Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular / Activity of three antiviral drugs against bovine herpesviruses 1, 2 and 5 in cell culture

The activity of three anti-herpetic drugs (Acyclovir [ACV], Gancyclovir [GCV] and Foscarnet [PFA]) was tested against bovine herpesvirus 1 (BoHV-1), 2 (BoHV-2) and 5 (BoHV-5) in vitro using the plaque reduction assay. Different drug concentrations were tested against one hundred 50 percent tissue culture infectious dose (TCID50) of the respective viruses. Drug concentrations lower than 200μg/mL resulted in viability rates of more than 80 percent for MDBK and Hep2 cells in the MTT test (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The selectivity index (IS) of the drugs was calculated dividing the concentration of the drug that is cytotoxic for 50 percent of the cells (CC50) by the concentration of the drug that was effective in reducing by 50 percent the number of viral plaques (EC50) for the three herpesviruses. Thus, ACV was shown to be moderately active against BoHV-1 (EC50: 112.9μg/mL; IS: 4.5), BoHV-2 (EC50: 114.2μg/mL; IS: 4.5) and BoHV-5 (EC50: 96.9μg/mL; IS: 5.3). GCV was effective against BoHV-2 (EC50: 33.5μg/mL; IS: 16.6), moderately effective against BoHV-5 (EC50: 123.2μg/mL; IS: 4.5) and poorly active against BoHV-1 (EC50: 335.8μg/mL; IS: 1.7). PFA exhibited the highest antiviral activity, being the only drug that, at concentration of 100μg/mL, completely inhibited plaque formation by all three viruses. PFA was the most effective in vitro against BoHV-1 (EC50: 29.5μg/mL; IS: 42.2), BoHV-2 (EC50: 45.2μg/mL; IS: 27.6) and BoHV-5 (EC50: 7.8μg/mL; IS: 160.6). Thus, the results indicate that PFA is a promising candidate for experimental therapeutic testing in vivo against bovine herpesviruses.

A atividade de três fármacos antivirais (Aciclovir [ACV], Ganciclovir [GCV] e Foscarnet [PFA]) foi testada in vitro frente aos herpesvírus bovino tipos 1 (BoHV-1), 2 (BoHV-2) e 5 (BoHV-5). Para isso, utilizou-se o teste de reducao de placas virais em cultivo celular, testando-se diferentes concentracoes dos farmacos frente a 100 doses infectantes para 50 por cento dos cultivos celulares (DICC50) dos respectivos virus. Pelo teste de MTT (3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide), verificou-se que concentracoes inferiores a 200ƒÊg/mL dos tres antivirais resultaram em indices de viabilidade de celulas MDBK e Hep2 superiores a 80 por cento. Com base na concentracao citotoxica para 50 por cento das celulas (CC50) e na concentracao dos farmacos efetiva para inibir em 50 por cento o numero de placas virais (EC50), calculou-se o indice de seletividade (IS) dos antivirais para os tres herpesvirus. Assim, o ACV demonstrou ser moderadamente ativo frente ao BoHV-1 (EC50: 112,9ƒÊg/mL e IS: 4,5), ao BoHV-2 (EC50: 114,2 ƒÊg/mL e IS: 4,5) e BoHV-5 (EC50: 96,9ƒÊg/mL e IS: 5,3). O GCV apresentou atividade moderada frente ao BoHV-2 (EC50: 33,5ƒÊg/mL e IS: 16,6) e, em menor grau, contra o BoHV-5 (EC50: 123,2ƒÊg/mL e IS: 4,5), sendo ineficaz frente ao BoHV-1 (EC50: 335,8ƒÊg/mL e IS: 1,7). O PFA apresentou atividade antiviral mais pronunciada, sendo o unico farmaco que, na concentracao de 100ƒÊg/mL, inibiu completamente a producao de placas pelos tres virus testados. O PFA foi o mais efetivo in vitro frente ao BoHV-1 (EC50: 29,5ƒÊg/mL e IS: 42,2), ao BoHV-2 (EC50: 45,2ƒÊg/mL e IS: 27,6) e ao BoHV-5 (EC50: 7,8ƒÊg/mL e IS: 160,6). Portanto, os resultados obtidos indicam que o PFA pode se constituir em um candidato para terapia experimental de infeccoes pelos herpesvirus de bovinos in vivo.

Two Cases of Acute Retinal Necrosis Treated With Systemic Antiviral Drugs and Intravitreal Antiviral Injections

PURPOSE:To report the use of intravitreal antiviral injections as adjunctive therapy in the managementof two immunocompetent patients with acute retinal necrosis. CASE SUMMARY: We performed two or three intravitreal injections of gancyclovir (2,000 microg/0.05 ml) on two patients (two eyes) with acute retinal necrosis resistant to intravenous acyclovir therapy (1,500 mg/m2/day). Both patients received intravitreal antiviral injections for the treatment of retinitis that progressed despite standard intravenous acyclovir therapy. The retinitis resolved, and visual acuity improved after 18 months of follow-up in both cases. CONCLUSIONS: Intravitreal antiviral injections may be a safe and efficacious adjunctive therapy in the management of patients with acute retinal necrosis resistant to intravenous acyclovir therapy.

Cytomegalovirus Retinitis After Intravitreous Triamcinolone Injection in a Patient with Central Retinal Vein Occlusion

To report a case of cytomegalovirus (CMV) retinitis after intravitreal injection of triamcinolone acetonide (IVTA). A 77-year-old woman with macular edema due to central retinal vein occlusion (CRVO) developed peripheral retinitis 4 months after IVTA. A diagnostic anterior chamber paracentesis was performed to obtain DNA for a polymerase chain reaction (PCR) test for viral retinitis. The PCR test was positive for CMV DNA. Other tests for infective uveitis and immune competence were negative. Four months after presentation, gancyclovir was intravitreously injected a total of 5 times, and the retinitis resolved completely. CMV retinitis is a rare complication of local immunosuppression with IVTA. It can be managed with timely injection of intravitreal gancyclovir until recovery from local immunosuppression.

Determination of acyclovir and gancyclovir using flow-injection chemiluminescence method / 西安交通大学学报(医学版)

Objective To develop a new flow-injection chemiluminescence(FI-CL) method for the determination of acyclovir and gancyclovir by using the CL system of Ce(IV)-Rhodamine B.Methods The redoxreaction of Ce(IV) and acyclovir/gancyclovir in H2SO4 medium could generate CL signal.Rhodamine B could obviously sensitize this signal,and the CL intensity was proportional to the concentration of acyclovir and gancyclovir.Therefore,a new FI-CL method has been described for the determination of acyclovir and gancyclovir.Results For acyclovir,the determination range was 3.0?10-5g/L-7.0?10-2g/L,with 1.56?10-5g/L as its determination limit.During 11 repeated measurements for 1.0?10-3g/L acyclovir,the relative standard deviation was 2.08%.For ganciclovir,the determination range was 5.0?10-5g/L-7.0?10-2g/L,with 2.35?10-5g/L as its determination limit.The relative standard deviation was 2.83%,with 11 repeated measurements of 1.0?10-3g/L ganciclovir.Conclusion This method has broad linear range,high sensitivity,and convenience and speediness,it therefore,can be successfully used to determine the content of ganciclovir in injections.