Diagnostic utility and validity of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase activity in horses with colic.

Little is known about the clinical usefulness in horses of the 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, a biomarker used in other species for the detection of pancreatitis. The main objectives of this study were to evaluate the prevalence of increased DGGR-lipase activity in horses with signs of colic and investigate its association with, and validity to diagnose, underlying gastrointestinal diseases, treatment method (medical or surgical), and outcome (survival or non-survival). Clinical data from 192 horses presented for colic to a teaching hospital were analysed retrospectively. DGGR-lipase activity was measured in frozen plasma collected within 24 h of presentation. Non-parametric tests and Chi-squared or Fisher's exact tests were used to evaluate differences and associations between DGGR-lipase activity and continuous and categorical variables or outcomes, respectively. Measures of the validity of DGGR-lipase as a diagnostic test were also calculated. Increased DGGR-lipase activity above published reference limits was demonstrated in 30.2% of horses with signs of colic, and was above 2x the upper reference limit (URL) in 15.6%. The median DGGR-lipase activity in horses with large bowel displacement or torsion was significantly higher than the median activity for large bowel impaction and for gastric impaction, dilation, or ulceration. DGGR-lipase activity > 2x URL was significantly associated with surgical treatment, strangulating disease, and non-survival. However, as a diagnostic or screening test for these target outcomes, DGGR-lipase activity was poor to fair consequent to poor sensitivity, poor negative likelihood ratio, and an area under the receiver operating characteristic curve, with optimal cut-offs based on the Youden Index, within reference limits.

Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity.

BACKGROUND: Genetic and epidemiologic evidence suggests that in horses, as in other species, different manifestations of hypersensitivity may occur together. HYPOTHESIS: Horses affected with insect bite hypersensitivity (IBH) show airway hyperreactivity (AH) to inhaled histamine, even in the absence of overt clinical signs of equine asthma (EA). ANIMALS: Twenty-two healthy controls (group C), 24 horses suffering from IBH alone (group IBH), and 23 horses suffering from IBH and EA (group IBH/EA). METHODS: The clinical histories were assessed using 2 standardized questionnaires, the Horse Owner Assessed Respiratory Signs Index (HOARSI), and IBH scoring. Horses were classified as EA-affected if their HOARSI was >1 and as IBH-affected if IBH score was >0. Confounding disorders were excluded by clinical examination. The arterial partial pressure of oxygen (PaO2 ) was measured and flowmetric plethysmography used to assess airway reactivity to increasing doses of inhaled histamine. RESULTS: The median histamine provocation concentration (PC) when ∆flow values increased by 35% (PC35) was significantly higher in group C (5.94 [1.11-26.33] mg/mL) compared to group IBH (2.95 [0.23-10.13] mg/mL) and group IBH/EA (2.03 [0.43-10.94] mg/mL; P < 0.01). The PC50 and PC75 showed very similar differences between groups. Furthermore, PaO2 was significantly lower in group IBH (84 ± 8 mmHg) and group IBH/EA (78 ± 11 mmHg) compared to group C (89 ± 6 mmHg; P < 0.01). CONCLUSIONS AND CLINICAL IMPORTANCE: IBH is associated with AH and decreased PaO2 , even in the absence of overt respiratory clinical signs.

Owner-reported coughing and nasal discharge are associated with clinical findings, arterial oxygen tension, mucus score and bronchoprovocation in horses with recurrent airway obstruction in a field setting.

REASONS FOR PERFORMING STUDY: In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO). OBJECTIVES: To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions. STUDY DESIGN: Cross-sectional study comparing healthy and RAO-affected horses. METHODS: Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing frequency' and 'nasal discharge'. Differences between these groups were examined using clinical examination, blood gas analyses, endoscopic mucus scores, cytology of tracheobronchial secretion and bronchoalveolar lavage fluid, and airway hyperresponsiveness determined by plethysmography with histamine bronchoprovocation. RESULTS: Frequently coughing horses differed most markedly from healthy control animals. Histamine bronchoprovocation-derived parameters were significantly different between the healthy control group and all RAO groups. Mucus grades and tracheobronchial secretion and bronchoalveolar lavage fluid neutrophil percentages had particularly high variability, with overlap of findings between groups. Owner satisfaction with the clinical status of the horse was high, even in severely affected horses. CONCLUSIONS: Owner-reported coughing and nasal discharge are associated with specific clinical and diagnostic findings in RAO-affected horses in field settings. While airway hyperresponsiveness differentiates best between healthy horses and asymptomatic RAO-affected horses, the absence of coughing and nasal discharge does not rule out significant neutrophilic airway inflammation. Owner satisfaction with the clinical status of the horse was uninformative.

[Symptoms and pathophysiological mechanisms of neuropathic pain syndromes]. / Symptome und pathophysiologische Mechanismen neuropathischer Schmerzsyndrome.

Neuropathic pain, caused by various central and peripheral nerve disorders, is especially problematic because of its severity, chronicity, and resistance to simple analgesics. Pathophysiologic changes responsible for generating pain following nerve lesions are usually independent of the etiology of the primary neuronal damage. Several fundamental mechanisms could be identified as principle conditions in the development of neuropathic pain; they include peripheral and central sensitization, disinhibition, sympathetically maintained pain, and cortical reorganization. Classifying neuropathic pain by these basic mechanisms is considered appropriate for basing new treatment approaches. In coming years, several advances are expected in the basic and clinical sciences of neuropathic pain which will provide new and improved therapies for patients continuing to experience this sometimes very disabling condition.

Up-regulation of cyclooxygenase-1 in neuroblastoma cell lines by retinoic acid and corticosteroids.

Cyclooxygenases-1 and -2 are both expressed in neuronal cells in vivo. In the neuroblastoma cell lines NG108 and N2a, however, only cyclooxygenase-1 was detectable. Differentiation of the cells with retinoic acid increased cyclooxygenase-1 mRNA and protein expression within 24 and 48 h, respectively. A further increase was observed when the cells were concomitantly treated with the glucocorticoid dexamethasone (a 2-3-fold increase compared with retinoic acid alone). In the absence of retinoic acid, dexamethasone only slightly up-regulated cyclooxygenase-1 expression. The inhibitor of protein synthesis cycloheximide abrogated the effect of dexamethasone, indicating the involvement of newly synthesised proteins. Retinoic acid increased the transcription of cyclooxygenase-1 mRNA, determined with a luciferase-coupled promoter construct. Dexamethasone only slightly augmented cyclooxygenase-1-promoter activity but increased cyclooxygenase-1 mRNA stability. Other corticosteroids, hydrocortisone and aldosterone, also up-regulated cyclooxygenase-1 whereas neurosteroids or oestrogen were ineffective. Up-regulation was mediated primarily by the glucocorticoid receptor, because the receptor antagonist RU486 strongly reduced the effects of all corticosteroids. This indicated that in NG108 cells, the mineralocorticoid aldosterone may bind to the glucocorticoid receptor. Treatment of NG108 or N2a cells with corticosteroids did not alter the morphological phenotype obtained during differentiation. We thus show that corticosteroids, which down-regulate cyclooxygenase expression in most cell types, up-regulate cyclooxygenase-1 during neuronal differentiation.

A new synthesis of chlorins.

A new synthesis of chlorins has been developed, based upon the acid-catalyzed condensation of dialdehydes AB with dipyrromethanes CD.

mRNA cloning and expression studies of the quail homologue of HIF-2alpha.

Hypoxia inducible factors (HIF) are candidate transcriptional regulators of vascular development. Unlike HIF-1alpha - the founding member of the HIF family - which is expressed more or less ubiquitously, HIF-2alpha (also called HRF, HLF and EPAS1) is highly expressed by vascular endothelial cells and was shown to activate the transcription of endothelial cell-specific receptor tyrosine kinases (tie-2 and flk-1/VEGF receptor 2) and of vascular endothelial growth factor (VEGF). Therefore HIF-2alpha is a candidate dual regulator of vascular development. Here we describe the quail homologue of HIF-2alpha. Sequence analysis reveals that HIF-2alpha is highly conserved between birds and mammals. Like the murine HIF-2alpha, the quail molecule is highly expressed by endothelial cells but also detectable in certain epithelial cells such as in the endoderm.