The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
David H Katz - One of the best experts on this subject based on the ideXlab platform.
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clinical efficacy of topical Docosanol 10 cream for herpes simplex labialis a multicenter randomized placebo controlled trial
Journal of The American Academy of Dermatology, 2001Co-Authors: Stephen L Sacks, David H Katz, Ronald A Thisted, Terry M Jones, Rick A Barbarash, Dennis J Mikolich, Gary E Ruoff, Joseph L Jorizzo, Lucy B Gunnilla, Mohammed H KhalilAbstract:Abstract Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. Objective: Our purpose was to determine whether Docosanol 10% cream (Docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. Methods: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either Docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. Results: The median time to healing in the 370 Docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients ( P = .008; 95% confidence interval [CI]: 2, 22). The Docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P = .002; 95% CI: 3, 16.5); (2) complete healing of classic lesions ( P = .023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions ( P P = .109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with Docosanol were mild and similar to those with placebo. Conclusion: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration. (J Am Acad Dermatol 2001;45:222-30.)
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Clinical efficacy of topical Docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial ☆ ☆☆ ★ ★★
Journal of The American Academy of Dermatology, 2001Co-Authors: Stephen L Sacks, David H Katz, Ronald A Thisted, Terry M Jones, Rick A Barbarash, Dennis J Mikolich, Gary E Ruoff, Joseph L Jorizzo, Lucy B Gunnilla, Mohammed H KhalilAbstract:Abstract Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. Objective: Our purpose was to determine whether Docosanol 10% cream (Docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. Methods: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either Docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. Results: The median time to healing in the 370 Docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients ( P = .008; 95% confidence interval [CI]: 2, 22). The Docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P = .002; 95% CI: 3, 16.5); (2) complete healing of classic lesions ( P = .023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions ( P P = .109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with Docosanol were mild and similar to those with placebo. Conclusion: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration. (J Am Acad Dermatol 2001;45:222-30.)
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the antiviral drug Docosanol as a treatment for kaposi s sarcoma lesions in hiv type 1 infected patients a pilot clinical study
AIDS Research and Human Retroviruses, 2001Co-Authors: Michael J Scolaro, Lucy B Gunnill, Laura E Pope, Mohammed H Khalil, David H Katz, James BergAbstract:Docosanol inhibits a broad spectrum of lipid-enveloped viruses in vitro including HSV-1, HSV-2, VZV, CMV, HHV-6, and HIV-1. These observations led us to conduct a pilot clinical study with docosano...
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topical application of Docosanol or stearic acid containing creams reduces severity of phenol burn wounds in mice
Contact Dermatitis, 2000Co-Authors: Mohammed H Khalil, David H Katz, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:Because of their reported antiviral and anti-inflammatory activities, cream formulations containing n-Docosanol (Docosanol) or stearic acid were tested for effects on chemically-induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.5, 3, and 6 h later. Progression of the wounds was assessed by a single evaluator after 8 h, using a numerical score of gross morphology. Docosanol- and stearic acid-containing creams substantially and reproducibly lessened the severity and progression of skin lesions compared to untreated sites with a 76% and 57% reduction in mean lesion scores, respectively. Untreated wounds appeared red and ulcerated; Docosanol cream-treated wounds showed only slight erythema.
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the anti herpes simplex virus activity of n Docosanol includes inhibition of the viral entry process
Antiviral Research, 1998Co-Authors: Laura E Pope, David H Katz, John F Marcelletti, Lee R Katz, M L Parish, P G SpearAbstract:n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-Docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-Docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1:2 of approximately 3 h. Reduced expression of viral genes in n-Docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins—an immediate post entry event—was indicated by a 75% reduction in the expression of b-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate—early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-Docosanol. © 1998 Elsevier Science B.V. All rights reserved.
Laura E Pope - One of the best experts on this subject based on the ideXlab platform.
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the antiviral drug Docosanol as a treatment for kaposi s sarcoma lesions in hiv type 1 infected patients a pilot clinical study
AIDS Research and Human Retroviruses, 2001Co-Authors: Michael J Scolaro, Lucy B Gunnill, Laura E Pope, Mohammed H Khalil, David H Katz, James BergAbstract:Docosanol inhibits a broad spectrum of lipid-enveloped viruses in vitro including HSV-1, HSV-2, VZV, CMV, HHV-6, and HIV-1. These observations led us to conduct a pilot clinical study with docosano...
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topical application of Docosanol or stearic acid containing creams reduces severity of phenol burn wounds in mice
Contact Dermatitis, 2000Co-Authors: Mohammed H Khalil, David H Katz, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:Because of their reported antiviral and anti-inflammatory activities, cream formulations containing n-Docosanol (Docosanol) or stearic acid were tested for effects on chemically-induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.5, 3, and 6 h later. Progression of the wounds was assessed by a single evaluator after 8 h, using a numerical score of gross morphology. Docosanol- and stearic acid-containing creams substantially and reproducibly lessened the severity and progression of skin lesions compared to untreated sites with a 76% and 57% reduction in mean lesion scores, respectively. Untreated wounds appeared red and ulcerated; Docosanol cream-treated wounds showed only slight erythema.
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the anti herpes simplex virus activity of n Docosanol includes inhibition of the viral entry process
Antiviral Research, 1998Co-Authors: Laura E Pope, David H Katz, John F Marcelletti, Lee R Katz, M L Parish, P G SpearAbstract:n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-Docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-Docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1:2 of approximately 3 h. Reduced expression of viral genes in n-Docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins—an immediate post entry event—was indicated by a 75% reduction in the expression of b-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate—early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-Docosanol. © 1998 Elsevier Science B.V. All rights reserved.
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anti herpes simplex virus activity of n Docosanol correlates with intracellular metabolic conversion of the drug
Journal of Lipid Research, 1996Co-Authors: Laura E Pope, Lee R Katz, J F Marcelletti, David H KatzAbstract:The 22carbon fatty alcohol, nDocosanol, exhibits in vitro antiviral activity against several lipidenveloped vi- ruses including herpes simplex viruses 1 and 2 by a mecha- nism that interferes with normal viral entry into target cells. We previously reported that mammalian cells incorporate significant quantities of radiolabeled nDocosanol. Herein, we report that cells extensively metabolize the internalized fatty alcohol. Thii is evidenced by incorporation of up to 60% of cell-associated radiolabel into phospholipids that copurify with phosphatidylcholine and phosphatidylethanolamine. Analysis by chemical (Vitride) reduction suggests that a sig- nificant portion of nDocosanol is oxidized to ndocosanoic acid and then incorporated as an acyl group on polar lipids. A measurable amount of radiolabel, however, is resistant to Vitride reduction, consistent with incorporation of n-do- cosanol into ether lipids. The rate and extent of metabolic conversion of nDocosanol "y with the cell type and surfac- tant used to suspend the compound. Furthermore, the anti- HSV activity of nDocosanol is quantitatively proportional to the amount of metabolism observed. BII These findings sug- gest that the anti-HSV activity of nDocosanol involves cellular uptake and metabolism of the drug.-Pope, L. E., J. F. Mar- celletti, L. R. Katz, and D. H. Katz. Anti-herpes simplex virus activity of nDocosanol correlates with intracellular metabolic conversion of the drug.J Lipid Res. 1996.57: 2167-2178.
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n Docosanol formulations and sucrose ester
1994Co-Authors: David H Katz, Mohammed H Khalil, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:It DESCRIBED A STABLE CREAM, therapeutically effective, IN WHICH THE COMPONENTS THERAPEUTIC KEY are one or more aliphatic alcohols chain with a length of between C-20 and C-28, of which one example is the N-Docosanol, INCLUDING sucrose cocoate, sucrose stearates O sUCROSE distearate, or mixtures thereof.
Mohammed H Khalil - One of the best experts on this subject based on the ideXlab platform.
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clinical efficacy of topical Docosanol 10 cream for herpes simplex labialis a multicenter randomized placebo controlled trial
Journal of The American Academy of Dermatology, 2001Co-Authors: Stephen L Sacks, David H Katz, Ronald A Thisted, Terry M Jones, Rick A Barbarash, Dennis J Mikolich, Gary E Ruoff, Joseph L Jorizzo, Lucy B Gunnilla, Mohammed H KhalilAbstract:Abstract Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. Objective: Our purpose was to determine whether Docosanol 10% cream (Docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. Methods: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either Docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. Results: The median time to healing in the 370 Docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients ( P = .008; 95% confidence interval [CI]: 2, 22). The Docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P = .002; 95% CI: 3, 16.5); (2) complete healing of classic lesions ( P = .023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions ( P P = .109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with Docosanol were mild and similar to those with placebo. Conclusion: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration. (J Am Acad Dermatol 2001;45:222-30.)
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Clinical efficacy of topical Docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial ☆ ☆☆ ★ ★★
Journal of The American Academy of Dermatology, 2001Co-Authors: Stephen L Sacks, David H Katz, Ronald A Thisted, Terry M Jones, Rick A Barbarash, Dennis J Mikolich, Gary E Ruoff, Joseph L Jorizzo, Lucy B Gunnilla, Mohammed H KhalilAbstract:Abstract Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. Objective: Our purpose was to determine whether Docosanol 10% cream (Docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. Methods: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either Docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. Results: The median time to healing in the 370 Docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients ( P = .008; 95% confidence interval [CI]: 2, 22). The Docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P = .002; 95% CI: 3, 16.5); (2) complete healing of classic lesions ( P = .023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions ( P P = .109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with Docosanol were mild and similar to those with placebo. Conclusion: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration. (J Am Acad Dermatol 2001;45:222-30.)
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the antiviral drug Docosanol as a treatment for kaposi s sarcoma lesions in hiv type 1 infected patients a pilot clinical study
AIDS Research and Human Retroviruses, 2001Co-Authors: Michael J Scolaro, Lucy B Gunnill, Laura E Pope, Mohammed H Khalil, David H Katz, James BergAbstract:Docosanol inhibits a broad spectrum of lipid-enveloped viruses in vitro including HSV-1, HSV-2, VZV, CMV, HHV-6, and HIV-1. These observations led us to conduct a pilot clinical study with docosano...
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topical application of Docosanol or stearic acid containing creams reduces severity of phenol burn wounds in mice
Contact Dermatitis, 2000Co-Authors: Mohammed H Khalil, David H Katz, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:Because of their reported antiviral and anti-inflammatory activities, cream formulations containing n-Docosanol (Docosanol) or stearic acid were tested for effects on chemically-induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.5, 3, and 6 h later. Progression of the wounds was assessed by a single evaluator after 8 h, using a numerical score of gross morphology. Docosanol- and stearic acid-containing creams substantially and reproducibly lessened the severity and progression of skin lesions compared to untreated sites with a 76% and 57% reduction in mean lesion scores, respectively. Untreated wounds appeared red and ulcerated; Docosanol cream-treated wounds showed only slight erythema.
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n Docosanol formulations and sucrose ester
1994Co-Authors: David H Katz, Mohammed H Khalil, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:It DESCRIBED A STABLE CREAM, therapeutically effective, IN WHICH THE COMPONENTS THERAPEUTIC KEY are one or more aliphatic alcohols chain with a length of between C-20 and C-28, of which one example is the N-Docosanol, INCLUDING sucrose cocoate, sucrose stearates O sUCROSE distearate, or mixtures thereof.
Lee R Katz - One of the best experts on this subject based on the ideXlab platform.
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topical application of Docosanol or stearic acid containing creams reduces severity of phenol burn wounds in mice
Contact Dermatitis, 2000Co-Authors: Mohammed H Khalil, David H Katz, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:Because of their reported antiviral and anti-inflammatory activities, cream formulations containing n-Docosanol (Docosanol) or stearic acid were tested for effects on chemically-induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.5, 3, and 6 h later. Progression of the wounds was assessed by a single evaluator after 8 h, using a numerical score of gross morphology. Docosanol- and stearic acid-containing creams substantially and reproducibly lessened the severity and progression of skin lesions compared to untreated sites with a 76% and 57% reduction in mean lesion scores, respectively. Untreated wounds appeared red and ulcerated; Docosanol cream-treated wounds showed only slight erythema.
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the anti herpes simplex virus activity of n Docosanol includes inhibition of the viral entry process
Antiviral Research, 1998Co-Authors: Laura E Pope, David H Katz, John F Marcelletti, Lee R Katz, M L Parish, P G SpearAbstract:n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-Docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-Docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1:2 of approximately 3 h. Reduced expression of viral genes in n-Docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins—an immediate post entry event—was indicated by a 75% reduction in the expression of b-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate—early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-Docosanol. © 1998 Elsevier Science B.V. All rights reserved.
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anti herpes simplex virus activity of n Docosanol correlates with intracellular metabolic conversion of the drug
Journal of Lipid Research, 1996Co-Authors: Laura E Pope, Lee R Katz, J F Marcelletti, David H KatzAbstract:The 22carbon fatty alcohol, nDocosanol, exhibits in vitro antiviral activity against several lipidenveloped vi- ruses including herpes simplex viruses 1 and 2 by a mecha- nism that interferes with normal viral entry into target cells. We previously reported that mammalian cells incorporate significant quantities of radiolabeled nDocosanol. Herein, we report that cells extensively metabolize the internalized fatty alcohol. Thii is evidenced by incorporation of up to 60% of cell-associated radiolabel into phospholipids that copurify with phosphatidylcholine and phosphatidylethanolamine. Analysis by chemical (Vitride) reduction suggests that a sig- nificant portion of nDocosanol is oxidized to ndocosanoic acid and then incorporated as an acyl group on polar lipids. A measurable amount of radiolabel, however, is resistant to Vitride reduction, consistent with incorporation of n-do- cosanol into ether lipids. The rate and extent of metabolic conversion of nDocosanol "y with the cell type and surfac- tant used to suspend the compound. Furthermore, the anti- HSV activity of nDocosanol is quantitatively proportional to the amount of metabolism observed. BII These findings sug- gest that the anti-HSV activity of nDocosanol involves cellular uptake and metabolism of the drug.-Pope, L. E., J. F. Mar- celletti, L. R. Katz, and D. H. Katz. Anti-herpes simplex virus activity of nDocosanol correlates with intracellular metabolic conversion of the drug.J Lipid Res. 1996.57: 2167-2178.
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n Docosanol formulations and sucrose ester
1994Co-Authors: David H Katz, Mohammed H Khalil, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:It DESCRIBED A STABLE CREAM, therapeutically effective, IN WHICH THE COMPONENTS THERAPEUTIC KEY are one or more aliphatic alcohols chain with a length of between C-20 and C-28, of which one example is the N-Docosanol, INCLUDING sucrose cocoate, sucrose stearates O sUCROSE distearate, or mixtures thereof.
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formulations d n Docosanol a base d ester de sucrose
1994Co-Authors: David H Katz, Laura E Pope, Mohammed H Khalil, John F Marcelletti, Lee R KatzAbstract:Creme therapeutique efficace stable dans laquelle les principaux composes therapeutiques sont un ou plusieurs alcools aliphatiques a chaine longue C-20 a C-28, dont n-Docosanol est un exemple, comprenant du cocoate de sucrose, du stearate de sucrose ou du distearate de sucrose, ou bien des melanges de ceux-ci.
John F Marcelletti - One of the best experts on this subject based on the ideXlab platform.
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synergistic inhibition of herpesvirus replication by Docosanol and antiviral nucleoside analogs
Antiviral Research, 2002Co-Authors: John F MarcellettiAbstract:Interactions between Docosanol (n-Docosanol, behenyl alcohol) and nucleoside or pyrophosphate analogs were investigated in vitro. The anti-HSV activity of acyclovir (ACV) was synergistically enhanced by treatment of cells with Docosanol as judged by inhibition of progeny virus production and plaque formation. This drug interaction between ACV and Docosanol was observed with laboratory strains of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), oral and genital clinical isolates of HSV, cytomegalovirus (CMV), and varicella zoster virus (VZV). Near optimal concentrations of Docosanol plus ACV inhibited HSV replication >99% more than either drug alone, including emergence of ACV-resistant variants. The response was observed with African Green Monkey kidney cells, normal human foreskin cells, and normal human lung cells. Treatment of cells with Docosanol also synergistically intensified the inhibition of HSV production by all tested nucleoside analogs, including trifluorothymidine (TFT), adenine arabinoside (Ara-A), and ribavirin. An additive anti-HSV effect was observed with Docosanol and phosphonoformate (PFA). No evidence was found for either synergistic inhibition of cellular DNA synthesis or induction of overt cellular toxicity when Docosanol was combined with ACV, TFT, Ara-A, ribavirin, PFA, 8-azaguanine, or 5-fluorouracil. The ability of Docosanol treatment to increase the antiviral activities of nucleoside analog antiviral drugs, coupled with a lack of toxic interactions, translates to substantial improvements in drug selectivity ratios.
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topical application of Docosanol or stearic acid containing creams reduces severity of phenol burn wounds in mice
Contact Dermatitis, 2000Co-Authors: Mohammed H Khalil, David H Katz, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:Because of their reported antiviral and anti-inflammatory activities, cream formulations containing n-Docosanol (Docosanol) or stearic acid were tested for effects on chemically-induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.5, 3, and 6 h later. Progression of the wounds was assessed by a single evaluator after 8 h, using a numerical score of gross morphology. Docosanol- and stearic acid-containing creams substantially and reproducibly lessened the severity and progression of skin lesions compared to untreated sites with a 76% and 57% reduction in mean lesion scores, respectively. Untreated wounds appeared red and ulcerated; Docosanol cream-treated wounds showed only slight erythema.
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the anti herpes simplex virus activity of n Docosanol includes inhibition of the viral entry process
Antiviral Research, 1998Co-Authors: Laura E Pope, David H Katz, John F Marcelletti, Lee R Katz, M L Parish, P G SpearAbstract:n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-Docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-Docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1:2 of approximately 3 h. Reduced expression of viral genes in n-Docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins—an immediate post entry event—was indicated by a 75% reduction in the expression of b-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate—early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-Docosanol. © 1998 Elsevier Science B.V. All rights reserved.
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n Docosanol formulations and sucrose ester
1994Co-Authors: David H Katz, Mohammed H Khalil, John F Marcelletti, Lee R Katz, Laura E PopeAbstract:It DESCRIBED A STABLE CREAM, therapeutically effective, IN WHICH THE COMPONENTS THERAPEUTIC KEY are one or more aliphatic alcohols chain with a length of between C-20 and C-28, of which one example is the N-Docosanol, INCLUDING sucrose cocoate, sucrose stearates O sUCROSE distearate, or mixtures thereof.
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formulations d n Docosanol a base d ester de sucrose
1994Co-Authors: David H Katz, Laura E Pope, Mohammed H Khalil, John F Marcelletti, Lee R KatzAbstract:Creme therapeutique efficace stable dans laquelle les principaux composes therapeutiques sont un ou plusieurs alcools aliphatiques a chaine longue C-20 a C-28, dont n-Docosanol est un exemple, comprenant du cocoate de sucrose, du stearate de sucrose ou du distearate de sucrose, ou bien des melanges de ceux-ci.