新鲜异体和自体骨软骨移植实验研究

目的评价异体和自体骨软骨移植的修复软骨缺损的差别。方法采用20只成年新西兰兔,造成直径4mm的软骨缺损,采用压配技术进行移植修复;术后12周行大体观察、HE染色、番红O染色行组织学检查,用改良的Wakitani标准评分,并行透射电镜检查。结果新鲜异体与自体骨软骨移植均成活,得分相近。结论新鲜异体和自体骨软骨移植在修复兔的软骨缺损,在组织学上无明显差异,新鲜异体骨软骨可以作为移植的供体。     

应用组织工程骨-软骨复合组织块修复猪软骨缺损

目的 比较应用组织工程骨-软骨复合组织块与单纯组织工程软骨修复猪膝关节软骨缺损的疗效.方法 用软骨细胞和成骨细胞构建组织工程软骨和组织工程骨,再将两者缝合形成骨-软骨复合组织块.在12只猪双侧股骨内髁负重区制造直径8mm的软骨缺损24个,并均分为组织工程骨-软骨复合组织块修复(A)组、组织工程软骨修复(B)组和空白支架(C)组.6个月后对修复部位行大体观察和组织学观察,免疫组化法检测Ⅱ型胶原的表达,并测定新生软骨的力学性能和糖胺聚糖(GAG)含量.结果 A组缺损区被新生透明软骨修复,新生软骨中的圆形细胞分布均匀.A组缺损区的新生软骨弹性模量和GAG含量高于B组.结论 组织工程骨-软骨复合组织块修复软骨缺损的效果明显优于组织工程软骨.     

自体骨软骨移植柱大小对移植软骨组织学特性影响的实验研究

目的探讨自体骨软骨移植(osteochondral autograft transfer system,OATS)修复软骨缺损术后骨软骨移植柱大小对移植软骨组织学特性的影响。方法选用18只健康成年新西兰白兔,随机分成2组,每组各8只。A组:使用骨软骨移植工具(Arthrex,Naples,FL)从右膝股骨内髁获取一圆柱形骨软骨柱(直径7毫米,深度5毫米),然后再将其植回原位。这些模型曾被设想为骨软骨移植柱与周围关节面几何形状完全匹配,但是实际上骨软骨移植柱与缺损部位之间存在和环形钻厚度一样的环形缝隙。B组:使用跟A组同样的方法获得右膝股骨内髁骨软骨缺损的模型,然后从左膝股骨髁同样部位取直径加大1mm的骨软骨柱(直径8mm,深度5mm)移植至缺损部位,以获得紧密匹配。分别在术后4、12、24周获取样本,然后使用蕃红O/固绿染色,再在显微镜下观察。结果在A组里,组织学检查显示在移植期间软骨厚度、细胞密度均增加,移植的关节软骨周围可见到圆形和多边行的簇状过度增生的软骨细胞,以及增生的纤维组织。相反,在B组里,移植的关节软骨的厚度、密度和周围正常软骨的几乎一样,没有明显的增厚,也没有明显的纤维组织增生。结论本实验提示骨软骨移植柱的大小在保留移植软骨的组织学特性上起重要的作用。临床参考:本研究提示骨软骨移植柱的稳定性可能影响修复软骨的组织学特性,因此建议在自体骨软骨移植中用稍大的骨软骨柱(直径约增大1m)植入缺损区域。     

RhIGF-I/CHA/ARBM重组人工骨移植组织学评估

目的从组织学角度探讨重组人胰岛素样生长因子-1(rhIGF-I)/珊瑚羟基磷灰石(CHA)/自体红骨髓(ARBM)重组构建复合活性人工骨修复骨缺损的能力。方法54只家兔制双侧桡骨干11mm全层缺损模型,分六组移植相应材料:A组(rhIGF-I/CHA/ARBM),B组(CHA/ARBM),C组(rhIGF-I/CHA),D组(CHA),对照组为E组(自体骨)和F组(缺损旷置),每组9只各18侧。2、4、8、12周经大体观察、组织学观察及Lane-Sandhu组织学评分、抗弯生物力学评估各组修复骨缺损效果。结果rhIGF-I/CHA/ARBM组组织学和生物力学综合评价与自体骨移植无显著性差异。结论rhIGF-I/CHA/ARBM具有较强的协同成骨能力,可替代自体骨移植,成为新型的复合活性人工骨。     

骨膜和软骨膜移植修复关节软骨缺损

关节的创伤和关节疾病均可导致关节软骨的缺损，临床上较为多见。因关节软骨的自身修复能力较差，缺损往往不能自行修复，从而引起不同程度的关节功能障碍。为此国内外许多学者就修复关节软骨缺损这一问题做了多方面的长期大量研究，如软骨下骨钻孔，自体和异体软骨移植，...     

RhIGF—Ⅰ／CHA／ARBM重组人工骨移植组织学评估

目的从组织学角度探讨重组人胰岛素样生长因子-Ⅰ（rhlGF-Ⅰ）／珊瑚羟基磷灰石（CHA），自体红骨髓（ARBM）重组构建复合活性人工骨修复骨缺损的能力。方法54只家兔制双侧桡骨干11mm全层缺损模型，分六组移植相应材料：A组（rhIGF-Ⅰ／CHA／ARBM），B组（CHA／ARBM），C组（rhIGF—Ⅰ，CHA），D组（CHA）。对照组为E组（自体骨）和F组（缺损旷置），每组9只各18侧。2、4、8、12周经大体观察、组织学观察及Lane-Sandhu组织学评分、抗弯生物力学评估各组修复骨缺损效果。结果rhIGF-Ⅰ／CHA／ARBM组组织学和生物力学综合评价与自体骨移植无显著性差异。结论rhIGF-Ⅰ／CHA／ARBM具有较强的协同成骨能力，可替代自体骨移植，成为新型的复合活性人工骨。     

自体骨膜─同种异体深冻骨移植修复关节骨软骨缺损的实验研究

目的：为了探寻修复关节骨软骨缺损简便而有效的方法。取健康家兔16只,单侧膝关节股骨关节面造成骨软骨缺损约4？8mm2,实验组采用自体骨膜一同种异体深冻骨修复缺损,对照组采用自体骨膜一骨块修复。结果：1、大体观察两组骨膜再生组织光滑完整,关节挛缩,关节内粘连轻微（P？0．05）。2、光镜观察两组在优势组织、表面特性、结构完整,与正常软骨连接等方面统计学上无显著性差异。3、电镜下两组再生组织软骨细胞细胞器丰富、生长活跃、结构正常。结果提示：1、同种异体深冻骨不影响骨膜生发层间充质细胞向软骨细胞转化。2、移植骨膜能够转化为类透明软骨。3、自体骨膜-同种异体深冻骨移植是修复关节骨软骨缺损简便而有效的方法。     

自体骨-骨膜复合组织移植修复膝关节软骨缺损的临床应用

目的 研究膝关节软骨大面积缺损后,利用自体骨-骨膜复合组织移植修复缺损的临床效果,探索出一种新的治疗方法.方法 将创伤后B、C型胫骨平台骨折合并关节软骨大面积缺损6例6膝,在开放手术骨折内固定的同时,在膝关节同一切口内将自体骨-骨膜移植到膝关节面的软骨缺损区,通过良好固定使骨膜面向关节腔,骨质与受区软骨下骨牢固结合,再及时给予术后的功能锻炼.结果 术后随访0.5 ～1.5年,平均1年.所有患者膝关节活动良好,疼痛症状基本消失.采用HSS膝关节评分标准综合评价,术后膝关节功能优3膝、良2膝,优良率83.3％.结论 对于B、C型胫骨平台骨折合并大面积关节软骨缺损,将自体骨-骨膜移植到膝关节面的软骨缺损区,使膝关节获得满意功能,减少了关节软骨面缺损为患者带来的伤残率.     

壳聚糖/磷酸甘油复合浓缩自体骨髓修复关节软骨的实验研究

目的探讨壳聚糖/磷酸甘油（C/GP）复合浓缩自体骨髓修复兔关节软骨缺损的效果。方法选择3个月龄新西兰大耳白兔24只,双下肢髁关节面上共制作3个直径4mm、深2mm的全层软骨缺损,自左到右为：壳聚糖/磷酸甘油复合浓缩自体骨髓组（A组）,壳聚糖/磷酸甘油组（B组）,空白对照组（C组）。分别于术后4,8,12周各处死8只,应用大体观察、组织学观察及组织学评分评估缺损软骨的修复情况。结果 C/GP复合浓缩自体骨髓组术后12周、组织切片显示新生组织中可见大量类透明软骨细胞出现,修复组织和周围软骨整合良好。A组各个时间点组织学评分均低于于其他2组（P〈0.05）。结论 C/GP复合浓缩自体骨髓提高了对兔关节软骨缺损的修复效果。     

不同面积同种异体兔关节软骨移植的实验研究

目的观察不同面积同种异体兔关节软骨移植后的成活情况,评价其可行性并确定适宜的移植面积。方法60只成兔分为3组,分别造成双膝关节直径3 mm（A组）、5 mm（B组）、9 mm（C组）的圆形、全层软骨缺损。15只幼兔作为移植供体,将相应大小的幼兔关节软骨移植于成兔关节软骨缺损处,术后2、4、12、24周取标本行大体、光镜、电镜组织学动态观察并进行质量评估。结果3个实验组不同时期均能获得不同程度透明软骨修复,小面积软骨移植修复组织更接近正常软骨组织,大块软骨移植能较好地保持关节面的平整,但细胞退变明显。三组间组织学和组织化学评分比较,差异有统计学意义（P＜0．01）。结论不同面积软骨移植均可成活,大块软骨移植是可行的。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.