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-Gingiva of an Oxodipine-treated dog. The stratified squamous epithelium adjacent to the tooth (on the lower aspect of the figure) is markedly hyperplastic with long anastornosing rete pegs. H&E. x 50.
Source publication
Subchronic oral exposure of dogs to Oxodipine, a new calcium channel blocker of the dihydropyridine-type, resulted in dose-related gingival hyperplastic changes. The doses at which an effect was elicited were 24 and 73 times the intended therapeutic dose for man. The effects were first noted after 7 weeks of treatment, and were limited to the high...
Citations
... Except for neoplastic lesions, there is a broad scale of possible tumour-like lesions arising in canine oral cavity. These lesions are mostly induced by chronic inflammation, mechanical injury or drug administration (Waner et al. 1988;Reichart et al. 1989;Head 2003;Agrawal 2015;Ullal et al. 2019). ...
Many types of tumorous and tumour-like lesions occur in the oral cavity of dogs. Even benign neoplasia often represents great inconvenience due to potential restrictions of therapeutic surgical approach in this area. Whereas in human medicine, there are statistical data describing areas of the oral cavity, that are more prevalent for development of particular neoplasia, in veterinary medicine, these data are not yet available. The aim of this study was to evaluate the prevalence of tumours in dogs with oral neoplasia, the occurrence site of the most common neoplastic lesions in the canine oral cavity, as well as the effect of age and sex on the prevalence of these lesions. In this study we investigated oral tumorous lesions from 659 dogs, out of which 352 lesions were diagnosed as tumours and 307 as tumour-like lesions. The most common tumours encountered were melanoma (42%, n = 148), squamous cell carcinoma (16%, n = 57) and canine acanthomatous ameloblastoma (10%, n = 35). The median age of dogs with oral neoplasia was 9.9 years, with the range of 0.2 to 17.5 years. There was no significant association between sex and the type of oral lesion (tumorous and tumour-like). Melanoma was most commonly present in the caudal maxillary region, squamous cell carcinoma on the mouth floor, canine acanthomatous ameloblastoma in the area of the rostral mandible, plasmacytoma on the tongue, osteosarcoma was most often diagnosed in the caudal parts of oral cavity and fibrosarcoma did not have a specific site of occurrence.
... 3,15 The incidence of gingival enlargement in dogs is increased in various breeds and after drug therapy, such as with anticonvulsants, calcium blocking agents and immunosuppressive agents. 31 Gingival enlargement due to phenytoin and phenytoin metabolites has been reported infrequently in cats. 8 As in the present report, a previous study on olive and gelada baboons found that gingival inflammation (gingivitis) occur with no evidence of periodontal pocketing or bone loss. ...
We here describe a case of recurrent gingival enlargement in an olive baboon (Papio anubis). This baboon (a male breeder that had not undergone any experimental procedures) also had shown mild gingival enlargement the 2 y prior to the current lesion. Clinical and histopathologic findings confirmed a diagnosis of idiopathic gingival enlargement.
... 6 In toxicologic studies conducted with this drug in dogs and rats, gingival hyperplasia was noticed as a side effect. 7,8 This was recognized as an animal model of human disease, since clinical and pathological features of the oxodipine-induced gingival hyperplasia in beagle dogs are similar to those described in humans treated with nifedipine. 9 The collagen ®bres of the hyperplastic gingivae in oxodipine-induced gingival hyperplasia in beagle dogs were investigated histochemically. ...
1 The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodi-pine-inducing gingival hyperplasia in a dog model.
2 Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone.
3 A significant positive correlation between GI, GHI and plasma testosterone was noted. Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI.
4 Since it is known that testosterone receptors are present in the gingiva, it is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels.
... The dose at which the effect occurred in both male and female rats in the 30-mo study was from about 75 to 675 times the recommended therapeutic dose for humans. In a 1-yr safety study carried out in beagle dogs with oxodipine, no constipatory effects were evident at any of the dose levels (18). ...
The constipatory effects of oxodipine, a dihyrdopyridine-type calcium antagonist, have been described in a 3-mo, 12-mo, and 30-mo feeding toxicity study in rats. This paper reports the occurrence of megacolon in rats as a result of the constipatory effects of chronic administration of oxodipine. The first mortality due to oxodipine was seen after about 1 yr of treatment at a dose of 225 mg/kg/day. The toxic effects noted were dose-, time-, and sex-related. Female rats appeared more sensitive to the constipatory effects of the drug. The dose at which the effect occurred in both male and female rats was from about 75 to 675 times the recommended therapeutic dose for humans. To the best knowledge of the authors, this is the first report of a calcium channel blocker causing constipation in rats.
Dental, oral, and maxillofacial diseases are some of the most common problems in small animal veterinary practice. These conditions create significant pain as well as localized and potentially systemic infection. As such, the World Small Animal Veterinary Association (WSAVA) believes that un‐ and under treated oral and dental diseases pose a significant animal welfare concern. Dentistry is an area of veterinary medicine which is still widely ignored and is subject to many myths and misconceptions. Effective teaching of veterinary dentistry in the veterinary school is the key to progression in this field of veterinary medicine, and to the improvement of welfare for all our patients globally.
These guidelines were developed to provide veterinarians with the information required to understand best practices for dental therapy and create realistic minimum standards of care. Using the three‐tiered continuing education system of WSAVA, the guidelines make global equipment and therapeutic recommendations and highlight the anaesthetic and welfare requirements for small animal patients.
This document contains information on common oral and dental pathologies, diagnostic procedures (an easily implementable and repeatable scoring system for dental health, dental radiography and radiology) and treatments (periodontal therapy, extractions). Further, there are sections on anaesthesia and pain management for dental procedures, home dental care, nutritional information, and recommendations on the role of the universities in improving veterinary dentistry. A discussion of the deleterious effects of anaesthesia free dentistry (AFD) is included, as this procedure is ineffective at best and damaging at worst. Throughout the document the negative effects of undiagnosed and/or treated dental disease on the health and well‐being of our patients, and how this equates to an animal welfare issue, is discussed.
This chapter deals with the digestive system. The major and minor salivary glands and their secretions also represent and integral part of the protective mechanism of the oral cavity, and derangement of saliva production may lead to loss of integrity of the oral mucosa. Drug-induced abnormalities of taste sensation are also well-described phenomena occurring in man although human studies are necessary for the detection of these effects. Inflammation of the oral cavity may involve the buccal mucosa, the gingiva (gingivitis), the tongue (glossitis), and the peridontal tissues (peridontitis). Therapeutic agents can induce inflammatory lesions in the tongue. Moreover, a protective layer of mucus, a visco-elastic material containing high molecular weight glycoproteins produced by the major and minor salivary glands, covers the stratified squamous mucosa of the oral cavity. Salivary secretions also possess digestive enzyme activity although in herbivores and carnivores, it is usually low in contrast to high digestive enzyme activity in omnivorous species.
Pathology represents a challenge for everybody involved in drug development. Even trained pathologists with expertise in toxicological pathology have to make the difficult prediction of whether any drug induced pathology in animals is likely to occur in humans. If so, are rodents or dogs likely to be more or less sensitive to the adverse effects of drugs than patients? Do the pathology findings completely preclude giving a new drug safety to humans? In order to aide researchers with these tough decisions, the author has compiled this valuable reference.
The new 4th edition of Histopathology of Preclinical Toxicity Studies is now completely in full color and continues to describe the pathology found in drug safety studies in laboratory animals with an evidence-based discussion of the relevance of these findings to the clinical investigation of new drugs for humans. Organized according to organ systems, this revision features a thoroughly updated bibliography and discusses new drug-induced pathologies and applicable species comparisons to aid in the preclinical safety assessment of new medicines. This updated reference is essential for those involved in drug safety evaluation, including pathologists, toxicologists and pharmacologists working in corporate, government, academic and research settings. NEW TO THE FOURTH EDITION: *This edition is in full color and features nearly 200 high-quality images *Provides extended commentary on the relevance of pathological findings and features a fully updated bibliography containing sources for further reading *Includes new content coverage on the commonly used transgenic animal models that are used in safety assessment, specific tumor types induced by drugs in rodents, and new drug-induced pathologies and lesions.
