Non Insecticidal Veterinary Shampoo Components

FOCAL POINT

KEY FACTS

★

Knowledge of shampoo ingredients and their uses and contraindications allows veterinarians to choose the most appropriate shampoo products for their patients.

Noninsecticidal

Veterinary Shampoo

Components

Texas A&M University

Christine A. Rees, DVM

ABSTRACT: The abundance of veterinary shampoos can make it difficult to decide which to choose for a particular patient. Becoming familiar with individual shampoo ingredients can make the decision easier. The chances of obtaining positive results from topical therapy are in-creased when tactile and visual findings, cytology results, and the primary concerns of owners are all considered. In addition, patients may benefit from a combination of several different topical therapies.

N

oninsecticidal shampoos are an essential adjuvant therapy for treating small animal dermatologic conditions. However, the abundance of products (more than 100 are listed in the most recent edition of the Compendium of Veterinary Products1_{) can cause confusion about which is}

appro-priate for a particular patient. The best way to deal with this situation is not to memorize all of the different products but to become familiar with the ingredi-ents. There are six shampoo-ingredient categories based on mechanism of ac-tion, including antibacterial, antifungal, antiseborrheic, moisturizing, antiprurit-ic (Table I), and residual-extending agents. The first four categories have been covered extensively in the literature and are therefore only briefly reviewed here.2–4_{Clinical cases illustrate the practical application of the information}

dis-cussed.

ANTIBACTERIAL INGREDIENTS

The five main antibacterial shampoo ingredients are benzoyl peroxide, chlorhexidine, povidone–iodine, triclosan, and ethyl lactate. All are useful for treating surface and superficial bacterial skin infections2–4_{; only benzoyl peroxide,}

however, is useful for treating deep bacterial skin infections because of its ability to penetrate deep within hair follicles and sebaceous glands.2–3

Benzoyl Peroxide

Benzoyl peroxide is an excellent antibacterial shampoo ingredient that has de-greasing and antiseborrheic (keratolytic) properties.2 _{Its antibacterial action}

re-sults from its ability to oxidize substances and has been shown to last for as long as 2 days.5 _{Precautions associated with benzoyl peroxide use are excessive drying}

and/or irritation of the skin and haircoat, bleaching of fabrics, odor, and lack of ■ Benzoyl peroxide is difficult to

manufacture and breaks down with time; heeding expiration dates and purchasing these products from well-known, reputable companies is therefore advised.

■ Povidone–iodine has relatively short residual activity and is inactivated by organic debris. ■ Tar is an effective antiseborrheic

agent because it has degreasing as well as keratoplastic properties.

■ A shampoo ingredient that was appropriate for a particular patient once may not be effective in the future.

Refereed Peer Review

latherability. Benzoyl peroxide is difficult to manufac-ture and breaks down with time; heeding expiration dates and purchasing these products from well-known, reputable companies is therefore advised.2 _Excessive

drying may be avoided by using a moisturizing spray or conditioner after benzoyl peroxide application.

Chlorhexidine

Chlorhexidine is a synthetic biguanide with antibac-terial, antifungal, and antiviral activities.5,6 _{It exerts its}

antibacterial effects by acting on the bacterial cell mem-brane, precipitating intracellular contents, and inhibit-ing ATP.7,8 _{Chlorhexidine differs from}

iodine-contain-ing products in that it is not inhibited or inactivated by organic debris (e.g., dirt, scale, crust).6_{Chlorhexidine is}

also known for its residual properties, lasting as long as 2 days.5,6_{No specific precautions have been}

document-ed at shampoo concentrations (4% or less). This prod-uct is nonirritating, nontoxic, and well tolerated. Povidone–Iodine

Povidone–iodine is an antibacterial agent with anti-fungal, antiviral, and antiprotozoal activity9,10 _that

works by iodinating and oxidizing sulfhydryl com-pounds, peptides, proteins, enzymes, vitamins, lipids, and cytosine found in the cytoplasm and cytoplasmic membranes.10,11_{Unlike chlorhexidine, povidone–iodine}

has relatively short residual activity (4 to 6 hours) and is inactivated by organic debris (e.g., dirt, crust, scale).6,12 _{The main precautions associated with}

povi-Small Animal/Exotics 20TH ANNIVERSARY Compendium January 1999

E X C E S S I V E D R Y I N G ■ O R G A N I C D E B R I S ■ R E S I D U A L P R O P E R T I E S TABLE I

Small Animal Shampoo-Ingredient Information

Activitya

Side Effects Ingredient Degreasing Antibacterial Antifungal Antipruritic Keratolytic Keratoplastic and Precautions

Aloe vera –

+

+

+

– – –

Benzoyl

+

– –

+

+

– Drying, minimal lather,

peroxide irritating to skin, bleaching;

watch expiration dates, use reputable companies

Chlorhexidine –

+

+

– – – –

Ethyl lactate –

+

– – – – –

Iodine –

+

+

– – – Staining, irritating to skin

Miconazole – –

+

– – – –

Oatmealb _{– – –}

₊

_{– – –}

Salicylic acid –

+

–

+

+

+

–

Selenium

+

–

+

–

+

+

Drying, staining,

sulfidec _{irritating to skin}

Sulfur –

+

+

d

₊

d

₊

₊

_{Odor, stains jewelry and}

light-coated animalsd

Tarc

₊

_{– – –}

₊

₊

_{Drying, staining, odor,}

irritating to skin, photosensitive, superficial necrolytic dermatitis

Triclosan –

+

– – – – –

a_{Residual-extending agents do not provide any of these properties and are thus not included.}

b_{Oatmeal shampoos may contain additional antipruritic agents, such as topical anesthetics (e.g., pramoxine), antihistamines (e.g.,} diphenhydramine), and cortisone (e.g., hydrocortisone), or oatmeal alone.

c_{Tar and selenium sulfide should not be used in cats because they are too irritating to feline skin.} d_{These effects are only seen with sulfur dip.}

done–iodine use are contact dermatitis, skin irritation, and staining.6,8,12

Triclosan

Triclosan is an antibacterial agent that is added into antiseborrheic shampoos to extend their spectrum of activity (i.e., provide more antibacterial properties). Tri-closan produces its effects by causing loss of plasma-membrane integrity and cell death through apoptosis in vitro.13_{Allergic contact dermatitis may occur.}14

Ethyl Lactate

Ethyl lactate is an antibacterial agent that penetrates hair follicles and sebaceous glands but has no proven benefits in treating deep pyoderma.15 _{This ingredient}

becomes effective by breaking down into two com-pounds within the skin, lactic acid and ethanol. Lactic acid acts by decreasing the skin’s pH and thus inhibit-ing bacterial lipases,5_{whereas ethanol renders fats}

solu-ble and decreases the amount of sebaceous secretions.4

Side effects (e.g., irritation, erythema, pruritus) are in-frequent.14

ANTIFUNGAL INGREDIENTS

The three main shampoo ingredients known for their antifungal properties are miconazole, chlorhexidine, and povidone–iodine. The latter two ingredients have been discussed previously.

Miconazole

Miconazole is an imidazole derivative that exerts its antifungal properties by inhibiting ergosterol synthe-sis.15_{Ergosterol is an essential component of the fungal}

cell membrane. Inhibition of ergosterol synthesis results in fungal cell death.15_{No specific side effects have been}

documented with miconazole shampoo formulations. ANTISEBORRHEIC INGREDIENTS

Seborrhea is an imbalance in the skin’s keratinization process in which skin cells (keratinocytes) tend to turn over more rapidly than usual, resulting in excessive scal-ing and crustscal-ing of the skin. The purpose of antisebor-rheic ingredients is to try to normalize this process by working at the skin’s surface to remove the excess scale (keratolytic properties) and at the basal layer to slow cell turnover (keratoplastic properties).2,3,5_{The two different}

forms of seborrhea are seborrhea oleosa (oily form) and seborrhea sicca (dry form).2 _{It is important to quantify}

the type of seborrhea that is present because different shampoo ingredients are used for each condition.

A degreasing agent with antiseborrheic properties is re-quired to gain the most effective control of seborrhea oleosa. The two ingredients with excellent degreasing

properties are benzoyl peroxide (discussed previously) and tar.2_{Seborrhea sicca is most commonly treated with}

sulfur and salicylic acid combination shampoos. Sulfur and salicylic acid have been shown to act synergistically to help remove scale.16_{At shampoo concentrations (i.e.,}

2% to 3%), these products are safe for use in dogs and cats. If the amount of scaling is minimal, a moisturizing spray or shampoo may be effective (see Moisturizing In-gredients below).

Tar

Tar is an effective antiseborrheic agent because it not only degreases but also has keratoplastic properties. Tar has been shown to slow skin-cell turnover by suppress-ing DNA synthesis at the basal layer.2_{Other properties}

include its ability to produce vasoconstriction and de-crease pruritus.2,3 _{Precautions associated with the}

topi-cal use of tar include unpleasant color (brown) and odor, skin irritation, excessive drying of skin and hair-coat, photosensitization, and superficial necrolytic der-matitis.2,3,5,17_{Tar is not approved for use in cats because}

it is extremely irritating to their skin.2 _{In addition,}

be-cause tar production techniques and refinement may affect its efficacy, tar shampoos should be purchased only from reputable companies.2,5

Sulfur

Sulfur is reportedly both keratoplastic and keratolyt-ic. The keratoplastic properties are thought to result from either the drug’s cytostatic capabilities or its reac-tion with cysteine in the skin to form cystine and hy-drogen sulfide (building blocks for normal keratiniza-tion). Sulfur’s keratolytic properties, which result from excess hydrogen sulfide formation, have been detected at high concentrations.2

Salicylic Acid

Salicylic acid is also keratoplastic and keratolytic; these effects are produced by decreasing the skin’s pH, which increases the hydration of the keratin and causes swelling of the stratum corneal cells. Salicylic acid also solubilizes the intercellular cement substance that holds the scale together.2

MOISTURIZING INGREDIENTS

Moisturizing ingredients help to rehydrate the skin and restore it to a more normal state.2,5 _{Almost all}

vet-erinary shampoos contain one or more of these ingredi-ents. Moisturizing products have not been associated with any side effects when used at the recommended shampoo ingredient concentrations. The two main groups of moisturizing ingredients include humectants and emollients/emulsifying agents.

Humectants

Humectants act to rehydrate the skin by attracting water from deep within the skin toward the surface. These ingredients are non-oily. Examples include natu-ral moisturizing factors (e.g., carboxylic acid, lactic acid, urea), sodium lactate, propylene glycol, glycerin, and polyvinylpyrrolidone.2

Emollients/Emulsifiers

Emollients and emulsifiers act by filling in the spaces between keratinocytes with oil. Examples of emollients include oils (e.g., almond, corn, cottonseed, coconut, olive, peanut, persia, safflower, sesame), animal fats (e.g., lanolin [sheep wool]), and hydrocarbons (e.g., mineral oil, paraffin, petrolatum2_).

Emulsifiers are often added to emollient solutions to help distribute the oils into a water solution; this makes the oil solution more effective because it can spread more evenly over the skin’s surface. Examples of emul-sifiers include cetyl alcohol, laureth-5, lecithin, PEG-4 dilaurate, stearic acid, and stearyl alcohol.2

ANTIPRURITIC INGREDIENTS

Oatmeal and aloe vera are added to veterinary sham-poos specifically for their antipruritic activities.18,19_The

antipruritic activity of other shampoo ingredients (dis-cussed in the text and Table I) probably results from antibacterial properties.2–4

Oatmeal

The use of oatmeal in topical preparations evolved from its use in folk medicine, which advocates home-made topical oatmeal preparations to soothe irritated skin for as long as 2 days.18,20_{The exact mechanism of}

action is unknown, but one report suggests that oat-meal inhibits prostaglandin biosynthesis.21

The only side effect reported with topical oatmeal use is allergic contact dermatitis in humans.22_{A recent}

double-blinded study concluded, however, that topical oatmeal did not induce allergic contact dermatitis in normal or atopic children.23

Aloe Vera

The stabilized viscous juice from the inner part of aloe vera leaves is used to produce topical preparations. This juice has antipruritic, healing properties as well as antibacterial and antifungal properties in vitro.19

Salicylic acid and magnesium lactate are the two chemical compounds within topical aloe preparations that produce its antipruritic effects.18 _{The mechanisms}

of action of these ingredients differ. Salicylic acid in-hibits the production of prostaglandin from arachidon-ic acid by inhibiting cyclooxygenase,24_whereas

magne-sium lactate has been shown to inhibit the conversion of histidine to histamine in mast cells via an enzyme called histidine carboxylase.25

Aloe vera is thought to produce its healing properties by increasing dermal perfusion and decreasing inflam-matory mediators (e.g., thromboxane, prostaglandin) in burn lesions.18 _{The exact concentration necessary to}

produce healing effects in a shampoo preparation is un-known. Side effects include the production of an eczematous, papular dermatitis in humans.26 _Side

ef-fects from topical aloe vera use in animals have not been documented.

RESIDUAL-EXTENDING INGREDIENTS Novosomes®

Novosomes® _{(Evasco Pharmaceuticals, Buena, NJ)}

are extremely stable, specially formulated nonphospho-lipid microvesicles (i.e., a type of liposome) with five to seven bilayers and a central holding area, 80% of which is comprised of water and/or lipids.27_Novosomes®

(ap-proximately 5 µm in diameter) are not susceptible to degradation by hydrolytic enzymes and are stable at temperatures as high as 80˚C. They have increased re-sistance to the autooxidative process when compared with regular liposomes.27

The particle charge on Novosomes®_{is formulated to}

tightly adhere to the skin and hair. The inner solution within the cargo area is slowly released as the various layers break down (requiring 7 to 10 days in average temperature conditions).27

Spherulites®

Spherulites® _{(Allerderm/Virbac, Fort Worth, TX) are}

composed of multiple layers (10 to 1000) of plant-de-rived surfactants and are 1 µm in diameter. Spherulites®

contain chitosanide—a multipurpose glycoprotein de-rived from chitin (crustacean shells)—which helps to form a film coating over the skin and hair, as well as an additional shampoo ingredient. Chitosanide also tightly binds the Spherulites®_{to the hair and skin by providing}

chemical differences in positive and negative charges. The shampoo ingredient within the Spherulites®_is

slow-ly released (over 8 days) as the different layers of the Spherulite®_{break down. Moisturizing agents, essential}

oils, and water- and fat-soluble vitamins can all be en-capsulated in the same Spherulite®_.28

CASE EXAMPLES Case 1

Signalment and History

A 2-year-old, spayed female Chihuahua was presented to the Texas Veterinary Medical Center with generalized scaling and a 1-year history of nonseasonal moderate

Small Animal/Exotics 20TH ANNIVERSARY Compendium January 1999

pruritus that was sometimes present without dermatolog-ic lesions. The patient was put on a food-elimination diet for 3 months using a commercially prepared veni-son and potato diet. No in-crease in pruritus was noted when the original diet was reinstituted.

Physical Examination

Physical examination re-vealed multifocal areas of alopecia on the dog’s face, shoulders, legs, neck, and ventrum (Figure 1). The skin was erythematous, licheni-fied, and dry with moderate amounts of scale. Both ears were slightly erythematous with a mild ceruminous dis-charge.

Differential Diagnoses

The main differential di-agnoses for this case were food hypersensitivity, aller-gic dermatitis secondary to atopy, and allergic contact dermatitis. Other differen-tial diagnoses included bac-terial skin infection, fungal skin infection, demodicosis, Malassezia dermatitis, and

seborrhea sicca (primary or secondary). The degree of pruritus and distribution of lesions helped to eliminate scabies from the differential diagnosis list. Because pru-ritus was not exacerbated on food rechallenge, a diag-nosis of food allergy was less likely. The distribution of lesions and the history were not consistent with a diag-nosis of contact allergy. Atopy was therefore the most probable underlying cause for this case. The other dif-ferential diagnoses were ruled out with diagnostic tests.

Diagnostic Tests

Several diagnostic tests were performed to reach the diagnosis. Multiple skin scrapings were negative for ec-toparasites. Impression smears of the skin revealed nu-merous surface cocci around and within keratinocytes (more than 40 per high-power field). Ear-swab cytology revealed inflammatory cells (neutrophils) and cocci bacteria. Chlorphenolac preparations and

dermato-phyte test media cultures were negative for dermato-phytes. An intradermal skin test had numerous positive reactions (grasses, weeds, trees, molds, and house dust mites; Figure 2).

Diagnosis and Treatment

The diagnosis for this dog was atopy and seborrhea sic-ca with a secondary bacterial skin and ear infection. The topical treatment used in this case was a shampoo containing a chlorhexidine and sulfur/salicylic acid combination with a residu-al-extending agent (Novo-somes®_).

The antibacterial proper-ties of chlorhexidine were beneficial for treating the pyoderma, the sulfur/salicylic acid combination aided in removing scale, and the Novosomes® _{extended the}

rehydrating properties of the bath. Other appropriate choices for this case includ-ed using a sulfur/salicylic acid and triclosan shampoo, an ethyl lactate shampoo with a residual-extending agent (Spherulites®_{), or a benzoyl peroxide shampoo}

with Novosomes®_{. A leave-on conditioner containing}

oatmeal and pramoxine was prescribed as a topical agent to help relieve the pruritus; any of the topical oatmeal conditioners or sprays would have been appro-priate to use in this case. Other medications used in this case included gentamicin sulfate otic (three drops in both ears every 12 hours for 14 days), lincomycin (22 mg/kg every 12 hours for 21 days), hyposensitiza-tion vaccines, and hydroxyzine (2.2 mg/kg every 8 hours for 14 days).

Case 2

Signalment and History

A 10-year-old, intact, male English springer spaniel was presented at the Texas Veterinary Medical Center with a 6-year history of oily, scaling, thickened skin with alopecia on the dorsum of all four feet, backs of

F O O D - E L I M I N A T I O N D I E T ■ S K I N S C R A P I N G S ■ C Y T O L O G Y ■ A T O P Y Figure 1—Alopecia, lichenification, and mild erythema on

the ventral cervical area of a dog.

Figure 2—Intradermal skin test reactions on the lateral thorax of a dog.

the ears, caudal thighs, and lateral thorax. This derma-tologic condition was mildly pruritic and nonseasonal. Previous treatment included oral and injectable steroids, various antibiotics, and ke-toconazole (unknown dose and frequency). According to the owner, steroids, cephalexin, and ketocona-zole had somewhat im-proved the dog’s condition in the past. The dog was fed a commercially prepared lamb and rice diet.

Physical Examination

Physical examination re-vealed several dermatologic abnormalities, including alopecia, erythema, licheni-fication, excess scale, and some crusts on the face, caudal aspect of both pinnae (Figure 3), ventral neck and ventrum, and extremities (especially the stifles and dorsum of the feet; Figure 4). The canals of both ears were erythematous with a ceruminous discharge.

Differential Diagnoses

Several differential diagnoses were considered, in-cluding allergic dermatitis (e.g., food allergy, atopy, contact allergy, flea hypersensitivity), ectoparasites (e.g., scabies, demodicosis), and a secondary skin infection (e.g., bacterial, fungal). Although the ears and stifle ar-eas were involved, the possibility of scabies was low be-cause pruritus was mild and the condition was present for a relatively short time (6 years).

Diagnostic Tests

Multiple skin scrapings were negative for ectopara-sites. Impression smears of the skin and crust revealed numerous cocci and some neutrophils and macro-phages (more than 30 per high-power field). Numerous cocci bacteria and neutrophils were noted on the ear-swab cytology. Otoscopic examination of both ears re-vealed patent ears with intact tympanic membranes. Chlorphenolac preparation and dermatophyte test me-dia cultures were negative for dermatophytes. Skin

biopsy showed evidence of superficial pyoderma with an underlying allergy. The complete blood count showed evidence of eosino-philia, which was thought to be associated with an in-ternal or exin-ternal parasite load; however, a fecal exami-nation and occult heart-worm test were negative for parasites. The urinalysis had abnormal amounts of bacte-ria, and neutrophils revealed cystitis.

Diagnosis and Treatment

The diagnosis for this dog was seborrhea oleosa, allergic dermatitis, and oti-tis externa with a secondary bacterial skin infection. Top-ical therapy consisted of twice-weekly baths with a benzoyl peroxide shampoo followed by a leave-on chlorhexidine cream rinse for the superficial pyoder-ma. Benzoyl peroxide was chosen in this case because the dog had oily skin with a secondary infection. (A 2% tar shampoo would be an appropriate alternative therapy because it is also a good degreasing agent.) A chlorhexidine leave-on con-ditioner was selected because it rehydrates the skin and provides some secondary residual antibacterial ef-fects. Any moisturizing agent would be appropriate and was considered necessary because benzoyl perox-ide tends to be drying. The otitis externa was treated with gentamicin sulfate otic (three drops every 12 hours for 14 days). A commercially prepared duck and potato diet was prescribed for an 8-week elimina-tion diet.

The dog was markedly improved at the end of the 8-week food trial (pruritus decreased more than 50%). At the conclusion of the trial, rechallenge with the dog’s old food confirmed food allergy (pruritus increased more than 50% within several days of food rechal-lenge). Challenging the dog with individual food ingre-dients revealed allergies to beef, egg, wheat, soy, and chicken.

Small Animal/Exotics 20TH ANNIVERSARY Compendium January 1999

C H L O R P H E N O L A C P R E P A R A T I O N ■ E O S I N O P H I L I A ■ F O O D A L L E R G Y Figure 3—Alopecia, lichenification, erythema, crust, and scale

along the back of the left pinna of a dog.

Figure 4—Alopecia, lichenification, erythema, and excoriation on the left lateral stifle of a dog.

DISCUSSION

Both of the patients discussed in the case examples had bacterial pyoderma and allergy, but they were treat-ed with different topical therapies because their skin and hair had different tactile properties. The dog in the first case had dry scale that required a moisturizing ker-atolytic and keratoplastic agent, whereas the second dog had oily scale requiring a degreasing and keratolyt-ic agent. The main complaint of the first dog’s owner was pruritus, thus a leave-on oatmeal with pramoxine conditioner was selected. The history of pruritus with-out any evidence of dermatologic lesions suggested that allergy was a reasonable differential diagnosis.

The haircoat and skin of the second dog were oily and the dog was mildly pruritic, thus a degreasing shampoo (benzoyl peroxide) and leave-on chlorhexi-dine conditioner were considered appropriate therapy. Systemic antibiotics were used in addition to the topi-cal therapy to treat the skin infection. Recheck visits help determine whether antibiotics have been adminis-tered for an appropriate length of time (minimum of 3 weeks). As in the first case, the dog in case 2 was still pruritic even though the pyoderma was cleared. This clinical information along with the biopsy results incated that food allergy was a reasonable differential di-agnostic concern.

These cases demonstrate that tactile and visual find-ings, cytology results, and the owners’ primary concerns should be considered when selecting topical therapy to maximize a patient’s chance of benefiting from it. As was done in these cases, owners should also be in-formed that their pets’ skin condition could change with time and thus a shampoo or conditioner that was once appropriate may not be in the future. Finally, these cases demonstrate that more than one topical therapy may be appropriate for a particular patient.

About the Author

Dr. Rees is affiliated with the Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, Texas. She is a Diplomate of the American College of Veterinary Derma-tology.

REFERENCES

1. Compendium of Veterinary Products, ed 4. Port Huron, MI, North American Compendium Inc, 1995–1996, p 1300. 2. Kwochka KW: Symptomatic topical therapy of scaling

disor-ders, in Griffin CE, Kwochka KW, MacDonald JM (eds):

Current Veterinary Dermatology. St Louis, Mosby–Year

Book, 1993, pp 191–202.

3. Scheidt VJ: The basic principles of shampoo therapy. Vet

Focus 2(2):58–61, 1990.

4. Ascher F, Maynard L, Laurent J, Goubet B: Controlled trial of ethyl lactate and benzoyl peroxide shampoos in the man-agement of canine surface pyoderma and superficial pyoder-ma, in von Tscharner C, Halliwell REW (eds): Advances in

Veterinary Dermatology, ed 1. London, Bailliere Tindall,

1990, pp 375–382.

5. Scott DW, Miller WH, Griffin CE: Dermatologic therapy, in Muller and Kink’s Small Animal Dermatology, ed 5. Phila-delphia, WB Saunders Co, 1995, pp 174–277.

6. Sebben JE: Surgical antiseptics. J Am Acad Dermatol 9(5): 759–765, 1993.

7. Sanchez IR, Nusbaum KE, Swaim SF, et al: Chlorhexidine diacetate and povidone–iodine cytotoxicity to canine embry-onic fibroblasts and Staphylococcus aureus. Vet Surg 17(4): 182–185, 1988.

8. Lozier SM: Topical wound therapy, in Harari J (ed):

Surgi-cal Complications and Wound Healing in the Small Animal Practice. Philadelphia, WB Saunders Co, 1993, pp 63–88.

9. Zamora JL: Povidone–iodine and wound infection. Surgery 95:121–122, 1984.

10. Zamora JL: Chemical and microbiologic characteristics and toxicity of povodone–iodine solutions. Am J Surg 151: 400–406, 1984.

11. Swaim SF, Lee AH: Topical wound medications: A review.

JAVMA 190(10):1588–1593, 1987.

12. Osuna DJ, DeYoung DJ, Walker RL, et al: Comparison of three skin preparation techniques in the dog. Part 2. Clinical trial in 100 dogs. Vet Surg 19(1)20–23, 1990.

13. Zuckerraun HL, Babich H, May R, Sinensky MC: Tri-closan: Cytotoxicity, mode of action, and induction of apop-tosis in human gingival cells in vitro. Part 1. Eur J Oral Sci 106:628–636, 1998.

14. Kwochka KW: Rational shampoo therapy in veterinary der-matology. Proc 11th Annu Kal Kan Symp Treat Small Anim

Dis:87, 1998.

15. Jawetz E: Antifungal agents, in Katzung BG (ed): Basic and

Clinical Pharmacology. Los Altos, CA, Appleton and Lange,

1987, pp 554–558.

16. Leyden JJ, McGinley KJ, Mills OH, et al: Effects of sulfur and salicylic acid in a shampoo base in the treatment of dan-druff: A double-blind study using counts and clinical grad-ing. Cutis 39:557,1987.

17. Rosenkrantz WS, Griffin CE, Walder E, et al: Superficial suppurative necrolytic dermatitis in miniature schnauzers: A retrospective analysis. Proc ACVD/AAVD: 99, 1991. 18. Basset NG (ed): Herbal Drugs and Phytopharmaceuticals.

Boca Raton, FL, CRC Press, 1994, pp 96–98.

19. Klein AD, Penneys NS: Aloe vera. J Am Acad Dermatol 18:714–720, 1988.

20. Haliwell REW: The use of shampoos in veterinary practice.

Vet Annu 36:127–141, 1996.

21. Saeed SA, Butt NM, McDonald-Gibson WJ, et al: In-hibitor(s) of prostaglandin biosynthesis in extracts of oat (Avena sativa) seeds. Biochem Soc Trans 9(5): 444, 1981. 22. Riboldi A, Pigatto PO, Altomare GF, et al: Contact allergic

dermatitis from oatmeal. Contact Dermatitis 18(5): 316– 317, 1988.

23. Pigatto P, Bigardi A, Caputo R, et al: An evaluation of aller-gic contact dermatitis potential of colloidal grain

sions. Am J Contact Dermatol 8(4):207–209, 1997.

24. Moore PK, Hoult GR: Selective actions of aspirin and sul-fasalazine-like compounds against prostaglandin synthesis and breakdown. Biochem Pharmacol 31:969–971, 1982. 25. Lehninger A (ed): Biochemistry, ed 2. New York, Worth,

1981, p 578.

Small Animal/Exotics 20TH ANNIVERSARY Compendium January 1999

26. Morrow DM, Rapaport MS, Strick RA: Hypersensitivity to aloe. Arch Dermatol 116:1064–1065, 1980.

27. Corll D: Novosomes® _{vs. liposomes. Evasco Pharmaceutic}

Newslet 1:1–2, 1998.

28. Koch HJ: Spherulites® _{Technical File. Fort Worth, TX,}