Circulating factors that modify lung cell DNA synthesis following exposure to inhaled oxidants. I. Effect of serum and lavage on lung fibroblasts following exposure of adult rats to 1 ppm ozone

Adult rats were exposed to 1 ppm (1.96 mg/m3) ozone or air for 2 wk. Animals were sacrificed at 3, 5, 7, or 14 d after the onset of exposure, and samples of plasma and lung lavage were obtained. Heat-inactivated plasma, from animals exposed to ozone for 7 or 14 d, significantly increased DNA synthesis by lung fibroblasts compared with plasma from air-exposed animals. Fractionation of plasma and lavage samples indicated that the factor responsible had an isoelectric point of 6.45-6.75 and a molecular weight of 32 +/- 2 kDa. This factor has a dose-dependent effect on lung fibroblast DNA synthesis in culture, but no significant effect on cultured pneumocyte DNA synthesis. The factor is detectable within 72 h of exposure, and may hold some promise as a marker of early oxidant lung injury.     

Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol.

Dendritic cells have been isolated from human tonsillar tissue and shown to act as accessory cells in a mitogenic response. The dendritic cells will induced receptors for the active metabolite of vitamin D3, 1,25(OH)2D3, in the responder E+ T cells. The dendritic cells themselves constitutively express receptors for the metabolite, and this distinguishes them from other non-T cells in lymphomedullary tissue. Expression of the 1,25(OH)2D3 receptor may be a dendritic cell property that facilitates their accessory cell role within the tissue microenvironment.     

Flexible tantalum stents implanted in aortas and iliac arteries: effects in normal canines

Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study.     

血管闭合器应用的现况与展望

股动脉径路是冠状动脉及外周血管介入诊疗的主要途径。然而,股动脉径路穿刺的围术期血管并发症仍是每个介入医生时常面对的问题。研究显示,与压迫止血比较,血管闭合器可减少围术期血管并发症,缩短患者制动时间,增加患者舒适度。现就相关内容及最新进展进行简要综述。     

Circulating factors that modify lung cell DNA synthesis following exposure to inhaled oxidants. III. Effects of plasma on lung pneumocyte and fibroblast DNA synthesis following exposure of adult rats to 85% oxygen

Previous studies, in which adult rats were exposed to 1 ppm ozone for 2 weeks, demonstrated the appearance in plasma of separate factors that stimulated DNA synthesis by cultured pneumocytes and lung fibroblasts in a dose-dependent and cell-specific fashion. Both factors had isoelectric points of 6.45-6.75, but differed by molecular mass. The pneumocyte factor had an estimated weight of 38 +/- 3 kDa, while the fibroblast factor had an estimated molecular weight of 32 +/- 2 kDa. To determine whether the appearance of these factors in plasma is specific for ozone injury or whether they appear in response to other oxidant injuries, adult rats were exposed to 85% O2 or air for up to 2 weeks. Animals were sacrificed at 3, 5, 7, or 14 days after the onset of exposure. Plasma samples were subjected to sequential preparative electrofocusing and high-performance liquid chromatography (HPLC). Heat-inactivated plasma fractions, with an isoelectric point of 6.45-6.75, contained a factor of 32 +/- 2 kDa, which enhanced lung fibroblast DNA synthesis at a single time point on day 5 of 85% O2 exposure, and a factor of 38 +/- 3 kDa, which enhanced pneumocyte DNA synthesis on days 5, 7, and 14 of 85% O2 exposure. Of the known growth factors, those most likely to have these physical characteristics are platelet-derived growth factor (PDGF) and insulin-like growth factor-1. Additional groups of animals were exposed to air or 85% O2 for 5 days for plasma collection. Animals exposed to 85% O2 had a 60% increase of plasma immunoreactive PDGF and a 90% increase of plasma immunoreactive IGF-1, compared with values for control animals exposed to air.     

An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis.

Female patients (n = 20) with osteoporosis, aged 66 +/- 5 yr were studied during a 24-h infusion of parathyroid hormone (PTH [1-34]) at a rate of 0.5 IU equivalents/kg.h, and then during a 28-d period of subcutaneous injections, at a dose of 800 IU equivalents per day. Thereafter half the patients received subcutaneous injections of calcitonin, 75 U/d for 42 d, and all patients were followed to the end of a 90-d cycle. Biochemical markers of bone formation (serum alkaline phosphatase, osteocalcin, and the carboxy-terminal extension peptide of pro-collagen 1) and bone resorption (fasting urine calcium, hydroxyproline, and deoxypyridinoline) were compared during treatment by the intravenous and subcutaneous route of PTH administration, and subsequently during calcitonin therapy. During intravenous PTH infusion there were significant reductions in all three bone formation markers, despite expected rises in urinary calcium and hydroxyproline. By contrast, the circulating markers of bone formation increased rapidly by > 100% of baseline values during daily PTH injections (P < 0.001). Significant increases in bone resorption markers were only seen at the end of the 28 d of injections, but were < 100% over baseline values, (P < 0.05). Quantitative bone histomorphometry from biopsies obtained after 28 d of PTH treatment confirmed that bone formation at both the cellular and tissue levels were two to five times higher than similar indices measured in a control group of biopsies from untreated osteoporotic women. Subsequent treatment of these patients with calcitonin showed no significant changes in the biochemical markers of bone formation and only a modest attenuation of bone resorption. Thus, PTH infusion may inhibit bone formation, as judged by circulating biochemical markers, whereas daily injections confirm the potent anabolic actions of the hormone. Sequential calcitonin therapy does not appear to act synergistically with PTH in cyclical therapeutic protocols.     

Echicetin: a snake venom protein that inhibits binding of von Willebrand factor and alboaggregins to platelet glycoprotein Ib

Echicetin, a new protein isolated from Echis carinatus venom by reverse phase and ion exchange chromatography specifically inhibited agglutination of fixed platelets induced by several platelet glycoprotein Ib (GPIb) agonists, such as bovine von Willebrand factor (vWF), alboaggregins, and human vWF in the presence of botrocetin. Unlike alboaggregins, echicetin bound to GPIb but did not induce agglutination of washed or fixed platelets. In contrast to disintegrins, it did not block adenosine 5'-diphosphate (ADP)-induced platelet aggregation in the presence of fibrinogen. The apparent molecular weight of echicetin measured on sodium dodecyl sulfate (SDS) gel electrophoresis was 26 Kd under nonreducing conditions. On reduction, echicetin showed 16 and 14-Kd subunits suggesting that the molecule is a dimer. Reduced echicetin retained its binding activity and its inhibitory effect on the agglutination of fixed platelets induced by bovine vWF. 125I-echicetin bound to fixed platelets with high affinity (kd = 30 +/- 1.8 nmol/L) at 45,000 +/- 2,400 binding sites per platelet. The binding was selectively inhibited by a monoclonal antibody to the 45-Kd N-terminal domain of platelet GPIb, but not by monoclonal antibodies to other regions on GPIb. Binding of 125I-bovine vWF to fixed platelets was strongly inhibited by echicetin. In contrast, bovine vWF showed a much weaker inhibitory activity on binding of 125I-echicetin to platelets. The half life of echicetin in blood was approximately 170 minutes with no detectable degradation. Echicetin significantly prolonged the bleeding time of mice, suggesting that it may inhibit vWF binding to GPIb in vivo as well as in vitro.     

Effect of surfaces on fluid-phase prekallikrein activation

The activation of prekallikrein by factor XII fragments (XIIf), during incubation in plastic tubes was previously noted to be increased by high molecular weight (HMW) kininogen as well as other plasma proteins. In this report, we investigated the mechanism responsible for this increase. Although we confirmed that HMW kininogen, bovine serum albumin, fibrinogen, cold insoluble globulin, and mixed phospholipids apparently increased prekallikrein activation, we found that the product of prekallikrein activation (kallikrein) lost substantial activity in less than 0.5 min after exposure to a variety of fresh surfaces. This loss was partially prevented by the presence of various proteins and phospholipids. Similar protection against inactivation of XIIf, the enzyme in this reaction, was also found. In contrast, no loss of the substrate, prekallikrein, was observed during incubation. The loss of kallikrein activity was found to be proportional to the surface area of the incubation vessel as well as the concentration of kallikrein. Further loss of kallikrein activity could also be prevented by pretreating the vessel with kallikrein. We therefore conclude that various substances apparently affect prekallikrein activation in a purified system by preventing the enzyme and product in the reaction mixture from losing activity due to adsorption to a surface.