脂质血管生长因子对皮肤创伤愈合中表皮细胞增殖周期的影响

应用从兔大网膜抽提的脂质血管生长因子在浅Ⅱ度烫伤模型上观察了对表皮细胞增殖周期的影响。结果显示，脂质血管生长因子从d3开始能明显增加表皮细胞DNA的合成，维持到d5，d7后趋于正常。G2＋M期从d7开始明显增加，表明此时表皮细胞已进入细胞分裂期。     

Evaluation of a Highly Skin Permeable Low-Molecular-Weight Protamine Conjugated Epidermal Growth Factor for Novel Burn Wound Healing Therapy

We evaluated the laser induced burn wound healing efficacy of a recombinant low-molecular-weight protamine conjugated epidermal growth factor (rLMWP-EGF). rLMWP-EGF was prepared by genetically combining LMWP with the N-terminal sequence of EGF; we obtained a homogeneous modified EGF without reduced biological activity. Because of the protein transduction domain of LMWP, rLMWP-EGF showed enhanced drug penetration across artificial skin constructs and excised mouse skin layers versus EGF and showed significantly improved burn wound healing efficacy, with accelerated wound closure and minimized eschar and scar formation, compared with EGF or no treatment. Histological examination also revealed that rLMWP-EGF permeated through the intact skin around the wound and facilitated residual epithelial cell proliferation in an integrated manner to reform an intact epidermis. Radiofrequency microwound formation was effective for reducing large hypertrophic scars formed after severe laser burning by collagen remodeling but rLMWP-EGF did not show a meaningful synergistic effect in burn scar reduction. However, rLMWP-EGF was helpful for forming skin with a more normal appearance and texture. Thus, rLMWP-EGF demonstrated therapeutic potential as a novel topical burn wound healing drug with no obvious toxic effect.     

壳聚糖对大鼠Ⅲ度烧伤创面表皮生长因子的影响研究

目的:研究壳聚糖对大鼠Ⅲ度烧伤创面表皮生长因子(EGF)和EGFmRNA表达的影响及意义。方法:105只Wistar大鼠除5只作为正常对照组外,其余建立烧伤模型后分为壳聚糖低、中、高浓度(1%、2%、4%)组及贝复济组(阳性对照组)和自然愈合组(模型组),每日2次连续21d于受伤处喷以相应药物,采用免疫组织化学法、核酸分子杂交法及图象分析法检测烧伤后3、7、14、21d时大鼠Ⅲ度烧伤创面EGF和EGFmRNA的表达。结果:与模型组比较,壳聚糖各浓度组均可增强EGF和EGFmRNA的表达,并呈浓度依赖性,尤以4%壳聚糖组作用更强(P<0.01或P<0.05)。结论:壳聚糖对大鼠Ⅲ度烧伤创面有促愈合作用,其促愈合机制与增强创面EGF和EGFmRNA表达有关。     

枯草芽孢杆菌喷雾剂对小鼠皮肤创伤愈合的影响

目的:观察枯草芽孢杆菌喷雾剂对小鼠皮肤创伤愈合疗效的影响。方法:采用小鼠皮肤创伤为模型,连续给药6d,第9天测定创面的缩小程度,并于第15天,观察各试验组的愈合率,并用直径12毫米的打孔器,取下创面新生皮肤并称重,观察肉芽生长的情况。结果:枯草芽孢杆菌喷雾剂高剂量组和磺胺嘧啶银组创面面积显著小于空白对照组(p<0.05);枯草芽孢杆菌喷雾剂的愈合率显著高于空白对照组(p<0.05)。结论:枯草芽孢杆菌喷雾剂能够显著缩小创面面积,增加创面肉芽的重量,增加创面的愈合率。     

烧伤创面应用生皮素治疗的临床观察

目的：观察生皮素（EGF）促进浅度烧伤,刃厚供皮区,残余创面的愈合作用及生皮素对磺胺嘧啶银的抗感染作用影响。方法：治疗组生皮素采用局部喷涂给药的方法,再以1%磺胺嘧啶银霜覆盖创面。对照组应用1%磺胺嘧啶银霜覆盖创面,共治疗289例烧伤伤员,516个创面,包括浅2度烧伤、深2度烧伤、残余小创面及供皮区区面,肉眼观察创面出现了上皮组织时间,浅2度创面用药后8d,深2度创面用药16d创面愈合率比较,创面完全愈合时间比较,创面表面细菌培养结果对比及生皮素对全身情况的影响。结果：浅2度烧伤和刃厚供皮区创面,应用生皮素创面完全愈合时间较对照组提前2-3d。深2度创面创面愈合时间,用药组比对照组提前2-3d。对残余小创面的愈合比较,用药组比对照组提前3-4d。细菌学调查结果表明治疗组与对照组间抗菌作用无显著性的差异。用药伤员未出现疼痛、皮疹、过敏反应和其它药物不良反应。     

无水磺胺嘧啶锌应用于烧伤创面后血锌和尿锌的含量变化研究

目的研究烧伤创面应用无水磺胺嘧啶锌后血锌和尿锌的含量变化。方法取烧伤患者浅Ⅱ度创面,用无水磺胺嘧啶锌粉剂1.0g撒于1%烧伤面积创面上,连续3d,1次/d,分别于用药前、用药后3d、用药后1wk测定血锌和24h尿锌含量。结果与用药前比较,用药后血锌含量无显著性变化(P>0.05),尿锌含量显著升高(P<0.01)。结论无水磺胺嘧啶锌应用于烧伤创面后,锌吸收量少,体内锌离子主要通过肾脏排泄。     

胶原蛋白海绵复合bFGF促进兔胫骨外露创面愈合的实验研究

目的研究胶原蛋白海绵复合bFGF对骨外露创面愈合的影响。方法 30只日本大耳白兔,随机分为A、B、C三组,每组10只。于胫骨上段前内侧作一1cm×1.5cm创面,暴露胫骨。A组创面喷洒bFGF后,胶原蛋白海绵覆盖,纱布包扎。B组覆盖胶原蛋白海绵扎。C组喷洒生理盐水。术后观察各组创面完全愈合的时间,测量并计算术后各时期创面收缩率。创面愈合后,取材,HE染色,显微镜下观察组织结构。结果大体观察:A、B、C组创面愈合时间分别为(25.12±1.46)d、(30.50±1.69)d、(33.38±1.77)d。A组较B、C组愈合时间提前,差异有统计学意义(P<0.01)。组织学观察:A组创面愈合质量优于B、C组。结论胶原蛋白海绵复合bFGF对兔胫骨外露创面愈合具有促进作用,提高创面愈合质量,减少瘢痕组织。     

表皮生长因子甘草锌复合膜治疗口腔溃疡的动物实验研究

探讨表皮生长因子甘草锌复合膜对口腔溃疡动物模型的疗效。方法：将24只家兔随机分为治疗组、对照组和空白组,各8只。以冰醋酸润湿脱脂棉,在家兔右侧靠口角黏膜处烧灼1 min,生理盐水冲洗5min,24 h形成溃疡。溃疡形成后每日8点、12点、16点对家兔进行麻醉,治疗组使用复合膜治疗2 h,对照组使用本院制剂溃疡糊剂治疗2 h,空白组不作治疗,疗程为5 d,每日测量家兔溃疡面最大直径,进行组间对比观察。结果：（1）治疗至第3天时,治疗组疗效优于对照组及空白组（P＜0.05）,对照组与空白组差异无统计学意义（P＞0.05）;治疗第5天时,治疗组及对照组疗效差异无统计学意义（P＞0.05）,但均优于空白组（P＜0.05）。（2）在外观治愈的家兔中,对照组家兔组织上皮已修复,但比正常组织薄,固有层纤维比正常组织疏松;治疗组家兔上皮表面不全角化,与正常组织形态基本一致。结论：表皮生长因子甘草锌复合膜疗效确切,可对口腔溃疡动物模型进行有效治疗。     

EGF和VEGF在创伤性骨折愈合中的变化与意义

目的探讨血清内皮生长因子(Epidermal Growth Factor,EGF)和血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)在创伤性骨折愈合中的变化及其意义。方法应用放射免疫分析对50例创伤性骨折患者进行了治疗前后血清EGF和VEGF检测,并与30名正常健康人作比较。结果创伤性骨折患者在治疗前后血清EGF和VEGF水平与正常对照组相比明显增高(P<0.05),手术治疗一月后两者水平与正常对照组相比差异无统计学意义(P>0.05),且治疗前后血清EGF和VEGF水平的变化呈正相关。结论血清EGF和VEGF水平与骨折愈合密切相关。     

表皮生长因子甘草锌复合膜治疗口腔溃疡的实验研究

目的:探讨表皮生长因子甘草锌复合膜对口腔溃疡动物模型的疗效.方法:将24只家兔随机分为治疗组、对照组和空白组,各8只.以冰醋酸润湿脱脂棉,在家兔右侧靠口角黏膜处烧灼1min,生理盐水冲洗5min,24h形成溃疡.溃疡形成后每日8:00、12:00、16:00对家兔进行麻醉,空白组不做治疗,治疗组和对照组分别使用复合膜和本院制剂溃疡糊剂治疗2h,疗程为5d,每日测量家兔溃疡面最大直径,进行组间对比观察.结果:(1)治疗至第3天时,治疗组疗效优于对照组及空白组(P<0.05),对照组与空白组差异无统计学意义(P>0.05);治疗第5天时,治疗组及对照组疗效差异无统计学意义(P>0.05),但均优于空白组(P<0.05).(2)在外观治愈的家兔中,对照组家兔组织上皮已修复,但比正常组织薄,固有层纤维比正常组织疏松;治疗组家兔上皮表面不全角化,与正常组织形态基本一致.结论:表皮生长因子甘草锌复合膜治疗口腔溃疡疗效确切.     

Effect of Molecular Size of PEGylated Recombinant Human Epidermal Growth Factor on the Biological Activity and Stability in Rat Wound Tissue

The purpose of this study was to investigate the effect of size of polyethylene glycol (PEG) conjugated to recombinant human epidermal growth factor (rhEGF) on its stability in skin wound tissue and in vitro biological activity to find the desirable conjugate as topical therapeutic agent for wound healing. Site-specific PEGylation at N-terminus of rhEGF was performed with monomethoxy PEG-Butyraldehyde derivatives (MW 2, 5, and 20 kDa). Mono-PEG-rhEGFs retained 60–70% of biological activity of native rhEGF, and the effect of PEG size was not significant. The improvement of stability in the rat skin wound tissue was dependent on the increase of the PEG size attached. The degradation half-lives of native rhEGF, mono-PEG-2K-, ?5K-, and ?20K-rhEGFs were 1.1, 3.1, 5.2, and 41.5 hr, respectively. Therefore, mono-PEG-20K-rhEGF was considered to be the most desirable in terms of the increase of stability and the preservation of biological activity. This study suggests that the high molecular weight PEG at N-terminus of rhEGF would give a satisfactory stabilizing effect and thus may improve therapeutic efficacy in clinical use.     

基于创面生长因子研究皮肤软组织扩张术对烧伤整形患儿创面修复的促进作用

目的 基于创面生长因子研究皮肤软组织扩张术对烧伤整形患儿创面修复的促进作用.方法 选取2019年1月—2020年1月我院103例烧伤整形患儿,根据手术方案的不同分为扩张组52例和移植组51例,分别行皮肤软组织扩张术和复合皮移植术.统计2组临床疗效、创面愈合时间、创面愈合率、皮肤血运恢复时间、术后24 h视觉模拟评分法(...     

人表皮活性因子柔性纳米脂质体的制备及相关性质研究

目的 制备人表皮活性因子（EGF）柔性纳米脂质体,并对其相关性质进行研究.方法 利用逆相蒸发-冷冻干燥法制备EGF柔性纳米脂质体,采用酶联免疫吸附法（ELISA）测定EGF的含量,电镜观察其形态,并考察其包封率或载药量、变形性及稳定性.结果 所制备的EGF柔性纳米脂质体为多室脂质体.其平均粒径为（81.62±3.67） nm,Zeta电位为（60.12±7.58） mV;平均包封率为（37.86±4.77）％;平均载药量为（6.58±1.27）％.证实了EGF柔性纳米脂质体具有高度的变形性;冻干的EGF柔性纳米脂质体具有较高的稳定性.结论 EGF柔性纳米脂质体的制备方法可行,含量测定方法简单、可靠,稳定性和变形性高,可能成为透皮转运的有效载体.     

Formulation of Solid Dosage Forms to Overcome Gastric pH Interaction of the Factor Xa Inhibitor, BMS-561389

Purpose The purpose of the study was to investigate the specific mechanism by which elevated gastric pH reduces the absorption of BMS-561389, a factor Xa inhibitor, and to develop a solid formulation strategy to overcome this gastric pH interaction. Methods A dissolution method in an acetate buffer at pH 5.5 was used to evaluate the dissolution behavior of the tablet formulation. A precipitation model was used to screen different excipients for their potential to minimize the pH-dependent absorption of BMS-561389. Excipients that showed promise in the precipitation model were incorporated in modified tablet formulations. Dissolution rate of the modified tablets was also determined by the acetate buffer method. A canine model for pH-dependent absorption was subsequently used to evaluate the tablet formulations. Results Dissolution studies suggested that the reduced absorption of the original formulation was the result of the precipitation of the poorly water-soluble free base during the initial dissolution of the salt. Modified tablets containing organic acids, sulfobutylether-β-cyclodextrin, or povidone showed enhanced dissolution as compared with the original formulation. Drug absorption from the tablet containing tartaric acid was substantially independent of gastric pH in the canine model. Conclusion A multitier approach was successful in identifying a solid dosage form that minimizes the pH-dependent absorption of this drug candidate.     

Desensitization by Different Strategies of Epidermal Growth Factor Receptor and ErbB4

Four transmembrane tyrosine kinases constitute the ErbB protein family: epidermal growth factor receptor (EGFR) or ErbB1, ErbB2, ErbB3, and ErbB4. In general, the structure and mechanism of the activation of these members are similar. However, significant differences in homologous desensitization are known between EGFR and ErbB4. Desensitization of ligand-occupied EGFR occurs by endocytosis, while that of ErbB4 occurs by selective cleavage at the cell surface. Because ErbB4 is abundantly expressed in neurons from fetal to adult brains, elucidation of the desensitization mechanism is important to understand neuronal development and synaptic functions. Recently, it has become clear that heterologous desensitization of EGFR and ErbB4 are induced by endocytosis and cleavage, respectively, similar to homologous desensitization. It has been reported that heterologous desensitization of EGFR is induced by serine phosphorylation of EGFR via the p38 mitogen-activated protein kinase (p38 MAP kinase) pathway in various cell lines, including alveolar epithelial cells. In contrast, the protein kinase C pathway is involved in ErbB4 cleavage. In this review, we will describe recent advances in the desensitization mechanisms of EGFR and ErbB4, mainly in alveolar epithelial cells and hypothalamic neurons, respectively.     

重组人表皮生长因子治疗外伤性角膜上皮缺损

目的探讨重组人表皮生长因子(recombinant human epidermal growth factor,rhEGF)滴眼液治疗外伤性角膜上皮缺损的临床效果。方法观察100例外伤性角膜上皮缺损病例,随机分成治疗组50例和对照组50例,治疗组采用重组人表皮生长因子滴眼液滴入结膜囊,每日4次,每次1～2滴;对照组采用0.3%妥布霉素滴眼液滴入结膜囊,每日4次,每次1～2滴。滴眼后3d、6d观察角膜上皮缺损修复情况。结果滴眼3d和6d,rhEGF治疗组外伤性角膜上皮缺损的治疗率均高于对照组,经χ2检验,治疗组与对照组在滴眼后3d、6d差别有高度显著性(P<0.01)。结论重组人表皮生长因子(rhEGF)能够特异性地和角膜上皮细胞及内皮细胞受体相结合,很好地促进角膜上皮细胞的再生和修复,缩短病程,是一种治疗外伤性角膜上皮缺损的有效方法。     

榛子叶多酚对小鼠皮肤胶原蛋白含量影响的研究

目的：研究榛子叶多酚对小鼠皮肤胶原蛋白含量的影响。方法：在4月龄小鼠背部皮肤涂抹榛子叶提取液共42天。取背部皮肤,用分光光度法测定小鼠皮肤中胶原蛋白的含量。结论：榛子叶多酚可提高皮肤中胶原蛋白含量,具有延缓皮肤衰老作用。     

Radiolabeling of Intact Dosage Forms by Neutron Activation: Effects on In Vitro Performance

Compressed tablets containing various quantities of stable isotopes of Ba, Er, and Sm for use in neutron activation studies were evaluated for the effect of stable isotope incorporation on tablet hardness and disintegration times. At concentrations likely to be used in scintigraphic studies employing neutron activation as a radiolabeling method, no significant effect on in vitro parameters were observed. While the incorporation of stable isotopes influenced tablet hardness to a greater degree than disintegration time, irradiation of tablets in a neutron flux of 4.4× 10¹³ n/cm² sec had a direct effect on tablet disintegration time. Thus, future neutron activation studies should focus on minimizing the amount of stable isotope to be incorporated with the formulation while using the shortest feasable irradiation time.