Carlos Albuquerque

Canine periodontitis: The dog as an important model for periodontal studies

Periodontal disease (PD) refers to a group of inflammatory diseases caused by bacterial plaque in the periodontium and ranges from an early stage (gingivitis) to an advanced stage (periodontitis). It is a multifactorial disease that results from the interaction of the host defence mechanisms with the plaque microorganisms. Early detection, diagnosis and treatment are essential in the control of this disease. PD has an enormous impact on human and veterinary medicine due to its high prevalence. The most common animal PD models use dogs and non-human primates, although other animals (rats, mice, hamsters, rabbits, miniature pigs, ferrets, and sheep) have also been employed. Dog models have contributed significantly to the current understanding of periodontology. The most important clinical aspects of canine PD are considered in this review and the various animal models are examined with an emphasis on the role of the dog as the most useful approach for understanding human PD and in the development of new therapeutic and preventive measures.

Interleukin-6 gene −174G>C and −636G>C promoter polymorphisms and prostate cancer risk

Prostate cancer (PCa) is one of the most commonly diagnosed internal malignancies affecting men. Due to the important roles of IL-6 in different physiological and pathophysiological processes, IL-6 polymorphisms may modulate PCa risk. IL-6 −174 G>C (rs 1800795, also designated −236 G>C) and −636 G>C (rs 1800796, also designated −572 G>C) promoter polymorphisms have been implicated in PCa susceptibility, albeit still controversial. A literature search using PubMed and Highwire databases was conducted, resulting in eight case–control studies concerning the IL-6 −174 G>C polymorphism (11,613 PCa cases and 13,992 controls) and four case–control publications regarding the IL-6 −636 G>C polymorphism (1,941 PCa cases and 3,357 controls). In order to derive a more precise estimation, a meta-analysis based upon these selected case–control studies was performed. There was no significant association between IL-6 −174 G>C polymorphism and PCa increased risk. Nevertheless, the presence of allele C and the CC genotype were statistically significantly associated with decreased PCa risk in the overall analysis for IL-6 −636 G>C polymorphism. Additional studies in larger samples and analyses of functional repercussions of these SNPs in prostate tumor cells are necessary to validate these findings.

Tongue nodules in canine leishmaniosis--a case report.

BackgroundCanine leishmaniosis (CanL) caused by Leishmania infantum is an endemic zoonosis in southern European countries. Infected dogs can present rare or atypical forms of the disease and diagnosis can be challenging. The present report describes a case of tongue nodules in a 3-year-old neutered female Labrador Retriever dog with leishmaniosis.FindingsA fine needle aspiration of the lingual nodules revealed amastigote forms of Leishmania inside macrophages. Differential diagnosis ruled out neoplasia, calcinosis circumscripta, solar glossitis, vasculitis, amyloidosis, eosinophilic granulomas, chemical and electrical burns, uremic glossitis and autoimmune diseases. Combined therapy with antimoniate meglumine and allopurinol for 30 days resulted in the normalization of hematological and biochemical parameters. Two months after diagnosis and the beginning of treatment, a mild inflammatory infiltrate was observed by histopathology, but an anti-Leishmania immunofluorescence antibody test (IFAT) was negative as well as a PCR on both tongue lesions and a bone marrow aspirate. Seven months after diagnosis, the dog’s general condition appeared good, there were no tongue lesions and a new IFAT was negative. Fifteen months after diagnosis this clinically favourable outcome continued.ConclusionsThe dog could have suffered a relapsing episode of CanL, but a new systemic or local infection cannot be excluded. Regular clinical re-evaluation should be maintained, as a future relapse can potentially occur. In conclusion, CanL should be considered in the differential diagnosis of nodular glossitis in dogs.

Detection and characterization of interleukin-6 gene variants in Canis familiaris: association studies with periodontal disease.

Periodontal disease (PD) is the most common inflammatory disease of the oral cavity of domestic carnivores. In Human Medicine molecular genetics research showed that several genes play a role in the predisposition and progression of this complex disease, primarily through the regulation of inflammatory mediators, but the exactly mechanisms are poorly understood. This study aims to contribute to the characterization of the genetic basis of PD in the dog, a classically accepted model in Periodontology. We searched for genetic variations in the interleukin-6 (IL6) gene, in order to verify its association with PD in a case-control study including 25 dogs in the PD case group and 45 dogs in the control group. We indentified and characterized three new genetic variations in IL6 gene. No statistically significant differences were detected between the control and PD cases groups. Our results do not support an evidence for a major role contribution of these variants in the susceptibility to PD in the analyzed population. Nevertheless, the sequence variant I/5_g.105G>A leads to an amino acid change (arginine to glutamine) and was predicted to be possibly damaging to the IL6 protein. A larger cohort and functional studies would be of extreme importance in a near future to understand the possible role of IL6 variants in this disease.

A case-control study between interleukin-10 gene variants and periodontal disease in dogs.

Periodontal disease (PD) refers to a group of inflammatory diseases that affect the periodontium, the organ which surrounds and supports the teeth. PD is a highly prevalent disease with a multifactorial etiology and, in humans the individual susceptibility is known to be strongly determined by genetic factors. Several candidate genes have been studied, namely genes related with molecules involved in the inflammatory response. Interleukin-10 (IL-10) is a cytokine with important anti-inflammatory and immunomodulatory roles, and several studies indicate an association between IL10 polymorphisms and PD. In dogs, an important animal model in periodontology, PD is also a highly prevalent naturally occurring disease, and only now are emerging the first studies evaluating the genetic predisposition. In this case-control study, a population of 90 dogs (40 dogs with PD and 50 healthy dogs) was used to study the IL10 gene, and seven new genetic variations in this gene were identified. No statistically significant differences were detected in genotype and allele frequencies of these variations between the PD cases and control groups. Nevertheless, one of the variations (IL10/2_g.285G>A) leads to an amino acid change (glycine to arginine) in the putative signal peptide, being predicted a potential influence on IL-10 protein functionality. Further investigations are important to clarify the biological importance of these new findings. The knowledge of these genetic determinants can help to understand properly the complex causal pathways of PD, with important clinical implications.

Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs

Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria. In humans, polymorphisms in the IL1A and IL1B genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case–control study was conducted in which a molecular analysis of dog IL1A and IL1B genes was performed. Of the eight genetic variants identified, seven in IL1A gene and one in IL1B gene, IL1A/1_g.388A >C and IL1A/1_g.521T >A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03–0.76), P= 0.022; 5.76 (1.03–32.1), P= 0.046, respectively). It suggests that in the studied population the IL1A/1_g.388C allele is associated with a decreased PD risk, whereas the IL1A/1_g.521A allele can confer an increased risk. Additionally, the IL1A/2_g.515G >T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that IL1 genetic variants may be important in PD susceptibility in canines.