe trial; the content of cytokines of IL-6 and TNF-?in hippocampus were reduced significantly. Conclusion: Taurine can effectively attenuate the cognitive dysfunction caused by A?1-40 in rats. The reduced cytokines content in hippocampus might contribute to this effect.

Objective To observe toxic effect of deoxynivalenol(DON)on articular cartilage and synovium of New Zealand rabbits's knee ioints.Methods Fifteen male rabbits were divided randomly into 3 groups:control, high-dosage,and low-dosage group.In high-dosage and low-dosage group,saline solution of DON was injected with a dose of 0.10 and 0.05 ms/kg every 48 h into ear vein of rabbits.Specimen of articular cartilage and synovium were through pathologY methods,and IL-1β,TNF-α,NO levels were assayed in joint liquid,after 20 days. Results Morphological changes were observed, such as synovium inflammative infiltration, chondrocytes deformation and necrosis under light microscope.The levels of IL-1β,TNF-α and NO had statistical significance in comDarison between 3 grouPs(F=19.396,18.195,22.136,P＜0.05).The levels of IL-1β,TNF-α and NO were significantly higher(all P＜0.05),high-dosage[(0.451±0.091),(0.575±0.122)μg/L;(70.27±11.53)μmol/L] and low-dosage group[(0.295±0.107),(0.387±0.131)μg/L;(45.32±12.24)μmol/L]compared with control ((0.1 13±0.049),(0.138±0.087)μg/L;(23.56±9.35)μmoL/L],and high-dosage compared with low-dosage group Conclusions DON results in articular and synovial impairment,which has the symptom similar to osteoarthritis. DON probably causes osteoarthritis.

Objective To evaluate the association of islet autoantibodies [ glutamic acid decarboxylase antibody(GADA),protein tyrosine phosphatase antibody(IA-2A)and insulin autoantibodies(IAA)1 with HLA- DQ genotypes in the first-degree relatives of autoimmune type 1 diabetes mellitus.Methods This was a cross- sectional and case-control study.Three hundred and fifty-one first-degree relatives with normal glucose tolerance of patients with type 1 diabetes mellitus and 376 healthy controls were recruited and measured for GADA,IA-2A and IAA by radioligand assay,and 156 first-degree relatives of patients with autoimmune type 1 diabetes mellitus and 278 controls were typed for genetic polymorphisms of HLA-DQ with PCR sequencing-based typing method.Results (1)DQA1*03,DQBI*0303,*0401 alleles and DQA1 * 03-DQBI * 0303,DQA1 * 05-DQBI * 0201,DQA1 * 03-DQBI * 0401 haplotypes were significantly increased in the first-degree relatives of autoimmune type 1 diabetes mellitus(P

OBJECTIVEThis study was to explore the cytotoxic effect and the related injury mechanism of deoxynivalenol (DON) on articular chondrocytes in human embryo.

METHODSArticular cartilage cells were isolated from knees of human embryo and cultured in DMEM/F12 medium. The cells of the 4th generation were divided into five groups and incubated with varying concentrations of DON as the followings: control group and group with DON of 0.1, 0.2, 0.4, 1.0 µg/ml. The effects of DON were observed 72 hours after incubation. Cell apoptosis was assayed by flow cytometry (FCM) with Annexin V-FITC/PI staining; MMP-13 and PGE2 were detected by ELISA kits; NO was measured by Griess assay with spectrophotometer. Inducible nitric oxide synthase (iNOS) and collagen II in cells were detected by FCM. The expression levels of iNOS, mRNA and collagen II mRNA were measured with RT-PCR.

RESULTSThe rates of cell apoptosis in DON groups were 6.78% - 19.05%, which were significantly higher than that in control (1.20%, F = 174.761, P < 0.05). The levels of NO in DON groups were 20.8 - 40.7 µmol/L, which were significantly higher than that in control (10.2 µmol/L, F = 91.966, P < 0.05). The levels of MMP-13 in DON groups were 0.25 - 0.56 µmol/L, which were significantly higher than that in control (0 µmol/L, F = 78.420, P < 0.05). The levels of PGE2 in DON groups were 3.2-20.6 µmol/L, which were significantly higher than that in control (11.6 µmol/L, F = 276.453, P < 0.05). The proportions of cells with positive iNOS in DON groups were 14.8% - 56.8% which were significantly higher than that in controls (7.1%, F = 214.614, P < 0.05). The proportions of cells with positive collagen II in groups with DON of 0.4 µg/ml and 1.0 µg/ml were 56.7% and 52.7%, which were significantly lower than that in control (62.2%, F = 5.134, P < 0.05). The relative absorbance values of iNOS mRNA in DON groups were 1.07 - 1.33, which were significantly higher than that in control (0.62, F = 8.358, P < 0.05). The levels of collagen II mRNA in groups with DON of 0.4 µg/ml and 1.0 µg/ml were 0.83 and 0.82, which were significantly lower than that in control (1.14, F = 7.887, P < 0.05).

CONCLUSIONDON could promote anabolism of NO in articular cartilage cells by which up-regulated the expression of PGE2 and MMP-13, which both promoted resolution of articular cartilage matrix such as collagen II. DON induced apoptosis in articular cartilage cells.

Cartilage, Articular ; cytology ; embryology ; Cells, Cultured ; Chondrocytes ; drug effects ; metabolism ; Dinoprostone ; metabolism ; Humans ; Matrix Metalloproteinase 13 ; metabolism ; Nitric Oxide ; biosynthesis ; Trichothecenes ; toxicity