Three cases of feline hypereosinophilic syndrome treated with imatinib mesylate (2023)

Molecular Genetics and Metabolism, Band 109, Ausgabe 4, 2013, S. 390-396

Cobalamin malabsorption, accompanied by selective proteinuria, is an autosomal recessive disease known as Imerslund-Gräsbeck syndrome in humans and is already found in dogs due to amniosis.AMN) mutations. The resulting B vitamin₁₂Deficiency causes dyshematopoiesis, lethargy, growth retardation, and life-threatening metabolic disorders in adolescence. We studied 3 border collie relatives with cobalamin malabsorption and mapped the disease site in affected dogs to a 2.9 Mb region of homozygosity on canine chromosome 2. The region includedCUBNO, the locus encoding cubilin, a peripheral membrane protein that together with AMN forms the functional intrinsic factor cobalamin receptor expressed in the ileum and a multiligand receptor in the renal proximal tubules. Cobalamin malabsorption and proteinuria with CUBN ligands were demonstrated by radiolabeled cobalamin uptake and SDS-PAGE studies, respectively.CUBNOIn both the ileum and kidney of affected dogs, mRNA and protein expression were reduced by about 10-fold and about 20-fold, respectively. DNA sequencing revealed a single base deletion in exon 53, which predicted a translation frameshift and early stop codon, likely triggering nonsense-mediated mRNA decay. The mutant allele segregated with the disease in the border collie family. Border collie disease indicates that aCUBNOMutations that are C-terminal away from the cobalamin-intrinsic factor binding site can abolish receptor expression and cause Imerslund-Gräsbeck syndrome.

Veterinary Immunology and Immunopathology, Band 202, 2018, S. 109-114

Thrombocytopenia is frequently encountered in veterinary practice when evaluating canine patients. It can occur in infectious, neoplastic, inflammatory, toxic, and immune-mediated conditions. Therefore, elucidating the underlying cause of thrombocytopenia can be challenging for veterinarians. In addition, determining whether an immune process might contribute to a patient's thrombocytopenia is important to refine the differences and improve understanding of a particular disease process. A possible test candidate for the development of a clinically applicable assay in dogs is flow cytometry. Therefore, the purpose of this study was to develop a clinically applicable direct and indirect flow cytometry assay for the detection of canine immunoglobulin-associated platelets. Direct and indirect flow cytometry was performed on nine healthy beagle dogs and twelve of the client's thrombocytopenic dogs at four time points: fresh, and after 24, 48, and 72 hours of storage at 4°C. In healthy dogs, there was no significant difference between fresh and 24- and 48-hour samples, but there was a significant difference between fresh and 72-hour samples. There were no significant differences between fresh and 24, 48, or 72 hour samples in dogs with thrombocytopenia. A cut-off value of ≤10% antibody binding was defined to distinguish negative and positive scores and was determined by serial direct flow assessments in a healthy dog. Based on this cut-off score, healthy and thrombocytopenic dogs were evenly classified at each time point. The mean intra-assay coefficient of variation for thrombocytopenic dogs was 4.32%. The indirect flow cytometry methods evaluated here did not provide reliable or repeatable results in healthy or thrombocytopenic dogs. Direct flow cytometry represents a potentially clinically useful test for the detection of immunoglobulin-associated platelets in dogs that can be processed and interpreted in a realistic time frame, allowing testing in larger numbers of patients. Based on the results of this study using our protocols, indirect flow cytometry in dogs was not clinically applicable.

Ticks and Tick-borne Diseases, Volume 11, Issue 3, 2020, Article 101406

Domestic Animal Endocrinology, Band 75, 2021, Artikel 106595

Insulin glargine (IGla) is a synthetic analogue of recombinant human insulin that is commonly used in humans as a 24-hour basal insulin. The 300 U/mL (U300) formulation of IGla is associated with a longer duration of action and less intraday variability, making it a superior basal insulin compared to the 100 U/mL (U100) formulation. We hypothesize that IGlaU300 has a flatter time-effect profile and longer duration of action in healthy cats compared to IGlaU100. Seven healthy, neutered, specifically bred male cats were studied in a randomized crossover design. The pharmacodynamics of IGlaU100 and IGlaU300 (0.8 U/kg, subcutaneous) was determined by the isoglycemic clamp method. The response time profile of IGlaU300 was flatter compared to IGlaU100, as indicated by the lower peaks (5.6 ± 1.1 mg/kg/min and 8.3 ± 1.9 mg/kg/min, respectively;PAG= 0.04) with no difference in total metabolic effect (ME;PAG= 0.7) or duration of action (16.8 ± 4.7 h vs. 13.4 ± 2.6 h;PAG= 0.2). The highest proportion of ME at 12 to 24 hours post-injection (35 ± 23% vs. 7 ± 8%;PAG= 0.048) and less intraday variability of GIR% (7.8 ± 3.7% vs. 17.4 ± 8.2%;PAG= 0.03) supports a flatter time history profile of IglaU300. There were no differences in the beginning and end of the effect. In summary, although both formulations have a similar duration of action, well below 24 hours, the ME of IGlaU300 is more evenly distributed over a 24-hour period in healthy cats, making it a better candidate for those that are injected once a day. in diabetics.

Topics in Companion Animal Medicine, Band 35, 2019, S. 11-17

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disorder characterized by abnormalities in ectodermal derivatives such as sweat glands, hair, and teeth. In animals, most cases have been reported in dogs, which present with characteristic congenital alopecia and develop abnormalities in the shape and number of teeth. Although the clinical phenotype of affected individuals is typical, this disease is almost unknown in veterinary clinical practice. In order to make it known, in this summary we have compiled the most important clinical and genetic aspects of XLHED, with special attention to dental anomalies.

Domestic Animal Endocrinology, Band 74, 2021, Artikel 106578

Lipid disorders are relatively common in dogs. Hyperlipidemia can be primary or secondary to other diseases. In humans, fenofibrate is used to control hypertriglyceridemia. There are no studies evaluating fenofibrate in hypertriglyceridaemia in dogs. The objective of the study was to evaluate the safety and efficacy of fenofibrate in the control of severe hypertriglyceridaemia in dogs. A total of 124 dogs (n=124) with severe hypertriglyceridaemia (>300 mg/dL, 3.39 mmol/L) were randomized to the fenofibrate group (n=64) and the diet group (n=60). Dogs in the fenofibrate group were treated with fenofibrate (10 mg/kg) once daily. Dogs in the diet group were treated with a low-fat (10%) diet. Serum concentrations of triglycerides (TG), total cholesterol (TC), liver enzymes, and creatine kinase were evaluated before and after 1 month of medical or dietary treatment. Triglyceride concentrations were reduced with fenofibrate (PAG< 0.001), and 85.93% of the dogs normalized their scores. Triglyceride concentrations also decreased with a low-fat diet (PAG< 0.001), but only 26.6% of the dogs normalized their values. Triglyceride concentrations were reduced with fenofibrate (PAG< 0.01) and with a low-fat diet (PAG<0.01). Of the cases with hypercholesterolemia, 53.7% and 50% of the dogs normalized their TC concentrations with fenofibrate and food, respectively. No significant side effects were observed (3% had diarrhoea). Fenofibrate was safe and effective in reducing and normalizing TG levels in dogs with severe hypertriglyceridemia, regardless of the cause of the hyperlipidemia. The low-fat diet effectively reduced, but did not normalize, TG concentrations. Fenofibrate and a low-fat diet were effective in reducing TC levels. This is the first study to examine fibrates in dogs with severe hypertriglyceridaemia and to compare the results with a low-fat diet.