Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

Objective: To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS.

Design: Multicenter, retrospective, case-control study from 2017 to 2021.

Setting: Private referral center and veterinary teaching hospital.

Extending social accountability mandates to biomedical research in Canadian faculties of medicine.

Background: Social accountability (SA), as defined by Boelen and Heck, is the obligation of medical schools to address the needs of communities through education, research and service activities. While SA is embedded within health profession education frameworks in medicine, they are rarely taught within graduate-level (MSc/PhD) education.

Methods: As these programs train future medical researchers, we invited first-year graduate students enrolled in a mandatory professionalism class at our institution ( = 111) to complete a survey on their perceptions of the importance of SA in their research, training, and future careers.

Left atrial measurement in lateral sternal recumbency in cats undergoing focused cardiac ultrasound examination.

Objective: To compare left atrial measurements carried out by an emergency and critical care (ECC) clinician on cats in lateral and sternal recumbency.

Animals And Procedures: A prospective observational study was conducted between December 2019 and January 2021 at the university teaching hospital at University of Liège. One hundred and two hospitalized cats were enrolled.

Parkin coregulates glutathione metabolism in adult mammalian brain.

We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis. To further examine the protective effects of parkin in an oxidative stress model, we first combined the loss of prkn with Sod2 haploinsufficiency in mice. Although adult prkn//Sod2 animals did not develop dopamine cell loss in the S.

Septic pericardial disease and mediastinal abscessation in a cat with an intrathoracic needle foreign body.

Objective: To describe the successful management of a cat with an intrathoracic sewing needle foreign body and septic pericardial effusion.

Case Summary: A 10-year-old neutered female domestic longhair cat was referred for an intrathoracic metallic foreign body identified via thoracic radiography. Two weeks prior, the cat may have ingested a sewing needle.

The use of caffeine as a respiratory stimulant in a cat.

Objective: To report the use of caffeine as a respiratory stimulant in a cat with hypoventilation.

Case Summary: A cat was mechanically ventilated due to persistent hypercapnia (P co  > 75 mm Hg) following median sternotomy and thymectomy. After 3 days of mechanical ventilatory support, the cat would initiate breaths but failed weaning due to persistent hypercapnia.

The accuracy of tactile assessment of canine nose temperature to identify rectal hyperthermia and hypothermia in dogs presenting on an emergency basis.

The goals of this study were to evaluate whether touch can identify a warm nose as opposed to a cold nose, to examine the correlation between thermographically measured nose temperatures and rectal temperatures, and to calculate the accuracy of tactile assessment of nose temperature in detecting rectal hyperthermia and hypothermia in dogs. A total of 100 dogs presenting to an emergency room was prospectively enrolled. Tactile nose assessment was carried out on triage.

Vascular contributions to 16p11.2 deletion autism syndrome modeled in mice.

While the neuronal underpinnings of autism spectrum disorder (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2 mouse model of 16p11.

Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy.

Hypertension is a risk factor for the vascular permeability and neovascularization that threatens vision in diabetic retinopathy. Excess reactive oxygen species derived from the Nox (NADPH oxidase) isoforms, Nox1 and Nox4, contributes to vasculopathy in diabetic retinopathy; however, if Nox1/4 inhibition is beneficial in hypertensive diabetic retinopathy is unknown. Here, we determined that diabetic spontaneously hypertensive rats had exacerbated retinal vascular permeability and expression of angiogenic and inflammatory factors, compared with normotensive diabetic Wistar Kyoto rats.

Comparison of 3 intraosseous catheter sites and methods of determining placement success in cadaver rabbits.

The study goals were to determine if intraosseous (IO) catheters can be placed with greater success into the humerus, femur, or tibia of cadaver rabbits, and to evaluate the accuracy of perceived success (PS) and objective clinical success (OCS) criteria against true intramedullary catheterization confirmed by fluoroscopy. This was a prospective study utilizing 12 rabbit cadavers. Twenty-two participants attempted IO catheter placement at 3 sites.

Assessment of urinary microparticles in normotensive patients with type 1 diabetes.

Aims/hypothesis: Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes.

Vascular Smooth Muscle-Specific EP4 Receptor Deletion in Mice Exacerbates Angiotensin II-Induced Renal Injury.

Aims: Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs is contraindicated in hypertension, as it may reduce glomerular filtration rate (GFR) and renal blood flow. However, the identity of the specific eicosanoid and receptor underlying these effects is not known. We hypothesized that vascular smooth muscle prostaglandin E2 (PGE2) E-prostanoid 4 (EP4) receptor deletion predisposes to renal injury via unchecked vasoconstrictive actions of angiotensin II (AngII) in a hypertension model.

A novel mouse model of advanced diabetic kidney disease.

Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN) such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis) are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice). Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen) were employed as a model of angiotensin-dependent hypertension.

NADPH oxidase 5 and renal disease.

Purpose Of Review: To highlight the latest novel developments in renal NADPH oxidase 5 (Nox5) biology, with an emphasis not only on diabetic nephropathy but also on many of the other renal disease contexts in which oxidative stress is implicated.

Recent Findings: Nox-derived reactive oxygen species have been shown to contribute to a wide variety of renal diseases, particularly in the settings of chronic renal disease such as diabetic nephropathy. Although much emphasis has been placed on the role of NADPH oxidase 4 in this setting, a growing body of work continues to uncover the key roles for other Nox family members, not only in diabetic kidney disease, but also in a diverse array of renal pathological conditions.

Glutaredoxin-2 is required to control oxidative phosphorylation in cardiac muscle by mediating deglutathionylation reactions.

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins.

Urinary podocyte microparticles identify prealbuminuric diabetic glomerular injury.

Microparticles (MPs) are small (0.1-1.0 µm) vesicles shed from the surface of cells in response to stress.

Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression.

NADPH oxidase (Nox) enzymes are a significant source of reactive oxygen species, which contribute to glomerular podocyte dysfunction. Although studies have implicated Nox1, -2, and -4 in several glomerulopathies, including diabetic nephropathy, little is known regarding the role of Nox5 in this context. We examined Nox5 expression and regulation in kidney biopsies from diabetic patients, cultured human podocytes, and a novel mouse model.

Long-term hemodynamic and molecular effects persist after discontinued renin-angiotensin system blockade in patients with type 1 diabetes mellitus.

Animal studies suggest temporary renin-angiotensin system (RAS) blockade enhances long-term vascular protective effects; however, this is not established in humans. Here we evaluated the long-term effects of prior RAS blockade on hemodynamic function, urinary measures of inflammation, and tissue antioxidant mRNA expression in patients with type 1 diabetes mellitus (T1DM) who participated in the 5-year Renin Angiotensin System Study (RASS). At 4 years after completing the RASS and discontinuing study medication, renal hemodynamic responses to clamped hyperglycemia were significantly greater in 18 patients in the RAS blockade group compared to 9 patients of the placebo-treated group.

Chronic over-expression of heat shock protein 27 attenuates atherogenesis and enhances plaque remodeling: a combined histological and mechanical assessment of aortic lesions.

Aims: Expression of Heat Shock Protein-27 (HSP27) is reduced in human coronary atherosclerosis. Over-expression of HSP27 is protective against the early formation of lesions in atherosclerosis-prone apoE(-/-) mice (apoE(-/-)HSP27(o/e)) - however, only in females. We now seek to determine if chronic HSP27 over-expression is protective in a model of advanced atherosclerosis in both male and female apoE(-/-) mice.

Promotion of autoimmune diabetes by cereal diet in the presence or absence of microbes associated with gut immune activation, regulatory imbalance, and altered cathelicidin antimicrobial Peptide.

We are exposed to millions of microbial and dietary antigens via the gastrointestinal tract, which likely play a key role in type 1 diabetes (T1D). We differentiated the effects of these two major environmental factors on gut immunity and T1D. Diabetes-prone BioBreeding (BBdp) rats were housed in specific pathogen-free (SPF) or germ-free (GF) conditions and weaned onto diabetes-promoting cereal diets or a protective low-antigen hydrolyzed casein (HC) diet, and T1D incidence was monitored.

Microparticles induce cell cycle arrest through redox-sensitive processes in endothelial cells: implications in vascular senescence.

Background: Chronic disease accelerates endothelial dysfunction in aging, a process associated with cell senescence. However, the mechanisms underlying this process are unclear. We examined whether endothelial cell (EC)-derived microparticles (MPs) facilitate EC senescence and questioned the role of reactive oxygen species in this process.

A maladaptive role for EP4 receptors in podocytes.

Inhibition of p38 mitogen-activated protein kinase and cyclooxygenase-2 reduces albuminuria in models of chronic kidney disease marked by podocyte injury. Previously, we identified a feedback loop in podocytes whereby an in vitro surrogate for glomerular capillary pressure (i.e.

Mechanical stretch and prostaglandin E2 modulate critical signaling pathways in mouse podocytes.

Elevated glomerular capillary pressure (Pgc) and hyperglycemia contribute to glomerular filtration barrier injury observed in diabetic nephropathy (DN). Previous studies showed that hypertensive conditions alone or in combination with a diabetic milieu impact podocyte cellular function which results in podocyte death, detachment or hypertrophy. The present study was aimed at uncovering the initial signaling profile activated by Pgc (mimicked by in vitro mechanical stretch), hyperglycemia (high glucose (HG), 25mM d-glucose) and prostaglandin E(2) (PGE(2)) in conditionally-immortalized mouse podocytes.

PGE(2) induces COX-2 expression in podocytes via the EP(4) receptor through a PKA-independent mechanism.

Cyclooxygenase-2 (COX-2)-dependent prostaglandin E(2) (PGE(2)) synthesis correlates with the onset of proteinuria and increased glomerular capillary pressure (P(gc)) glomerular disease models. We previously showed that an in vitro surrogate for P(gc) (cyclical mechanical stretch) upregulates the expression of both COX-2 and the PGE(2) responsive E-Prostanoid receptor, EP(4) in cultured mouse podocytes. In the present study we further delineate the signaling pathways regulating podocyte COX-2 induction.