Hair Follicle Density in Weanling Yorkshire Pig Skin
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1 Hair Follicle Density in Weanling Yorkshire Pig Skin
2 Hair Density Age of Pig Mean Hair Follicle Density per cm 2 (± SEM) 8 Week 68.9 ± Week 29.7 ± Months 8.4 ± 0.39
3 Ear Skin is Different than other Areas! Thickness is thinner compared to other body sites and is thicker on the outside (convex) surface than the inner (concave) surface Hair follicle hair density is greater on the convex surface Glandular density is different between surfaces Cartilage is present Blood vessels traverse cartilage and is different than other body regions
4 Normal Mouse Ear Monteiro-Riviere et al. Immunohistochemical characterization of the basement membrane epitopes in bis (2-chloroethyl) sulfide induced toxicity in mouse ear skin. Journal Applied Toxicology 19: , 1999.
5 Mean Concentration of Lipid Extraction Monteiro-Riviere, Inman, Mak, Wertz, Riviere. Effect of selective lipid extraction from different body regions on epidermal barrier function. Pharmaceutical Research 18: , 2001.
6 TEM- SC Monteiro-Riviere NA, Inman AO, Mak V, Wertz P, Riviere JE: Effect of selective lipid extraction from different body regions on epidermal barrier function. Pharmaceutical Research 18: , 2001.
7 Extraction with Cyclohexane 1 min - 3X Monteiro-Riviere NA, Inman AO, Mak V, Wertz P, Riviere JE: Effect of selective lipid extraction from different body regions on epidermal barrier function. Pharmaceutical Research 18: , 2001.
8 Extraction with Cyclohexane/Ethanol (4:1)- 1 min- 3X Monteiro-Riviere NA, Inman AO, Mak V, Wertz P, Riviere JE: Effect of selective lipid extraction from different body regions on epidermal barrier function. Pharmaceutical Research 18: , 2001.
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11 Topical Site Differences in Piroxicam Absorption in Pigs In Vitro vs. In Vivo Monteiro-Riviere NA, Inman AO, Riviere JE, McNeil SC, Francoeur ML: Topical penetration of piroxicam is dependent on the distribution of the local cutaneous vasculature. Pharmaceutical Research 10: , 1993.
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13 COMMERCIALLY AVAILABLE 3-D HUMAN SKIN CULTURE MODELS Full-thickness human skin cultures Lacks non-keratinocytes (melanocytes (some have been added), Merkel cells, Langerhans cells) Lacks appendages No dermis nor vascular system (working on this)
14 Differentiated Skin Tissue Models Grown on a polycarbonate membrane (Organogenesis) 3D-Nylon Mesh (ATS) Air-liquid interface (Skinethic) Microporous membrane (Mattek) Newer models
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16 Day 0 Monteiro-Riviere et al. Comparison of an in vitro skin model to normal human skin for dermatological research. Microscopy Research and Technique 37: , 1997.
17 Monteiro-Riviere et al. Comparison of an in vitro skin model to normal human skin for dermatological research. Microscopy Research and Technique 37: , 1997.
18 Disadvantages Difficulty of reproducing results and standardizing between laboratories Intralaboratory variability and Intra /Interlot variability Subjectivity of recording techniques Difficulty to extrapolate to humans Absorption of compounds is much higher than normal The stratum corneum can increase from Day 0- Day 3. Note: These differences in skin structure and function may mimic many disease-induced changes to normal skin (e.g. hyperproliferation)
19 Advantages of In Vitro Models Ease of screening large number of compounds Can screen potential toxic agents that would be unethical to study in animals Don t have to deal with IACUC approval that has made animal research almost impossible to conduct
20 Flow-Through Diffusion Cell-10µM QD-PEG621 for 24hr Zhang L, Yu WW, Colvin VL, Monteiro-Riviere NA:Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes. Toxicology Applied Pharmacology 228: ,2008.
21 Flow-Through Diffusion Cell- 10µM QD-PEG621 for 24hr
22 Our Flexing Device Rouse JG, Yang J, Ryman-Rasmussen JP,Barron AR, Monteiro-Riviere NA: Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin. Nano Letters 7: , 2007.
23 Flexing of Baa (FITC)-NLS over 8 hr Scale bars = 50 µm
24 Flexing of Baa (FITC)-NLS over 24 hr. Scale bars = 50 µm
25 Xia, Monteiro-Riviere, Riviere. Skin Penetration and Kinetics of Pristine Fullerenes (C60) Topically Exposed in Industrial Organic Solvents. Toxicology Applied Pharmacology 242:29-37, In Vivo Tape Stripping Analysis of C60 in Different Solvents by slle After Multiple Doses for 4 days 1.6 C60 Amount on Tape-Strips (ug) C60/Chloroform C60/Cyclohexane C60/Toluene C60 Saturated Mineral Oil Tape-Strip Number
26 Monteiro-Riviere NA: Anatomical Factors that Affect Barrier Function. In Dermatotoxicology. (Eds. H. Zhai, KP Wilhelm, HI Maibach), 7 th ed, CRC Press, Chapter 4, pp.39-50, 2008.
27 Acknowledgements North Carolina State University s Center for Chemical Toxicology Research & Pharmacokinetics U.S. EPA-Science to Achieve Results (STAR) RD & RD U. S. Air Force Office of Scientific Research- FA The National Academies Keck Future s Initiative Grant NIH- ES
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