In Vivo confocal endomicroscopy of small intestinal mucosal morphology in dogs

Background: Confocal endomicroscopy (CEM) is an endoscopic technology that permits in vivo cellular and subcellular imaging of the gastrointestinal mucosa. Objective: To determine the feasibility of CEM to evaluate small intestinal mucosal topologic morphology in dogs and to characterize the appearance in healthy dogs. Animals: Fourteen clinically healthy research colony dogs. Methods: Experimental study. Dogs were anesthetized for standard endoscopic evaluation of the small intestine followed by CEM. Two fluorophores were used to provide contrast: fluorescein (10% solution, 15 mg/kg IV) before administration of topical acriflavine (0.05% solution) via an endoscopy spray catheter. A minimum of 5 sites within the small intestine were assessed and at each location, sequential adjustment of imaging depth allowed collection of a three-dimensional volume equivalent to an 'optical biopsy'. CEM-guided pinch biopsies were obtained for histologic examination. Results: CEM provided high-quality in vivo cellular and subcellular images. Intravenous administration of fluorescein provided sufficient contrast to allow assessment of the vasculature, cellular cytoplasmic features and goblet cell numbers, and distribution. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing evaluation of nuclear morphology. Quality of captured images was occasionally affected by motion artifact, but improved with operator experience. Conclusion and Clinical Importance: CEM provides in vivo images that allow for cellular and subcellular assessment of intestinal mucosal morphology during endoscopy. This has implications for aiding in vivo diagnosis of gastrointestinal disease. \ua9 2013 by the American College of Veterinary Internal Medicine

Break-taking behaviour pattern of long-distance freight vehicles based on GPS trajectory data

This paper focuses on the break-taking behaviour pattern of long-distance freight vehicles, providing a new perspective on the study of behaviour patterns and simultaneously providing a reference for transport management departments and related enterprises. Based on Global Positioning System (GPS) trajectory data, we select stopping points as break-taking sites of long-distance freight vehicles and then classify the stopping points into three different classes based on the break-taking duration. We then explore the relationship of the distribution of the break-taking frequency between the three single classifications and their combinations, on the basis of the break-taking duration distribution. We find that the combination is a Gaussian distribution when each of the three individual classes is a Gaussian distribution, contrasting with the power-law distribution of the break-taking duration. Then we experimental analysis the distribution of the break-taking durations and frequencies, and find that, for the durations, the three single classifications can be fitted individually by an Exponential distribution and together by a Power-law distribution, for the frequencies, both the three single classifications and together can be fitted by a Gaussian distribution,so that can validate the above theoretical analysis. Key words: break-taking behaviour, long-distance freight vehicle, statistical analysi

Ti alloy with enhanced machinability in UAT turning

Metastable β-titanium alloys such as Ti 15V 3Al 3Cr 3Sn are of great technological interest thanks to their high fatigue strength-to-density ratio. However, their high hardness and poor machinability increase machining costs. Additionally, formation of undesirable long chips increases the machining time. To address those issues, a metastable β-titanium alloy (Ti 15V 3Al 3Cr 2Zr 0.9La) with enhanced machinability was developed to produce short chips even at low cutting speeds. A hybrid ultrasonically assisted machining technique, known to reduce cutting forces, was employed in this study. Cutting force components and surface quality of the finished work-pieces were analyzed for a range of cutting speeds in comparison with those for more traditional Ti 15V 3Al 3Cr 3Sn. The novel alloy demonstrated slightly improved machining characteristics at higher cutting speeds and is now ready for industrial applications

Assessment of molecular signalling mechanisms for eosinophilia in rottweilers

Rottweilers are predisposed to eosinophilic diseases, including hypereosinophilic syndrome. The immunopathogenesis of idiopathic eosinophilia is poorly characterised in dogs and man. Studies in people have suggested cytokines, particularly interleukin (IL)-5, play a role in instigating and perpetuating eosinophilia. This study sought to establish whether differences in gene expression, and concentration of selected, cytokines and chemokines were associated with eosinophilia in Rottweilers. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assays were used to quantify messenger ribonucleic acid (mRNA) encoding cytokines IL-4, -5, -10, -12p19, -12p35, -12p40, -18, interferon gamma (IFN-γ) and chemokines eotaxin-2 and -3 from peripheral blood mononuclear cell (PMBC) samples obtained from healthy dogs (breeds other than Rottweiler) with normal eosinophil blood counts (n = 5) and Rottweilers with normal (n = 6), mildly increased (n = 7) and high (n = 3) eosinophil blood counts. Quantification of plasma IFN-γ and IL-5 was performed using commercially available canine-specific enzyme-linked immunosorbent assays ELISAs. Cytokine mRNA was measurable in all samples, although eotaxin-2 and -3 were not detected. No significant differences in gene expression of any cytokine were found between groups (based on eosinophil count or breed). No significant difference in plasma IL-5 or IFN-γ concentration was present between groups. In conclusion, there were no significant differences in cytokine mRNA profiles or plasma IL-5 and IFN-γ levels between Rottweilers with increased eosinophil counts and Rottweiler and non-Rottweiler dogs with normal eosinophil counts

Gastrokine mRNA expression in gastric tissue from dogs with helicobacter colonisation but without inflammatory change during treatment

Gastrokines (GKNs) are bioactive substances secreted by gastric cells. Evidence supports functional roles for GKNs in gastric homeostasis, immune responses and tumour suppression. Down-regulation has been reported in Helicobacter pylori associated gastritis and other inflammatory gastrointestinal conditions in mice and people. The aim of this study was to evaluate GKN gene expression in dogs positive for other Helicobacter spp. both before and after treatment. Expression of Gkn-1 and Gkn-2 mRNA was studied in endoscopic biopsy samples collected from seven healthy dogs over three time-points pre- (T0) and at 1 and 18 weeks post-treatment for Helicobacter spp. colonisation (T1 & T2). The relative expression software tool (REST) was used to provide efficiency corrected expression ratios for comparisons between groups and these results were compared to a standard 2\u394\u394CT methodology. Compared with T1 Gkn1 and Gkn2 mRNA expression was greater at T0 by a mean factor of 2.53 (SE\ua0=\ua01.83\u20133.54) for Gkn1 (P\ua0=\ua00.000) and 2.85 (SE\ua0=\ua02.23\u20133.75) for Gkn2 (P\ua0=\ua00.000). This difference was attenuated when comparisons were made between T0 and T2. Histopathological evidence of gastritis was not present in any Helicobacter spp. positive sample. When compared to post-eradication samples Gkn gene expression is increased in the presence of Helicobacter spp. in dogs without evidence for concurrent inflammation. Further evaluation is required to determine the relevance of this finding, however given a suspected role in gastric homeostasis, up-regulation of GKN1 and GKN2 could limit development of gastritis in Helicobacter spp. positive dogs

Vascular hamartoma in the oesophagus of a dog

A four-and-a-half-year-old male, neutered mixed-breed dog presented for evaluation of lethargy, melaena and haematemesis. Haematologic examination showed a severe regenerative, normocytic, hypochromic anaemia and mild hypoproteinaemia. Endoscopic assessment showed a dark red, raised irregular mass in the distal oesophagus. Computed tomographic angiography showed a non-contrast enhancing, ovoid soft tissue mass located between the aorta and the oesophagus without evidence of oesophageal varices. Supportive care was provided but the dog was euthanised five days later due to recurrent oesophageal bleeding. Necropsy confirmed the lesion in the distal oesophagus. Histologic examination showed a mass with large, multifocal, submucosal and subserosal, well-organized and well-differentiated vascular channels. The vascular channels were distended by numerous red cells and thrombi, consistent with a vascular hamartoma. A hamartoma is defined as an excessive but focal, monoclonal proliferation of cells and tissues native to the organ in which it occurs. Vascular hamartoma should be considered as a differential diagnoses for a space occupying lesion of the gastrointestinal tract or as a cause of repeated gastrointestinal blood loss

Association of von Willebrand factor blood levels with exercise hypertension

Purpose A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices. Methods Sixty-four participants (57 ± 10 years, 71 % male) with indication for exercise stress testing underwent cardiovascular assessment at rest and during moderate intensity exercise, from which 20 participants developed an HRE (defined as moderate exercise systolic BP ≥170 mmHg/men and ≥160 mmHg/women). Rest, exercise and post-exercise blood samples were analysed for haemostatic markers, including von Willebrand factor (vWf), and haemodynamic measures of brachial and central blood pressure (BP), aortic stiffness and systemic vascular resistance index (SVRi). Results HRE participants had higher rest vWf compared with normotensive response to exercise (NRE) participants (1,927 mU/mL, 95 % CI 1,240–2,615, vs. 1,129 mU/mL, 95 % CI 871–1,386; p = 0.016). vWf levels significantly decreased from rest to post-exercise in HRE participants (p = 0.005), whereas vWf levels significantly increased from rest to exercise in NRE participants (p = 0.030). HRE participants also had increased triglycerides, rest BP, aortic stiffness and exercise SVRi (p < 0.05 for all). Rest vWf predicted exercise brachial systolic BP (β = 0.220, p = 0.043; adjusted R 2 = 0.451, p < 0.001) independent of age, sex, body mass index, triglycerides, rest brachial systolic BP and aortic stiffness. Conclusions Increased rest blood levels of vWf are independently associated with moderate intensity exercise systolic BP. These findings implicate abnormalities in haemostasis as a possible factor contributing to HRE at moderate intensity

Spironolactone reduces aortic stiffness via blood pressure-dependent effects of canrenoate

Spironolactone is thought to improve aortic stiffness via blood pressure (BP) independent (antifibrotic) effects, but the exact mechanism is unknown. We used metabolomics and hemodynamic measures to reveal the underlying actions of spironolactone in people with a hypertensive response to exercise (HRE). Baseline and follow-up serum samples from 115 participants randomized to 3 months spironolactone (25 mg/day) or placebo were analysed using liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy. Hemodynamic measures recorded at baseline and follow-up included aortic pulse wave velocity (stiffness) and 24 h ambulatory BP. Aortic stiffness was significantly reduced by spironolactone compared with placebo (−0.18 ± 0.17 vs 0.30 ± 0.16 m/s; p 0.05 for all). However, the spironolactone metabolite canrenoate was associated with the change in daytime systolic BP (r = −0.355, p = 0.017) and 24 h pulse pressure (r = −0.332, p = 0.026). This remained highly significant on multiple regression and was independent of age, body mass index and sex. Canrenoate appears to be an active metabolite with BP-dependent effects on the attenuation of aortic stiffness in people with HRE. This finding, together with the lack of change in endogenous metabolites, suggests that the antifibrotic effects of spironolactone could be BP-dependent

Serum metabolic profile predicts adverse central haemodynamics in patients with type 2 diabetes mellitus

Aims People with type 2 diabetes mellitus (T2DM) have abnormal peripheral and central haemodynamics at rest and during exercise, probably due to metabolic perturbations, but mechanisms are unknown. We used untargeted metabolomics to determine the relationships between metabolic perturbations and haemodynamics (peripheral and central) measured at rest and during exercise. Methods Serum samples from 39 participants with T2DM (62 ± 9 years; 46 % male) and 39 controls (52 ± 10 years; 51 % male) were analysed by liquid chromatography–mass spectrometry, nuclear magnetic resonance spectroscopy and principal component analysis. Scores on principal components (PC) were used to assess relationships with haemodynamics including peripheral and central BP, central augmentation index (AIx) and central augmentation pressure (AP). Results Participants with T2DM had higher resting and exercise haemodynamics (peripheral and central BP, central AIx and central AP) compared to controls (p < 0.05). PC that comprised of a signature metabolic pattern of T2DM was independently associated with resting and exercise central AIx and central AP (p < 0.05). Conclusions Serum metabolic profile was associated with central, but not peripheral, haemodynamics in T2DM participants, suggesting that metabolic irregularities may explain abnormal central haemodynamics in T2DM patients