Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris

Objective: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). Methods: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. Results: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p,0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p,0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p,0.01. Conclusion: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that th

Horseshoe characteristics as possible risk factors for fatal musculoskeletal injury of Thoroughbred racehorses

abstract: 201 Thoroughbred racehorses that died or were killed at California race-tracks between August 1992 and July 1994 were examined PM. Shoe characteristics were compared between case horses affected by fatal musculoskeletal injury (FMI, 155 horses), suspensory apparatus failure (SAF, 79), and cannon bone condylar fracture (CDY, 41) and 46 control horses that died for reasons unrelated to the appendicular musculoskeletal system. Multivariable logistic regression was used to estimate odds ratios for FMI, SAF and CDY. Toe grabs were identified as possible risk factors for FMI, SAF and CDY. The odds of FMI, SAF and CDY were 1.8, 6.5 and 7.0, respectively, times greater for horses shod with low toe grabs than for horses shod without toe grabs on front shoes. Horses shod with regular toe grabs on front shoes had odds 3.5, 15.6 and 17.1 times greater for FMI, SAF and CDY, respectively, compared with horses shod without toe grabs. The odds of horses shod with rim shoes were a third of those shod without rim shoes for either FMI or SAF. It is suggested that the apparent association between toe grab type and CDY may, in part, be attributable to concurrent SAF and CDY injuries in many horses. It is concluded that avoiding the use of toe grabs should decrease the incidence of FMI, especially SAF, in Thoroughbred racehorses

Postmortem evaluation of homotypic variation in shoe characteristics of 201 Thoroughbred racehorses

abstract: Shoe characteristics of Thoroughbred racehorses that died or were killed at California race-tracks between August 1992 and July 1994 were measured. Percentage of agreement was used to compare shoe characteristics between limbs. Using χ² analysis, shoe characteristics were compared between horses grouped by age and sex. Toe grabs were present on 90.5% of horses, and rim shoes were present on 15.9% of horses. Heel traction devices were less frequent on front (2.5%) than rear (6%) hooves. Pads were present on 24.9% of horses, with bonded rim pads commonest. Special types of shoes were present on 5% of horses. Percentage of agreement between left and right front hooves and between left and right rear hooves was high (20/25 variables; % agreement ≥99). In contrast, percentage of agreement between left front and left rear hooves and between right front and right rear hooves was low (2/25 variables; % agreement ≥99). Presence of a pad was significantly associated with age, and several shoe variables (size, presence of a special shoe, overall wear matched) were significantly associated with sex

Association between long periods without high-speed workouts and risk of complete humeral or pelvic fracture in Thoroughbred racehorses: 54 cases (1991-1994)

abstract: Thoroughbred racehorses in California that were destroyed because of a complete humeral or pelvic fracture were investigated to determine whether a two-month or longer period without official high-speed workouts (lay-up) is associated with humeral or pelvic fracture. Age, sex, activity, number of lay-ups, number of days from a race or official timed workout to fracture, number of days from end of last lay-up to fracture, mean duration of lay-ups, and total number of days in race training were compared between horses with humeral fractures and horses with pelvic fractures. A case-crossover study was used to estimate relative risk for fracture of the humerus or pelvis occurring within hazard periods of 10 and 21 days following lay-up, compared with periods following more regular participation in official racing or timed workout events. Horses with pelvic fractures were more often female, older, and had 0 or ≥ 2 lay-ups. Horses with humeral fractures were typically 3-year-old males that had 1 lay-up. Horses with pelvic fractures had more total days in race training, fewer days from last exercise event to fracture, and a greater number of days from end of last lay-up to fracture than horses with humeral fractures. Return from lay-up was strongly associated with risk for humeral fracture during hazard periods of 10 and 21 days (relative risk = 71 and 45, respectively). Risk of humeral fracture may be reduced if horses are cautiously reintroduced into race training after lay-up

Sensitivity and specificity of western blot testing of cerebrospinal fluid and serum for diagnosis of equine protozoal myeloencephalitis in horses with and without neurologic abnormalities

abstract: Objective - To determine sensitivity and specificity of western blot testing (WBT) of CSF and serum for diagnosis of equine protozoal myeloencephalitis (EPM) in horses with and without neurologic abnormalities. Design - Prospective investigation. Animals - 65 horses with and 169 horses without neurologic abnormalities. Procedure - CSF and serum from horses submitted for necropsy were tested for Sarcocystis neurona-specific antibody with a WBT. Results of postmortem examination were used as the gold standard against which results of the WBT were compared. Results - Sensitivity of WBT of CSF was 87% for horses with and 88% for horses without neurologic abnormalities. Specificity of WBT of CSF was 44% for horses with and 60% for horses without neurologic abnormalities. Regardless of whether horses did or did not have neurologic abnormalities, sensitivity and specificity of WBT of serum were not significantly different from values for WBT of CSF. Ninety-four horses without EPM had histologic evidence of slight CNS inflammation. Conclusions and Clinical Relevance - The low specificity of WBT of CSF indicated that it is inappropriate to diagnose EPM on the basis of a positive test result alone because of the possibility of false-positive test results. The high sensitivity, however, means that a negative result is useful in ruling out EPM. There was no advantage in testing CSF versus serum in horses without neurologic abnormalities. Slight CNS inflammation was common in horses with and without S. neurona-specific antibodies in the CSF and should not be considered an indication of CNS infection with S. neurona

Fatal musculoskeletal injuries incurred during racing and training in Thoroughbreds

abstract: Review of PM records from Thoroughbred racehorses that sustained a fatal, exercise-related injury at a California race track during a 9-month period in 1991 revealed that 79 horses had a fatal musculoskeletal injury (FMI) while racing, with an incidence risk of 1.7/1000 race entrants. While training, 71 horses incurred an FMI. Age and sex distributions of California race entrants during the same period depended on race track. Males were at twice the risk for sustaining an FMI while racing compared with females, and 4-years olds were at twice the risk compared with 3-year-olds. These findings suggested that differences in fatal injury rates among race tracks may be attributable in part to differences in entrants' age and sex distribution among race tracks

Relationship between race start characteristics and risk of catastrophic injury in Thoroughbreds: 78 cases (1992)

abstract: A retrospective longitudinal study was carried out of 25 male and 53 female Thoroughbreds that incurred catastrophic musculoskeletal injury (CMI) during racing which resulted in them being killed, and all California race entrants in 1992. PM examination records were reviewed, and race start information was obtained. Incidence risk of CMI was 1.7/1000 entrants. A higher risk of CMI was found at 2 race-meets with fair conditions, with incidence risks of 4.9 and 5.5/1000 entrants. Risk of injury in male horses was 1.7 times greater than that in female horses, and influence of age on risk depended on race type. Risk of injury for horses 2 to 5 years old was 2 times greater for claiming horses than for maiden horses. Race length or racing surface type (dirt vs turf) or condition (fast, muddy, yielding) were not significantly associated with risk of CMI. It is suggested that researchers should consider controlling for age and sex, race-meet and race type whenever possible in studies of risk of CMI

Hoof size, shape, and balance as possible risk factors for catastrophic musculoskeletal injury of Thoroughbred racehorses

abstract: 95 Thoroughbred racehorses that died between 1994 and 1996 examined through the California Horse Racing Board Postmortem Program were used in this investigation. 38 quantitative measures of hoof size, shape and balance were obtained from orthogonal digital images of the hoof and were compared between case horses with forelimb catastrophic musculoskeletal injuries (CMI, 70 animals), suspensory apparatus failure (SAF, 43), and cannon bone condylar fracture (CDY, 10) injuries and control horses whose death was unrelated to the musculoskeletal system (non-CMI, 25). Comparison of group means between cases and controls was done using ANOVA and multivariable logistic regression was used to estimate odds ratios. Odds of CMI were 0.62 times lower for a 5-mm increase in ground surface width difference and 0.49 times lower for a 100-mm² increase in sole area difference. Odds of SAF were 6.75 times greater with a 10° increase in toe-heel angle difference and 0.58 times lower with a 100-mm² increase in sole area difference. Odds of CDY were 0.26 times lower with a 3° increase in toe angle, 0.15 times lower with a 5-mm increase in lateral ground surface width, and 0.35 times lower with a 100-mm² increase in sole area difference. It is suggested that decreasing the difference between toe and heel angles should decrease risk of SAF for Thoroughbred racehorses and should be considered in addition to increasing toe angle alone to help prevent catastrophic injury. It is added that trimming the hoof to perfect mediolateral symmetry may not be a sound approach to avoiding injury