Objective To investigate the effects of growth differentiation factor 11 ( GDF11 ) on β-cell function in db/db mice and its possible mechanism. Methods Twenty eight-week-old male db/db mice were randomizedtoi.p. administration of GDF11(0.3mg·kg-1·day-1)or equivalent PBS(n=10)for 6 weeks.10age-matched male db/m were used as normal control, received equivalent PBS injection for 6 weeks. Blood glucose levels, body weights and food intake were monitored weekly. IPGTT and glucose-stimulated insulin secretion ( GSIS) were analyzed. After 6 weeks of intervention, serum HbA1C , TG, TC, and FFA were measured respectively. The concentrations of hormones in serum and pancreas were evaluated. The mRNA expression of Pdx-1, MafA, Nkx6. 1, and insulin2 were determined by RT-PCR. The expression of phosphorylated Smd2 (P-Smad2), Smad2 in islet were examined by western blot. Results Compared with NC group, GDF11 administration decreased FBG, HbA1C , modified lipid profiles. GDF11 improved glucose tolerance and augmented GSIS. Moreover, GDF11 increased serum insulin and pancreatic insulin content, while decreased serum glucagon concentration. The expression of Pdx-1, MafA, Nkx6. 1, and Insulin2 were significantly increased in GDF11 group. GDF11 elevated the expression of P-Smad2 in islets. Conclusion s GDF11 may preserve β-cell function and facilitate the secretion and production of insulin. Diminishing the metabolic abnormalities, alleviating the secretion of glucagon, as well as maintaining the key transcript factor activation may contribute to the amelioration of β-cell function after GDF11 administration. Smad2 pathway may be related to the protective effects of GDF11.

Objective To investigate the effect of growth differentiation factor 11 ( GDF11 ) on aorta in apolipoprotein E-Null( ApoE-/-) mice and its possible mechanisms. Methods Four-week-old healthy male ApoE-/-mice were fed with high-fat diet for 1 week and were then divided into 4 groups:vehicle group(n=10), GDF11 group (n=10),adeno-associated virus-green fluorescent protein group(AAV-GFP group, n=10), and AAV-GDF11 group ( n=10 ) . The mice received intraperitoneal injection with phosphate buffered saline, GDF11 protein, a single injection of purified AAV-GDF11 or AAV-GFP through the tail vein, respectively. After 4 weeks, serum GDF11/8 level and endothelium-dependent vasodilatation were detected. After 12 weeks, serum GDF11/8, interleukin-6 (IL-6), tumor necrosis factor-α( TNF-α), total cholesterol ( TC), triglycerides ( TG), oxidized low density lipoprotein(ox-LDL), and free fatty acids(FFA)levels were measured, the plaque areas in aortic enface and cross sections were measured by oil red O or HE staining, the macrophages/T lymphocytes infiltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, TNF-α, and IL-10 were determined by real-time PCR. Results Compared with vehicle or AAV-GFP groups, GDF11 and AAV-GDF11 groups presented improved endothelium-dependent vasodilatation, decreased levels of blood inflammatory factors, blood lipid, reduced plaque on face area sections[Vehicle group : GDF11 group:(31. 23 ± 3. 12)% vs (17. 18 ± 2. 17) %;AAV-GFP group : AAV-GDF11 group:(38.01±4.43)% vs(14.54±2.86)%,P<0.05]andcrosssections[Vehiclegroup :GDF11 group:(19. 87 ± 2. 11)% vs (10. 32 ± 1. 47)%;AAV-GFP group : AAV-GDF11 group:(23. 02 ± 2. 76)%vs (9.06±1.63)%, P<0. 05]. There were less macrophages and T lymphocytes infiltration in plaques and lower mRNA expressions of inflammatory factors at aortic wall. Conclusion GDF11 reduces the area of atherosclerotic lesion in ApoE-/-mice, which may be involved in endothelial protection, such as to reduce inflammatory reaction, and to change cellular composition in plaques.

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.
Administration, Oral ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Medicine, Chinese Traditional ; Metabolomics ; Proton Magnetic Resonance Spectroscopy ; Qi ; Rats ; Spleen

OBJECTIVETo discuss the influence of reducing buccolingual width of artificial crown on distribution of biting force and masticatory efficiency in unilateral distal-extension implant denture and provide valuable information for the design of buccolingual width. To find a design that the biting force of implant prothesis was less evident than those on the contralateral natural teeth without compromising masticatory efficiency.

METHODST-Scan II occlusal analyzer and 722 grating spectrophotometer were used to analyze the distribution of biting force and masticatory efficiency in unilateral distal-extension implant denture. Heat-cured resin crowns with three different buccolingual width (group A: standard buccolingual width; group B: the buccolingual width was reduced by 1/4; group C: the buccolingual width was reduced by 1/3) were designed as follow, one was contoured with standard buccolingual width, the other two were made with reducd buccolingual width by 1/4 and 1/3.

RESULTSThe ratio of biting force (ROF) of group C was 16.25%, which was significantly lower than group A (27.38%) and B (22.60%) (P < 0.0083). The X axis displacement of center of occlusal force (COF) of group C was 2.0 mm, which was significantly difference with group A (1.5 mm, P = 0.004). The masticatory efficiency absorbance A value (MEA) of group C was 0.217, which was significantly lower than group A (0.345, P = 0.005) and B (0.289, P = 0.004).

CONCLUSIONSAccording to the study, the buccolingual width of the crown reduced by 1/4 was a more ideal design for unilateral distal-extension implant denture.

Adult ; Aged ; Bite Force ; Crowns ; Dental Occlusion ; Dental Prosthesis Design ; Dental Prosthesis, Implant-Supported ; Female ; Humans ; Male ; Mastication ; Middle Aged ; Spectrophotometry

OBJECTIVETo study the levels and roles of cytokines TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).

METHODSThe levels of TNF-α, IL-6 and IL-10 in BALF were measured using ELISA in children with MPP at acute stage (n=45) and at remission stage (n=30). Twenty children without lung lesions severed as the control group.

RESULTSThe TNF-α, IL-6 and IL-10 levels in BALF were higher in children with MPP at acute stage than those in the control group (P<0.05). The levels of TNF-α and IL-6 in BALF at remission stage were reduced to the levels similar to the control group and were significantly lower than those at the acute stage in children with MPP. However, the levels of IL-10 in BALF remained at higher levels at remission stage in children with MPP.

CONCLUSIONSThe levels of TNF-α, IL-6 and IL-10 in BALF increase in children with MPP at acute stage, suggesting that the cytokines may be involved in the pathogenesis of MPP.

Adolescent ; Bronchoalveolar Lavage Fluid ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Interleukin-10 ; analysis ; Interleukin-6 ; analysis ; Male ; Pneumonia, Mycoplasma ; etiology ; immunology ; Tumor Necrosis Factor-alpha ; analysis

Stimulation of cardiac mAChRs by carbachol (CCh) produces a biphasic inotropic response. The mechanisms of the positive inotropic response by higher concentration of CCh appear to be paradoxical. This article was aimed to study the mechanism of the positive inotropic effect of CCh in guinea pig ventricular myocytes. The effects of CCh on L-type calcium current (I(Ca)) and Na/Ca exchange current (I(Na/Ca)) were observed in voltage-clamped guinea pig ventricular myocytes by using Axon 200A amplifier. The results showed that CCh (100 micromol/L) increased both forward mode and reverse mode I(Na/Ca) from (1.2+/-0.1) pA/pF to (2.0+/-0.3) pA/pF for forward mode (P<0.01) and from (1.3+/-0.5) pA/pF to (2.1+/-0.8) pA/pF for reverse mode (P<0.01), respectively. CCh had no effect on I(Ca). The stimulating effect of CCh on I(Na/Ca) could be blocked by application of atropine, a nonselective blocker of muscarinic receptors, which means that the stimulating effect of CCh is through the activation of muscarinic receptors. We made a further study by using methoctramine, a selective antagonist of M2 muscarinic receptors. It completely abolished I(Na/Ca) induced by 100 micromol/L CCh, indicating that the effect of CCh on I(Na/Ca) was mediated by M2 muscarinic receptors. It is generally accepted that contraction in cardiac myocytes results from elevation of intracellular Ca2+ concentration. Ca2+ enters the cells through two pathways: L-type Ca2+ channels and, less importantly, reverse mode Na/Ca exchange. The calcium influx via both pathways promotes the contraction of cardiac myocytes. Because CCh had no effect on L-type Ca2+ current, the increase in Na/Ca exchange current might be the main factor in the positive inotropism of CCh. These results suggest that the positive inotropic effect of CCh in guinea pig heart is through stimulation of Na/Ca exchange and is mediated by M2 muscarinic receptors.
Animals ; Calcium Channels, L-Type ; physiology ; Carbachol ; pharmacology ; Cardiotonic Agents ; pharmacology ; Diamines ; pharmacology ; Female ; Guinea Pigs ; Heart Ventricles ; Male ; Myocytes, Cardiac ; metabolism ; physiology ; Patch-Clamp Techniques ; Receptor, Muscarinic M2 ; physiology ; Sodium-Calcium Exchanger ; physiology

OBJECTIVETo observe the sedative and analgesic effects of transcutaneous electrical acupoint stimulation (TEAS) in patients with artificial abortion operation.

METHODSNinety patients, with American Society of Anesthesiologists (ASA) physical status I - II, and scheduled for artificial abortion operation, were randomly divided into three groups, 30 cases in each group. The patients in group A were treated with TEAS on Neiguan (PC 6) and Taichong (LR 3), in group B with paracervical block anesthesia (BA), and in group c with both TEAS and BA. Continuous monitoring of the mean arterial blood pressure (MAP), heart rate (HR), oxygen saturation and bispectral index (BIS) of the patients lasted to 30 min after the operation. The BIS, Visual Analogue Scale (VAS) during the operation and the adverse reactions after the operation were analyzed.

RESULTSAfter 15 minutes TEAS, the BIS in group A and C were decreased significantly, with no significant difference between the two groups (P > 0.05) and being both better than that in group B (both P < 0.05), which had no significant change. There were no significant differences in the VAS among the three groups (all P > 0.05), while the adverse reactions in both group A and C were lower than that in group B (both P < 0.05).

CONCLUSIONTEAS has sedative and analgesic effect during artificial abortion operation and can decrease the adverse reactions.

Abortion, Induced ; adverse effects ; Acupuncture Analgesia ; Acupuncture Points ; Adult ; Electroacupuncture ; Female ; Heart Rate ; Humans ; Oxygen ; metabolism ; Pain ; metabolism ; physiopathology ; Pain Management ; Pain Measurement ; Young Adult

The effects of 5-(N,N-dimethyl)amiloride (DMA) (a blocker of Na(+)/H(+) exchanger or Na(+)/Ca(2+) exchanger) on calcium transient and cell contraction in isolated ventricular myocytes in normal rats and rats with myocardial hypertrophy were examined using ion imaging system with a charge coupled digital camera (CCD camera). Loading myocytes with Fura-2, electrically triggered Ca(2+) transients and cell shortening were measured simultaneously. The results showed that 10 micromol/L DMA increased Ca(2+) transient and cell shortening from 209.60+/-54.96 and 3.07+/-0.97 micrometer to 238.50+/-80.41 and 4.07+/-1.02 micrometer, respectively (P<0.05), which was completely abolished by application of KB-R7943, a specific reverse mode Na(+)/Ca(2+) exchanger blocker. After blocking L-type Ca(2+) channels by nicardipine, DMA also enhanced Ca(2+) transient and cell shortening. In rats with myocardial hypertrophy, DMA showed the common pharmacologic profile as in normal rats but more intense stimulating effects on Ca(2+) transient and cell contraction. The results suggest that DMA increase Ca(2+) transient and cell contraction via stimulating reverse mode Na(+)/ Ca(2+) exchange, and the stimulating effect is more pronounced in rats with myocardial hypertrophy than in normal ones.
Amiloride ; analogs & derivatives ; pharmacology ; Animals ; Calcium ; metabolism ; Cardiomyopathy, Hypertrophic ; drug therapy ; Heart Ventricles ; cytology ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar ; Sodium-Calcium Exchanger ; antagonists & inhibitors ; pharmacology

With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.
Drug Discovery ; methods ; Drug Therapy ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Humans ; Medicine, Chinese Traditional

OBJECTIVETo observe the effect of moxibustion at Sanyinjiao (SP 6) on delivery stage of primipara.

METHODSSixty cases of primipara were divided into a moxibustion at Sanyinjiao group, a non-acupoint group and a blank group. When the diameter of wormb mouth opened to 2-3 cm, showing that it entered into active stage of uterine contraction, moxibustion at Sanyinjiao (SP 6) for primipara was applied in moxibustion at Sanyinjiao group; moxibustion was applied at 1 cun towards radialis from the region where 2 cun above Kongzui (LU 6) in non-acupoint group, 30 minutes treatment was for both groups. There was no intervention in blank group. After delivery, the time of first,second and third delivery stages and postpartum bleeding 2 hours after delivery were compared among three groups.

RESULTSThe active duration of first delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (P < 0.05, P < 0.01); the duration of the second delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (both P < 0.05) as well; the postpartum bleeding 2 hours after delivery in moxibustion at Sanyinjiao group was less than other two groups and the difference was statistic significant between moxibustion at Sanyinjiao group and blank group (P < 0.05).

CONCLUSIONBy moxibustion at Sanyinjiao (SP 6), the active duration of first delivery stage and the duration of second delivery stage are markedly shortened, postpartum bleeding 2 hours after delivery is obviously reduced, and the safety of vaginal delivery is increased.

Acupuncture Points ; Adult ; Delivery, Obstetric ; Female ; Humans ; Labor Onset ; Moxibustion ; Postpartum Hemorrhage ; therapy ; Pregnancy ; Young Adult