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freenet.de
The vast majority of the world population is infected with at least one member of the human herpesvirus family. Herpes simplex virus (HSV) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. Since the milestone development in the late 1970s of acyclovir (Zovirax), a nucleosidic inhibitor of the herpes DNA polymerase, no new non-nucleosidic anti-herpes drugs have been introduced. Here we report new inhibitors of the HSV helicase-primase with potent in vitro anti-herpes activity, a novel mechanism of action, a low resistance rate and superior efficacy against HSV in animal models. BAY 57-1293 (N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide), a well-tolerated member of this class of compounds, significantly reduces time to healing, prevents rebound of disease after cessation of treatment and, most importantly, reduces frequency and severity of recurrent disease. Thus, this class of drugs has significant potential for the treatment of HSV disease in humans, including those resistant to current medications.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11927946&dopt=Abstract
peds.uab.edu
Herpes simplex virus (HSV) infections are ubiquitous. Children are infected with HSV resulting in totally asymptomatic acquisition to life-threatening disease. Therapy of HSV diseases of children can be considered according to severity and time of acquisition. Neonatal herpes simplex virus infections take one of three forms--disease localized to skin, eye, or mouth (SEM), encephalitis, or multiorgan disseminated disease. Treatment consists of intravenous (IV) administration of acyclovir. Supportive care for patients with life-threatening disease is an integral component of patient management. Mucocutaneous HSV infections in the immunocompromised host can be treated with either intravenous acyclovir or one of the orally bioavailable antiviral therapies. For hospitalized patients, therapy consists of IV acyclovir at 5 mg/kg every 8 hours for 7 to 14 days. For ambulatory patients, therapy is tailored according to age. For children less than 12 years of age, oral acyclovir is administered at a dosage of 20 mg/kg every eight hours. Although no controlled studies have been performed with valaciclovir or famciclovir, the pharmacokinetics of these medications would suggest superiority over acyclovir. Dosage recommendations have not been established for young children. For postpubertal children, dosage should mirror that of adults. Valaciclovir is administered at 500 mg twice daily. Famciclovir is administered at 125 mg three times daily. Herpes simplex keratoconjunctivitis is treated with topical triflurothymidine. Two drops are applied to the infected eye five times daily until resolved. Recurrences are managed in a similar manner. Some physicians administer oral acyclovir at the doses noted above in order to prevent frequent recurrences. Genital HSV infections can be treated with acyclovir, valaciclovir, or famciclovir. Episodic treatment of recurrent episodes is usually not necessary in childhood. Importantly, all data on the use of these compounds for these conditions have been generated in adults. Physician judgment is required for the management of recurrent herpes labialis, erythema multiforme, and herpes gladitorum. No controlled studies have been performed in children, although experience with acyclovir, valaciclovir, and famciclovir have resulted in their use.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11931730&dopt=Abstract [PubMed - as supplied by publisher]
J Virol. 1996 Oct;70(10):7341-6.
Infection of primary CD4+ and CD8+ T lymphocytes by Epstein-Barr virus enhances human immunodeficiency virus expression.
Guan M, Zhang RD, Wu B, Henderson EE.
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
CD4+ and CD8+ T lymphocytes purified from normal adult donors by flow cytometry could be infected with Epstein-Barr virus (EBV) as measured by the accumulation of components of the EBV replicative cycle, viral DNA and viral transcripts encoding EBER1 and BRLF1. EBV infection resulted in enhanced replication of human immunodeficiency virus type 1 (HIV-1) IIIB in CD4+ lymphocytes as measured by accumulation of reverse transcriptase and formation of syncytia. Furthermore, a small percentage of CD8+ T cells became permissive after infection with EBV. Inactivation of transforming functions by irradiation with UV light greatly reduced the ability of EBV to enhance HIV-1 replication in T4+ T cell, suggesting that live virus is needed for enhancement. These results demonstrate a direct synergy between EBV and HIV-1 during coinfection of T cells in vitro and may explain the beneficial effect of acyclovir in combination with antiretroviral chemotherapy as well as the increased incidence of T-cell lymphomas associated with EBV in patients with AIDS.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8794395&dopt=Abstract
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