Normal Cats Research Articles

Ensemble responses of auditory midbrain neurons in the cat to speech stimuli at different signal-to-noise ratios

Originally reserved for those who are profoundly deaf, cochlear implantation is now common for people with partial hearing loss, particularly when combined with a hearing aid. This combined intervention enhances speech comprehension and sound quality when compared to electrical stimulation alone, particularly in noisy environments, but the physiological basis for the benefits is not well understood. Our long-term aim is to elucidate the underlying physiological mechanisms of this improvement, and as a first step in this process, we have investigated in normal hearing cats, the degree to which the patterns of neural activity evoked in the inferior colliculus (IC) by speech sounds in various levels of noise allows discrimination between those sounds. Neuronal responses were recorded simultaneously from 32 sites across the tonotopic axis of the IC in anaesthetised normal hearing cats (n=7). Speech sounds were presented at 20, 40 and 60dB SPL in quiet and with increasing levels of additive noise (signal-to-noise ratios (SNRs) –20, –15, –10, –5, 0, +5, +10, +15, +20dB). Neural discrimination was assessed using a Euclidean measure of distance between neural responses, resulting in a function reflecting speech sound differentiation across various SNRs. Responses of IC neurons reliably encoded the speech stimuli when presented in quiet, with optimal performance when an analysis bin-width of 5-10ms was used. Discrimination thresholds did not depend on stimulus level and were best for shorter analysis binwidths. This study sheds light on how the auditory midbrain represents speech sounds and provides baseline data with which responses to electro-acoustic speech sounds in partially deafened animals can be compared.

Effects of 0.024% latanoprostene bunod on intraocular pressure and pupil diameter in normal cats and cats with congenital glaucoma.

To evaluate the effects of latanoprostene bunod on intraocular pressure (IOP) and pupil diameter (PD) in normal cats and cats with feline congenital glaucoma (FCG). Five normal and 5 FCG cats. This masked, controlled crossover study comprised a 1-day Pre-treatment phase followed by two 10-day Treatment phases, each followed by a 10-day Recovery phase. During treatment, all cats received twice daily 0.005% latanoprost (LAT) or 0.024% latanoprostene bunod (LBN) in a randomized eye. Following Recovery, the same eye was treated with the opposite drug. Contralateral eyes served as saline-treated controls. Intraocular pressure and PD measurements were performed three times daily during all study phases. Data were analyzed via constrained longitudinal data analysis models. Neither drug significantly reduced IOP in normal cats. In FCG cats, statistically significant reductions in mean (95% CI) IOP were observed relative to controls 4 h after LAT and LBN treatment (-5.5 mmHg [-8.4, -2.5], p < .001, -7.2 mmHg [-10.2, -4.3], p < .001, respectively). These differences represented 28.4% and 37.9% IOP reductions, respectively. Mean IOP reduction after 4 h was significantly greater with LBN treatment compared to LAT (-1.8 mmHg [-3.2, -0.4], p = .012). However, these IOP reductions were not considered clinically significant. Both drugs similarly reduced PD in normal and FCG cats. Transient IOP reduction was observed after topical administration of LAT and LBN in FCG cats; and mean IOP difference was statistically significantly greater in LBN-treated eyes. However, the apparent enhanced hypotensive effect of LBN is not clinically significant.

Trabecular Meshwork Abnormalities in a Model of Congenital Glaucoma Due to LTBP2 Mutation.

To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation in LTBP2. Eyes from 41 cats, including 19 normal and 22 homozygous for LTBP2 mutation, across various postnatal stages (birth, 2 weeks, 5 weeks, and 12 weeks) were paraformaldehyde fixed, anterior segments dissected, post-fixed in glutaraldehyde, osmicated, and processed and sectioned for transmission electron microscopy. Cell morphology, nuclear shape, and intertrabecular space (ITS) were quantitatively assessed, and the structure of the fibrillar extracellular matrix in the TM was systematically evaluated. The earliest differences in TM morphology between PCG and normal cats were identified at 2 weeks postnatally. Elastic fibers in the TM were discontinuous and disorganized (P = 0.0122), and by 5 weeks of age PCG cats presented significantly less ITS (P = 0.0076) and morphologically rounder TM cells than normal cats (P = 0.0293). By 12 weeks of age, the ITS was further collapsed (P < 0.0001), and the TM cells were morphologically elongated and attenuated in PCG compared to controls (P = 0.0028). In this feline model of PCG due to LTBP2 mutation, development of ultrastructural TM extracellular matrix abnormalities are first observed by 2 weeks and cellular abnormalities by 5 weeks of age. By 12 weeks of age, when intraocular pressure becomes significantly elevated, the TM morphologic abnormalities are already well established. These findings suggest that the postnatal period between 0 and 5 weeks of age is critical for TM and PCG development and progression in cats.

Evaluation of Intervertebral Disc Space Width Between 10th and 11th Thoracic Vertebrae in Cats Using Radiography and Magnetic Resonance Imaging.

It is well known that the T10-T11 intervertebral disc space is usually narrower than the adjacent intervertebral disc spaces in most dogs. However, whether the T10-T11 disc space is narrower than the adjacent disc spaces is not well-established in cats. To measure the intervertebral disc space width of the T10-T11 disc space and to compare it with that of the adjacent disc spaces using radiography and magnetic resonance imaging (MRI). In Groups 1 (101 clinically normal cats) and 2 (32 cats without spinal diseases from T8 to T13), dorsal width (DW), central width (CW) and ventral width (VW) of the T8-T13 disc spaces were measured by radiography or MRI. Significant differences of the DW, CW and VW among disc spaces measured by radiography and MRI were evaluated. Intra- and interobserver reliabilities were measured by intraclass correlation coefficient. In Groups 1 and 2 using radiography, the DW and CW of the T10-T11 disc space were significantly narrower than those of adjacent disc spaces (p<0.05). The DW of the T8-T12 disc spaces was significantly narrower than that of the T12-T13 disc space in Group 1 using radiography. In Groups 1 and 2 using radiography, the CW and VW of the T8-T11 disc spaces were significantly narrower than those of the T11-T13 disc spaces. In Group 2 using MRI, the DW of the T10-T11 disc space was significantly narrower than that of the T11-T13 disc spaces. The VW of the T8-T11 disc spaces was significantly narrower than that of the T11-T13 disc spaces. The T10-T11 intervertebral disc space on radiography is statistically narrower than the adjacent intervertebral disc spaces in normal cats. The cranial thoracic intervertebral disc spaces (T8-T11) are usually narrower than the caudal thoracic intervertebral disc spaces (T11-T13) on radiography and MRI.

Effects of Telmisartan on Intraocular Pressure, Blood Pressure, and Ocular Perfusion Pressure in Normal and Glaucomatous Cats.

To determine the effect of telmisartan on intraocular pressure (IOP), blood pressure (BP), and ocular perfusion pressure (OPP) in normal and glaucomatous cats. A four-week study was conducted in six normal adult cats, followed by a longer six-month study performed in 37 cats with spontaneous glaucoma and 11 age-matched normal cats. Telmisartan (1 mg/kg/day) or placebo-vehicle were administered orally once daily. IOP was measured by rebound tonometry. BP readings were obtained by oscillometric method. OPP was calculated as mean arterial pressure (MAP) - IOP. IOP and BP were obtained three times a week for the first study and weekly for the second study. Baseline IOP was significantly higher, and OPP was significantly lower in glaucomatous cats than in normal cats (P < 0.0001). These differences between glaucomatous and normal cats persisted throughout the study, regardless of treatment (P < 0.001). No significant differences in IOP, BP, or OPP were detected between any study phases in the first, normal feline cohort or between telmisartan- and placebo-treated glaucomatous cats at any timepoint in the second study. Oral telmisartan was well tolerated and did not have a detrimental effect on BP or OPP in cats but did not lower IOP or improve OPP in cats with glaucoma. While showing telmisartan could not be used as a sole therapy for IOP lowering, our data affirmed a lack of detrimental effects of telmisartan on BP and OPP in a translationally-relevant, spontaneous, large animal glaucoma model.

Feline respiratory disease complex: insights into the role of viral and bacterial co-infections.

Feline respiratory disease complex (FRDC) is a highly prevalent syndrome in cats that often result in fatal outcomes. FRDC etiology is complex, and often, multiple viral and bacterial pathogens are simultaneously associated with disease causation. There is limited information about the role of co-infections in pathogenesis and the current prevalence of pathogens in North America. We aimed to conduct a study using technical advances in molecular diagnosis and statistical modeling analysis to elucidate the occurrence of pathogens and how co-infections affect disease severity. We attained information from three diagnostic laboratories in North America regarding the occurrence of Bordetella bronchiseptica, Chlamydia felis, Mycoplasma, Felid alphaherpesvirus 1 (FeHV-1), feline calicivirus (FCV), and influenza A, along with age, seasonality, sex, and clinical signs. We also evaluated the role of co-infections in disease severity. These pathogens were also investigated in clinically normal cats (control). The most detected pathogens were Mycoplasma, FCV, and FeHV-1. Most pathogens were detected in the control group, highlighting the challenge of interpreting positive testing results. Co-infections of Mycoplasma and FCV, as well as Mycoplasma and FeHV-1, were important predictors of disease severity. Age, sex, and season had a minor impact on pathogen occurrence. This study provides new insights into FRDC and underlines the relevance of diagnostic panels to screen for a range of pathogens, providing knowledge for timely diagnosis and therapeutic interventions.

Analysis of serum proteomic in cats with polycystic kidney disease-1 gene mutation

Feline autosomal dominant polycystic kidney disease (PKD) is common in Persian and Persian-cross cats. This study aims to investigate proteins that can be potential biomarkers for early disease diagnosis in cats with PKD1 heterozygous gene mutations and compare them with chronic kidney disease cats and normal wild-type cats. Thirty-three client-owned cats of variable breeds (ten PKD1 gene mutation cats, twelve wild-type cats with normal blood profiles, and eleven wild-type cats with chronic renal disease) were enrolled in this study. This study used serum-based proteomic profiling analysis in cats. Abdominal ultrasounds were examined in all cats. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). One hundred and fifty-nine proteins were significantly differentially expressed between each group. The proteins identified in this study are known to regulate the apoptosis pathway. The apoptosis regulator Bcl-2 (BCL2) was overexpressed in the chronic kidney disease (CKD) group, while apoptotic peptidase activating factor 1 (APAF1) and BCL2-associated X apoptosis regulator (BAX) were only expressed in the PKD group. Ingenuity pathway analysis revealed that proteins uniquely expressed in the PKD group were linked to the Wnt signaling pathway and MAPK pathway. Asparagine synthetase domain-containing and secreted frizzled-related proteins were interesting proteins that should be studied further for the possibility of a candidate protein for disease detection. The proteomic profiles identified in this study could be used as potential novel biomarkers for the early detection of PKD in cats.

Assessing breathing effort by barometric whole-body plethysmography and its relationship with prognosis in client-owned cats with respiratory distress.

Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated. Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival. Fifty-two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014. This is a prospective observationalstudy. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole-body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow-up data, including disease category, clinical outcomes, and survival, were prospectively collected. Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158-1240) than normal cats (269 mL/kg; range, 168-389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher-than-normal MV/BW trends. A cutoff value of 373 mL/kg (1.4-fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.02-1.35; P = .03). Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress.

A novel ITGA2B double cytosine frameshift variant (c.1986_1987insCC) leads to Glanzmann's thrombasthenia in a cat.

Glanzmann's thrombasthenia (GT) is a congenital platelet disorder affecting approximately 1:1 000 000 people globally and characterized by impaired platelet aggregation and clot retraction. Autosomal recessive, loss-of-function, variants in ITGA2B or ITGB3 of the αIIbβ3 receptor cause the disease in humans. A cat affected by Glanzmann's and macrothrombocytopenia was presented to the UC Davis VMTH. Severe thrombopathia in this cat has an underlying genetic etiology. A single affected patient, 2 age-matched clinically healthy controls, and a geriatric population (n = 20) of normal cats. Physical examination and clinical pathology tests were performed on the patient. Flow cytometry and platelet aggregometry analyses for patient phenotyping were performed. Patient and validation cohort gDNA samples were extracted for Sanger sequencing of a previously identified ITGA2B (c.1986delC) variant. Reverse transcriptase PCR was performed on patient and healthy control PRP samples to verify ITGA2B variant consequence. A novel c.1986_1987insCC autosomal recessive variant in ITGA2B was identified. This variant was absent in a population of 194 unrelated cats spanning 44 different breeds. Complete loss of ITGA2B transcript and protein expression was verified by RT-PCR and flow cytometry, explaining the underlying etiology of GT, and likely macrothrombocytopenia, in this cat. This study emphasizes the role of precision medicine in cardiovascular disease of cats and identified yet another variant that may be of utility for screening in the feline population. This study provides a small-volume, standardized, successful protocol for adequate platelet RNA isolation and subsequent molecular assessment of gene expression in cats.

Real-time prediction of bladder urine leakage using fuzzy inference system and dual Kalman filtering in cats

The use of electrical stimulation devices to manage bladder incontinence relies on the application of continuous inhibitory stimulation. However, continuous stimulation can result in tissue fatigue and increased delivered charge. Here, we employ a real-time algorithm to provide a short-time prediction of urine leakage using the high-resolution power spectrum of the bladder pressure during the presence of non-voiding contractions (NVC) in normal and overactive bladder (OAB) cats. The proposed method is threshold-free and does not require pre-training. The analysis revealed that there is a significant difference between voiding contraction (VC) and NVC pressures as well as band powers (0.5–5 Hz) during both normal and OAB conditions. Also, most of the first leakage points occurred after the maximum VC pressure, while all of them were observed subsequent to the maximum VC spectral power. Kalman-Fuzzy method predicted urine leakage on average 2.2 s and 1.6 s before its occurrence and an average of 2.0 s and 1.1 s after the contraction started with success rates of 94.2% and 100% in normal and OAB cats, respectively. This work presents a promising approach for developing a neuroprosthesis device, with on-demand stimulation to control bladder incontinence.

Correlation of temperature-sensing microchip and rectal temperature measurements in cats.

Rectal temperature (RT) is the reference standard for clinical evaluation of body temperature in mammals. However, the use of a rectal thermometer to measure temperature can cause stress and other problems, especially in cats. There is a need for clinical techniques that reduce both stress and defensive behavior as part of the provision of better medical care. Subcutaneous temperature-sensing identification microchips fulfil the current legal requirements and provide a reading of subcutaneous temperature (MT). The clinical study tried to determine whether there is agreement between MT and RT in normal (n = 58), hospitalized (n = 26) and sedated/anesthetized (n = 36) cats. Three measurements were taken using both methods (MT and RT) in each cat. Correlation between MT and RT, and differences between MT and RT, were estimated for pairs of data-points from the same individual, and all data pairs in each group were considered overall. There was a strong positive correlation between MT and RT (r = 0.7 to 1.0) (p < 0.0005). The mean differences (d) were always negative and although statistically significant, these d values are likely of no biological importance. The overall d was ‑0.1°C in normal cats (p < 0.0005), -0.1°C in hospitalized cats (p = 0.001) and -0.1°C in sedated/anesthetized cats (p = 0.001). The limits of agreement between MT and RT appear narrow enough for MT to be acceptable estimate of RT. The overall limits of agreement (95%) were ‑0.71°C and 0.53°C (in normal cats); ‑0.51°C and 0.34°C (in hospitalized cats) and ‑0.60°C and 0.42°C (in sedated/anesthetized cats). MT may provide a good alternative to RT measurement in cats. However, this study was mostly performed in animals that were normothermic. Therefore, further studies in larger groups of cats under different conditions are needed to compare trends and assess variation with time.

Parameters related to diagnosing hypertrophic cardiomyopathy in cats.

The initial diagnostic markers are important for general practitioners to identify cats suspected of having cardiac disease, particularly hypertrophic cardiomyopathy (HCM). The aim of this study is to investigate the indicators that suggest feline cardiac disease, especially HCM. This is a retrospective study, using the data from 354 cats, to identify various clinical parameters that indicate the presence of cardiac disease in cats in order to develop a model to predict the likelihood of HCM in cats. Among all the parameters gathered, heart sound and LA size are the most significant in predicting the likelihood of HCM in cats. After undergoing statistical analysis, we created a formula that could help screen cats with HCM and normal cats before further diagnosis, such as echocardiography. The formula Y1 = -3.637 +2.448 (LA size) +2.683 (murmur) +1.274 (gallop) is the fittest model with an area under curve from the ROC analysis of 0.889. A new set of data was used to validate the model. This predictive model has 40% accuracy but correctly predicts 90% of the truly normal cats, making this model beneficial in helping veterinarians exclude truly normal cats from cats suspected of having HCM. The model may assist in distinguishing normal cats from those suspected of having HCM. Further diagnosis with echocardiography remains the gold standard for the final diagnosis of cardiac diseases in cats.

Reduction of urinary felinine in domestic cats with renal diseases leads to decreased catty odor.

Cats with progressive renal diseases often exhibit a weakened urinary odor, in contrast to normal cat urine which emits odorants with catty odor, such as 3-mercapto-3-methyl-1-butanol, 3-mercapto-3-methylbutyl formate, 3-methyl-3-methylthio-1-butanol, and 3-methyl-3-(2-methyldisulfanyl)-1-butanol. Felinine, an amino acid, is a precursor of these odorants and metabolized from its precursor, 3-methylbutanol glutathione (MBG), via 3-methylbutanol-cysteinylglycine (MBCG). While previous studies have reported felinine excretion in normal cats, its levels in cats with renal diseases remain unclear. This study investigates the urinary excretion of felinine and its precursors in cats with renal diseases and explores whether changes in these metabolites are linked to reduced volatile felinine derivatives with catty odor. Liquid chromatography/mass spectrometry quantified urinary felinine, MBCG, and MBG in 40 normal cats and 66 cats with renal diseases (classified into mild, moderate, and severe renal diseases), revealing a significant decrease in urinary felinine levels in cats with advanced renal disease, while urinary MBG levels increased. The felinine-to-MBG ratio was significantly lower in cats with severe renal disease compared to normal cats and those with mild renal disease. Gas chromatography/mass spectrometry analysis further showed that the emission of felinine derivatives decreased markedly with renal disease progression. A significant correlation was found between urinary felinine excretion and its major derivative, 3-methyl-3-methylthio-1-butanol. These findings suggest that impaired felinine metabolism, likely due to reduced kidney enzyme activity, contributes to both diminished urinary felinine levels and reduced sulfurous odor in cats with renal diseases.

Ovarian cauterization versus Cacl2 Injection For "In Situ Ovariectomy" In Female Cats

Overpopulation of stray and unwanted cats has been a serious issue in every country and different individuals have different motivations for their spaying or neutering. The current experiment aimed to evaluate the feasibility and safety of ovarian cauterization compared to CaCl2 injection for ovarian tissue damage in female cats. Each ovary of three cycling normal cats in reproductive age was punctured at four sites and 40 W was applied to 5 seconds at each point using monopolar electro-coagulation, resulting in 800 J (Joules) of thermal energy. Ovaries of another three cats were injected with 0.25 ml of 20% CaCl2 in 95% ethanol solution. Macroscopic and microscopic lesions were assessed depending on a number of evaluating criteria. Operative time, intraoperative and postoperative complications, and estrogen level estimation showed significant difference between both techniques. The cauterization technique proved easy applicable and safe, and there were no intra-abdominal thermal injuries. Histologic evaluation proved essential to clarify the ovarian functional activity. Ovarian cauterization seems to be feasible and safe, and 40 W (800 J) thermal energy allowed incomplete ovarian thermal damage.

Decreased circulating transforming growth factor-beta (TGF-β) and kidney TGF-β immunoreactivity predict renal disease in cats with naturally occurring chronic kidney disease.

The aim of the present study was to compare the circulating transforming growth factor-beta (TGF-β) of clinically normal age-matched and naturally occurring chronic kidney disease (CKD) cats and to determine the correlation between the TGF-β expression and histopathological changes in cats with CKD. A total of 11 clinically normal age-matched and 27 cats with naturally occurring CKD were included in this study. Circulating TGF-β was quantified by immunoassays. Kaplan-Meier analysis was used to calculate the association between survival time and the concentration of circulating TGF-β. A general linear model was used to compare the circulating TGF-β between groups. Immunohistochemical analyses revealed TGF-β expression in renal tissues from cats with CKD that died during the study (n = 7) and in available archived renal tissue specimens taken at necropsy from cats that had previous CKD with renal lesions (n = 10). Correlations of the TGF-β expression and clinical parameters (n = 7) and histopathological changes (n = 17) were analysed using Spearman's rank correlation. The median survival time of cats with a lower concentration of circulating TGF-β was shorter than that of cats with a higher concentration. The area under the curve of circulating TGF-β for predicting CKD was 0.781, indicating good differentiation. The study indicated a significant difference in circulating TGF-β concentrations between clinically normal cats and those with CKD and demonstrated that TGF-β expression is correlated with tubular atrophy. The study findings suggest that decreased serum TGF-β and tubular atrophy with TGF-β immunoreactivity may be significant in cats with CKD.

Effect of Butorphanol with and without Medetomidine on Intraocular Pressure in Cats

This study aimed to determine the effects of intramuscular administration of butorphanol with and without medetomidine on intraocular pressure (IOP) in cats. Sixteen clinically normal cats were used. Cats were randomly received two-treatment regimen. The first regimen was 0.2mg/kg butorphanol, and the second regimen was a mixture of 0.1mg/kg butorphanol and 0.05mg/kg medetomidine. IOP values were recorded before treatment (T0) and following the treatment at 10 (T10), 20 (T20), 30 (T30), and 40 min (T40) in both groups. Administration of butorphanol with and without medetomidine did not cause a statistically significant change in IOP values. The IOP did not change over time (p = 0.41). The mean values of IOP in butorphanol, and butorphanol-medetomidine groups were 20.00 ± 2.29 and 20.38 ± 2.35 mm Hg, respectively. In conclusion, intramuscular administration of butorphanol with or without medetomidine had no significant effect on IOP in cats.

Urine concentrating ability in cats with hyperthyroidism: Influence of radioiodine treatment, masked azotemia, and iatrogenic hypothyroidism.

Hyperthyroid cats often have urine specific gravity (USG) values <1.035. It remains unclear how USG changes after treatment, if USG can be used to predict azotemia after treatment, or how iatrogenic hypothyroidism influences USG values. To determine the proportion of hyperthyroid cats with USG <1.035 vs ≥1.035; if USG changes after treatment; and whether USG <1.035 correlated with unmasking of azotemia or hypothyroidism. Six hundred fifty-five hyperthyroid cats treated with radioiodine; 190 clinically normal cats. Prospective, before-and-after study. Hyperthyroid cats had serum thyroxine, thyroid-stimulating hormone, and creatinine concentrations, and USG measured before and 6 months after successful treatment with radioiodine. Of untreated hyperthyroid cats, USG was ≥1.035 in 346 (52.8%) and <1.035 in 309 (47.2%). After treatment, 279/346 (80.6%) maintained USG ≥1.035, whereas 67/346 (19.4%) became <1.035; 272/309 (88%) maintained USG <1.035, whereas 37/309 (12%) became ≥1.035. Only 22/346 (6.4%) with USG ≥1.035 developed azotemia after treatment, compared with 136/309 (44%) with <1.035 (P < .001). Of cats remaining nonazotemic, 38% had USG <1.035, compared with 20% of normal cats (P < .001). The 137 cats with iatrogenic hypothyroidism had lower USG after treatment than did 508 euthyroid cats (1.024 vs 1.035), but USGs did not change after levothyroxine supplementation. USG <1.035 had high sensitivity (86.1%) but moderate specificity (65.2%) in predicting azotemia after treatment. Hyperthyroidism appears not to affect USG in cats. However, cats with evidence of sub-optimal concentrating ability before radioiodine treatment (USG < 1.035) are more likely to develop azotemia and unmask previously occult chronic kidney disease. Iatrogenic hypothyroidism itself did not appear to affect USG values.

Aqueous Humor TGF-β2 and Its Association With Intraocular Pressure in a Naturally Occurring Large Animal Model of Glaucoma.

Transforming growth factor (TGF)-β2 has been widely implicated in human glaucoma pathology. The purpose of this study was to determine the source of TGF-β2 in aqueous humor (AH) and its relationship with intraocular pressure (IOP) in an inherited large animal model of glaucoma. Sixty-six glaucomatous cats homozygous for LTBP2 mutation, and 42 normal cats were studied. IOP was measured weekly by rebound tonometry. AH was collected by anterior chamber paracentesis from each eye under general anesthesia, and serum samples collected from venous blood concurrently. Concentrations of total, active and latent TGF-β2 in AH and serum samples were measured by quantitative sandwich immunoassay. For comparisons between groups, unpaired t-test or Mann Whitney test were used, with P < 0.05 considered significant. The relationships between TGF-β2 concentrations and IOP values were examined by Pearson's correlation coefficient and generalized estimating equation. IOP and AH TGF-β2 concentrations were significantly higher in glaucomatous than in normal cats. AH TGF-β2 showed a significant, robust positive correlation with IOP in glaucomatous cats (r = 0.83, R2 = 0.70, P < 0.0001). Serum TGF-β2 did not correlate with AH TGF-β2 and was not significantly different between groups. TGF-β2 mRNA and protein expression were significantly increased in local ocular tissues in glaucomatous cats. Enhanced, local ocular production of TGF-β2 with a robust positive association with IOP was identified in this spontaneous feline glaucoma model, providing a foundation for preclinical testing of novel therapeutics to limit disease-associated AH TGF-β2 elevation and signaling in glaucoma.

Measurement of Ghrelin as a Marker of Appetite Dysregulation in Cats with and without Chronic Kidney Disease.

Appetite abnormalities and weight loss are important comorbidities in the treatment of chronic kidney disease (CKD) in cats. Ghrelin, a key hormone involved in the regulation of appetite and metabolism, is a potential marker of appetite dysregulation in cats with CKD. The aim of this study was to compare the plasma concentrations of acylated, desacyl, and total ghrelin in normal cats and cats with CKD. Storage methodology was investigated prior to evaluating ghrelin concentrations in normal and CKD cats to facilitate clinical sample collection. Twelve normal cats and twelve cats with CKD were enrolled. Plasma acylated and total ghrelin concentrations were measured using radioimmunoassay. Desacyl ghrelin was calculated (total ghrelin minus acylated ghrelin). Cats with CKD had significantly increased total ghrelin and calculated desacyl ghrelin concentrations in comparison to normal cats (p < 0.0001 and p = 0.0001). There was no significant difference in active ghrelin concentrations between groups. Both total ghrelin and calculated desacyl ghrelin were significantly correlated with serum creatinine concentrations (p < 0.0001, r = 0.70 and p < 0.0001, r = 0.73). Elevated plasma desacyl ghrelin concentrations in cats with CKD provides evidence for dysregulation of appetite in feline CKD.

Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants.

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). The aim of this study was to conduct a large-scale epidemiological study of ADPKD caused by the conventional PKD1 variant in Japan and to search for novel polymorphisms by targeted resequencing of the PKD1 using a next-generation sequencer. A total of 1281 cats visiting the Veterinary Medical Center of the University of Tokyo were included in this study. DNA was extracted from the blood of each cat. We established a novel TaqMan real-time PCR genotyping assay for the conventional PKD1 variant, and all cases were examined for the presence of this variant. Targeted resequencing of all exons of the PKD1 was performed on the DNA of 23 cats with the conventional PKD1 variant, six cats diagnosed with cystic kidneys but without this variant, and 61 wild-type normal cats. Among the 1281 cats examined in this study, 23 (1.8%) harboured the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds and Exotic Shorthairs than in the other breeds, although the number of cases in each breed was small. Furthermore, we identified four variants unique to cats with cystic kidneys that were not found in wild-type normal cats, all of which were in exon 15. In particular, two (chrE:g.42848725delC, pGly1641fs and chrE:g.42850283C>T, pArg2162Trp) were candidate variants. This study revealed that the conventional PKD1 variant was prevalent in Scottish Fold, Persian and Exotic Shorthair breeds in Japan, and variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, would be key factors in the pathogenesis of ADPKD in cats.