AIMTo investigate the effects of omapatrilat (OMA) on endothelin-1-induced proliferation of cardiac fibroblasts (CFs).

METHODSIsolated and cultured CFs from neonatal Sprague-Dawley rats (SD) were randomly divided into 7 groups: (1) Control, (2) ET-1, (3) OMA, (4) ET-1 + OMA 10(-9) mol/L, (5) ET-1 + OMA 10(-8) mol/L, (6) ET-1 + OMA 10(-7) mol/L and (7) ET-1 + OMA 10(-6) mol/L. CFs were counted by MTT assay. Cell cycle distribution was determined with a flow cytometer (FCM). [3H]-Proline incorporation was evaluated by scintillation counting. Nitric oxide (NO) was measured by colorimetry.

RESULTS10(-7) mol/L ET-1 significantly increased A490 value and [3H]-Pro incorporation and decreased NO secretion compared with the control group (P < 0.01). 10(-9)-10(-6) mol/L OMA inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P < 0.01 vs. ET-1). In the ET-1 group, the percentage of cells in the S phase was higher than control, which was inhibited by l0(-6) mol/L OMA (P < 0.01 vs. ET-1 and control).

CONCLUSIONOMA can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen ; biosynthesis ; Endothelin-1 ; pharmacology ; Fibroblasts ; cytology ; drug effects ; Myocytes, Cardiac ; cytology ; drug effects ; Nitric Oxide ; metabolism ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiazepines ; pharmacology

OBJECTIVETo observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.

METHODSTotally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.

RESULTS(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).

CONCLUSIONSThe ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.

Animals ; Colforsin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; physiopathology ; Heart Failure, Diastolic ; drug therapy ; Isoproterenol ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Wistar

Objective To establish a closed-chest pulmonary embolism-reperfusion animal model by Swan-Ganz catheter and to explore the mechanisms of pulmonary embolism(PE)-reperfusion injury(RI). Methods Experiments were made on 14 mongrel dogs,ranging in weight from 15 to 18 kg,anesthetized with 3% pentobarbital sodium.The dogs were intubated with I.D.7 endotracheal tubes.Under sterile conditions,a 7 F Swan-Ganz catheter via the external jugular vein was positioned in the unilateral pulmonary diaphragmatic lobe(DL)artery.Occlusion/reperfusion of the DL artery was controlled with 1.2 ml diluted contrast agent filled into/drawn from the balloon.After the 24 h PE,the balloon was deflated to result in 4 h reperfusion of the DL.Measurements of blood gases and tumor necrosis factor-?(TNF-?)were made at normal condition,at 24 h PE and at 4 h reperfusion.Thin-section CT scans were performed at normal condition,24 h PE,30 min,1,2,3 and 4 h reperfusion,respectively.At the end of each experiment, tissue specimens of bilateral diaphragmatic lobes were obtained for both wet/dry(W/D)weight ratio and for pathological study.Results Reperfusion pulmonary edema(RPE)was an acute,mixed,noncardiogenic edema that was observed in all 14 dogs who had been successfully established as PE/RI animal models.RPE demonstrated heterogeneous ground-glass opacifications that predominated in the areas distal to the recanalized vessels.It manifested pathologically as an edematous lung infiltrated by inflammatory cells.The mean ofPaO_2 and TNF-? of 4 h reperfusion was(81?4)mm Hg(l mm Hg=0.133 kPa)and(16.0? 2.5)pg/ml,which were significantly different(P

Objective To study changes of aspartate(ASP) and glutamaic acid(GLU) in cerebral cortex of neonatal Sprague-Dawely(SD) rats after hypoxia-ischemia and nitric oxide synthase(NOS) immunoactive expression in cerebral neurons were examined to explore mailuoning′s protective effect on hypoxia-ischemia brain damage(HIBD).Methods The HIBD model was established as follows.The right common carotids of the neonatal SD rats 7 days were temporaily ligatured for 1 hour.Then the neonatal SD rats were exposed to 8% oxygen and 92% nitrogen gas mixture for 2 hours. The ASP and GLU were determined in right cerebral cortex using chromatograph,compared with sham-operated group and mailuoning administrated. Ultrastructure changes of neurons in the right cerebral cortex of neonatal SD rats were observed after sham-operated,hypoxia-ischemia and mailuoning administrated using electronmicroscope.Results The level of excitatory amino acid was promoted in right cerebral cortex after hypoxia-ischemia.The volume of excitatory amino acid was reduced sharply mailuoning administrated. Ultrastructure of neurons in the cerebral cortex showed serious injure after hypoxia-ischemia and ultrastructure of neurons in the cerebral cortex appeared slight damage.Conclusion Mailuoning may possess protective effects to the neurons after hypoxia-ischemia through supplying blood to neurons reducing release of excitatory amino acid.

OBJECTIVETo observe the effect of Spleen-invigorating Prescription (SIP) on dendritic cell function in patients with chronic hepatitis B.

METHODSA total of 60 patients with chronic HBV of Pi-deficiency syndrome type were enrolled and randomized to 2 groups, 30 in each group. Patients in the control group were given intramuscular injection with human interferon alpha 1b, 3 times a week, while those in the treated group were given orally with SIP twice a day, the therapy lasted for 6 months. Dendritic cells (DCs) were isolated from peripheral blood and cultured, then the expression of surface markers, HLA-DR, CD86, CD80, CD40, CD14 and CD11c were detected before and after treatment by flow cytometry, and the function of DCs was also evaluated by mixed lymphocyte reaction (MLR) determination once before treatment and once after treatment.

RESULTSThe expressions of DCs' surface CD86, CD80, CD40 and CD11c in the treated group were higher (P < 0.05, P < 0.01) and the changes of stimulating index, IFN-gamma and IL-12 were superior in the treated group to those in the control group (P < 0.05).

CONCLUSIONSSIP can significantly improve DC's function, so, one of mechanisms of SIP in improving clinical efficacy may be the regulation of immune function.

Adult ; Antiviral Agents ; therapeutic use ; B7-1 Antigen ; analysis ; B7-2 Antigen ; analysis ; Dendritic Cells ; cytology ; drug effects ; immunology ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Syndrome ; Yang Deficiency ; drug therapy ; Young Adult

To describe the effects of endogenous testosterone levels on the visuospatial ability.Thevisuospatial ability,testosteronewere included as the key words,retrieving 46 papers in the database.35 relevant papers have been reviewed in the paper,as the results,we have found that the visuospatial ability of male was better than female.The performances of the visuospatial tasks in males were associated with the lev-els of endogenous testosterone,and the effects comprised two aspects:the organizational function and activa-tional function of the testosterone.The latter have received more attention from researchers.Until now,most studies of activational effects of testosterone on visuospatial ability remained on the level of behavioral re-search.The mental rotation task,navigation task and virtual reality scenes tasks were implied in these stud-ies.A nonlinear relationship has aroused a great controversy.Latest research suggests that further investiga-tion of the neural mechanisms related to visual-spatial ability is needed,using ERP and MRI techniques,to assess the relationship of endogenous testosterone levels with the relevant neural basis of visuospatial ability.

ObjectiveTo compare the predictive value of anatomic scoring system, physiological scoring system, and the combination of two systems in death prediction of patients with severe trauma in intensive care unit (ICU). Methods A retrospective analysis of patients with severe trauma admitted to department of critical care medicine of Daping Hospital, the Third Military Medical University, and Zunyi Medical University from January 2011 to December 2014 was conducted. The patients meeting the following criteria were enrolled: over 16 years old, admitted to hospital shorter than 24 hours after trauma, length of ICU stay≥48 hours, and injury severity score (ISS)≥16. Patients were divided into two groups: survivors and non-survivors. The data of anatomic scoring system, including ISS and new injury severity score (NISS), and physiological scoring system, including acute physiology and chronic health evaluationⅡ(APACHEⅡ) score were collected. The predictive power for death of the scoring system alone or combination in patients with severe trauma was evaluated.Results A total of 614 patients with severe trauma were enrolled, and there were 153 deaths with a mortality rate of 24.9%. ISS, NISS, APACHEⅡ, ISS+ APACHEⅡ, NISS+ APACHEⅡ of non-survivors were significantly higher than those of survivors (ISS: 29.15±7.75 vs. 24.31±6.50, NISS: 41.96±12.01 vs. 29.64±8.19, APACHEⅡ: 23.71±6.58 vs. 17.02±5.49, ISS+ APACHEⅡ: 52.86±10.00 vs. 41.33±8.70, NISS+ APACHEⅡ: 65.67±13.46 vs. 46.66±10.43, allP< 0.01). The area under receiver operating characteristic curve (AUC) of ISS, NISS, APACHEⅡ, ISS+ APACHEⅡ, NISS+ APACHEⅡ was 0.687, 0.792, 0.782, 0.809, and 0.860, respectively. Both of ISS+ APACHEⅡ and NISS+ APACHEⅡ had higher AUC than that of ISS, NISS or APACHEⅡ alone; and the AUC of NISS+ APACHEⅡ was significantly larger than that of ISS+ APACHEⅡ(allP< 0.05). NISS+ APACHEⅡ showed the largest AUC in death prediction of severe trauma patients. The cut-off value, sensitivity, specificity, positive predict value (+PV), negative predict value (-PV), positive likelihood ratio (+LR), negative likelihood ratio (-LR), and Youden index of NISS+ APACHEⅡ, which had the greatest AUC, were 56, 75.2%, 82.0%, 58.1%, 90.9%, 4.17, 0.30, and 0.572, respectively.Conclusion The combination of anatomic scoring system and physiological scoring system is better than single scoring system for death prediction in patients with severe trauma in ICU, and it may be considered to be a new method for early identification of death risk in patients with severe trauma.

Coronary Sinus ; abnormalities ; Humans ; Male ; Middle Aged ; Subclavian Vein ; Vena Cava, Superior

Background Haze formation is a key factor of vision reduce following corneal refractive surgery.Transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) are documented to participate in haze formation.Laboratory study showed that bevacizumab can not only inhibit corneal neovascularization,but also promote the healing of corneal epithelial basement membrane.However,the impact of bevacizumab on corneal healing after Off-flap epipolis laser in situkeratomileusis (Off-flap Epi-LASIK) is unclear.Objective The present study was to investigate the inhibition effect of bevacizumab on corneal haze after off-flap Epi-LASIK and its active mechanism.Methods Off-flap Epi-LASIK was performed in 24 adult pigmented rabbits and these rabbits were randomized into three groups.Bevacizumab of 0.1 ml (2.5 mg) was subconjunctivally injected 10 minutes after surgery in 16 rabbits and the same amount of bevacizumab was repeatedly injected 4 days after the initial injection in 8 eyes of 16 eyes.In addition,equivalent amount of normal saline solution was used in the same way in the other 8 rabbits.Another 2 health rabbits were used as the blank controls.Operative eyes were examined by slit lamp biomicroscope daily after surgery and haze was scored based on SundarRayde criteria.Corneas were obtained 4 weeks after operation for hematoxylin & eosin and periodic acid Schiff staining.Expressions of TGF-β1 and α-SMA in corneal tissue were detected by immunochemistry.Results Corneal epithelium healed completely in all eyes 4-5 days after operation.The haze scores were lower in the bevacizumab single injection group and repeat injection group than those in the normal saline solution group (P＜0.05) in 1 week and 4 weeks after operation.However,no significant difference was seen in the haze scores between the bevacizumab single injection group and repeat injection group (P ＞ 0.05).The hostopathological examination showed that the fibrosis response of cornea tissue was slight in the bevacizumab single injection group and repeat injection group comparison with the normal saline solution group.At 1 week after operation,the expression levels of TGF-β1 were (49.8 ± 2.1) PU and (38.6 ±4.4) PU in the bevacizumab single injection group and repeat injection group,and those of 4 weeks were (37.7 ±4.8) PU and (28.3 ± 3.5) PU,indicating significant decrease in the TGF-β1 expression compared with (65.1 ±5.3) PU and (51.6±2.2) PU of the normal saline solution group in both 1 week and 4 weeks (P＜0.01).The expression levels of α-SMA in corneas were (67.2±10.0) PU and (32.7±3.1) PU at 1 week,and (34.2±5.7) PU and (22.8±3.0) PU at4 weeks after operation in the bevacizumab single injection group and repeat injection group,which were significantly lower than (87.8±7.7) PU and (59.4±5.6) PU in the normal saline solution group in both 1 week and 4 weeks (P＜0.05).Meanwhile,the expression levels of TGF-β1 and α-SMA were declined in the bevacizumab repeat injection group compared with single injection group (P＜0.01).Periodic acid Schiff staining exhibited that the basement membrane of cornea was intact and continued in bevacizumab injection group.But corneal basement membrane was discontinuous in the normal saline solution group.Conclusions Subconjunctival injection of bevacizumab downregulates the expressions of TGF-β1and α-SMA in cornea after Off-flap Epi-LASIK and thus prevents haze formation.

Tumor angiogenesis provides adequate oxygen and nutrition for tumor development and supports tumor growth and metastasis. Stromal cell derived factor 1 (SDF-1) and its receptor C-X-C motif chemokine receptor 4 (CXCR4) in pancreatic cancer microenvironment are involved in tumor growth such as promoting tumor cell proliferation, migration, and angiogenesis. In this study, anti-CXCR4 nanobody (CXCR4 Nb) and anti-programmed cell death ligand 1 (PD-L1) &CXCR4 bispecific nanobody (PX4 BsNb) were expressed in Escherichia coli system and purified by nickel column affinity chromatography. We investigated the anti-angiogenesis activity and mechanism of CXCR4 Nb by in vivo and in vitro experiments. Ethical approval was obtained for collection of human peripheral blood mononuclear cell (hPBMC) samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University. The results showed that CXCR4 Nb at 0.1 μmol·L^-1 could effectively inhibit the proliferation and migration of human umbilical vein endothelial cells (HUVEC) promoted by pancreatic stellate cells in vitro. CXCR4 Nb and PX4 BsNb at 0.3 mg·kg^-1 obviously decreased tumor angiogenesis and inhibited the tumor growth in NOD/SCID mice, the inhibitory rates were 28.8% and 36.1%, respectively. CXCR4 Nb significantly inhibited tumor growth and angiogenesis with great safety, which provides support for application of CXCR4 Nb and anti-angiogenesis therapy of pancreatic cancer.