Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.

Lamivudine for chronic hepatitis B: a brief review

Until recently, the only generally approved treatment for chronic hepatitis B was alpha-interferon; however, it gives only moderate efficacy in terms of sustained response (biochemical, virological and histological). In fact, only 20 percent to 40 percent of treated patients respond to therapy, with lower percentages (~ 10 percent) among patients infected with precore-mutant strains of HBV (HBeAb HBV-DNA positive). The FDA of the USA approved the use of lamivudine in adult patients affected by chronic hepatitis B in 1998. In this review, we focused on the pharmacokinetic and pharmacodynamic properties and efficacy and tolerability of lamivudine in the treatment of chronic hepatitis B cases that are both HBeAg and anti-HBe-positive.

Interactions between antiplasmodial 3,6-diamino-1'-dimethyl-9-anilinoacridine and hematin and concanamycin A.

Antiplasmodial 9-anilinoacridine derivatives exert their effects either by inhibiting DNA topoisomerase (topo) II or by interfering with heme crystallization within the parasite acidic food vacuole. Previous studies have shown that analogs of 9-anilinoacridine containing 3,6-diamino substitutions (in the acridine ring) inhibit Plasmodium falciparum DNA topo II in situ, whereas those with a 3,6-diCl substitution act by inhibiting beta-hematin formation, a property also seen with 3,6-diamino-1'-dimethyl-9-anilinoacridine (DDAA). To understand this seemingly anomalous property of DDAA, studies of its interaction with hematin and localization within the parasite food vacuole were undertaken. A weak interaction with hematin was demonstrated spectroscopically. Antagonism of DDAA inhibition of Plasmodium falciparum growth in culture by concanamycin A, a macrolide antibiotic inhibitor of vacuolar H(+)-ATPase derived from Streptomyces sp, was equivocal.

Comportamiento clínico y terapeutico del herpes zoster en el centro nacional de dermatología Doctor Francisco José Gómez Urcuyo enero 2002 - diciembre 2006 / Clinical and therapeutic behavior of herpes to zoster in center national of dermatology Doctor Francisco Jose Gómez Urcuyo January 2002 - December 2006

El Herpes Zóster es una infección producida por el virus Varicela - Zoster, siendo el único virus herpes capaz de producir dos cuadros diferentes: Varicela, como una enfermedad eruptiva de la infancia y Zóster, como una virosis de la edad adulta o de la senectud. En nuestro país, ha sido un problema poco estudiado y no se cuenta con investigaciones que reflejen el comportamiento real en el Centro Dermatológico Nacional "Dr. Francisco José Gómez Urcuyo", se realizó un estudio descriptivo, de corte transversal, no probalilístico con el objetivo de determinar el comportamiento clínico y terapéutico del Herpes Zóster. El universo lo conformaron 721 pacientes que fueron atendidos por primera vez en la consulta externa con diagnóstico de Herpes Zóster, la muestra fue constituida por 614 pacientes en los que se encontraron todos los datos completos. Dentro de los principales resultados, 326 pacientes fueron del sexo femenino y 286 masculinos. La gran mayoría de los pacientes (94 porciento) procedían del área urbana y sólo un 6 porciento eraan del área rural. 270 (45 porciento) fueron mayores de 50 años...

N-terminal amino acids of bovine alpha interferons are relevant for the neutralization of their antiviral activity

The structure-function relationship of interferons (IFNs) has been studied by epitope mapping. Epitopes of bovine IFNs, however, are practically unknown, despite their importance in virus infections and in the maternal recognition of pregnancy. It has been shown that recombinant bovine (rBo)IFN-alphaC and rBoIFN-alpha1 differ only in 12 amino acids and that the F12 monoclonal antibody (mAb) binds to a linear sequence of residues 10 to 34. We show here that the antiviral activities of these two IFNs were neutralized by the F12 mAb to different extents using two tests. In residual activity tests the antiviral activity dropped by more than 99 percent with rBoIFN-alphaC and by 84 percent with rBoIFN-alpha1. In checkerboard antibody titrations, the F12 mAb titer was 12,000 with rBoIFN-alphaC and only 600 with rBoIFN-alpha1. Since these IFNs differ in their amino acid sequence at positions 11, 16 and 19 of the amino terminus, only these amino acids could account for the different neutralization titers, and they should participate in antibody binding. According to the three-dimensional structure described for human and murine IFNs, these amino acids are located in the alpha helix A; amino acids 16 and 19 of the bovine IFNs would be expected to be exposed and could bind to the antibody directly. The amino acid at position 11 forms a hydrogen bond in human IFNs-alpha and it is possible that, in bovine IFNs-alpha, the F12 mAb, binding near position 11, would disturb this hydrogen bond, resulting in the difference in the extent of neutralization observed

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

The objective of this prospective study was to evaluate the efficacy and complications of the use of an intraocular sustained-release ganciclovir implant for the treatment of active cytomegalovirus (CMV) retinitis in AIDS patients. Thirty-nine eyes of 26 patients were submitted to ocular surgery. All patients underwent complete ocular examination before and after surgery. The surgical procedure was always done under local anesthesia using the same technique. The mean time for the surgical procedure was 20 min (range, 15 to 30 min). The average follow-up period was 3.7 months. Of all patient, only 4 presented recurrence of retinitis after 8, 8, 9 and 2 months, respectively. Three of them received a successful second implant. All 39 eyes of the 26 patients presented healing of retinitis as shown by clinical improvement evaluated by indirect binocular ophthalmoscopy and retinography. Retinitis healed within a period of 4 to 6 weeks in all patients, with clinical regression signs from the third week on. Six (15.4 percent) eyes developed retinal detachment. None of the patients developed CMV retinitis in the contralateral eye. The intraocular implant proved to be effective in controlling the progression of retinitis for a period of up to 8 months even in patients for whom systemic therapy with either ganciclovir or foscarnet or both had failed. The intraocular sustained-release ganciclovir implant proved to be a safe new procedure for the treatment of CMV retinitis, avoiding the systemic side effects caused by the intravenous medications and improving the quality of life of the patients.

Actualidades en el tratamiento de la infección por el virus de la inmunodeficiencia humana (VIH) / Update on the treatment of human immunodeficiency virus infection (HIV)

El síndrome de inmunodeficiencia adquirida fue descrito desde 1981. El primer medicamento con efecto antirretroviral aprobado fue la zidovudina en 1987. Desde entonces han surgido una gran cantidad de nuevos medicamentos y combinaciones de éstos para intentar la curación o, al menos, el control de la progresión de esta terrible infección. Existen nuevas formas de monitorizar la evolución y respuesta al tratamiento que han permitido establecer esquemas de tratamiento específicos para cada caso. La meta en el tratamiento de la infección por virus de la inmunodeficiencia humana es lograr la supresión de la replicación viral. En este artículo se revisan las nuevas opciones de tratamiento y seguimiento del paciente con infección por el virus de la inmunodeficiencia humana

Medicamentos antivirales / Antiviral drugs

Se revisan los mecanismos y sitios de acción de los diferentes agentes y drogas contra los virus más frecuentes que producen enfermedades de importancia clínica y epidemiológica. El desarrollo de la biología molecular y las tecnologías de avanzada han permitido conocer las distintas etapas de la multiplicación de los ácidos nucleicos y proteínas de los virus; estos pasos pueden constituir puntos críticos o blancos donde actúen sustancias químicas de origen natural o diseñadas especialmente mediante técnicas sofisticadas que entorpecen, e incluso detienen la duplicación viral. El objetivo principal es acercar al médico de asistencia a este tema de poca aplicación práctica en nuestro entorno clínico. La terapia antiviral ha entrado en una época de progreso que va desde la impotencia terapéutica a la posibilidad actual de tratar muchas enfermedades virales. No estarán lejos los días en que los médicos necesitarán conocer tanto sobre el tratamiento de las infecciones virales como sobre sus similares bacterianass

Determinación de la actividad antiviral de un xilomanano sulfatado de origen natural en distintas condiciones experimentales / Determination of the antiviral activity of a natural sulphated xylomannan under different experimental conditions

Se analizó la influencia de distintas condiciones experimentales sobre la determinación de la actividad antiviral del xilomanano sulfatado F6, aislado del alga roja patagónica Nothogenia fastigiata, sobre la multiplicación de los virus herpes simplex tipos 1 y 2 (HSV-1 y HSV-2). En las condiciones ensayadas, la concentración inhibitoria 50 por ciento (CI50) de F6 resultó independiente de la multiplicidad de infección (en el rango 0,1-0,0001 UFP/célula), del tipo de ensayo antiviral empleado (inhibición del rendimiento viral o reducción en la formación de placas), de la cepa de virus (F, KOS, B2006, Field) y de la línea celular (Vero, HEp-2, BHK-21). La independencia del efecto inhibitorio de F6 respecto de la multiplicidad de infección representa una ventaja para este polisacárido respecto de otros compuestos antivirales que sólo son activos frente a muy bajas dosis de virus

Modulation of thymidine kinase activity: a biochemical strategy to enhance the activation of antineoplastic drugs

Thymidine kinase is a key enzyme responsible for the activation of several anticancer and antiviral drugs. As the first enzyme in the salvage pathway of thymidine, it is regulated by the feedback inhibition exerted by the end-product of the pathway, namely thymidine 5'-triphosphate. 5'-Aminothymidine is a non-toxic analogue of thymidine capable of interfering with this regulatory mechanism. In fact, it has been shown that 5'-aminothymidine increases the cytotoxicity and metabolism of various thymidine analogues currently in use of the clinic as antineoplastic agents. This mini-review article focuses in the evidence supporting the role of 5'-aminothymidine as a potential prototype drug for a new class of anticancer agents: drugs which affect the regulation of key metabolic pathways that determine the efficacy of agents with cytotoxic activity. The mechanism of action, antineoplastic activities and basis for selectivity in tissue culture models are also described

Antivirales de uso clínico actual / Antiviral drugs for clinical use

Numerosos fármacos antivirales han sido aprobados para ser empleados en adultos y niños, incluidos recién nacidos e individuos con defectos de la inmunidad, para el tratamiento de infecciones virales respiratorias, de la piel y las mucosas; el sistema nervioso central. Uno de los principales blancos de estos medicamentos es la ADN polimerasa, que incorpora nucleótidos trifosfatos en el extremo 3'OH de las cadenas de ADN y ha sido exitosamente inhibida por análogos de nucleósidos como adenina arabinósido y aciclovir. El descubrimiento de los retrovirus ha enfocado la atención hacia transcriptasa reversa, que copia el ARN viral en ADN proviral biténico, éste se integra al ADN huésped y luego es transcrito por la ARN polimerasa celular a nuevas répticas de ARN viral. Los esfuerzos para bloquear la transcriptasa reversa han resultado en drogas como la zidovudina (azidotimidina) usada para tratar el síndrome de inmunodeficiencia adquirida (SIDA) y sus análogos dideoxicitidina, dideoxiadenosina y dideoxilinosina