acyclovir and ibacitabine

Topics: Acyclovir; Adolescent; Adult; Aged; Bromodeoxycytidine; Child; Clinical Trials as Topic; Deoxycytidine; Double-Blind Method; Female; Humans; Keratitis, Dendritic; Male; Middle Aged

We tested the in vitro sensitivity of Macropodid Herpesvirus 2 to eight commonly used anti-herpetic compounds using plaque reduction tests, March and April, 1995. The virus was most susceptible to inhibition by (E)-5-(2'-bromovinyl)-2'-deoxyuridine and adenine 9-beta-D-arabino-furanoside. Both compounds have been used for anti-herpetic therapy in humans and may prove useful in the treatment of macropodoids in captivity.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinonucleosides; Bromodeoxycytidine; Bromodeoxyuridine; Cell Line; Cytarabine; Deoxycytidine; Herpesviridae; Herpesviridae Infections; Idoxuridine; Macropodidae; Microbial Sensitivity Tests; Neutralization Tests; Thymidine; Trifluridine; Vidarabine

A rapid screening test for resistance to acyclovir, mediated by a lack of thymidine kinase (TK) activity in herpes simplex virus (HSV), was developed by utilizing the uptake of [125I]iododeoxycytidine (IdC) by infected Vero cells. Cells infected with TK+ virus demonstrate uptake of IdC within 3 hr of infection. The assay can detect as few as 690 pfu of virus. Cells infected with TK virus have an uptake of IdC similar to that of uninfected cells, whereas cells infected with TK+ generally have an uptake greater than 10 times that of uninfected cells if tested when obvious viral cytopathic effect is present. All 19 clinical HSV isolates tested were correctly identified as TK+. Of 17 blinded HSV isolates tested, all six TK- isolates were correctly identified. A single strain with an ID50 of 3.4 micrograms/ml and an altered TK substrate specificity was incorrectly classified as TK+. The assay is a useful, rapid screening test for viral TK activity.

Topics: Acyclovir; Animals; Bromodeoxycytidine; Cell Line; Chlorocebus aethiops; Deoxycytidine; Drug Resistance, Microbial; Herpes Simplex; Humans; Kidney; Microbial Sensitivity Tests; Simplexvirus; Thymidine Kinase

A plaque autoradiography assay to detect and quantitate thymidine kinase (TK) mutants of herpes simplex virus type 1 (HSV-1) and HSV-2 in clinical samples is described. This method utilizes the selective incorporation of [125I]iododeoxycytidine, a pyrimidine analog selectively phosphorylated by the HSV TK. Only cells infected with TK-competent virus will efficiently incorporate iododeoxycytidine and are the only cells detected by autoradiography. Furthermore, this assay discriminates between TK+ virus (TK competent) and TKA virus (TK altered or reduced). This ability to differentiate TK+ from TKA virus is enhanced when infected cells are labeled with [14C]thymidine in tandem with iododeoxycytidine labeling. Reconstruction experiments with mixtures of TK+ (HSV-1 Patton) virus and TK-deficient (TK-) (B2006) or TKA (IUDRr) mutants were performed to determine the limits of detection of this technique. Ten percent TK- or TKA virus was the lower limit for the detection of TK mutants in a mixed population, whereas 1 in 1,000 TK+ virus revertants could be detected in a TK- virus population. In reconstructed populations and 45 clinical samples, a good correlation existed between the increase in 50% inhibitory dose for acyclovir and the percent TK mutant virus present. Similarly, the results of this technique correlated well with the acyclovir phosphorylating activity of extracts from cells infected with isolates or reconstructed mixtures. Plaque autoradiography with [125I]iododeoxycytidine was able to distinguish mixed populations of TK+ and TK- virus and homogeneous populations of TKA virus. The tandem use of [125I]iododeoxycytidine and [14C]thymidine readily identified TKA virus, which appeared as TK+ virus when labeled with [14C]thymidine alone. This technique provides a sensitive screen for antiviral resistance due to alterations in the viral TK and can be used to analyze clinical samples.

Topics: Acyclovir; Autoradiography; Bromodeoxycytidine; Deoxycytidine; Herpes Simplex; Humans; Mutation; Simplexvirus; Thymidine; Thymidine Kinase; Viral Plaque Assay

Topics: Acyclovir; Amantadine; Antiviral Agents; Biguanides; Bromodeoxycytidine; Cytarabine; Deoxycytidine; Humans; Idoxuridine; Methisazone; Morpholines; Trifluridine; Vidarabine

Infection of the cornea due to herpes simplex virus continues to be a problem for ophthalmologists despite treatment of the disease with antiviral drugs. These drugs are known to produce some toxic effects and prolonged administration is sometimes necessary. Using tensile strength measurements to assess tissue repair, healing of a 5 mm perforating corneal stromal incision was measured after treatment with different antiviral drugs four times a day for eighteen postoperative days. Results suggest that 3% adenine arabinoside, 3% acycloguanosine, 1% trifluorothymidine, and 1% iododesoxycytidine ointments do not delay (p greater than 0.05) normal stromal healing.

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxycytidine; Cicatrix; Deoxycytidine; Keratitis, Dendritic; Rabbits; Tensile Strength; Trifluridine; Vidarabine; Wound Healing

Topics: Acyclovir; Antiviral Agents; Bromodeoxycytidine; Deoxycytidine; Deoxyuracil Nucleotides; Eye Diseases; Humans; Idoxuridine; Ophthalmic Solutions; Trifluridine; Vidarabine; Virus Diseases

Five clinically-used antiviral drugs (3% adenine arabinoside ointment; 3% acycloguanosine ointment; 0.24% idoxuridine ointment; 1% trifluorothymidine drops) were compared with a control (petrolatum base) to determine their toxic effects on rabbit corneal epithelium after injury by iodine vapors: --Only trifluorothymidine significantly retarded healing of epithelial erosions. --Histopathologic examination after seven-day treatment showed that all five drugs, except vidarabine and to a lesser degree acycloguanosine, caused toxic changes in the regenerating epithelium.

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxycytidine; Cornea; Deoxycytidine; Epithelium; Guanine; Idoxuridine; Rabbits; Trifluridine; Vidarabine; Wound Healing