Carpal joint injuries in cats - an epidemiological study.

OBJECTIVE: Injuries of the carpal joint are rare in cats. The most common cause is a fall from a height, known as 'high-rise syndrome'. So far, only limited data about carpal joint injuries (CJI) in cats are available. The aim of this study was to investigate the epidemiology, aetiology, location, and type of CJI in cats. METHODS: Case records of cats diagnosed with CJI between 1998 and 2010 were retrospectively analysed. Data concerning signalment, history and type of CJI, accompanying systemic injuries and further orthopaedic injuries were collected. RESULTS: During the study period, 73 cats were diagnosed with CJI (87 injured carpal joints) and the prevalence in our hospital population was 0.26% (73 out of  28,482). Cats with CJI were more likely to be presented in the period from April-October (85%, p = 0.003) compared with the rest of the year. Carpal joint injuries were caused by a fall from a height in 72.6% of the cases. Of all carpal joints, the antebrachiocarpal joint was predominantly injured (50.6%, p = 0.001) and this was commonly caused by a fall from the fourth floor or higher (p = 0.002). The carpometacarpal joint was predominantly affected by a fall from heights up to the third floor (p = 0.004). CLINICAL SIGNIFICANCE: The data of this study confirm previous data with respect to time of occurrence and cause of injury. Of note, the height of the fall appears to influence the location of the injury within the carpus of cats.

Intraosseous lipoma in the ulna and radius of a two-year-old Leonberger.

This report describes a case of intraosseous lipoma in a two-year-old Leonberger. The dog was presented with a history of ten month lameness in the right forelimb. A massive swelling from the elbow to the carpus of the right forelimb was visible. Treatment with anti-inflammatory medications by the local veterinarian for ten months was unsuccessful and the dog was presented at the university clinic. Radiographic images showed that the diaphyseal part of the ulna was affected by extensive cyst-like osteolysis. Furthermore, the distal metaphysis of the radius showed cyst-like osteolytic changes. The soft-tissue mass and parts of the ulna periosteum were surgically resected. Histopathological analysis of the mass in combination with clinical, surgical and radiographic findings was diagnostic for an intraosseous lipoma. The dog had a good long-term outcome as it was free of any signs of recurrence at the follow-up examinations performed after 18 months and after five years. To the authors' knowledge, this is the first description of intraosseous lipoma in a dog.

Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina.

AIMS/HYPOTHESIS: Diabetic retinopathy is the result of increased oxidative and nitrosative stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia. Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of diabetic complications and on pericyte loss in the diabetic retina. METHODS: We administered epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body weight once weekly or 128 IU/kg body weight three times a week. The treatment lasted for 3 months. Oxidative stress and formation of AGEs were assessed by immunoblotting, expression of Ang-2 (also known as Angpt2) by RT-PCR, activation of protein kinase B (AKT) and heat shock protein (HSP)-27 levels by immunofluorescence, and incipient retinal vascular changes by quantitative morphometry of retinal digest preparations. RESULTS: Diabetes increased variables of oxidative stress and nitrosative stress (N(epsilon)-carboxymethyl-lysine, nitrotyrosine and methylglyoxal-type AGEs) in retina, kidney and heart of diabetic rats. Epoetin delta reduced oxidative and nitrosative stress in all tissues, and AGEs in the retina. It also reduced increased retinal Ang-2 expression and pericyte loss, and ameliorated p-AKT and HSP-27 levels. CONCLUSIONS/INTERPRETATION: Epoetin delta has antioxidative properties in organs affected by diabetes and may prevent incipient microvascular damage in the diabetic retina.

Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy.

AIMS/HYPOTHESIS: Hyperglycaemia-induced mitochondrial overproduction of reactive oxygen species (ROS) is central to the pathogenesis of endothelial damage in diabetes. R-(+)-alpha-lipoic acid has advantages over classic antioxidants, as it distributes to the mitochondria, is regenerated by glycolytic flux, and has a low redox potential. METHODS: To assess the effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy, three groups of male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats treated with 60 mg/kg bodyweight R-(+)-alpha-lipoic acid i.p. for 30 weeks. Quantitative retinal morphometry included acellular occluded capillaries and pericyte numbers. The effects of R-(+)-alpha-lipoic acid on parameters of oxidative and nitrative stress, AGE and its receptor and nuclear factor kappa B (NFkappaB) were assessed by immunoblotting, and NFkappaB activation by electrophoretic mobility shift assay. Angiopoietin-2 and vascular endothelial growth factors were also determined by immunoblotting. RESULTS: After 30 weeks of diabetes, the number of acellular capillaries was significantly elevated in diabetic rats (57.1+/-10.6 acellular capillary segments [ac]/mm(2) of retinal area) compared with non-diabetic (19.8+/-5.1 ac/mm(2); p<0.001). Treatment with 60 mg/kg R-(+)-alpha-lipoic acid reduced the numbers by 88% (p<0.001 vs diabetic). Pericyte loss was also significantly inhibited in diabetic rats treated with R-(+)-alpha-lipoic acid (non-diabetic: 1,940+/-137 pericytes/mm(2)capillary area; untreated diabetic: 1,294+/-94 pericytes/mm(2)capillary area vs treated diabetic: 1,656+/-134 pericytes/mm(2); p<0.01). R-(+)-alpha-lipoic acid treatment reduced oxidative stress, normalised NFkappaB activation and angiopoietin-2 expression, and reduced vascular endothelial growth factor in the diabetic retina by 43% (p<0.0001). CONCLUSIONS/INTERPRETATION: R-(+)-alpha-lipoic acid prevents microvascular damage through normalised pathways downstream of mitochondrial overproduction of ROS, and preserves pericyte coverage of retinal capillaries, which may provide additional endothelial protection.

Early loss of arteriolar smooth muscle cells: more than just a pericyte loss in diabetic retinopathy.

Incipient diabetic retinopathy is characterized by increased capillary permeability and progressive capillary occlusion. The earliest structural change is the loss of pericytes (PC) from the retinal capillaries. With the availability of the XLacZ mouse, which expresses the LacZ reporter in a PC/vascular smooth muscle cell (vSMC) specific fashion, we quantitatively assessed the temporal dynamics of smooth muscle cells in arterioles under hyperglycemic conditions. We induced stable hyperglycemia in XLacZ mice. After 4, 8, and 12 weeks of diabetes retinae were isolated and beta-galactosidase/lectin stained. The numbers of smooth muscle cells were counted in retinal whole mounts, and diameters of retinal radial and branching arterioles and venules were analyzed at different distances apart from the center of the retina. After eight weeks of diabetes, the numbers of vSMCs were significantly reduced in radial arterioles 1000 microm distant from the optic disc. At proximal sites of branching arterioles (400 microm distant from the center), and at distal sites (1000 microm), vSMC were significantly reduced already after 4 weeks (to a maximum of 31 %). These changes were not associated with any measurable variation in vessel diameters. These data indicate quantitatively that hyperglycemia not only causes pericyte loss, but also loss of vSMCs in the retinal vasculature. Our data suggest that arteriolar vSMC in the eye underlie similar regulations which induce early pericyte loss in the diabetic retina.

Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity.

Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.