DISCUSSIONIncreasingly the scientific community has recognized the similar anatomy and physiology be-tween swine and humans, with the swine dermal system being very comparable to humans with regards to the anatomical, physiological, metabolic, and histological features. Other organs and systems (cardiovascular, digestive, renal) are also analogous to human systems. Thus, the absorption, distribution, metabolism, and elimination of drugs in swine are generally very pre-dictive of human metabolism, distribution, pharmaco/toxicokinetics. This has led to an increase in the use of miniature swine in preclinical research, including dermal toxicology and DMPK, and recognition by regulatory authorities that swine are an appropriate animal model for these evaluations. Animal model skin similarities and differences have been previously reported (Ban-ga 2011, Zhai et al., 2008, Riviere 2008, Swindle 2008, Monterio-Riviere 1991 & 1996). Skin histological variations by species are easily identified when magnified sufficiently to allow visu-alization of layers, pelage and adnexa. Among the many factors which are known to affect per-cutaneous drug uptake are the thickness of stratum corneum, hair follicle density for certain classes of drugs, biochemical makeup of the epidermal mortar (brick & mortar concept), skin regional blood flow, and polar vs. nonpolar drug absorption characteristics. Some species (hu-man, swine, NHP) have skin which is adherent to underlying structures while others have thin non-adherent or ‘loose’ skin (rat, mouse, rabbit, guinea pig, hamster). Swine are known to be good models for human dermal pharmacology, dermal toxicology and skin wound healing/burn studies. Selection of dermal testing models for best human translational research requires an understanding of the skin surface topography, microanatomy, pelage density, hair follicle densi-ty, skin glands or adnexa, biochemistry, physiology, and genetics. Although the sample size/spe-cies is small for this histological study, this abbreviated study still gives a general understanding of comparative dermal anatomy and histology.

CONCLUSIONThe swine (Yucatan & Hanford) skin images reported herein are visually most like the human skin image from a microanatomy perspective.

REFERENCES1. Banga AK (2011). Ch 1 Percutaneous Absorption and Enhancement Strategies, and Ch 2 Ex-

perimental Methods and Tools for Transdermal Delivery by Physical Enhancement Methods In: Transdermal and Intradermal Delivery of Therapeutic Agents, CRC Press: Boca Raton, p1-26, p27-51.

2. Zhai H, Wilhelm KP, Maibach HI (Eds). Marzulli & Maibach’s Dermatotoxicology. Informa Health Care, 7th Ed, 2008.

3. Riviere JE (2008). Comparative Aspects of Topical Delivery. Powerpoint Presented at Skin Forum EU Meeting, (CCTRP) June 2008. http://www.skin-forum.eu/presentations/Riviere%2 Skin%20Forum%20June%2008.pdf

4. Swindle MM, DVM (2008). Sinclair Technical Bulletin, Porcine Integumentary System Mod-el-Part1.pdf.http://www.sinclairbioresources.com/Downloads/TechnicalBulletins/Por-cine%20Integumentary%20System%20Model-Part%201.pdf

5. Monteiro-Riviere NA, and J Riviere (1996). The pig as a model for cutaneous pharmacology and toxicology research. In Tumbleson ME, Schook LB (Eds). Advances in Swine in Biomedical Research, Vol 2. New York: Plenum Press, 425-458.

6. Monteiro-Riviere NA (1991). Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin. In: Dermal and Ocular Toxicology: Fundamentals and Methods DW Hobson). CRC Press, Inc., New York, New York, Chapter 1, 3-71.

7. Monteiro-Riviere NA, Bristol DG, Manning TO, and Riviere JE (1990). Interspecies and interregional analysis of the comparative histological thickness and laser Doppler blood flow measurements at five cutaneous sites in nine species, J. Invest. Dermatol. 95: 582-586.

COMPARATIVE PHOTOMICROGRAPHIC EXAMINATION OF INTEGUMENT FROM EIGHT SPECIES OF MAMMALS INCLUDING TWO LINEAGES OF RESEARCH MINISWINE

Brown L. ¹, Kim D.Y. 3, Hanks C. ¹, Schnapp S. ¹, Brocksmith D.², White D. ¹, Stricker-Krongrad A.², Liu J.¹, Bouchard G.F.¹

¹Sinclair Research Center, LLC, Auxvasse, MO, USA; ²Sinclair BioResources, LLC, Auxvasse, MO, USA; 3Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia, MO, USA

ABSTRACTIntroduction: Skin is the largest organ in the body. Animals have skin which is generally similar to human skin, however, species specific anatomical and biochemical differences exist. The in-tegument of animal models may vary in skin surface topography, overall thickness and thickness of specific layers, stratum corneum, epidermis, dermis density and collagen content, regional blood flow, pelage (hair count), hair follicle size or density, and sub-dermal characteristics. De-termination of which animal model most closely matches the skin of humans is important for translational dermal research.

Objective/Rationale: Prepare magnified images of comparative skin histology and perform sim-ple image analysis for differences or similarities.

Methods: Animal skin samples collected included Yucatan miniswine, Hanford miniswine, Cy-nomolgus monkey, Beagle dog, NZW rabbit, Hartley guinea pig, Sprague-Dawley rat, and CD-1 mouse. The human skin was acquired from a medical school. Samples were fixed in neutral buffered formalin, processed, sectioned, stained with H&E, examined by microscope and photo-graphed by veterinary dermatopathologist (DYK). The resulting skin images generated by Olym-pus MicroSuiteTM were compared side-by-side at equivalent magnification.

Results: Visual comparison of images suggest the skin of swine and human look the most sim-ilar while the skin of rodents (rat, mouse) has a much thinner epidermis. The skin of rabbit and guinea pig appear to consist predominantly of hair shafts/hair follicles combined with thin epi-dermis. Monkey and dog skin were next most similar to the human skin.

Conclusion(s): The swine (Yucatan & Hanford) skin images are visually most like those of the human images.

INTRODUCTIONSkin is the largest organ in the body. Animals have skin which is generally similar to human skin, however, species specific anatomical and biochemical differences exist. The integument of an-imal models may vary in skin surface topography, overall thickness and thickness of specific layers, stratum corneum, epidermis, dermis density and collagen content, regional blood flow, pelage (hair), hair follicle density, and sub-dermis characteristics. Hairless or nude animals have empty hair follicles but the density may be reduced from the haired counterpart. Hair follicles are important to drug absorption for certain drug classes. Determination of which animal model most closely matches the skin of humans is important for translational dermal research.

Objective/Rationale: Prepare magnified images of comparative skin histology and perform quick image analysis by the human eye.

Methods: Animal skin samples were collected humanely from research animals either at nec-ropsy, termination or in surgery under anesthesia. Included were Yucatan miniswine, Hanford miniswine, Cynomolgus monkey, Beagle dog, NZW rabbit, Hartley guinea pig, Sprague-Dawley rat, and CD-1 mouse (Table 1). Human skin images were obtained from a medical school.

Species

Human

Miniswine

Monkey(NHP)

Dog

Rabbit

Guinea Pig

Albino Rat

Albino Mouse

Miniswine

Genetic Group Gender Age Hair

DensityHair

ColorIntegument

ColorSkin Site Sampled

FormalinFixation

H&EStain

Caucasian

StandardYucatan

Hanford

Cynomolgus

Beagle

Hartley

Sprague-Dawley

NZW

CD-1

Not Recorded

Male

Male

Male

Male

Female

Female

Adult

5 yrs

YoungAdult

Female

4.3 yrs

6 yrs

3.5 Months

2.5 Months

3 Months

2Months

Thin‘Hairless’

Well Haired Pelage

Thin

WellHaired

WellHaired

WellHaired

WellHaired

WellHaired

Grey

White

White

White

White

White

Brown

Tri

White

White

White

White

White

White

White

Slate Grey

Upper Back

Lumbar Back

Lumbar Back

Lumbar Back

Shoulder

Lumbar Back

Lumbar Back

Lumbar Back

Lumbar Back

1Skin samples taken from the dorsum or lumbar back, or other designated site of normal animals. Samples were elliptical scalpel incisions for fixation and preparation of histology. Samples (3-4 mm wide by 1.5-2 cm long, deep to adipose) were fixed in 10% NBF in labeled spec-imen jars. Thick fixation cassettes with cardboard inserts were used to keep the skin from curling. 40X H&E jpeg color lateral profile images were obtained showing the stratum corneum, epidermis and the dermis.

Species

Human

Miniswine,Yucatan

Monkey(NHP), Cyno

Dog, Beagle

Rabbit, NZW

Guinea Pig, Hartley

Albino Rat, S-D

Albino Mouse,CD-1

Miniswine,Hanford

Hair Follicle(H)

Primary Hair (PH)

Secondary Hair (SH)

Sebaceous Gland (S)

Apocrine Gland (A)1

Eccrine Gland (E)

TABLE 1: CHARACTERISTICS OF SKIN SAMPLES USED IN STUDY

The human skin sample was acquired from the local University School of Medicine following established protocols and informed consent. Samples were fixed in neutral buffered formalin, processed, sectioned, stained with H&E, examined by microscope and photographed by pro-fessional dermatopathologist (DYK). The resulting skin jpeg images (Figures 1-9) generated by Olympus MicroSuiteTM were compared side-by-side at equivalent magnification.

Results: The results suggest the adherent skin of swine and human look the most similar. The loose skin of rodents (rat, mouse) has a much thinner epidermis. The skin of rabbit and guinea pig appear to consist predominantly of hair shafts combined with thin epidermis. Table 2 lists the image legends for each species.

TABLE 2: IMAGE LEGENDS

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