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Biomedical subjects

L B Allen

Publications and source records attributed to L B Allen.

53 records · Page 3Linked to original sources
PubMed1975

In vitro and in vivo effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on types 1 and 3 parainfulenza virus infections.

1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) had significant in vitro activity against type 1 parainfluenza (Sendai) and type 3 parainogenic (HA-1) viruses. Activity was manifested as inhibition of both viral cytopathogenic effect and of recoverable virus or viral hemagglutinin titer. The minimum Sendai virus inhibitory concentration was determined to be approximately 3.2 mug/ml. Previous studies had determined the minimum concentration inhibiting HA-1 virus was approximately 1-10 mug/ml. The effect of time of addition of ribavirin to virus-infected cells was determined; maximal activity was seen when the drug added just prior to either virus or within 4-8 h after each virus, although anti-Senadi viral effects were still apparent when ribavirin was added as late as 24 h after the virus. Ribavirin had no effect on adsorption of HA-1 or Sendai virus to cells. Lethal Sendai virus infections of mice were significantly inhibited by multiple intraperitoneal ribavirin treatment, starting either 4 h before or up to 24 h after virus inoculation. Therapy starting 48, 72 or 96 h after virus exposure had a moderate degree of efficacy. Treatment using an aerosol chamber also was of moderate effectiveness, although the procedure was considered traumatic to the animals. A nonlethal, principally upper respiratory tract infection of hamsters induced by the HA-1 virus was inhibited by ribavirin therapy. Treatment administered intraperitoneally, per os or by aerosol chamber resulted in reduced 23-day antibody titers to the virus, presumably because of reduction of virus in the animal. In a separate experiment, intraperitoneal ribavirin therapy resulted in a 1 log10 or less reduction in virus titer in nasal washings from HA-1 virus-infected hamsters, whereas, when the drug was administered intranasally in a dry powder aerosol spray, nasal virus titers were reduced up to 2 log10 and a moderate virus-induced lung consolidation was completely inhibited.

Adsorption↗
PubMed1975

Effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on Friend leukemia virus infections in mice.

Ribavirin, when administered intraperitoneally to mice infected with Friend leukemia virus, significantly inhibited development of the disease as determined by inhibition of virus-induced splenomegaly and viable virus titers in the spleen and plasma of the infected animals. The drug was effective whether administered ip in multiple daily treatments, treatments every three days, or single injection. Greatest efficacy was seen when therapy began early in the infection, presumably while the virus was in its eclipse phase.

Animals↗
PubMed1974

In vitro antiviral activity of 6-substituted 9-beta-D-ribofuranosylpurine 3', 5'-cyclic phosphates.

A series of twelve recently synthesized 6-substituted derivatives of 9-beta-d-ribofuranosylpurine 3',5'-cyclic phosphate (RPcMP) were evaluated for in vitro antiviral activity, using inhibition of viral cytopathogenic effect as the primary parameter for evaluation. Inhibition of the development of intra- and extracellular virus titer was used as a secondary criterion with certain viruses. Five derivatives were considered to have significant antiviral activity. 6-Hydroxylamino-RPcMP was active against type 1 herpes simplex, cytomegalo-, and vaccinia viruses. 6-Thio-RPcMP was inhibitory to types 1 and 2 herpes simplex, cytomegalo-, vaccinia, and type 3 parainfluenza viruses. The 6-methylthio derivative was active against types 1 and 2 herpes simplex, cytomegalo-, and vaccinia viruses, and types 1A, 2, 8, and 13 rhinoviruses; alteration of this 6-substitution to 6-ethylthio or to 6-benzylthio weakened the herpes- and vaccinia virus activity of the compound, but each continued to have significant antirhinovirus activity. The effect of time of addition of 6-methylthio-RPcMP to type 1 herpes simplex virus-infected cells was determined; the compound was most active when added prior to the virus. Early removal of the compound from the infected cells markedly reduced its antiviral effectiveness.

Animals↗
PubMed1973

In vitro effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses.

Virazole (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a highly soluble new synthetic nucleoside having significant, reproducible activity against a broad spectrum of deoxyribonucleic acid and ribonucleic acid viruses in vitro. The drug inhibited viral cytopathogenic effects in monolayers of cells infected for 3 days with type 3 adeno, types 1 and 2 herpes, myxoma, cytomegalo, vaccinia, infectious bovine rhinotracheitis, types 1A, 2, 8, 13, and 56 rhino, types 1 and 3 parainfluenza, vesicular stomatitis, subacute sclerosing panencephalitis, Semliki Forest, Newcastle disease, and measles viruses. Hemagglutinin production by influenza A(2), influenza B, and type 1 parainfluenza viruses in chicken embryo cells was reduced by Virazole treatment. Recoverable intra- and extracellular virus titers were reduced by the drug in experiments with type 1 herpes, vaccinia, type 3 parainfluenza, and vesicular stomatitis viruses. Plaque formation by type 1 herpesvirus was also inhibited by exposure of the infected cells to Virazole. Pretreatment of cells with the compound, followed by its removal before addition of type 1 herpesvirus, severely lessened the antiviral activity; the compound was still moderately effective in reducing the viral effects on the cells when added as long as 22 hr after the virus. Parallel experiments, in which the antiviral activity of a number of known active drugs was compared, indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials. The CCED(50) of Virazole to chicken embryo cells was approximately 1,000 mug/ml, although concentrations as low as 10 mug/ml caused slight (15%) inhibition in total cellular protein after 72 hr of incubation.

Amides↗
PubMed1973

Effect of 1-beta-D-ribofuranosyl1-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on herpes and vaccinia keratitis and encephalitis in laboratory animals.

Topical application of 1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) significantly inhibited the development of herpetic keratitis in the eyes of rabbits, as determined by both infectivity and Draize scoring parameters. Significant inhibition of the infection was demonstrated with 10% concentrations of Virazole; a 1% solution had a moderate effect, whereas doses of 0.1 and 0.01% had little activity in this system. A 5% concentration of Virazole similarly inhibited vaccinia keratitis in rabbits. Encephalitis-induced mortality in hamsters initially infected intraocularly with herpesvirus was significantly prevented or inhibited by topical application of 5, 10, and 20% concentrations of Virazole. Surviving, treated hamsters had no signs of herpes keratitis. The 20% concentration was the approximate LD(50) in hamsters. Virazole administered subcutaneously or intraperitoneally to mice did not appreciably alter the course of herpes virus- or vaccinia virus-induced encephalitis in these animals, although in a herpesvirus experiment direct injection of the drug into the brains 3 hr prior to virus inoculation resulted in a significant survivor increase.

Amides↗
PubMed1972

Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide.

Virazole is a synthetic nucleoside active in tissue culture against at least 16 DNA and RNA viruses. Applied topically, it inhibits herpetic keratitis in rabbits and tail lesions induced by herpes, vaccinia, and vesicular stomatitis viruses in mice. Injected intraperitoneally into mice, it inhibits splenomegaly and hepatomegaly induced by Friend leukemia virus and respiratory infections caused by influenza A(O), A(2), and B viruses and parainfluenza 1 virus. infections is also effective.

Adenoviridae↗
PubMed1972

Target-organ treatment of neurotropic virus diseases: efficacy as a chemotherapy tool and comparison of activity of adenine arabinoside, cytosine arabinoside, idoxuridine, and trifluorothymidine.

A sensitive in vivo system was studied for use in evaluating relatively small quantities of antiviral compounds. Swiss mice were injected intracerebrally with 10 LD(50) of type 1 herpes simplex virus (HSV) or vaccinia virus. Test compounds were injected intracerebrally into mice at a standard time interval after virus inoculation. Significant increases in the number of survivors in drug-treated, infected animals as compared to saline-treated virus controls was the criterion for evaluation of antiviral activity. 9-beta-d-Arabinofuranosyladenine (Ara-A) was used to determine an optimal time of therapy for this system. Significant survival increases occurred when the drug was injected 3, 6, 12, and 48 hr after HSV inoculation, with maximal effect occurring after the 6-hr treatment interval. Determination of brain virus titer of 6-hr Ara-A- and saline-treated mice at various intervals indicated that treatment with the drug delayed development of detectable levels of HSV by 1 day. 1-beta-d-Arabinofuranosylcytosine (Ara-C), trifluorothymidine (TFT), and 5-iodo-2'-deoxyuridine (IDU) were also evaluated with the use of the 6-hr treatment time against HSV and vaccinia virus. Ara-A and TFT increased the number of survivors among mice infected with either virus, whereas Ara-C increased the survivors among HSV-infected, but not vaccinia virus-infected, mice. IDU was inactive against both viruses.

Adenine↗
PubMed1972

Target-organ treatment of neurotropic virus disease with interferon inducers.

Interferon inducers were used against vaccinial encephalitis to study the target-organ treatment of neurotropic disease and to correlate interferon levels and the antiviral state following such treatment. A 45-mug amount of statolon, 30 mug of polyribinosinic-polyribocytidylic acid complex (poly I.poly C), or 0.0154 HA unit of Sendai virus given intracerebrally protected 100% of mice challenged the next day with 1,000 median lethal doses (LD(50)) of vaccinia virus. Significant protection against 1,000 LD(50) of vaccinia virus persisted for 1, 4, or 3 weeks after poly I.poly C, statolon, or Sendai virus (154 HA units), respectively. These doses of poly I.poly C and statolon were also used to study postinfection treatment. Mice challenged with 1, 10, 100, or 1,000 LD(50) were treated intracerebrally with poly I.poly C or statolon 24 or 48 hr later. Significant increases in survival time were seen in mice challenged with 1 to 100 LD(50) of vaccinia virus and treated 24 hr later. At challenges of 10 or 100 LD(50), statolon was more effective than poly I.poly C in increasing survival times. When treatment was delayed until 48 hr after infection, significant increases in survival time occurred only when the challenges were in the range of 1 to 10 LD(50), with poly I.poly C and statolon being equally effective. Interferon was measured by Finter's dye-uptake method, with L-929 cells and Semliki Forest virus. Poly I.poly C, statolon, or Sendai virus, given intracerebrally to mice, produced serum interferon peaks of 5,120 units/ml at 2 hr, 2,560 units/ml at 12 hr, or 320 units/ml at 18 hr, respectively. Corresponding brain interferon peaks were 640 units/g at 2 hr, 640 units/g at 4 to 24 hr, and 960 units/g at 72 hr.

Animals↗
PubMed1970

Simple method of evaluating scrapie in mice.

Mice in advanced scrapie characteristically clasp their hindlegs together. As the disease progresses into the clasping stage, mice exhibit a sequence of identifiable hindleg reactions which have categorized and assigned relative scores permitting objective, quantitative evaluation of disease.

Animals↗
PubMedDate not supplied

A simple method of drying virus on inanimate objects for virucidal testing.

A simple method for drying virus on inanimate objects (cover slips) under vacuum in the cold is described. Following this procedure virus maintains high titers (10(6-7)) for periods of 1-3 wk at -70 degrees C depending on the virus. For virucidal assay of disinfectants, cover slips are exposed to medium simulating the disinfectant (virus control) or disinfectant in an upright position in an Ultra-Vu cuvette. Cover slips are readily removed and placed in tissue culture medium for dilution of virus and determination of virus titer. Cytotoxicity of disinfectant is determined by exposing cover slip without virus to disinfectant, then placing it in medium, diluting the medium and incubating with the indicator cells. The use of this technique results in high titers of virus on cover slips, which are inanimate objects requiring minimal manipulation. The titration of virus or cytotoxicity in microplates is cell, medium, serum, and labware economical.

Antiviral Agents↗
PubMedDate not supplied

Effect of the estrous cycle on susceptibility of female mice to intravaginal inoculation of herpes simplex virus type 2 (HSV-2).

In order to explore the effect of sexual maturity on the susceptibility of mice to genital herpesvirus infections, mice were separated into the four stages of the estrous cycle and inoculated intravaginally with varying doses of HSV-2, strain 186. Deaths were observed as indicators of susceptibility and were recorded as follows: proestrous, 33%; estrous, 16%; metestrous, 9% and diestrous, 75%. To determine the course of infection in animals inoculated at different stages of estrous, cotton swabs were used to collect vaginal specimens at various times post-virus inoculation for virus titration. All mice inoculated during diestrous were positive for virus as early as 6 hours post-virus inoculation and had titers that increased over a 3 day period. Mice inoculated in other stages of estrus were positive only briefly (at 6 h) or had no detectable virus. In order to verify the susceptibility associated with diestrous, mice were ovariectomized to produce a continuous diestrous (pseudodiestrous) and when inoculated greater than or equal to 66.7% died. In contrast, none of the mice which had been ovariectomized and treated with estrogen to simulate the estrus stage died. We postulate that in stages other than diestrous virus may adsorb to epithelial cells in the lumen of the vagina and/or be expelled from the body by nonspecific resistance functions, thus reducing the likelihood of vaginal infection.

Animals↗