摘要:

Sangivamycin, 4-amino-5-carboxamido-7-(β-D-ribo-furanosyl)-pyrrolo[2,3-d]-pyrimidine is a structural analog of adenosine belonging to a group of nucleosides classified as pyrrolopyrimidines. Sangivamycin, an adenosine deaminase resistant analog, was found to inhibit the replication of three strains of herpes simplex virus type 1 (HSV-1) by 50% (ED50) at a concentration approximately equal to the concentration which inhibits cell growth by 50% (LD50). Both Vero cells and rabbit corneal stromal cells in exponential growth were about 10-fold more sensitive to the drug than quiescent cells. The selectivity indices of sangivamycin indicated that the drug was not a highly selective antiviral agent and, therefore, would offer no advantage over drugs currently available for the treatment of herpetic keratitis.

ISSN:0271-3683    

DOI:10.3109/02713688709020100

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Low levels (<5 units/eye) of interferon (IFN) were detected in the eyes of BALB/c and C57BL/6 mice one to five days after instillation of 107pfu/eye of herpes simplex virus type 1 (HSV) onto scarified corneas. This dose of virus produced herpetic keratitis characterized by dendritic epithelial lesions one day post infection in both strains of mice. The disease progressed to severe necrotizing stromal keratitis in the eyes of all BALB/c mice, but only three of 10 eyes of C57BL/6 mice by 21 days after infection. Footpad immunization 30 days prior to ocular infection protected both strains from stromal disease, but did not enhance IFN production in the eye. At lower inoculating doses of virus (<105pfu/eye), C57BL/6 mice showed greater resistance to stromal disease and produced less virus over a shorter period of time than BALB/c mice. No IFN was detected at any time after infection with doses of virus less than 107pfu/eye, nor was IFN detected in plasma of any infected mice. The failure to detect high levels of IFN in homogenates of eyes did not reflect an inability of ocular tissues to produce IFN since IFN-βwas detected as early as two hours after topical treatment with the potent IFN inducer, carboxymethylacridanone (CMA). The two mouse strains produced similar levels of IFN in the eye in response to CMA. These data indicated that the relative resistance of mice to HSV eye infection was not related to the rapid local production of IFN, nor was resistance related to systemic IFN production in plasma or spleen.

ISSN:0271-3683    

DOI:10.3109/02713688709020101

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

The use of recombinant human interferon alpha subtype D (RIFNαD) was effective in reducing shedding of herpes simplex virus type-1 induced by iontophoresis of 6-hydroxydopamine and epinephrine. A post stimulation treatment schedule of RIFNαD, one drop four times a day was as effective as pre-treatment, using the same dose regimen. The levels of interferon (IFN) present in the assay system are not sufficient to produce an antiviral effect. The levels of IFN required to suppress cell growth are substantially higher than the concentrations detected in the assay system.

ISSN:0271-3683    

DOI:10.3109/02713688709020102

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Because of reported differences in potency, recombinant DNA-derived human alpha interferons (IFNs) were reevaluated for use against acute Herpes Simplex Virus type 1 (HSV-1) infection of the rabbit eye. The IFNs used topically were IFN-alpha2(IFN-α2) and a consensus of known human IFN-αs, designated IFN-αCon. Prophylactic treatment with IFN-αCon, at 1 or 15×106U/eye/day beginning 48 hours before HSV-1 inoculation and therapeutic treatment with 5 or 15×106U/eye/day beginning 4 hours after inoculation with either IFN-αCon1or IFN-α2appeared to prevent or significantly reduce the development of corneal epithelial involvement. The effects were dose dependent with no evidence for decreased activity at the higher dose. The duration of HSV-1 shedding into tear film was not significantly reduced.

ISSN:0271-3683    

DOI:10.3109/02713688709020103

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Forty-five patients with virologically confirmed dendritic keratitis were treated in a randomized, double-blind controlled study with a basic therapy of trifluorothymidine (TFT) eye drops. In addition they received different human recombinant interferon (rHu IFN) eye drops. The following results were obtained for average healing times: TFT plus one drop daily of rHu IFN-alpha 2 arg (30 million iu/ml): 3.3 days, TFT plus rHu IFN-gamma (30 million iu/ml): 3.9 days, TFT plus a mixture of alpha plus gamma (0.3 million iu/ml each): 6.1 days, TFT plus a mixture of alpha plus gamma (1.5 million iu/ml each): 3.3 days. High-titer gamma interferon did not significantly differ from high-titer alpha interferon in the combination therapy of dendritic keratitis. A mixture of alpha plus gamma at a moderate titer (1.5 million iu/ml each) was as effective as a high-titer mono-preparation. Adding a low-titer interferon mixture gave no better therapeutic results than antiviral monotherapy. Thus it seems possible to save about 90% of interferon commonly used in the combination therapy of dendritic keratitis by applying a mixture of different suitable interferons instead of interferon monospecies.

ISSN:0271-3683    

DOI:10.3109/02713688709020104

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Twelve squirrel monkeys were inoculated in both eyes with the Rodanus strain of herpes simplex virus type 1 (HSV-1) and were examined for the presence of acute epithelial keratitis. All of the eyes developed dendritic keratitis within 72 hours after inoculation. The twelve monkeys plus two additional similarly infected monkeys were also examined for the presence of clinical recurrences of ocular herpes infections and spontaneous shedding of virus in their tears. Two of the eyes developed stromal disease, and 13 of the monkeys had at least one episode of recurrent clinical epithelial disease. Virus was isolated from two of the eyes with recurrent dendrites.

ISSN:0271-3683    

DOI:10.3109/02713688709020105

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

When herpes simplex virus (HSV) is inoculated onto the snout of the inbred strain NIH mouse, clinical disease of the eye ensues only after a delay, due to spead of virus to the eye occuring via neural pathways. This report is concerned with the detailed description of eye disease. Physical signs observed include mydriasis, iritis and keratitis. The incidence of combinations of physical signs has been analysed by the computer and presented as pie-charts to show the complexity and evolution of the eye disease.

ISSN:0271-3683    

DOI:10.3109/02713688709020106

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

ISSN:0271-3683    

DOI:10.3109/02713688709020107

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor