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Biomedical subjects

R Marsella

Publications and source records attributed to R Marsella.

At least 19 recordsLinked to original sources
PubMed2006

Studies on the role of routes of allergen exposure in high IgE-producing beagle dogs sensitized to house dust mites.

The current study aimed to investigate the role played by oral, epicutaneous, and inhalation routes of exposure to house dust mites (HDM). The colony of high IgE-producing beagle dogs has been shown to develop pruritic dermatitis compatible with atopic dermatitis following environmental exposure (EE) to HDM. In crossover experiments, the response to EE was compared to two modified challenges, oral exposure (OE) and snood and muzzle exposure (SME). For OE, HDM were fed daily for 3 days. For SME, ingestion of allergen was prevented but there was inhalation and epicutaneous exposure to all body regions except to one ear. In all experiments, dogs were challenged for three consecutive days, and evaluated before, 6 h after exposure and daily thereafter, for 5 days. After a wash-out period, groups were crossed-over so that each dog was randomly challenged to all three protocols. Clinical scores were analysed using least squares analysis of variance. All dogs developed pruritic dermatitis regardless of the protocol. With OE, lesions developed in the same body regions as with EE although scores were lower. This difference became more evident after the first 3 days when OE scores decreased and EE scores continued to increase. The scores of covered and uncovered ears did not differ with SME. Scores for the remainder of the body were significantly lower than for EE. The development of lesions on covered ears supports the importance of inhalation or a systemic reaction to epicutaneous exposure in other areas. It is concluded that all routes are important and have additive effects, that route of exposure does not determine the distribution of lesions and that continuous epicutaneous exposure probably plays the most important role.

Allergens↗
PubMed2004

Investigation on the effects of topical therapy with 0.1% tacrolimus ointment (Protopic) on intradermal skin test reactivity in atopic dogs.

Tacrolimus ointment (TAC) is an effective treatment for atopic dermatitis in humans and dogs. The purposes of the present study were to evaluate the effect of 4 weeks of TAC on intradermal skin testing (IST), and in case of suppression, to investigate if reactivity returned to baseline by 2 or 4 weeks post treatment. Intradermal skin test was performed using saline, histamine, lipopolysaccharide (LPS, 0.4 mg mL(-1)), house dust (25 PNU mL(-1)) and house dust mite (1 : 40 000 w/v) at weeks 0, 4, 6 and 8 on nine dogs enrolled in a blinded, crossover, clinical trial, using 0.1% TAC or placebo once daily for 4 weeks. Reactions were evaluated at 15 min, and at 4 and 6 h. Ointment was applied after the 15-min evaluation on weeks 0 and 4. Data were analysed using the statistical software SAS System for Windows. At week 4, TAC did not affect 15-min IST, but some reactions in the TAC group were suppressed at 6 h compared to baseline. In the TAC group, 4-h IST reactivity was reduced 2 weeks after discontinuation but returned to baseline by 4 weeks. In conclusion, TAC has no effect on immediate reactions but decreased some late-phase reactions. Therefore, no withdrawal is recommended to evaluate only immediate reactions, but a 4-week withdrawal may be necessary for evaluation of late-phase reactions.

Administration, Cutaneous↗
PubMed2004

Investigation on the clinical efficacy and safety of 0.1% tacrolimus ointment (Protopic) in canine atopic dermatitis: a randomized, double-blinded, placebo-controlled, cross-over study.

Topical tacrolimus is successfully used in people with atopic dermatitis. Preliminary studies in dogs with atopic dermatitis using tacrolimus in a compounded lotion formulation indicated that tacrolimus significantly decreased erythema and pruritus according to investigator, but no significant improvement was reported by the dog owners. The objectives of this study were to evaluate the clinical efficacy and safety of the commercially available 0.1% tacrolimus ointment (Protopic) in dogs with atopic dermatitis. The study was designed as a double-blinded, placebo-controlled, cross-over study. Selected dogs were allocated to either tacrolimus or placebo for 4 weeks. After 4 weeks there was a wash-out period of 2 weeks and treatments were switched. Twelve dogs completed the study. Clinical signs were scored. Blood samples were collected for complete blood count, chemistry panels and tacrolimus levels at week 0 and 4 of each treatment. Tacrolimus ointment significantly decreased severity of symptoms for both owners and investigators at the end of the trial. When the same dogs received the placebo, there were no differences between week 0 and week 4 scores. Dogs with localized disease responded better than dogs with generalized disease. Tacrolimus was detected in the blood of animals receiving the active ingredient. Levels were below the level of toxicity and no adverse effects were reported in any of the dogs. No changes in complete blood count and chemistry parameters were detected between groups or within groups. In conclusion, tacrolimus appears to be a safe alternative treatment in dogs with atopic dermatitis, especially in those with localized disease.

Administration, Cutaneous↗
PubMed2004

Evaluation of adrenal function in small-breed dogs receiving otic glucocorticoids.

The objectives of this study were to evaluate adrenal function after otic glucocorticoid [Tresaderm (dexamethasone) and Otomax (betamethasone)] therapy in small-breed dogs without evidence of otitis and to evaluate the length of time needed for resolution of adrenal suppression after discontinuation of treatment. Fourteen clinically healthy, privately owned, small-breed dogs with normal ears and normal adrenocorticotropin (ACTH) stimulation tests were assigned to one of two treatment groups, receiving one of the medications at the manufacturer's recommended dosage twice daily for 2 weeks. All of the dogs in the betamethasone treatment group had normal ACTH stimulation tests after 2 weeks of treatment. In contrast, 5/7 (71.43%) in the dexamethasone group, had suppressed adrenocortical responses to exogenous ACTH. Three of these five dogs (42%) returned to normal values 1 week after ceasing the medication and two (28.57%) returned to normal values 2 weeks after ceasing the medication. In conclusion, it appears that adrenal function can be suppressed for up to 2 weeks in dogs receiving otic dexamethasone. A follow-up study repeating this work in dogs with inflamed ears is needed before further clinical recommendations can be made.

Administration, Topical↗
PubMed2001

The ACVD task force on canine atopic dermatitis (II): genetic factors.

Canine atopic dermatitis is commonly diagnosed in pruritic animals. Many studies have attempted to determine the inheritance pattern of both atopic dermatitis and of elevated allergen-specific IgE production. Despite many clinical, laboratory and breeding studies, the mode of inheritance and genetic mutations underlying this disease currently remain elusive.

Animals↗
PubMed2001

The ACVD task force on canine atopic dermatitis (VII): mediators of cutaneous inflammation.

Controversy still exists on the role of various inflammatory mediators in the pathogenesis of canine atopic dermatitis. The objective of this article is to review the most recent information available on the inflammatory mediators that have been implicated in the pathogenesis of this disease. Studies on the role of histamine, serotonin, leukotrienes and various cytokines are presented in a comparative manner reviewing the experimental evidence for a role in the pathogenesis and the arguments against it.

Animals↗
PubMed2001

The ACVD task force on canine atopic dermatitis (XXII): nonsteroidal anti-inflammatory pharmacotherapy.

The pharmacotherapy of canine atopic dermatitis has relied primarily on the use of glucocorticoids and anti-histamines. During the last decade, other anti-inflammatory drugs have been investigated in clinical trials. This paper will review the studies using misoprostol, cyclosporine, tacrolimus, phosphodiesterase inhibitors, capsaicin, leukotriene inhibitors and serotonin-reuptake inhibitors for treatment of dogs with atopic dermatitis. For each drug the mechanism of action, the rationale for use in atopic dermatitis, the clinical efficacy, reported adverse effects and strength of recommendation for treatment of canine atopic dermatitis are described. At the time of this writing, there is fair evidence to support the recommendation for using cyclosporine, misoprostol and pentoxifylline for treatment of canine atopic dermatitis. This recommendation can be strengthened by the performance of additional blinded randomized controlled trials with larger number of dogs. In contrast, there is insufficient evidence to recommend for or against treatment with tacrolimus, leukotriene inhibitors, serotonin-reuptake antagonists and capsaicin.

Animals↗
PubMed2001

The ACVD task force on canine atopic dermatitis (XXIII): are essential fatty acids effective?

Essential fatty acids (EFAs) exhibit the potential to affect allergic inflammation through the modulation of prostaglandin and leukotriene production, the inhibition of cellular activation and cytokine secretion as well as the alteration of the composition and function of the epidermal lipid barrier. Because of these multi-faceted effects, EFA have been proposed for treatment of canine atopic dermatitis (AD) since 1987. To date, more than 20 trials have been performed, reporting the efficacy of either oral EFA supplements or EFA-rich diets. Unfortunately, most of these studies were found to exhibit one or more of the following deficiencies: heterogeneity of diagnoses used as inclusion criteria, short duration of supplementation, lack of randomization of treatment allocation, lack of blinding of investigators and/or owners, lack of placebo or active controls, lack of documentation of plasma or skin EFA profiles during supplementation, as well as lack of standardization of the basal diets or supplements which could have provided additional EFA. Consequently, there is presently insufficient evidence to recommend for or against the use of EFA to control clinical signs of canine AD. Evidence of efficacy must await the performance of blinded, randomized and controlled trials of at least 3 months duration in which diets are identical for all of study subjects. In these trials, clinical efficacy should be evaluated in relation to plasma and cutaneous EFA treatment-induced alterations.

Animals↗
PubMed2001

The ACVD task force on canine atopic dermatitis (XII): the relationship of cutaneous infections to the pathogenesis and clinical course of canine atopic dermatitis.

Dogs and human beings with atopic dermatitis (AD) frequently exhibit concurrent skin infections with Staphylococcus sp. bacteria or Malassezia yeast, and treatment of such infections is an important facet of managing these patients. Staphylococci appear to colonize atopic skin readily, and bacterial products on the skin could augment cutaneous inflammation via immediate hypersensitivity responses to the bacteria, by superantigen-mediated lymphocyte activation, or other non-specific mechanisms. Similarly, skin colonization by Malassezia yeast could contribute to clinical signs of AD; yeast components could induce inflammation via non-specific mechanisms, such as alteration in mediator release, or via antigen-specific hypersensitivity reactions. Clinical and experimental evidence exists that secondary microbial infections can both initiate and perpetuate episodes of AD in dogs and humans, and could even participate in promotion of pro-allergic immunologic responses. Mechanistic details of these complex interactions are under extensive investigation in human beings; only a few observations have been extended to include dog with AD.

Animals↗
PubMed2001

Double-blinded, placebo-controlled, cross-over pilot study on the efficacy of zileuton for canine atopic dermatitis.

Nine dogs meeting the diagnostic criteria for canine atopic dermatitis were enrolled in a double-blind, placebo-controlled, cross-over clinical trial. In this pilot study, zileuton (a 5-lipoxygenase inhibitor) given orally at 2 mg kg(-1) three times daily for 4 weeks significantly decreased erythema in dogs with atopic dermatitis but had no effect on pruritus. Zileuton was well tolerated and no adverse clinical signs were noted. However, one dog developed mild alanine aminotransaminase elevation, which resolved within 1 week of discontinuation of therapy. Monitoring of alanine aminotransaminase may be necessary in dogs receiving zileuton. Further studies with larger number of dogs are needed to evaluate the efficacy of zileuton as treatment for canine atopic dermatitis.

Administration, Oral↗
PubMed2001

Sulphido-leukotriene production from peripheral leukocytes and skin in clinically normal dogs and house dust mite positive atopic dogs.

Pathogenesis of canine atopy has not been completely elucidated. In humans, sulphido-leukotrienes (s-LT) play a role in atopy, and increased production of s-LT occurs in the skin and peripheral leukocytes after allergen challenge. The study population included 16 clinically normal and 13 atopic dogs. All atopic dogs had in common a positive reaction (4+) to the intradermal injection of house dust mite (allergen of reference). Blood samples and skin biopsies were collected. Sulphido-LT synthesis by peripheral leukocytes after stimulation was measured, and no statistically significant difference was found between clinically normal and atopic dogs. Sulphido-LT concentrations in skin samples from stimulated and unstimulated sites were measured, and no statistically significant difference was detected between clinically normal and atopic dogs or between lesional and nonlesional skin within the atopic group. Clinical signs of atopic dogs were graded by owners and no correlation was found between their severity and cutaneous concentrations of s-LT. In this study there was no increase in s-LT synthesis in atopic dogs.

Animals↗
PubMed2001

Update on the role of leukotrienes in the pathogenesis of atopy: a comparative review.

The pathogenesis of atopic disease (AD) is controversial in humans and dogs. In humans, leukotrienes (LT) are thought to play an important role in this disease and LT inhibitors are commonly used as treatment for AD. Leukotrienes are a heterogeneous group of biologically active compounds that mediate many aspects of inflammatory and allergic reactions. This paper will review the role of LT in atopic disease in a comparative manner. Leukotriene inhibitors and their therapeutic use in the management of atopic disease in humans and dogs are discussed.

Animals↗
PubMed2001

Intradermal skin test reactivity to histamine and substance P is blunted in dogs with atopic dermatitis.

Skin reactivity to intradermal injections (0.1, 0.5 and 1 nM) of substance P (SP) was evaluated in 20 clinically normal dogs and 20 dogs with atopic dermatitis (AD). Saline and histamine were used as negative and positive controls, respectively. Wheal diameters were measured. Reactions were evaluated for erythema and induration and a subjective score, on a scale from 0 to 4+, was given. Evaluations were performed at 3, 5, 10, 15 and 30 min after the injections. Wheal diameters for histamine and SP injections were significantly smaller in dogs with AD compared with clinically normal dogs. In both groups, reactions to the various concentrations of SP were not significantly different from each other and were always smaller than histamine reactions. Erythema was not seen with SP injections. In addition, subjective scores for SP injections were significantly lower in dogs with AD compared with controls. The results of this study are similar to those reported in human medicine, where a role for SP in AD is proposed and desensitization of receptors to both SP and histamine is hypothesized. Further studies are needed to investigate the role of SP in the pathogenesis of canine AD.

Animals↗
PubMed2000

Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration.

OBJECTIVE: To evaluate the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl-metabolite, metabolite 1 (M1), in dogs after IV administration of a single dose and oral administration of multiple doses. ANIMALS: 7 sexually intact, female, mixed-breed dogs. PROCEDURE: A crossover study design was used so that each of the dogs received all treatments in random order. A drug-free period of 5 days was allowed between treatments. Treatments included IV administration of a single dose of PTX (15 mg/kg of body weight), oral administration of PTX with food at a dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration of PTX without food at a dosage of 15 mg/kg (q 8 h) for 5 days. Blood samples were taken at 0.25, 0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last dose of PTX was administered PO, and at 5, 10, 20, 40, 80, and 160 minutes after PTX was administered IV. RESULTS: PTX was rapidly absorbed and eliminated after oral administration. Mean bioavailability after oral administration ranged from 15 to 32% among treatment groups and was not affected by the presence of food. Higher plasma PTX concentrations and apparent bioavailability were observed after oral administration of the first dose, compared with the last dose during the 5-day treatment regimens. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, oral administration of 15 mg of PTX/kg results in plasma concentrations similar to those produced by therapeutic doses in humans, and a three-times-a-day dosing regimen is the most appropriate.

Administration, Oral↗
PubMed1999

Advances in flea control.

With an increase in our knowledge of flea life cycle and biology, flea control has improved tremendously over the past 10 years. Treatment programs should be tailored to each case. The goal of effective flea control is to eliminate adults and to prevent reinfestation and the development of new generations of fleas. New products are of great benefit to flea-infested and flea-allergic animals and allow a safe and effective way to control fleas. Even if the consistent use of a topical adulticide alone is tempting, rotation and a combination of products should still be used to delay resistance. In addition, environmental flea control is a wise approach, especially in cases of severe infestation or in situations where there is a flea-allergic animal. Finally, in order to avoid failures and resistance, it is important to treat all pets in the household.

Animals↗