Drugs online research references
Antiviral Res. 2003 Apr;58(2):159-65.
Synergy of bovine lactoferrin with the anti-cytomegalovirus drug cidofovir in vitro.
van der Strate BW, De Boer FM, Bakker HI, Meijer DK, Molema G, Harmsen MC.
Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration (GUIDE), University Centre for Pharmacy, Ant Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Human cytomegalovirus (HCMV) causes severe morbidity and mortality in immunocompromised patients. Treatment of HCMV infections with conventional antiviral drugs like ganciclovir and cidofovir has major drawbacks (i.e. serious side effects). Therefore, combination therapies using drugs with different antiviral mechanisms should be envisaged. Potential synergy between lactoferrin (LF), an antibacterial, antimycotic and antiviral protein, and the antiviral drugs acyclovir, ganciclovir, foscarnet and cidofovir was investigated, using an in vitro test system with the recombinant RC256 HCMV strain. RESULTS: Combination of LF with acyclovir and foscarnet resulted in antagonism. When LF and ganciclovir were combined, neither synergy nor antagonism was observed. Strikingly, the combination of LF with cidofovir resulted in marked synergy. The synergistic effect could be explained by inhibition of two subsequent steps in the viral replication cycle: HCMV penetration into the target cells and intracellular synthesis of HCMV DNA. In conclusion, LF might be a potential candidate for combination therapy with cidofovir.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12742576&dopt=Abstract
itsa.ucsf.edu
The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12743269&dopt=Abstract
Nephrol Dial Transplant. 2003 Jun;18(6):1135-41.
High serum concentrations of the acyclovir main metabolite 9-carboxymethoxymethylguanine in renal failure patients with acyclovir-related neuropsychiatric side effects: an observational study.
Hellden A, Odar-Cederlof I, Diener P, Barkholt L, Medin C, Svensson JO, Sawe J, Stahle L.
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. anders.hellden
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