OPG-Fc treatment in growing pigs leads to rapid reductions in bone resorption markers, serum calcium, and bone formation markers.

Inhibition of the receptor activator of NF-κB ligand (RANKL) is a novel therapeutic option in the treatment of osteoporosis and related diseases. The aim of this study was to evaluate bone metabolism and structure in pigs after RANKL inhibition. 12 growing pigs were assigned to 2 groups with 6 animals each. The OPG group received recombinant human OPG-Fc (5 mg/kg IV) at day 0, the control group was given 0.9% NaCl solution. Serum levels of OPG-Fc, calcium (Ca), phosphorus (P), and bone turnover markers were evaluated every 5 days, and pigs were euthanized on day 20. Serum OPG-Fc concentration peaked at day 5 and coincided with significantly decreased Ca, P, and bone turnover markers. By day 15, measureable OPG-Fc serum levels could only be detected in 2/6 animals. With OPG-Fc clearance starting at day 10, serum Ca and P concentrations were not different between the 2 groups. TRACP5b, P1CP, and BAP levels significantly decreased by 40-70% relative to vehicle controls in the OPG-Fc group between days 5 and 10, indicating that pharmacologic concentration of OPG-Fc led to systemic concomitant inhibition of bone formation and resorption in young growing pigs. Dual X-ray absorptiometry data derived from the proximal femur did not differ between the 2 groups. µCT analysis of selected bone sites demonstrated an OPG-Fc-induced improvement of specific bone architectural indices and bone mineralization.

Bone and cellular immune system of multiparous sows are insensitive to ovariectomy and nutritive calcium shortage.

Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore, our aim was to analyze the effects of ovariectomy (OVX) and nutritive calcium shortage on multiparous Large White sows. 32 animals were randomly assigned to 4 groups in a cross design with OVX vs. sham and physiological calcium supplementation (0.75% calcium) vs. dietary calcium shortage (0.3% calcium). The observation period was 10 months with blood sampling every 2 months for hematological, immunological, and biochemical bone marker measurements. At the termination of the experiment, animals were sacrificed. Samples of trabecular bone of distal radius, proximal tibia, and sixth lumbar vertebra were subjected to micro-computed tomography imaging and ashed afterwards. Dual X-ray absorptiometry scans of the proximal femora were performed with prepared bones being placed in a water bath for mimicking soft tissue. Analyses of bone marker and cytokine profile kinetics, distribution of leukocyte subpopulations, and morphometrical and densitometrical analyses showed no evidence of any impact of OVX or calcium shortage. In conclusion, the skeleton of adult sows of a conventional breed is seemingly protected from effects of OVX and calcium shortage.

Psychosocial issues in the cancer patient.

STUDY DESIGN: Systematic review of the literature. OBJECTIVE: To identify psychosocial issues affecting patients with a diagnosis of a spinal column or cord tumor. METHODS: Using the keywords "cancer communication," "psychosocial care," "cancer patient," and "spine cancer patient," a review of the English literature was performed on Medline, EMBASE, and PsycInfo, a database of the psychology and psychiatry literature in the United States. The relevant articles were reviewed; in addition, relevant references from selected articles were searched. The Spine Oncology Study Group, an international panel of spine oncology surgeons, medical and radiation oncologists, identified 2 key questions to be addressed in the course of the systematic review of the literature. Pertinent manuscripts were rated as being of high, moderate, low, or very low quality. Using the Grading of Recommendations, Assessment, Development, and Evaluation evidence-based review system, the 2 key questions were answered using literature review and expert opinion. RESEARCH QUESTIONS: 1. Who are the allied health care professionals necessary for the comprehensive care of the spine tumor patient? 2. Does compassionate communication (in giving life altering information) affect outcome? What tools can be used in communication with the spine tumor patient? RESULTS: Systematic review of the 3 databases yielded 228 articles pertaining to the psychosocial care of spine tumor patients; systematic review yielded 326 articles addressing communication in cancer patients. Systematic search of the Medline, EMBASE, and PsycInfo databases failed to identify any articles that specifically addressed the 2 questions of interest in the spine tumor patient population. The literature search identified low and very low quality evidence; 2 randomized controlled studies were identified. Although neither specifically pertained to the spine tumor patient population, these articles were reviewed and graded as low-quality evidence. CONCLUSION: A multidisciplinary group of allied health care professionals is a necessary prerequisite for the effective psychosocial care of the spine tumor patient. Compassionate communication, in the form of group sessions, telephone support groups, or internet based groups, can alleviate the psychosocial discomfort experienced by spine tumor patients.

Competitive segregation of Si and P on Fe(96.5)Si(3.5) (100) and (110).

Annealing an Fe(96.5)Si(3.5) (100)/(110) bicrystal, containing 90 ppm P, leads immediately to a strong segregation of silicon. The Si atoms, however, desegregate subsequently and are displaced by P, whose segregation enthalpy is larger than that of silicon. The corresponding surface structures formed on both faces have been studied using complementary methods: Scanning tunneling microscopy (STM) to obtain atomically resolved geometrical information and Auger electron spectroscopy (AES) for the determination of the surface composition. Si substitutes surface Fe atoms on both faces and forms ordered surface alloys, whereas P occupies hollow sites on the surface. Si and P form c(2 x 2) superstructures on the (100) surface, whereby each segregated phosphorus atom blocks in the average one silicon segregation site. The (110) surface, on the other hand, is characterized by a c(1 x 3) Si superstructure. Due to the anisotropy of this surface the P/Si exchange proceeds by the formation of silicon coverage decreasing domain boundaries within the silicon structure, which are simultaneously occupied by P atoms. Furthermore the comparison of the AES and STM derived phosphorus coverages indicates a P multilayer segregation on the (110) surface.

Metabolic and hormonal responses of low birthweight infants to intravenously infused calories not exceeding the maintenance energy expenditure.

Eithe low birthweight infants were studied for their metabolic and hormonal responses to intravenous alimentation when the caloric input was varied. The study was made during three consecutive 12-hour periods, when solutions of glucose, glucose and amino-acids, and glucose and amino-acid and lipids were successively infused. Hypertonic glucose led to a fall in plasma free fatty acids and amino-acids. Supplementation with an amino-acid mixture increased the concentration of amino-acids but not above the fasting level. Thus, hypertonic glucose was an effective means for avoiding hyperaminoacidaemia. Blood urea was little changed, also indicating satisfactory use of amino-acids. The number and distribution of calories infused throughout the third 12-hour period, when lipid was infused, were also important factors contributing to the avoidance of hyperaminoacidaemia. The caloric needs of low birthweight infants kept at neutral temperatures should be individually assessed in the light of recent data. The administration of an unnecessarily large load of calories and nutrients to parenterally-fed infants can thereby be avoided.

Studies on hypothalamic estradiol binding during estrous cycle and after ovariectomy.

Specific binding of 3H-estradiol (1 microgram kg-1 injected s.c. 1 h before sacrifice) in the hypothalamus, anterior pituitary and uterus of cycling and ovariectomized female rats was investigated. Preoptic-anterior hypothalamic area (POA-AH) and median eminence-basal hypothalamus (ME-BH) were separated by gross dissection from the bulk of hypothalamus. Pieces of parietal cortex served as controls. The lowest amount of 3H-estradiol specifically bound to cytoplasmic and nuclear receptors in POA-AH and ME-BH was found in proestrus, while in estrus-metestrus it was the highest. In contrast to hypothalamic estrogen sensitive areas, the lowest uterine binding was found in estrus and the highest in diestrus-proestrus. Changes in estradiol binding in the anterior pituitary were similar to that in the uterus. Ovariectomy made 48 h before 3H-estradiol injection markedly increased the nuclear binding in POA-AH and ME-BH compared to that observed in cycling animals. However, it decreased nuclear binding in the uterus. Cytoplasmic binding seems to be decreased in the hypothalamus as well as in the uterus of ovariectomized animals as compared to the highest level observed during estrous cycle in intact ones.