PubMed · 14976103
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Andrew Molyneux. 2004-02-21. Nicotine replacement therapy.. https://doi.org/10.1136/bmj.328.7437.454
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The effect of various classes of chemical enhancers was investigated for the transdermal delivery of the anesthetic lidocaine across pig and human skin in vitro. The lipid disrupting agents (LDA) oleic acid, oleyl alcohol, butenediol, and decanoic acid by themselves or in combination with isopropyl myristate (IPM) showed no significant flux enhancement. However, the binary system of IPM/n-methyl pyrrolidone (IPM/NMP) improved drug transport. At 2% lidocaine dose, this synergistic enhancement peaked at 25:75 (v/v) IPM:NMP with a steady state flux of 57.6 +/- 8.4 microg cm(-2) h(-1) through human skin. This observed flux corresponds to a four-fold enhancement over a 100% NMP solution and over 25-fold increase over 100% IPM at the same drug concentration (p < 0.001). NMP was also found to co-transport through human skin with lidocaine free base and improve enhancement due to LDA. These findings allow a more rational approach for designing oil-based formulations for the transdermal delivery of lidocaine free base and similar drugs.
Previous reports have shown that transcutaneous immunization (TCI) with proteins or peptides in combination with adjuvants efficiently induces specific cellular and humoral immune responses. However, depending on the kind of skin pretreatment, induction of cellular immune responses was restricted to generation of either specific cytotoxic T lymphocytes (CTLs) or T-helper (Th) cells. In this study, we induced antigen-specific CTL responses together with the appropriate Th responses by TCI of C57BL/6 mice. We applied ovalbumin protein or an ovalbumin-derived fusion peptide containing a CTL and Th epitope together with a combination of cholera toxin (CT) and CpG oligodeoxynucleotide (CpG) onto cold wax-depilated and hydrated bare skin. TCI with the ovalbumin fusion peptide induced more robust CTL and Th responses than that with ovalbumin protein. The fusion peptide in combination with the nontoxic CT derivative CTA1-D2D1 and CpG induced an antigen-specific CTL response, albeit less efficiently than in combination with complete CT. Further, we compared the potency of HPV-16 E7 oncoprotein-derived peptides containing single (CTL) or multiple (CTL + Th + B cell) epitopes to induce effective CTL responses. Strong E7-specific CTL responses were detected only after TCI with the E7 multiepitope peptide. This peptide was also shown to protect mice against tumor growth after challenge with HPV-16 E7-positive tumor cells. TCI with E7 protein and CT/CpG led to formation of an E7-specific humoral immune response.
OBJECTIVES: Pilot study to compare the effects of a continuous combined hormone replacement therapy (HRT) regimen with an interrupted progestogen regimen administered transdermally, upon the endometrium of postmenopausal women, the incidence of amenorrhoea and relief of menopausal symptoms. METHODS: Fifty-nine postmenopausal women aged 50-63 years were randomised to either (i) continuous combined regimen: combined oestrogen/progestogen skin patches (releasing continuous 50 microg estradiol and 20 microg levonorgestrel/day) or (ii) interrupted regimen: oestrogen-only patches (releasing 80 microg estradiol/day) for 4 days followed by combined oestrogen/progestogen patches (releasing continuous 50 microg estradiol and 20 microg levonorgestrel/day) for 3 days, for 6 months. An endometrial biopsy was performed at end of treatment for histological analysis. RESULTS: Thirty-three women (56%) completed the study. Significantly higher rates of amenorrhoea were observed with the interrupted than continuous combined regimen (P<0.0001; 25% versus 7% at 6 months). The interrupted regimen was also associated with fewer days of bleeding overall (total 20 versus 44 days during months 4-6; P=0.001). Both regimens improved vasomotor symptoms. No endometrial hyperplasia or atypical changes were observed in endometrial biopsies. CONCLUSIONS: Although significantly less bleeding was observed with the interrupted regimen, it did not have a sufficiently high incidence of amenorrhoea to render it clinically useful.