OBJECTIVETo observe the therapeutic effect and relevant mechanism of shuxuening Injection (SI) in treating patients with active ulcerative colitis (UC).

METHODSTotally 91 patients with active UC were randomly assigned to 2 groups, 44 in the control group and 47 in the treatment group. Patients in the control group received routine treatment, while patients in the treatment group additionally received intravenous injection of SI (15 mL), twice daily for 14 days in total. Colonoscopy was performed before and after treatment. The therapeutic effect was assessed by Mayo scoring system and the grading of activities evaluated by Baron endoscope. Serum levels of IL-6 and TNF-α were detected by ELISA. The activity of SOD was detected by xanthine oxidase method. The content of MDA was detected by thiobarbituricacid (TBA). Besides, 20 healthy subjects were recruited as the healthy control group.

RESULTSTotally 82 patients completed the study (40 in the control group and 42 in the treatment group). There was no statistical difference in serum levels of IL-6, TNF-α, SOD, MDA, the Mayo score and endoscope grading between the two groups before treatment (P >0. 05). Compared with the healthy control group, serum levels of IL-6, TNF-α, MDA significantly increased (P <0.01), and the serum SOD level decreased (P < 0. 05) in the treatment grup and the control group before treatment. Compared with before treatment in the same group, serum levels of IL-6, TNF-α, MDA, the Mayo score and endoscope grading all decreased in the treatment group and the control group after treatment (P <0. 01, P <0. 05). Compared with the control group after treatment, serum levels of IL-6, TNF-α, MDA, the Mayo score and endoscope grading all decreased (P <0.01, P <0.05), the serum SOD level increased (P <0.05) in the treatment group after treatment. The serum SOD level was obviously negative correlated with serum levels of IL-6, TNF-a, Mayo score, and endoscope score (r = -0. 621, -0.638, -0. 509, -0.787, P <0.01). The serum MDA level was obviously positive correlated with serum levels of IL-6, TNF-α, Mayo score, and endoscope score (r =0.711, 0. 882, 0. 525, 0. 639, P <0.01).

CONCLUSIONSI could improve inflammatory injury and clinical symptoms of patients with active UC, and its mechanism might be associated with antioxidant and scavenging oxygen free radicals.

Colitis, Ulcerative ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Inflammation ; drug therapy ; Interleukin-6 ; blood ; Tumor Necrosis Factor-alpha ; blood

Objective To explore if continuous administration of adenosine by peripheral pathway can attenuate myocardial hypertrophy and pulmonary arterial hypertension(PAH)caused by chronic hypoxia and analyze the dose-effect relationships between them.Methods Forty-eight Sprague-Dawley(SD)rats were randomly divided into 8 groups:the hypoxia group(n=6),the hypoxia ade-nosine-treated groups [n=18,adenosine was administrated with different doses 50,100,150 ?g/(kg?min),the hypoxia adenosine-treated group A,B,C],the control group(n=6),the control adenosine-treated control groups [n=18,adenosine was administrated with different doses 50,100,150 ?g/(kg?min),the control adenosine-treated control group A,B,C].On the 21st day of the experiment,the Medlab-U/4CS was used to determined the right ventricular systolic pressure(RVSP)and the mean pulmonary arterial pressure(mPAP)of each rat.The ratio of the weight of right ventricle/left ventricle and septum[RV/(LV+S)] and the ratio of the weight of right ventricle/body weight(RV/BW)were also calculated.The morphological changes in myocardium cells and pulmonary vascular structure were observed.SAS 8.0 software was used to analyze the data.Results Twenty-one days after hypoxia,RVSP,mPAP,RV/(LV+S),RV/BW in hypoxia groups were higher significantly than those in control group and hypoxia adenosine-treated groups(Pa

Objective To study the effect of fluorine on the bone histomorphometry of humbar in rats.Methods Ninety 2-month-old SPF Sparague-Dawley rats,half male and female,were randomly divided into 9 groups:control[(childhood(CS),adult(AS),long-time(NS)]group and drug group[childhood high-fluoride and low-fluoride group(CHS,CLS),adult high-fluoride and low-fluoride(AHS,ALS),long-term high-fluoride and low-fluoride(CLHS,CLLS)].The control group was administered orally with solution of 0.9%NaCl,while the drug group was given orally with different dose of NaF at the same time. Sections of the fifth lumbar were made which was undecalicified for bone histomorphometric analysis, including the percentage of trabecular bone area (% Tb.Ar),trabecular thickness(Tb.Th), trabecular number(Tb.N), trabecular separation(Th.Sp) ; broken trabecular bone area cells (Oc.N), osteoclast perimeter percentage (% Oc.Pm), the percentage of labeled perimeter (% L.Pm), bone mineral apposition rate(MAR), osteoblast perimeter(Ob.PM), trabecular bone perimeter formation rate (BFR/BS),trabecular bone area formation rate (BFR/BV), the total area of bone formation rate (BFR/TV). Results [1]The percentage of Tb.Ar, Tb.Th, Tb.N,%L.Pm, MAR, BFR/BS, BFR/BV and BFR/TV of CHS group [(50.63 ±7.44)%, (150.26 ± 27.51 )μm, (3.44 ± 0.47)N/mm, (50.63 ± 7.44)%, (0.85 ± 0.03)μm/d, (8.45 ± 2.36)μm/d ×100, (381.16 ± 41.62)%/year, (75.07 ± 4.81)%/year] was higher than that of CS group [(29.71 + 9.32)%,(110.93 ± 28.19)μm, (2.68 ± 0.34)N/mm, (24.00 ± 1.22)%, (0.65 ± 0.03)μm/d, (5.43 ± 0.18)μm/d × 100,(141.32 ± 9.29)%/year, (58.14 ± 2.3)%/year, all P < 0.05)]. The %Tb.Ar, Tb.Th, %L.Pm, MAR, BFR/BS,BFR/BV, BFR/TV and Ob.PM of CLS group [(40.76 ± 6.43)%, (164.25 ± 45.65)μm, (42.02 ± 6.12)%, (0.85 ±0.04)μm/d, (8.95 ± 3.73)μm/d × 100, (378.73 ± 35.39)%/year, (73.52 ± 8.71)%/year, (1.41 ± 0.05)μm] were increased (all P < 0.05). [2]Compared with AS group, the %Tb.Ar,Oc.N, %Oc.Pm, %L.Pm, MAR, BFR/BS,BFR/BV and BFR/TV of AHS group[ (50.62 ± 5.76)%, (0.51 ± 0.05)N/mm, (1.13 ± 0.05)%, (42.3 ± 7.02)%,(1.28 ± 0.09)μm/d, (12.91 ± 1.52)μm/d × 100, (390.12 ± 43.56)%/year, (65.21 ± 22.13)%/year] was higher than that of AS group[ (42.73 ± 5.22)%, (0.41 ± 0.17)N/ram, (0.77 ± 0.52)%, (28.43 ± 6.93)%, (0.80 ± 0.03)μm/d, (9.83 ± 1.44)μm/d × 100, (324.43±53.44)%/year and(48.35 ± 9.36)%/year, all P < 0.05)] . The %Tb.At, Oc.N, %Oc.Pm, %L.Pm, MAR, BFR/BS, BFR/BV and BFR/TV of ALS group [(51.14 ± 6.22)%, (0.49 ±0.61)N/mm, (1.17 ± 0.11)%, (45.06 ± 6.92)%, (1.39 ± 0.08)μm/d, (12.87 ± 1.35)μm/d × 100, (394.6 ±50.23)%/year and(66.31 ± 18.93)%/year] were higher than that of AS group(P < 0.05) .[3] The Ob.PM ,Oc.N and %Oc.Pm of CLHS group[ (1.47 ± 0.27)μm, (0.58 ± 0.13)N/mm, (1.14 ± 0.07)%] were obviously increased(P <0.05), as compared with NS group [ (0.82 ± 1.20)μm, (0.42 ± 0.25)N/mm and (0.75 ± 0.64)%, all P < 0.05].Conclusions The short-term administration of NaF on rats in the growing period increases the bone formation and osteoblast activities of young rats and adult rats. The long-term administration of NaF on rats does not increase the bone formation of rats in growth period. The osteoblast activities as well as the bone absorption of lumbar vertebra were strengthened. The likelihood of bone fracture became larger. The negative effects on bone metabolism and bone quality of rats were gradually displayed along with the prolongation of sodium fluoride usage.

To construct the Bac-to-Bac expression system of Bombyx mori nucleopolyhedrovirus (BmNPV), a transfer vector was constructed which contained an Escherichia coli (E. coli) mini-F replicon and a lacZ: attTN7: lacZ cassette within the upstream and downstream regions of the BmNPV polyhedrin gene. B. mori larvae were cotransfected with wild-type BmNPV genomic DNA and the transfer vector through subcutaneous injection to generate recombinant viruses by homologous recombination in vivo. The genomic DNA of budded viruses extracted from the hemolymph of the transfected larvae was used to transform E. coli DH10B. Recombinant bacmids were screened by kanamycin resistance, PCR and restriction enzyme (REN) digestion. One of the bacmid colonies, BmBacJS13, which had similar REN profiles to that of wild-type BmNPV, was selected for further research. To investigate the infectivity of BmBacJS13, the polyhedrin gene was introduced into the bacmid and the resultant recombinant (BmBacJS13-ph) was transfected to BmN cells. The budded viruses were collected from the supernatant of the transfected cells and used for infecting BmN cells. Growth curve analysis indicated that BmBacJS13-ph had a similar growth curve to that of wild-type BmNPV. Bio-assays indicated that BmBacJS13-ph was also infectious to B. mori larvae.

By reverse transcription-polymerase chain reaction (RT-PCR), an open reading frame of pathogenesis-related protein 1 (PR1) was isolated from Panax notoginseng and named as PnPR1. Molecular and bioinformatic analyses of PnPR1 revealed that an open reading frame of 501 bp was predicted to encode a 166-amino acid protein with a deduced molecular mass of 18.1 kD. Homology analysis showed that the deduced amino acid sequence of PR1 protein of Panax notoginseng had a high similarity with other higher plants had the same conservative structure domain of cysteine-rich secretory protein (CAP). The recombinant expressed plasmid pET28a(+)-PnPR1 was expressed in Escherichia coli BL21. The expression conditions were optimized by induction at different times, different temperatures, different IPTG concentrations and different giving times. The optimum expression condition was 0.4 mmol.L-1 IPTG at 28 degrees C for 20 h. The successful expression of PnPR1 provides some basis for protein purification and preparation of the monoclonal antibody.
Amino Acid Sequence ; Cloning, Molecular ; Escherichia coli ; metabolism ; Molecular Weight ; Open Reading Frames ; genetics ; Panax notoginseng ; chemistry ; Phylogeny ; Plant Proteins ; genetics ; metabolism ; Plants, Medicinal ; chemistry ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment

OBJECTIVERecent studies showed that adenosine played important roles in vasodilation. This study aimed to investigate the effects of adenosine, its A1 and A2b receptor agonists on pulmonary artery hypertension (PAH) induced by chronic hypoxia in rats by continuously subcutaneous administration with an osmotic pump for 14 days, and to see if rennin angiotensin system and inducible nitric oxygen synthase (iNOS)/nitric oxide (NO) mediate the effects.

METHODFifty-six male SD rats were randomly assigned to seven groups. Each group included eight rats. They were normoxic group, hypoxic group, adenosine-treated group [adenosine was administered at a dose of 150 µg(kg·min) under the hypoxic condition], adenosine A1 receptor agonist CPA-treated group [CPA was administered at a dose of 20 µg/(kg·min) under the hypoxic condition], CPA plus selective adenosine A1 antagonist DPCPX-treated group [CPA and DPCPX were administered simultaneously under the hypoxic condition, the dose of CPA was the same as the above, and the dose of DPCPX was 25 µg/(kg·min)], adenosine A2b receptor agonist NECA-treated group [NECA was administered at a dose of 30 µg/(kg·min) under the hypoxic condition], NECA plus selective adenosine A2b receptor antagonist MRS-treated group[ NECA and MRS1754 were administered simultaneously under the hypoxic condition, the dose of NECA was the same as the above, and the dose of MRS1754 was 50 µg/(kg·min)]. Osmotic pumps containing adenosine or selective adenosine A1 receptor agonist (CPA), or nonselective but potent adenosine A2b receptor agonist (NECA) were placed subcutaneously 7 days after hypoxia and continuously administered the agents for 14 days.Mean pulmonary artery pressure (mPAP) was detected after administration of the agents. Then blood samples were taken from heart for measurement of renin activity, angiotensin II (AngII) and endothelin-1 (ET-1) concentration by radioimmunoassay, NO by measuring nitrate. Small pulmonary arteries were prepared for immunoreactivity staining of proliferating cell nuclear antigen (PCNA) and iNOS.

RESULT(1) Chronic hypoxia induced PAH [mPAP: (31.38 ± 3.42) mm Hg]. Adenosine or CPA or NECA administered for 14 days by subcutaneous route attenuated the mPAP [(21.17 ± 3.56) mm Hg, (22.88 ± 2.95) mm Hg, (19.81 ± 2.39) mm Hg, respectively], which showed significant difference when compared with hypoxia group (P < 0.05 respectively). (2) Plasma rennin activity and AngII level in hypoxia group [(2.51 ± 0.25) ng/(ml·h), (83.01 ± 9.38) pg/ml] were significantly higher than that in normoxic group (P < 0.05, respectively).(3) Adenosine treatment decreased the rennin activity and AngII level when compared with hypoxic group(P < 0.05, respectively);CPA and NECA attenuated respectively the rennin activity and AngII level of rats induced by chronic hypoxia (P < 0.05, respectively). (4) Adenosine administration for 14 days attenuated the wall thickness induced by chronic hypoxia (P < 0.05). CPA showed no effect on wall thickness, but NECA significantly attenuated the wall thickness (P < 0.05). (5) The number of iNOS staining positive cells in small pulmonary artery was higher in hypoxia group than in that in normoxic rats (23.75 ± 7.91 vs. 8.00 ± 2.20, P < 0.05). Adenosine or CPA, or NECA administration increased respectively the iNOS expression in rats treated with chronic hypoxia. Chronic hypoxia caused significant decrease of nitric oxide level. Adenosine treatment increased the nitric oxide level in rats treated with chronic hypoxia. CPA and NECA also increased respectively the nitric oxide level in rats treated with chronic hypoxia. Chronic hypoxia caused significant increase of ET-1 level. The ET-1 level in rats treated with adenosine, CPA or NCEA respectively were lower than that in chronic hypoxia rats (P < 0.05). (6) Adenosine treatment partially attenuated the number of PCNA-positively stained cells. NECA treatment also attenuated the PCNA expression, but CPA showed no effect.

CONCLUSIONAdenosine and its agonists CPA, NECA administered continually by subcutaneous route attenuate mPAP of rats induced by chronic hypoxia. CPA attenuates mPAP through reduction of RA/AngII activity and balance of NO/ET-1 level. NECA attenuates mPAP by inhibiting PCNA expression and proliferation of mooth muscle of pulmonary artery.

Adenosine ; administration & dosage ; pharmacology ; Angiotensin II ; blood ; Animals ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Hypertension, Pulmonary ; drug therapy ; etiology ; metabolism ; Hypoxia ; complications ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type II ; metabolism ; Proliferating Cell Nuclear Antigen ; metabolism ; Pulmonary Artery ; drug effects ; physiopathology ; Purinergic P1 Receptor Agonists ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Renin ; blood

Objective: To observe the effects of liraglutide on angiogenesis and myocardium protection in acute myocardial infarction (AMI) rats with its mechanisms. Methods: Rat's AMI model was established by left anterior descending of coronary ligation. AMI rats were randomly divided into 3 groups: Control group, the rats received subcutaneous injection of normal saline, Low dose (LS) group and High dose (HS) group, rats received subcutaneous injection of liraglutide 70μg/(kg?d) and 140μg/(kg?d) respectively; in addition, Sham operation group, rats received normal saline. n=6 in each group, all animals were treated for 2 weeks. 4 weeks later, cardiac structure and function were assessed by echocardiography, morphological changes of myocardium were observed by HE staining, collagen volume fraction (CVF) was calculated by Masson staining, myocardial microvessel density (MVD) and protein expression of vascular endothelial growth factor (VEGF) in marginal zone of infracted region were detected by immunohistochemistry, VEGF protein level was examined by Western blot analysis. Results: Compared with Sham operation group, Control group showed decreased LVEF, LVFS and increased LVEDd, LVESd, CVF, all P<0.01; while MVD and VEGF protein level were similar between 2 groups, P>0.05. Compared with Control group, LS group and HS group had obviously increased LVEF, LVFS, P<0.01 and decreased LVEDd, LVESd, P<0.05, obviously decreased CVF, P<0.01; obviously elevated MVD and VEGF protein level, P<0.01. Compared with LS group, HS group presented obviously increased LVEF, LVFS, P<0.01 and decreased LVEDd, LVESd, CVF, P<0.05; elevated MVD and VEGF protein level, P<0.01 or P<0.05. Conclusion: Liraglutide could improve angiogenesis in AMI rats which might be related to increased VEGF expression and reduced collagen deposition; therefore improve left ventricular systolic function for cardiac protection. The effect had certain relationship to liraglutide dosage.

OBJECTIVETo observe the effects of continuous subcutaneous adenosine infusion on pulmonary hypertension in chronically hypoxic rats.

METHODSTwenty-four SD rats were randomized into normoxic group, hypoxic group and adenosine-treated hypoxic group. Hypoxic environment was simulated in a chamber filled with 10% oxygen and 90% nitrogen. After 7 days of hypoxia, adenosine were administered subcutaneously in the rats in adenosine-treated group at the rate of 100 microg kg(-1) min(-1) via an Alzet micro-osmotic pump for 14 days, while the pumps in the other two groups contained normal saline. After 21 days of hypoxia, pulmonary artery pressure and tail-cuff blood pressure were measured, with the plasma rennin activity (RA), angiotensin II (AngII), endothelin (ET)-1, and nitric oxide (NO) determined. Inducible nitric oxide synthase (iNOS) expression in the pulmonary artery of the rats was detected using immunohistochemical method.

RESULTSThe mean pulmonary artery pressure (mPAP) was significantly higher in the hypoxic group than that in the normoxic group (P<0.01) and in the adenosine-treated group (P<0.01). Plasma ET-1 was significantly higher but plasma NO significantly lower in the hypoxic group than in the normoxic group (P<0.01) and the adenosine-treated group (P<0.01). iNOS expression in the pulmonary artery was higher in the hypoxic group than in normoxic group (P<0.01), and adenosine significantly increased iNOS expression in comparison with the normoxic and hypoxic groups (P<0.01). Plasma RA and AngII in the hypoxic group were significantly higher than those in the normoxic group (P<0.01) and the adenosine-treated (P<0.01).

CONCLUSIONAdenosine administered by continuous subcutaneous infusion alleviates chronically hypoxia-induced pulmonary hypertension in rats, in which rennin angiotensin system, ET-1, and iNOS/NO play a role.

Adenosine ; administration & dosage ; therapeutic use ; Animals ; Chronic Disease ; Endothelin-1 ; blood ; Hypertension, Pulmonary ; blood ; drug therapy ; etiology ; Hypoxia ; complications ; Infusions, Subcutaneous ; Male ; Nitric Oxide Synthase Type II ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System ; drug effects

OBJECTIVETo explore the characteristics of distribution of pulse pressure (PP) in Chinese population and its relationship to major cardiovascular diseases in them.

METHODSData from the Third National Blood Pressure Survey involved 882,681 subjects aged over 18 in 1991 were reanalysed for the relationship between PP and risks of major cardiovascular diseases, with t-test, chi2 test and logistic regression model. PP is defined as the difference between systolic and diastolic blood pressure.

RESULTS(1) Overall mean PP was (44.61 +/- 13.59) mm Hg for the subjects aged over 18, higher in men [(44.92 +/- 12.72) mmHg] than that in women [(44.34 +/- 14.32) mmHg]. PP increased progressively with age, and its increase accelerated significantly at age over 50 but higher in women than in men. Proportion of the subjects with PP equal to or greater than 60 mmHg was more in those aged 60 or over than that in younger ones. (2) Prevalence of stroke and myocardial infarction (MI) increased with PP and age, whether in the normotensives, or in the hypertensives or in the isolated systolic hypertensives. (3) Results of multivariate logistic regression analysis revealed that risks of stroke in the subjects with PP of (45-59) mmHg, (60-74) mmHg and over 75 mmHg were 1.9, 3.5 and 5 times as in those with PP less than 45 mm Hg, respectively, adjusted for other risk factors, and their risks of myocardial infarction (MI) were 1.2, 1.5 and 1.7 times, respectively. Furthermore, PP was significantly and independently related to the risks of stroke and MI, even adjusted for systolic and diastolic pressures.

CONCLUSIONSPrevalence of stroke and MI increased with the breadth of PP and age. Broader PP may be an important and independent predictor of risks of stroke and MI, especially in the aged people.

Adolescent ; Adult ; Aged ; Blood Pressure ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Hypertension ; epidemiology ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction ; epidemiology ; Prevalence ; Risk Factors ; Stroke ; epidemiology

OBJECTIVETo observe the expressions of α-SMA, integrin α5 and fibronectin (Fn) in acute paraquat poisoned rats and the effect of PDTC. To investigate the mechanism of paraquat-induced pulmonary fibrosis.

METHODSSprague-Dawley rats were randomly divided into three experimental groups: Control group (6 rats), PQ group (36 rats) and PQ+PDTC group (36 rats). On the 1st, 3rd, the 7th, the 14th, the 28th and the 56th day after exposure, the protein expression of α smooth muscle actin (α-SMA) was evaluated by western blot. The mRNA levels of integrin α5 and fibronectin (Fn) were analyzed with real-time quantitative PCR (RT-PCR). Meanwhile, the lung pathological changes were observed and semi-quantified.

RESULTST With the time passing, the expression of α-SMA in PQ group increased gradually compared with control group (P < 0.05 or P < 0.01). The increasing extent was gently on the 3 rd, the 7 th day. While increasing extent was rapidly from the 28 th to the 56 th day. RT-PCR showed PQ significantly increased Fn mRNA level on all time points and increased integrin α5 mRNA level from the 7 rd to 56 th day compared with control group (P < 0.05 or P < 0.01). PDTC treatment significantly deceased α-SMA, Fn, and integrin α5 levels compared with PQ group in corresponding time points (P < 0.05 or P < 0.01) Noteworthy, in PQ+PDTC group, the occurrence of pathological changes were drastically attenuated and pathologic score significantly decreased (P < 0.05 or P < 0.01).

CONCLUSIONSα-SMA, integrin α5 and fibronectin could play an important role in the development of pulmonary fibrosis caused by paraquat poisoning. PDTC, asa strong NF-κB inhibitor, may inhibit NF-κB activity and further significantly decreased expressions of α-SMA, integrin α5 and fibronectin which were important part of ECM, leading to drastically attenuated pulmonary fibrosis. However, the mechanisms of PDTC intervention still remains to be explored.

Actins ; metabolism ; Animals ; Disease Models, Animal ; Fibronectins ; metabolism ; Integrin alpha5 ; metabolism ; Male ; Paraquat ; poisoning ; Pulmonary Fibrosis ; chemically induced ; metabolism ; Pyrrolidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates ; pharmacology