Effects of different molecular weight hyaluronan products on the expression of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis

Hyaluronan or hyaluronic acid (HA) has been used to treat osteoarthritic knees for more than 30 years. Here, we tested the hypothesis that HA with high molecular weight (MW) would have greater effects than HA with low MW on the expression of the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)‐2 and MMP‐9] during early development of osteoarthritis (OA). We compared the levels of MMP‐2, MMP‐9, urokinase‐type PA (u‐PA), and PA inhibitor‐1 (PAI‐1) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without three different MW HA products (Hyalgan and Artz with low MW, and Synvisc with high MW). Gelatin zymography revealed that three different HA products could decrease the secretion of MMP‐2 in all tissue cultures and MMP‐9 in meniscal and synovial cultures time‐dependently. Enzyme‐linked immunosorbent assay showed that Artz and Synvisc had significant inhibition on u‐PA and PAI‐1 levels after 24 h, but Hyalgan did at 96 h. Compared with Hyalgan and Artz, Synvisc provided the greatest ability to inhibit MMP‐2, MMP‐9, u‐PA, and PAI‐1 expression. Our studies clearly demonstrate that the therapeutic effects of using HA to treat early OA may be partially dependant on downregulation of the PA/plasmin system and gelatinases expression, which delay the structural progression of the disease. HA with high MW might have a greater ability than that with low MW to offer effective protection for articular cartilage. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:475–484, 2008     

蛛网膜下腔不同剂量罗哌卡因复合PCEA分娩镇痛的临床研究

目的 :比较不同剂量罗哌卡因 (Rop)蛛网膜下腔注射复合硬膜外病人自控镇痛 (PCEA)进行分娩镇痛的效果及对产程的影响。方法 :12 0例单胎足月的自愿初产妇随机分为Ⅰ～Ⅵ组 ,每组 2 0例 ,分别蛛网膜下腔注入 :Ⅰ组Rop2 .0mg、Ⅱ组Rop 2 .5mg、Ⅲ组Rop 3.5mg、Ⅳ组Rop 5 .0mg、Ⅴ组Rop 2 .0mg +芬太尼 2 0 μg、Ⅵ组芬太尼 2 0 μg。六组均于L2～ 3 腰穿注药后留置硬膜外导管行PCEA ,硬膜外腔采用 0 .1%Rop与 2 .0 μg/mL芬太尼混合液持续输注 5mL/h ,自控镇痛每次给药 3mL ,锁定时间 10min。结果 :Ⅰ组～Ⅳ组镇痛起效时间平均 (5 .9± 1.5 )min。Ⅴ组平均 (2 .0± 1.5 )min ,比其他组起效较快 (P <0 .0 5 ) ,Ⅵ组平均 (6 .2± 1.8)min。六组蛛网膜下腔注药起效稳定后阻滞平面T9～ 11。各组蛛网膜下腔给药后阻滞平面与PCEA 1h后的阻滞平面比较未见明显变化。六组镇痛效果均达到满意程度 ,各组视觉模拟镇痛 (VAS)评分 :随着蛛网膜下腔注射Rop剂量增加 ,VAS评分值有减少趋势 (P >0 .0 5 )。各组Bromage运动评分 :以Ⅳ组分值较高 ,其运动阻滞程度较为显著 (P <0 .0 5 ) ;各组对产程、产后出血量、胎儿Apgar评分、器械助产率、剖宫产率的影响差异无显著性 (P >0 .0 5 ) ,但是催产素的使用率Ⅳ组较其它组显著增     

骶管的临床应用解剖学研究

对华北地区出土自然干燥成人２００个骶骨的骶管后壁和骶管裂孔形态进行观察，并测量了骶骨裂孔各径线。结果为骶管后壁完整的１１０例，占５５％，约４５％骶管后壁有裂或孔。骶管裂孔以三角形为多见，约占４４．５％，其次为不规则形、长方形或马蹄形，骶管裂孔高为２４．３５ｍｍ±３．２４ｍｍ，底宽为１５．２ｍｍ±１．３７ｍｍ，骶孔尖矢径小于２ｍｍ的有２例，占１％，并对骶管阻滞麻醉方法进行探讨。     

缺铁性贫血前期患者红细胞参数测定的临床意义

[目的 ]探讨缺铁性贫血前期红细胞参数的改变。 [方法 ]实验组 6 5名 ,血红蛋白 >1 1 0 g/L ,平均红细胞血红蛋白含量 <2 7pg ,对照组 4 0名 ,血红蛋白 >1 1 0 g/L ,平均红细胞血红蛋白含量 2 7～ 31 pg ,比较两组的红细胞比积 ,平均红细胞容积 ,平均红细胞血红蛋白含量 ,平均红细胞血红蛋白浓度 ,红细胞体积分布宽度 ,血清铁蛋白SF ,瑞氏染色观察红细胞改变。 [结果 ]发现实验组的平均红细胞体积 ,平均红细胞血红蛋白含量 ,血清铁蛋白明显较对照组降低 ,红细胞比积也有降低 ,而红细胞数量明显增加。 [结论 ]实验组的血红蛋白含量正常 ,但存在铁贮备降低的情况 ,称之为缺铁性贫血前期 ,其红细胞参数的最明显的特征是血红蛋白 ,平均红细胞血红蛋白浓度正常 ,红细胞数量明显增加 ,而平均红细胞体积和平均红细胞血红蛋白含量明显降低。     

菊三七组织培养的研究

目的　探讨菊三七诱导愈伤组织的过程 ,为快速繁殖幼苗奠定基础。方法　以菊三七的根、茎、叶为外植体 ,采用 MS培养基 ,附加不同的植物激素进行实验。结果　以菊三七的叶片为外植体 ,在培养基 MS 1.0 mg/ LNAA 4 .0 m g/ L 6- BA上 ,愈伤组织诱导率可达 64%。愈伤组织在适宜的分化培养基上 ,成苗率可达 86.7%。结论　通过诱导愈伤组织的途径 ,可以达到快速繁殖菊三七的目的     

Arteriographic demonstration of both kinking at the origin and compression between the great vessels of an anomalous right coronary artery arising in common with a left coronary artery from above the left sinus of valsalva

Angled angiographic views demonstrated two areas of significant systolic narrowing in an anomalous right coronary artery arising in common with a left coronary artery from above the left sinus of Valsalva: (1) an ostial stenosis due to kinking as the anomalous artery turned sharply to the right after its origin from the aorta; (2) compression of the proximal segment as it coursed between the aorta and pulmonary artery. Appropriate angiographic studies to evaluate the presence of these changes may help to elucidate their significance.     

血管内超声探测冠状动脉病变与其危险因素的关联性

目的 :通过血管内超声 （IVU S）观察冠状动脉病变与冠心病 （CHD）危险因素的关系。方法 :根据是否伴 CHD危险因素分无危险因素患者 4 0例 ;伴 CHD危险因素患者 10 4例 ,再将伴 CHD危险因素患者按血管狭窄程度分狭窄 <75 %组 4 3例 ,狭窄≥ 75 %组 6 1例。所有患者均行冠状动脉造影 （CAG）及 IVU S检查。结果 :1狭窄 <75 %组、狭窄≥ 75 %组与无危险因素组比病程短 ,且血管狭窄≥ 75 %组病程更短 （P<0 .0 5 ） ,不稳定型心绞痛及急性心肌梗死发病率高。 2狭窄≥ 75 %组的血管病变长度较无危险因素组及狭窄 <75 %组明显延长 （均 P<0 .0 1）。 3狭窄≥75 %组多为脂质性及偏心性斑块 ,无危险因素组则以纤维性及同心性斑块为主。 4狭窄 <75 %组、狭窄≥ 75 %组可见明显的正性血管重构 ,多于无危险因素组。狭窄≥ 75 %组比狭窄 <75 %组有更多的负性血管重构。结论 :CHD伴危险因素患者 ,CHD的病程短、进展快 ,冠状动脉病变不稳定 ,有明显的血管重构 ,正性重构以软斑块为主 ,此时冠状动脉内血栓和斑块破裂现象也更多见。负性重构则加速斑块生长导致管腔严重狭窄     

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

Aim:

Sustained pulmonary vasoconstriction as experienced at high altitude can lead to pulmonary hypertension (PH). The main purpose of this study is to investigate the vasorelaxant effect of echinacoside (ECH), a phenylethanoid glycoside from the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa, on the pulmonary artery and its potential mechanism.

Methods:

Pulmonary arterial rings obtained from male Wistar rats were suspended in organ chambers filled with Krebs-Henseleit solution, and isometric tension was measured using a force transducer. Intracellular Ca²⁺ levels were measured in cultured rat pulmonary arterial smooth muscle cells (PASMCs) using Fluo 4-AM.

Results:

ECH (30–300 μmol/L) relaxed rat pulmonary arteries precontracted by noradrenaline (NE) in a concentration-dependent manner, and this effect could be observed in both intact endothelium and endothelium-denuded rings, but with a significantly lower maximum response and a higher EC₅₀ in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCl₂. However, IMT, 4-AP, and Gli did not inhibit ECH-induced relaxation. Under extracellular Ca²⁺-free conditions, the maximum contraction was reduced to 24.54%±2.97% and 10.60%±2.07% in rings treated with 100 and 300 μmol/L of ECH, respectively. Under extracellular calcium influx conditions, the maximum contraction was reduced to 112.42%±7.30%, 100.29%±8.66%, and 74.74%±4.95% in rings treated with 30, 100, and 300 μmol/L of ECH, respectively. After cells were loaded with Fluo 4-AM, the mean fluorescence intensity was lower in cells treated with ECH (100 μmol/L) than with NE.

Conclusion:

ECH suppresses NE-induced contraction of rat pulmonary artery via reducing intracellular Ca²⁺ levels, and induces its relaxation through the NO-cGMP pathway and opening of K⁺ channels (BK_Ca and K_IR).     

Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated Ah-type baroreceptor neurons of rats

Background

Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated.

Methods

Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated.

Results

Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2^nd-order capsaicin-resistant EPSCs were identified and ∼50% of them were blocked by ketamine concentration-dependently with IC₅₀ estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types).

Conclusions

These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.     

Radiolabeling and evaluation of 64Cu-DOTA-F56 peptide targeting vascular endothelial growth factor receptor 1 in the molecular imaging of gastric cancer

Noninvasive imaging of vascular endothelial growth factor receptor 1 (VEGFR1) remains a great challenge in early diagnosis of gastric cancer. Here we reported the synthesis, radiolabeling, and evaluation of a novel ⁶⁴Cu-radiolabeled peptide for noninvasive positron emission tomography (PET) imaging of VEGFR1 positive gastric cancer. The binding of modified peptide WHSDMEWWYLLG (termed as F56) to VEGER-1 expressed in gastric cancer cell BCG823 has been confirmed by immune-fluorescence overlap. DOTA-F56 was designed and prepared by solid-phase synthesis and folded in vitro. ⁶⁴Cu-DOTA-F56 was synthesized in high radiochemical yield and high specific activity (S.A. up to 255.6 GBq/mmol). It has excellent in vitro stability. Micro-PET imaging of ⁶⁴Cu-DOTA-F56 identifies tumor in BCG823 tumor-bearing mice, while that of ¹⁸F-FDG does not. Immunohistochemical analysis of excised BCG823 xenograft showed colocalization between the PET images and the staining of VEGFR1. These results demonstrated that ⁶⁴Cu-DOTA-F56 peptide has potential as a noninvasive imaging agent in VEGFR1 positive tumors.