Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific

Performing heritage: the use of live 'actors' in heritage presentations

This paper investigates the phenomenon of 'living history' presentations of heritage, using live 'actors' to portray historical characters. Its aim is to discuss these presentations in the context of what may be understood as 'heritage', and of the nature of 'performance'. Four case studies of heritage sites, each important as a tourist attraction, have been selected for detailed study, together with a number of other examples of heritage performance. It is clear from the empirical work that different performance strategies are employed within the heritage industry and by individual 'actors'. Most of the performers take part as a leisure activity, and many do not consider themselves to be 'performing' at all. The greatest concern of participants lies in the degree of authenticity of the performance. Through 'living history', the 'actors' are drawn into an experience of heritage which has real meaning for them, and which may contribute both to a sense of identity and to an enhanced understanding of society, past and present. The popularity of such presentations with visitors also indicates that similar benefits are perceived by the 'audience'

Health-related quality of life following surgical attenuation of congenital portosystemic shunts versus a healthy control population of dogs

OBJECTIVES: To design a health-related quality of life questionnaire for dogs with congenital portosystemic shunts, use it in a cohort of dogs treated with suture attenuation and compare results with those obtained from a healthy control cohort. MATERIALS AND METHODS: Data were collected from the hospital records of dogs treated with suture ligation of an intrahepatic or extrahepatic congenital portosystemic shunt at two referral centres. Owners were asked to complete a questionnaire assessing their dog's health-related quality of life preoperatively (retrospectively) and at the time of follow-up. Owners of control dogs also completed the questionnaire. RESULTS: One hundred and twenty-eight dogs with congenital portosystemic shunts and 131 control dogs were recruited. Median follow-up time was 64 months (range 19.7 to 157.2). The median long-term health-related quality of life score was excellent for both intrahepatic and extrahepatic shunt cases and similar to that of control dogs. The long-term portosystemic shunt clinical sign scores for both intrahepatic and extrahepatic congenital portosystemic shunt dogs were significantly worse than the those of the control group. CLINICAL SIGNIFICANCE: Suture attenuation of congenitial portosystemic shunts is associated with an excellent health-related quality of life score at long-term follow-up

Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs

Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Western men and Eastern arts: The significance of Eastern martial arts disciplines in British men's narratives of masculinity

Previous Western sociological research on Eastern martial arts has identified a tension between ‘traditional’ Eastern forms of practice and ‘modernized’ Western methods of training and competition. In particular, the ‘sportization’ of Eastern styles, where combat-centred arts based upon moral philosophies have transformed more or less into competitive activities following Western models of rationalized sport, has been an important theme. However, it is also suggested that Eastern martial arts hold special significance in the West for their seemingly esoteric nature. In this regard, such martial arts are considered significant because they are not ‘sports’, but rather disciplines, with fairly different connotations for practitioners. Drawing on interview data, this paper explores how Western practitioners of Eastern martial arts articulate this difference, principally by examining the place of martial artistry in British men's narratives of masculinity. Comparing themselves favourably to assumed, typical visions of Western sporting masculinity, such men draw upon the imagined uniqueness of their martial arts to construct a sense of moral superiority over other men. In so doing, they contribute to a rejection of what they believe to be ‘mainstream’ sporting Western masculinity, thus indicating the role that ‘alternative’ visions of physical culture can play in men's active constructions of gender

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells.

C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established