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Objective To investigate the role of signal transducer and activator of transcription (STAT1) signaling pathway in osteoblast apoptosis,and to study the effect of STAT1 inhibitor (fludarabine) on osteoblast.Methods The viability of the osteoblasts in different concentration of fludarabine was detected by cell counting kit-8 (CCK-8) assay.Osteoblasts were divided into 4 groups:control group,dexamethasone (Dex) group,fludarabine (Flu) group,and Dex + Flu group.Enzyme linked immunosorbent (ELISA) was used for determining the protein expression of Bcl-2 Associated X Protein (BAX),STAT1 and phosphorylation-sigual transducers and activators of transcription 1 (p-STAT1),and cleaved caspase-3 to reflect the apoptosis in all groups.Results Treatment with Dex increased the protein expression of apoptosis-related proteins and p-STAT1 in time-dependent and dose-dependent manner.Exposure of the cells to Flu,which was a selective STAT1 inhibitor,resulted in a decreased the protein levels of apoptosis-related proteins.Conclusions Our results suggest that fludarabine could suppress Dex-induced apoptosis through the inhibition of STATl-mediated up-regulation cleaved caspase-3 expression in osteoblasts.
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ABSTRACT: Equid alphaherpesvirus type 1 (EHV-1) is distributed worldwide and is a major agent of abortion, respiratory and neurological disease in horses. No specific treatment is available for EHV-1 infection, yet the potential of antiviral therapy has been explored. In this study we investigated the in vitro activity of Acyclovir, Ganciclovir, Foscarnet, Famciclovir, Vidarabina and Cidofovir against EHV-1. For this, the MTT test was performed, in which all the tested drugs showed no toxicity up to 200μg/mL. Subsequently, different drug concentrations were submitted to viral plaque reduction assays in cell culture. The selectivity index (SI) of the compounds was determined using the cytotoxic concentration for 50% of cells (CC50), obtained by MTT, and effective drug concentration to inhibit by 50% the number of viral plaques (EC50). Ganciclovir (SI: 490; EC50: 1.9 μg/mL) was the most efficient and safest drug against EHV-1, followed by Cidofovir (SI: 150, EC50: 5.7μg/mL), Acyclovir (SI: 37.4, EC50: 22.2μg/mL), Famciclovir (SI: 25.1, EC50: 24.5μg/mL), Vidarabine (SI: 12.2, EC50: 40.9μg/mL) and Foscarnet (SI: 6.9, EC50: 49.5 μg/mL), respectively. These results indicated that Ganciclovir (followed by Cidofovir), is a promising candidate for use in in vivo experiments.
RESUMO: O alfaherpesvírus equino tipo 1 (EHV-1) está amplamente distribuído nos rebanhos equinos de todo o mundo e é um dos principais agentes causadores de abortos, doença respiratória e neurológica em equinos. Ainda não há tratamento específico para a infecção pelo EHV-1 em equinos, mas o potencial da terapia antiviral tem sido investigado. Neste trabalho, foi investigada a atividade anti-herpética in vitro dos fármacos Aciclovir, Ganciclovir, Foscanet, Famciclovir, Vidarabina e Cidofovir frente ao EHV-1. Para isso, foi realizado o teste de MTT, em que todas as drogas não apresentaram citotoxicidade até a dose de 200μg/mL. A seguir, diferentes concentrações dos fármacos foram submetidas ao teste de redução de placas virais em cultivo celular. O índice de seletividade (IS) dos compostos foi determinado usando a concentração citotóxica para 50% dos cultivos celulares (CC50), obtida pelo MTT, e pela concentração dos fármacos efetiva para inibir em 50% o número de placas virais (EC50). O Ganciclovir (IS: 490; EC50: 1,9μg/mL) foi o mais eficiente e seguro frente ao EHV-1, seguido pelo Cidofovir (IS: 150; EC50: 5,7 μg/mL), Aciclovir (IS: 37,4; EC50: 22,2μg/mL), Famciclovir (IS: 25,1; EC50: 24,5μg/mL), Vidarabina (IS: 12,2; EC50: 40,9μg/mL) e Foscarnet (IS: 6,9; EC50: 49,5μg/mL). Estes resultados indicam que o Ganciclovir constitui-se em um candidato para uso em experimentos in vivo.
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Objective To compare the efficacy of vidarabine monophosphate and ribavirin for treating hand-foot-mouth disease (HFMD) in children.Methods 120 children with HFMD and admitted to a hospital from April 2013 to April 2015 were randomly divided into observation group and control group,60 cases in each group,observation group treated with vidarabine monophosphate,control group treated with ribavirin,the therapeutic efficacy between two groups were compared.Results After treatment,the negative conversion rate of intestinal virus EV and EV71,as well as Coxsackie virus A16(CA16) in observation group were 87.0％,85.7％,and 93.1％ respectively,in control group were 64.0％,69.8％,and 78.6％ respectively,difference between two groups was statistically significant (all P＜0.05).The average length of hospital stay in observation group was shorter than control group ([4.5 ± 1.3] days vs [6.2 ± 1.2] days,P＜0).05),symptom(fever,stomatitis,skin rash) control time in observation group were all shorter than control group(all P＜0.05).Whether patients with or without complication,therapeutic effect of the observation group was better than that of control group;myocardial enzyme data,C reactive protein (CRP),and white blood cell(WBC) in observation group were all lower than control group(all P＜0.05).Conclusion Efficacy of vidarabine monophosphate for treating children with HFMD is better than ribavirin,but it needs further study.
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OBJECTIVE:To establish a method for the determination of ethanol,acetonitrile,dichloromethane,ethyl acetate, pyridine in vidarabine monophosphate. METHODS:Headspace GC was performed on the column of Agilent DB-624,programmed temperature,inlet temperature was 200 ℃,the detector was flame ionization detector,detecting temperature was 250 ℃,nitrogen was carrier gas,flow rate was 3 ml/min,split ratio was 1∶1,the top bottles equilibrium temperature was 100 ℃,and equilibrium time was 45 min,injection volume was 1 ml. external standard was used for quantitative analysis. RESULTS:The peaks of five re-sidual solvents could be completely separated from the other peaks respectively,The linear rang was 24.7-296.3 μg/ml for ethanol (r=0.999 6)、1.9-23.2 μg/ml for acetonitrile(r=0.999 0),2.8-33.6 μg/ml for dichloromethane(r=0.998 0),24.7-295.9 μg/ml for ethyl acetate(r=0.999 5),1.0-11.9 μg/ml for pyridine(r=0.998 6);RSDs of precision and reproducibility tests were lower than 4.35%;recoveries were 102.4%(RSD=2.0%,n=9)、102.1%(RSD=3.4%,n=9)、105.5%(RSD=4.8%,n=9)、100.3%(RSD=4.8%, n=9)、98.3%(RSD=4.0%,n=9). The minimum quantifation limit was 0.304 4-0.988 0 μg/ml and the minimum detection limit was 0.101 5-0.329 3 μg/ml. CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for the determination of residual solvents in vidarabine monophosphate.
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OBJECTIVE:To investigate the stability of Vidarabine monophosphate for injection combined with Aciclovir injec-tion. METHODS:HPLC method was adopted. The content variations of two drugs in mixture were determined within 8 h at 5 ℃, 25℃,35℃under dark and light. The changes in appearance,property,pH value and insoluble particles(within 24 h)were inves-tigated before and after compatibility. RESULTS:There were no significant changes in appearance and pH value at 5 ℃,25 ℃, 35 ℃ under dark,and insoluble particles were in line with Chinese Pharmacopoeia(2010 edition),and the relative content of vida-rabine monophosphate and aciclovir were above 99%(compared with 0 h)within 8 h. Under the light conditions,as the tempera-ture raised and the extension of storage time,the content of vidarabine monophosphate did not significantly decrease,but that of aciclovir had declined significantly(4 h and after 4 h),while pH value also had a certain degree of rise;the insoluble particles had no obvious change. CONCLUSIONS:The mixture of vidarabine monophosphate and aciclovir in 0.9% Sodium chloride injections is stable under dark conditions within 8 h;it is suggested that the mixture should be used up within 4 h after mixing and protect from light to guarantee the safety of drug use in the clinic.
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Objective:To establish an HPLC method for the determination of the related substances in vidarabine monophosphate for injection. Methods:The known impurities vidarabine and adenine in vidarabine monophosphate for injection were analyzed by an external standard method on a Kromasil 100-5 C18 column(250 mm × 4. 6 mm,5μm)with the mobile phase consisting of water(contai-ning 10 mmol·L-1 tetrabutyl ammonium hydroxide and 10 mmol·L-1 potassium dihydrogen phosphate)-methanol(80:20)at a flow rate of 1. 0 ml·min-1,the detection wavelength was set at 258nm,the column temperature was at 30℃,and the sample size was 20μl. Meanwhile,the unknown impurities were examined by a self-control method. Results:Good linear relationships of vidarabine and adenine were obtained within the range of 0.0765 ~1.530 7μg·ml-1(r =0.999 9)and 0.078 0 ~1.560 0 μg·ml-1(r =0. 999 9). The corresponding average recovery was 99. 8% with RSD of 0. 2%(n=9)for vidarabine and 97. 0% with RSD of 1. 2%(n=9)for adenine. Conclusion:The method can be used to determine the related substances in vidarabine monophosphate for injec-tion.
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Objective To explore effect of vidarabine monophosphate combined with astragalus injection on serum cardiac troponin I ( cTnI), interleukin 1β(IL-1β), interleukin-10 (IL-10) and tumor necrosis factor-α(TNF-α) in children with hand-foot-and-mouth disease.Methods 60 cases with hand-foot-and-mouth disease from March 2013 to March 2015 in the hospital were selected and divided into two groups treated by different therapy, 30 cases in each group.The control group received conventional treatment + ribavirin injection, and experimental group received vidarabine monophosphate combined with astragalus injection on the basis of conventional treatment, one time per day.All patients were treated for a course of 7 days.The serum cTnI,IL-1β,IL-10 and TNF-αlevels were compared before and after treatment.Results After treatment, the serum cTnI, IL-1β, IL-10 and TNF-αlevels in two groups decreased than those of pre-treatment (P<0.05), the above indicators of experimental group were lower than those of control group (P<0.05).Conclusion The combination of vidarabine monophosphate and astragalus injection could significantly decrease serum cTnI, IL-1β, IL-10 and TNF-αlevels in children with hand-foot-and-mouth disease.
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Objective To explore curative effect of Xiyanping and vidarabine in treatment for children with viral encephalitis and its impact on T cells subgroup.Methods Methods In June 2012~October 2014, randomly selected 106 cases of children patients with viral encephalitis, as the research object.Randomized divided into observation group (n=53) cases, control group(n=53).Both two group were performed routine therapy, and then control group was given Xiyanping treatment, observation group was given Xiyanping combined with vidarabine treatment.1 continuous week treatment, compared two groups of T cell subgroup number and symptoms disappear time.Results In the two groups after treatment of T cell subgroup CD3 +, CD4 +,CD8 +was significant increase in the number of observation group increased number was significantly higher than the control group,and statistically significant differences ( P<0.05 ) .The observation group’s antifebrile time ( 2.5 ±1.1 ) d; headache, vomiting disappear time ( 3.6 ±2.2 ) d;disturbance of consciousness disappear time (2.6 ±1.3) d and length of hospital stay (9.3 ±2.4) d were significantly lower than the control group (4.7 ±2.8) d, (6.5 ±2.3)d, (4.3 ±2.2) d, (14.2 ±3.6) d, which were statistically significant differences (P<0.05).Observation group’s curative effect for instituting accounted for 73.58%, good rate 92.45%, were significantly higher than the control group 52.83%, 77.36%.which were statistically significant differences (P<0.05).The complication rate of observation group was 16.98%, mortality was 0%,were significantly lower than that of 33.96%, 9.43% of the control group;Cure rate of observation group (90.57%) was significantly higher than that of 49.06% of control group. Observation group severe sequela incidence 11.32% was significantly lower than that of 39.62% of control group and statistically significant differences (P<0.05).Conclusion Xiyangping combined with vidarabine in treatment for children with infantile viral encephalitis can significantly increase the number of T cell subgroup, improve immune function in children with, and curative effect is remarkable and high security.
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Objective To study optimal compatibility scheme of vidarabine monophosphate for injection combined with aciclovir injection. Methods L18(35) of orthogonal design was used with five factors: temperature, illumination,storage time,solvent and solvent dosage;the insoluble particles were observed by GWJ-4 type particle analyzer.The content of vidarabine monophosphate and aciclovir was detected by HPLC.Optimization of the best scheme of vidarabine monophosphate for Injection combined with aciclovir injection was studied.Results The regression equation of vidarabine monophosphate and aciclovir were A=3.78 ×104C+2.32, r=0.9997(n=5)and A=7.11 ×105C-4.65, r=0.9995(n=5),The results showed that the relationship between the range of 200-900μg/mL(vidarabine monophosphate) and the range of 1000-4500μg/mL(aciclovir) was good.The optimal compatibility conditions are the follows:temperature of 25,as far as possible away from light;Vidarabine monophosphate for injection 1 (0.1 g/branch) and 1 acyclovir injection (10 mL:0.5 g) mixed with 100 mL 0.9% sodium chloride injection,and dropping out within 4 h after compatibility. Conclusion The optimal compatibility scheme has good repeatability,injection solution stability is good.It prouides scientific reference for the safty of clinical rational drug use.
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Objective To observed the clinical effect of vidarabine and interferonα-2b aerosol inhalation in the treatment of children with infantile herpangina.Methods 58 children with infantile herpangina were divided ran-domly into the observation group and control group,29 cases in each group.All children were given theroutine nursing and general supportive therapy.The patients in the control group were treated by ribavirin and those in the observation group treated by vidarabine and interferon aerosol inhalation.The fever clearance time,the disappearance time of her-pes,the days of hospitalization and cases of adverse reaction was observed and recorded.Results The cooling time, bleb disappear time and hospital stay of the observation group were lower than those of the control group,the difference were statistically significant(P <0.05).Comparation of the clinical effects of the two groups showed that the test group were significantly better than those in the control group(P <0.05).The total effective rate in the observation group was 96.6%,which was higher than 75.9% in the control group(χ2 =5.22,P <0.05).No obvious adverse e-vents took place in both groups.Conclusion Vidarabine and interferon aerosol inhalation in treating infantile herpan-gina takes a good effect,no obviously adverse reaction and is worth being widely applied in clinic.
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Objective To expore the mechanism of low-dose interfone-γ(IFN-γ) influences on differentiation of oligodendrocyte precursor cell. Methods The cerebral cortex samples were obtained from one day old SD rats to form mixed single cell suspensions. After culturing in full medium for 7 to 10 days, succession and differential velocity adherent technique were performed to acquire oligodendrocyte precursor cell and cultured in serum-free medium. IFN-γ, AG490 and Fludarabine were added during the culture of oligodendrocyte precursor cell and reverse transcription-polymerase chain reaction, Western blot and flow cytometry were performed to evaluate the expression of intracellular P27kip1 and its influence on the differentiation of oligodendrocyte precursor cell. Results (1)The expression of P27kip1 mRNA and protein was lower in IFN-γ group than in control group (t=85. 535, P<0. 05;t= 12. 481, P<0. 05), while the expression of P27kip1 mRNA and protein in IFN-γ+AG490 group and IFN-γ+Fludarabine group were both higher than those in IFN-γ group (P<0. 05). (2) The phosphorylation levels of JAK2/STAT1 in INF-γ group were higher than that in the other three groups (P<0. 05). (3) The percentage of myelin basic protein positive cells was (68. 42 ± 2. 53)% in IFN-γ group, lower than that in control group [(88.21 ± 1.97)%](t=10.682, P < 0.05). Myelin basic protein positive cells in IFN-γ + AG490 group were (57. 63 ±2. 75) %, lower than those in the IFN-γ group. The same figure in IFN-γ+Fludarabine group were (79. 53±4. 15)% , higher than those in IFN-γ group (t = 3.957, P<0.05). Conclusions Low-dose IFN-γ can regulate the expression of intracellular P27kip1 through JAK2/STAT1 signal transduction pathway and Fludarabine may participate in this process and improve the differentiation and maturation of oligodendrocyte precursor cell.
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Objective To evaluate the efficacy of Flu/CTX conditioning regimen for the treatment of severe aplastic anemia in pa- tients receiving allogeneic hematopoietic stem cell transplantation. Methods Nine patients with severe aplastic anemia received HLA identi- cal peripheral blood hematopoietic stem cell transplantation (PBSCT) using Flu/CTX conditioning regimen, which consisted of fludarbine [30 mg/(m2 d) for5 days (-7 to -3) ], CTX [50mg/(kg d) for4 days(-5 to-2)]. All patients received cyclosporin A (CsA) and mycophenolet mofetil (MMF) for prophylaxis of graft-versus-host disease(GVHD). Results The Fiu/CTX regimen was very well toler- ated, with no severe regimen related toxicity. In all patients, the median days of neutrephil exceeding 0. 5×109/L and platelet exceeding 20 ×109/L were 12 days (range 10-16 days) and 16 days (range 14-19 days), respectively. Complete chimerism was achieved in all pa- tients at one month after PBSCT. Two patients had acute GVHD and one had chronic GVHD. In the 39-month median follow-up duration, all patients were alive in disease-free situation. Conclusion The Flu/CTX conditioning regimen may reduce transplantation-related toxicities and can achieve full chimerism and high long-term disease-free survival. Allogeneic hematopoietic stem cell transplantation using intravenous Fiu/CTX conditioning regimen is a safe and effective treatment method for the patients with severe aplastic anemia.
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Objective To evaluate the efficacy and feasibility of Flu/ivBu/Tl" conditioning regimen for the treatment of refractory or relapsed acute non-lymphocytic leukemia in patients receiving allogeneic hematopoietie stem cell transplantation. Methods Seven patients with refractory or relapsed acute non-lymphocytic leukemia received HLA identical peripheral blood hematopoietie stem cell transplantation (PBSCT) following Flu/ivBu/TY conditioning regimen, which consisted of fludarbine, busulfex and thiotepa. All patients received cyclos-porin A (CsA) and mycophenolet mofetil (MMF) for prophylaxis of graft - versus - host disease (GVHD). Results The Flu/IVBu/TT regimen was tolerated very well, without severe regimen related toxicity. In the 31-month median follow-up duration, 5 of 7 patients were a-live in disease-free situation. Conclusion The Flu/ivBu/TT conditioning regimen reduced transplantation-related toxicities and offered high long-term disease-free survival, and was tolerated very well. Allogeneie hematopoietie stem cell transplantation using Flu/ivBu/TT condition-ing regimen is a safe and effective option for the patients with refractory/relapsed acute non-lymphocytic leukemia.
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We present four cases of herpes zoster treated successfully with vidarabine-5-monophosphate, two patients receiving chernotherapy and radiation therapy due to Hodgkins lymphoma or colon cancer, a patient combined with viral meningitis, and a patient with herpes zoster ophthalmicus. Viclarabine can be used to treat herpes zoster in immunosuppressed patients or patients with malignancy or patients with severe complications.
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Humans , Colonic Neoplasms , Herpes Zoster Ophthalmicus , Herpes Zoster , Hodgkin Disease , Meningitis, ViralABSTRACT
We have experienced a case with acute fulminant hepatitis induced by Herpesvirus homin-us. The patient, 11day-old male baby, was admitted with the chief complaints of poor sucking and jaundice for 3 days duration. On adimission, we performed bacterial cultures, liver function tests, blood coagulation test, TORCH study and routine hematologic studies. During these studies, bleeding tendency was n-oticed at the blood sampling sites. The patients took and fulminant course and expired about 3hrs. after admission despite of vigorous ressucitations. Electronmicroscopic examination of the liver necropsy tissue showed Viral particles in the nuclei of hepatocytes which was considered as Herpesvirus hominus.