Abstract: The stimuli that elicit thirst were studied in four ponies. Nineteen hours of water deprivation produced an increase in plasma protein from 67 +/- 0.1 g/litre to 72 +/- 2 g/litre, a mean (+/- se) increase in plasma sodium from 139 +/- 3 to 145 +/- 2 mmol/litre and an increase in plasma osmolality from 297 +/- 1 to 306 +/- 2 mosmol/litre. Undeprived ponies drank 1.5 +/- 0.9 kg/30 mins; 19 h deprived ponies drank 10.2 +/- 2.5 kg/30 mins and corrected the deficits in plasma protein, plasma sodium and plasma osmolality as well as compensating for the water they would have drunk during the deprivation period. In order to determine if an increase in plasma osmolality would stimulate thirst, 250 ml of 15 per cent sodium chloride was infused intravenously. The ponies drank when osmolality increased 3 per cent and when plasma sodium rose from 136 +/- 3 mmol/litre to 143 +/- 3 mmol/litre. Ponies infused with 15 per cent sodium chloride drank 2.9 +/- 0.7 kg; those infused with 0.9 per cent sodium chloride drank 0.7 +/- 0.5 kg. In order to determine if a decrease in plasma volume would stimulate thirst, ponies were injected with 1 or 2 mg/kg bodyweight (bwt) frusemide. Plasma protein rose from 68 +/- 2 g/litre pre-injection to 75 +/- 2 g/litre 1 h after 1 mg/kg bwt frusemide and to 81 +/- 1 g/litre 1 h after 2 mg/kg bwt frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 microM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 microM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation.

Abstract: REASONS FOR PERFORMING STUDY: There has been no large study of horses with suspected sacroiliac (SI) joint region pain in which the clinical diagnosis has been supported by either abnormal radiopharmaceutical activity in the SI joint region or by periarticular infiltration of local anaesthetic solution. OBJECTIVES: To describe the clinical features of horses with SI joint region pain, to document the age, breed, sex, discipline, size and conformation of affected horses and to compare these with the author's (SD) normal case population and to document the results of infiltration of local anaesthetic solution around the SI joint region. METHODS: Horses were selected for inclusion in the study based upon the exclusion of other causes of lameness or poor performance, together with clinical signs suggestive of SI joint pain and abnormal radiopharmaceutical activity in the SI joint region and/or a positive response to periarticular infiltration of local anaesthetic solution. RESULTS: Sacroiliac joint region disease was identified in 74 horses between November 1997 and March 2002. Dressage and showjumping horses appeared to be at particular risk (P < 0.001). Affected horses were generally slightly older than the normal clinic population (P < 0.0001), taller at the withers (P < 0.0001) and of greater bodyweight (P < 0.01). There was a significant effect of breed (P < 0.001), with a substantially higher proportion of Warmblood horses (51%) in the SI pain group compared to the normal clinic population (29%). There was no correlation between conformation and the presence of SI joint region pain. The tubera sacrale appeared grossly symmetrical in most (95%) horses. Poor development of the epaxial muscles in the thoracolumbar region and asymmetry of the hindquarter musculature were common. Twenty-six horses (35%) showed restricted flexibility of the thoracolumbar region and 10 (16%) had an exaggerated response to pressure applied over the tubera sacrale. Fourteen horses (19%) were reluctant to stand on one hindlimb for prolonged periods. The majority of horses (75%) had a straight hindlimb flight and only 18% moved closely behind or plaited. In all horses restricted hindlimb impulsion was the predominant feature; invariably this was most obvious when the horse was ridden. Stiffness, unwillingness to work on the bit and poor quality canter were common. Sacroiliac joint region pain was seen alone (47%), or in conjunction with thoracolumbar pain (16%), hindlimb lameness (20%), forelimb lameness (7%) or a combination of problems (10%). Seventy-three horses (99%) had abnormalities of the SI joint region identified using nuclear scintigraphy. Infiltration of local anaesthetic solution around the SI joint region produced profound improvement in gait in all 34 horses in which it was performed. CONCLUSIONS AND POTENTIAL RELEVANCE: Careful clinical examination combined with scintigraphic evaluation of the SI joint region and local analgesia can enable a more definitive diagnosis of SI joint region pain than has previously been possible.

Abstract: REASONS FOR PERFORMING STUDY: There is limited knowledge available of factors influencing response to treatments of the DIP-joint in horses with lameness responding to diagnostic analgesia of the DIP-joint. For this reason a multivariable statistical analysis was performed. HYPOTHESIS: Horses with lameness reduced by > or = 75% 10 min after intra-articular analgesia of the DIP-joint, can be treated successfully by intra-articular medication of the joint. Multiple factors influence the response to treatment. METHODS: The study was performed retrospectively based on clinical records of horses treated with either polysulphated glycosaminoglycan (PSGAG) or methylprednisolone acetate (MPA) in the DIP-joint between January 1996 and January 2003. Information was collected from clinical records and from the owners of the horses via a detailed questionnaire, in which they described their perception of the outcome a minimum of one year after treatment. Allocation of the horses to the 2 treatment groups was done mainly because of a change in treatment policy. In Regime A all horses received 3 intra-articular injections of PSGAG approximately 8 days apart, whereas in Regime B all horses received a single intra-articular injection of MPA as a first treatment. If the horse did not improve sufficiently to return to work by 4 weeks, a series of 3 intra-articular PSGAG injections was administered. RESULTS: Of the horses receiving Regime A, 67% had a successful outcome, compared with 46% of the group receiving Regime B. A significantly better result was obtained in dressage horses than in jumping horses (eventing and showjumping). Other variables such as age, duration of lameness, distribution of lameness, degree of lameness, response to DIP-joint analgesia and radiographic observations were also associated with success of treatment. CONCLUSIONS AND POTENTIAL RELEVANCE: There is a rationale for using either PSGAG or MPA intra-articularly in the treatment of lameness, reduced > or = 75% within 10 min of analgesia of the DIP-joint.