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1.
The calcineurin inhibitor cyclosporin A and the phosphodiesterase 4 inhibitor cilomilast exhibit potent immunomodulatory properties which make them interesting therapeutics for the treatment of skin disorders like canine and human atopic dermatitis. Cyclosporin A and phosphodiesterase 4 inhibitors have already demonstrated clinical efficacy in the therapy of canine and human atopic dermatitis. Their direct impact on keratinocytes, especially canine keratinocytes, is less obvious. Thus, an investigation was carried out to ascertain whether cyclosporin A and cilomilast modulate keratinocyte proliferation and secretion of proinflammatory mediators. Cyclosporin A inhibited canine and murine keratinocyte proliferation, whereas cilomilast had no affect. Cyclosporin A and cilomilast reduced the lipopolysaccharide-induced prostaglandin E2 synthesis in canine and murine keratinocytes. Both immunomodulators also inhibited the production of the CXC chemokine KC and CCL2 in the murine keratinocyte cell line MSC-P5. The two immunomodulators also significantly reduced the interferon-gamma-induced production of interferon-gamma-inducible protein 10 in human keratinocytes (HaCaT cells). Thus, cyclosporin A and cilomilast directly modulate keratinocyte functions which might contribute to the anti-inflammatory and immunomodulatory action of these compounds in the treatment of allergic skin diseases.  相似文献   

2.
Abstract Cyclosporin has been increasingly used for the treatment of skin diseases in small animals. Reported uses include the treatment of atopy, cutaneous lupus erythematosus, feline acquired alopecia resembling pseudopelade of humans, pemphigus erythematosus, pemphigus foliaceus, perianal fistulae and sebaceous adenitis. In addition, cyclosporin has been used anecdotally for several other skin diseases. Few side effects have been noted at doses therapeutic for dermatologic diseases. Current suggestions for monitoring, and the value of trough cyclosporin serum concentrations for prediction of toxicity and efficacy are discussed.  相似文献   

3.
Treatment of canine scabies with milbemycin oxime.   总被引：3，自引：1，他引：2       下载免费PDF全文
The purpose of this study was to determine the efficacy of orally administered milbemycin oxime in the treatment of canine scabies. Forty dogs were treated. Mean drug dosage for all dogs was approximately 2 mg/kg body weight. Twenty-seven dogs received 3 doses separated by 7 d, and 13 dogs received 2 doses separated by 14 d. All dogs were clinically normal following treatment and no adverse reactions were detected.  相似文献   

4.
Dermal microdialysis, a relatively noninvasive technique, allows investigation of the changes in cellular mediators released during cutaneous allergic responses. This technique was used to evaluate the effect of cyclosporin A, an immunosuppressive drug used for treatment of canine atopic dermatitis, on the cutaneous release of two pro-inflammatory mediators following intradermal allergen challenge. Four beagle dogs spontaneously sensitized to Ascaris suum were treated for 1 month with oral cyclosporin A. At days 0, 15 and 30 of the treatment, dialysis probes were inserted into the skin of the back, and 20 microL of A. suum antigen was injected intradermally at each site. At timed intervals, dialysate was collected and assayed for histamine and prostaglandin D(2) and the wheal area was measured. Mean histamine concentration and wheal area were significantly lower at days 15 and 30 of treatment, compared with day 0. However, prostaglandin D(2) concentration was not significantly reduced. The inhibition in histamine release after intradermal challenge, by cyclosporin, confirms its anti-inflammatory action in the dog. Dermal microdialysis provides a useful tool for investigating canine allergic reactions and their modulation by drugs.  相似文献   

5.
Client education is the most important step in seizure management. The owner should be well informed about canine epilepsy and the present limitations regarding treatment. Regular follow-up should be performed for drug monitoring, evaluation of the metabolic profile, and assessment of seizure frequency. Other methods of treatment may become available in the future to treat the dog with epilepsy. Potassium bromide, the first anticonvulsant discovered, is being reevaluated as an anticonvulsant in the dog. The dose advocated is 50 mg per kg once daily. This author has no experience with this drug. GABA-mimetic drugs have been shown to exert potent anticonvulsant effects against chemically and electrically induced seizures in rats. Surgical treatment of intractable epilepsy, such as division of the corpus callosum, is being performed in man. Also in man, cerebellar stimulation is effective in controlling intractable epilepsy. Recently, acupuncture treatment has been shown to reduce seizure frequency in a few epileptic dogs. Unfortunately, the ideal anticonvulsant drug still does not exist. Every patient should be evaluated as an individual. Administration of multiple drugs should be avoided whenever possible to minimize side effects and drug interactions.  相似文献   

6.
Cyclosporin is currently considered a new and interesting drug in veterinary dermatology for the treatment of immune-mediated skin diseases, and a safe and effective alternative to immunosuppressive therapy with glucocorticoids. The authors report a case of granulomatous folliculitis and furunculosis and of sebaceous adenitis in two cats and a case of alopecia areata in a dog, successfully controlled with cyclosporin.  相似文献   

7.
Promeris Duo (PD) is a novel topical flea and tick preventative for dogs, which is also licensed for treatment of canine demodicosis. In this article, we present 22 dogs that all developed pemphigus foliaceus (PF)-like cutaneous drug reactions at the site of PD application. In eight dogs, the lesions were restricted to the application site (localized group). Signs of systemic illness were reported in three dogs, and four required immunosuppressive treatment. Direct immunofluorescence for IgG was positive in four dogs, although circulating antikeratinocyte IgG could not be detected in any tested sera. Complete remission was achieved in all dogs, with one patient still remaining on treatment. Fourteen dogs developed skin lesions at the application site as well as other noncontiguous areas (distant group). Systemic signs were reported in 11 dogs, and immunosuppression was required in 10 cases. Direct and indirect immunofluorescence tests were positive for antikeratinocyte autoantibodies in 10 of 13 and six of 10 patients with distant disease, respectively. Complete remission was achieved in 10 of 13 dogs with distant disease; one-third are still on treatment. Histological changes were similar to canine PF. Desmosomal architectural changes, assessed by desmoglein-1 immunostaining, were also similar to those of dogs with spontaneous autoimmune PF. Apoptosis did not appear to contribute to lesion formation, in either autoimmune or PD-associated PF. In conclusion, PD has the potential of triggering a variant of PF that resembles spontaneously occurring autoimmune PF at clinical, morphological, immunological and treatment outcome levels.  相似文献   

8.
Allergen-specific immunotherapy (ASIT) has been used for years to treat dogs with atopic dermatitis (AD) and humans with atopic diseases. The efficacy of ASIT has been well documented for humans with respiratory atopic diseases and stinging insect allergy, but its effectiveness seems more controversial for patients with AD. In spite of insufficient evidence derived from randomized controlled trials, multiple open studies and a large body of clinical observations suggest that ASIT is effective in controlling the clinical signs of dogs with AD. As a result of the scarcity of evidence from controlled trials, the true efficacy of ASIT, and the optimal protocols for allergen dose and frequency of injection are currently unknown. Allergen-specific immunotherapy nevertheless may be included in the treatment of canine AD because of its potential advantages and limited disadvantages compared to other forms of therapy. There is no evidence, however, for the preference of any specific treatment protocol. The predictive value of historical, clinical and immunologic features related to the efficacy of ASIT in dogs with AD are discussed in this paper. Adverse reactions, and the requirements for monitoring of patients receiving ASIT, then are reviewed and detailed. Finally, this review highlights aspects of ASIT where further research and controlled studies are needed.  相似文献   

9.
Current Concepts in the Management of Acute Spinal Cord Injury   总被引：3，自引：0，他引：3  
Acute injury to the spinal cord initiates a sequence of vascular, biochemical, and inflammatory events that result in the development of secondary tissue damage. Experimental studies and clinical trials in humans have demonstrated that the extent of this secondary tissue damage can be limited by pharmacologic intervention at appropriate intervals after injury. High doses of methylprednisolone sodium succinate (MPSS) improve the outcome of acute spinal cord injury in humans if treatment is initiated within 8 hours of injury. Starting therapy more than 8 hours after injury is detrimental to outcome. The clinical efficacy of methylprednisolone in improving the outcome of canine spinal cord injuries has not yet been demonstrated and its use by veterinarians is controversial. Many dogs are not seen by a veterinarian within the 8-hour window after injury, and these dogs frequently are treated with nonsteroidal anti-inflammatory drugs or large doses of dexamethasone or prednisone before methylprednisolone treatment can be initiated, thus increasing the risk of severe adverse effects. Other drugs that may provide safer and more effective alternatives to methylprednisolone include thyrotropin-releasing hormone (TRH), the 21-aminosteroids, and kappa opioid agonists. Recent studies suggest that modulation of the influx of inflammatory cells and activation of endogenous microglial cells may provide another means of improving the outcome of acute spinal cord injuries. Many drugs being developed to treat acute spinal cord injury have shown promising results when evaluated experimentally. However, any proposed therapeutic strategy should be evaluated in prospective blinded clinical trials before being adopted in clinics.  相似文献   

10.
Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing.  相似文献   

11.
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.  相似文献   

12.
Oxcarbazepine has been proven to be a promising new antiepileptic drug for the treatment of human epilepsy. Unlike carbamazepine, it is not oxidatively metabolized in humans, and therefore causes almost no induction of hepatic enzymes at clinically effective dosages. Though showing similar efficacy to carbamazepine, it has been reported to cause significantly fewer side-effects. It was the purpose of the present study to determine whether oxcarbazepine might be suitable for the treatment of canine epilepsy. In single-dose experiments, 40 mg/kg oxcarbazepine as a suspension was administered to seven dogs via gastric tube. Plasma concentrations reached peak concentrations of 2.4-8.8 μg/mL at about 1.5 h and declined with an elimination half-life of approximately 4 h. The corresponding concentrations of its metabolite, 10.11-dihydro-10-hydroxycarbamazepine, did not exceed 1 μg/mL. During continued treatment for 8 days, doses of 30 and 50 mg/kg were administered orally in capsules to two dogs three times a day. Plasma concentrations showed a pronounced decline from day 3. and the terminal half-life decreased to 2 h and 1 h. This is considered to be the result of oxcarbazepine inducing its own metabolism. The data reveal that oxcarbazepine, compared with former results with carbamazepine, offers no advantage for the treatment of epileptic dogs.  相似文献   

13.
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14.
Assessment of antiepileptic drugs as substrates for canine P-glycoprotein   总被引：2，自引：0，他引：2  
OBJECTIVE: To determine whether antiepileptic drugs (AEDs) are substrates for canine P-glycoprotein (P-gp). Sample Population-OS2.4/Doxo cells (canine osteosarcoma cells induced via exposure to doxorubicin to highly express P-gp). PROCEDURES: Competitive inhibition of rhodamine 123 efflux from OS2.4/Doxo cells was used to determine whether AEDs were substrates for canine P-gp. Flow cytometry was used to quantify mean fluorescence intensity of cells treated with rhodamine alone and in combination with each experimental drug. RESULTS: Known P-gp substrate drugs ivermectin and cyclosporin A altered rhodamine efflux by 90% and 95%, respectively. Experimental drugs altered rhodamine efflux weakly (diazepam, gabapentin, lamotrigine, levetiracetam, and phenobarbital) or not at all (carbamazepine, felbamate, phenytoin, topirimate, and zonisamide). CONCLUSIONS AND CLINICAL RELEVANCE: At clinically relevant doses, it appeared that AEDs were weak substrates (diazepam, gabapentin, lamotrigine, levetiracetam, and phenobarbital) or were not substrates (carbamazepine, felbamate, phenytoin, topirimate, and zonisamide) for canine P-gp. Therefore, it seems unlikely that efficacy of these AEDs is affected by P-gp expression at the blood-brain barrier in dogs.  相似文献   

15.
Canine haemobartonellosis, canine hepatozoonosis, and feline cytauxzoonosis   总被引：1，自引：0，他引：1  
Although Lyme borreliosis (Lyme disease), ehrlichiosis, Rocky Mountain spotted fever, and babesiosis occur more frequently in dogs or cats, from a clinical standpoint, other tick-borne diseases such as canine haemobartonellosis, canine hepatozoonosis, and feline cytauxzoonosis are just as important to recognize. Information concerning these less common tick-borne diseases are discussed, including their causative agents and their relationship to disease pathogenesis, diagnosis, treatment, and prevention.  相似文献   

16.
P‐glycoprotein (P‐gp), encoded by the ABCB1 (MDR1) gene, dramatically impacts drug disposition. P‐gp is expressed in the intestines, biliary canaliculi, renal tubules, and brain capillaries where it functions to efflux substrate drugs. In this capacity, P‐gp restricts oral absorption, enhances biliary and renal excretion, and inhibits central nervous system entry of substrate drugs. Many drugs commonly used in veterinary medicine are known substrates for canine P‐gp (vincristine, loperamide, ivermectin, others). Because these drugs have a narrow therapeutic index, defective P‐gp function can cause serious adverse drug reactions due to enhanced brain penetration and/or decreased clearance. P‐gp dysfunction in dogs can be intrinsic (dogs harboring ABCB1‐1Δ) or acquired (drug interactions between a P‐gp inhibitor and P‐gp substrate). New human drug candidates are required to undergo assessment for P‐gp interactions according to FDA and EMA regulations to avoid adverse drug reactions and drug–drug interactions. Similar information regarding canine P‐gp could prevent adverse drug reactions in dogs. Because differences in P‐gp substrates have been documented between species, one should not presume that human or murine P‐gp substrates are necessarily canine P‐gp substrates. Thus, our goal was to develop a cell line for assessing drugs as canine P‐gp substrates.  相似文献   

17.
Naturally occurring cancer in companion animals parallels cancer in man more closely than does experimentally induced cancer in inbred laboratory animals. In dogs and cats, as in man, a role for immune responses is indicated in the development of tumors. A survey is presented based on the literature and our own studies concerning the immunological and immunotherapeutic aspects of canine and feline mammary neoplasia. In dogs bearing mammary neoplasms, circulating immune complexes appear to play a negative role in the generation of effective antitumor immune responses. The functional role of peripheral blood lymphocytes and tumor-infiltrating lymphocytes in dogs and cats with mammary tumors is not yet fully established. No tumor antigen responsible for humoral or cellular responses has yet been identified. Extracorporeal perfusion of serum of dogs with mammary tumors and subcutaneous administration of mitomycin- and neuraminidase-treated autologous tumor cells are associated with improved prognosis. The opposite was true for i.v. treatment with BCG or Corynebacterium parvum vaccine in our study, in contrast to a previous report. A number of other treatment modalities in cats and dogs with mammary carcinomas failed to induce tumor regression. Canine and feline mammary carcinomas are good candidates for modern immunotherapeutic approaches.  相似文献   

18.
Abstract— Products of the 5-lipoxygenase metabolic pathway may be important mediators of inflammation in canine skin. Pharmacologic blockade of this pathway may therefore decrease clinical signs associated with canine atopy. To test this hypothesis, 31 dogs were entered on a randomized, double-blind, placebo-controlled, crossover trial to assess the efficacy of an investigational oral 5-lipoxygenase inhibitor (WY-50295) in treating canine atopy. Dogs were treated for 11 days with the drug and 11 days with the placebo, in random order, with a 3-day washout period between the treatment periods. Clinical signs were assessed daily by the owner in all 31 dogs, using a subjective scoring scale. Twelve of the dogs were additionally evaluated at intervals by the investigators and similarly scored. Analysis of variance revealed no significant differences ( P > 0.05) in owner or investigator scores assigned during placebo treatment, drug treatment, and no treatment periods. In an end-of-study evaluation, 24.1 per cent of owners reported satisfactory response to placebo capsules and 17.2 per cent reported satisfactory response to the drug, demonstrating a strong placebo effect. Short-duration treatment with WY-50295 did not appear to be effective in reducing clinical signs of atopy.  相似文献   

19.
A series of experiments was conducted to study cyclosporin A (CsA) pharmacokinetics in dogs and the factors influencing variability of blood concentrations. In a first study, influence of feeding on drug absorption and blood profile was evaluated. Administration of CsA as micro-emulsion (ME) formulation with food decreased the bioavailability by 22% and increased the individual variability of drug absorption. In a second study, pharmacokinetic profiles from laboratory fasted beagle dogs receiving orally CsA ME formulation were analyzed. CsA was measured in blood samples by high-performance liquid chromatography (HPLC, 34 profiles) and fluorescent polarization immunoassay (FPIA, 16 profiles). A two-compartment model with first-order absorption was used to calculate the pharmacokinetic parameters. Using FPIA, blood concentrations were 1.5 to 1.7 times higher than when using HPLC, but elimination half-life and MRT were similar. The coefficient of variation of key pharmacokinetic parameters ranged from 27 to 34% following HPLC assay. The same range of variation was obtained after FPIA assay. In a third study, in a clinical trial evaluating CsA for the treatment of canine atopic dermatitis, a single blood sample was collected in dogs which had received CsA for 28 days. No significant correlation was found between clinical improvement and CsA blood concentrations. Considering the large margin of safety of CsA in dogs, the limited inter-individual variability and the lack of correlation between blood concentrations and clinical response, routine monitoring of blood CsA does not appear necessary in dogs with atopic dermatitis.  相似文献   

20.
Dogs were treated with the anti-epileptic drug valproic acid (VPA) for 2 weeks in order to determine whedier therapeutic plasma levels could be maintained. VPA (as the sodium salt) was administered in a dosage of 170–180 mg/kg/day divided into three equal doses in the form of enteric-coated tablets. Due to the rapid elimination of this drug in dogs, therapeutic plasma levels were reached only intermittently. However, the concentrations maintained may be sufficient for anti-epileptic therapy in dogs because the lower plasma protein binding of VPA in this species gives rise to higher central concentrations compared with man. Furthermore, some VPA metabolites previously shown to exert anticonvulsant activity (2-en-VPA and 3-keto-VPA) were found in relatively high concentrations in dog plasma.
We would recommend the dosages used in this study as a basis for assessment of VPA in the treatment of canine epilepsy.  相似文献   

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