The antiviral activity of 5-methoxymethyl-2′-deoxyuridine (MMUdR) was compared with that of 5-iodo-2′-deoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside (Ara-A). At concentrations of 2 to 4 μg/ml, MMUdR was inhibitory to herpes simplex virus type 1, but concentrations as high as 128 μg/ml were not inhibitory to three other herpesviruses tested (equine rhinopneumonitis virus, murine cytomegalovirus, and feline rhinopneumonitis virus) or to vaccinia virus. The other nucleosides, in contrast, were inhibitory at similar concentrations (1 to 8 μg/ml) against all viruses tested. The inhibition of HSV-1 by MMUdR appeared to be the result of interference with virus replication rather than the result of drug toxicity to host cells. The drug was not toxic to host cells at 100 times the antiviral concentrations, and pretreatment of host cells with high concentrations of MMUdR had no effect on subsequent virus replication. Combination of MMUdR with either IUdR, Ara-A, or Ara-C gave an enhanced antiviral effect, suggesting that the mechanism of action of MMUdR is different from that of the other three drugs. Antiviral indexes were calculated for each compound and were found to be >250, 80, 40, and 8 for MMUdR, IUdR, Ara-A, and Ara-C, respectively. These were defined as the minimum dose at which toxicity was observed microscopically divided by the dose which reduced plaque numbers by 50%.
Summary. The functional and morphological effcct.s of cyclophosphamide (Cy) on the immuin; response of the chicken were investigated. Chickens given Cy on day.s 1. 2 and 4 after hatching failed to produce antihody for at lea-st 6 weeks and had low lt'veLs of serum IgG. Birds surviving for more than 6 weeks recovered their iniuiunocompctence. The elfect of Cy on ccli-niediated immunity (CMl) was IcsK persistent. Allogeneic -skin grafts applied to one-week-old treated birds were not rejected but grafts were rejected from 3-week-old recipients. At no time was graft versus host activity completely eliminated by Cy treatment.Morphological changes in the lymphoid organs reflected the results of functional tests. Early after treatment, lymphocytes were eliminated from thymu-s. bursa and .spleen. Lymphoid regeneration usually occurred in the thymus by 3 weeks after treatment. Bursal regeneration was observed less frequently, and usually only in birds older than (i weeks. In many birds, chronic degenerative changes in the epithelial cells were apparent, especially in the bursa.It was speculated that in those birds where thymus or bursa regeneration failed to occur there was damage to the epithelial component of the organs. Possibly the bursal epithelial cells were more susceptible to the action of Cy than were thymic epithelial cells.
5-Methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000mg/kg given daily for 9 days were not immunosupporessive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus.
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