单侧隐睾大鼠对侧睾丸的损害与Bcl-2和Bax基因表达

目的:探讨单侧隐睾大鼠对侧睾丸生精细胞凋亡与Bcl-2/Bax基因表达的关系。方法:20只健康SD雄性大鼠(22日龄)随机分成隐睾组和对照组,每组10只。通过手术建立单侧隐睾动物模型。术后90 d取对侧睾丸,采用原位缺口末端标记(TUNEL)法检测生精细胞凋亡,免疫组化SP法检测Bcl-2/Bax基因表达。结果:与对照组相比,隐睾组对侧睾丸生精细胞凋亡显著增多(P<0.01),重量显著减轻(P<0.01),Bax表达显著升高(P<0.01),Bcl-2表达显著降低(P<0.01)。凋亡细胞主要是初级精母细胞和圆形精子细胞。结论:单侧隐睾大鼠对侧睾丸的生精细胞凋亡增多与Bcl-2基因表达降低、Bax基因表达升高密切相关。细胞内Bc l-2/Bax比值是影响生精细胞凋亡的重要因素之一。     

己烯雌酚摄入对大鼠生精细胞凋亡及Bax和Bcl-2蛋白表达的影响

目的研究青春期己烯雌酚(diethylstilbestrol,DES)摄入对SD(Sprague-Dawley)大鼠性成熟后睾丸生精细胞凋亡的影响,并初步探讨其机制。方法30只35d龄雄性SD大鼠,随机分为DES 0.01、0.1、1.0、10.0μg/kg·d~(-1)4个实验组和1个对照组(编码为BDa、BDb、BDc、BDd和BC组,每组n=6)。于青春期[出生后第36天(postnatal day 36,PND 36)至49d(PND 49)],实验组每日皮下注射相应剂量的DES,对照组仅注射溶媒。于大鼠性成熟后(PND 64)处死各组大鼠切取双侧睾丸,采用TUNEL法检测大鼠睾丸生精细胞凋亡,用免疫组化方法检测凋亡相关蛋白Bcl-2和Bax在生精细胞中的表达。结果与对照组相比,BDa组大鼠性成熟后生精细胞凋亡无明显变化,BDb、BDc和BDd 3组生精细胞凋亡增加,且随DES摄入剂量增加而有增加趋势。BC、BDa组生精细胞Bax相对弱表达而Bcl-2强表达,伴随DES摄入剂量增加,Bax表达逐渐增强而Bcl-2表达逐渐减弱,BDd组Bax强表达而Bcl-2弱表达。结论青春期较大剂量DES摄入可使大鼠性成熟后睾丸生精细胞凋亡增加,且随DES摄入剂量增加而有加强趋势。凋亡相关蛋白Bax和Bcl-2参与青春期DES摄入所致的生精细胞凋亡过程。     

铅致大鼠睾丸细胞凋亡的实验研究及临床意义

目的探讨铅致大鼠睾丸生精细胞凋亡及其机制。方法40只成年雄性Wistar大鼠随机均分为4组:对照组,低、中、高剂量实验组。实验组分别腹腔注射醋酸铅5、10、20mg/kg体重,对照组注射等体积生理盐水,3周后手术取睾丸,用原位末端脱氧核苷酸转移酶标记(Tunel法)及免疫组化技术检测睾丸组织生精细胞凋亡及凋亡相关蛋白Bcl-2、Bax的表达。结果3周后,中、高剂量组细胞凋亡及Bax基因表达较对照组差异有显著性(P<0.01),低剂量组较对照组无显著性。3个实验组的Bcl-2基因表达较对照组差异有显著性,且各组间亦有显著性(P<0.01)。结论铅负荷至一定程度时可致大鼠生精细胞凋亡,且呈一定量效关系,这种作用可能与Bcl-2基因低表达和Bax基因高表达有关。     

精索静脉曲张大鼠睾丸自噬对生精细胞的影响

目的:研究精索静脉曲张(VC)大鼠模型中睾丸不同水平自噬对生精细胞凋亡的影响。方法:雄性SD大鼠54只随机分为6组:空白对照组、雷帕霉素对照组、氯喹对照组各6只,VC组、VC+雷帕霉素组、VC+氯喹组各12只。采用HE染色观察睾丸、附睾组织形态学变化,并对睾丸及附睾中精子形成情况进行评分,TUNEL染色检测生精细胞凋亡指数(AI),Western印迹检测LC3、p62、Bax、Bcl-2的表达。结果:空白对照组、雷帕霉素对照组、氯喹对照组大鼠睾丸及附睾组织均未发生明显形态学变化,精子形成情况评分及AI亦无显著差异(P>0.05);VC组大鼠睾丸及附睾组织发生明显病理损伤,精子形成情况评分显著降低(P<0.01),AI显著升高(P<0.01),但VC+雷帕霉素组较VC组明显改善,而VC+氯喹组较VC组轻度加重。此外,与空白对照组比较,VC组自噬相关蛋白LC3(包括LC3-Ⅱ/LC3-Ⅰ的比值)和促凋亡蛋白Bax表达显著增加(P<0.01),抑凋亡蛋白Bcl-2表达则显著降低(P<0.01);且VC+雷帕霉素组LC3与Bcl-2表达显著高于VC组(P<0.01),p62和Bax表达则显著低于VC组(P<0.01);而VC+氯喹组LC3与Bcl-2表达显著低于VC组(P<0.01),p62和Bax的表达则显著高于VC组(P<0.01)。结论:VC可诱导大鼠睾丸自噬和生精细胞凋亡,上调自噬可抑制生精细胞凋亡,阻滞自噬则可促进生精细胞凋亡。     

腹股沟区皮下埋藏睾丸对生精细胞凋亡及Bcl-2/Bax蛋白表达的影响

目的:通过观察腹股沟区皮下埋藏睾丸生精细胞的凋亡及Bcl-2/Bax蛋白表达,探讨二者的关系。方法:以健康育龄期36只雄性新西兰大白兔为实验动物,随机分成实验组18只、对照组18只。实验组动物将双侧睾丸分别移位埋藏至双侧腹股沟区皮下,以制备睾丸埋藏修复阴囊皮肤缺损模型;对照组未作处理。动物模型建立后第8周末,每组随机取6只大白兔测量睾丸表面温度后进行睾丸活检。睾丸组织行原位末端标记(TUNEL)法检测生精细胞凋亡、免疫组化法结合图像分析仪检测睾丸生精细胞Bcl-2、Bax蛋白的表达。结果:对照组的睾丸表面温度为(36.15±0.64)℃,实验组为(38.02±0.36)℃,两组比较差异有统计学意义(P<0.05)。模型建立后第8周末实验组睾丸生精小管中生精细胞的凋亡指数(AI)为(89.69士3.76)%,对照组为(7.73±4.95)%,两者比较有显著差异(P<0.05)。实验组Bax表达显著升高(P<0.05),Bcl-2表达显著降低(P<0.05),凋亡细胞主要为初级精母细胞和圆形精子细胞。结论:腹股沟区皮下埋藏睾丸局部温度升高诱导睾丸的生精细胞凋亡增加,生精细胞凋亡增加与Bcl-2蛋白表达降低、Bax蛋白表达升高密切相关。Bcl-2/Bax的改变是高温引起生精细胞凋亡的机制之一。     

雷公藤多甙抑制大鼠精子发生的研究

目的探讨雷公藤多甙对大鼠精子发生的抑制作用及其可能的信号通路。方法成年雄性大鼠给予雷公藤多甙(16 mg/kg)灌胃,每日1次,在2及6周检测血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)和可的松水平;光镜观察睾丸组织的形态学变化;原位末端标记法(TUNEL)观察睾丸生精细胞凋亡;免疫组织化学法观察凋亡通路相关蛋白Bax/Bcl-2的表达。结果给药组与对照组相比,性激素、肾上腺皮质激素均无显著变化(P均>0.05);给药2周后精子数下降和畸形率上升(P<0.05),给药4和6周精子数下降和畸形率升高更显著(P<0.001);组织学检查给药组大鼠生精小管内各级精母细胞和精子细胞数明显减少,生精细胞排列紊乱,原始精原细胞和支持细胞(Sertoli细胞)未见明显改变。与正常对照组相比,生精小管内生精细胞凋亡显著增加(2周P<0.05,4和6周P<0.001)。凋亡相关蛋白Bax表达明显上调,Bcl-2表达无显著差异。结论雷公藤对大鼠精子发生的抑制作用表现为增加生精细胞凋亡,导致精子计数下降,精子的畸形率升高。雷公藤多甙使睾丸Bax表达增加,与诱导生精细胞凋亡相关,可能是相关的信号通路之一。进一步研究雷公藤多甙作用的分子信号机制有助于今后降低剂量、减少毒副作用,探讨其作为一种安全的男性避孕药可能性。     

五子衍宗丸对实验性少弱精子症大鼠的保护作用与机制研究

目的:观察五子衍宗丸对实验性少弱精子症大鼠的保护作用与机制研究。方法:取60只雄性SD大鼠,随机分成正常组、模型组、阳性药组(生精胶囊1.6 g/kg),五子衍宗丸低、中、高剂量组(1、2、4 g/kg),除正常组外,其他各组灌服雷公藤多苷30 mg/(kg·d),连续6周,建立少弱精子症模型。从造模的第3周开始,各组按剂量灌胃给药,连续给药4周后计算睾丸和附睾脏器指数,检测附睾精子质量、精子凋亡率、精子线粒体通透性转换孔(MPTP)开放情况,HE染色观察大鼠睾丸病理组织学改变,Hochest染色观察大鼠睾丸细胞凋亡情况。结果:五子衍宗丸能提高少弱精子症大鼠睾丸和附睾脏器指数,增加附睾精子浓度、精子活力和精子活率,降低精子凋亡率,抑制MPTP异常开放;HE染色显示五子衍宗丸能增加少弱精子症大鼠睾丸生精小管内各级生精细胞层次和数量,Hochest染色显示五子衍宗丸明显抑制睾丸生精小管内生精细胞凋亡。结论:五子衍宗丸能明显提高少弱精子症大鼠精子质量,降低少弱精子症模型大鼠的各级生精细胞(包括精子)凋亡率,其机制可能与抑制大鼠精子线粒体MPTP开放有关。     

邻苯二甲酸二丁酯孕期暴露导致性发育期子代大鼠睾丸细胞凋亡和空泡化

目的:探讨邻苯二甲酸二丁酯(DBP)孕期暴露对性发育期子代大鼠睾丸细胞凋亡的影响。方法:受孕SD大鼠10只,随机分为空白对照组和DBP染毒组,妊娠12~19 d,空白对照组和DBP染毒组分别给予橄榄油1 ml/d和DBP 500 mg/(kg·d)灌胃,于性发育期(PND45)取出睾丸标本,透射电镜观察睾丸细胞结构,HE染色观察各级生精细胞发育情况,TUNEL法检测睾丸细胞凋亡情况,免疫组化和Western印迹观察凋亡调控蛋白Bcl-2、Bcl-XL、Bax和p53的表达。结果:电镜观察见DBP染毒后性发育期子代大鼠睾丸细胞凋亡增加和细胞空泡化,HE染色见各级生精细胞明显减少,TUNEL检测结果显示DBP染毒组细胞凋亡指数明显高于空白对照组(12.00±5.22 vs 3.17±1.47,P0.01),免疫组化和Western印迹提示DBP染毒组促凋亡蛋白Bax和p53的表达较空白对照组显著升高(P0.05)。结论:DBP孕期染毒导致性发育期雄性子代大鼠睾丸生殖细胞和支持细胞凋亡增加及细胞空泡化,促凋亡蛋白Bax和p53的表达明显增高。     

JQ1对脂多糖所致小鼠生精功能障碍的影响

目的 探讨JQ1对脂多糖(LPS)所致小鼠生精功能障碍的影响及相关机制。方法 40只8周龄雄性C57BL/6J小鼠，随机分为溶媒对照组(DMSO+NS)、模型组(DMSO+LPS)和药物干预组(JQ1+LPS),每组小鼠的数量分别为n=13、n=15和n=12,单次腹腔注射LPS诱导炎症动物模型。取材后，称量睾丸、附睾尾的重量，采用精子计数法检测小鼠精子数量，伊红染色检测精子的畸形率，苏木精-伊红(HE)染色检测睾丸形态变化；TUNEL试剂盒检测睾丸生殖细胞凋亡情况；Western blot检测凋亡基因(Bax和Bcl2)的表达情况；生化试剂盒检测睾丸丙二醛(MDA)、谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)表达情况。结果 LPS导致小鼠附睾尾重量显著下降(P<0.05),精子数量显著下降(P<0.001);精子畸形率显著升高(P<0.01);睾丸形态结构破坏，生精小管萎缩，管腔直径变小，各级生精细胞排列紊乱，管腔内精子数量减少；睾丸中凋亡细胞数量显著上调(P<0.01);Bax/Bcl2的比值显著上升(P<0.01);MDA含量显著增加(P<...     

青春期前己烯雌酚暴露对大鼠性成熟后生精细胞凋亡的影响及其机制初探

目的:研究青春期前己烯雌酚(d iethylstilbestrol,DES)暴露对SD大鼠性成熟后睾丸生精细胞凋亡的影响并初步探讨其机制。方法:30只21日龄雄性SD大鼠,随机分为DES 0.01、0.1、1.0、10.0μg/(kg.d)4个实验组和1个对照组(编码为ADa、ADb、AD c、ADd和AC组,每组6只)。于青春期前[出生后第22 d(postnatal day 22,PND22)至35 d(PND35)],实验组每日皮下注射相应剂量的DES,对照组仅注射溶媒。于大鼠性成熟后(PND 64)处死各组大鼠切取双侧睾丸,采用TUNEL法检测大鼠睾丸生精细胞凋亡,用免疫组化方法检测凋亡相关蛋白Bc l-2和Bax在生精细胞中的表达。结果:与对照组相比,ADa组大鼠性成熟后生精细胞凋亡无明显变化,ADb、AD c和ADd 3组生精细胞凋亡增加,且随DES暴露剂量增加而有增加趋势。AC、ADa组生精细胞Bax相对弱表达而Bc l-2强表达,伴随DES暴露剂量增加,Bax表达逐渐增强而Bc l-2表达逐渐减弱,ADd组Bax强表达而Bc l-2弱表达。结论:青春期前较大剂量DES暴露可使大鼠性成熟后睾丸生精细胞凋亡增加,且随DES暴露剂量增加而有加强趋势。凋亡相关蛋白Bax和Bc l-2参与青春期前DES暴露所致的生精细胞凋亡过程。     

Effect of methanol extract of Ricinus communis seed on reproduction of male rats

Aim:To investigate the effect of methanol extract of Ricinus communis seed(RCE)on male rats reproductivefunctions.Methods:Thirty-two male albino rats were divided into four groups.Groups 1,2 and 3 were gavagedwith 0.2 mL of 2.5% tween 80(RCE vehicle;control)or 20 mg/(kg·d)and 40 mg/(kg·d)of RCE,respectively,for30 days,and group 4 was also gavaged with 40 mg/(kg·d)of RCE,but was allowed a recovery periold of 30 days.Five untreated female rats were cohabited with male rats in each group from day 25 of RCE treatment for 5 days,except group 4,where cohabitation began on day 25 of the recovery period.All male rats were sacrificed 24 h afterthe experiments.The female rats were laparatomized on day 19 of pregnancy and the number and weight of litterswere recorded.Results:There was a significant decrease(P<0.01)in the weight of the reproductive organs,sperm functions and serum levels of testosterone in RCE treated rats.There was disorganization in the cytoarchitec-ture of the testes,disruption of the seminiferous tubules and erosion of the germinal epithelium.The number andweight of litters of rats in groups 2 and 4 decreased significantly(P<0.05)but no changes were observed in group3.RCE caused no changes in liver,kidney,heart or body weights in male rats.Conclusion:RCE has a reversiblenegative impact on male reproductive functions,which appears to be mediated via gonadal disruption in testosteronesecretion.(Asian J Androl 2006 Jan;8:115-121)     

Differential expression of bladder neurotrophic factor mRNA in male and female rats after bladder outflow obstruction

PURPOSE: We validated a male rat model of bladder outflow obstruction and compared the expression of bladder neurotrophic factor mRNA in male and female rats 6 weeks after bladder outlet obstruction. MATERIALS AND METHODS: We examined the proximal urethra in male Wistar rats. Urethral lumen reducing ligatures were placed in 15 females and 19 males, while 10 male and 10 female controls underwent sham surgery. Awake cystometry was performed 6 weeks after surgery. Ribonuclease protection assay was used to measure changes in bladder neurotrophic factor mRNA expression in the 2 sexes. RESULTS: Average bladder capacity in rats with bladder outlet obstruction increased 3-fold in males and 4.4-fold in females compared with controls, while bladder weight increased 2.2 and 4.3-fold, respectively. Filling and threshold pressure increased significantly and nonvoiding bladder contractions were recorded in 100% of female and 80% of male rats with bladder outlet obstruction. An 8-fold increase in bladder brain derived neurotrophic factor mRNA was noted in each sex after obstruction. A 2-fold increase in bladder nerve growth factor mRNA after obstruction was only observed in females. CONCLUSIONS: This male rat model of bladder outlet obstruction was created by placing lumen reducing ligatures at the urethrovesical junction. The dramatic increase in bladder brain derived neurotrophic factor mRNA expression and differential expression of nerve growth factor mRNA in male and female rats with bladder outlet obstruction suggest that additional neurotrophic factors may contribute to the lower urinary tract neuroplasticity associated with bladder outlet obstruction and this contribution may be gender dependent.     

Sex differences in urethral pressure response to electrical stimulation of the hypogastric nerves in rats

PURPOSE: This experiment was performed to study the pharmacology of transmitters mediating the response, and the characteristics of the hypogastric nerve (HGN) of female rats, because electrical stimulation of the HGN was found to unexpectedly reduce urethral pressure in female rats. MATERIALS AND METHODS: Male and female Wistar rats (weighing about 250 gm.), 10 weeks and 6 months old, respectively, were used under anesthesia. Fluid was infused from the bladder neck into the urethral lumen at a constant rate (0.5 ml./10 minutes), and infusion pressure signals were measured. Bilateral HGNs were electrically stimulated at 5 and 10 Hz for 30 s. RESULTS: Electrical stimulation of the HGN reduced urethral infusion pressure in about 80% of the female rats, and the introduction of N(omega)-nitro-L-arginine methylester (L-NAME, 30 mg./rat, i.v.) elevated the urethral pressure response from a reduced state. Prazosin (0.1 mg./kg., i.v.) and hexamethonium (10 mg./kg., i.v.), which inhibited elevation of urethral pressure in male rats, also reversed and inhibited the elevation of urethral pressure in the female rats treated with L-NAME. CONCLUSION: The HGN in female rats contained nerve endings that released nitric oxide (NO) and norepinephrine (NE). NO released during HGN stimulation inhibited the release of (NE) and reduced urethral infusion pressure in female rats. Nerves with synapses in the pelvic ganglia released NE in both male and female rats, but nerves that released NO did not have synapses in the ganglia. Only NE was released from the HGN nerve endings in male rats.     

雷藤氯内酯和雷公藤内酯酮对大鼠骨髓细胞染色体与微核的影响

目的 :观察雷藤氯内酯 (T4)和雷公藤内酯酮 (T7)对SD雄性大鼠骨髓细胞染色体与微核的影响 ,了解其抗生育时的安全性。　方法 :雄性SD大鼠 ,随机分为用药组 (T4、T7)和阴性对照组 3组 ,每组 10只。用药组大鼠灌服抗生育剂量T4为 80 μg/ (kg·d)或T7为 317μg/ (kg·d) ,连续用药 10周后采用骨髓细胞染色体和微核制片方法进行分析 ,阴性对照组给等量的载体 (1%羧甲基纤维素钠 )。　结果 :用药组与对照组比较 ,3组之间骨髓细胞染色体畸变平均值差异无显著性 (P >0 .0 5 ) ;骨髓细胞微核出现率差异也无显著性 (P >0 .0 5 )。　结论 :提示抗生育剂量的T4和T7在对SD大鼠遗传学影响方面无明显的诱变作用。     

1,25-二羟基维生素D3对致死剂量脂多糖攻击的大鼠CD_4~＋CD_（25）~＋Treg细胞的调节作用

目的：观察不同剂量1,25-二羟基维生素D3（1,25-（OH）2D3）短期应用对大鼠受致死剂量脂多糖（LPS）攻击后的保护作用,并探讨此保护作用是否与1,25-（OH）2D3对CD4＋CD25＋Treg细胞的调节作用有关。方法：将大鼠分成3个剂量组,每组20只。分别给予1,25-（OH）2D3 0.125μg/只、0.25μg/只、1μg/只灌胃,3次/周,共2周。另设对照组给予赋形剂。给药后第15天腹腔注射致死剂量LPS（10mg/kg）,每组10只用于观察96 h内的死亡率;其余10只大鼠注射LPS 6 h后抽取外周血并留取脾脏标本。流式细胞仪检测大鼠外周血及脾脏CD4＋CD25＋Treg细胞数量,实时定量PCR检测脾脏Foxp3mRNA水平,ELISA检测外周血IL-10和TGF-β水平。结果：用1,25-（OH）2D3预处理的各组大鼠死亡率均显著低于对照组,用药各组外周血及脾脏CD4＋CD25＋Treg细胞数量、脾脏Foxp3mRNA表达水平、外周血IL-10及TGF-β水平也显著高于对照组。结论：1,25-（OH）2D3能够有效保护大鼠抵抗致死剂量LPS的攻击,这种保护作用可能与1,25-（OH）2D3上调CD4＋CD25＋Treg细胞的数量和功能有关。     

氨基胍对大鼠胰腺移植保护作用的实验研究

目的:探讨诱导型一氧化氮合酶抑制剂氨基胍对大鼠移植胰腺的保护作用。方法:糖尿病大鼠模型30只随机分成3组：（1）空白对照组（n=6），仅开腹手术，不作移植;（2）移植对照组（n=6），仅作胰腺移植;（3）氨基胍处理组（n=18），移植胰腺恢复血运前经阴茎背静脉注入盐酸氨基胍（AG）溶液，剂量分别为60，80，100 mg/kg。再灌注4h后检测血清一氧化氮（NO）水平，血糖以及淀粉酶活性，定量分析胰腺组织中的结构型一氧化氮合酶（cNOS）和诱导型一氧化氮合酶（iNOS）活性，并对胰腺进行组织形态学和组织化学检查。结果:与移植对照组比较，氨基胍处理组血NO水平及淀粉酶活性明显降低，胰腺病理损害较轻，其中以AG 80 mg/kg亚组效果更显著（P＜0.01），且该亚组血糖及iNOS活性与表达也明显低于移植对照组（P＜0.01）。结论:诱导型一氧化氮合酶选择性抑制剂氨基胍在大鼠胰腺移植中起到保护作用。其作用机制可能与抑制NO的过量产生，减轻其作为自由基的细胞毒性有关。     

Effect of celecoxib on fasciocutaneous flap survival and revascularization

OBJECTIVES: To study the effect of celecoxib (Celebrex; Pfizer, Cambridge, Mass) on (1) primary ischemic time and (2) revascularization of fasciocutaneous free flaps in a rat model. METHODS: In the ischemia study, 50 male Sprague-Dawley rats were divided into 2 groups of 25 rats each, a control group and a celecoxib group. Five rats in each treatment group were exposed to ischemic times of 4, 6, 8, 10, and 12 hours. Survival of the flap was assessed 7 days after reversal of the ischemia. Probit curves and the critical ischemic time were calculated. In the revascularization study, 30 male Sprague-Dawley rats were divided into 2 groups of 15 rats each. One group was fed celecoxib, while the other was fed a normal diet. All rats had a 3 x 6-cm fasciocutaneous flap based on the inferior epigastric artery elevated and exposed to 2 hours of primary ischemia. The flap was then sutured back into the wound bed. Each of these groups was then divided into 3 groups of 5 rats whose pedicles were divided on postoperative day 5, 6, or 7. Percentage survival of the flap was measured 7 days later. In both parts of the study, the experimental group was fed celecoxib, 1500 ppm, throughout the interoperative period. In each animal, a 3 x 6-cm ventral fasciocutaneous groin flap based on the left superficial epigastric artery was elevated. RESULTS: In the ischemia study, respective flap survival rates from the control and celecoxib groups at the various ischemic times were as follows: 4 hours, 100% and 100%; 6 hours, 80% and 100%; 8 hours, 80% and 80%; 10 hours, 60% and 60%; and 12 hours, 20% and 10%. The median lethal ischemic times were 9.7 and 9.6 hours, respectively. There was no statistical difference in flap survival between the celecoxib and control groups. In the revascularization study, ligation of the flap pedicle on day 5, 6, or 7 did not result in any difference in the percentage of flap survival among the 3 groups. CONCLUSION: Celecoxib appears to have no deleterious effect on free tissue transfer survival or healing, as evidenced by revascularization in a fasciocutaneous free flap model.     

Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded rats.

HLU suppressed bone formation and resulted in bone loss in the tibial metaphysis of 6-month-old male rats. A human therapeutic dose of intermittent PTH (1 microg/kg/day) prevented the skeletal changes associated with HLU. INTRODUCTION: Skeletal unloading of skeletally mature rats results in trabecular thinning in the proximal tibial metaphysis, which is in part caused by a decrease in bone formation. We examined the efficacy of PTH in preventing the detrimental skeletal effects that occur with hindlimb unloading (HLU). MATERIALS AND METHODS: Six-month-old male Fisher 344 rats were HLU and treated with vehicle or recombinant human PTH(1-34) at 1, 5, 20, or 80 microg/kg/day for 2 weeks. The bone response was measured by microCT analysis of bone structure, histomorphometric analysis of static and dynamic bone parameters, and Northern blot analysis of mRNA levels for bone matrix proteins. The PTH-treated HLU animals were compared with vehicle-treated HLU and pair-fed normal weight-bearing controls. RESULTS: Unloading resulted in a decrease in cancellous bone volume that was caused in part by a dramatic 83% decrease in bone formation. All dose rates (1-80 microg/kg/day) of human PTH(1-34) significantly increased bone formation rates compared with vehicle-treated HLU controls. There was a dose response, and the highest dose rate of the hormone increased bone formation compared with normal weight-bearing rats by 708% (p < 0.0001). The increases in bone formation were accompanied by increases in mRNA levels for type 1 collagen, osteocalcin, and osteonectin. Also, treatment with PTH resulted in increases in mineral apposition rate and double-labeled perimeter, but the latter was disproportionally increased at high dose rates. A therapeutic dose of PTH (1 microg/kg/day) prevented disuse-induced trabecular thinning, whereas high-dose PTH (80 microg/kg/day) increased trabecular thickness compared with normal weight-bearing rats. CONCLUSIONS: These findings reveal that administration of a therapeutic dose of PTH to HLU rats prevents the decrease in bone formation and trabecular thinning, whereas high dose rates of the hormone increase bone formation and trabecular thickness to values that exceed normal values.     

The effect of aging on fracture healing in the rat

Summary The effect of age on the biomechanical properties of healing tibial fractures was studied by comparing the fracture healing in 2-year-old male Wistar rats with the fracture healing in 3-month-old male Wistar rats after 40 and 80 days of healing. There were no significant differences in the mechanical parameters after 40 days of healing, but after 80 days, a considerable delay in the fracture healing process was noted in the old rats compared with the young adult rats when evaluated by maximum load, maximum stress, stiffness, and energy absorption in a three-point bending procedure. In the contralateral, nonfractured bones, the tibiae from the old animals sustained higher loads and had higher stiffness than the bones from the young adult animals, but stress values, elastic modulus, and capacity for energy absorption was much lower in the old animals.     

Acute and long-term effects of a single dose of the fungicide carbendazim (methyl 2-benzimidazole carbamate) on the male reproductive system in the rat.

The effects of carbendazim (methyl 2-benzimidazole carbamate) on the testis, efferent ductules, and sperm were determined in the adult rat after a single oral dose. Two experimental trials were performed: a time response between 2 hours and 32 days after exposure using 0 and 400 mg/kg, and a dose response at 2 and 70 days after exposure using 0 to 800 mg/kg doses. In experiment 1, effects were seen throughout the 32-day period, beginning 8 hours after exposure; the effects included first an increase in testis weight, then decreases in testicular spermatid numbers and in the percentage of morphologically normal cauda sperm. In experiment 2, significant testicular and efferent ductal alterations occurred in animals treated with doses of 100 mg/kg or greater. A dose-dependent increase in testicular weight 2 days after treatment was accompanied by increases in seminiferous tubular diameter and excessive loss of immature germ cells in a stage-dependent manner. There was also a dose-dependent increased incidence of occlusions in the efferent ductules. The occluded ductules were characterized by severe inflammation and exhibited disorganization of the epithelium. At 70 days, there were dose-dependent decreases in mean testis weight and mean seminiferous tubular diameter; however, only minimal long-term effects were seen at 50 mg/kg. In testes exhibiting seminiferous tubular atrophy of greater than 25% (100 mg/kg or greater doses), all of the testes were associated with efferent ductules containing occlusions. Caput sperm numbers were significantly reduced in these testes. Occlusions, abnormal ductules, fibrosis, spermatic granulomas, and mineralization were observed in the ductuli efferents. Long-term effects of carbendazim on the testis were induced primarily by ductal occlusions. Results show that carbendazim produces more severe short- and long-term effects on the male reproductive system than the fungicide benomyl.