The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.     

Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

The aim of the study was to subclassify the soma-dendritic α₂-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective α₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC₅₀ values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K _d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K _d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC₅₀ values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates – against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 μM. These findings identify the soma-dendritic α₂-autoreceptors of the LC as the rat variant of the α_2A/D-adrenoceptor, i.e. α_2D. Not only presynaptic but also soma-dendritic α₂-autoreceptors may at least predominantly be α_2A/D throughout the nervous system. Received: 3 March 1997 / Accepted: 21 April 1997     

功能性消化不良与幽门螺杆菌关系探讨

功能性消化不良是一种人群中发病率很高的消化系统症状群，其发病机理未完全阐明，本文通过对２７４２例各类型功能性消化不良患者的胃粘膜的幽门螺杆菌感染情况作分析，发现动力障碍型ＨＰ阳性率６５．３％，溃疡型ＨＰ阳性率７４％，胃食管反流型ＨＰ阳性率２４％，特发型ＨＰ阳性率２１．４％，前两型与后两型的阳性率差异有显著性（Ｐ〈０．０５），而前两型之间阳性率差异无显著性（Ｐ〉０．０５），说明ＨＰ与动力障碍型和溃疡     

Muscle glycogen repletion from endogenous carbon sources during recovery from high intensity exercise in the fasted rat

During recovery from high intensity exercise, substantial and rapid muscle glycogen repletion from endogenous carbon sources is reported in a variety of vertebrate species, the rat being the only reported exception. The major aim of this study was to re-examine the process of glycogen repletion during recovery from high intensity exercise in the rat. In response to 3 min of vigorous swimming, muscle glycogen concentrations decrease markedly from initial levels of 20.2±1.5 and 21.2±0.9 μmol g^-1 to 6.4±1.1 and 7.9±1.4 μmol g^-1 in the tibialis anterior and plantaris muscles respectively. The equivalent of 58% of the glycogen carbons mobilized during exercise by the plantaris and 73% of that mobilized by the tibialis anterior muscle is repleted within 1 h following exercise. Using the hepatectomized rat as experimental model, a secondary aim of the study was to evaluate whether the liver is essential for the repletion of muscle glycogen. Although the absence of significant differences in the magnitude of post-exercise muscle glycogen repletion between sham-operated and hepatectomized rats suggests that the resynthesis of muscle glycogen can take place in the absence of hepatic gluconeogenesis, the present study identifies several limitations in the use of acute hepatectomy. Overall, the present study indicates that, in contrast to published views, the rat resembles other vertebrates in that it can support extensive muscle glycogen repletion from endogenous carbon sources during the recovery phase following high intensity exercise.     

Failure of coconut oil to accelerate psoriasis clearance in narrow-band UVB phototherapy or photochemotherapy

Despite a widely held belief that the use of emollients prior to broad-band UVB irradiation accelerates clearance of psoriasis, only one single-blind controlled study exists in support of this. No similar study has been carried out with photochemotherapy (PUVA) or narrow-band UVB (311–313 nm) phototherapy. As some emollients absorb UV radiation, and thereby inhibit psoriasis clearance, there is a need to identify emollients suitable for pre-irradiation use. Coconut oil may be useful in this respect. In two randomized groups of patients with chronic plaque psoriasis undergoing either routine PUVA(n=14) or narrow-band UVB phototherapy (n=15), a single-blind controlled (half-body) study was undertaken to assess the died of pre-irradiation application of coconut oil. Patients were given PUVA twice weekly, or TL-01 therapy thrice weekly. The initial UV dose was 70% of previously determined minimal phototoxic (MPD) or minimal erythema doses (MED), with 40% incremental steps at each visit (reduced if adverse effects occurred). Psoriasis severity was scored on each side after every three treatments. No significant acceleration of psoriasis clearance was seen in either group. We do not, therefore, recommend the routine use of emollients prior to PUVA or TL-01 therapy when using near erythemogenic irradiation regimens.     

Regional patterns of bone loss and altered bone remodeling in response to calcium deprivation in laboratory rabbits

Summary This study explores the effects of a calcium-deficient diet on patterns of bone remodeling, and examines regional differences in the amount of bone lost. Skeletally mature female rabbits (n=6) were fed a calcium-deficient diet (0.10% Ca²⁺ and 0.50% P) for 14 weeks. A separate group of rabbits (n=4) were fed a maintenance diet (1.2% Ca²⁺ and 0.45% P). Bone mineral content, serum calcium, and serum phosphorus were measured each week during the experimental period. Following sacrifice, the L₃ vetebra, femoral head, proximal tibial metaphysis, and tibial midshaft were analyzed histomorphometrically. Rabbits had 20% less vertebral bone after only 14 weeks of a calcium-deficient diet. As in human postmenopausal osteoporosis, bone loss in calcium-deficient rabbits occurs in the trabecular bone of the lumbar spine before that in the trabecular bone of the lower extremity. Calcium-deficient diets alone do not lead to increased osteoid volume or thickness. Because bone loss is relatively rapid and because the pattern of loss is similar in some respects to that found in humans, adult rabbits may provide an attractive model of calcium deficiency osteoporosis in a skeletally mature mammal in which remodeling is predominant over modeling.