Evaluation of responses to immunosuppressive therapy in dogs with suspected non-regenerative immune-mediated anaemia: 11 cases (2012-2018).

OBJECTIVES: We aimed to determine the response time to immunosuppressive therapy and time required to achieve a 5% increase in haematocrit among dogs with non-regenerative immune-mediated anaemia. MATERIALS AND METHODS: Client-owned dogs diagnosed with non-regenerative immune-mediated anaemia in Hokkaido University Veterinary Teaching Hospital between December 2012 and May 2018 were enrolled. The first treatment regimen included prednisolone (2 mg/kg/day) and ciclosporin (up to 10 mg/kg/day) for 8 weeks. Dogs that did not respond to the first regimen proceeded to the second regimen comprising prednisolone and mycophenolate mofetil (15 mg/kg, twice a day). Reticulocyte count and haematocrit were monitored every 1 to 2 weeks. Treatment response was defined as an absolute reticulocyte count more than 60×103 /µL or increasing haematocrit. RESULTS: During the study period, 23 dogs fulfilled the inclusion criteria for non-regenerative immune-mediated anaemia. Twelve dogs were excluded from this study for various reasons and response to therapy was evaluated in the remaining 11 dogs. Treatment responses were observed in 8 of 11 dogs, and the median time to response was 39.5 days (range 8 to 92 days). Two responders were unable to continue the first treatment regimen and were switched to the second regimen owing to anorexia and nausea, possibly induced by ciclosporin; withdrawal of ciclosporin improved their symptoms. The time required to achieve a 5% increase in haematocrit was assessed in the other six dogs, with a median of 55.5 days (range 8 to 135 days). CLINICAL SIGNIFICANCE: Here we report the response to a standardised treatment protocol in dogs with non-regenerative immune-mediated anaemia. Knowledge of potential side effects and expected therapeutic outcomes may be of use for veterinary practitioners treating this condition.

Prognostic value of left atrial stiffness estimated using echocardiography in dogs with myxomatous mitral valve disease.

INTRODUCTION: No studies have investigated the prognostic value of left atrial stiffness (LASt) estimated using echocardiography in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: Seventy-two dogs had MMVD and 46 dogs were healthy dogs. MATERIALS AND METHODS: Clinical retrospective cohort study. The survival information of MMVD dogs that underwent echocardiographic examination was obtained. The peak velocities of early diastolic transmitral flow (E) and mitral annular motion as determined by pulsed wave Doppler (E') were determined. The left atrial reservoir strain (εS) was determined by two-dimensional speckle tracking echocardiography of the left atrium. The LASt was estimated by the formula: E/E'/εS. The 95% prediction interval of LASt was computed from the data of the healthy dogs. RESULTS: Seventeen dogs having MMVD died of cardiac-related causes with 55 MMVD dogs censored. The MMVD dogs with LASt > its 95% upper prediction limit (LASt > 0.56; n = 26; median survival time, 484 days; 95% confidence interval, 283 days-indeterminable) had shorter survival times (P<0.001) than those with LASt ≤ its 95% upper prediction limit (LASt ≤ 0.56; n = 46; median survival time, >1112 days; 95% confidence interval, indeterminable). Multivariable Cox's proportional hazard analysis demonstrated that the ratio of the left atrial dimension to the aortic annulus dimension and LASt were independent predictors of cardiac-related death among conventional echocardiographic indices, εS and LASt in MMVD dogs. CONCLUSIONS: In dogs with MMVD, increased LASt estimated using echocardiography is an independent predictor of cardiac-related death, and LASt can be more useful for prognostication than εS.

Cell death signalling is competitively but coordinately regulated by repressor-type and activator-type ethylene response factors in tobacco (Nicotiana tabacum) plants.

Ethylene response factors (ERFs) comprise one of the largest transcription factor families in many plant species. Tobacco (Nicotiana tabacum) ERF3 (NtERF3) and other ERF-associated amphiphilic repression (EAR) motif-containing ERFs are known to function as transcriptional repressors. NtERF3 and several repressor-type ERFs induce cell death in tobacco leaves and are also associated with a defence response against tobacco mosaic virus (TMV). We investigated whether transcriptional activator-type NtERFs function together with NtERF3 in the defence response against TMV infection by performing transient ectopic expression, together with gene expression, chromatin immunoprecipitation (ChIP) and promoter analyses. Transient overexpression of NtERF2 and NtERF4 induced cell death in tobacco leaves, albeit later than that induced by NtERF3. Fusion of the EAR motif to the C-terminal end of NtERF2 and NtERF4 abolished their cell death-inducing ability. The expression of NtERF2 and NtERF4 was upregulated at the early phase of N gene-triggered hypersensitive response (HR) against TMV infection. The cell death phenotype induced by overexpression of wild-type NtERF2 and NtERF4 was suppressed by co-expression of an EAR motif-deficient form of NtERF3. Furthermore, ChIP and promoter analyses suggested that NtERF2, NtERF3 and NtERF4 positively or negatively regulate the expression of NtERF3 by binding to its promoter region. Overall, our results revealed the cell death-inducing abilities of genes encoding activator-type NtERFs, including NtERF2 and NtERF4, suggesting that the HR-cell death signalling via the repressor-type NtERF3 is competitively but coordinately regulated by these NtERFs.

A novel multi-target strategy to attenuate the progression of Parkinson's disease by diamine hybrid AGE/ALE inhibitor.

Instead of a conventional 'one-drug-one-target approach', this article presents a novel multi-target approach with a concept of trapping simultaneously as many detrimental factors as possible involved in the progression of Parkinson's disease. These factors include reactive carbonyl species, reactive oxygen species, Fe3+/Cu2+ and ortho-quinones (o-quinone), in particular. Different from the known multi-target strategies for Parkinson's disease, it is a sort of 'vacuum cleaning' strategy. The new agent consists of reactive carbonyl species scavenging moiety and reactive oxygen species scavenging and metal chelating moiety linked by a spacer. Provided that the capacity of scavenging o-quinones is demonstrated, this type of agent can further broaden its potential therapeutic profile. In order to support this new hypothetical approach, a number of simple in vitro experiments are proposed.

Changes in fears and worries related to COVID-19 during the pandemic among current employees in Japan: a 5-month longitudinal study.

OBJECTIVES: This study investigates and describes the time course of fears and worries about COVID-19 among current employees during this outbreak. STUDY DESIGN: This was a longitudinal study. METHODS: This study was a part of the Employee Cohort Study in Japan. The study comprised 4120 individuals from February 2019. A baseline survey in March 2020, a 2-month follow-up survey in May 2020, and a 5-month follow-up survey in August 2020 were conducted. Questions surveyed respondents' global fear and worry and six items related to COVID-19. A mixed model for repeated measures of an analysis of variance was used. RESULTS: A total of 1421 respondents completed the baseline survey. At 2- and 5-month follow-ups, 1032 and 1181 respondents completed surveys, respectively. Of those, 64 and 33 individuals who were temporarily laid off or on leave were recorded as missing values. Global fear and worry about COVID-19 significantly increased from March to August 2020. Fears of personal or family infection, limiting one's activities and national and local government policies also significantly increased with time. In contrast, fears of lack of knowledge and difficulty of obtaining hygiene products significantly decreased. CONCLUSION: To conduct efficient risk communication during a pandemic, knowing the concerns of the populace, providing correct information and a sufficient supply of products, and setting clear guidelines are essential.

Predictors of Cerebral Aneurysm Rupture after Coil Embolization: Single-Center Experience with Recanalized Aneurysms.

BACKGROUND AND PURPOSE: Recanalization after coil embolization is widely studied. However, there are limited data on how recanalized aneurysms rupture. Herein, we describe our experience with the rupture of recanalized aneurysms and discuss the type of recanalized aneurysms at greatest rupture risk. MATERIALS AND METHODS: A total of 426 unruptured aneurysms and 169 ruptured aneurysms underwent coil embolization in our institution between January 2009 and December 2017. Recanalization occurred in 38 (8.9%) of 426 unruptured aneurysms (unruptured group) and 37 (21.9%) of 169 ruptured aneurysms (ruptured group). The Modified Raymond-Roy classification on DSA was used to categorize the recanalization type. Follow-up DSA was scheduled until 6 months after treatment, and follow-up MRA was scheduled yearly. If recanalization was suspected on MRA, DSA was performed. RESULTS: In the unruptured group, the median follow-up term was 74.0 months. Retreatment for recanalization was performed in 18 aneurysms. Four of 20 untreated recanalized aneurysms (0.94% of total coiled aneurysms) ruptured. In untreated recanalized aneurysms, class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .025). In the ruptured group, the median follow-up term was 28.0 months. Retreatment for recanalization was performed in 16 aneurysms. Four of 21 untreated recanalized aneurysms (2.37% of total coiled aneurysms) ruptured. Class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .02). CONCLUSIONS: The types of recanalization after coil embolization may be predictors of rupture. Coiled aneurysms with class IIIb recanalization should undergo early retreatment because of an increased rupture risk.

Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer's Disease.

There is an urgent need to propose effective treatments for Alzheimer's disease (AD). Although the origin of the disease is poorly understood, several therapeutic options have been proposed. The new therapeutic approaches targeting biometal-mediated neurodegenerative pathways appear to be interesting ones. As a continuation of our preceding studies, two novel series of advanced glycation endproducts (AGE)/advanced lipid peroxidation endproducts (ALE) inhibitors have been developed as multifunctional scavengers. This extended work allowed us to highlight the new hydroxypyridinone-diamine hybrid IIa-3 bearing a C4 alkyl linker between the two pharmacophores. This derivative exhibited preserved potent capacities to trap reactive carbonyl species (vicinal diamine function) as well as reactive oxygen species and transition metals (hydroxypyridinone moiety) in comparison with previously described lead compound 1. In addition, its good predicted absorption, distribution, metabolism and excretion (ADME) properties were correlated with a better efficacy to inhibit in vitro methylglyoxal-induced apoptosis in neuronal-like PC12 cells. This new promising agent revealed improved druglikeness and ability to prevent biometal-mediated oxidative and carbonyl stress amplification involved in AD pathogenesis.

Right ventricular function and dyssynchrony measured by echocardiography in dogs with precapillary pulmonary hypertension.

INTRODUCTION: Assessment of the right ventricular (RV) function by echocardiography is important in dogs with pulmonary hypertension (PH). Few reports are available on RV function and dyssynchrony in dogs, especially in the context of precapillary PH. ANIMALS: The study included 79 client-owned dogs: 25 dogs with precapillary PH and 54 control dogs. METHODS: Dogs with precapillary PH were prospectively enrolled between December 2013 and February 2017. The echocardiographic indices of RV function, including RV strain and the dyssynchrony index by speckle-tracking echocardiography, were measured. Multivariate analysis was used to determine independent predictors of the RV dyssynchrony index. RESULTS: Dogs with precapillary PH showed RV dilation, hypertrophy and right atrial dilation. Impaired echocardiographic indices of RV function, including RV strain, were observed. In addition, RV dyssynchrony occurred in dogs with precapillary PH. Multivariate analysis revealed that tricuspid regurgitation velocity and RV dilation were independent predictors of the RV dyssynchrony index. CONCLUSIONS: Echocardiographic RV function indices are impaired in dogs with precapillary PH. In addition, RV dilation and elevated systolic pulmonary arterial pressure estimated by echocardiography are associated with RV dyssynchrony.

The Repeatability and Left Atrial Strain Analysis Obtained via Speckle Tracking Echocardiography in healthy Dogs.

INTRODUCTION: In left atrial (LA) strain-derived two-dimensional speckle tracking echocardiography, the reference intervals in healthy dogs can provide useful information to evaluate the LA function in dogs with heart disease. ANIMALS: Six laboratory beagles and 120 privately owned dogs without cardiac diseases were recruited. MATERIALS AND METHODS: The LA strain and strain rate (SR) and echocardiographic indices were obtained in dogs who underwent standard echocardiography and offline analysis for LA strain and SR measurement by speckle tracking echocardiography. RESULTS: The intra-observer within-day variations of strain variables showed adequate repeatability (coefficient of variation <20%). The mean values of strain were 25.37 for the LA reservoir function, 11.06 for the LA conduit function, and 14.17 for the LA booster-pump function; the strain was significantly correlated with the LA fractional volume change at each phasic function. The left atrial longitudinal strain during early ventricular diastole showed moderate correlation with the peak velocity of early diastolic transmitral flow (r = 0.5560) and ratio of peak velocity of early diastolic transmitral flow to peak velocity of late transmitral flow (r = 0.5515). In multiple regression analysis, only age was significantly related to the strain/SR and volumetric change indices, indicating conduit function. CONCLUSIONS: Left atrial speckle tracking echocardiographic analysis provided useful information to assess the LA function in healthy dogs. The influencing factors on strain and SR variables including the age, body weight, and heart rate should be considered in interpretation of these parameters in a clinical setting.

Epidemiology of massive hepatocellular carcinoma in dogs: A 4-year retrospective study.

Hepatocellular carcinoma (HCC) is the most common primary liver tumour in dogs. However, the clinical features and risk factors of HCC have not been confirmed. The objective of this study was to investigate the clinical features and risk factors for canine HCC. Medical records of 44 dogs diagnosed with HCC at Hokkaido University Veterinary Teaching Hospital between 2013 and 2017 were retrospectively reviewed. All dogs evaluated at the teaching hospital during the study period were used as the reference population for breed, age, sex predispositions or possible related factors for HCC, including concurrent disorders. Clinical characteristics of HCC were determined using propensity score matching analysis. The prevalence of HCC diagnosis was 0.96%. Multivariate analysis revealed that dogs diagnosed with HCC were significantly older (odds ratio [OR], 1.20; 95% confidence intervals [CI], 1.07-1.33) than the reference population. Welsh Corgis (OR, 3.68; 95% CI, 1.56-8.67) and Beagles (OR, 4.33; 95% CI, 1.58-11.90) were significantly predisposed to HCC. Twenty-seven of 44 dogs with HCC had at least one concurrent disorder. The most common concurrent disorder was hyperadrenocorticism (n = 10), and the adjusted odds of hyperadrenocorticism in dogs with HCC were 4.13 higher than those of the reference population (95% CI, 1.95-8.76). Propensity score matching analysis revealed that thrombocytosis (n = 30/43), increased alanine aminotransferase (n = 41/44), increased alkaline phosphatase (n = 42/44), and hypercalcemia (n = 13/32) were significantly associated with HCC diagnosis. The results of this study suggest that Welsh Corgis and Beagles are breeds with a predisposition for HCC and that hyperadrenocorticism might be a potential risk factor.

Sleep during low-frequency repetitive transcranial magnetic stimulation is associated with functional improvement in upper limb hemiparesis after stroke.

Many studies have reported that repetitive transcranial magnetic stimulation (rTMS) is beneficial for post-stroke patients with upper limb hemiparesis. It was reported that application of rTMS during sleep could possibly strengthen neural plasticity. The purpose of this study was to investigate the relationship between sleep during low-frequency rTMS session and improvement of motor function in affected upper limb in post-stroke patients after inpatient rehabilitation combined with rTMS using the bispectral index (BIS) monitor. During 15-day hospitalization, each patient received rTMS and intensive occupational therapy. Low-frequency rTMS with 1 Hz was applied over the contralesional motor cortex. During rTMS session, adhesive sensor was put on each patient's forehead and connected to the BIS monitor. The mean score for the maximum change of BIS values during each rTMS session (ΔBIS) was calculated. We regarded the patients with and over 10 of mean ΔBIS as Asleep group and under 10 as Awake group. Fugl-Meyer assessment (FMA) and Action Research Arm Test (ARAT) were evaluated on admission and discharge. Awake group included six patients and Asleep group included seven patients. There was no significant difference in clinical characteristics and in increase of FMA between two groups. Asleep group was significantly superior to Awake group in the increase of ARAT (p < 0.05). There was a significant correlation between the mean of ΔBIS and increase of ARAT (ρ = 0.78, p = 0.002). Sleep during low-frequency rTMS may contribute to improvement of motor function in the affected upper limb.

Transcranial Doppler Ultrasound Examination in Dogs with Suspected Intracranial Hypertension Caused by Neurologic Diseases.

BACKGROUND: Transcranial Doppler ultrasound examination (TCD) is a rapid, noninvasive technique used to evaluate cerebral blood flow and is useful for the detection of intracranial hypertension in humans. However, the clinical usefulness of TCD in diagnosing intracranial hypertension has not been demonstrated for intracranial diseases in dogs. OBJECTIVES: To determine the association between the TCD variables and intracranial hypertension in dogs with intracranial diseases. ANIMALS: Fifty client-owned dogs with neurologic signs. METHODS: Cross-sectional study. All dogs underwent TCD of the basilar artery under isoflurane anesthesia after magnetic resonance imaging (MRI). Dogs were classified into 3 groups based on MRI findings: no structural diseases (group I), structural disease without MRI evidence of intracranial hypertension (group II), and structural disease with MRI evidence of intracranial hypertension (group III). The TCD vascular resistance variables (resistive index [RI], pulsatility index [PI], and the ratio of systolic to diastolic mean velocity [Sm/Dm]) were measured. RESULTS: Fifteen, 22, and 13 dogs were classified into groups I, II, and III, respectively. Dogs in group III had significantly higher Sm/Dm (median, 1.78; range, 1.44-2.58) than those in group I (median, 1.63; range, 1.43-1.75) and group II (median, 1.62; range, 1.27-2.10). No significant differences in RI and PI were identified among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings suggest that increased Sm/Dm is associated with MRI findings of suspected intracranial hypertension in dogs with intracranial diseases and that TCD could be a useful tool to help to diagnose intracranial hypertension.

The repeatability and characteristics of right ventricular longitudinal strain imaging by speckle-tracking echocardiography in healthy dogs.

INTRODUCTION: To assess the repeatability and characteristics of echocardiographic indices of the right ventricular (RV) function derived from speckle-tracking echocardiography. ANIMALS: Fourteen laboratory Beagles and 103 privately owned dogs without cardiac disease were involved in this study. MATERIALS AND METHODS: Right ventricular longitudinal strain, strain rate, and a strain-related index for assessing RV dyssynchrony derived from speckle-tracking echocardiography were obtained by two different observers using five Beagles. Within-day, between-day, and interobserver coefficients of variation and the intraclass correlation coefficient of speckle-tracking echocardiography indices were determined. Both speckle-tracking echocardiography and conventional indices of RV function, including the peak velocity of systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, fractional area change, and the Tei index, were obtained from 14 Beagles and 103 privately owned dogs. Relationships between echocardiographic indices and the body weight, heart rate, age, and sex were estimated by regression analysis. RESULTS: Speckle-tracking echocardiographic indices showed good within-day repeatability, between-day and interobserver repeatability were moderate to good. In large dogs, RV longitudinal strain, strain rate, and fractional area change were significantly decreased, while the index of RV dyssynchrony, systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, and the Tei index were increased. All speckle-tracking and conventional echocardiographic indices were correlated with the body weight. DISCUSSION AND CONCLUSIONS: The speckle-tracking echocardiography indices were highly repeatable and body weight affected speckle-tracking echocardiography indices in dogs. Further studies are needed to apply speckle-tracking echocardiography indices in dogs with cardiac disease.

A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling.

Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length. Consistently, we observed that Rb depletion increased the levels of fatty acids with the corresponding carbon chain length and number of carbon-carbon double bondssuch as myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0) and all forms of FA 18:1. Microarray analysis revealed that Rb depletion induced significant upregulation of enzymes involved in elongation and desaturation of fatty acids. Among these, we found that elongation of long chain fatty acid family member 6 (Elovl6) and stearoyl-CoA desaturase 1 (Scd1) are the most robustly controlled by Rb possibly through E2F and sterol regulatory element-binding protein transcription factors. Depletion of Elovl6 or Scd1 significantly suppressed colony formation, sphere formation and xenograft tumor growth of Rb-deficient tumor cells. Suppression of self-renewal by the SCD1 inhibitor was rescued upon supplementation of the mono-unsaturated fatty acids generated by this enzyme. This study suggests a novel role for Rb in suppressing the malignant progression of tumors by controlling the lipid composition.

The RB-IL-6 axis controls self-renewal and endocrine therapy resistance by fine-tuning mitochondrial activity.

Retinoblastoma (RB) protein inactivation during tumor progression is often associated with acquisition of immature phenotypes and resistance to therapy. Determination of an RB inactivation signature in a context of gaining undifferentiated phenotype in a p53-null sarcoma system revealed a critical role for interleukin (IL)-6. Using a Gene Set Enrichment Analysis (GSEA), we discovered that poorly differentiated breast cancers are enriched for this RB inactivation signature. Accelerated IL-6 secretion following RB inactivation in an RB-intact luminal-type breast cancer cell line MCF-7 promoted a positive feed forward loop between IL-6 and STAT3 driving tumor growth and endocrine therapy resistance. In addition, some of RB-intact basal-like type breast cancer cell lines exhibited a similar phenotype following RB depletion. The mechanism whereby RB inactivation increases IL-6 production in MCF-7 cells appeared to involve fatty acid oxidation (FAO)-dependent mitochondrial metabolism and c-Jun NH(2)-terminal kinase (JNK). In addition, IL-6, via STAT3-mediated feedback to mitochondria, autonomously adjusts mitochondrial superoxide to levels suitable to maintain stem cell-like activity. The gene expression profile of luminal-type breast cancer patients with low RB expression revealed high enrichment of genes involved in mitochondrial respiration and downstream targets of IL-6. These findings unveiled an unexpected strategy whereby RB suppresses malignant features of cancer cells through metabolic reprogramming and cell-autonomous inflammation.

Washout Ratio in the Hepatic Vein Measured by Contrast-Enhanced Ultrasonography to Distinguish Between Inflammatory and Noninflammatory Hepatic Disorders in Dogs.

BACKGROUND: Perflubutane microbubbles, a second-generation ultrasound contrast agent, are phagocytized by Kupffer cells. This characteristic may be useful to differentiate diffuse hepatic diseases in dogs. HYPOTHESIS/OBJECTIVES: To determine whether the washout ratio in the hepatic vein (HV) measured by contrast-enhanced ultrasonography (CEUS) can distinguish between inflammatory and noninflammatory hepatic disorders in dogs. ANIMALS: Forty-one client-owned dogs with hepatic disorders including 14 with hepatitis, 7 with primary hypoplasia of the portal vein (PHPV), 9 with congenital portosystemic shunt (cPSS), and 11 with other hepatopathy were enrolled. Six dogs without hepatic disease also were evaluated as healthy controls. METHODS: Dogs with hepatic disorders were prospectively included. Contrast-enhanced ultrasonography of the HV was performed for 2 minutes. Washout ratio was defined as the attenuation rate from peak intensity to the intensity at the end of the CEUS study. RESULTS: Washout ratio in the hepatitis group (median, 18.0%; range, 2.0-37.0%) was significantly lower than that of the PHPV (median, 52.2%; range, 11.5-86.3%), cPSS (median, 60.0%; range, 28.6-77.4%), other hepatopathy (median, 70.5%; range, 26.6-88.4%), and normal (median, 78.0%; range, 60.7-91.7%) groups. The area under the receiver operating characteristic curve for hepatitis was 0.960, with a 95% confidence interval (CI) of 0.853-0.990. Washout ratio ≤37.1% resulted in a sensitivity of 100% (95% CI, 78.5-100%) and specificity of 85.2% (95% CI, 67.5-94.1%) for the prediction of hepatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Washout ratio can distinguish hepatitis from the other noninflammatory disorders with high accuracy. This result might reflect impaired Kupffer cell phagocytosis in dogs with hepatitis.

Serial measurement of pancreatic lipase immunoreactivity concentration in dogs with immune-mediated disease treated with prednisolone.

OBJECTIVES: In this pilot study, serum canine pancreatic lipase immunoreactivity was measured repeatedly in dogs with various immune-mediated diseases that were treated with immunosuppressive doses of prednisolone. METHODS: Ten client-owned dogs with newly diagnosed immune-mediated disease that had normal canine pancreatic lipase immunoreactivity concentrations (≤200 µg/l) were treated with 2 to 2.2 mg/kg prednisolone orally once daily as the initial treatment. Serum samples were obtained from each of the dogs prior to treatment and at 1- to 4-week intervals during immunosuppressive treatment. The highest canine pancreatic lipase immunoreactivity concentration detected during immunosuppressive treatment was defined as the peak canine pancreatic lipase immunoreactivity. RESULTS: Peak canine pancreatic lipase immunoreactivity concentrations were classified as normal in two dogs, questionable (201 to 399 µg/l) in three dogs, and abnormal (≥400 µg/l) in five dogs. Peak canine pancreatic lipase immunoreactivity concentrations were significantly higher than baseline canine pancreatic lipase immunoreactivity concentrations but there was no evidence of clinical pancreatitis. CLINICAL SIGNIFICANCE: It remains unclear whether the five of 10 dogs with elevated canine pancreatic lipase immunoreactivity during prednisone treatment had subclinical pancreatitis or whether the abnormal results were a consequence of prednisolone administration.

Left Atrial Strain at Different Stages of Myxomatous Mitral Valve Disease in Dogs.

BACKGROUND: Decreased function of the left atrium (LA) is a useful prognostic indicator in dogs with myxomatous mitral valve disease (MMVD). In humans, LA strain is a novel severity indicator of mitral regurgitation, but its clinical utility in dogs has not been confirmed. OBJECTIVES: To examine whether LA strain as evaluated with speckle-tracking echocardiography is associated with MMVD stage in dogs. ANIMALS: Fifty-two client-owned dogs with MMVD. METHODS: Cross-sectional study. Dogs were classified as stage B1, B2, C, or D, according to the American College of Veterinary Internal Medicine consensus. Physical examination findings and echocardiographic variables were compared among the groups. To assess the comparative accuracy of echocardiographic variables in identifying dogs with the presence or history congestive heart failure (CHF), receiver operating characteristic curves and multivariate logistic analysis were used. RESULTS: There were no significant differences in parameters of LA strain between B1 and B2 groups. However, LA longitudinal strain during atrial contraction (εA ) (median, 19.1%; interquartile range, 15.3-24.3% in B1, 19.6%; 14.1-21.4% in B2, 6.2%; 3.18-11.2% in C/D) and during ventricular systole (εS ) (32.7%; 28.9-39.2% in B1, 35.6%; 31.7-41.9% in B2, 23.6%; 16.9-26.1% in C/D) were significantly lower in stages C/D than in stages B1 and B2. In multivariate logistic regression analysis, εA and peak early diastolic mitral inflow velocity were identified as independent indicators of stage C/D. CONCLUSIONS AND CLINICAL IMPORTANCE: εA was the best predictor of the presence or history of CHF. Further studies are needed to determine the clinical implications of these findings for treatment decisions and prognosis determination.

Localization of Toll-like Receptor (TLR) 2 and TLR4 mRNA in the Colorectal Mucosa of Miniature Dachshunds with Inflammatory Colorectal Polyps.

Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa (n = 5) and non-inflamed mucosa (n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles (n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles (P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium.

Multifunctional diamine AGE/ALE inhibitors with potential therapeutical properties against Alzheimer's disease.

An important part of pathogenesis of Alzheimer's disease (AD) is attributed to the contribution of AGE (Advanced Glycation Endproducts) and ALE (Advanced Lipid peroxidation Endproducts). In order to attenuate the progression of AD, we designed a new type of molecules that consist of two trapping parts for reactive carbonyl species (RCS) and reactive oxygen species (ROS), precursors of AGE and ALE, respectively. These molecules also chelate transition metals, the promoters of ROS formation. In this paper, synthesis of the new AGE/ALE inhibitors and evaluation of their physicochemical and biological properties (carbonyl trapping capacity, antioxidant activity, Cu(2+)-chelating capacity, cytotoxicity and protective effect against in vitro MGO-induced apoptosis in the model AD cell-line PC12) are described. It is found that compounds 40b and 51e possess promising therapeutic potentials for treating AD.