PEMFs对绝经后骨质疏松症的影响

目的:探讨低频率低强度脉冲电磁场(PEMFs)对绝经后骨质疏松症大鼠的影响.方法:选取3-5月龄雌性SD大鼠,随机分为五组,即阴性对照组(Sham),模型组(Model),阳性对照组(XLGB),脉冲磁场照射组(PEMFs)和给药十照射治疗组(X+P),除Sham实行假性手术外,其余四组经手术分别摘取两侧卵巢(OVX).OVX术后1月按照分组开始治疗,3个月后处死动物,测量大鼠骨转化生化指标(血清ALP,OC和尿DPD),股骨总BMD,BMC,股骨干骺端骨小梁微结构(BV/TV,Conn.D,SMI,Tb·N、Tb·Th、Th·Sp及Tb·Ar),骨生物力学性能(Stress)变化并计算,结果:XLGB、PEMFs、X+P组BMD、BMC、Th·"N、Tb·Th值显著增强,SMI,Th·Sp值显著减小(P<0.01);ALP值有所减小BV/TV,Conn.D值有所增加(P<0.05);Sham组Stress值有明显差异(P<0.01),PEMFs组有一定差异(P<0.05);提示经过磁场照射和(或)药物治疗后股骨生物力学显著增强,骨组织结构骨质疏松症状得到明显改善.结论:PEMFs对绝经后雌激素缺乏引起的OP大鼠有较好的治疗作用.     

Micro-CT观察重组人甲状旁腺素在骨折愈合过程中的作用

目的使用Micro-CT,探讨重组人甲状旁腺激素(rh PTH)在2月龄雄性大鼠骨折愈合过程中的作用。方法应用2月龄雄性SD大鼠建立单侧闭合性股骨骨折内固定模型,随机分为甲状旁腺素治疗组和对照组,术后分别皮下注射重组人甲状旁腺素(1-34)10μg/(kg.d)或等剂量生理盐水安慰剂(对照组),分别于术后第2、7、14、21和42天取双侧股骨标本,分别行X线检查和Micro-CT观察,并进行骨结构的定量分析。结果术后第21天,甲状旁腺素组骨折断端两侧的骨痂之间连续性良好,骨折线已模糊不清。甲状旁腺组较对照组,在术后第42天骨体积(bone Volume,BV)、骨体积分数(BV/TV)、骨密度(bone mineral density,BMD)和骨小梁模式因子(trabecular bone pattern factor,Tb.Pf)明显高于对照组;而骨小梁分离度(trabecular separation,Tb.Sp)和各向异性的程度(degree of anisotropy,DA)低于对照组。结论低剂量重组人甲状旁腺激素可提高大鼠骨折BV、BV/TV、Tb.Pf和BMD而降低Tb.Sp和DA,从而促进骨折的愈合。     

ERα基因过表达对去卵巢骨质疏松小鼠骨密度及钙磷代谢的影响

目的: 探讨雌激素受体α(ERα)基因过表达对去卵巢骨质疏松小鼠骨代谢及钙磷代谢的影响,为靶向基因治疗骨质疏松症提供实验依据。方法: 选择SPF级雌性小鼠30只,随机分为假手术组、模型组和ERα过表达组,每组10只。采用双侧卵巢切除法制备绝经后骨质疏松小鼠模型,模型建立完成后,ERα过表达组通过椎体髓腔注射的方法转染携带小鼠ERα基因的重组腺病毒载体,模型组转染空载病毒,假手术组不作处理。实时荧光定量PCR(qRT-PCR)检测小鼠骨组织ERα基因表达;分别于造模后检测小鼠股骨骨密度(BMD);采用Micro-CT扫描测量骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁分离度(Tb.Sp)、骨体积分数(BV/TV),并进行股骨生物力学强度检测;采用全自动生化仪检测血清中钙(Ca)、磷(P)、骨钙素(BGP)、碱性磷酸酶(ALP)含量;采用免疫组化检测骨组织中基质金属蛋白酶的组织抑制剂1(TIMP-1)和单核细胞趋化蛋白-1(MCP-1)的蛋白表达水平。结果: 与假手术组相比,模型组小鼠骨组织ERα基因表达水平显著降低、BMD、BV/TV、Tb.Th、最大载荷、刚性系数、Ca和P降低,而Tb.Sp、BGP和ALP显著升高(P＜0.05);ERα过表达组小鼠骨组织ERα基因表达水平、BMD、BV/TV、Tb.Th、最大载荷、刚性系数、Ca和P较模型组小鼠显著上升;而Tb.Sp、BGP和ALP显著降低(P＜0.05)。与假手术组相比,模型组小鼠骨组织中TIMP-1平均光密度值显著降低而MCP-1平均光密度值升高,而ERα过表达组TIMP-1平均光密度值显著升高而MCP-1显著降低(P＜0.05)。结论: ERα基因过表达通过调节骨密度、骨参数、骨代谢、钙磷代谢指标及组织中TIMP-1和MCP-1的表达水平,改善骨质疏松。     

去卵巢大鼠腰椎骨微结构变化的动态观察

目的:动态观察去卵巢大鼠腰椎骨微结构的变化。方法:将90只3月龄雌性SD大鼠按体重进行分层随机抽样分组,分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。手术前(0周)处死基础组大鼠,手术后3、6、12、24周时,分批处死假手术和去卵巢组大鼠各8-10只。从每组随机取6只大鼠的第5腰椎行micro-CT扫描及三维结构重建,选取椎体1 mm处,2.0 mm×3.5mm,厚0.9 mm的骨组织为感兴趣区域(interesting area),进行骨形态计量学分析。结果:与同一时间点假手术组大鼠比较,去卵巢3周时,第5腰椎体积骨密度(v BMD)、骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间隙(Tb.Sp)和结构模型指数(SMI)均无显著变化;去卵巢6周时,Tb.Th显著下降(P0.05),而其他指标均无显著变化;从去卵巢12周到24周时,不仅Tb.Th显著下降(P0.05),而且v BMD、BV/TV和Tb.N也显著下降(P0.05),同时Tb.Sp和SMI显著增加(P0.05)。结论:3月龄大鼠在去卵巢后的6周时骨小梁厚度变薄,12周以后,体积骨密度和骨体积分数下降,骨小梁数目减少。     

黑升麻提取物对去势大鼠体温的影响

目的:观察黑升麻提取物对去势大鼠体温的影响。方法:雌性Sprague-Dawley(SD)大鼠30只,随机分为假手术(Sham)组、去势(OVX)组及去势后黑升麻提取物治疗(OVX+BC)组,每组10只。使用相应药物分别治疗并监测体温8周。结果:1与Sham组比较,OVX组及OVX+BC组大鼠的平均体温明显升高(P0.05);2与OVX组比较,OVX+BC组大鼠的平均体温明显减低(P0.05)。结论:大鼠去势后会出现体温升高。黑升麻提取物可以使去卵巢大鼠体温下降,达到缓解围绝经期潮热症状的目的。     

人体颈椎松质骨显微结构和力学性能的区域性差异研究

目的:探讨人体脊柱松质骨骨骼显微结构和力学性能的区域性差异,为松质骨三维结构采样部位的选取提供参考。方法:显微CT扫描6块颈6椎体标本获得三维图像,依据椎体内解剖位置的不同,将松质骨划分为6个位置组:外侧、内侧、腹侧、背侧、头侧和尾侧。利用显微结构参数骨体积分数(Bone volume to tissue volume,BV/TV)、骨表面积和骨体积的比值(Bone surface to bone volume,BS/BV)、骨小梁数量(Trabecular number,Tb.N)、骨小梁厚度(Trabecular thickness,Tb.Th)、骨小梁分离度(Trabecular separation,Tb.Sp)和个体化骨小梁分割方法(Individual trabeculae segmentation,ITS)分析6个位置组内松质骨显微结构,并利用有限元分析,获得6个位置组内松质骨的力学性能参数表观弹性模量和表观剪切模量。分别两两对比外侧和内侧,腹侧和背侧,头侧和尾侧松质骨的显微结构参数(BV/TV、BS/BV、Tb.N、Tb.Th、Tb.Sp和个体化骨小梁分割得到的参数)和力学性能参数(表观弹性模量和表观剪切模量)。结果:头侧和尾侧的主要显微结构参数BV/TV、Tb.Th、Tb.N等和表观弹性模量均存在显著差异(P0.05)。腹侧和背侧、内侧和外侧的主要显微结构参数BV/TV、Tb.Th、Tb.N等无显著差异。外侧和内侧的表观弹性模量在非主方向即内外方向和腹背放上上存在显著差异(P0.05),在主方向即头尾上无显著差异。结论:在实验中采集椎体松质骨样本以及临床上利用高分辨率CT分析椎体松质骨结构时,感兴趣区域要同时涵盖头侧和尾侧。     

去卵巢致骨质疏松症大鼠腺垂体FS细胞中Cx43、S-100蛋白表达--激光扫描共聚焦显微镜观察

检测间隙连接蛋白Cx43、神经组织蛋白S-100在去卵巢致骨质疏松症(OVX-OP)大鼠腺垂体滤泡星形细胞(FS细胞)中的表达.实验采用10月龄未孕产SD雌性大鼠40只,随机均分为卵巢切除组(OVX组,n=20)和假性手术对照组(Sham组,n=20).于术后6周末用双能X线骨吸收测量法(DEXA)测量大鼠全身及腰椎4-6(L4-6)骨密度(BMD).取两组大鼠垂体,制成连续切片.应用FITC标记的IgG探针,对腺垂体组织中Cx43和S-100进行间接免疫荧光染色,并用激光扫描共聚焦显微镜(LSCM)定位和定量分析腺垂体FS细胞中Cx43、S-100的表达.结果发现,术后6周末OVX组大鼠全身及L4-6BMD均明显低于Sham组值(P<0.01,P<0.01).Cx43阳性荧光反应主要定位于相邻的FS细胞的胞浆中和/或胞膜上.OVX组Cx43阳性表达荧光强度和表达阳性率均显著低于Sham组(P<0.01).S-100蛋白表达定位于FS细胞的胞浆中,两组间S-100阳性表达荧光强度和表达阳性率无显著差异(P>0.05).本研究提示,SD大鼠OVX术后6周出现骨质疏松变化;OVX大鼠腺垂体FS细胞数量无明显变化、而Cx43表达显著下降,后者的变化可能与大鼠OVX-OP发生相关.     

生物衍生松质骨支架材料的Micro—CT量化分析

目的：在骨组织工程中,如何制备出理想的支架材料一直是研究重点;目前主要的有天然生物支架材料、人工合成有机材料和无机材料等;生物衍生骨即天然生物支架材料的一种,由于其与天然骨在形态结构上较为相似,是近年来研究较多的支架材料之一;既往形态学研究局限于在二维层面,对于其三维结构参数分析较少。故本实验主要运用Micro-CT对生物衍生松质骨的三维结构参数进行分析,量化评价其作为骨组织工程支架材料的结构参数。方法：截取新鲜猪松质骨,经脱脂脱蛋白部分脱钙及去抗原处理后,制作成生物衍生骨支架;应用Micro．CT扫描,重建三维图并量化分析其结构参数,统计软件SPSS分析各参数间的相关性。结果：经Micro．CT扫描,得到二维CT图和三维重建图。各三维结构参数的值分别为：BV／TV（20．48±5．14）％;BS／BV（41．66±5．39）1／ram;Porosity（79．52±5．14）％;Tb．Th（0．10±0．01）mm;Tb．N（1．99±0．47）l／mm;Tb．Sp（0．32±0．05）mm;Tb．Pf（2．03±4．70）1／mm;SMI（1．28±0．35）;DA（1．60±0．23）;Corm．Dn（158．53±106．09）I／mm3。各参数间相关系数具有统计学意义的为：（1）Porosity与BS／BV、Tb．Th;（2）BV／TV与BS／BV、Tb．Th;（3）BS／BV与Coma．Dn、Porosity、BV/TV、;（4）Tb．Th与Porosity、BV厂IV、Conn．Dn;（5）DA与Corm．Dn;（6）Conn．Dn与Bs／BV、Tb．Th、DA。结论：Micro-CT扫描、量化分析是评价支架材料结构参数的理想方法;也证明生物衍生骨支架符合骨组织工程对支架材料的三维结构要求,尤其在孔径大小、孔隙率、表面积体积比等三维结构参数,此外,也可为其他支架材料的制备在三维结构上的要求提供参考依据。     

降钙素对骨质疏松大鼠骨密度形态计量学与骨代谢的影响

目的探讨降钙素(密盖息)对骨质疏松大鼠骨密度、骨形态计量学影响以及与血钙、磷、维生素D代谢和生长因子的关系。方法用摘除大鼠双侧卵巢的方式制备骨质疏松模型(OVX),实验动物分为4个组:模型对照组、密盖息治疗组,盐酸雷洛昔芬治疗组,假手术组。应用HOLOGIC第4代双能X线4500W骨密度仪测定大鼠腰椎、股骨上段骨密度值(BMD);以骨形态计量学测股骨骨小梁面积、矿化沉积率;用ELISA法测定血清IGF-1水平和血清25OHVitD浓度以及血淋巴细胞维生素D受体(VDR)含量。结果密盖息治疗组、盐酸雷洛昔芬治疗组均较OVX组腰椎、股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。密盖息治疗组较盐酸雷洛昔芬治疗组股骨上段骨密度增高,两组之间差异有显著性(P<0.01)。密盖息治疗组骨小梁面积明显增加、矿化沉积率增高。密盖息治疗组、盐酸雷洛昔芬治疗组血清IGF-1浓度值、血清25-OHVitD浓度值升高,与OVX组比较差异有显著性(P<0.01)。各组血淋巴细胞VDR含量无明显变化,与OVX组比较差异无显著性(P>0.05)。结论密盖息能够预防腰椎、股骨上段骨密度丢失,使骨小梁面积明显增加、矿化沉积率增高并且血清IGF-1及血清25-OHVitD浓度值升高,但对VDR含量无明显作用。     

外泌体miR-338对骨质疏松大鼠骨代谢水平、骨小梁微结构和骨生物力学的影响

摘要 目的：探讨外泌体miR-338对骨质疏松大鼠骨代谢水平、骨小梁微结构和骨生物力的影响。方法：采用健康成年SPF级SD雄性大鼠进行骨髓间充质干细胞（BMSCs）分离。采用双侧卵巢摘除手术方法构建了骨质疏松大鼠模型。采用qRT-PCR法检测miR-338的表达水平;检测大鼠的骨密度,骨小梁微结构和骨生物力学指标。结果：与空白对照组相比,OP模型组、OP+ ExoBMSCs、抑制组和过表达组miR-338的表达水平明显更高（P＜0.05）;抑制组的miR-338的表达水平低于OP模型组、OP+ExoBMSCs和过表达组（P＜0.05）;与空白对照组相比,OP模型组、OP+ ExoBMSCs、抑制组和过表达组OC、PINP、BALP的表达水平明显更低（P＜0.05）;抑制组的OC、PINP、BALP的表达水平明显高于OP模型组、OP+ ExoBMSCs和过表达组（P＜0.05）;与空白对照组相比,OP模型组、OP+ ExoBMSCs、抑制组和过表达组BV/TV、Th.N、Tb.Th、Conn.D水平更低,而Tb.Sp、SMI明显更高（P＜0.05）;抑制组组的BV/TV、Th.N、Tb.Th、Conn.D水平明显高于OP模型组、OP+ ExoBMSCs和过表达组,而Tb.Sp、SMI更低（P＜0.05）;与空白对照组相比,OP模型组、OP+ ExoBMSCs、抑制组和过表达组BMD、最大荷载、最大应力、最大位移、刚度水平更低（P＜0.05）;抑制组的BMD、最大荷载、最大应力、最大位移、刚度水平高于OP模型组、OP+ExoBMSCs和过表达组（P＜0.05）。结论：BMSCs源性的miR-338可影响骨质疏松大鼠骨代谢、骨小梁微结构和骨生物力学状态。     

藏红花提取液对去卵巢大鼠骨密度及骨代谢生化指标的影响

目的：研究中药藏红花提取液对去卵巢大鼠股骨骨密度及血清骨代谢生化指标的影响。方法：选用48只4月龄SD雌性大鼠,随机分为6组：假手术组、模型组、戊酸雌二醇组、藏红花低、中、高剂量组。术后4周各组分别给予相应制剂灌胃,术后12周处死,分别测定股骨骨密度、子宫指数、雌二醇、血钙、血磷、碱性磷酸酶。结果：与模型组相比,藏红花各剂量组股骨骨密度明显升高（p〈0.01）,雌二醇测定值升高（p〈0.01）,碱性磷酸酶显著降低（p〈0.01）,血钙及血磷无统计学差异（p〉0.05）;与戊酸雌二醇组比较,藏红花各剂量组子宫指数显著降低（p〈0.01）。结论：藏红花提取液有助于抑制去卵巢大鼠骨量的丢失,改善骨代谢,对骨质疏松症具有防治作用。     

Dietary boron supplementation enhanced the action of estrogen, but not that of parathyroid hormone, to improve trabecular bone quality in ovariectomized rats

This study investigated whether boron would enhance the ability of 17beta-estradiol (E2) or parathyroid hormone (PTH) to improve bone quality in ovariectomized OVX rats. Adult OVX rats were treated for 5 wk with vehicle, boron (5 ppm as boric acid), E2 (30 microg/kg/d, sc), PTH (60 microg/kg/d, sc), or a combination of boron and E2 or PTH, respectively. The E2 treatment corrected many adverse effects of OVX on bone quality, increased bone Ca, P, and Mg contents, and decreased trabecular plate separation. Dietary boron supplementation had no effects on these bone parameters in OVX rats. When OVX rats were treated with boron and E2 together, trabecular bone volume (Tb.BS/TV) and plate density were increased significantly more than that caused by E2 alone. The boron and E2 combination also increased trabecular bone surface (Tb.BV/TV) and decreased trabecular plate separation in OVX rats. In contrast, whereas daily PTH injection also increased bone Ca, Mg, and P contents, Tb.BV/TV, Tb.BS/TV, trabecular plate density and thickness, and decreased trabecular plate separation in OVX rats, the combination of boron and PTH had no additional improvement in bone quality over that achieved by PTH alone. In summary, this study shows for the first time that boron enhanced the action of E2, but not that of PTH, to improve trabecular bone quality in OVX rats.     

葛根异黄酮对去卵巢大鼠骨质疏松症的影响

通过对3月龄Wister大鼠,手术切除双侧卵巢后7天,每天灌胃TIP40mg/kg和10mg/kg,并设去卵巢组(OVX)、假手术组(Sham)和尼尔雌醇阳性对照组(OVX-E2),在给药3个月时,测定大鼠股骨骨矿密度(BMD)、骨钙及血清钙水平等,研究葛根异黄酮(TIP)对由雌激素缺乏引起的骨质疏松症的防治作用。结果TIP40mg/kg的BMD比去卵巢组显著提高了18.1%;使胫骨和血清钙含量显著增加;使去卵巢大鼠的脾脏重量系数和胸腺重量系数明显恢复;并可明显控制大鼠的体重。葛根异黄酮可能具有雌激素样活性,并有改善骨质疏松症的生物学活性。     

Therapeutic effect of risedronate on cancellous and cortical bone in ovariectomized osteopenic rats: a comparison with the effects of alfacalcidol.

The purpose of the present study was to compare the therapeutic effects of risedronate (RIS) and alfacalcidol (ALF) on cancellous and cortical bone in ovariectomized osteopenic rats. Forty-two female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 microg/kg, p.o., daily). Treatment was started 6 weeks after surgery and continued for 6 weeks. Evaluation at 12 weeks after surgery revealed that ovariectomy (OVX) decreased the cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis as a result of an increase of the bone formation rate/bone surface (BFR/BS), BFR/BV, and eroded surface (ES/BS), while having no effect on the cortical area (Ct Ar) of the tibial diaphysis. OVX also decreased the maximum load of the femoral distal metaphysis, while having no effect on any mechanical property parameters of the femoral diaphysis. RIS (at all the doses) increased the BV/TV relative to the value in the OVX-Vehicle group, but the value was not restored to that observed in the Sham group. The effects of RIS (1.0 mg/kg and 2.5 mg/kg) were similar, and greater than those of RIS (0.1 mg/kg). ALF also increased the BV/TV relative to the OVX-Vehicle group, but the value was not restored to that observed in the Sham group, similar to the results of RIS (1.0 mg/kg and 2.5 mg/kg) treatment. The alterations of the structural parameters induced by RIS (at the doses) were attributable to suppression of the increase of ES/BS, BFR/BS, and BFR/BV. The alterations of the structural parameters induced by ALF were attributable to suppression of the increase of ES/BS and attenuation of the increase of BFR/BV, while the BFR/BS was maintained. ALF also increased the Ct Ar to beyond the value observed in the Sham group. RIS (at all the doses) had no effect on the mechanical properties of the femoral distal metaphysis, whereas ALF prevented the loss of the maximum load of the femoral distal metaphysis. Thus, the results of the present study show differential effects of RIS and ALF on cancellous and cortical bone in ovariectomized osteopenic rats.     

Suppressive effects of genistein dosage and resistance exercise on bone loss in ovariectomized rats.

This study was designed to determine whether combined treatments with genistein dosage and moderate resistance exercise would exhibit synergistically preventive effects on bone loss following the onset of menopause. Forty-one 12 wk-old female SD rats were assigned to five groups: 1) Sham operated (Sham); 2) ovariectomized (OVX-Cont); 3) OVX received genistein (OVX-GEN); 4) OVX exercised (OVX-EXE); and 5) OVX treated with both genistein and exercise (OVX-GEN-EXE). All rats were fed a low Ca (0.1%) diet ad libitum. Daily genistein dosage was 12 mg/kg body weight. Exercising rats took 40 sets of 1-min run interspersed with 1-min rest with a 100 g weight on the back on an uphill treadmill at 20 m/min. The experimental duration consisted of the adaptation and treatment periods of 4 weeks each. Uterine weight in OVX-Cont, OVX-GEN, OVX-EXE and OVX-GEN-EXE decreased to about 15% of that in Sham (p < 0.001). The femoral BMD (mg/cm2; mean +/- SE), assessed by DEXA (Lunar), of OVX-Cont was significantly lowered to 206 +/- 5 by -9%, as compared to 226 +/- 2 of Sham (p < 0.001). The BMD of OVX-GEN, OVX-EXE and OVX-GEN-EXE were 217 +/- 2, 217 +/- 2 and 222 +/- 2, respectively, and genistein dosage and resistance exercise equally increased the BMD of OVX rats by 5% (p < 0.01). Combined treatment of genistein and exercise more successfully recovered their decreased BMD by 8% (p < 0.001). BMD of the fourth lumbar vertebrae in OVX-Cont was declined to 191 +/- 7 by -15%, as compared to 225 +/- 4 in Sham (p < 0.001). OVX-EXE and OVX-GEN-EXE gained the BMD by 6% to 205 +/- 4 and 203 +/- 3, respectively, as compared to that of OVX-Cont (p < 0.01). These results suggest the possibility that the combined treatment of genistein dosage and resistance exercise have more beneficial effects by acting rather independently than their separate trials on the prevention of ovx-induced bone loss in femurs.     

Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength.     

Inducible nitric oxide synthase inhibitor aminoguanidine, differently affects Morris water maze tasks of ovariectomized and naïve female rats

The role of ovarian hormones, nitric oxide, and their interaction on learning and memory has been widely investigated. The objective of present study was to investigate different effects of chronic administration of inducible nitric oxide synthase inhibitor, aminoguanidine (AM) on learning and memory of ovariectomized (OVX) and na?ve (Sham) female rats. Thirty-two rats were divided into four groups: 1) Sham, 2) OVX, 3) Sham-AM and 4) OVX-AM. The animals of Sham-AM and OVX-AM chronically received 100 mg/kg/day of aminoguanidine during 8 weeks before 5 test days. The animals in Sham and OVX groups received 1 ml/kg saline instead of aminoguanidine. The animals were tested in Morris water maze and the escape latency and traveled path to reach the platform were compared between groups. On the fifth day, the platform was removed, and the animals were allowed to swim for 60 s ( prob trial). The time spent in the target quadrant (Q1) was compared between groups.Results showed that the escape latency and traveled path in OVX group were significantly higher than in the Sham group (p<0.01). Both escape latency and traveled path in the Sham-AM group was significantly higher than in the Sham group (p<0.01) however, there was no significant difference between OVX-AM and OVX groups.The time spent by the animals of OVX group in the target quadrant (Q1) during the probe trial was significantly lower than that in the Sham group (p<0.01). The animals of the Sham-AM group spent shorter times in the target quadrant in comparison with the Sham group (p<0.01). There was no significant difference between the OVX and OVX-AM groups in the time spent in tarthe get quadrant. It is concluded that the effect of aminoguanidine on learning and memory is different in the presence or absence of ovarian hormones but it needs further investigation.     

Prevention of bone loss by EM-800 and raloxifene in the ovariectomized rat

Some undesirable effects are associated with chronic estrogen and progestin administration used to prevent bone loss in postmenopausal women, thus leading to poor compliance and the need for improved therapeutic and preventive agents. We have thus studied the ability of the new antiestrogen EM-800 (SCH 57050) to prevent bone loss and lower serum cholesterol levels and compared its effects with those of raloxifene. Ovariectomized (OVX) female rats were treated by oral gavage for 37 weeks with increasing daily doses (0.01, 0.03, 0.1, 0. 3 or 1 mg/kg) of EM-800 or raloxifene. At 35 weeks after OVX, lumbar spine bone mineral density (BMD) was 19% lower than in intact animals (P<0.01), while the OVX animals given EM-800 or raloxifene had 90-93 and 85-90%, respectively, of the BMD values observed in intact rats. Similar effects were observed on femoral BMD. Bone histomorphometry measurements were performed on proximal tibia. At the 0.01 mg/kg dose, EM-800 prevented the effect of OVX on TBV by 34% (P<0.01), while raloxifene had no detectable effect. Treatment with 1 mg/kg EM-800 and raloxifene resulted in, respectively, 68% (P<0.01) and 64% (P<0.01) prevention of the OVX-induced decrease in TBV. In addition, the administration of 0.01 and 0.03 mg/kg EM-800 caused, respectively, 54% (P<0.01) and 56% (P<0.01) inhibitions of serum cholesterol levels, while raloxifene administered at the same doses caused, respectively, 24% (P<0.01) and 41% (P<0.01) decreases of the value of the same parameter. At the highest doses used (0.1-1 mg/kg), both compounds lowered serum cholesterol levels by approximately 65% (P<0.01). No stimulatory effect of EM-800 was observed on the endometrial epithelial cells at doses up to 1 mg/kg, while hypertrophy of uterine epithelium was observed with raloxifene. EM-800 and raloxifene achieve the same degree of effectiveness on bone and serum cholesterol at higher doses, but EM-800 is at least three to ten times more potent than raloxifene at lower concentrations and has no stimulatory effect on uterine epithelium. The present data show the potent effect of EM-800 preventing bone loss and lower serum cholesterol levels without the negative effect on the endometrium, thus suggesting the particular interest of this new fully tissue-specific selective estrogen receptor modulator.