SeedStor: A Germplasm Information Management System and Public Database.

SeedStor (https://www.seedstor.ac.uk) acts as the publicly available database for the seed collections held by the Germplasm Resources Unit (GRU) based at the John Innes Centre, Norwich, UK. The GRU is a national capability supported by the Biotechnology and Biological Sciences Research Council (BBSRC). The GRU curates germplasm collections of a range of temperate cereal, legume and Brassica crops and their associated wild relatives, as well as precise genetic stocks, near-isogenic lines and mapping populations. With >35,000 accessions, the GRU forms part of the UK's plant conservation contribution to the Multilateral System (MLS) of the International Treaty for Plant Genetic Resources for Food and Agriculture (ITPGRFA) for wheat, barley, oat and pea. SeedStor is a fully searchable system that allows our various collections to be browsed species by species through to complicated multipart phenotype criteria-driven queries. The results from these searches can be downloaded for later analysis or used to order germplasm via our shopping cart. The user community for SeedStor is the plant science research community, plant breeders, specialist growers, hobby farmers and amateur gardeners, and educationalists. Furthermore, SeedStor is much more than a database; it has been developed to act internally as a Germplasm Information Management System that allows team members to track and process germplasm requests, determine regeneration priorities, handle cost recovery and Material Transfer Agreement paperwork, manage the Seed Store holdings and easily report on a wide range of the aforementioned tasks.

Short, natural, and extended photoperiod response in BC2F4 lines of bread wheat with different photoperiod-1 (Ppd-1) alleles.

Flowering is a critical period in the life cycle of flowering plant species, resulting in an irreversible commitment of significant resources. Wheat is photoperiod sensitive, flowering only when daylength surpasses a critical length; however, photoperiod insensitivity (PI) has been selected by plant breeders for >40 years to enhance yield in certain environments. Control of flowering time has been greatly facilitated by the development of molecular markers for the Photoperiod-1 (Ppd-1) homeoloci, on the group 2 chromosomes. In the current study, an allelic series of BC2F4 lines in the winter wheat cultivars 'Robigus' and 'Alchemy' was developed to elucidate the influence on flowering of eight gene variants from the B- and D-genomes of bread wheat and the A-genome of durum wheat. Allele effects were tested in short, natural, and extended photoperiods in the field and controlled environments. Across genetic background and treatment, the D-genome PI allele, Ppd-D1a, had a more potent effect on reducing flowering time than Ppd-B1a. However, there was significant donor allele effect for both Ppd-D1a and Ppd-B1a, suggesting the presence of linked modifier genes and/or additional sources of latent sensitivity. Development of Ppd-A1a BC2F4 lines derived from synthetic hexaploid wheat provided an opportunity to compare directly the flowering time effect of the A-genome allele from durum with the B- and D-genome variants from bread wheat for the first time. Analyses indicated that the reducing effect of Ppd-A1a is comparable with that of Ppd-D1a, confirming it as a useful alternative source of PI.

Repair of sheep long bone cortical defects filled with COLLOSS, COLLOSS E, OSSAPLAST, and fresh iliac crest autograft.

COLLOSS and COLLOSS E are osteoinductive bone void fillers consisting of bone collagen and noncollagenous proteins from bovine and equine bone, respectively. The aim of this study was to compare COLLOSS, COLLOSS E, iliac bone autograft, sintered beta tricalcium phosphate (beta-TCP; OSSAPLAST), and COLLOSS E plus OSSAPLAST. Materials were placed for 4, 8, or 24 weeks in 5-mm cortical bone defects in sheep long bones. Histological sections in a plane perpendicular to the long axis of the bone were used to measure the total repair area (original defect plus callus) and the area of bone within the total repair area. The incidence of defect union was also evaluated. At 4 and 8 weeks, defects treated with COLLOSS and COLLOSS E with or without OSSAPLAST had total repair and bone areas equivalent to autograft, and larger than OSSAPLAST-treated defects. At 8 weeks, the incidence of defect union was higher in defects treated with autograft or COLLOSS E plus OSSAPLAST than in untreated defects. At 24 weeks, the incidence of union was 100% in all treatment groups and 0% in untreated defects. The incidence of union was related to the degree of remodeling between 8 and 24 weeks. This was greater in all treated than nontreated defects. In conclusion, COLLOSS and COLLOSS E were equivalent to each other and to autograft, and superior to beta-TCP, in this study model.

A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant's efficacy for bone regeneration. The biomaterial carriers were a 'putty' carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to "ungrafted" negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

Long-term ovariectomy decreases ovine compact bone viscoelasticity.

Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low-amplitude 3-point bending at frequencies of 1-20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tandelta, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tandelta at low (6-12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long-term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA).

In vivo healing after capsular plication in an ovine shoulder model.

Traditionally, arthroscopic management of shoulder instability has been reserved for patients with isolated Bankart lesions without any capsular laxity or injury. To date, there are no animal studies evaluating the healing potential of capsular plication and/or capsulo-labral repair. The purpose of this in vivo animal study was to determine if the histological capsular healing of an open capsular plication simulating an arthroscopic plication is equivalent to the more traditional open capsular shift involving cutting and advancing the capsule. Twenty-six skeletally mature sheep were randomized to either an open capsular plication simulating arthroscopic plication (n = 13), or an open traditional capsular shift (n = 13). A sham operation (n = 4) was also performed involving exposure to visualize the capsule. Normal non-operated control shoulders were also analyzed. A pathologist blinded to the treatment evaluated both hematoxylin and eosin (H&E) sections and polarized light microscopy. Qualitative scoring evaluated fibrosis, mucinous degeneration, fat necrosis, granuloma formation, vascularity, inflammatory infiltrate and hemosiderin (0 to 3 points). Both the capsular plication and open shift groups demonstrated healing by fibrosis at the site of surgical manipulation. There were no statistical differences in the capsular healing responses between the two groups with regard to fibrosis, granuloma formation and vascularity. The open shift group demonstrated significantly more mucinous degeneration (p = 0.038). Fat necrosis was present in 4/13 specimens in the open shift group and none in the capsular plication specimens. Both groups demonstrated disorganized collagen formation under polarized light microscopy. There were no differences between non-operated control specimens and sham surgery specimens. Our findings support the hypothesis that histologic capsular healing is equivalent between the plication group and the open shift group. In addition, the open shift group demonstrated significantly more changes indicative of tissue injury. This basic science model confirms capsular healing after simulated arthroscopic plication, providing support for arthroscopic capsular plication in practice.

The potential of sheep for the study of osteopenia: current status and comparison with other animal models.

There is a great need to develop an animal model for postmenopausal osteoporosis; a model that will be useful for the understanding of the pathogenesis of the disease as well as the investigation of new therapies. The requirements for such an animal model are discussed and ones that have been used in the past include nonhuman primates, dogs, cats, rodents, rabbits, guinea pigs, and minipigs. Advantages and disadvantages of these models are briefly reviewed. Sheep are a promising model for various reasons; they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and have hormone profiles similar to women. Ovariectomy results in a slight loss of bone from the ovine iliac crest, and biochemical markers such as osteocalcin are well characterized. Physiological disadvantages are lack of natural menopause, that normal estrus cycles are restricted to fall and winter and that they have a different gastrointestinal system. Sheep have cortical bone that is plexiform in structure although haversian remodeling is seen in older animals. When and if biomechanical incompetence of bone follows ovariectomy is presently unknown. There is no ideal model for the study of postmenopausal osteoporosis; all have advantages and disadvantages. Researchers in this field must recognize the limitations of the model they choose, and select one that will fulfill their needs.

Dual-energy X-ray absorptiometry in sheep: experiences with in vivo and ex vivo studies.

As different large animal models of osteopenia and osteoporosis are explored, the use of DXA to rapidly, non-invasively and accurately estimate BMD will become widespread. We used DXA in live sheep and cadaveric material and the areas of trabecular bone that are most accessible on a simple, repeatable basis in the sheep were the lumbar vertebrae (L4-L6/L5-L7), the CAL and the DR. We performed dual-energy X-ray absorptiometry (DXA) using an Hologic QDR 1000-W bone densitometer to measure bone mineral density (BMD) at various regions of interest in anesthetized sheep and cadaveric specimens of sheep. In vivo measurements of L4-L6/L5-L7, the calcaneus (CAL) and distal radius (DR) in 48 intact 3 to 5-year-old ewes (same breed) were performed. Correlations between the different bones were investigated. In an in vivo precision study, BMD of L3-L6/L7, CAL and DR was determined with one animal repositioned between 10 scans of each bone. In another study, ex-vivo BMD measurements of the proximal and distal femur, proximal tibia, and proximal humerus were performed on isolated bones of 45 ewes of similar age. Excised vertebrae were scanned on the Hologic QDR 1000-W and on a Lunar DPX (at another site) and the data were compared. Correlations of BMD between individual vertebrae in anesthetized sheep were excellent (r = 0.944- 0.843; P < 0.0001). Correlation between BMD of individual vertebrae and CAL was good (r = 0.677-0.630), while correlation between BMD of individual vertebrae and DR was also good (r = 0.551-0.507; P < .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in bone mineral density and bone-specific alkaline phosphatase in ovariectomized ewes.

An animal model of human osteoporosis which adequately meets many of the criteria needed to test new therapeutic agents is currently unavailable. The old ewe may serve this purpose, as changes in bone remodeling occur within 3 months, and a difference in bone mass has been indicated 6 months after ovariectomy. In the current study, we have measured longitudinal changes in bone mass and bone-specific alkaline phosphatase (BSAP) for six months in 7-9 year old ovariectomized (OVX) ewes. Thirty ewes were divided into three groups: sham-treated (n = 9), OVX (n = 12) and OVX with estrogen implants (OVXE, n = 9). Bone mineral density (BMD) was determined at 0, 3 and 6 months in the vertebrae (L4-L6/L5-L7), calcaneus (CAL) and distal radius (DR) using dual-energy X-ray absorptiometry (DEXA). Bone-Specific Alkaline Phosphatase (Tandem-R Ostase; Hybritech) was determined at monthly intervals. Body weight did not significantly change in any group during treatment compared to sham, although a trend of increasing body weight at 3 and 6 months was apparent in both OVX groups. Luteinizing hormone increased in all OVX ewes as a function of time as expected, demonstrating successful ovariectomies. Uterine weight was significantly increased (p < 0.01) in the OVXE animals compared to Sham and OVX groups. BMD did not change significantly during the 6-month treatment period in the CAL or DR. BMD in the vertebrae (L4-L6/L5-L7) was significantly lower in the OVX group compared to sham (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response effects of estradiol implants on bone mineral density in ovariectomized ewes.

In a longitudinal in vivo study, we studied the effect of two different doses of 17 beta-estradiol (E2) administered in the form of a subcutaneous implant, on bone mineral density (BMD) of the lumbar vertebrae (L4, L5, L4-L6/L5-L7), the calcaneus (CAL) and the distal radius (DR) in ovariectomized (OVX) ewes. The BMD of various regions of the femur, tibia and humerus were studied at autopsy. Skeletally mature ewes (n = 45) were divided into four groups: sham operated (n = 12), OVX (n = 15), OVX plus one E2 implant (OVXE, n = 12) and OVX plus two E2 implants (OVX2E, n = 6). BMD of L4, L5, L4-L6/L5-L7, CAL and DR was determined at 0, 6 and 12 months using dual-energy X-ray absorptiometry. In-vivo precision of BMD for the last three lumbar vertebrae ranged from 1.4-4.3%, and 1.5% and 3.5% for CAL and DR respectively. In the in vivo study, there were no significant changes in the mean BMD in the sham group at any time point (each group served as its own control). In the OVX group, mean BMD was significantly lower at L5 and DR at 6 months and significantly lower at L4 at 12 months. In the OVXE group, the mean BMD was significantly higher at L5, CAL and DR at 12 months. In the OVX2E group, BMD was significantly higher at CAL but significantly lower at L4 at 12 months. None of the treatments produced significant changes of mean BMD of L4-L6/L5-L7 at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone.

Departing from the premise that it is the large-amplitude signals inherent to intense functional activity that define bone morphology, we propose that it is the far lower magnitude, high-frequency mechanical signals that continually barrage the skeleton during longer term activities such as standing, which regulate skeletal architecture. To examine this hypothesis, we proposed that brief exposure to slight elevations in these endogenous mechanical signals would suffice to increase bone mass in those bones subject to the stimulus. This was tested by exposing the hind limbs of adult female sheep (n = 9) to 20 min/day of low-level (0.3g), high-frequency (30 Hz) mechanical signals, sufficient to induce a peak of approximately 5 microstrain (micro epsilon) in the tibia. Following euthanasia, peripheral quantitative computed tomography (pQCT) was used to segregate the cortical shell from the trabecular envelope of the proximal femur, revealing a 34.2% increase in bone density in the experimental animals as compared with controls (p = 0.01). Histomorphometric examination of the femur supported these density measurements, with bone volume per total volume increasing by 32% (p = 0.04). This density increase was achieved by two separate strategies: trabecular spacing decreased by 36.1% (p = 0.02), whereas trabecular number increased by 45.6% (p = 0.01), indicating the formation of cancellous bone de novo. There were no significant differences in the radii of animals subject to the stimulus, indicating that the adaptive response was local rather than systemic. The anabolic potential of the signal was evident only in trabecular bone, and there were no differences, as measured by any assay, in the cortical bone. These data suggest that subtle mechanical signals generated during predominant activities such as posture may be potent determinants of skeletal morphology. Given that these strain levels are three orders of magnitude below strains that can damage bone tissue, we believe that a noninvasive stimulus based on this sensitivity has potential for treating skeletal complications such as osteoporosis.

Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

In search of an animal model for postmenopausal diseases.

The purpose of this review is to discuss the use of the aged ovariectomized ewe as a cost-effective large animal model to study coronary artery disease (CAD), osteoporosis, osteoarthritis (OA), and oral bone loss--conditions seen after menopause. Earlier studies from our laboratory showed a significant decline in the bone mineral density (BMD) of the iliac crest following ovariectomy in sheep, while subsequent studies demonstrated decreased bone loss (measured by dual energy X-ray absorptiometry (DXA)) in the lumbar vertebrae following ovariectomy. We examined the effects of estrogen deficiency and estrogen therapy on the terminal aorta of the aged ovariectomized (OVX) ewes and demonstrated subintimal thickening in the distal aorta of animals that were estrogen deficient when compared to the control groups. A popular model to study OA is the knee joint of sheep following medial or lateral meniscus removal combined with exercise, but there is a need for an estrogen-deficient large animal model of OA to study articular cartilage changes occurring after menopause. We saw an effect of ovariectomy on the biomechanical properties (aggregate modulus and shear modulus) of articular cartilage. Estrogen deficiency had a detrimental effect on the articular cartilage of the knee even though the cartilage of the OVX animals appeared grossly normal. In another study, 13.5 months following ovariectomy, we found an increase in estrogen receptor binding capacity of the articular cartilage suggesting that articular cartilage is a sex-hormone sensitive tissue. There is intense interest in the correlation between systemic osteoporosis and bone loss of the mandible and maxilla. We studied mandibular bone loss in OVX sheep using DXA. The mean BMD of the OVX group versus sham and estradiol-treated animals was lower, indicating that systemic bone loss in OVX ewes may be accompanied by oral bone loss. Coronary artery disease, osteoporosis, osteoarthritis (OA) and oral bone loss all have a major impact on women's heath after menopause and we found that certain characteristics of these conditions can be reproduced in the skeletally mature or aged estrogen-deficient sheep. It is premature to promote the sheep as the only model to study estrogen deficiency and the many differences from small animal omnivores and non-human primates need to be overcome and a search for more economical models must continue. This model, however, may offer the opportunity to study postmenopausal conditions and the safety and efficacy of new therapeutic agents.

The use of dual-energy x-ray absorptiometry in animals.

The use of dual-energy absorptiometry (DXA) to measure bone mineral content (BMC) and bone mineral density (BMD) is widespread in humans and has been adapted to animals because of the need to examine bone and body composition in longitudinal studies. In this review, the indications and techniques for DXA in small-sized animals (rodents, cats, and rabbits) and large-sized animals (dogs, swine, nonhuman primates, sheep, and horses) are discussed. Now that software has been developed for measuring BMD in small laboratory animals, the most frequent use of DXA in animals is in rats. An ultrahigh-resolution mode of acquisition is used for their small bones but also is necessary for other small-sized animals such as rabbits and cats. In larger-sized animals such as dogs, pigs, and sheep, software used in humans has been adapted successfully to measure BMC/BMD and body composition. The human spine and left and right hip protocols are adapted easily to animals of this size, and the software for body composition has been adapted to dogs. Measurement of bone mass around metallic implants is possible in animals and most studies have involved dogs. To ensure precision of DXA in the noninvasive measurement of BMD in animals, attention to positioning and ability of the operator to define the same region of interest using clearly defined anatomical landmarks on the scan image cannot be overemphasized. This is one of the essential requirements for successful densitometry in animals.

Animal models of osteoporosis--necessity and limitations.

There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty) is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

The effect of intramedullary polymethylmethacrylate on healing of intercalary cortical allografts in a canine model.

The purpose of this study was to evaluate the effect of intramedullary polymethylmethacrylate (PMMA) bone cement on the healing of intercalary allografts. Thirteen adult beagles had bilateral intercalary femoral allografts implanted. The medullary canal of one randomly assigned allograft in each dog was filled with PMMA. Healing was followed clinically and femora were evaluated radiographically, biomechanically, histologically, and histomorphometrically 9 months after surgery. There was an increased percent of eroded surface at the endosteal area of the center region of grafts containing PMMA and there was an increased percent osteoblast surface in this area in grafts not containing PMMA. There was an increased percent eroded surface at the periosteal area in the center region in grafts not containing PMMA and there was an increased percent osteoblast surface at the periosteal area in the graft adjacent to the host junction in grafts containing PMMA. There was no significant difference between PMMA-treated and untreated allografts in any other parameters measured. The results from this study suggest that, although the pattern of incorporation is altered, intramedullary PMMA does not appear to effect allograft healing adversely.

Comparison of efficacy of a single daily dose of 400 mg acebutolol and 100 mg atenolol in the treatment of arterial hypertension.

A double-blind, crossover comparison of once-daily acebutolol (400 mg) and once-daily atenolol (100 mg) was carried out in 33 patients with mild to moderate essential hypertension. After 8-weeks' treatment with acebutolol, the reduction (12%) in mean arterial pressure was, on average, slightly greater than that on atenolol (11%), but the difference was not significant. The mean 22-hour serum concentration of acebutolol plus its acetyl metabolite was 24% of the peak level, whereas that of atenolol was 12%. Routine laboratory monitoring showed no important changes. Acebutolol gave a statistically significant lesser reduction in pulse rate than atenolol, and a lesser incidence, approaching statistical significance (p less than 0.1), of side-effects.

Central and peripheral temperature changes in sheep following ovariectomy.

OBJECTIVES: To determine if ovariectomized ewes undergo periodic body temperature rises (hot flashes) similar to women at menopause. METHODS: Eighteen mature ewes were assigned to ovariectomy (OVX), ovariectomy+17 beta-estradiol implant (OVXE) or Sham. Electronic temperature loggers placed subcutaneously over the carotid artery and within the abdomen (core) and subcutaneously in the thigh and axilla (peripheral) were programmed to record body temperatures every 2.5 min for 59 days. Circadian rhythm changes were avoided by dividing readings into 1 h intervals. Hot flashes were defined as a 0.2 or 0.4 degrees C increase over the minimum temperature recorded for a 1 h interval for each sheep. RESULTS: Logger placement did not reflect core and peripheral temperatures. The carotid and abdominal sites were most useful. The percentage of readings considered HF at the carotid site was 63% OVX, 54% OVXE and 37% Sham (P<0.001), and at the abdominal site were 32% OVX, 15% OVE and 17% Sham (P<0.001). When only the first 7 days after ovariectomy were analyzed, the percentage of readings considered to be HF at the carotid site was 75% OVX, 63% OVXE, and 49% Sham (P<0.001), and at the abdominal site was 35% OVX, 15% OVXE and 17% Sham (P<0.001). CONCLUSIONS: Ovariectomy in the ewe does illicit changes in body temperature compared with control ewes, which may be interpreted as HF. However, shifts in the circadian rhythm were not apparent. Estradiol treatment led to milder and less frequent HF. Periodic HF in species other than rats have heretofore not been reported.

Direct current electrical stimulation increases the fusion rate of spinal fusion cages.

STUDY DESIGN: A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. OBJECTIVES: To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. METHODS: Twenty-two sheep underwent lumbar discectomy and fusion at L4-L5 with an 11- x 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-microA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-microA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. RESULTS: The histologic fusion rate increased as the direct current dose increased from 0 microA to 40 microA to 100 microA (P < 0.009). Histologically, all animals in the 100-microA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P < 0.120), left lateral bending (P < 0.017), right axial rotation (P < 0.004), left axial rotation (P < 0.073), extension (P < 0.078), and flexion (P < 0.029) over nonstimulated levels. CONCLUSION: Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months.

The sheep as a model for osteoporosis in humans.

There is great interest in large animal models for studying different aspects of osteoporosis. Several laboratories around the world have used ovariectomized sheep as a model because of their ease of housing and handling, low expense compared to other large animals, availability and acceptance in society as a research animal. They have been used to study the response to new therapies for post-menopausal osteoporosis, low-magnitude mechanical stimulation, orthopedic implants in osteoporotic bone and bioactive ceramics to strengthen vertebral bodies. To produce severely osteopenic bone comparable to that seen in humans, a combination of estrogen deficiency following ovariectomy plus a calcium-wasting diet is currently being investigated.