Effect of Adenine Arabinoside on Severe Herpesvirus hominis Infections in Man

Ch’ien, Lawrence T.; Cannon, Nassif J.; Charamella, Leigh J.; Dismukes, William E.; Whitley, Richard J.; Buchanan, R. A.; Alford, Charles A.

doi:10.1093/infdis/128.5.658

Cited by 96 publications

(8 citation statements)

References 16 publications

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“…A wide range of agents and procedures which are able to inhibit or suppress HSV replication in vivo or in vitro with varying degrees of success have emerged (with others being added to the list continually). Noteworthy among these are: several antimitotic chemicals (253), cancer cell extracts (2), human gamma globulin (1), trifluorothymidine (261), trifluorodeoxyuridine (124), lysine (123), iododeoxycytidine (144), iododeoxyuridine (IudR or IDU; 56, 138, 261), polyinosinic-cytidylic acid (179,231,260), interferon (126), ara-c (109), ara-c with L-asparaginase (34), arabinofuranosyladenine (138,200), phosphonoacetic acid (238), adenine arabinoside (45,199), rifamycin (181), ethyl ether (186), various photodynamic dyes (1C4), X irradiation (7,139), a vaccinia virus vaccine (72), a herpesvirus vaccine (127, 251), cryotherapy (19,83,104), and psychotherapy (25). However, HSV has proven to be resistant to glutathione (124), fl-methazone (124), pyran copolymers (231), lysozyme (124), 6-azauridine (138), and kethoxal (256).…”

Section: Treatment Of Recurrent Hsvmentioning

confidence: 99%

The latent herpes simplex virus.

Docherty¹,

Chopan²

1974

Bacteriological Reviews

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Section: Treatment Of Recurrent Hsvmentioning

confidence: 99%

The latent herpes simplex virus.

Docherty¹,

Chopan²

1974

Bacteriological Reviews

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“…Of them, 5-iodo-2'-deoxyuridine and 1-fl-D-arabinofuranosylcytosine (cytosine arabinoside) have been administered systemically to treat human infections of serious life-threatening character (2, 8). In the past 3 years, 9-fl-D-arabinofuranosyladenine (adenine arabinoside, ara-A) also has been used in clinical trials against serious or life-threatening human HVH infections; this purine nucleoside has proved to be much less toxic than cytosine arabinoside or 5-iodo-2'-deoxyuridine (1,2). In fact, evidence of any severe immediate side effects has not been documented at doses of 10 to 20 mg per kg per day during or after 14-to 20-day treatment courses (1, 2).…”

mentioning

confidence: 99%

“…In fact, evidence of any severe immediate side effects has not been documented at doses of 10 to 20 mg per kg per day during or after 14-to 20-day treatment courses (1, 2). At these doses, there has been some evidence of clinical and virological response based upon studies in patients with both HVH and varicella-zoster infections (1,2).…”

mentioning

confidence: 99%

Determination of Plaque Inhibitory Activity of Adenine Arabinoside (9-β- d -Arabinofuranosyladenine) for Herpesviruses Using an Adenosine Deaminase Inhibitor

Bryson

Connor

Sweetman

et al. 1974

Antimicrob Agents Chemother

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The in vitro susceptibility of type 1 and type 2 strains of Herpesvirus hominis to 9-/3-D-arabinofuranosyladenine (adenine arabinoside, ara-A) was measured in a system where deamination was inhibited. Under these conditions, it was possible to measure the activity of low concentrations of ara-A. It was determined that plaque inhibitory concentration for type 1 viruses was less than 3 ,g/ml for all strains tested. The plaque inhibitory concentration for 7 of 10 type 2 strains was also less than 3 ug/ml. The method used identified and controlled the interaction between antiviral agent (ara-A) and the indicator system, human skin fibroblastic cells. Otherwise, metabolism of ara-A resulted in rapid enzymatic degradation and loss of antiviral activity.Various antiviral compounds have been demonstrated to inhibit Herpesvirus hominis (HVH) infections. Of them, 5-iodo-2'-deoxyuridine and 1-fl-D-arabinofuranosylcytosine (cytosine arabinoside) have been administered systemically to treat human infections of serious life-threatening character (2, 8). In the past 3 years, 9-fl-D-arabinofuranosyladenine (adenine arabinoside, ara-A) also has been used in clinical trials against serious or life-threatening human HVH infections; this purine nucleoside has proved to be much less toxic than cytosine arabinoside or 5-iodo-2'-deoxyuridine (1, 2). In fact, evidence of any severe immediate side effects has not been documented at doses of 10 to 20 mg per kg per day during or after 14-to 20-day treatment courses (1, 2). At these doses, there has been some evidence of clinical and virological response based upon studies in patients with both HVH and varicella-zoster infections (1, 2).Recently, we designed a system which enabled us to determine inhibition of viral replication in tissue culture at concentrations of ara-A much lower than previously reported. The system requires that the activity of the enzyme adenosine deaminase (ADA) be completely inhibited in cell culture monolayers so that relatively low input concentrations of ara-A remain stable throughout a test period. Otherwise, the animal cells used in establishing challenge infection will rapidly metabolize ara-A through the action of ADA to 9-fl-D-arabinofuranosylhypoxanthine (ara-Hx). Under conditions where enzymatic activity is inhibited as rapidly as new ADA is produced by tissue culture cells, it is possible to determine accurately the relationship between concentrations of ara-A and the antiviral activity.Using this system, we examined 20 serotyped strains of HVH for sensitivity to ara-A and report our findings herein. MATERIALS AND METHODSTissue culture and virology. Ten type 1 and ten type 2 HVH strains were kindly supplied by A. Nahmias. Each was passaged once in confluent monolayers of mycoplasma-negative, human skin diploid fibroblastic (HSF) tissue culture cells. This cell strain originated in the cell culture laboratory of this institution and was derived from foreskin tissue of a newborn baby. Completely infected cultures were harvested, and portions were stored at ...

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“…Trials with cytosine arabinoside in zoster and iododeoxyuridine in herpes encephalitis have indicated the inadequacy of these drugs (Boston Interhospital Group, 1975;Stevens et al, 1973). At the present time, adenosine arabinoside is undergoing clinical trials and shows some promise (Ch'ien et al, 1973;Whitley, 1976). mised patients, evaluation of antiviral agents is particularly important.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic effects of polyinosinic• polycytidylic acid in man

Freeman

Al‐Bussam

O’Malley

et al. 1977

Journal of Medical Virology

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Twenty-four patients with cancer and concomitant infections with either herpes virus hominis or varicella zoster virus were treated with polyinosinic-polycytidylic acid (rIn.rCn) to determine: 1) the reliability of rIn.rCn to induce interferon production, and 2) the toxicity of the drug. Seven additional patients with herpes zoster were observed as controls. Two lots of rIn.rCn were used; Lot 1 was consistently effective in stimulating serum interferon at doses of 9 and 12 mg/kg, whereas Lot 2 was effective at doses of 3-12 mg/kg. There was no correlation between rIn.rCn doses within these ranges and the resultant interferon levels. Generally, peak serum interferon occurred within the first day. Toxicity to rIn.rCn consisted of fever in 21/24 patients, mild elevation of liver enzymes in 8/24 patients, and laboratory abnormalities of coagulation in 9 patients. The coagulation abnormalities appeared linearly related to the dose of rIn.rCn used. All these abnormalities were reversible, and none were considered severe of life-threatening. Since rIn.rCn was effective in stimulating interferon and since toxicity was considered acceptable, a randomized double-blind study was initiated to determine whether rIn.rCn is effective in the treatment of herpes zoster.

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Effect of Adenine Arabinoside on Severe Herpesvirus hominis Infections in Man

Cited by 96 publications

References 16 publications

The latent herpes simplex virus.

The latent herpes simplex virus.

Determination of Plaque Inhibitory Activity of Adenine Arabinoside (9-β- d -Arabinofuranosyladenine) for Herpesviruses Using an Adenosine Deaminase Inhibitor

Pharmacologic effects of polyinosinic• polycytidylic acid in man

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