透明质酸对白细胞介素1β与软骨滑膜联合培养模型的作用

目的:观察不同浓度透明质酸对白细胞介素1β与软骨滑膜联合培养模型中软骨基质代谢的影响与抑制炎性反应的作用,从而阐明粘保护剂治疗骨性关节炎的可能机制。方法:实验于2006-03/11在华中科技大学附属协和医院骨科实验室完成。①实验材料:新鲜狗尸体4具,取肱骨头附近的全厚软骨以及滑膜组织。透明质酸钠购于中国山东正大福瑞达制药有限公司产品。②实验干预和分组:以100μg/L的白细胞介素1β与软骨滑膜联合培养。将0.2,1,2g/L透明质酸加入模型中得到3组透明质酸组,只含白细胞介素1β为阳性对照组,只含培养液为阴性对照组。③实验评估:每3天收集1次培养皿中的溶液标本,3,6,20d收集培养皿中的软骨滑膜标本,行生化和免疫组织化学检查。结果:①溶液标本与组织标本聚氨基葡萄糖检测结果:第3,6天溶液标本中透明质酸组高于阴性对照组(P<0.05);第20天时3种剂量透明质酸组溶液中聚氨基葡萄糖低于阳性对照组(P<0.05)。②溶液标本中前列腺素E2、基质金属蛋白酶3、含氮产物检测结果:第3天时阳性对照组基质金属蛋白酶3浓度高于阴性对照组(P<0.05),第20天,1g/L,2g/L透明质酸组基质金属蛋白酶3浓度较阳性组低[(1.289±2.122),(0.458±0.454),(1.425±0.211)μg/L,P<0.05],第3天时阳性对照组前列腺素E2浓度明显高于阴性对照组(P<0.05),第6天,0.2g/L,1g/L透明质酸组含氮产物浓度低于阳性和阴性对照组[(1.288±0.280),(1.345±0.768),(2.234±0.570),(1.845±0.767)mmol/L(P<0.05)。结论:实验结果支持粘保护剂治疗骨性关节炎的两种机制,即透明质酸对软骨保护的生物学合成作用与透明质酸的炎性抑制反应。     

Bone marrow-derived macrophage contributes to fibrosing steatohepatitis through activating hepatic stellate cells

The role of macrophages in fibrosing steatohepatitis is largely unclear. We characterized the origin and molecular mechanisms of macrophages and its targeted therapy of fibrosing steatohepatitis. Fibrosing steatohepatitis was established in Alms1 mutant (foz/foz) and C57BL/6J wildtype mice fed high-fat/high-cholesterol or methionine- and choline-deficient diet. Bone marrow transplantation was performed to track the macrophage origin in fibrosing steatohepatitis. Macrophages were depleted using liposomal clodronate. Primary macrophages were isolated from bone marrow for adoptive transfer into mice. We found that macrophage infiltration is induced in two mouse models of fibrosing steatohepatitis and human nonalcoholic steatohepatitis-fibrosis patients. Bone marrow-derived macrophages (BMMs) contribute to the hepatic macrophage accumulation in experimental fibrosing steatohepatitis. Depletion of hepatic BMMs by liposomal clodronate during liver injury attenuated fibrosing steatohepatitis, whilst BMMs depletion after liver injury delayed the regression of fibrosing steatohepatitis. The pro-fibrotic effect of macrophages was associated with reduced activation of hepatic stellate cells (HSCs), collagen deposition and hepatic expression of key pro-fibrotic factors (TIMP1, TIMP2, and TGFβ1) and endoplasmic reticulum stress markers (GRP78, IRE1α, and PDI). Conversely, adoptive transfer of BMMs significantly aggravated fibrosing steatohepatitis. Moreover, macrophage-conditioned medium directly promoted the phenotypic transition of primary quiescent HSCs to activated HSCs; it enhanced activation and proliferation but decreased apoptosis of HSC cell lines (LX-2 and HSC-T6). The effect of BMMs in promoting fibrosing steatohepatitis was mediated by inducing key pro-fibrosis factors and signaling pathways including cytokine/chemokine, TGFβ and complement cascade as assessed by cDNA expression array. Complement 3a receptor (C3ar1) was a predominant effector of macrophage mediated fibrosing steatohepatitis. Knockout of C3ar1 in mice blunted development of fibrosing steatohepatitis. In conclusion, BMMs promoted the progression of fibrosing steatohepatitis during injury, whereas macrophages reduced fibrosing steatohepatitis in the recovery phase of liver injury. Increasing anti-fibrotic macrophages and decreasing pro-fibrotic macrophages are promising approaches for fibrosing steatohepatitis. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

BACKGROUND: A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. METHODS: From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. RESULTS: Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n = 7), radiotherapy alone (n = 10) and radiotherapy with adjuvant chemotherapy (n = 5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P = 0.017 and 0.036). A trend of better outcome with radiation dose > 6600 cGy and the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P = 0.0355). Survival was not significantly affected by age, gender or method of diagnosis. CONCLUSION: Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival.      

Conscious sedation for interventional neuroradiology: a comparison of midazolam and propofol infusion

Purpose

The aim of this study was to compare two conscious sedation techniques, midazolam (M) and propofol (P), for interventional neuroradiology by assessment of the incidence of complications and satisfaction scores.

Methods

Forty patients were randomized to receive 0.75 μg · kg^?1 fentanyl and a M or P bolus followed by an infusion; (M I5 μg · kg^?1 + 0.5 μg · kg^?1 · min^?1: P 0.5 mg · kg^?1 + 25 μg · kg^?1 min^?1). The incidences of complications and untoward events requinng intervention were documented. These included respiratory depression, excessive pain, inappropriate movements and the inability to examine the patient. The satisfaction of the anaesthetic technique from the perspective of both the neuroradiologist and the patient was scored.

Results

The incidence and types of complications were not different between the two groups. Pain occurred in 12 patients (6M, 6P), inappropriate movements in 17 (7M, 10P) and respiratory changes in 10 patients (2M, 8P).

Conclusions

Both techniques were satisfactory and the incidence of complications was similar for both groups.     

国产麻黄的形态组织学研究——Ⅰ.北方主产的七种麻黄

据文献记载和作者的调查,我国产麻黄属(Ephedra)植物共有13种3变种1变型。本文报道我国北方生产的7种麻黄生药形态组织学比较研究结果。7种麻黄是:草麻黄Ephedra sinica Stapf、木贼麻黄E.equisetina Bunge、中麻黄E.intermedia Schrenk ex Mey.、膜果麻黄E.przewalskii Stapf,单子麻黄E.monosperma Gmel.ex Mey.、雌雄麻黄E.fedtschenkoae Pauls和细子麻黄E.reaeliana Florin。文中附有生药性状与组织构造特征比较表及生药组织图。     

三年来我室TDM室间质评结果回顾

目的：对我室３年来ＴＤＭ室间质评估结果的准确性作一个客观的评价,同时分析存在的问题及产生这些问题的原因。方法：对我室３年来参加室间质评的茶碱,苯妥英,地高辛３个监测品种的平均成绩进行纵向及横向对比,分析。结果;茶碱和苯妥英成绩较好,地高辛成绩呈逐年上升的趋势。结论;通过采取一系列有效措施后,我的治疗药物监测可成为临床用药较为可靠的参考。     

ELONGATED STYLOID PROCESS SYNDROME (EAGLE'S SYNDROME)

A 45 year old man presented with persistent pain in throat and otalgia. Clinical and radiographic evaluation confirmed the diagnosis of elongated styloid process syndrome. Surgical shortening of the styloid processes gave relief. The etiopathogenesis, presentation and management of the condition is discussed.KEY WORDS: Eagle''s syndrome, Styloid process     

Genotoxic effects of cyclopenta-fused polycyclic aromatic hydrocarbons in different types of isolated rat lung cells

The genotoxic effects of the environmental contaminants benz[j]aceanthrylene (B[j]A), benz[l]aceanthrylene (B[l]A) and benzo[a]pyrene (B[a]P), and the metabolism of radiolabelled B[j]A, were studied using rat lung microsomes and various types of isolated rat lung cells from control and Aroclor 1254 (PCB) treated animals. All three compounds (10 or 20 microg/plate) resulted in low, but detectable, levels of His+ revertants in the Salmonella assay when plated with control lung microsomes. The two cyclopenta polycyclic aromatic hydrocarbons (CP-PAH) B[j]A and B[l]A, gave increased levels of revertants when plated with microsomes from PCB-treated animals. Clara cells, type 2 cells and alveolar macrophages isolated from control rats were exposed to B[j]A, B[l]A or B[a]P (30 microg/ml, 1 h), but neither of the cell types showed any DNA damage when measured by alkaline filter elution. However, both B[j]A and B[l]A (30 microg/ml, 2 h) caused DNA adducts in all three cell types, measured by the 32P-post- labelling technique, whereas no B[a]P adducts were detected (30 microg/ml, 2 h). The total DNA adduct levels in Clara cells, type 2 cells and macrophages exposed to B[j]A were 0.085 +/- 0.033, 0.053 +/- 0.001 and 0.170 +/- 0.030 fmol/microg DNA, respectively, whereas the total levels in cells exposed to B[l]A were 0.140 +/- 0.070, 0.140 +/- 0.030 and 0.220 +/- 0.080 fmol/microg DNA, respectively. Cells exposed to B[j]A revealed only one adduct which corresponds with the B[j]A-1,2- oxide DNA adduct. Judged from high performance liquid chromatography (HPLC) analysis using radiolabelled B[j]A (30 microg/ml, 30 min), the major metabolite formed in control microsomes was B[j]A-1,2-diol. Thus, oxidation at the cyclopenta ring appears to be the most important activation pathway for B[j]A with control rat lung cells. Exposure of lung cells to CP-PAH (30 microg/ml, 2 h) isolated from PCB pretreated rats resulted in slightly increased DNA adduct levels in Clara cells and macrophages when compared to cells isolated from control rats. Furthermore, the adduct pattern had shifted, and no apparent B[j]A-1,2- oxide adduct could be detected on the thin layer chromatography (TLC) plate. In contrast, the major metabolite formed with microsomes from PCB-treated animals was still the B[j]A-1,2-diol.      

The role of PKA and PKCε pathways in prostaglandin E2-mediated hypernociception

Background and purpose:

Protein kinase (PK) A and the ε isoform of PKC (PKCε) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKCε to the development of prostaglandin E₂ (PGE₂)-induced mechanical hypernociception.

Experimental approach:

Prostaglandin E₂-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKCε was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws.

Key results:

Hypernociception induced by PGE₂ (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKCε (PKCεI) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE₂ but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKCε, while the hypernociception induced by paw injection of PKCε agonist was not affected by an inhibitor of PKA (AKAPI).

Conclusions and implications:

Taken together, these findings are consistent with the suggestion that PKA activates PKCε, which is a novel mechanism of interaction between these kinases during the development of PGE₂-induced mechanical hypernociception.