A randomized clinical trial of elk velvet antler in rheumatoid arthritis

This article examines the effects of elk velvet antler on joint pain and swelling, patient/physician global assessment of disease activity, functional ability, quality of life, blood levels of C-reactive protein, and adverse events in persons with stage 2 to 3 rheumatoid arthritis experiencing residual symptoms after standard treatment. Patients (N=168) were enrolled in a 6-month randomized, triple-blind, placebo-controlled clinical trial. Instruments included the Arthritis Impact Measurement Scale, the Health Assessment Questionnaire, tender and swollen joint counts, and 100 mm-length visual analogue scales, along with blood tests. There were no significant differences between groups on any measures. The pattern of change of the measures across time points was essentially the same for both groups. Although some patients reported clinical improvements in their symptoms, there were no statistically significant differences between groups. Overall, elk velvet antler does not effectively manage residual symptoms in patients with rheumatoid arthritis.     

Effects of high voltage stimulation on cutaneous wound healing in rabbits

The primary purpose of this study was to determine whether high voltage stimulation (HVS) enhances wound healing. Forty female rabbits were assigned to experimental or control groups and followed for four or seven days. We classified the groups as Exp4, Con4, Exp7, and Con7, respectively. Each animal was anesthetized, and a full-thickness incision, 3.5-cm long, was made on its back. After 24 hours, Exp4 and Exp7 rabbits received HVS with a negative polarity for two hours twice daily. Although tensile-strength values were 36% higher for Exp4 rabbits than for Con4 rabbits, no significant differences in tensile strength or percentage of wound closure existed between the two groups. After seven days, Con7 rabbits had a higher percentage of wound closure and significantly greater tensile-strength measures than Exp7 rabbits. Histologic examination of the wounds did not provide clear-cut evidence of differences between the experimental and control groups. Results suggest that 1) HVS did not significantly improve wound healing for Exp4 rabbits and 2) HVS as given, may have hampered the healing process for Exp7 rabbits.     

超短波对糖尿病大鼠创面愈合的影响

目的：探讨超短波治疗对糖尿病大鼠创面局部不同时间点溃疡面积、创面愈合率的影响。方法：健康成年雄性SD大鼠90只,随机分为正常组、糖尿病组和超短波组各30只。糖尿病组和超短波组建立糖尿病模型,3组大鼠制作皮肤溃疡模型,正常组、糖尿病组大鼠不进行任何干预,超短波组大鼠行超短波治疗。结果：在伤后第3、7、14及21天,超短波组及糖尿病组不同时间点创面面积均明显大于正常组（ P＜0．05,0．01）,超短波组不同时间点创面面积均明显小于糖尿病组（P＜0．01）;超短波组及糖尿病组不同时间点创面愈合率均明显低于正常组（P＜0．05,0．01）,超短波组不同时间点创面愈合率明显高于糖尿病组（ P＜0．01）。结论：超短波治疗可促进糖尿病溃疡创面缩短愈合时间,加快愈合速度,为其在促进糖尿病患者创面愈合的治疗中提供理论依据。     

Extracorporeal shock wave treatment improves incisional wound healing in diabetic rats

Impaired wound healing in surgical patients with diabetes increases the incidence of infection, prolongs hospitalization, and even increases the rate of mortality. Low-energy extracorporeal shock wave treatment (ESWT) was reported to accelerate chronic wound healing by promoting revascularization and tissue regeneration; however, it is not known if ESWT could also improve healing of acute surgical incisional wounds in diabetes. In this study, using a rat model of diabetes, we investigated the effect of low-energy ESWT on collagen content in wound tissues and its efficacy in incisional wound healing. A single dorsal incisional wound was inflicted in streptozotocin-induced diabetic rats, and they received ESWT at different time post-wounding. Rats were sacrificed on days 7 and 14 post-wounding. Wound breaking strength, hydroxyproline content, histological characteristics and the expression of transforming growth factor beta 1 (TGF-β1) were analyzed. As a result, the wound breaking strength was significantly enhanced and the hydroxyproline content in wound tissues was increased at each time point examined. The number of fibroblasts was signicantly increased, and the new collagen fibers were more abundant at the wound site after ESWT. Furthermore, the expression of TGF-β1 was up-regulated after ESWT on day 7 post-wounding. These results suggest that low-energy ESWT can increase collagen content, enhance wound breaking strength and improve the healing of incisional wound in diabetic rats. The increased collagen content may be attributed, at least in part, to the up-regulation of TGF-β1 expression in wound tissues.     

重组人血小板源生长因子促进糖尿病大鼠创面愈合机制的初步研究

目的:研究重组人血小板源生长因子(rhPDGF)对糖尿病大鼠全层皮肤缺损创面的修复作用及其可能机制。方法:在26只糖尿病大鼠背部制备4个全层皮肤缺损创面,创面随机分成3组,rhPDGF治疗组,凝胶剂基质组,空白组。观察伤后3,7和14d组织肉芽形成、胶原沉积、再上皮化速率,以及炎症细胞的浸润情况,并采用免疫组织化学方法观察创周和创基修复细胞增殖状况。结果:伤后7d,组织学检查显示,经rhPDGF治疗的创面伤后7d肉芽组织生长活跃,其毛细血管胚芽与成纤维细胞数量显著多于其他组,大量的炎症细胞浸润和胶原沉积,rhPDGF治疗组伤腔容积减小至(0.03±0.03)mL,明显低于凝胶剂基质对照组(0.06±0.03)mL(P<0.05)和空白对照组(0.07±0.05)mL(P<0.05)。伤后7d,rh-PDGF治疗组的创面收缩明显,再上皮化速率达到46.1%,明显高于凝胶剂基质对照组(23.2%)和空白对照组(25.6%)。伤后14d,rhPDGF治疗组再上皮化速率达到99.9%,明显高于凝胶剂基质对照组(91.7%)和空白对照组(91.3%)。同时伤后组织中各类修复细胞PCNA的表达有显著差异。结论:rhPDGF对糖尿病大鼠创面有促修复作用,其对炎症细胞的趋化和修复细胞的增殖影响扮演重要角色。     

Effect of povidone-iodine on wound healing in control, diabetic and steroid depressed rats

A comparative study was made on the effect of povidone-iodine on wound healing in normal, diabetic and steroid depressed states in the excision wound model in rats. Healing was assessed by the rate of contraction of wounds and epithelialization after three weeks of topical application. Normal and diabetic groups were comparable (P < 0.02) concerning the above-mentioned parameters as well as collagen formation. The steroid group showed significant retardation in healing time (P < 0.001), epithelialization (P < 0.001) and collagen formation (P < 0.001) showing that povidone-iodine did not overcome the steroid effect.     

Androgen receptor-mediated inhibition of cutaneous wound healing

Impaired wound healing states in the elderly lead to substantial morbidity, mortality, and a cost to the US Health Services of over $9 billion per annum. In addition to intrinsic aging per se causing delayed healing, studies have suggested marked sex-differences in wound repair. We report that castration of male mice results in a striking acceleration of local cutaneous wound healing, and is associated with a reduced inflammatory response and increased hair growth. Using a hairless mouse model, we have demonstrated that testosterone reduction stimulates the healing response not through hair follicle epithelial/mesenchymal cell proliferation, but directly via effects on wound cell populations. We suggest that endogenous testosterone inhibits the cutaneous wound healing response in males and is associated with an enhanced inflammatory response. The mechanisms underlying the observed effects involve a direct upregulation of proinflammatory cytokine expression by macrophages in response to testosterone. Blockade of androgen action systemically, via receptor antagonism, accelerates healing significantly, suggesting a specific target for future therapeutic intervention in impaired wound healing states in elderly males.     

羊膜负载表皮干细胞促进糖尿病大鼠创面的愈合

背景:表皮干细胞作为皮肤组织的特异性干细胞,具有强大增殖及多向分化潜能,与创面修复紧密相关.近期研究表明糖尿病皮肤创面愈合过程中表皮干细胞数量减少、活性降低是导致其创面难愈的重要原因.目的:观察表皮干细胞在糖尿病大鼠创面愈合中的作用.方法:分离培养及鉴定SD大鼠表皮干细胞,并以BrdU标记.建立糖尿病SD大鼠创面模型,抽签法随机分为3组:表皮干细胞组创面移植羊膜负载BrdU标记的表皮干细胞;羊膜组创面移植羊膜;空白对照组创面未给予干预. 观察创面愈合情况、计算创面愈合率,苏木精-伊红及免疫组织化学SP法检测创面愈合组织中BrdU及增殖细胞核抗原表达.用图像分析软件测量阳性细胞积分吸光度平均值.结果与结论:表皮干细胞组治疗后7d创面缩小明显,治疗后14 d创面基本愈合,创面愈合率明显高于羊膜组、空白对照组 (P < 0.01).表皮干细胞组创面及新生表皮中可见BrdU阳性细胞,而另两组皮肤创面组织中始终未见BrdU阳性细胞.各组创面组织中可见增殖细胞核抗原阳性细胞表达,但表皮干细胞组的阳性细胞积分吸光度平均值与羊膜组、空白对照组比较差异有显著性意义(P < 0.01).结果证实糖尿病大鼠创面愈合过程中表皮干细胞与创缘表皮移行、创面的上皮化有直接关联,可有效促进其创面愈合.     

重组人血小板源性生长因子凝胶剂促进糖尿病大鼠创面愈合的实验研究

目的 :研究重组人血小板源性生长因子 (rh PDGF BB)凝胶剂对糖尿病大鼠皮肤切割伤创面修复的作用及其量效关系。方法 :13只糖尿病大鼠在背部各制备 4个全层皮肤缺损创面 ,面积 2 .5 4 cm2 ,将创面分成5组 ,即 rh PDGF BB凝胶剂高剂量 (14 .0μg/ cm2 创面 )、中剂量 (7.0μg/ cm2 创面 )、低剂量 (3.5μg/ cm2 创面 ) 3组 ,凝胶剂基质对照组以及空白对照组。创面局部应用制剂 14 d,观察伤后不同时间各组创面面积、伤腔容积变化及组织学改变。结果 :伤后 14 d rh PDGF BB高、中、低剂量治疗组创面面积分别缩小至 (0 .2 2±0 .30 ) cm2、(0 .0 5± 0 .0 6 ) cm2和 (0 .32± 0 .32 ) cm2 ,中剂量组明显小于凝胶剂基质对照组 (0 .2 3± 0 .2 2 ) cm2 (P<0 .0 5 )和空白对照组 (0 .2 2± 0 .2 5 ) cm2 (P<0 .0 5 )。伤后 7d rh PDGF BB高、中、低剂量治疗组伤腔容积减小至(0 .0 4± 0 .0 3) m l、(0 .0 2± 0 .0 2 ) ml和 (0 .0 6± 0 .0 3) ml,只有中剂量组明显小于凝胶剂基质对照组 (0 .0 6±0 .0 3) m l(P<0 .0 5 )和空白对照组 (0 .0 7± 0 .0 5 ) m l(P<0 .0 5 )。组织学检查显示 ,经 rh PDGF BB中剂量治疗的创面伤后 7d肉芽组织生长活跃 ,其毛细血管胚芽与成纤维细胞数量显著多于其他组 ,伤后 14 d rh     

重组人血小板源性生长因子与胰岛素联合局部应用对老龄糖尿病大鼠烧伤创面的作用

目的:文献报导单一局部应用重组人血小板源性生长因子或胰岛素对糖尿病创面的愈合具有促进作用.拟验证局部联合应用重组人血小板源性生长因子和胰岛素对老龄糖尿病大鼠烧伤创面愈合的作用.方法:实验于2006-10/2007-05在甘肃省中医学院SPF级动物实验室完成.①实验材料及分组:SPF级健康Wistar老龄大鼠88只,年龄1年以上,雌雄不限,体质量300～350 g.随机分为烫伤对照组20只,糖尿病烫伤对照组20只,糖尿病重组人血小板源性生长因子对照组16只,糖尿病胰岛素对照组16只,糖尿病重组人血小板源性生长因子、胰岛素治疗组16只.实验用鱼精蛋向锌胰岛素为上海第一生化药业有限公司产品;重组人血小板源性生长因子凝胶剂为北京金赛狮生物制药技术开发有限公司产品.②实验过程:除烫伤对照组外,其他组大鼠通过高脂、高蛋白、高糖饲养后腹腔注射链尿佐菌素,建立老龄Ⅱ型糖尿病动物模型,并以高脂、高蛋白、高糖饲养.8周后各组给予深Ⅱ度烫伤.③实验评估:于伤后第1,3,7,14,21天时相点测量创面面积,计算创面愈合率:观察组织形态学、检测创面羟脯氨酸含量:采用免疫组织化学检测血管内皮细胞生长因子、CD34的表达:计算微血管密度.实验过程对动物的处理符合动物伦理学标准.结果:与糖尿病烫伤对照组、糖尿病重组人血小板源性生长因子对照组、糖尿病胰岛素对照组相比,糖尿病重组人血小板源性生长因子、胰岛素治疗组老龄大鼠创面愈合率加快(P＜0.05),创面上皮化加速,羟脯氨酸含量增加(P＜0.05),血管内皮细胞生长因子、CD34阳性表达,微血管密度值增加(P＜0.05).结论: 局部联合应用重组人血小板源性生长因子和胰岛素可通过协同作用促创面胶原的合成,增加创面的血管形成,加速老龄性糖尿病大鼠创面愈合.     

Effects of vitamin E on oxidative stress and membrane fluidity in brain of streptozotocin-induced diabetic rats

Background: Diabetics and experimental animal models exhibit high oxidative stress due to persistent and chronic hyperglycemia, thereby deplete the activity of the antioxidative defense system and thereby promote the generation of free radicals. The current study examined the effects of vitamin E on oxidative stress and membrane fluidity in the brain of diabetes-induced rats. Methods: Sprague–Dawley male rats were randomly assigned to normal and streptozotocin (STZ)-induced diabetic groups. The diabetic groups were fed a vitamin E-free diet, 40 mg vitamin E/kg diet, or 400 mg vitamin E/kg diet. Diabetes was induced with STZ after 3 weeks of the experimental diet, then the rats were sacrificed 9 days later to determine the oxidative stress and cell membrane fluidity in the brain. Results: Dietary vitamin E strengthened the antioxidative defense system with an increased activity of the antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and increased vitamin E content, in the brain of the diabetes-induced exeperimental rats. Accordingly, vitamin E was found to reduce the accumulation of reactive oxygen species (ROS), such as superoxide radical decrease the generation of oxidative damage substances, such as the carbonyl value, increase the membrane fluidity lowered by oxidative damage, and significantly improve the lipid composition. Conclusions: Vitamin E was found to be excellent for strengthening the antioxidative defense system, reducing the generation of ROS and damaging oxidative substances, and maintaining membrane fluidity in the brain of diabetes-induced rats.     

Effects of hydralazine on streptozotocin-induced diabetic rats: prevention of hyperlipidemia and improvement in cardiac function

The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). STZ-induced diabetes results in a loss of body weight, hyperglycemia and hypoinsulinemia. These effects are not altered after hydralazine treatment. STZ-diabetes also produced a significant bradycardia, elevation of blood pressure, hyperlipidemia and decreases in the levels of triiodothyronine and thyroxine. Hydralazine treatment successfully prevented all these alterations. In addition, cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement. Thus, hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats.     

Hypoglycemic effect of insulin-transferrin conjugate in streptozotocin-induced diabetic rats

Transferrin (Tf) receptor-mediated transcytosis of insulin-transferrin conjugate (In-Tf) has been demonstrated in cultured human enterocyte-like Caco-2 cells. In the present report, oral delivery of insulin as a Tf conjugate in streptozotocin (STZ)-induced diabetic rats was investigated. Human insulin was conjugated at a 1:1 molar ratio to iron-loaded human Tf by a disulfide linkage. The stability of In-Tf and the free insulin released from In-Tf was studied in the presence of rat liver slices by using radioimmunoassay. The release of free insulin involved a disulfide reduction reaction that was inhibited by the pretreatment of the liver slice with a sulfhydryl-reactive reagent N-ethylmaleimide. A protease inhibitor cocktail also showed a partial inhibition of insulin degradation. The biological activity of the conjugate was tested in STZ-induced diabetic rats with s.c. administration, and the conjugate exhibited a slow but prolonged hypoglycemic effect compared with that of the native human insulin. In-Tf also displayed a slow but prolonged hypoglycemic effect after oral administration in fasted STZ-induced diabetic rats in a dose-dependent manner. Furthermore, In-Tf was detected in the serum of rats at 4 h after oral administration of the conjugate, indicating that In-Tf can overcome the barriers in the gastrointestinal tract and be absorbed as an intact conjugate. These results demonstrate that transepithelial transport via TfR-mediated transcytosis is a feasible approach for developing the oral delivery of insulin, as well as other peptide drugs.     

丹参对复合全身放射损伤大鼠创面的影响

目的:丹参能有效促进溃疡和表皮创面愈合,观察丹参对大鼠放射损伤复合局部创伤(简称放创复合伤)创面的影响。方法:实验于2003-01/07在第三军医大学药理学教研室完成。大鼠接受6Gy全身照射后在背部作圆形全层切除,局部给予丹参1g/cm2,连续7d。结果:伤后3～23d,丹参治疗组创面愈合速度明显快于对照组,其完全愈合时间为(19.17±2.93)d,较对照缩短3.83d。且治疗组创面蛋白和羟脯氨酸含量也明显高于对照。结论:丹参能加快放创复合伤创面愈合,且提高创面愈合质量。     

Statins ameliorate glomerular permeability changes in streptozotocin-induced diabetic rats

AIMS: Statins reduce albumin excretion rate and retard the progression of diabetic nephropathy. Whether statins alter size selectivity of glomerular filtration in diabetic rats is not known. METHODS: The creatinine clearance and the permeability of glomeruli to a group of fluorescein isothiocyanate dextrans of varying molecular weights were studied in rats with streptozotocin-induced diabetes that were treated with either 10 mg/kg rosuvastatin or simvastatin for 5 weeks. RESULTS: Statin therapy did not significantly alter the increased creatinine clearance in diabetic rats. During the 5 hours of urine collection there was near-complete filtration of 4-, 10-, and 20-kD dextrans in all rat groups studied. The filtration of 70- and 40-kD dextrans was significantly increased in diabetic rats after 5 weeks of diabetes. Rosuvastatin but not simvastatin was associated with partial normalization of glomerular filtration of the 70- and 40-kD dextrans. Treatment with mevalonate (150 mg/kg in drinking water for 5 weeks) reversed the favorable effects of rosuvastatin on glomerular permeability. CONCLUSIONS: Statin treatment of rats with streptozotocin-induced diabetes ameliorates glomerular permeability changes. The favorable effect of rosuvastatin is probably related to the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, because mevalonate treatment reversed the favorable effects of rosuvastatin.     

Electrical stimulation effects on cutaneous wound healing in rabbits. A follow-up study

The purpose of this study was to determine the effects of high voltage monophasic pulsed electrical stimulation on wound healing using positive polarity. Forty-four rabbits were assigned to experimental or control groups and followed for four or seven days. We classified the groups as Exp4, Con4, Exp7, and Con7, respectively. Each animal was anesthetized, and a full-thickness incision, 3.5-cm long, was made on its back. After 24 hours, the Exp4 and Exp7 rabbits received high voltage electrical stimulation for two hours twice daily. Wound closure for the Exp4 rabbits (50%) was significantly less than that of the Con4 rabbits (78%). After seven days, however, the Exp7 and Con7 rabbits had similar wound-closure values (80% and 82%, respectively). Tensile-strength values for the control and experimental animals were comparable at both time periods. Histologic examination of the wounds suggested a more rapid rate of epithelization between the Exp4 and Exp7 rabbits compared with the Con4 and Con7 rabbits. The results of this study are inconclusive, but may indicate that positive-polarity stimulation enhanced wound closure between four and seven days of treatment.     

新型中药复合海绵敷料对大鼠皮肤创面修复的效果研究

目的:探讨新型中药复合海绵敷料对大鼠创面的修复效果。方法:将30只Wistar大鼠随机分为3组。实验组用中药复合海绵敷料覆盖创面,阳性对照组用海绵基质覆盖创面,阴性对照组用凡士林纱布处理。分别于治疗后第3d、7d、14d观察大鼠创面愈合情况,测定创面面积并取创面做病理分析;治疗后第3d、7d测创面炎症积分。结果:治疗后第7d、14d,实验组创面愈合率分别为[(71.32±0.08)%]、[(90.44±0.07)%]显著高于阳性对照组[(60.66±0.09)%]、[(81.03±0.04)%]和阴性对照组[(50.01±0.10)%]、[(71.65±0.10)%](P0.05);治疗后第3d、7d,实验组创面炎症积分分别为(3.20±0.42)分、(1.70±0.48)分,阳性对照组为(4.18±0.60)分、(2.55±0.52)分,阴性对照组为(5.67±0.50)分、(3.89±0.33)分,实验组与后两组比较,差异有显著性意义(P0.05)。结论:新型中药复合海绵敷料对大鼠创面的愈合有促进作用,能够干预创面炎症反应,适宜作为创伤修复敷料。     

糖尿病大鼠骨代谢变化与立普妥、胰岛素的干预效应

目的:近年细胞培养实验发现他汀类药物可以促进骨形成,采用动物实验观察胰岛素和他汀类药物立普妥对糖尿病大鼠骨代谢的影响,为糖尿病伴骨质疏松的治疗提供实验依据。方法:实验于2005-08/2006-01在大连医科大学病理教研室完成。①实验分组:SD雄性大鼠55只,随机选择10只为空白对照组,余45只经鼠尾静脉注射链尿佐菌素造成糖尿病大鼠模型。其中40只符合造模标准,随机分为糖尿病未治疗组、胰岛素治疗组、立普妥治疗组及胰岛素 立普妥治疗组,每组10只。②实验方法:所有大鼠皆给予相同普通饮食。胰岛素治疗组及胰岛素 立普妥治疗组于实验第4天接受中效胰岛素治疗,6～8U/d分两次颈背部皮下注射。胰岛素剂量按每只鼠每周血糖进行调整。立普妥治疗组及胰岛素 立普妥治疗组于实验第4天给予立普妥1.25mg/kg灌胃。糖尿病未治疗组和空白对照组给予等量生理盐水灌胃。③实验评估:9周末用乙醚麻醉,每组取4只大鼠去眼球取血之后处死。14周末应用同样方法处死剩余大鼠。均取腰椎骨,常规脱钙石蜡包埋,行苏木精-伊红染色。骨组织形态计量学测量平均骨小梁厚度和平均骨小梁间距或弥散度。血中Ⅰ型胶原氨基端肽测定采用竞争性放射免疫检测方法(碘标记)。结果:实验期间大鼠死亡5只,其中糖尿病未治疗组1只于第3周死亡,胰岛素组2只于第6周死亡,胰岛素 立普妥治疗组2只于第7周死亡。①骨组织病理形态学变化:9周末立普妥治疗组、胰岛素 立普妥治疗组及糖尿病未治疗组光镜下见骨质疏松表现。14周末立普妥治疗组及胰岛素治疗组骨组织微观结构恢复至空白对照组水平。②平均骨小梁厚度:9周末:糖尿病未治疗组、胰岛素治疗组、立普妥治疗组及胰岛素 立普妥治疗组均明显低于空白对照组(P<0.01)。14周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显低于空白对照组(P<0.05)。③平均骨小梁间距或弥散度:9周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显高于空白对照组(P<0.05)。14周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显高于空白对照组(P<0.05)。④Ⅰ型胶原氨基端肽水平:9周末:立普妥治疗组和胰岛素 立普妥治疗组均明显高于空白对照组(P<0.01)。14周末:胰岛素治疗组、立普妥治疗组和胰岛素 立普妥治疗组均明显高于空白对照组(P<0.01)。结论:①糖尿病大鼠造模9周出现明显的骨质疏松。②糖尿病大鼠骨质变化表现为骨吸收超过骨形成作用,主要以骨吸收增强为主。③立普妥及胰岛素可以促进糖尿病大鼠骨质的形成,抑制糖尿病大鼠骨质疏松的发生发展。