Oral Manifestations of Chronic Kidney Disease and Renal Secondary Hyperparathyroidism: A Comparative Review.

Recent epidemiological studies have demonstrated that significant associations exist between oral disease and diseases involving non-oral tissues. Occasionally, the roles may be reversed and the oral cavity can be severely affected by systemic disease originating in another part of the body. Renal secondary hyperparathyroidism is a common endocrinopathy that occurs as a consequence of chronic azotemic kidney disease. Renal osteodystrophy, the most dramatic clinical consequence of renal secondary hyperparathyroidism is uncommon, but can result in demineralization of maxillofacial bones, loosening of teeth, and pathological jaw fractures. The purpose of this report is to update the current understanding of the pathophysiology of this endocrine disease and to compare the oral manifestations of renal secondary hyperparathyroidism in humans and companion animals. A 50-year review of the veterinary literature was undertaken to examine the clinical presentation of renal osteodystrophy in dogs, and to determine what clinical consequences of renal secondary hyperparathyroidism have been reported in domestic cats.

Acromegaly in humans and cats: Pathophysiological, clinical and management resemblances and differences.

OBJECTIVE: Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. DESIGN: A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. RESULTS: Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. CONCLUSION: Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.

Optimised isolation method for RNA extraction suitable for RNA sequencing from feline teeth collected in a clinical setting and at post mortem.

Advanced next generation sequencing approaches have started to reveal the cellular and molecular complexity of the microenvironment in many tissues. It is challenging to obtain high quality RNA from mineralised tissues. We developed an optimised method of RNA extraction from feline teeth collected in a clinical setting and at post mortem. Teeth were homogenised in phenol-guanidinium solution at near-freezing temperatures and followed by solid-phase nucleic acid extraction utilising a commercially available kit. This method produced good RNA yields and improved RNA quality based on RNA integrity numbers equivalent (RINe) from an average of 3.6 to 5.6. No correlation was found between RNA purity parameters measured by A260:280 or A230:260 ratios and degree of RNA degradation. This implies that RNA purity indicators cannot be reliably used as parameters of RNA integrity. Two reference genes (GAPDH, RPS19) showed significant changes in expression levels by qPCR at low and moderate RINe values, while RPL17 was stable at all RINe values tested. Furthermore, we investigated the effect of quantity and quality of RNA on the quality of the resultant RNA sequencing (RNA-Seq) data. Thirteen RNA-seq data showed similar duplication and mapping rates (94 to 95%) against the feline genome regardless of RINe values. However one low yield sample with a high RINe value showed a high duplication rate and it was an outlier on the RNA-seq multidimensional scaling plot. We conclude that the overall yield of RNA was more important than quality of RNA for RNA-seq quality control. These results will guide researchers who wish to perform RNA extractions from mineralised tissues, especially if collecting in a clinical setting with the recognised restraints that this imposes.

Chronic Gingivostomatitis with Esophagitis in Cats.

BACKGROUND: Chronic gingivostomatitis in cats (FCG) is a debilitating disease with potentially deleterious effects on overall health. HYPOTHESIS/OBJECTIVES: Little is known about the pathophysiology and overall impact of FCG. The aims of our study were to investigate whether gingivostomatitis occurs concurrently with esophagitis, if FCG treatment contributes to esophagitis and if esophagitis exacerbates signs of FCG. ANIMALS: Fifty-eight cats with clinical signs of FCG and 12 healthy control cats exhibiting no signs of oral disease, all client-owned. METHODS: Prospective study. Physical, oral and endoscopic examinations were performed on all cats. Measurements of salivary and esophageal lumen pH were obtained from both groups. Biopsies were acquired from sites of esophageal inflammation in cats with FCG and from normal-appearing esophageal mucosa in control cats. RESULTS: The majority of cats with clinical signs of FCG exhibited some degree of esophagitis especially in the proximal (44/58) and distal (53/58) parts (P < 0.001) with or without columnar metaplasia, compared to controls. All cats lacked signs related to gastrointestinal disease. Salivary and esophageal lumen pH were not statistically different compared to controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Feline chronic gingivostomatitis seems to occur concurrently with esophagitis. Esophagitis also should be managed in cats with chronic gingivostomatitis because it may aggravate the existing condition.

Pharmacokinetics of propranolol in healthy cats during euthyroid and hyperthyroid states.

OBJECTIVE: To examine the pharmacokinetic profile of propranolol in cats before and during experimentally induced hyperthyroidism. ANIMALS: 8 conditioned, random-source, young adult, female cats. PROCEDURE: Propranolol was administered i.v. as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 micrograms/kg of body weight, s.c., once daily) to induce hyperthyroidism (serum thyroxine concentration, 217 +/- 17 nmol/L). Blood samples were obtained at appropriate intervals before and during hyperthyroidism and were analyzed for plasma propranolol concentration by use of high-performance liquid chromatography. RESULTS: In all cats, a two-compartment model best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a significant (P < 0.05), but small reduction in propranolol area under the curve (19,932 +/- 7,900 min.micrograms/L vs 15,911 +/- 1,400 min.micrograms/L) after i.v. administration. In contrast, after oral administration during the hyperthyroid state, a twofold increase (P < 0.05) in propranolol area under the curve (105,430 +/- 57,600 min.micrograms/L vs 226,811 +/- 112,000 min.micrograms/L) and peak serum propranolol concentration (651 +/- 247 micrograms/L vs 1191 +/- 590 micrograms/L) were attributed to significant (P < 0.05) increase in propranolol bioavailability caused by increased fractional absorption (57 +/- 28% vs 137 +/- 73%) and decreased total body clearance (58 +/- 27 ml/min/kg vs 30 +/- 19 ml/min/kg). Mean arrival time after oral dosing was significantly lengthened by hyperthyroidism (100 +/- 38 minutes vs 157 +/- 71 minutes). CLINICAL RELEVANCE: Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats.

Periodontal disease. Etiology and pathogenesis.

Periodontal disease is the number-one cause of the early loss of teeth in dogs and cats. Some of the factors in the adult animal that play a major role in the development of periodontal diseases are discussed in this article, including overcrowding, malocclusions, diet, developmental defects, and metabolic and systemic disease.

A novel mutation in CLCN1 associated with feline myotonia congenita.

Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1:100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a 'swarm of bees'. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine ß-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.

Systemic effects of periodontal disease in cats.

BACKGROUND: Periodontal disease in cats is a local disease that may have systemic consequences that are affected by treatment. OBJECTIVE: To test the hypotheses that systemic health indices would be correlated with the severity of periodontitis, and would improve with treatment. ANIMALS AND METHODS: Apparently otherwise healthy cats from an in-bred colony were randomly assigned to a treatment group (n = 30), or a control group (n = 18), which was left untreated for 3 months. Periodontal disease was scored at baseline in the treatment group according to calculus, gingivitis, and alveolar bone loss measured from dental radiographs. Blood, urine and saliva were collected from both groups before, and 16, 45, and 90 days after dental treatment. Assays included haematology, urinalysis, serum biochemistry, serum IgG, salivary IgA, lymphocyte subsets and proliferation, and plasma malonyldialdehyde (MDA). Correlations between the severity of periodontitis and assays at baseline were assessed, and the effect of treatment determined using linear mixed model methodology. RESULTS: The severity of periodontitis was associated with age, bodyweight, total globulins (Globs), Alanine aminotransferase, and IgG, and negatively associated with albumin, haemoglobin, haematocrit, and Aspartate aminotransferase (AST). Treatment significantly reduced IgG, total Globs, AST, and eosinophils, and increased cholesterol. Other leucocyte assays and plasma MDA concentrations were not affected by the treatment. Cats ate dry food faster 1 week after, than they did 1 week before treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Although the clinical significance of these findings are unknown, we conclude that periodontitis is not simply a localized disease, but also impacts on systemic health and wellbeing.

Inflammatory cytokines and the nuclear vitamin D receptor are implicated in the pathophysiology of dental resorptive lesions in cats.

Dental resorptive lesions (RL) are a common oral disease in cats (Felis catus) associated with pain and tooth destruction. The aetiology of RL in cats is unknown, but inflammation is often seen in conjunction with RL. Vitamin D involvement has been suggested because 1,25-dihydroxyvitamin D (1,25(OH)(2)D) stimulates osteoclastogenesis, through up-regulation of the nuclear vitamin D receptor (nVDR). The aim of this study is to determine the involvement of inflammatory cytokines and the possible role of vitamin D in the pathophysiology of RL using quantitative PCR. We measured the mRNA expression of cytokines with stimulatory (IL-1beta, IL-6, and TNF-alpha) and inhibitory effects (IL-10 and IFN-gamma) on osteoclastogenesis, and the mRNA expression of the receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), and nVDR in RL samples. We found increased expression of mRNA levels for inflammatory cytokines and nVDR, but not for RANKL and OPG, in tissue from RL-affected cats compared with tissue from radiological confirmed healthy controls. The mRNA levels of nVDR were positively correlated with mRNA levels of pro-inflammatory (IL-1beta, IL-6, TNF-alpha, and IFN-gamma), anti-inflammatory (IL-10), pro-resorptive (IL-1beta, IL-6, and TNF-alpha), and anti-resorptive (IFN-gamma and IL-10) cytokines in the course of resorptive lesions. These data are consistent with our view that both inflammation and an overexpression of the nVDR are likely to be involved in RL in cats.

Gastro-oesophageal reflux during thiopentone or propofol anaesthesia in the cat.

Lower oesophageal pH was monitored in 50 cats anaesthetized with either thiopentone or propofol. Gastro-oesophageal reflux, as evidenced by a decrease in lower oesophageal pH to less than 4.0 or an increase to more than 7.5, occurred in 16% (4/25) and 12% (3/25) of the cats anaesthetized with thiopentone and propofol, respectively, the difference between the two groups being non-significant. Reflux usually occurred shortly after the induction of anaesthesia and had a mean duration of about 23 min. The refluxate was always acidic (pH < 4.0). Gastric contents of pH below 2.5 were refluxed on three occasions, two in the thiopentone group and one in the propofol group. Regurgitation and flow of gastric contents from the mouth occurred in only one cat anaesthetized with propofol. None of the cats that exhibited reflux developed any signs of postanaesthetic oesophagitis or stricture formation.

The use of polymeric liquid enteral diets for nutritional support in seriously ill or injured small animals: clinical results in 200 patients.

This prospective, multicenter study evaluated the use of four polymeric liquid enteral (PLE) diets manufactured for dogs and cats in 200 ill or injured patients. Polymeric liquid enteral diets were administered by free-choice feeding, syringe, or feeding tube for up to 208 days. Overall results indicated a 4.9% incidence of vomiting in dogs and a 7.9% incidence in cats; an 8.9% incidence of diarrhea in dogs and an 18.4% incidence in cats. Patients fed the PLE diets seven days or longer had an average increase in body weight of 1.4% in dogs, an average decrease in body weight of 3.8% in cats, increases in lymphocyte counts, and mild decreases in serum albumin.