Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50-mg tablets. In a randomized, 3-way crossover study, healthy volunteers (n = 40) received three 7-day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm(2)), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm(2)), and (C) 150 mg oral diclofenac applied as 50-mg tablets 3 times daily. Thirty-nine participants completed all 3 regimens. Systemic exposure was greater with oral diclofenac (AUC(0-24), 3890 +/- 1710 ng x h/mL) than with topical treatments A (AUC(0-24), 233 +/- 128 ng x h/mL) and B (AUC(0-24), 807 +/- 478 ng x h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase-1 (COX-1), and COX-2. Topical diclofenac did not inhibit platelet aggregation and inhibited COX-1 and COX-2 less than oral diclofenac. Treatment-related adverse events were mild and limited to application site reactions with diclofenac sodium gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3). Systemic exposure with diclofenac sodium gel 1% was 5- to 17-fold lower than with oral diclofenac. Systemic effects with topical diclofenac were less pronounced.
In this study, the clinical and histopathological aspects of 50 plantar warts are reported in relation to the type of papillomavirus present in the lesions, as detected by immunofluorescence tests, using specific guinea pig fluorescein-labelled IgG. Warts of plantar localization are not caused by the same human papillomavirus (HPV) since they are found to be associated with both HPV type 1 (HPV-1) and HPV type 2 (HPV-2). HPV-1 is always associated with deep and painful plantar warts (myrmecia), whereas HPV-2 is found to be associated with superficial, painless plantar warts (vulgaris or often mosaic type). Histologically, these two types of plantar warts are quite different. In myrmecia (HPV-1), characterized by an endophytic growth, large eosinophilic, keratohyaline-like granules are observed in the cytoplasm and nucleus of infected, often vacuolated cells. These granules appear early in stratum spinosum and are very numerous in stratum granulosum. In the mosaic type (HPV-2), the histopathological aspect is not different from that of common warts; these lesions have an exophytic growth and are characterized by foci of clear vacuolized cells which are found in stratum granulosum. Their cytoplasm contains round, basophilic keratohyalin granules which often have a heterogenous aspect. These differences are observed in other localizations of morphologically related warts associated with HPV-1 and HPV-2 and seem to be related to a specific cytopathogenic effect of HPV-1 an HPV-2 in human papillomas.
The SC pharmacokinetic profile of terbinafine 1% FFS indicates that this novel formulation is efficient in delivering high amounts of terbinafine to the skin for a prolonged time and supports its use in the treatment of dermatophytoses with a single application.
The humoral and cell-mediated immune response to human papillomavirus type 1 (HPV-1) has been studied in 162 patients carrying papillomas of various clinical types: deep plantar wart or myrmecia, common wart, flat wart, and anogenital wart. Circulating antibodies were detected by immunodiffusion and microcomplement fixation, using purified HPV-1 particles as type-specific antigen. A significant association between myrmecia and anti-HPV-1 antibodies was found (39% of the cases). Cell-mediated immunity was evaluated by a study of delayed hypersensitivity (DH). The main capsid components of HPV-1 (HPV-1 CP), consisting mostly of a polypeptide of molecular weight 54,000, were injected intradermally. In addition to the type-specific antigens, HPV-1 CP contain other antigenic determinants shared by various types of human papilloma-viruses and masked in intact viral particles. The DH tests to HPV-1 CP showed no differences between the carriers of different papilloma types, confirming the presence of common antigenic determinants. Moreover, they gave rise to an increase or to new anti-HPV-1 antibody production mostly in myrmecia carriers (78% and 33% of the cases, respectively), and to new DH to HPV-1 CP in all groups of papilloma carriers (33% to 56%, depending on the clinical papilloma type).
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