Inflammatory pain in the rabbit: a new, efficient method for measuring mechanical hyperalgesia in the hind paw.

The discovery of novel analgesic compounds that target some receptors can be challenging due to species differences in ligand pharmacology. If a putative analgesic compound has markedly lower affinity for rodent versus other mammalian orthologs of a receptor, the evaluation of antinociceptive efficacy in non-rodent species becomes necessary. Here, we describe a new, efficient method for measuring inflammation-associated nociception in conscious rabbits. An electronic von Frey device is used, consisting of a rigid plastic tip connected to a force transducer in a hand-held probe. The plastic tip is applied to the plantar surface of a hind paw with increasing force until a withdrawal response is observed. The maximum force (g) tolerated by the rabbit (i.e., withdrawal threshold) is recorded. In young, conscious rabbits (500-700 g), baseline hind paw withdrawal thresholds typically fell within the 60-80 g range. Three hours after injection of the inflammatory agent carrageenan (3%, 200 microL, intra-plantar), withdrawal thresholds dropped by approximately 30-40 g, indicating the presence of punctate mechanical hyperalgesia. The development of hyperalgesia was dose dependently prevented by the NSAID indomethacin (ED50=2.56 mg/kg, p.o.) or the bradykinin B2 receptor peptide antagonist HOE 140 (intra-paw administration). An established hyperalgesia was dose dependently reversed by morphine sulfate (ED50=0.096 mg/kg, s.c.) or the bradykinin B1 receptor peptide antagonist [des-Arg10, Leu9]-kallidin (ED50=0.45 mg/kg, s.c.). Rabbits treated with the novel B(1) receptor small molecule antagonist compound A also showed dose-dependent reversal of hyperalgesia (ED50=20.19 mg/kg, s.c.) and analysis of plasma samples taken from these rabbits showed that, unlike other rabbit pain models, the current method permits the evaluation of pharmacokinetic-pharmacodynamic (PK-PD) relationships (compound A plasma EC50=402.6 nM). We conclude that the Electrovonfrey method can be used in rabbits with inflammatory pain to generate reliable dose- and plasma concentration-effect curves for different classes of analgesics.

Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system.

BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated with naloxone. Naloxone restored the altered cellular and tissue physiology by removing beta-endorphins from specific receptors. However, this is only possible if the circulating Ca concentration is adequate. The aim of the present study was to evaluate the efficacy of parenteral naloxone administration in inducing fast mineralization and callus remodelling in a group of sheep with a standardised bone lesion. METHODS: Twenty ewes were randomly assigned to 4 treatment groups. Group A acted as control, group B received a solution of calcium gluconate, group C a solution of naloxone, and group D a solution of calcium gluconate and naloxone. A transverse hole was drilled in the left metacarpus, including both cortices, then parenteral treatment was administered intramuscularly, daily for four weeks. Healing was evaluated by weekly radiographic examination for eight weeks. For quantitative evaluation, the ratio of the radiographic bone density between the drill area and the adjacent cortical bone was calculated. After eight weeks the sheep were slaughtered and a sample of bone was collected for histopathology RESULTS: Group D showed a higher radiographic ratio than the other groups. Sheep not treated with naloxone showed a persistently lower ratio in the lateral than the medial cortex (P < 0.01). Histopathology of bone samples showed more caverns and fewer osteoblasts in group D than in the other groups (P

A rodent model of HIV protease inhibitor indinavir induced peripheral neuropathy.

HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here, we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours. After 2 intravenous injections of indinavir (50 mg/kg, 4 days apart), adult rats developed hind paw mechanical hypersensitivity, which peaked around 2 weeks post first injection (44% reduction from baseline). At this time, animals also had (1) significantly changed thigmotactic behaviour (62% reduction in central zone entries) comparing with the controls and (2) a significant reduction (45%) in hind paw intraepidermal nerve fibre density. Treatment with gabapentin, but not amitriptyline, was associated with a complete attenuation of hind paw mechanical hypersensitivity observed with indinavir treatment. Furthermore, we found a small but significant increase in microglia with the effector morphology in the lumbar spinal dorsal horn in indinavir-treated animals, coupled with significantly increased expression of phospho-p38 in microglia. In summary, we have reported neuropathic pain-related sensory and behavioural changes accompanied by a significant loss of hind paw skin sensory innervation in a rat model of indinavir-induced peripheral neuropathy that is suitable for further pathophysiological investigation and preclinical evaluation of novel analgesics.

Metastasis of renal cancer to the wrist and hand: a case report.

Metastases to the hand and wrist are rare. The lung, breast and kidneys are the most common sites of primary lesions that metastasize in the hand. Phalanges are more commonly involved than metacarpals and wrist. We report the case of a neglected, large metastatic tumour involving a patient's left wrist and metacarpus originating form renal adenocarcinoma cancer, which appeared 2 years prior to the diagnosis of the primary neoplasm. The tumour was resected, but without oncologic margins. After obtaining histological veri- 􀏐ication (clear cell renal cell carcinoma) the patient had been proposed amputation, but he refused and was given chemotherapy. Imaging towards possible other distant metastases (CT and PET scanning) was negative. At 6 months follow -up the patient showed good general condition, no local recurrence, and regained some hand function.

Effects of exogenous growth hormone on bone mineralization and remodeling and on plasma calcitriol in intact pigs.

Growing pigs were given subcutaneous (SC) injections of 40 micrograms porcine GH/kg body weight (BW) or its vehicle twice daily for 2 months. Animals were pair-fed with a diet containing 1.1% Ca, 0.6% P, and 1000 IU vitamin D3/kg. At slaughter, several bone characteristics including histomorphometric data (using double tetracycline labeling) were measured on tibia and metacarpals. GH accelerated growth, with greater (p < 0.01) tibial and metacarpal weights, greater tibial length (p < 0.01) and diameters (outside and inside, p < 0.01), and greater tibial ash weight (p < 0.02) in GH-treated pigs than in controls. The similar values of apparent bone density (weight/volume) and ash/bone volume or ash/dry matter in the two groups suggest adequate coupling between bone growth and mineralization in GH-treated pigs. Histomorphometric data for the distal metacarpal metaphysis indicated greater trabecular bone volume (p < 0.01), osteoblastic surface (p < 0.01), and mineral apposition rate (p < 0.05) in GH-treated pigs. The osteoclast surface, lacuna depth, and osteoid-related parameters in GH-treated and control pigs were similar. The plasma PTH of the two groups of pigs were similar throughout the experiment. These data and the elevated plasma alkaline phosphatase activity (p < 0.05) in GH-treated pigs suggest that GH specifically affects bone formation. GH had no effect on the plasma 25-OH vitamin D3 but 1,25(OH)2 vitamin D3 (calcitriol) was higher (p < 0.01) in treated pigs throughout the experiment. This suggests that calcitriol may help adapt bone mineralization to accelerated bone formation during growth hormone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients.

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.

Effects of experimental conditions on the release of 45calcium from prelabeled fetal mouse long bones.

Embryonic/neonatal bones in culture are commonly used for the study of osteoclastic resorption in vitro. For this purpose, the release of 45calcium (45Ca) from prelabeled bones is measured as an index of resorption. We studied 45Ca release from two types of long bone explants after different preparation methods: 17-day-old fetal mouse radii/ulnae with and without cartilage ends (intact radii/ulnae and shafts, respectively), and intact 18-day old metacarpals/metatarsals. In addition, we examined the effect of different culture conditions, such as cultures performed under the surface of the medium or at the interphase of medium and air, on 45Ca release and histology. When intact radii/ulnae were cultured under the surface of the medium, there was always a significant amount (10%) of net basal 45Ca release (corrected for physicochemical exchange) that was not due to osteoclastic resorption, as it could not be suppressed by inhibitors of resorption even at high concentrations. Moreover, histologically TRAcP-positive cells were almost absent after culture and the bone marrow/stromal cells in the center of the bone appeared necrotic, possibly due to a lack of oxygen. Under these culture conditions, osteoclasts could survive in shafts as well as in PTH-stimulated intact radii/ulnae, but a constant amount of 10% 45Ca, not due to resorption, was still released in the medium. When these explants were cultured at the interphase of medium and air, basal and stimulated 45Ca release originated from osteoclastic resorption. In contrast, in 18-day-old fetal mouse metacarpals/metatarsals, the experimental conditions applied did not affect 45Ca release, which was always due to resorption of the explants by osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between water-borne fluoride, dental fluorosis and skeletal development in 11-15 year old Tanzanian girls.

Dental fluorosis was evaluated by a classification system, previously shown to be sensitive, and skeletal changes evaluated by bone maturity and structure. Dental fluorosis was more severe in posterior than in anterior teeth in both jaws irrespective of fluoride concentration of the drinking water. There appeared to be no dependence between fluoride content of the water and skeletal maturity or structure, but there was a definite relationship between the degree of dental fluorosis and skeletal maturity within the high fluoride area. Fluoride concentrations in the drinking water above 3 parts/10(6) seemed to affect all mineralizing tissues under formation. The unique pattern of enamel formation and mineralization renders it the only hard tissue which permits an early diagnosis of the biological effect of even low fluoride doses on the human body.

Radiologic assessment of bone maturity and cortical thickness in experimental osteo-fluorosis in the young pig.

Radiographs of the left forelimb were obtained after slaughter in 16 14-month-old pigs. From age 8-14 months, eight pigs in the experimental group received 2 mg F-/kg body weight per day. Bone maturity in F-animals was the same as in controls. Cortical thickness was increased by 10 per cent in the fluorotic animals (p less than 0.01) and their plasma-fluoride levels increased throughout the experimental period to approximate those reported for man in endemic fluorosis areas. Thus fluoride given in the dose used and over that period, did not affect maturation in the long bones but increased cortical bone mass in the diaphyses.

Metacarpal bone mass in systemic lupus erythematosus.

We report the prevalence of metacarpal cortical thinning in systemic lupus erythematosus (SLE). Fifty-eight ambulant female patients attending a lupus clinic (mean age 32.4 years), were found to have significant thinning of metacarpal cortices (p < 0.05) when compared with 63 normal females (mean age 34.1 years). However, metacarpal bone mass was within the normal range. Measurements were made at 6 metacarpals of the 2 hands using a computer-aided technique (digitized radiogrammetry). Femoral cortical width and Singh index at the left femur, as well as the vertebral index at L3 were also recorded. The trabecular indices were in the range of normality, but the SLE group had more patients in the immediately pre-osteopenic range. Metacarpal bone loss was not related to disease duration or corticosteroid therapy. The prevalence of osteopenia in SLE is probably underestimated and the pathogenesis is likely to be multifactorial.

Effects of alendronate on metacarpal and lumbar bone mineral density, bone resorption, and chronic back pain in postmenopausal women with osteoporosis.

The purpose of this study was to investigate the effect of alendronate on metacarpal and lumbar bone mineral density (BMD), bone resorption, and chronic back pain in postmenopausal women with osteoporosis. Eighty postmenopausal women with osteoporosis, 59-88 years of age, were divided into two groups of 40 each according to the site of BMD measurement: the metacarpus (M) and the lumbar spine (L). All of them were treated with alendronate (5 mg/day) for 12 months. Metacarpal or lumbar BMD was measured by computed X-ray densitometry or dual-energy X-ray absorptiometry in the M or the L group, respectively, at baseline and every 6 months. Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) were measured by enzyme-linked immunosorbent assay, and chronic back pain was evaluated by face scale score at baseline and every 6 months in both groups. There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, urinary NTX level, face scale score, or number of prevalent vertebral fractures per patient between the two groups. Urinary NTX level was reduced and chronic back pain was improved similarly in both groups. Whereas metacarpal BMD did not significantly change in the M group (0.20% increase), lumbar BMD increased by 8.15% in the L group. These results suggest that although alendronate increases BMD of the lumbar spine, which is rich in cancellous bone, and improves chronic back pain, with suppression of bone resorption in postmenopausal women with osteoporosis, it may fail to increase cortical BMD of the metacarpus, a distal site of the upper extremity.

Porcine somatotropin and dietary lysine influence bone mineralization and mechanical properties of bones in finishing swine.

The femur, a rib, and a third metacarpal were collected from 108 barrows (initial weight = 57 kg) and analyzed to determine the effects of porcine somatotropin (pST) and dietary lysine on bone mineralization and mechanical properties. In Exp. 1, pigs were injected daily with 4 mg of pST and fed diets containing 1.0% Ca and .9% P and either .6, .8, 1.0, 1.2, or 1.4% lysine. Control pigs (placebo injection) received the .6% lysine diet. Bone wall thickness (BWT) of the femur increased (linear, P < .05) but ash content decreased (linear, P < .10) as dietary lysine level increased. Stress and ash content of the rib also decreased (linear, P < .05) with increasing dietary lysine level. In Exp. 2, pigs were injected with either 4 or 8 mg/d of pST and fed diets containing 1.1% Ca and 1.0% P and either .8, 1.0, 1.2, or 1.4% lysine. Control pigs received the .8% lysine diet. Increasing pST dosage increased BWT of the femur (linear, P < .10) but decreased ash content (linear, P < .10). In the rib, increasing pST dosage reduced stress, modulus of elasticity (linear, P < .10), and ash content (linear, P < .01). Increasing lysine level resulted in increased BWT of the femur and decreased ash content of rib, femur, and metacarpal (linear, P < .10). These data indicate that pST administration in conjunction with increasing lysine levels decreases bone ash content but increases BWT of finishing pigs.

Effects of testosterone on skeletal growth in lambs as assessed by labeling index of chondrocytes in the metacarpal bone growth plate.

The effects of testosterone on the epiphyseal growth plate of metacarpal bones of growing sheep were evaluated in 20 rams, 20 wethers, and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each testosterone treatment group were slaughtered at 14-d intervals from 49 to 133 d, and then at 28-d intervals until 217 d, for a total of 10 slaughter ages. Immediately after slaughter, the cannon bones were dissected of extraneous tissue, weighed, and their lengths measured. Growth plates from the metacarpal bones were isolated and explants were cultured for 24 h in medium containing [3H]thymidine. After autoradiography, labeling index was calculated as the ratio of labeled to total nuclei in the resting and proliferative zones of the growth plate. Testosterone increased (P < .03) weight and length of the metacarpal bone. Increased bone length due to testosterone was associated, in part, with a higher (P < .05) labeling index in chondrocytes of the proliferative zone of the growth plate. Labeling indices in the resting zone chondrocytes of rams were higher near the time of puberty. Accelerated growth followed by cessation of growth occurs concurrently with puberty in males of several species and is accompanied by an increase in the blood concentration of testosterone. Testosterone may mediate this accelerated growth by first increasing bone growth and then depleting the source of stem cells in the cartilage growth plate, the site where growth in length of long bones occurs.

Influence of multiple injections of vitamin E on intramuscular collagen and bone characteristics in suckling lambs.

We studied the influence of vitamin E on intramuscular collagen characteristics and on metacarpal growth plate evolution in suckling lambs. Twenty-four 5-d-old Ile de France suckling male lambs were divided into four equal weight groups, and weekly i.m. injections of DL-alpha-tocopheryl acetate (Control group, 0 IU; Group 1, 625 IU; Group 2, 1,000 IU; and Group 3, 1,500 IU) were given until the lambs were 33 d old. Blood samples were withdrawn for plasma alpha-tocopherol, cholesterol, and triglyceride analyses when the lambs were slaughtered at 40 d of age. Hot carcass weight, metacarpal and metatarsal bone characteristics, and metacarpal growth plate width were measured. After 24 h at 2 to 4 degrees C, semitendinosus muscles were removed for intramuscular collagen analyses. Weight was not influenced by treatment, but lambs in Group 1 had a higher (P < .01) intramuscular collagen content than the other groups. A positive quadratic correlation was found between total collagen and vitamin E doses (r = .511; P < .05). Amount and percentage of soluble collagen increased in muscles of all three vitamin E-treated groups compared with the control group. However, hydroxylysyl pyridinoline concentration decreased with vitamin E injection, but the difference compared to control lambs was only significant for the group injected with 1,000 IU. Amount of soluble collagen was strongly correlated to total collagen concentration (r = .879; P < .0001). It was also related to the alpha-tocopherol/(cholesterol + triglycerides) ratio in plasma (r = .431; P < .04). However, the correlation between soluble collagen percentage and alpha-tocopherol concentration in plasma was not significant (r = .369; P < .08). Bone length, weight, and diameter did not change, but the thickness of metacarpal growth plate increased as the DL-alpha-tocopheryl acetate dose increased; in Groups 2 and 3, the growth plate was significantly wider than in Group 1 and the controls. Growth plate width correlated with alpha-tocopherol/(cholesterol + triglycerides) ratio in plasma (r = .481; P < .02).

Influence of incremental zeranol implant doses on the chemical and physical characteristics of third metacarpal bone and chemical composition of liver and soft tissue from feedlot steers.

Chemical and physical characteristics of third metacarpal bones and liver and rib soft tissue composition from feedlot steers were determined. Steers were selected (32 from each experimental location) to represent the range in slaughter weight and composition for each treatment group in three (total n = 1,088) feedlot experiments. Steers were implanted with 0, 24, 36, 48, 60, 72, 84, or 96 mg of zeranol at approximately 140 d before slaughter. Cattle at each location were fed for the same number of days and slaughtered as a group. Zeranol dose had no effect on the chemical composition of bone, liver, or rib soft tissue with the following exceptions: zeranol decreased (P < .01) bone Ca concentration and increased (P < .07) liver P concentration. Zeranol implantation decreased medullary cavity anterioposterior (AP) diameters and AP cortical width (P < .08). Loads withstood by the bones up to flexure (P < .08) and the strain at flexure (P < .09) were inversely related to the quadratic of zeranol dose. However, modulus of elasticity at flexure and breaking increased numerically with zeranol dose. Stress withstood by bones at flexure was greater (P < .09) for implanted steers. Strain data indicate that metacarpals from steers receiving zeranol would exhibit less deformation upon loading to flexure (P < .09) than controls. These data indicate that administration of intermediate doses of zeranol altered bone deposition of Ca, which resulted in modified third metacarpal physical and mechanical characteristics.

Alterations in metacarpal characteristics in steers and heifers sequentially implanted with Synovex from 45 days of birth.

Forty-two heifers and 38 steers sired by either Charolais (n = 47) or Salers (n = 33) from Bos indicus x Hereford dams were used to determine the effects of an anabolic agent on metacarpal characteristics and accompanying weight gain and carcass characteristics. Calves were blocked by sex and sire breed and either not implanted or implanted with Synovex-C within 45 d of birth, and with Synovex-S or -H at weaning and 84 and 169 d postweaning. Calves grazed oat pastures immediately after weaning for 169 d, after which calves received a feedlot diet for 124 d and were slaughtered. Live weight and hip height were recorded at initial implanting, weaning, d 84 and d 169 postweaning, and at approximately 28-d intervals during the feedlot period. Metacarpal and carcass characteristics were determined after slaughter. Metacarpals from implanted calves had greater medio-lateral axis (P < .01), cortical areas (P < .05), and cross-sectional areas (P < .05) and tended to have a greater breaking load (P < .08) than bones from nonimplanted calves. Implanted steers had shorter (P < .05) metacarpals than nonimplanted steers. Implanted calves had a greater (P < .05) ADG to weaning and over the postweaning grazing and feedlot periods than control calves. The implant did not alter backfat thickness but decreased (P < .05) percentage of kidney, pelvic, and heart fat and quality grade and tended (P < .07) to improve yield grade in heifers, but not in steers. Implanted calves tended (P < .08) to have a lower marbling score.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone ossification and carcass characteristics of wethers given silastic implants containing estradiol.

Administration of growth promotants with estrogenic activity via hastening closure of the growth plate could have an economic impact on lambs because closure results in ovine carcasses being classified as yearlings. Twelve wether lambs approximately 12 mo old were given silastic implants filled with estradiol-17 beta and allotted randomly to be slaughtered 30, 60, 90, or 220 d after implantation to determine time of growth plate closure in relation to date of implanting. Seven comparable wethers not implanted served as controls. Four wethers implanted at 2 mo of age and slaughtered 220 d later also were included. Implanted wethers had serum concentrations of estradiol averaging 13.9 pg/ml over the 220-d implant period; controls averaged 2.7 pg/ml. Estradiol implants increased carcass maturity scores but fat deposition was not altered. Growth plate widths decreased (P less than .05) as wethers grew older and implants were in place for longer periods of time. Metacarpal growth plates in 12-mo-old lambs were completely ossified 220 d after implanting, but control wethers and wethers implanted at 2 mo maintained growth plate widths. Neither metacarpal nor metatarsal bone lengths differed (P less than .05) between control and implanted wethers. Growth plate ossification was not complete until 570 d of age in implanted lambs, even though bone length had stopped increasing by 408 d. Therefore, even though estradiol and other growth stimulants with estrogenic activity increase rate of ossification of the metacarpal growth plate, bone length or mature size is not limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of zeranol and two dietary levels of calcium and phosphorus on performance, carcass and bone characteristics, and calcium status in growing lambs.

Seventy-two crossbred wether lambs (average initial weight, 25.1 kg) were used to determine the interaction between zeranol treatment and two dietary levels of Ca and P (.8 and .6% vs .4 and .3% Ca and P, respectively) in a 2 x 2 factorial arrangement on performance, carcass and bone characteristics, and serum concentrations of parathyroid hormone (PTH) and Ca. Lambs were implanted on d 0 and 56 with 12 mg of zeranol. Lambs had ad libitum access to feed for 105 d. On d 99, blood samples were collected. Implanted lambs had 12% greater (P less than .01) daily feed intake, 26% greater (P less than .10) ADG, and a 12% improvement in (P less than .10) feed efficiency compared with nonimplanted lambs. Zeranol-treated lambs had increased (P less than .05) bone cortical area, breaking load, and width of the metacarpal compared with nonimplanted lambs. Lambs fed the .8% Ca and .6% P diet had a higher (P less than .05) percentage of bone ash than lambs fed the .4% Ca and .3% P diet. However, there were no differences (P greater than .05) in the percentage of Ca, P, Mg, or Zn in metacarpal bones due either to higher dietary Ca and P or to implant treatments. Serum concentration of PTH was greater (P less than .10) in lambs fed .8% Ca and .6% P than in those receiving .4% Ca and .3% P. Serum concentrations of PTH and Ca pooled across treatments were greater (P less than .05) before feeding than at 1 h after feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital metacarpal fusion associated with polydactyly.

A case of congenital fusion of metacarpal bones with polydactyly is reported. The fusion occurred between the proximal parts of the third and the fourth metacarpal bones. The same type of anomaly was induced in rat fetuses by oral administration of myleran. The anomalies for which the critical period is the same as both metacarpal fusion and polydactyly, were analysed. From the results of the experimental study, the authors propose that the cause of the metacarpal fusion associated with polydactyly is the combination of a disorder of ectoderm-mesoderm interaction and a deficit of mesenchymal cells in the limb bud.

Effect of Clostridium botulinum toxin type A injections into the deep digital flexor muscle on the range of motion of the metacarpus and carpus, and the force distribution underneath the hooves, of sound horses at the walk.

In the treatment of laminitis, reducing deep digital flexor muscle (DDFM) activity might diminish its pull on the distal phalanx, thereby preventing displacement and providing pain relief. Injection of Clostridium botulinum toxin type A into the DDFM of horses is potentially therapeutic. However, the effects of C. botulinum toxin type A on the gait characteristics of sound horses at the walk are not known. The aim of this study was to test if a reduced DDFM activity would lead to (1) alterations of the sagittal range of motion of the metacarpus (SROM) and range of motion of the carpal joint (CROM); (2) changes in the force distribution underneath the hoof (toe vs. heel region: balance index); and (3) changes in the force distribution between the treated and untreated limb (symmetry index). The DDFMs of the left forelimbs of seven sound Royal Dutch Sport Horses were injected with 200 IU C. botulinum toxin type A using electromyography and ultrasound guidance. Measurements using an inertial sensor system and dynamically calibrated pressure plate were performed before and after injections. The SROM and CROM of the treated limb were significantly increased after C. botulinum toxin type A injections. No significant changes were detected in the balance index or in the symmetry index, indicating that no lameness was induced. C. botulinum toxin type A injections into the DDFM of sound horses do not appear to result in substantial gait alterations at the walk.