Hinged circular fixator construct for correction of congenital metatarsal deformity in a foal.

A five-week-old American Quarter Horse colt was presented for evaluation of a left hindlimb deformity and lameness. Radiographs of the left hindlimb revealed a varus deformity with recurvatum originating in the mid-diaphysis of the third metatarsal bone. Surgical correction was undertaken by performing an osteotomy through the centre of rotation of angulation located within the mid-diaphysis of the third metatarsal bone, and a four-ring hinged circular external fixator construct was applied. Distraction of the osteotomy site was performed over an 11 day period. Notable complications included failure of a fixation pin, infection of the surgical site, and temporary laxity of the supporting tendons and ligaments of the contralateral metatarsophalangeal joint. The fixator was maintained until there was sufficient bone formation to allow frame removal, 152 days after the initial surgery. Use of a hinged circular construct allowed for partial correction of the deformity with resultant lengthening and resolution of the lameness in this colt.

Mucosal injury and inflammatory cells in response to brief ischaemia and reperfusion in the equine large colon.

REASON FOR PERFORMING STUDY: Intestinal ischaemia and reperfusion (I/R) can activate inflammatory cells in the equine colon, although effects on different types of inflammatory cells have received little attention. OBJECTIVES: To assess early mucosal injury, the reaction of mucosal neutrophils, eosinophils, mast cells and macrophages, and cyclooxygenase (COX)-1 and -2 expression in response to I/R in the equine large colon. METHODS: Large colon ischaemia was induced for 1 h (1hI) followed by 4 h of reperfusion in 6 horses, and mucosal biopsies were sampled before and after ischaemia, and after 1, 2 and 4 h of reperfusion. Semithin sections (500 nm) of epon-embedded biopsies were stained with toluidine blue for histomorphometric evaluation. The number and distribution of mucosal macrophages (CD163), neutrophils (calprotectin), eosinophils (LUNA) and mast cells (toluidine blue) were determined, and mucosal COX-1 and -2 expression was identified. RESULTS: Ischaemia caused epithelial cell and nuclear swelling (mean ± s.e. nuclear width; control: 2.7 ± 0.2 µm vs. 1hI: 4.2 ± 0.2 µm; P<0.01), subepithelial oedema (control: 0.2 ± 0.1 µm vs. 1hI: 3.2 ± 0.2 µm; P<0.01) and increased epithelial apoptosis (control: 14.3 ± 4.1 apoptotic cells/mm mucosa vs. 1hI: 60.4 ± 14.0 apoptotic cells/mm mucosa; P<0.01). COX-2 expression (P<0.01) was evident after ischaemia. Reperfusion caused paracellular fluid accumulation (control: 0.9 ± 0.1 µm vs. 1hI: 0.6 ± 0.6 µm vs. 1hI + 4hR: 1.6 ± 0.2 µm; P<0.05). Epithelial repair started at 1 h of reperfusion (P<0.001), followed by migration of neutrophils into the mucosa after 2 h (control: 72.3 ± 18.4 cells/mm(2) mucosa vs. 1hI + 2hR: 1149.9 ± 220.6 cells/mm(2) mucosa; P<0.01). Mucosal eosinophils, mast cells and macrophages did not increase in numbers but were activated. CONCLUSIONS: Epithelial injury and COX-2 expression caused by short-term hypoxia were followed by intense inflammation associated with epithelial repair during reperfusion. POTENTIAL RELEVANCE: Equine colonic mucosa subjected to a brief period of ischaemia can repair during reperfusion, despite increased mucosal inflammation.

Ultrastructural changes in the equine colonic mucosa after ischaemia and reperfusion.

REASON FOR PERFORMING STUDY: Ultrastructural changes in the epithelium can provide information on early changes in barrier properties, repair and inflammation in equine colon after ischaemia and reperfusion (I/R). OBJECTIVES: To describe the morphology and ultrastructure of the epithelium in equine large colonic mucosa after I/R, and the response of inflammatory cells to injury. METHODS: Ischaemia was induced for 1 h followed by 4 h of reperfusion in a 40 cm segment of the pelvic flexure in 6 horses. Mucosal biopsies before and after ischaemia, and after 1, 2 and 4 h of reperfusion were fixed in glutaraldehyde/paraformaldehyde and osmium tetroxide, and embedded in epon. Morphological and ultrastructural changes were evaluated in toluidine blue-stained semithin sections by light microscopy and in thin sections stained with uranyl acetate/lead citrate by transmission electron microscopy. RESULTS: Ischaemia caused swelling of epithelial cells and their organelles, opening of tight junctions, detachment from the basement membrane, early apoptosis and single cell necrosis. Autophagy was a prominent feature in epithelial cells after ischaemia. Reperfusion was characterised by apoptosis, epithelial regeneration and restoration of apical cell junctions. Phagocytic-like vacuoles containing cellular debris and bacteria were evident in epithelial cells after reperfusion. Paracellular and subepithelial clefts formed, accompanied by infiltration of neutrophils, lymphocytes and eosinophils into the epithelium. Subepithelial macrophages and luminal neutrophils had increased phagocytic activity. CONCLUSIONS: Ischaemia caused ultrastructural damage to the colonic epithelium, but epithelial cells recovered during reperfusion. POTENTIAL RELEVANCE: Transmission electron microscopy can demonstrate subtle ultrastructural damage to epithelial cells and evidence of recovery after I/R in equine colon.

Industrial scale-up of countercurrent chromatography: predictive scale-up.

This study describes how scale-up in countercurrent chromatography (CCC) can be simply predicted on a process scale CCC device by running a preliminary analytical-sized sample and having knowledge of the stationary-phase retention at scale-up conditions. Results have shown that simple experimentation can lead within a day to a process with the capability of several kilograms per day (tons per year) compound yield, and that this is feasible with benchtop CCC units.

Creatine: a review of efficacy and safety.

OBJECTIVE: To provide an overview of the data on the efficacy and safety of the nutritional supplement creatine. DATA SOURCES: Human studies in English in MEDLINE, Current Contents, BIOSIS, Science Citation Index, and the popular media (including a LEXIS-NEXIS search and information from the World Wide Web and lay media) for 1966 to July 1999 using the search terms creatine, creatine supplement#, creatine monophosphate, and creatine NOT kinase. DATA SYNTHESIS: Creatine use is common among professional athletes. Its use has spread to college athletes, recreational athletes, and even children. Most creatine supplement regimens include a loading dose of 20 to 30 grams divided in 4 equal doses for 5 to 7 days, followed by a 2 gram per day maintenance dose. The increased creatine in the muscle may allow larger stores of phosphocreatine to build, and provide extra energy in the form of adenosine triphosphate. Despite the many clinical trials, high-quality research is lacking. Laboratory investigations of endurance isotonic exercises, strength and endurance during isotonic exercises, isokinetic torque, isometric force, and ergometer performance have yielded roughly an equal number of published studies showing a positive effect or lack of effect. Field studies (i.e., on subjects participating in sports activities) are less impressive than laboratory studies. Performance was more often improved for short-duration, high-intensity activities. Reports have linked creatine to weight gain, cramping, dehydration, diarrhea, and dizziness. Creatine may decrease renal function, but only two case reports of this effect have been published. Creatine appears to be well tolerated in short-term trials. CONCLUSION: While creatine may enhance the performance of high-intensity, short-duration exercise, it is not useful in endurance sports. Because commercially marketed creatine products do not meet the same quality control standards of pharmaceuticals, there is always a concern of impurities or doses higher or lower than those on the labeling. Consumers should balance the quality of information supporting the use of creatine with the known and theoretical risks of using the product, including possible renal dysfunction.

Analogues of substance P. Peptides containing D-amino acid residues in various positions of substance P and displaying agonist or receptor selective antagonist effects.

Agonist and antagonist analogues of substance P were synthesized by replacing at least two of the amino acid residues with D-Trp, D-Phe, D-Val, or D-Pro residues. The syntheses of these compounds were achieved by solid-phase methodology using the hydroxymethyl resin. The analogues were tested for agonist and antagonist activity on guinea pig ileum and rat spinal cord preparations. Two types of antagonists were obtained. The first type of compounds, e.g., [N alpha-Z-Arg1,N epsilon-Z-Lys3,D-Trp7,8,D-Met11]-SP-OMe (1), antagonized SP and SP(6-11)-hexapeptide on the ileum but only SP(6-11)-hexapeptide on the spinal cord. The second type of antagonists, e.g., [N alpha-Z-Arg1,N epsilon-Z-Lys3,D-Pro9,10]-SP-OMe (17), were inactive on the ileum but were potent antagonists of the hexapeptide on the spinal cord. Two of the antagonists, [N alpha-Z-Arg1,N epsilon-Z-Lys3,D-Trp7,8,D-Met11]-SP (3) and [D-Trp7,8,9]-SP (43), were also tested in vivo. Both of these depressed hypotensive responses to SP and SP(6-11)-hexapeptide in rabbits.

Antagonists of substance P. Further modifications of substance P antagonists obtained by replacing either positions 7, 9 or 7, 8 and 11 of SP with D-amino acid residues.

Antagonists of SP and the C-terminal (6-11)-hexapeptide have been obtained by multiple D-amino acid substitutions in various positions of SP and by protecting the N alpha-Arg1 and N epsilon Lys3 amino groups with benzyloxycarbonyl groups. On the guinea pig ileum a number of these antagonized both SP and the hexapeptide. Except [N alpha-Z-Arg1,D-Pro2,N epsilon-Z-Lys3,Asn5,Arg6,D-Phe7,D-Trp9]-SP-OMe (4) and the corresponding amide 7, which were more potent antagonists of SP than the hexapeptide, all the others, e.g., [N alpha-Z-Arg1,D-Pro2,4,N epsilon-Z-Lys3,D-Phe7,8,Sar9,D-Met11]-SP-OMe (9), [N alpha-Z-Arg1,D-Pro2,4,N epsilon-Z-Lys3,D-Phe7,8,Sar9,MeLeu10,D-Met11]-SP -OMe (11), were more potent antagonists of the hexapeptide. On the rat spinal cord preparation, most of the antagonists were only active against the hexapeptide. A few antagonized SP, but these also reduced carbachol or both carbachol and glutamate responses. Two of the antagonists, [D-Pro2,Asn5,Lys6,D-Phe7,D-Trp9]-SP-OMe (2) and [Boc-D-Pro4,D-Phe7,8,Sar9,D-Met11]-SP(4-11)-OMe (10), were inactive on the ileum but still antagonized the hexapeptide on the spinal cord. The smallest peptides to antagonize SP and the hexapeptide were two heptapeptides, 6 and 21, [Z-Asn5,Arg6,D-Phe7,8,Gly9 psi (CH2S)D-Leu10,D-Met11]-SP(5-11)-OMe (21) being more potent than 6. None of the antagonists showed significant analgesic activity without side effects. Some of the antagonists were shown to release histamine from isolated rat peritoneal cells.