Vascular endothelial growth factor concentrations in the cerebrospinal fluid of dogs with neoplastic or inflammatory central nervous system disorders.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key molecular driver of angiogenesis and vascular permeability and is expressed by a wide variety of neoplasms. Although blood VEGF concentrations have been quantified in intracranial tumors of dogs, cerebrospinal fluid (CSF) VEGF concentration might be a more sensitive biomarker of disease. OBJECTIVE: Concentrations of VEGF in CSF are higher in dogs with central nervous system (CNS) neoplasia compared to those with meningoencephalomyelitis and other neurologic disorders. ANIMALS: One hundred and twenty-six client-owned dogs presented to a veterinary teaching hospital. METHODS: Case-control study. Cerebrospinal fluid was archived from dogs diagnosed with CNS neoplasia and meningoencephalomyelitis. Control dogs had other neurological disorders or diseases outside of the CNS. A commercially available kit was used to determine VEGF concentrations. RESULTS: Detectable CSF VEGF concentrations were present in 49/63 (77.8%) neoplastic samples, 22/24 (91.7%) inflammatory samples, and 8/39 (20.5%) control samples. The VEGF concentrations were significantly different between groups (P < .0001), and multiple comparison testing showed that both neoplastic and inflammatory groups had significantly higher concentrations than did controls (P < .05), but did not differ from each other. Gliomas and choroid plexus tumors had significantly higher VEGF concentrations than did the control group (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid VEGF concentrations may serve as a marker of neoplastic and inflammatory CNS disorders relative to other conditions.

The cutaneous trunci muscle reflex: a predictor of recovery in dogs with acute thoracolumbar myelopathies caused by intervertebral disc extrusions.

OBJECTIVE: To determine whether changes in the cutaneous trunci muscle (CTM) reflex are an early predictor of outcome in dogs with severe acute thoracolumbar intervertebral disc extrusion (IVDE). STUDY DESIGN: Multicenter prospective cohort study. ANIMALS: Dogs (n = 36) with acute IVDE causing paraplegia, loss of nociception in pelvic limbs and tail, and an abnormal CTM reflex postoperatively. METHODS: The caudal border of the CTM reflex was established 24 hours after surgery and at discharge, and was reported as moving cranially, caudally, or staying static. Dogs were re-evaluated at 12-20 weeks and at 7-36 months postoperatively. Outcome was classified as improved or unimproved, successful or unsuccessful, and ascending myelomalacia or not, and compared with early movement of the CTM reflex by construction of contingency tables and performing a Fisher's exact test. RESULTS: By discharge (mean, 4.7 days; SD = 2.10), CTM reflex progression was caudal in 19 dogs, static in 11, and cranial in 6. Five of 6 dogs with cranial movement developed ascending myelomalacia (P < .0001). Seventeen of 19 dogs with caudal movement showed an improvement by 12-20 weeks (P = .0046) and none developed ascending myelomalacia (P = .0013). CONCLUSIONS: Postoperative changes of the caudal border of the CTM reflex are an early indicator of outcome in dogs with severe acute IVDE. Cranial movement of the CTM reflex is significantly associated with the development of ascending myelomalacia. Caudal movement is significantly associated with improvement, but not associated with a long-term successful outcome.

The sensory field and repeatability of the cutaneous trunci muscle reflex of the dog.

OBJECTIVE: To describe the cutaneous trunci muscle (CTM) reflex in dogs. STUDY DESIGN: Prospective descriptive study. ANIMALS: Normal dogs (n = 155) and 10 dogs with thoracolumbar myelopathies. METHODS: The CTM reflex caudal border was assessed from the ilial crests moving cranially until a CTM contraction was elicited. The lateral borders were evaluated at 4 levels and the distance from the midline to the lateral border was expressed asa percentage of the trunk hemicircumference. The caudal border was assessed in 10 dogs with myelopathies by 4 different observers and by 1 observer on 3 occasions;the inter- and intraobserver kappa coefficient was calculated. RESULTS: The CTM reflex was elicited in all dogs. Its caudal border was at L5 or L6 in 153 dogs and at L1 and L3 in 2 dogs. The lateral field of the reflex occupied>50%of the hemicircumference of the trunk at each level tested. The mean difference in measurement of the reflex caudal border was 0.55 cm between observers and 0.28 cm for the same observer. The inter- and intraobserver kappa coefficient was 0.67 and 0.87, respectively. CONCLUSIONS: The CTM reflex is elicited caudal to L5 in most normal dogs, and the lateral sensory field extends to 50% or more of the circumference of the trunk.Inter- and intraobserver differences in assessment of the caudal border are low.

The vitamin K-dependent gamma-glutamyl carboxylase gene contains a TATA-less promoter with a novel upstream regulatory element.

The expression of the vitamin K-dependent gamma-glutamyl carboxylase gene in liver is developmentally regulated. Since the gene product catalyzes an essential post-translational modification of the vitamin K-dependent blood coagulation proteins, the regulation of carboxylase expression is critical for hemostasis. We analyzed the activity of the rat carboxylase gene 5'-regulatory DNA sequences in rat hepatoma cell lines at different states of differentiation. These studies demonstrated that the 2.6-kb 5'-flanking sequence has differentiation-dependent transcriptional activity. Transient gene expression assays, examining the effects of nested deletions and site-directed mutagenesis of putative regulatory sequences, together with electrophoretic mobility shift assays (EMSAs) were used to identify sequences critical for the developmentally regulated transcription of the rat carboxylase gene. We identified a DNA sequence (-76 to -65; GTTCCGGCCTTC) not known to bind to transcription factors, yet which functions as an upstream promoter element. In vivo genomic DNA footprinting confirms the presence of nuclear protein-DNA interactions at this site in the endogenous carboxylase gene in differentiated hepatoma cells. Therefore, this DNA sequence has specific nuclear protein-binding activity and functional properties consistent with a regulatory element that plays a critical role in the developmental expression of the carboxylase gene, and hence the regulation of vitamin K-dependent blood coagulation protein synthesis.