Assessment of synovial fluid biomarkers in healthy foals and in foals with tarsocrural osteochondrosis.

Although alterations in biomarkers of cartilage turnover in synovial fluid (SF) have been demonstrated in horses with osteochondrosis (OC), there have been few investigations of such alterations in animals <1 year old. In this study tarsocrural SF samples from foals aged 18, 22 and 52 weeks of age were assessed for: (1) 'turnover' biomarkers of type II collagen (CPII and C2C) and proteoglycan (CS846 and glycosaminoglycans [GAG]); (2) matrix metalloproteinase (MMP) activity; (3) insulin-like growth factor (IGF)-1; (4) transforming growth factor (TGF)-ß1; (5) prostaglandin (PG) E(2); and (6) leukotriene B(4). Using a linear mixed model, the concentration of biomarkers was compared between animals that developed or did not develop radiographic evidence of OC at 24 or 48 weeks of age. The CPII:C2C ratio tended to be higher in OC-affected joints compared to controls at all ages, and this difference was statistically significant at 22 weeks of age. The concentrations of CS846 and IGF-1, and the CS846:GAG ratio were reduced in OC-affected joints relative to controls at 18 weeks of age only. At 52 weeks of age, the PGE(2) concentration was lower in joints with OC. Overall, there appears to be a consistent anabolic shift in type II collagen turnover in juvenile joints affected by OC. Aberrant proteoglycan turnover is not a hallmark of the late repair of this lesion but reduced concentrations of IGF-1 in SF may be associated with early-stage lesions.

Early changes in biomarkers of skeletal metabolism and their association to the occurrence of osteochondrosis (OC) in the horse.

REASON FOR PERFORMING STUDY: Diagnosis of osteochondrosis (OC) is based on clinical signs and radiography, but alternative methods for detection at an early stage would be useful. OBJECTIVES: To determine in the juvenile horse the relationship between serum concentrations of a number of biomarkers that reflect changes in cartilage and bone turnover and age, feeding level, growth, and the occurrence of OC. METHODS: Foals were assigned to a high (n = 20) or moderate (n = 19) feeding level group from birth to age 1 year. Bodyweight, withers height and cannon width were measured. Osteoarticular status was assessed radiographically at 5.5 and 11 months in all foals, and by necropsy at 12 months for 8 foals/group. Serum biomarkers of bone (osteocalcin, CTX-1) and cartilage (CPII, C2C) metabolism were assayed at 8 time points between ages 2 and 52 weeks. Ratios between biomarkers of tissue formation and degradation were calculated at each time point. RESULTS: Consistent age-related patterns in biomarker serum concentrates were found, indicating a markedly higher metabolism before age 20 weeks but concentrations were not affected by feeding level. Bodyweight was correlated negatively to C2C and CTX-1, and withers height was positively correlated to osteocalcin and the osteocalcin/CTX-1 and CPII/ C2C ratios. Osteocalcin concentration at 2 weeks and CPII/ C2C ratio at 20 weeks had strong positive correlations to OC, as diagnosed radiographically at 5.5 months. Osteocalcin had a strong correlation with radiographically detected OC at 11 months but at that time there was no significant relationship between CPII/C2C ratio and OC. CONCLUSIONS: Occurrence of OC lesions is significantly associated with anabolic changes in bone metabolism during the first weeks post partum, given the strong relation with osteocalcin. POTENTIAL RELEVANCE: Measuring osteocalcin concentrations during the first few weeks post partum may have potential value for the prediction of risk for OC development.

Third metacarpal bone mineral density assessment in the standing horse by dual X-ray absorptiometry: suitability, precision and accuracy.

Bone mineral density (BMD) is correlated to mechanical properties of bone. In the horse, dual energy X-ray absorptiometry (DXA) has yet only been performed ex-vivo, but a new portable DXA device would be ideal for in-vivo BMD measurement. We explored field suitability, precision and accuracy of this device for in-vivo third metacarpal density assessment. Precision was analysed by calculating measurement variation under repeated measurement tests with (reproducibility) and without (repeatability) limb repositioning. Repeatability and reproducibility were tested ex-vivo, at the same time that intra- and inter-operator reproducibility were assessed in-vivo. In order to test accuracy, bone mineral content (BMC) of several bone samples determined by DXA and ashing were compared. Repeatability was 1.47% and reproducibility 1.69% ex-vivo. In-vivo reproducibility varied between 2.91 and 4.06% for intra-operator test and between 3.13 and 5.53% for inter-operator test. BMC measured by DXA and ash weight were highly correlated (R2>0.99). In conclusion, under described conditions this DXA device is usable, accurate and precise. Its sensitiveness reaches 8.23% in an individual longitudinal monitoring. Using the third metacarpal bone as an example, we have shown that this device is suitable for experimental or clinical monitoring.

Augmented age-associated innate immune responses contribute to negative inotropic and lusitropic effects of lipopolysaccharide and interferon gamma.

Innate immunity not only mediates early host defenses to infection, but also contributes to septic hemodynamic compromise through nitric oxide synthase (NOS2) induction and inhibition of cardiovascular adrenergic responses. Because of increased age-related susceptibility to sepsis, we hypothesized that hearts from old (28-29 months) adult rats would exhibit greater beta-adrenergic hyporesponsiveness than young (6-8 months) following lipopolysaccharide (LPS, 6 mg/kg) with and without interferon gamma (INF-gamma, 5000 units). LPS/INF-gamma depressed baseline +dP/dt and isoproterenol-stimulated inotropy in both old and young hearts. beta-adrenergic inotropic (+dP/dt) and lusitropic responses were more depressed in old v young LPS/INF-gamma hearts. Additionally isoproterenol-stimulated cAMP elaboration was less in old (1950+/-160 fmol/min/g) v young (2440+/-170 fmol/min/g, P=0.05) LPS/INF-gamma hearts. LPS alone also depressed basal +dP/dt and prolonged myocardial relaxation in old and young hearts, but suppressed isoproterenol +dP/dt responses only in old hearts. Depressed beta-adrenergic inotropic responses were augmented with the selective NOS2 inhibitor N-iminoethyl-L-lysine. To establish biochemical mechanisms for this, we tested whether induction of NOS2 and innate immune system receptors (CD14 and Toll-like receptor 4, TLR4) were enhanced in old v young hearts. Induction of myocardial NOS2 and CD14 (not present in control) by LPS/INF-gamma was approximately 2-3-fold greater in old compared to young animals. TLR4 was constitutively expressed in old and young hearts and was unaffected by LPS/INF-gamma. These findings indicate that advanced age is associated with augmented cardiac beta-adrenergic depression and enhanced CD14-NOS2 signaling in response to cytokines. Upregulation of cardiovascular innate immunity may have clinical implications for increased mortality in older individuals with systemic inflammatory response syndromes.

[Inhalation of regurgitated fluid during anesthesia]. / Les inhalations per-anesthésiques de liquide régurgité.

Since the observations of HALL in 1940 and MENDELSON in 1946 numerous clinical and experimental reports have completed our knowledge of the consequences of inhalation of fluid during anesthesia. Apart from the pulmonary signs, this syndrome includes cardiovascular signs. The course of the pulmonary disease is often unfavourable. Frequently, diagnostic problems are raised a posteriori in the light of respiratory distress and abnormal pulmonary radiological signs. It is then sometimes difficult to distinguish the role of the position on the operating table, the role of massive transfusion without adequate filtration, a state of shock, or unrecognised inhalation of fluid. The various problems are exposed. The interest of prevention and treatment is discussed.