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Objective To investigate the effects of Sacubitril/Valsartan on amino terminal probrain natriuretic peptide (NT-proBNP),high sensitivity C-reactive protein (hs-CRP),soluble suppression of tumorigenicity 2(sST2)levels and on left ventricular(LV)structure in NYHA Ⅳ heart failure with reduced ejection fraction(HFrEF) patients.Methods A total of 67 HFrEF patients with NYHA Ⅳ were randomly divided into the control group (n =30)receiving conventional medical treatment,and the observation group(n=32)receiving Sacubitril/Valsartan instead of ACEI(or ARB if ACEI induced cough) in conventional medical treatment.NT-proBNP levels were determined by fluorescer-enhanced chemiluminescence.hs CRP levels were detected by latecx enhanced immunoturbidimetric assay.sST2 levels were determined by enzyme-linked immunosorbent assay (ELISA).The modified Simpson method was used to detect left ventricular end-diastolic diameter (LVEDD),LV posterior wall(LVPW)and LV ejection fraction(LVEF).Two groups of patients were treated and followed-up for 6 months.Results Clinical efficacy was better in the observation group than in the control group(effective rate,20 cases or 61.3％ vs.8 cases or 26.7％,P＜0.05).As compared with the control group,the observation group of patients had an increased LVEF[(46.7±9.2) ％ vs.(41.8±8.0)％,P＜0.05]and a decreased LVEDD[(52.6±6.7)mm vs.(58.8±7.5)mm,P＜0.05].After vs.before treatment,NT-proBNP,hs-CRP and sST2 levels were decreased in both control and observation groups [(1 427 ± 219) μg/L vs.(2 615 ± 273)μg/L,(1.14 ± 1.02) mg/L vs.(1.55±1.38)mg/L,(0.30±0.12)μg/L vs.(0.41±0.10)μg/L,all P＜0.05],and the decrements were much more in the observation group than in the control group (P＜0.05).The annual accumulated frequence and duration of hospitalization were less in the observation group than in the control group[(0.8±0.6)times vs.(1.8±1.0) times,(10.2±5.8)d vs.(16.5±7.2)d,P＜0.05].The maintenance dose of tolasemide was lower in the observation group than in the control group [(15.2±8.4)mg vs.(20.6±10.8)mg,P＜0.05].Conclusions Sacubitril/valsartan therapy is safe and effective and it can reduce hs-CRP and sST2 levels and improve the ventricular remodeling in HFrEF patients of HYHA Ⅳ.
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<p><b>OBJECTIVE</b>To investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats.</p><p><b>METHODS</b>Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0.</p><p><b>RESULTS</b>The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC, from 4 820±197 to 4 205±186 ng·mL·) and AUC(from 5 237±280 to 4 514±210 ng·mL·) significantly decreased in response to the 14-day pretreatment with SGD. The values of V(L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t(h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUCand AUCvalues decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel.</p><p><b>CONCLUSIONS</b>SGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.</p>
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Animals , Male , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Therapeutic Uses , Injections, Intravenous , Paclitaxel , Blood , Chemistry , Pharmacokinetics , Rats, Sprague-Dawley , Reference Standards , Time FactorsABSTRACT
Objective Studies are rarely reported on how to avoid complement system attack during the transplantation of bone marrow mesenchymal stem cells (BMSCs).We explored the effect of the overexpression of CD59 on complement membrane attack-induced damage to rat BMSCs (rBMSCs) during autologous transplantation.Methods BMSCs from SD rats were cultured and treated with CD59 overexpression plasmid or rBMSC empty vector or left untreated,followed by detection of the expression of CD59 in the rBMSCs by flow cytometry.Then the rBMSCs were incubated with autologous rat serum (ARS),inactivated ARS (iARS),CD59+ARS,or CD59+iARS or not incubated.The cytotoxicity of the serum complement on the rBMSCs was observed by PI staining and the apoptosis of the rBMSCs determined by flow cytometry.Results The expression of CD59 was significantly higher in the rBMSCs treated with CD59 than in those untreated (7,4.9％ vs 50.5％,P＜0.05).The apop tosis rate was remarkably lower in the rBMSCs not incubated ([8.4± 1.1] ％) and those incubated with CD59+ARS ([19.1 ±3.1] ％) than in those incubated with ARS ([40.3±4.3] ％) (P＜0.05).The deposition of the complement membrane attack complex was significantly decreased in the rBMSCs not incubated (50.1％) and those incubated with CD59+ARS (71.0％) as compared with those incubated with ARS (99.7％) (P＜0.05).The apoptosis rate of the rBMSCs treated with CD59 was markedly lower than that of those left untreated (P＜0.05).Conclusion The overexpression of CD59 inhibits the damage induced by complement to rBMSCs by reducing the formation of the complement membrane attack complex during autologous transplantation.
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Objective To investigate correlations of hyperuricemia and matrix metalloproteinase -9 level with left ventricular remodeling in patients with type 2 diabetes and the clinical effect of intervention for hyperuricemia.Methods 100 type 2 diabetic patients with hyperuricemia in our hospital from June 2011 to June 2012 were selected as hyperuricemia group,50 type 2 diabetic cases with normal uric acid were considered as DM group.Levels of blood glucose,blood lipids,glycosylated hemoglobin and matrix metalloproteinase-9 were detected.All patients underwent echocardiography.Patients in hyperuricemia group were randomly divided into treatment group (receiving allopurinol and alkaline urine-alkalify therapy added to hypoglycemic treatment,n=50) and control group (receiving hypoglycemic treatment,n=50).After 6 months of treatment,levels of blood glucose,blood lipids,glycosylated hemoglobin,matrix metalloproteinase-9 and echocardiography were rechecked.Results The levels of triglyceride (TG),blood uric acid,MMP-9,left ventricular posterior wall thickness (LVPWT),interventricular septal thickness (IVST) and left ventricular mass index (LVMI) were increased in hyperuricemia group versus DM group[(2.3±0.5) mmol/L vs.(1.6±0.30) mmol/L,(498.9±32.5) μmol/L vs.(322.8±35.6) μmol/L,(765±38) g/L vs.(420±26) pg/L,(11.0±1.1) mm vs.(9.2±0.8) mm,(11.5±1.6) mm vs.(10.1±1.1) mm,(138.7±35.6) g/m2 vs.(115.0±10.4)g/m2,t=4.945,5.124,4.895,3.985,3.965,3.989,respectively,all P＜0.05].Levels of TG,blood uric acid,MMP,LVPWT,IVST were decreased in treatment group after treatment versus before treatment [(1.6±0.5) mmol/L vs.(2.3±0.6) mmol/L,(323.0±30.5) μmol/L vs.(496.6±32.6) μmol/L,(766±34) pg/L vs.(410±25)pg/L,(9.1±0.8) mm vs.(11.0±1.1) mm,(9.2±1.1) mm vs.(11.6±1.5) mm,(116±10.5)g/m2 vs.(138.8±35.2) g/m2,t=3.386,4.525,4.865,3.256,3.895,3.985,all P＜0.05].Correlation analysis showed that LVMI had positive correlations with levels of blood uric acid,TG,MMP-9 (r=0.435,0.348,0.356,respectively).Conclusions Hyperuricemia involves in left ventricular remodeling,and therapeutic intervention on the hyperuricemia can reverse this remodeling.
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Objective: To explore the effect of valsartan on inflammatory cytokines in patients with hypertension combining paroxysmal atrial ifbrillation (PAF). Methods:A total of 60 patients with hypertension combining PAF converted to sinus rhythm were studied and the patients were divided into 2 groups. Control group, the patients received felodipine and Valsartan group. n=30 in each group, all patients were treated for 6 months. In addition, there was a Normal group including 30 healthy subjects. The levels of high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and left atrial diastolic diameter (LADd), the sinus rhythm maintenance rate were examined and compared before and after treatment among different groups. Results: Compared with Normal group, the levels of hs-CRP, IL-6 and LADd were obviously higher in patients at both Control group and Valsartan group, all P Conclusion: Valsartan may inhibit inflammatory response and improve atrial structure remodeling, therefore better maintain the converted sinus rhythm in patients with hypertension combining PAF. The anti-inlfammatory effect of valsartan might be independent from its anti-hypertension effect.