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Diabetes mellitus is a common endocrinopathy in dogs and in most cases is analogous to type 1 diabetes mellitus (T1DM) in humans.

The organization and delivery of a curriculum is the responsibility of the faculty in educational institutions. Curricular revision is often a hotly debated topic in any college faculty. At the University of Illinois, a 2006 mandate for curriculum modernization from the American Veterinary Medical Association Council on Education provided impetus for a long-discussed curricular revision. After two iterations and a lengthy development process, a new curriculum was gradually implemented at Illinois with the August 2009 matriculation of the Class of 2013. The goals of the revision included earlier clinical exposure for veterinary students through introductions to clinical rotations in years 1 to 3 and an integrated body systems approach in lecture/laboratory courses. A new Clinical Skills Learning Center facilitates development of clinical skills earlier in the curriculum and promotes the development of those skills throughout all 4 years of the curriculum. New outcomes assessments include comprehensive written examinations and Objective Structured Clinical Examinations (OSCEs) in years 2 and 3. Curriculum management, including grading of clinical rotations in all 4 years, is achieved through a commercially available software package. For the past 5 years, when candidates were asked why they chose to apply to Illinois, the new curriculum (27.4%) was the most common answer given during interviews. The Illinois revision has resulted in measurably increased veterinary student self-confidence (p

The purpose of this study was to assess Arizona veterinarians’ perceptions and consensus regarding the importance of items in the domains of clinical skills, knowledge, and attributes of Day One graduates of veterinary school and to determine demographic predictors for items on which consensus was low. In this survey-based prospective study, respondents were asked to rate the importance of 44 items on a 5-point Likert scale ranging from 1 ( not at all important) to 5 ( extremely important). Responses were visualized as divergent stacked bar charts and evaluated via summary quantitative and qualitative analyses. Several items had a median score of 5. For clinical skills, items were the ability to formulate a preventive health care plan, the ability to interpret test results, and basic safe handling and restraint of animals; for knowledge, knowledge of pain management and anesthesia; and for attributes, teamwork, problem-solving skills, and client communication skills. The majority of items (80%) had a strong or very strong consensus measure, 18% had a moderate consensus measure, and 2% had a weak consensus measure. Six items (14%) varied by at least one demographic category. We found demographic differences between large and small animal practices in the clinical skill of ability to perform a necropsy, knowledge of large animal theriogenology, and knowledge of canine theriogenology. In conclusion, we found differences in the importance of items and agreement among practitioners, suggesting that critical evaluation of the mapped curriculum, particularly with regard to core curriculum compared with electives and clinical tracks, may benefit students and future employers.

Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)-1 and GLP-2 are hormones secreted from specialized K cells (GIP) and L cells (GLP-1, GLP-2) in the intestinal mucosa. These hormones play major roles in health and disease by modulating insulin secretion, satiety, and multiple intestinal functions. The aim of this study was to describe the distribution of K cells and L cells in the intestines of healthy cats. Samples of duodenum, mid-jejunum, ileum, cecum, and colon were collected from 5 cats that were euthanized for reasons unrelated to this study and had no gross or histologic evidence of gastrointestinal disease. Samples stained with rabbit-anti-porcine GIP, mouse-anti-(all mammals) GLP-1, or rabbit-anti-(all mammals) GLP-2 antibodies were used to determine the number of cells in 15 randomly selected 400× microscopic fields. In contrast to other mammals (eg, dogs) in which K cells are not present in the ileum and aborally, GIP-expressing cells are abundant throughout the intestines in cats (>6/high-power field in the ileum). Cells expressing GLP-1 or GLP-2 were most abundant in the ileum (>9/high-power field) as in other mammals, but, although GLP-1–expressing cells were abundant throughout the intestines, GLP-2–expressing cells were rarely found in the duodenum. In conclusion, the distribution of GIP-secreting K cells in cats is different from the distribution of K cells that is described in other mammals. The difference in distribution of GLP-2– and GLP-1–expressing cells suggests that more than 1 distinct population of L cells is present in cats.

Summary Canine obesity leads to shortened life span and increased disease incidence. Adipose tissue depots are known to have unique metabolic and gene expression profiles in rodents and humans, but few comparisons of depot gene expression have been performed in the dog. Using microarray technology, our objective was to identify differentially expressed genes and enriched functional pathways between subcutaneous and gonadal adipose of lean and obese dogs to better understand the pathogenesis of obesity in the dog. Because no depot × body weight status interactions were identified in the microarray data, depot differences were the primary focus. A total of 946 and 703 transcripts were differentially expressed (FDR P

The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic effect, and it is effective in controlling blood glucose (BG) with minimal side effects in people with type 2 diabetes. Exenatide also delays gastric emptying, increases satiety, and improves β-cell function. We studied the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered, purpose-bred cats were used in a randomized, cross-over design. BG concentrations during an oral glucose tolerance test were determined in these cats previously. Two isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose tolerance test) were performed in each cat on separate days, one without prior treatment (IGC) and the second with exenatide (1 μg/kg) injected subcutaneously 2 h before (ExIGC). BG, insulin, and exenatide concentrations were measured, and glucose infusion rates were recorded and compared in paired tests between the two experiments. After exenatide injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0- to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG concentration and a return of insulin concentration to baseline despite a continuous increase in serum exenatide concentrations. Insulin area under the curve (AUC) during ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4; P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC. Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent manner, similar to its effect in other species. Although this effect was not accompanied by a greater ability to dispose of an intravenous glucose infusion, other potentially beneficial effects of exenatide on pancreatic β cells, mainly increasing their proliferation and survival, should be investigated in cats.

Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and have other beneficial effects in glucose homeostasis. We aimed to study the incretin effect in cats and to compare the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, total glucose-dependent insulinotropic peptide (GIP) and total glucagon-like peptide 1 (GLP-1). Ten healthy cats were used in a repeated measures design. Glucose, lipid, or amino acids were administered through nasoesophageal tubes on separate days. Blood glucose (BG) concentrations were matched between experiments by measuring BG every 5 min and infusing glucose intravenously at a changing rate. Intravenous glucose infusion with no prior treatment served as control. The incretin effect was estimated as the difference in insulin area under the curve (AUC) after oral compared with intravenous glucose. Temporal changes and total amount of hormone secretions were compared between treatment groups with the use of mixed models. Total glucose infused (TGI) at a mean dose of 0.49 g/kg resulted in slightly higher BG compared with 1 g/kg oral glucose (P = 0.038), but insulin concentrations were not significantly different (P = 0.367). BG and the TGI were not significantly different after the 3 oral challenges. Total GIP AUC was larger after lipids compared with amino acids (P = 0.0012) but GIP concentrations did not increase after oral glucose. Insulin and GIP concentrations were positively correlated after lipid (P < 0.001) and amino acids (P < 0.001) stimulations, respectively, but not after oral glucose stimulation. Total GLP-1 AUC was similar after all three oral stimulations. Insulin and GLP-1 concentrations were positively correlated after glucose (P = 0.001), amino acids (P < 0.001), or lipids (P = 0.001) stimulations. Our data indirectly support an insulinotropic effect of GIP and GLP-1. Potentiation of insulin secretion after oral glucose is minimal in cats and is mediated by GLP-1 but not GIP.

Hypercortisolism (HC) is a common disease in dogs. This article will review the laboratory tests that are available for diagnosis of HC and laboratory tests for differentiating between causes of HC. An emphasis will be made on the clinical process that leads to the decision to perform those tests and common misconceptions and issues that arise when performing them. To choose between the adrenocorticotropic hormone (ACTH)-stimulation test and the low-dose dexamethasone suppression test (LDDST), the advantages and disadvantages of both tests should be considered, as well as the clinical presentation. If the index of suspicion of HC is high and other diseases have been appropriately ruled out, the specificity of the ACTH stimulation test is reasonably high with an expected high positive predictive value. Because of the low sensitivity, a negative result in the ACTH stimulation test should not be used to rule out the diagnosis of HC. The LDDST is more sensitive but also less specific and affected more by stress. A positive result on the urine cortisol:creatinine ratio does not help to differentiate HC from other diseases. A negative result on the urine cortisol:creatinine ratio indicates that the diagnosis of HC is very unlikely. The LDDST is useful in differentiating pituitary-dependent HC from an adrenal tumor in about two thirds of all dogs with HC. Differentiation of HC from diabetes mellitus, liver diseases, and hypothyroidism cannot be based solely on endocrine tests. Clinical signs, imaging studies, histopathology, and response to treatment should all be considered.

Although veterinary clinicians commonly rely on panels of laboratory tests with individual results flagged when abnormal, care should be taken in interpreting normal test results as well. There are several examples of this in evaluating patients with endocrine disease. The finding of a normal leukogram (absence of a stress leukogram) can be indicative of adrenal insufficiency in dogs, and this disorder can be especially elusive when there are no overt indicators of mineralocorticoid deficiency. Cats with hyperthyroidism can have normal serum thyroid hormone concentrations, normal hematocrits, and normal serum concentrations of creatinine despite the presence of disease that affects these parameters. A normal serum phosphorus concentration, in the face of azotemia, isosthenuria, and hypertension can point a clinician toward a diagnosis of primary hyperaldosteronism rather than primary renal disease. A normal serum parathyroid hormone concentration in the face of hypercalcemia is inappropriate and can indicate the presence of primary hyperparathyroidism. Similarly, hypoglycemia accompanied by a normal serum insulin concentration can be found in cases of hyperinsulinism. These normal findings in abnormal patients, and their mechanisms, are reviewed.

Identifying dietary effects on appetite-regulating hormones will enhance our understanding of appetite control. Before complex diets are tested, effects of specific macronutrients or feeding frequency should be identified. The objectives of this nutrition study were to identify differences in endocrine response with feeding frequency (Exp. 1) and after a single dose of a sole macronutrient (Exp. 2). A control diet supplying similar energy content from carbohydrate, protein, and fat was fed to maintain ideal BW. In Exp. 1, 8 healthy adult (1.9 ± 0.1 yr old) female hound cross dogs with an average BW of 22 kg (4.8 ± 0.8 BCS based on a 9-point scale) were randomly allotted to 1 of 2 treatments (fed once or twice daily) in a crossover design. After a 14-d adaptation period, a blood sample was taken (10 mL) before feeding, and samples were collected every 2 h postprandially for 24 h. In Exp. 2, dogs were randomly allotted to 1 of 4 treatments in a 4 × 4 Latin square design. After a 6-d adaptation period, the normal meal on d 7 was replaced with a bolus of maltodextrin (50 g in water; CARB), canned chicken (50 g; PROT), lard (25 g; fat), or water (200 mL). A blood sample (10 mL) was taken at 0, 30, 60, 90, 120, 150, 180, 240, 300, and 360 min postprandial. Total ghrelin, active glucagon-like peptide-1 (GLP-1), insulin, and glucose concentrations were measured. Data were analyzed to compare changes from baseline and area under the curve (AUC) among treatments. In Exp. 1, all hormones were quite variable throughout the day, with a few insulin and GLP-1 differences because of feeding frequency. In Exp. 2, CARB produced a marked peak in glucose and insulin concentrations compared with PROT, fat, or water, resulting in increased glucose (P < 0.001) and insulin (P = 0.07) incremental AUC values. On the other hand, the fat treatment led to increased GLP-1 concentrations over time. Ghrelin AUC was not different among treatments. The circulating hormone data were highly variable and indicate that diet plays a role in insulin and GLP-1 secretion, but more research is required to elucidate these effects.

Background: Serum fructosamine (SF) concentrations depend on plasma glucose concentrations and are used to evaluate glycemic control in animals with diabetes mellitus (DM). Despite the strong association between obesity and DM, the effects of body weight (BW) and body condition on SF concentrations in clinically healthy cats have not been reported. Objective: The aim of the study was to evaluate the effects of BW, body condition score (BCS), sex, and age on SF concentrations in healthy cats. Methods: BW, BCS, and SF concentrations were determined in 84 clinically healthy client-owned cats (50 neutered males, 33 spayed females, and 1 intact female) of known age. The cats were enrolled prospectively in the study. Results: Mean BW, median BCS, and mean SF concentrations for the 84 cats were 5.4 kg, 5/9, and 268.7±45.5 μmol/L (range 197–399), respectively. BW was weakly but significantly correlated with SF (r=.26; P=.02), whereas BCS was not. Cats weighing >5.4 kg and cats with BCS>5/9 had higher mean SF concentrations compared with cats weighing

Antimicrobial peptides (AMPs) are small proteins involved in defense against pathogenic organisms. Defensins and cathelicidin are the most frequently studied human AMPs. Our goals were to determine the distribution of AMPs and evaluate their mRNA expression in normal canine skin. Skin biopsies were taken from six healthy beagles. The relative transcript level of canine cathelicidin (cCath) and β-defensin (cBD)-1, cBD2 and cBD3 mRNA was quantified using quantitative real-time polymerase chain reaction. Indirect immunofluorescence (IIF), using polyclonal antibodies against cBD2, cBD3 and cCath, was used to evaluate protein localization in the skin of healthy dogs. The Pfaffl method, using experimentally determined primer efficiencies of amplification, was used to determine the expression level of cCath, cBD1 and cDB3 relative to cDB2. The levels of cCath, cBD3 and cBD1 mRNA were 358, 296 and 177 times higher than those of cBD2, respectively. Using IIF, cBD2 and cBD3 protein fluorescence was detected in all layers of the epidermis, whereas cCath was detected predominantly in the stratum granulosum and corneum. In addition, antimicrobial peptide detection was limited to the infundibular portion of the pilosebaceous units. We have validated useful methods to evaluate AMPs in canine skin. Further studies are needed to compare AMP expression in healthy dogs with that of dogs with inflammatory skin conditions.

Background: Insulin detemir and insulin glargine are synthetic long-acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time-action profile, while insulin detemir has significantly less within-subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. Objectives: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. Animals: Ten young, healthy, neutered, purpose-bred cats. Methods: Randomized, cross-over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection. Results: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8 ± 0.8 and 1.3 ± 0.5 hours for insulin detemir and insulin glargine, respectively, P= .03). End of action of insulin detemir was reached at 13.5 ± 3.5 hours and for insulin glargine at 11.3 ± 4.5 hours (P= .18). Time-to-peak action of insulin detemir was reached at 6.9 ± 3.1 hours and for insulin glargine at 5.3 ± 3.8 hours (P= .7). The time-action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others. Conclusion and Clinical Importance: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once-a-day drugs. Peak effects of both insulin analogs are pronounced in some cats.

Human recombinant synthetic insulin analogs allow better control of blood glucose concentrations while minimizing the risk of hypoglycemic events in diabetic human patients. Little information is available regarding the use of insulin analogs in cats and dogs. Insulin lispro is an ultrashort-acting analog that has been used in the intensive treatment of dogs with diabetic ketoacidosis. Insulin glargine and insulin detemir are long-acting, and are used in people as basal insulin replacement. Both are associated with reduced risk of hypoglycemia, while detemir also is associated with less undesired weight gain. In cats, insulin detemir and insulin glargine have longer durations of action than traditionally used insulin formulations, and both have been used successfully in once-a-day regimens for treatment of diabetes. Insulins detemir and glargine may have shorter durations of action in cats than in people, and more variability in their effects.

A 4-year-old Yorkshire terrier was presented for an esophageal foreign body. After removal of the foreign body, clinical signs of gagging, regurgitation, and vomiting continued unabated for >6 weeks. The dog had enlarged submandibular salivary glands that were histologically normal. Treatment with phenobarbital resulted in a rapid and dramatic resolution of clinical signs. After 3 months, the dog was weaned of phenobarbital and was free of any signs of disease 6 months later.

The mechanisms contributing to BW gain following ovariohysterectomy in domestic cats are poorly understood. Moreover, the effects of food restriction to maintain BW following spaying have been poorly studied. Thus, our primary objective was to determine the effects of spaying and food restriction to maintain BW on adipose and skeletal muscle mRNA abundance and activity levels in cats. After a 4-wk baseline period (wk 0), 8 adult (approximately 1.5 yr old) domestic shorthair cats were spayed and fed to maintain BW for 12 wk. After 12 wk, cats were fed ad libitum for an additional 12 wk. Body composition was determined, activity levels were measured, and adipose and muscle biopsies were collected at wk 0, 12, and 24. Fasting blood samples were collected at wk 0, 6, 12, 18, and 24. To maintain BW post-spay, food intake was decreased (P < 0.05) by 30%. During this phase, mRNA abundance of adipose tissue lipoprotein lipase and leptin was decreased (P < 0.05), representing only 52 and 23% of baseline expression, respectively. Interleukin-6 mRNA, however, was increased (P < 0.05) 2-fold. Physical activity was decreased (P < 0.05) by wk 12, most dramatically during the dark period (approximately 20% of baseline activity). During ad libitum feeding (wk 12 to 24), food intake, BW, body fat percentage, and total fat mass were greatly increased (P < 0.05). Compared with wk 0, circulating leptin concentrations tended to increase (P < 0.10) by wk 18 and 24 (4.45 vs. 10.02 and 9.14 ng/mL, respectively), whereas glucose (91 vs. 162 mg/dL) and triacylglyceride (30 vs. 48 mg/dL) concentrations were increased (P < 0.05) by wk 24. Adipose tissue lipoprotein lipase, hormone sensitive lipase, and adiponectin mRNA were decreased (P < 0.05) at wk 24. Adipose interleukin-6 mRNA was increased (P < 0.05) at 24 wk. Physical activity was further decreased (P < 0.05) by wk 24, during the light (60% of baseline) and dark (33% of baseline) periods. In summary, spaying and food restriction affect physical activity levels and several genes associated with lipid metabolism (decreased lipoprotein lipase), food intake (decreased leptin expression), and insulin insensitivity (increased interleukin-6). By identifying these changes, targets for nutritional intervention or lifestyle management have been identified that may curb the risk of obesity and related disorders in spayed cats.

The objective of this study was to measure changes in body composition, physical activity and adipose and skeletal muscle gene expression of cats fed a high-protein (HP) diet or moderate-protein (MP) diet, following ovariohysterectomy. Eight cats were randomized onto HP or MP diets and were fed those diets for several months prior to baseline. All cats underwent an ovariohysterectomy at baseline (week 0) and were allowed ad libitum access to dietary treatments for 24 weeks. Food intake was measured daily, and BW and body condition score were measured weekly. Blood, adipose and skeletal muscle tissue samples were collected, physical activity was measured, and body composition was determined using DEXA (dual-energy X-ray absorptiometry) at weeks 0, 12 and 24. Caloric intake increased soon after ovariohysterectomy, resulting in increased (P < 0.05) BW at weeks 12 and 24 compared to week 0. Body condition score and body fat percentage increased (P < 0.05) over time. Blood glucose increased (P < 0.05) linearly over time. Non-esterified fatty acids were decreased (P < 0.05) at weeks 12 and 24 compared to week 0. Blood leptin increased (P < 0.05) over time. Total physical activity decreased (P < 0.05) from week 0 to weeks 12 and 24 in all cats. Adipose tissue mRNA abundance of adiponectin, hormone sensitive lipase, toll-like receptor-4, uncoupling protein-2 (UCP2) and vascular endothelial growth factor decreased (P < 0.05) linearly over time, regardless of diet. Skeletal muscle mRNA abundance for glucose transporter-1, hormone sensitive lipase and UCP2 were decreased (P < 0.05), regardless of dietary treatment. Our research noted metabolic changes following ovariohysterectomy that are in agreement with gene expression changes pertaining to lipid metabolism. Feeding cats ad libitum after ovariohysterectomy is inadvisable.

Glucocorticoids are one of the two main classes of hormones, along with mineralocorticoids, which are secreted from the adrenal cortex. Since the discovery of the anti-inflammatory properties of the natural glucocorticoid hydrocortisone, a large number of artificial glucocorticoids have been synthesized to attempt to increase efficacy and decrease side effects. These drugs are now considered one of the most commonly prescribed agents in veterinary practice. The effect of these drugs has been shown to vary significantly between species. Cats appear to tolerate glucocorticoids well, resulting in these drugs being recommended for a wide variety of conditions; however, there are few studies on the effects of glucocorticoids in cats. In this paper we review some of the available literature on glucocorticoid use in the cat.

Objective: Description of acute respiratory failure in a cat due to profound hypokalemia associated with primary hyperaldosteronism. Case summary: A cat was presented with weakness and paraparesis that deteriorated rapidly into acute ventilatory failure. The serum potassium concentration declined despite intravenous fluid therapy. Positive pressure ventilation was required to support ventilatory function. A functional adrenocortical adenoma was found at necropsy in conjunction with a serum aldosterone concentration of greater than 3329 pmol/L. New or unique information provided: Respiratory failure secondary to profound hypokalemia is a rare, although recognized, condition. There are few reports that focus on this aspect of respiratory failure in the veterinary literature and primary hyperaldosteronism has not been reported as a cause of respiratory failure in cats.

Objective—To evaluate clinical and laboratory findings, treatment, and clinical outcome in cats with blastomycosis. Design—Retrospective case series. Animals—8 cats with naturally occurring blastomycosis. Procedures—Medical records of the University of Illinois Veterinary Teaching Hospital were searched for cases of blastomycosis in cats diagnosed via cytologic or histopathologic findings. Clinical and laboratory findings, treatment, and clinical outcome were determined. Radiographs were reviewed for the 8 cases. Results—All cats were systemically ill. Respiratory tract signs and dermal lesions were most commonly observed. All cats had radiographic evidence of respiratory tract disease. Seven of the 8 cats had ill-defined soft-tissue opacities (nodules or masses) or alveolar consolidation of the lungs. Antemortem diagnosis was achieved cytologically in 6 of the 8 cats, and 3 were successfully treated and survived. Conclusions and Clinical Relevance—In contrast to previous reports, diagnosis was achieved antemortem in most of the cats (all by cytologic identification of the organism). Clinical signs, laboratory findings, and outcome were similar to previous descriptions of this rare disease in cats.

A 3-year-old Boxer was presented with progressive diarrhea, vomiting, and lethargy of 5-months duration. The dog had watery black feces, a mature neutrophilia, and microcytic anemia. Cytologic evaluation of a direct fecal smear stained with Wright's-Giemsa revealed numerous encapsulated, narrow-based, budding organisms consistent with Cryptococcus sp. Pyogranulomatous inflammation and Cryptococcus organisms also were observed in ultrasound-guided fine-needle aspirates of the small intestine and mesenteric lymph nodes, and in histologic sections of colonic biopsies obtained by endoscopy. Multifocal chorioretinitis by fundic examination was consistent with systemic mycosis, and the reciprocal antigen titer (1600) on a cryptococcal antigen latex agglutination test for Cryptococcus neoformans was markedly increased. Using immunohistochemistry, the organism was identified further as C neoformans var. grubii (C neoformans var. neoformans serotype A). After 3 weeks of antifungal treatment, ultrasound examination revealed urinary bladder wall thickening, and Cryptococcus organisms were found in a urine sediment preparation. After 4 months of treatment, the dog was clinically normal and had no abnormal findings on CBC, serum biochemistry, urinalysis, or fecal cytology; however, the antigen titer remained unchanged, mesenteric lymphadenomegaly and jejunal wall thickening were still evident, and cytologic evaluation of fine-needles aspirates of the jejunal wall revealed budding Cryptococcus organisms. Intestinal involvement in dogs with cryptococcosis is rare, and diagnosis by fecal cytology has not been documented previously.

The role of the Ca2+-induced Ca2+ release channel (ryanodine receptor) in MIN6 pancreatic β-cells was investigated. An endoplasmic reticulum (ER)-targeted “cameleon” was used to report lumenal free Ca2+. Depolarization of MIN6 cells with KCl led to release of Ca2+ from the ER. This ER Ca2+ release was mimicked by treatment with the ryanodine receptor agonists caffeine and 4-chloro-m-cresol, reversed by voltage-gated Ca2+ channel antagonists and blocked by treatment with antagonistic concentrations of ryanodine. The depolarization-induced rise in cytoplasmic Ca2+ was also inhibited by ryanodine, which did not alter voltage-gated Ca2+ channel activation. Both ER and cytoplasmic Ca2+ changes induced by depolarization occurred in a dose-dependent manner. Glucose caused a delayed rise in cytoplasmic Ca2+ but no detectable change in ER Ca2+. Carbamyl choline caused ER Ca2+ release, a response that was not altered by ryanodine. Taken together, these results provide strong evidence that Ca2+-induced Ca2+ release augments cytoplasmic Ca2+ signals in pancreatic β-cells.

Aim : Deletion of amino acids 32–71 in human growth hormone (Δ32–71-GH) causes severe autosomal dominant GH deficiency. These experiments test whether retention of Δ32–71-GH in the endoplasmic reticulum (ER) lumen leads to aberrant Ca 2+ regulation. Design : COS cells were transfected with Δ32–71-GH, wild-type-GH or empty plasmid, and the ability of the cells to release Ca 2+ from the ER and transmit a Ca 2+ signal to the cytoplasm was investigated using cytoplasmic Ca 2+ dyes and ER-targeted cameleon Ca 2+ reporters. Results : Resting free Ca 2+ , the rate of Ca 2+ release from the ER and the size of the ionophore-releasable ER Ca 2+ pool were not altered by Δ32–71-GH. Stimulation of endogenous Ca 2+ -mobilizing receptors for histamine and thrombin resulted in similar changes in cytoplasmic and ER Ca 2+ in cells expressing wild-type and Δ32–71-GH. Conclusion : Ca 2+ regulation is preserved despite retention of misfolded GH in the ER.

It is increasingly recognised that diabetic remission is possible in the cat. This systematic review, following Cochrane Collaboration (CC) guidelines, critically appraises the level of evidence on factors influencing remission rate and factors predicting remission. A systematic online, bibliographic search and reference list examination was conducted. A level of evidence was assigned to each identified article by five internists using the Newcastle–Ottawa Scale for follow-up, cohort, case-series and case-control studies, the CC's risk of bias tool for trials and the Cochrane Effective Practice and Organisation of Care Group risk of bias criteria for before and after trials. Twenty-two studies were included in the review, assessing influence of pharmaceutical intervention ( n = 14) and diet ( n = 4), as well as diagnostic tests ( n = 9) and feline patient characteristics ( n = 5) as predictors of remission. The current level of evidence was found to be moderate to poor. Common sources of bias included lack of randomisation and blinding among trials, and many studies were affected by small sample size. Failure to provide criteria for the diagnosis of diabetes, or diabetic remission, and poor control of confounding factors were frequent causes of poor study design. Addressing these factors would significantly strengthen future research and ultimately allow meta-analyses to provide an excellent level of evidence. No single factor predicts remission and successful remission has been documented with a variety of insulin types and protocols. Dietary carbohydrate reduction might be beneficial, but requires further study. A lack of well-designed trials prevents reliable remission rate comparison. Factors associated with remission resemble those in human medicine and support the hypothesis that reversal of glucotoxicity is a major underlying mechanism for feline diabetic remission.

These studies examined the importance of phospholipase Cbeta (PLCbeta) in the calcium responses of pituitary cells using PLCbeta3 knockout mice. Pituitary tissue from wild-type mice contained PLCbeta1 and PLCbeta3 but not PLCbeta2 or PLCbeta4. Both Galphaq/11 and Gbetagamma can activate PLCbeta3, whereas only Galphaq/11 activates PLCss1 effectively. In knockout mice, PLCbeta3 was absent, PLCbeta1 was not up-regulated, and PLCbeta2 and PLCbeta4 were not expressed. Since somatostatin inhibited influx of extracellular calcium in pituitary cells from wild-type and PLCbeta3 knockout mice, the somatostatin signal pathway was intact. However, somatostatin failed to increase intracellular calcium in pituitary cells from either wild-type or knockout mice under a variety of conditions, indicating that it did not stimulate PLCbeta3. In contrast, somatostatin increased intracellular calcium in aortic smooth muscle cells from wild-type mice, although it evoked no calcium response in cells from PLCbeta3 knockout animals These results show that somatostatin, like other Gi/Go-linked hormones, can stimulate a calcium transient by activating PLCbeta3 through Gbetagamma, but this response does not normally occur in pituitary cells. The densities of Gi and Go, as well as the relative concentrations of PLCbeta1 and PLCbeta3, were similar in cells that responded to somatostatin with an increase in calcium and pituitary cells. Calcium responses to 1 nM and 1 microM TRH and GnRH were identical in pituitary cells from wild-type and PLCbeta3 knockout mice, as were responses to other Gq-linked agonists. These results show that in pituitary cells, PLCbeta1 is sufficient to transmit signals from Gq-coupled hormones, whereas PLCbeta3 is required for the calcium-mobilizing actions of somatostatin observed in smooth muscle cells.

The purpose of this study was to investigate the effects of methimazole on renal function in cats with hyperthyroidism. Twelve cats with naturally occurring hyperthyroidism and 10 clinically normal (i.e., control) cats were included in this study. All cats initially were evaluated with a history, physical examination, complete blood count, serum biochemistry profile, basal serum total thyroxine concentration, complete urinalysis, and urine bacterial culture. Glomerular filtration rate (GFR) was estimated by a plasma iohexol clearance (PIC) test. After initial evaluation, hyperthyroid cats were treated with methimazole until euthyroidism was achieved. Both groups of cats were then reevaluated by repeating the initial tests four to six weeks later. The mean (+/-standard deviation) pretreatment estimated GFR for the hyperthyroid cats was significantly higher (3.83+/-1.82 ml/kg per min) than that of the control cats (1.83+/-0.56 ml/kg per min). Control of the hyperthyroidism resulted in a significantly decreased mean GFR of 2.02+/-0.81 ml/kg per minute when compared to pretreatment values. In the hyperthyroid group, the mean increases in serum urea nitrogen (SUN) and creatinine concentrations and the mean decrease in the urine specific gravity after treatment were not statistically significant when compared to pretreatment values. Two of the 12 hyperthyroid cats developed abnormally high serum creatinine concentrations following treatment. These results provide evidence that cats with hyperthyroidism have increased GFR compared to normal cats, and that treatment of feline hyperthyroidism with methimazole results in decreased GFR.

Objective— The purpose of this study was to determine the signalment, history, clinical signs, diagnosis, treatment, outcome, and factors affecting outcome of dogs and cats surgically treated for bile peritonitis. Study Design— Retrospective study. Animals or Sample Population— Twenty-four dogs and two cats surgically treated for bile peritonitis. Methods— The medical records of dogs and cats surgically treated for biliary effusions at the Ohio State University and Michigan State University between 1987 and 1994 were reviewed. Statistical analysis was performed to compare factors affecting outcome. Results— The cause of the biliary effusion was determined in 24 animals, and resulted from disruption of the biliary tract secondary to trauma (n = 13) or necrotizing cholecystitis (n = 11). Determination of the bilirubin concentration of the abdominal effusion was the only diagnostic test that was 100% effective in diagnosing bile leakage before surgical intervention. The bilirubin concentration of the effusion was consistently at least two times higher than the serum bilirubin concentration. Bacteriologic culture and sensitivity revealed that a septic, biliary effusion was usually associated with multiple types of gram-negative bacteria. The overall survival rate was 50% (13 of 26). The peripheral white blood cell count was significantly lower in survivors (mean 20,608/uL) compared with nonsurvivors (mean 35,712/uL). The immature neutrophil count was also significantly lower in survivors (mean 686/uL) than in nonsurvivors (4,852/uL). Only 27% (3 of 11) of the animals with a septic biliary effusion survived. In contrast, 100% (6 of 6) of the animals in which no bacteria were isolated from the abdominal effusion survived. Open abdominal drainage was not a successful treatment for 7 of 9 animals with septic biliary effusions. Survival was not significantly affected by the distribution of the peritonitis, cause of biliary effusion, or duration of clinical signs before surgical intervention. Conclusions— Patients with sterile biliary effusions have a much lower mortality rate than those with septic biliary effusions. The successful treatment of sterile biliary effusions does not require open abdominal drainage, and is not affected by the duration of the effusion. Clinical Relevance— This retrospective study provides information that may aid the surgeon in the diagnosis and treatment of bile peritonitis.

Background Filaggrin is a structural protein that has attracted increasing interest over the past decade for its role in the pathogenesis of human atopic dermatitis (AD). Null mutations in its sequence are considered risk factors in the development of AD. Hypothesis/Objectives To investigate canine filaggrin mRNA and protein expression in the skin of atopic beagles with experimentally induced AD compared with breed-matched healthy control dogs. Methods All dogs were environmentally challenged for 3 days consecutively with allergens to which the atopic dogs had been sensitized. Skin biopsy specimens were taken from six healthy and seven atopic beagles before and after allergen challenge. Canine filaggrin mRNA was measured using quantitative real-time PCR. Indirect immunofluorescence was used to localize the filaggrin protein in canine skin. Analysis of variance with Tukey's multiple comparison test (over-time effect) and unpaired Student's t-test (treatment effect) were used. Values of P ≤ 0.05 were considered significant. Results Analysis of variance showed a significantly higher expression of filaggrin mRNA in atopic dogs compared with healthy control dogs (P = 0.004 on day 3 and P = 0.01 on day 10) and a decreased mRNA expression on day 3 in healthy control dogs (effect of time, P = 0.006). On blinded evaluation, filaggrin immunofluorescence was distributed homogeneously in the stratum granulosum and the stratum corneum in healthy dogs. Atopic dogs showed a patchy immunofluorescence pattern, which was exacerbated after environmental challenge. Conclusions and clinical importance Altered epidermal filaggrin mRNA expression and protein distribution was detected in this experimental model.

The objective was to evaluate the effects of dietary macronutrients and feeding frequency on blood glucose, insulin, total ghrelin and leptin. A total of twelve adult lean neutered male cats were used in three tests, all cross-over studies composed of a 15 d adaptation and blood sampling on day 16. In trial 1, differences between two- and four-meal feeding were tested. On day 16, blood samples were collected every 2 h for 24 h. In trial 2, macronutrient boluses were tested. Instead of the control diet, the morning meal on day 16 was replaced with an isoenergetic bolus of carbohydrate (maltodextrin), protein (chicken meat), fat or water. Fasted and ten postprandial blood samples were collected. In trial 3, diets high in fat (HF), protein (HP), carbohydrate (HC) or a control diet were tested. On day 16, fasted and ten postprandial blood samples were collected. Data were analysed to identify baseline and AUC changes. Cats fed four meals daily had greater (P = 0·03) leptin incremental AUC0–24 h compared with cats fed twice daily. The carbohydrate bolus increased glucose (P P 0–6 h and tended to increase (P = 0·09) leptin net AUC0–6 h. Cats fed the control and HC diets had greater (P = 0·03) glucose incremental AUC compared with the HF and HP conditions. Circulating hormone data were highly variable and indicated changes due to dietary macronutrients and feeding frequency, but further study is needed to identify impacts on appetite and contributing mechanisms.

Antimicrobial peptides (AMPs) are small immuno-modulatory proteins important in defense against pathogenic organisms. Defensins and cathelicidin are the most frequently studied human AMPs. An increase in AMPs in atopic humans has been reported recently. Our goals were to determine the distribution of AMPs and evaluate their mRNA and protein expression in non-lesional (Day 0), acute lesional skin (Day 3) and post-challenged skin after resolution of skin lesions (Day 10) using a canine model of atopic dermatitis (AD). All dogs were environmentally challenged for three consecutive days with house dust mite. Clinical evaluation of atopic beagles was performed using a CADESI score at each time point before and after environmental challenge. Skin biopsies were taken from six healthy and seven atopic beagles before and after allergen challenge (Day 0, Day 3 and Day 10). The transcription of canine cathelicidin (cCath) and beta-defensins (cBD)-1, -2 and -3 mRNA was quantified using quantitative-RT-PCR while the protein distribution of cBD2, cBD3 and cCath was detected by indirect immunofluorescence. A significant effect, over-time, was seen in CADESI score in AD beagles with an increase score after challenge (Day 3). Quantitative analysis showed a significant difference in mRNA transcript levels between groups (with atopic dogs having more than controls) for all AMPs but cBD2. No effect over time was evident for either group. No significant differences were seen for the AMP protein patterns of distribution (homogenous distribution). Although, these results showed no differences in AMP's localization after allergen exposure in each group; atopic dogs had a higher mRNA expression of AMPs when compared with healthy dogs, a similar finding to humans.

Quantitative evaluation of renal function in small animal general practice has remained essentially unchanged for decades. Glomerular filtration rate (GFR) is considered the gold standard for evaluating functional renal mass in veterinary medicine. For practical and financial reasons, GFR testing was previously available only at referral veterinary hospitals. Newer techniques for estimating GFR now allow the routine performance of this test in any small animal practice.

During the development of obesity, adipose tissue undergoes major expansion and remodeling, but the biological processes involved in this transition are not well understood. The objective of this study was to analyze global gene expression profiles of adipose tissue in dogs, fed a high-fat diet, during the transition from a lean to obese phenotype. Nine female beagles (4.09 ± 0.64 yr; 8.48 ± 0.35 kg) were randomized to ad libitum feeding or body weight maintenance. Subcutaneous adipose tissue biopsy, blood, and dual x-ray absorptiometry measurements were collected at 0, 4, 8, 12, and 24 wk of feeding. Serum was analyzed for glucose, insulin, fructosamine, triglycerides, free fatty acids, adiponectin, and leptin. Formalin-fixed adipose tissue was used for determination of adipocyte size. Adipose RNA samples were hybridized to Affymetrix Canine 2.0 microarrays. Statistical analysis, using repeated-measures ANOVA, showed ad libitum feeding increased ( P < 0.05) body weight (0 wk, 8.36 ± 0.34 kg; 24 wk, 14.64 ± 0.34 kg), body fat mass (0 wk, 1.36 ± 0.24 kg; 24 wk, 6.52 ± 0.24 kg), adipocyte size (0 wk, 114.66 ± 17.38 μm2; 24 wk, 320.97 ± 0.18.17 μm2), and leptin (0 wk, 0.8 ± 1.0 ng/ml; 24 wk, 12.9 ± 1.0 ng/ml). Microarrays displayed 1,665 differentially expressed genes in adipose tissue as weight increased. Alterations were seen in adipose tissue homeostatic processes including metabolism, oxidative stress, mitochondrial homeostasis, and extracellular matrix. Adipose transcriptome changes highlight the dynamic and adaptive response to ad libitum feeding and obesity development.

Fluoroquinolones were discovered in the 1960s as a derivative of the antimalarial drug chloroquine. Over the past 40 years, many fluoroquinolones have been developed for use in human and veterinary medicine. As with all classes of antibiotics, resistance to fluoroquinolones is a serious concern, and multiple avenues for resistance are being investigated. Resistance-associated point mutations in bacterial DNA and, more recently, plasmid-mediated resistance have been reported in both human and veterinary bacterial isolates. This article reviews the history and most current literature on fluoroquinolones approved for use in dogs and cats and the spectra of activity, mechanisms of action, resistance patterns, and recommendations for appropriate clinical use of these drugs.

Antimicrobial peptides (AMPs) are small proteins involved in defense against pathogenic organisms. Defensins and cathelicidin are the most frequently studied human AMPs. Our goals were to determine the distribution of AMPs and evaluate their mRNA expression in normal canine skin. Skin biopsies were taken from six healthy beagles. The relative transcript level of canine cathelicidin (cCath) and β-defensin (cBD)-1, cBD2 and cBD3 mRNA was quantified using quantitative real-time polymerase chain reaction. Indirect immunofluorescence (IIF), using polyclonal antibodies against cBD2, cBD3 and cCath, was used to evaluate protein localization in the skin of healthy dogs. The Pfaffl method, using experimentally determined primer efficiencies of amplification, was used to determine the expression level of cCath, cBD1 and cDB3 relative to cDB2. The levels of cCath, cBD3 and cBD1 mRNA were 358, 296 and 177 times higher than those of cBD2, respectively. Using IIF, cBD2 and cBD3 protein fluorescence was detected in all layers of the epidermis, whereas cCath was detected predominantly in the stratum granulosum and corneum. In addition, antimicrobial peptide detection was limited to the infundibular portion of the pilosebaceous units. We have validated useful methods to evaluate AMPs in canine skin. Further studies are needed to compare AMP expression in healthy dogs with that of dogs with inflammatory skin conditions.

Serum fructosamine (SF) concentrations depend on plasma glucose concentrations and are used to evaluate glycemic control in animals with diabetes mellitus (DM). Despite the strong association between obesity and DM, the effects of body weight (BW) and body condition on SF concentrations in clinically healthy cats have not been reported.The aim of the study was to evaluate the effects of BW, body condition score (BCS), sex, and age on SF concentrations in healthy cats.BW, BCS, and SF concentrations were determined in 84 clinically healthy client-owned cats (50 neutered males, 33 spayed females, and 1 intact female) of known age. The cats were enrolled prospectively in the study.Mean BW, median BCS, and mean SF concentrations for the 84 cats were 5.4 kg, 5/9, and 268.7 ± 45.5 μmol/L (range 197-399), respectively. BW was weakly but significantly correlated with SF (r=.26; P=.02), whereas BCS was not. Cats weighing5.4 kg and cats with BCS5/9 had higher mean SF concentrations compared with cats weighing5.4 kg and cats with BCS5/9, respectively. Cats categorized as normal weight to obese by BW (BW ≥ 4.0 kg) had higher mean SF concentrations compared with cats categorized as lean (BW4.0 kg). For domestic shorthair cats, the same was true for BCS: cats with BCS ≥ 4/9 had higher mean fructosamine concentrations than those with BCS4/9. Male cats had significantly higher mean SF concentrations compared with female cats (285.1 ± 45.3 vs 244.5 ± 33.9 μmol/L, P.001). Age did not affect mean SF concentrations.BW is positively correlated with SF concentration, and lean cats have lower SF concentrations than normal and obese cats. In contrast to previous reports, mean SF concentrations were higher in male cats than in female cats, even when males and females were matched based on BW, BCS, and age.

Fourteen cats received either daily prednisolone (4.4 mg/kg per os [PO]) or dexamethasone (0.55 mg/kg PO) for 56 days. These doses were clinically equipotent. Serum fructosamine and urine glucose were measured on days 0, 28, and 56. Insulin sensitivity, glucose tolerance, and peak insulin secretion were measured in each group prior to and at the end of the courses of glucocorticoid administration. On day 56, the prevalence of glucosuria was significantly greater (P=0.027), and a trend was seen toward greater fructosamine concentrations (P=0.083) in dexamethasone-treated cats compared to prednisolone-treated cats. The results of this pilot study also showed a trend toward a greater decrease in insulin sensitivity (P=0.061) and a significantly lower compensatory increase in insulin secretion (P=0.081) in the dexamethasone-treated cats than in cats administered prednisolone. These preliminary data suggest that dexamethasone exhibits greater diabetogenic effects in cats than equipotent doses of prednisolone. Further study is justified to support this hypothesis.

The objective of the present study was to measure the differences in body composition, adipose tissue gene expression, blood metabolite and hormone concentrations, and insulin sensitivity in kittens exposed to high-protein (HP) or high-carbohydrate (HC) nutritionin uteroand through the growth period. Eight dams were randomised onto two test diets, and fed the diets throughout gestation and lactation. Male offspring were evaluated for 9 months. Kittens were weaned at 2 months of age onto the same treatment diet as the dam and were allowed to consume dietsad libitum. The HC diet contained 34·3 % crude protein (CP), 19·2 % fat and 30·8 % digestible carbohydrate, while the HP diet contained 52·9 % CP, 23·5 % fat and 10·8 % digestible carbohydrate. Blood samples were collected at 6 months after birth. Body composition was determined at 2 and 8 months of age and an intravenous glucose tolerance test, neutering and adipose tissue biopsy conducted at 8 months of age. Physical activity was quantified at 6 and 9 months. Energy intake, DM intake and body weight were not different between groups. At 2 months, blood TAG were greater (P P P