Attenuation of intra-operative surgical stress response has no influence on post-operative degranulation of polymorphonuclear granulocytes.

Degranulation of polymorphonuclear (PMN) granulocytes, complement activation, and the endocrine metabolic response to hysterectomy were compared in two groups of patients receiving either general anaesthesia (GA group) or combined epidural analgesia and general anaesthesia (GAE group). The B-leucocyte and the cortisol responses were attenuated in the GAE group. There was no sign of complement activation. The post-operative rise in elastase-alpha-1-proteinase levels 4 h post-operatively on the first, second and third post-operative days was similar in the two groups. Plasma lactoferrin values were significantly elevated 4 h post-operatively and reached pre-operative values on Day 1 in both groups. Attenuation of the surgical stress response during uncomplicated hysterectomy did not influence the post-operative increase in proteinase activity. Mediators generated at the site of surgical trauma may account for the PMN degranulation observed after major surgery.     

Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis.

BACKGROUND: During haemodialysis (HD), polymorphonuclear cells (PMNs) and platelets are activated and release various granule products, including myeloperoxidase (MPO) and platelet factor 4 (PF4). MPO triggers the generation of reactive oxygen species, leading to irreversible protein, carbohydrate and lipid modification. PF4 probably also contributes to oxidative stress. As previously shown, HD-induced PMN degranulation is almost completely abolished during citrate anticoagulation, most probably due to its calcium chelation ability. METHODS: In the present study, apart from HD-induced PMN and platelet degranulation, oxidative stress was analysed during three modes of anticoagulation. Heparin, dalteparin and citrate (HDhep, HDdal and HDcit) were compared in a randomized, crossover fashion in eight chronic HD patients. Multiple blood samples were taken during the third HD session of each modality, from both the afferent and efferent line. Besides the degranulation markers MPO and PF4, various markers of oxidative stress were measured, including oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) and carboxymethyllysine (CML). RESULTS: During HDhep and HDdal, marked degranulation was observed shortly after the start of HD. In contrast, during HDcit, PF4 and MPO levels remained unaltered, suggesting no release at all. After 1 week of HDcit, ox-LDL levels were markedly reduced [median 26% (3-65%), P=0.01], if compared with HDhep and HDdal. As regards MDA and CML, no differences were found. CONCLUSIONS: This study shows first, that HD-induced PMN and platelet degranulation are early, most probably calcium-dependent processes and, secondly, that the formation of ox-LDL is clearly dependent on the type of anticoagulant applied.     

Effect of demineralized bone matrix on polymorphonuclear leukocyte degranulation.

The potential use of allogenic demineralized bone matrix to augment or treat bone defects or nonunions in animals and humans is currently being investigated. Demineralized bone matrix induces osteogenesis by a multistep cascade of endochondral ossification that is mediated by bone-induction factors. The migration and activation of polymorphonuclear leukocytes appear to be critical in the initiation of the cascade of osteogenesis induced by demineralized bone matrix. This study examined the effects of demineralized bone matrix on the degranulation of polymorphonuclear leukocytes. Demineralized bone matrix stimulated the release of polymorphonuclear leukocyte-specific, but not azurophilic, granules in a time and dose-dependent manner. The ability of the bone matrix to induce this degranulation was independent of its size and species. The mechanism by which this degranulation occurs is not completely understood; however, it is known that it does not occur by means of a receptor that requires guanidine triphosphate-dependent regulatory proteins as does polymorphonuclear-leukocyte degranulation induced by N-formyl peptide. The factor that stimulates degranulation is not type-I collagen but rather appears to be a cytokine that has a heparin-binding domain and a molar mass of 10-70 kDa. Loss of the ability of demineralized bone matrix to induce degranulation of polymorphonuclear leukocytes correlated positively with the loss of its ability to induce bone formation.     

Hemodialysis-induced hypotension: impact of technologic advances

Hemodialysis-induced hypotension is one of the most serious complications in renal replacement therapy. The main cause of intradialytic hypotension is hypovolemia due to an imbalance between the amount of fluid removed and the refilling capacity of the intravascular compartment. Hypotension occurs when compensatory mechanisms for hypovolemia are overwhelmed by excessive fluid removal. As long as renal replacement therapy is limited to only a few hours per week, intradialytic hypotension will continue to be a relevant problem. Research has mainly focused on enlarging the compensatory capacity for ultrafiltration-induced hypovolemia. This article critically discusses the technical approaches that have been introduced into therapy in recent years with the promise of reducing dialysis-induced hypotensive episodes.     

Hypothermia augments polymorphonuclear leukocyte degranulation and interleukin-8 production from human umbilical vein endothelial cells and increases lipopolysaccharide-induced polymorphonuclear leukocyte-endothelial cell interaction when followed by normothermia

OBJECTIVE: To determine if hypothermia followed by normothermia (rewarmed to 37 degrees C) changes the inflammatory response of polymorphonuclear leukocytes (PMNs) and human umbilical vein endothelial cells (HUVEC). DESIGN: Prospective, controlled, in vitro study. SETTING: University laboratory. PARTICIPANTS: PMNs from 4 healthy volunteers and HUVEC. MEASUREMENTS AND MAIN RESULTS: PMNs and HUVEC were incubated for 3 hours at 20 degrees C, 30 degrees C, or 37 degrees C followed by 37 degrees C again. PMN degranulation, cytokine production from HUVEC, and PMN-HUVEC interaction were compared among the 3 experimental temperatures. Interleukin (IL)-8-induced PMN degranulation measured by myeloperoxidase concentrations was significantly higher in the 20 degrees C and 30 degrees C groups than the 37 degrees C groups. Bacterial lipopolysaccharide (LPS)-induced IL-8 production from HUVEC, measured by enzyme-linked immunosorbent assay, was significantly higher in the 20 degrees C group than the other 2 groups; however, tumor necrosis factor-alpha was not detectable in any of the groups. LPS-induced cell injury measured by cellular (51)Cr release was significantly higher in the 20 degrees C and 30 degrees C groups than in the 37 degrees C groups. This injury was significantly inhibited by IL-8 antibody. CONCLUSION: Hypothermic (20 degrees C and 30 degrees C) incubation followed by rewarming augmented IL-8-induced PMN degranulation and LPS-induced IL-8 production from HUVEC and LPS-induced PMN-endothelial interaction. IL-8 plays an important role in this increased injury. This increased inflammatory response may support the positive outcomes of normothermic CPB.     

Charcot神经性骨关节病急性期炎症指标与骨转换率的相关性分析

【摘要】 目的 探讨Charcot神经性骨关节病(CNO)急性期患者临床检验中炎症指标与骨转换率的相关性。方法 对2010年1月至2014年12月在我院住院的15例确诊为CNO急性期的患者进行回顾性分析,记录患者入院时炎症指标及骨转换指标,分析两者之间的相关性。结果 CNO患者血清TNF-α以及多项成骨及骨吸收指标均有上升,且TNF-α与β-胶原降解产物(β-crosslaps)、N端骨钙素(N-MID.Os)、总I型胶原氨基端前肽(PINP)以及骨碱性磷酸酶(BALP)均成正相关;IL-10与N-MID.Os、PINP及BALP均成负相关;IL-6、IL-8及IL-1β与骨转换指标没有明显相关性。结论〓CNO患者血清中TNF-α与多项骨转换指标的异常提示炎症性关节病的存在及骨代谢的紊乱,成骨及破骨活性均增强。TNF-α与多项骨转换指标相关,该相关性可能特异存在于炎症性骨关节病中,可能为CNO的早期诊断提供一定的价值。     

The influence of tourniquet ischaemia on post-operative degranulation of polymorphonuclear granulocytes.

Degranulation of polymorphonuclear granulocytes following minor surgery and the contributory role of temporary tissue ischaemia in a limb were examined in 22 otherwise healthy patients undergoing elective arthroscopy under general anaesthesia with and without tourniquet. Apart from an increase in lactate levels following tourniquet release there was no difference in complement split product C3d, cortisol, leukocyte or creatinine kinase levels between the two groups. There was a post-operative increase in the plasma E alpha 1-proteinase inhibitor concentration, whereas lactoferrin values decreased 4 h following tourniquet deflation. Anaesthesia and minor surgery are followed by post-operative release of polymorphonuclear neutrophil elastase. This release is not related to complement activation and is apparently unaffected by 50 min of lower limb ischaemia. Anaesthesia and minor surgery do not cause lactoferrin release.     

Reduction of degranulation of polymorphonuclear leukocytes by immunosuppression in patients following cadaveric renal transplantation

Plasma levels of main granulocyte components of patients after cadaveric renal transplantation were compared 9 days postoperative with the plasma levels of patients undergoing aortofemoral and iliacofemoral bypass operation or abdominal surgery. Lactoferrin values were significantly lower in patients under immunosuppression with cyclosporine and prednisolone, whereas plasma levels of myeloperoxidase were comparable in all 3 groups of patients. Plasma E-alpha 1 PI values were significantly lower in patients undergoing bypass operation compared to abdominal surgery but did not differ from patients undergoing cadaveric kidney transplantation. Within 22 days postoperatively, there was no difference in the plasma levels of main granulocyte components in patients after kidney transplantation with and without postoperative complications. In vitro incubation of heparinized whole blood and isolated granulocytes obtained from healthy subjects in the presence of CsA, azathioprine, or prednisolone were performed. Only CsA caused inhibition of spontaneous degranulation of polymorphonuclear neutrophils showing significant lower elastase and lactoferrin release. However, in vivo administration of CsA and prednisolone in transplant patients displayed no effect on in vitro degranulation of both whole blood samples and isolated granulocytes. Our data demonstrate that CsA after in vitro incubation inhibits spontaneous granulocyte degranulation but not after in vivo administration. However, in vivo administration of CsA and prednisolone reduces lactoferrin release under certain conditions, e.g., postoperative stress or during hemodialysis therapy.     

晚期糖基化终末产物与骨性关节炎相关性的研究进展

晚期糖基化终末产物(advanced glycation end products,AGEs)是衰老致骨性关节炎的重要因素,主要通过受体(receptors for advanced glycation end products,RAGE)途径,引起软骨基质降解与软骨细胞凋亡、促进软骨及滑膜组织的炎性反应等方式在OA发病中发挥重要作用。AGEs是OA领域的研究新热点,但其分子机制还未完全阐明,对AGEs的研究将有助于明确OA的发病机制,同时为OA的治疗策略提供了新的观念。     

Impact of dialyzer membrane on apoptosis and function of polymorphonuclear cells and cytokine synthesis by peripheral blood mononuclear cells in hemodialysis patients

Abstract:  In an in vivo crossover trial, we compared a cellulosic with a synthetic dialyzer with respect to polymorphonuclear cells (PMN) function and apoptosis, cytokine serum levels and synthesis by peripheral blood mononuclear cells (PBMC), and complement activation. Twenty hemodialysis (HD) patients were assigned in alternate order to HD with cellulose acetate (CA) or polysulfone (PS) dialyzer. After 2 weeks, patients were crossed over to the second dialyzer and treated for another 2 weeks. Apoptosis was assessed by flow cytometry in freshly isolated PMN. Phagocytosis and production of peroxide by PMN were studied by flow cytometry in whole blood. PBMC were isolated from blood samples and incubated for 24 h with or without lipopolysaccharide (LPS). There was no impact of dialyzer biocompatibility on PMN apoptosis and function, cytokine synthesis by PBMC or on their serum levels, serum levels of C3a, and terminal complement complex (TCC). Nevertheless, after HD, serum levels of complement correlated negatively with PMN phagocytosis and peroxide production, and positively with PMN apoptosis and cytokine production by PBMC. Although the results did not show a dialyzer advantage on the immunologic parameters, complement activation may have modulated cell function and apoptosis after HD.     

桡骨小头骨折与前臂骨间膜损伤的相关性研究

 目的 探讨桡骨小头骨折与前臂骨间膜损伤的相关性。方法 2007 年9 月至2010 年6月, 前瞻性观察26 例桡骨小头骨折患者, 男15 例, 女11 例;年龄21~53 岁, 平均(37.6±7.3)岁。桡骨小头骨折根据Mason 分型, I型7 例, II型9 例, III型10 例。所有患者均在1 周内行伤侧尺桡骨全长X线、CT及MR 检查(包括肘及腕关节), 以明确是否合并前臂骨间膜损伤及损伤程度、部位。桡骨小头骨折类型和骨间膜损伤程度的相关性采用Spearman 秩相关进行统计学分析。结果 Mason I~III型桡骨小头骨折均可伴前臂骨间膜损伤, 其中7 例Mason I型骨折中2 例、9 例Mason II型骨折中4 例、10 例MasonIII型骨折中7 例伴前臂骨间膜损伤。桡骨小头骨折与前臂骨间膜损伤呈正相关。桡骨小头骨折程度越严重, 前臂骨间膜损伤的发生率越高, 损伤程度也越重。Mason I型及 II型骨折中的6 例前臂骨间膜损伤均为膜部损伤, 而10 例MasonIII型骨折中的7 例前臂骨间膜损伤, 3 例为中央束断裂, 4 例为膜部损伤。结论 各类型桡骨小头骨折均可伴前臂骨间膜损伤, 桡骨小头骨折与前臂骨间膜损伤呈正相关。对于桡骨小头骨折, 尤其是MasonIII型骨折, 建议行前臂MR 检查, 以明确是否有骨间膜损伤。     

There is no relationship between concentration,motility and vacuolated cells

To determine whether there are differences between concentration and motility in the vacuolated spermatozoa of fertile donors, randomized men and infertile patients, semen samples were compared. Based on the percentages of concentration and motility, samples were divided into three groups: Group I, fertile donors, concentration >20×10⁶/ml, motility >50%; Group II, patients, concentration <20×10⁶/ml, motility <50%; Group III, randomized men, concentration >20×10⁶/ml, motility >50%. In each group samples were assessed morphologically by the strict criteria of Kruger et al. The results showed that there was no difference between Group I and Group II, but there were differences between Group III and Group II, and Group III and Group I. We conclude that there is no relationship between concentration, motility and vacuolated cells.     

Exploring correlation between bone metabolism markers and densitometric traits in extended families from Spain

Osteoporosis is a common multifactorial disorder characterized by low bone mass and reduced bone strength that may cause fragility fractures. In recent years, there have been substantial advancements in the biochemical monitoring of bone metabolism through the measurement of bone turnover markers. Currently, good knowledge of the genetics of such markers has become an indispensable part of osteoporosis research. In this study, we used the Genetic Analysis of Osteoporosis Project to study the genetics of the plasma levels of 12 markers related to bone metabolism and osteoporosis. Plasma phenotypes were determined through biochemical assays and log-transformed values were used together with a set of covariates to model genetic and environmental contributions to phenotypic variation, thus estimating the heritability of each trait. In addition, we studied correlations between the 12 markers and a wide variety of previously described densitometric traits. All of the 12 bone metabolism markers showed significant heritability, ranging from 0.194 for osteocalcin to 0.516 for sclerostin after correcting for covariate effects. Strong genetic correlations were observed between osteocalcin and several bone mineral densitometric traits, a finding with potentially useful diagnostic applications. In addition, suggestive genetic correlations with densitometric traits were observed for leptin and sclerostin. Overall, the few strong and several suggestive genetic correlations point out the existence of a complex underlying genetic architecture for bone metabolism plasma phenotypes and provide a strong motivation for pursuing novel whole-genome gene-mapping strategies.     

Neutrophil and eosinophil degranulation during hemodialysis are mediated by the dialysis membrane

During hemodialysis of heparinized blood without having a patient in the circuit, the serum concentrations of lactoferrin, myeloperoxidase (MPO) and eosinophil cationic protein (ECP) steadily increased, indicating neutrophil and eosinophil degranulation. The increments in serum of these granular proteins were more pronounced using plate dialyzers than capillary dialyzers. The release of granule constituents does not seem to reflect merely a sequestration of granulocytes in the dialyzer, since the increase of the serum concentrations of lactic dehydrogenase was very modest. The intracellular contents of lactoferrin, MPO, lysozyme and ECP were reduced after experimental dialysis in the granulocytes isolated from the blood, indicating that the cells in association with degranulation were not entrapped in the dialyzer. The relatively modest increase of the plasma concentrations of lysozyme during experimental hemodialysis, in spite of the reduction of the intracellular content of lysozyme, was explained by the propensity of lysozyme for adhering to the dialysis membrane. Serum samples obtained at different times during dialysis did not induce an enhanced release of granular proteins from isolated granulocytes in vitro. The earlier observed increase during hemodialysis of the serum concentrations of granular proteins in uremic patients can be explained by the dialysis membrane triggering granulocytes to degranulate.     

绝经后女性骨代谢生化指标与骨质疏松性腰椎骨折之间的相关性

目的探讨骨代谢标志物对预测绝经后骨质疏松患者合并腰椎骨折风险的诊断价值。方法采用双能X线骨密度仪、酶联免疫检测法(ELISA)和速率法对70例绝经后骨质疏松症腰椎无骨折患者和70例绝经后骨质疏松症腰椎骨折患者的髋部及腰椎骨密度、各项骨代谢生化指标进行检测,并分析骨代谢生化指标的变化与骨质疏松症、骨质疏松性腰椎骨折之间的相关性。结果绝经后骨质疏松性腰椎骨折的发生风险与年龄、体重、身高、体重指数、骨密度等一般指标和骨钙素N端中分子片段(N-MID osteocalcin,N-MID)、骨碱性磷酸酶(bone alkaline phospha,BAP)、钙离子(calcium ionic,Ca~(2+))、骨吸收标志物β-Ⅰ型胶原羧基端肽(β-C-terminal telopeptide of type I collagen,β-CTx)等生化指标之间无关联,而与血清I型原胶原氨基端延长肽(propeptide of type I procollagen,PINP)、抗酒石酸酸性磷酸酶5b(TRAP-5b)和25-羟维生素D(25-hydroxy vitamin,25-(OH)D)之间存在显著相关性(P=0.002、0.007、0.001),其中与PINP、TRAP-5b呈正相关,与25-(OH)D呈负相关。结论绝经后女性血清PINP、TRAP-5b和25-(OH)D与骨质疏松性骨折的发生存在显著的相关性,骨代谢标志物与骨密度的联合检测对预测绝经后骨质疏松腰椎骨折具有一定的临床意义。     

Hyaluronan-based antiadhesive membrane has no major effect on intraperitoneal growth of colonic tumour cells

BACKGROUND: A relationship between post-surgical adhesion formation and peritoneal tumour implantation has been proposed. Hyaluronan (HA)-based agents reduce adhesion formation, but the effect on peritoneal tumour is not established. This study investigated the influence of a HA-containing agent on intraperitoneal tumour in an experimental model. METHODS: 66 Balb/c mice underwent laparotomy and damage was inflicted to the parietal peritoneum. The animals were randomized into five groups. Groups 1 and 2 received HA-carboxymethylcellulose bioresorbable membrane and no treatment, respectively. Mice in groups 3-5 were injected intraperitoneally with 10(5) colon 26-B cells after the laparotomy. Treatment consisted of HA membrane, no HA agent and placement of HA membrane on the non-traumatized peritoneal wall, respectively. Animals were killed after 14 days; adhesions were scored in groups 1 and 2, and the tumour mass in groups 3-5. 45 Wag/Rij rats underwent the same procedures and treatment as mice in groups 3-5. In rats, 10(6) CC-531 cells were injected. Rats were killed after 3 weeks and the tumour mass was scored. Results: HA membrane resulted in a significant reduction of adhesions, but had no major effect on the intraperitoneal tumour mass in mice and rats. CONCLUSION: HA-carboxymethylcellulose bioresorbable membrane has no major effect on intraperitoneal tumour implantation and growth in an experimental model.     

骨质疏松症中医证型与骨转换标志物相关性研究

骨质疏松症因其发病隐匿，早期诊断困难，被称为“无形杀手”。骨转换标志物可及时反映骨转换状态，灵敏度高、特异性强，有助于了解骨质疏松症骨代谢状态、预测骨折风险、监测疗效。骨质疏松不同中医证型之间骨转换标志物存在差异，通过现代医学技术对骨质疏松症中医证型与骨转换标志物进行相关研究将为中医药辨证论治提供新的思路及客观证据支持。本文综述了骨质疏松症辨证分型存在的问题以及不同证型与骨转换标志物的相关性研究，以期为骨质疏松症现代化辨证论治研究提供参考与思路。     

Heparin and glutathione II: correlation between decondensation of bull sperm cells and its nucleons.

The correlation between the kinetics of bull sperm nuclear and nucleon decondensation induced by the action of physiological concentrations of heparin/GSH was studied. Sperm and nucleon suspensions were incubated at 37 degrees C in salt medium, at a constant concentration of either heparin or GSH and increasing concentrations of the other reagent. Even though nucleons are pretreated with DTT/CTAB, when they are incubated alone with GSH for 96 h, they remain intact, no matter which concentration is employed, and it was impossible to observe the slightest sign of nuclei decondensation. Therefore, rupture of disulfide bridges is not the main mechanism to induce nuclei decondensation and perhaps the GSH role resides in potentate the heparin effect by increasing its negative charge. Nevertheless, nucleons reach 95% of chromatin decondensation in the presence of heparin plus GSH or heparin alone. The fact that the correlation between heparin and GSH concentrations needed to induce sperm nuclei decondensation was 3- to 4-fold greater that in nucleons might be due to the complete lack of nucleon membranes. Heparin/GSH seem to induce nuclei decondensation by an ionic chromatin charge neutralization mechanism.     

Decreased fluidity of polymorphonuclear leukocyte membrane in streptozocin-induced diabetic rats

Using flow cytometry with the excimer-forming lipid technique with pyrenedecanoic acid, we measured membrane fluidity of polymorphonuclear leukocytes (PMNs) from 20 streptozocin (STZ)-induced diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats (body wt 243 +/- 11 g) with an injection of 25 mg/kg i.v. STZ. Membrane fluidity of PMNs was significantly lower at 2 wk after the STZ injection when serum glucose reached the plateau (31.1 +/- 5.8 mM), and after 3 wk, membrane fluidity remained unchanged. In 7 STZ-resistant rats for which serum glucose was less than 10 mM at 2 wk after the STZ injection, gradual normalization in membrane fluidity was observed. PMN membrane fluidity at each week correlated inversely with respective serum glucose levels 1 wk previously (r = -0.76) but not with serum lipid levels. Cross-incubation studies ascribed this observation to factors in the diabetic rat serum. Glycosylated protein, which was separated from diabetic rat serum, decreased membrane fluidity of control rat PMNs. Human diabetic subjects have an increased risk for infection, which may be due partly to altered membrane fluidity of their PMNs.     

Reduced bone volumetric density and weak correlation between infection and bone markers in cystic fibrosis adult patients

Summary

In our current adult CF population, low BMD prevalence was only 20 %, lower than that historically described. We found a mild increase of serum RANK-L levels, independent from the bone resorption level. The increased fracture risk in CF may be explained by a lower tibial cortical thickness and total vBMD.

Introduction

Bone disease is now well described in cystic fibrosis (CF) adult patients. CF bone disease is multifactorial but many studies suggested the crucial role of inflammation. The objectives of this study were, in a current adult CF population, to assess the prevalence of bone disease, to examine its relationship with infections and inflammation, and to characterize the bone microarchitecture using high resolution peripheral scanner (HR-pQCT).

Methods

Fifty-six patients (52 % men, 26?±?7 years) were assessed in clinically stable period, during a respiratory infection, and finally 14 days after the end of antibiotic therapy. At each time points, we performed a clinical evaluation, lung function tests, and biochemical tests. Absorptiometry and dorso-lumbar radiographs were also performed. A subgroup of 40 CF patients (63 % men, 29?±?6 years) underwent bone microarchitecture assessment and was age- and gender-matched with 80 healthy controls.

Results

Among the 56 CF patients, the prevalence of low areal BMD (T-score?<??2 at any site), was 20 % (95 % CI: [10.2 %; 32.4 %]). After infections, serum RANK-L (+24 %, p?=?0.08) and OPG (+13 %, p?=?0.04) were increased with a stable ratio. Microarchitectural differences were mostly observed at the distal tibia, with lower total and cortical vBMD and trabecular thickness (respectively ?9.9, ?3.0, and ?5 %, p?<?0.05) in CF patients compared to controls, after adjustment for age, gender, weight, and height.

Conclusions

In this study, bone disease among adult CF patients was less severe than that previously described with only 20 % of CF patients with low BMD. We found a mild increase of biological marker levels and an impaired volumetric density of the tibia that may explain the increased fracture risk in CF population.