Glucose metabolism in injured tissue: a longitudinal study

Injured tissue is characterized by increased glucose uptake and increased lactate production as compared to normal tissue. These metabolic changes have been attributed to the presence of inflammatory cells in injured tissues. To correlate these metabolic changes with changes in the inflammatory cell population at various times after injury, we studied the lambda-carrageenan hindlimb wound model in anesthetized rats. Perfusion studies demonstrated that at 3 and 5 days after injury glucose uptake was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. At 3, 5, and 10 days after injury, lactate production from glucose was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. These metabolic changes were not related to differences in body weight or food intake. There was no difference in glucose oxidation or in oxygen consumption in injured hindlimbs, compared with hindlimbs from pair-fed control animals. The increased glucose uptake and increased lactate production from glucose was coincident with the presence of inflammatory cells--predominantly macrophages--at the site of injury. It is suggested that the glucose metabolism in injured tissue reflects the metabolism of the inflammatory cells at the site of injury.     

Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.     

Histology of a lengthened human tibia.

We describe the histology of a specimen taken from an amputated leg seven months after a 15 cm bone gap in the tibia had been closed by bone transport. Lengthening appeared to have occurred by repeated minor trauma to the bone, with the fractured trabeculae in sufficiently close contact for the repair process to proceed. Osteogenesis did not occur through a cartilage phase, but the fracture gaps were bridged by collagen fibres, around which new bone formed. Microfractures had repaired by primary healing with woven bone and with no microcallus. Small regions of bone were necrotic. Resorption of the necrotic bone and remodelling of the immature bundle and woven bone were still at an early stage, suggesting that complete remodelling in man may take years rather than months.     

Effects of N-methyl-thiotetrazole cephalosporin on haemostasis in patients with reduced serum vitamin K1 concentrations.

Two patients with low random serum vitamin K1 concentrations but with normal prothrombin times and normal biological assays of the vitamin K dependent coagulation proteins were treated with an N-methyl-thiotetrazole cephalosporin (cefotetan) postoperatively. Four to six days later both patients developed a prolonged prothrombin time and a noticeable and specific lowering of the clotting activities of factors II, VII, IX and X, though the serum vitamin K1 concentrations remained unchanged. Crossed immunoelectrophoresis of prothrombin showed the appearance of a second peak corresponding to descarboxyprothrombin (PIVKA II). These abnormalities corrected after vitamin K administration. These data are consistent with the hypothesis that cephalosporins with an N-methyl-thiotetrazole side chain inhibit the hepatic utilisation of vitamin K but that this only causes hypoprothrombinaemia when liver reserves of vitamin K are low.     

Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency

A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations. These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma.