1.Potassium channels and the modulators in vascular smooth muscle cells
Yuge JIANG ; Hai WANG ;
Chinese Pharmacological Bulletin 1986;0(05):-
It is well documented that vascular tone is the key determinant of blood vessel resistance and blood flow. But vascular tone could be regulated by modulating the activity of potassium channel directly. Potassium channel openers promote vasodilation by inhibiting the activity of voltage dependent calcium channels and reducing Ca 2+ influx. In this case, inhibition results from membrane hyperpolarisation, which arises due to the stimulation of K + efflux through smooth muscle K + channels. While K + channels are blocked, vasoconstriction could be observed as a result of membrane depolarization, which opens voltage dependent calcium channels. The influx of Ca 2+ can promote smooth muscle contraction by making myosin light chain phosphorylation and arising thick myofilament and thin myofilament relative movements. In this article, the gene structure, current character, Pharmacological and physiological effects of the four subtypes potassium channels are reviewed.
2.Advance in study and application of magnesium potassium phosphate cement as a new generation of biomaterials for skeleton system repair
Daqing HAN ; Hai WANG ; Liqin JIANG
International Journal of Biomedical Engineering 2013;36(6):376-380
A kind of magnesium potassium phosphate cement developed for bone repair was cleared by FDA in 2009 and has been presently in clinical use in America.The biomaterial has the powerful adhesive capability to bind bone,ligament,and tendon to bone,as well as possessing good biocompatiblity,appropriate biodegradability and osteogenicity; to data,it is the only material which possesses the combination of adhesivity and osteogenicity among bone repair biomaterials.The clinical application of the innovative biomaterial will unprecedentedly alter the treatment in orthopedic surgery and related disciplines.To provide a comprehensive appreciation of the innovative biomaterial,this article summaries its development,characteristics of composition and preparation,formation mechanism,application study and superiority.
4.Effects of total flavonoids of propolis on apoptosis of myocardial cells of chronic heart failure and its possible mechanism in rats.
Hai-hua WANG ; Jin ZENG ; Hai-zhen WANG ; Yu-xin JIANG ; Jing WANG ; Ping-ping ZHOU
Chinese Journal of Applied Physiology 2015;31(3):201-206
OBJECTIVETo investigate the effects of total flavonoids of propolis (TFP) on apoptosis of myocardial cells of chronic heart failure and its possible mechanism in rats.
METHODSSix male SD rats were randomly selected as normal control group, the remaining rats were made as chronic heart failure (CHF) model by intraperitoneal injection of adriamycin. The rats in the successful model were randomly divided into five groups (n = 6): CHF group, total flavonoids of propolis low dose group (LD group), total flavonoids of propolis middle dose group (MD group), total flavonoids of propolis high dose group (HD group), digoxin group (DIG group). After six week treatment, cardiac function indexes of rats were recorded by signal acquisition system; brain natriuretic peptide (BNP), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) content in plasma were detected; Myocardial morphological changes and collagen fiber hyperplasia by HE and Masson staining were observed; Myocardial apoptosis was detected with TUNEL method and protein connexin 43(P-Cx43) expression was detected by Western blot method.
RESULTSCompared with NC group, left ventricular systolic pressure(LVSP) and maximal rise/fall velocity of left ventriculad pressure (± dP/dt(max)) absolute value in CHF group were significantly lowered (P < 0.01) while left ventricular end diastolic pressure (LVEDP) was increased significantly (P < 0.01); Contents of plasma BNP, cTnI, TNF-α and IL-6 in the CHF group were significantly improved (P < 0.01). Compared with CHF group, LVSP, ± dP/dt(max) absolute value in MD and HD groups were increased (P < 0.05), and LVEDP was significantly lowered (P < 0.01); LVEDP in LD group was significantly lowered (P < 0.01), changes in LVSP and ± dp/dt(max) absolue value were not obvious (P > 0.05). BNP, cTnI, TNF-α and IL-6 contents in MD and HD groups were significantly reduced (P < 0.01), but those plasma indicator changes were not obvious in LD group (P > 0.05). Western blot showed that P-Cx43 expression in CHF group was significantly higher than that in NC group (P < 0.01) and that in all TFP treatment groups it was decreased compared with CHF group (P < 0.05, P < 0.01), among which pairwise comparisons also showed differences (P < 0.05), myocardial apoptosis index (%)(22.62 ± 3.39) in CHF group was higher than that in NC group( 1.12 ± 0.24) (P < 0.01); compared with CHF group, the apoptosis index of myocardial cells (%) in LD,MD and HD groups, (15.79 + 2.8), (9.28 + 2.1) and (4.73 + 1.14) respectively, were significantly lower than those in the CHF group( P < 0.01). The expression level of P-Cx43 positively correlated with the apoptotic index (r = 0. 861, P < 0.01).
CONCLUSIONTotal flavonaids of propolis have inhibitory effect on apoptosis of myocardial cells of chronic heart failure induced by adriamycin in rats, and the mechanism may be closely related to the regulation of Cx43 expression, especially the regulatory phosphorylation status.
Animals ; Apoptosis ; Chronic Disease ; Connexin 43 ; metabolism ; Disease Models, Animal ; Doxorubicin ; adverse effects ; Flavonoids ; pharmacology ; Heart Failure ; drug therapy ; Interleukin-6 ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Natriuretic Peptide, Brain ; blood ; Phosphorylation ; Propolis ; chemistry ; Rats ; Rats, Sprague-Dawley ; Troponin I ; blood ; Tumor Necrosis Factor-alpha ; blood
5.Lead compound optimization strategy (2)--structure optimization strategy for reducing toxicity risks in drug design.
Hai-Long LIU ; Jiang WANG ; Dai-Zong LIN ; Hong LIU
Acta Pharmaceutica Sinica 2014;49(1):1-15
Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites
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Cytochrome P-450 Enzyme System
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metabolism
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Drug Design
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Drug Discovery
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methods
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Drug Recalls
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Drug-Related Side Effects and Adverse Reactions
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prevention & control
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Humans
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Structure-Activity Relationship
6.Effects of mild moxibustion on imbalance of Th1/Th2 in rabbits with atherosclerosis and its regulating rules.
Shan WU ; Ling-Ling WANG ; Hai-Hong CAI ; Wen JIANG
Chinese Acupuncture & Moxibustion 2014;34(2):163-167
OBJECTIVETo observe effects of mild moxibustion and lovastatin on immunologic function in rabbits with chronic hyperlipidaemia and atherosclerosis (AS) to initially explain regulating rules of mild moxibustion on immunologic function.
METHODSAmong thirty-two Japanese male big-ear rabbits, 8 rabbits were randomly selec ted as a blank group, the rest 24 rabbits were fed with method of endothelial injury and high-fat diet to establish AS model. The blank group was raised with normal diet and free water. After ten weeks of model establishment, the rest 24 rabbits were randomly divided into a model group, a moxibustion group and a medicine group, eight rabbits in each one. Moxibustion was applied at "Shenque" (CV 8) and "Zusanli" (ST 36) for 10 min per acupoint per day in the moxibustion group, while intragastric administration of 3.6 mg/kg lovastatin capsule was applied in the medicine group. After treatment, serum was acquired. Spectrophotometry method was adapted to measure cholesterol (TC) and high-density lipoprotein (HDL-C) and evaluated atherosclerosis index (AI), while enzyme-linked immunosorbent assay method was used to measure interferon-gamma (IFN-gamma) and interleukin-4 (IL-4).
RESULTS(1) The serum TC and HDL-C in the model group were significantly higher than those in the blank group, moxibustion group and medicine group (all P < 0.01). The mean value of AI was 1.683 +/- 0.486 in the moxibustion group, which was obviously lower than 20.301 +/- 4.022 in the model group (P < 0.01). (2) The ratio of Th1/Th2 was 0.569 +/- 0.143 in the moxibustion group and 0.445 +/- 0.079 in the medicine group, which were significantly lower than 0.917 +/- 0.255 in the model group (both P < 0.01), but there was no statistically significant difference between the moxibustion group and the medicine group (P > 0.05).
CONCLUSIONThe moxibustion for AS could reduce atherosclerosis index, influence drift and bias of helper T cell and regulate balance between humoral immunity and cellular immunity. As a result, status of relative balance of immunity is acquired, which could slow down the development of atherosclerosis and process of thrombus burst.
Animals ; Atherosclerosis ; immunology ; therapy ; Humans ; Hyperlipidemias ; immunology ; therapy ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Male ; Moxibustion ; Rabbits ; Th1 Cells ; immunology ; Th2 Cells ; immunology
7.Effects of heat stress response on neutrophil apoptosis and respiratory burst function
gang, ZHAO ; hai, GAO ; xue-ming, WANG ; wei, JIANG
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(08):-
Objective To explore effects of heat stress response on neutrophil apoptosis and respiratory burst function. MethodsNeutrophils from each of 18 healthy volunteers were divided into 3 parts,and one part was served as control group,and the other two parts were induced by heat shock or cadmium chloride for heat stress response and named as heat shock group and cadmium chloride group.The neutrophils were incubated in culture medium.At 0,2,3,4,and 6 h following heat stress induction,the heat shock protein(HSP70) expression and the respiratory burst were detected in the neutrophils respectively by using PCR technique and flow cytometer.Level of apoptosis was observed by immuno-fluorescence and flow cytometer DNA ploid at 24 h after heat stress induction. Results In the heat shock and cadmium chloride groups,HSP70 expression at each time point and cell apoptosis at 24 h were significantly higher than those of control group(P
8.Relationship between carbachol hyperstimulation-induced pancreatic acinar cellular injury and trypsinogen or NF-kappaB activation in rats in vitro.
Zheng, HAI ; Chunfang, JIANG ; Jinxiang, ZHANG ; Linfang, WANG ; Kaifeng, FANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2006;26(1):34-5, 58
The relationship between M3 cholinergic receptor agonist (carbachol) hyperstimulation-induced pancreatic acinar cellular injury and trypsinogen activation or NF-kappaB activation in rats was studied in vitro. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc), and NF-kappaB inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The cellular injury was evaluated by measuring the leakage of LDH from pancreatic acinar cells. The results showed that as compared with control group, 10(-3) mol/L carbachol induced a significant increase of the intracellular trypsin activity and the leakage of LDH from pancreatic acinar cells. Pretreatment with 2 mmol/L pefabloc could significantly decrease the activity of trypsin and the leakage of LDH from pancreatic acinar cells (P < 0.01) following the treatment with a high concentration of carbachol (10(-3) mol/L) in vitro. The addition of 10(-2) mol/L PDTC didn't result in a significant decrease in the activity of trypsin and the leakage of LDH from pancreatic acinar cells treated with a high concentration of carbachol (10(-3) mol/L) in vitro (P > 0.05). It was concluded that intracellular trypsinogen activation is likely involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro. NF-kappaB activation may not be involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro.
Carbachol/*pharmacology
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Cholinergic Agonists/pharmacology
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NF-kappa B/*metabolism
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Pancreas/metabolism
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Pancreas/*pathology
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Rats, Wistar
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Receptor, Muscarinic M3/agonists
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Trypsinogen/*metabolism
9.Operative treatment to spinal multi-level tuberculosis
Yingang ZHANG ; Bing WANG ; Wentao ZHANG ; Hai JIANG ; Xiong GUO
Chinese Journal of Rehabilitation Theory and Practice 2003;9(9):558-559
ObjectiveTo investigate the effect of operation treating spinal multi-level tuberculosis.Methods45 patients with multi-level spine tuberculosis were treated with debridement completely and anterior or lateral-anterior intervertebrae autograft. Of them, 5 patients added to anterior instrumentation.Results45 patients had been followed up for 12 to 40 months.The back pain of 40 cases were relieved within 5 weeks after operation, erythrocyte sedimentation rate decreased 3 weeks after operation. 38 patients who involved in kyphosis decreased their kyphosis mostly and only one patient lost 3 degrees in follow-up.15 patients who involved in neurological deficits improved one or two grades (Frankel). Grafts fused in 44 patients and there were no recurrent in follow-up.Conclusions Operative treatment is efficacious to multi-level body spine tuberculosis.
10.Delayed postoperative infection in deep site of fracture of lumbar vertebrae treated through anterior approach: a case report.
Gang-xiang WANG ; Xiang-jiang ZHU ; Hai-dong ZHOU
China Journal of Orthopaedics and Traumatology 2015;28(1):55-57
Adult
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Humans
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Lumbar Vertebrae
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injuries
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Male
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Spinal Fractures
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surgery
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Surgical Wound Infection
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therapy