关节软骨源性微载体生物相容性及异位成软骨特性观察

目的 观察改良后软骨源性微载体的微观结构及主要成分,其对软骨细胞增殖的影响及体内异位成软骨特性.方法 将新鲜猪软骨片粉碎后,梯度筛滤后得到直径大200～400 μm的软骨源性微载体,经1%十二烷基硫酸钠（SDS）脱细胞处理后,Hoechst 33258荧光染色观察其DNA残留,采用扫描电镜对其微结构进行观察,通过甲苯胺蓝、番红花O组织学染色和Ⅱ型胶原免疫荧光染色观察微载体的主要成分;体外复合软骨细胞后,通过MTT观察软骨源性微载体对软骨细胞增殖的影响;将复合有软骨细胞的软骨源性微载体包埋于裸鼠皮下观察其异位成软骨能力.结果 改良后的微载体形态近似椭圆形,直径200～400 μm,微丝覆盖其表面,微丝长度40～90 nm;脱细胞处理后Hoechst 33258荧光染色阴性;甲苯胺蓝和番红花O组织学染色及Ⅱ型胶原免疫组化染色阳性;在MTT检测细胞增殖中,第1天以后软骨源性微载体组及条件培养基组的OD值均高于完全培养基组（P〈0.05）;复合有软骨细胞的软骨源性微载体具有异位成软骨能力.结论 本实验成功制备的软骨源性微载体,可作为天然微载体高效扩增软骨细胞,可为组织工程提供优质种子细胞;其具有异位成软骨能力,有望成为软骨组织工程的新型支架.     

关节软骨源性微载体生物相容性及异位成软骨特性观察

目的 观察改良后软骨源性微载体的微观结构及主要成分,其对软骨细胞增殖的影响及体内异位成软骨特性.方法 将新鲜猪软骨片粉碎后,梯度筛滤后得到直径大200～400 μm的软骨源性微载体,经1%十二烷基硫酸钠（SDS）脱细胞处理后,Hoechst 33258荧光染色观察其DNA残留,采用扫描电镜对其微结构进行观察,通过甲苯胺蓝、番红花O组织学染色和Ⅱ型胶原免疫荧光染色观察微载体的主要成分;体外复合软骨细胞后,通过MTT观察软骨源性微载体对软骨细胞增殖的影响;将复合有软骨细胞的软骨源性微载体包埋于裸鼠皮下观察其异位成软骨能力.结果 改良后的微载体形态近似椭圆形,直径200～400 μm,微丝覆盖其表面,微丝长度40～90 nm;脱细胞处理后Hoechst 33258荧光染色阴性;甲苯胺蓝和番红花O组织学染色及Ⅱ型胶原免疫组化染色阳性;在MTT检测细胞增殖中,第1天以后软骨源性微载体组及条件培养基组的OD值均高于完全培养基组（P〈0.05）;复合有软骨细胞的软骨源性微载体具有异位成软骨能力.结论 本实验成功制备的软骨源性微载体,可作为天然微载体高效扩增软骨细胞,可为组织工程提供优质种子细胞;其具有异位成软骨能力,有望成为软骨组织工程的新型支架.     

Histochemical studies of bladder tumors

Twenty seven bladder tumors, three ureteral tumors and one renal pelvic tumor were studied by means of light microscopic histochemical methods for demonstration and identification of acid mucopolysaccharides. Alcian blue (pH 1.0), alcian blue (pH 2.5), periodic acid-Schiff (PAS) and aldehyde-fuchusin stainings were performed. These stainings showed that all tumor specimens contained acid mucopolysaccharides. For identifying individual acid mucopolysaccharides, enzyme digestion procedures were performed prior to staining with alcian blue. (streptomyces hyaluronidase, testicular hyaluronidase, chondroitinase ABC, chondroitinase AC, keratanase, heparinase, heparitinase.) According to these experiments, high-grade, and high-stage tumors contained large amounts of sulfated mucopolysaccharides. Squamous cell carcinomas of the bladder contained especially large amounts of chondroitin sulfate AC.     

The effect of holmium laser radiation on stress, temperature and structure of cartilage

It is difficult to permanently alter the shape of cartilage in a controlled way. In otolaryngology and plastic surgery several procedures are done to alter the shape of cartilage, for example the correction of a deviated nasal septum and surgery for bat ears. The aim of this paper is to study the main parameters which are necessary for the phenomenon of reshaping of cartilage under non-destructive laser radiation. We have measured temperature and stress in cartilage when it is being reshaped with a holmium laser, It has been shown that laser-induced stress relaxation in cartilage takes place when the tissue temperature exceeds 70°C. We have determined the conditions which allow the shape of cartilage to be altered without producing any pronounced alteration to matrix structure or chondrocytes.     

磁共振延迟增强软骨成像在实验性关节软骨退变定量测定中的应用研究

目的 探讨磁共振延迟增强软骨成像在检测关节软骨退变中的应用价值.方法 选用20只新西兰大白兔,随机分为甲、乙、丙、丁四组.甲组左膝关节行常规磁共振成像,扫描结束后即刻处死,取股骨髁软骨行苏木精-伊红染色(HE)、阿利辛兰染色(AlcianBlue,AB)及蛋白多糖含量测定.乙、丙、丁各组每只兔左膝关节内注射0.2ml(10U)木瓜蛋白酶.乙、丙、丁各组于注射木瓜蛋白酶前及注射后分别于24、48、72h先行相同常规磁共振成像,后行磁共振延迟增强软骨成像(dGEMRIC),测定关节软骨T1驰豫时间值并取平均值.扫描结束后处死动物,取左膝股骨髁部软骨行大体观察、HE、AB染色及蛋白多糖含量测定.结果 注射木瓜蛋白酶后24、48h,蛋白多糖含量与甲组比较,统计学均有差异(P=0.048和0.045,P<0.05),注射后72h,统计学没有差异(P=0.455,P>0.05).T1map图像软骨色阶由注射前的粉红色转为注射后的蓝色,注射木瓜蛋白酶后24、48、72h的T1弛豫率分别降低了316.09ms、244.01ms和143.98ms.经t检验,注射后24、48h与注射前比较有统计学差异(P=0.047和0.045,P<0.05).结论 本研究采用的dGEM-RIC成像技术能够通过定量检测T1弛豫时间值反映软骨退变早期软骨内的生化改变.     

The histochemistry of complex carbohydrates in the prostatic tumor

Seventy five prostatic specimens from cancer, BPH and normal controls were studied by light microscopic histochemical methods for the demonstration of complex carbohydrates and some proteins: 1) alcian blue (AB) (pH 1.0), 2) alcian blue (AB) (pH 2.5), 3) Periodic Acid-Schiff (PAS), 4) peroxidase labelled-Ricinus communis agglutinin-diaminobenzidine (PO-RCA-DAB), 5) Concanavalin A-peroxidase-diaminobenzidine (ConA-PO-DAB), 6) ConA-PO-DAB-periodic acid-m-aminophenol Fast black salt K (ConA-PO-DAB-PA-AP-FBK). For identifying individual acidic and neutral carbohydrates, following procedures of enzyme digestion were performed upon some tissue sections prior to the above histochemical staining: a) sialidase (prior to staining with AB at pH 2.5), b) streptomyces hyaluronidase (prior to staining with AB at pH 2.5), c) testicular hyaluronidase (prior to staining with AB at pH 1.0 or pH 2.5), d) chondroitinase ABC (prior to staining with AB at pH 1.0 or pH 2.5), e) chondroitinase AC (prior to staining with AB at pH 1.0 or pH 2.5), f) alpha-amylase (prior to staining with PAS). In addition, the tissue specimens from prostatic cancer were stained immunohistochemically for demonstration of prostatic acid phosphatase (PAP) and the serum PAP levels were also measured by radioimmunoassay. The histochemical differences in the prostatic tissue among normal control, BPH and cancer as follows. In the tissue of prostatic cancer, chondroitin sulfate A, C and hyaluronic acid were present in the interstitium. Chondroitin sulfate, hyaluronic acid and sialic acid were present in the cytoplasm of cancer cells. In the tissue of BPH chondroitin sulfate B and hyaluronic acid was present in the interstitium and hyaluronic acid was present in the cytoplasm of epitherial cells. In the epithelial basement membrane of the tissue from BPH, chondroitin B and hyaluronic acid were present. 1,2-Glycol groups of neutral complex carbohydrates in the interstitium of prostatic cancer were shown to exist in smaller amounts than in that of BPH. In the cytoplasm of cancer cells the intensity of both PO-RCA-DAB and ConA-PO-DAB staining could be divided into three groups: strong, moderate and weak. In the prostatic cancer there was a good correlation between the intensity of PO-RCA-DAB staining and tumor grade, and intensity of ConA-PO-DAB staining was correlated well with serum PAP level. The cytoplasm of cancer cells showed a positive reaction to PAP immunostaining and no appreciable difference was observed according to tumor grade.(ABSTRACT TRUNCATED AT 400 WORDS)     

软骨寡聚基质蛋白对BMP 2诱导骨髓间质干细胞分化的影响

 目的 探讨过表达软骨寡聚基质蛋白（cartilage oligomeric matrix protein,COMP）对BMP-2诱导骨髓间质干细胞成骨及成软骨分化的影响。方法 用BMP-2诱导骨髓间质干细胞分化,通过脂质体转染含人COMP基因的质粒使骨髓间质干细胞过表达COMP,空载质粒作为对照。以RT-PCR检测成骨相关基因Ⅰ型胶原、RUNX2、骨桥蛋白、骨钙蛋白以及成软骨相关基因Ⅱ型胶原、SOX9、蛋白聚糖的表达变化;通过碱性磷酸酶染色观察成骨过程中的碱性磷酸酶活性,茜素红染色观察成骨终末阶段矿化结节的生成情况,阿利新蓝染色观察细胞基质蛋白多糖的合成情况。结果 COMP组目的基因COMP mRNA的表达显著升高;骨桥蛋白mRNA表达水平较对照组低,呈现出一致的下调趋势（P<0.05）;Ⅰ型胶原、RUNX2、骨钙蛋白mRNA表达水平在诱导早期均高于对照组（P<0.05）,但在诱导晚期均明显低于对照组（P<0.05）;成软骨指标（Ⅱ型胶原、SOX9、蛋白聚糖）的基因表达水平强于对照组,呈一致的上调趋势（P<0.05）;SOX9 mRNA表达水平高于对照组,仅在第7天时差异具有统计学意义（P<0.05）;细胞成骨染色（碱性磷酸酶染色、茜素红染色）均弱于对照组,而阿利新蓝染色强于对照组。结论 COMP能抑制BMP-2诱导骨髓间质干细胞成骨分化,促进BMP-2诱导骨髓间质干细胞成软骨分化。     

Cartilage shaping with the Er:YAG laser: an in vivo experimental study

Reshaping and preserving the new shape of cartilage grafts is important for reconstruction of congenital or acquired deformities. In this in vivo study the authors investigated the effect of the Er:YAG laser on cartilage reshaping in comparison with scalpel stripping. The study consisted of two groups (N = 9). After measuring the angle between two margins of the ear, the cartilage in the right ear in rabbits was reshaped using the Er:YAG laser in group I, and scalpel incisions were used to reshape the left-ear cartilage in group II rabbits. Changes in the shape of the ears were evaluated at 10 days, and 1 and 6 months. The laser-reshaped ears were flattened and preserved the new flattened shape at the end of 6 months. The ultrastructural changes in the cartilage were evaluated based on the results from histopathological examination and electron microscopy. The authors conclude that cartilage can be reshaped using the Er:YAG laser. The mechanical effect of laser ablation and the thermal effect of laser radiation caused ultrastructural changes in the cartilage tissue, resulting in permanent changes in cartilage shape.     

Staining of intracellular granules in fresh epiphyseal cartilage by cationic dyes

Hand-cut sections of fresh epiphyseal cartilage from young rats were stained at pH 4.5 in 0.01% solutions of various cationic dyes of the thiazine, oxazine, azine, triphenylmethane, acridine, and phthallocyanin classes. The intracellular β-and γ-metachromatic granules, previously demonstrated in fresh tissues with toluidine blue, were also demonstrated well with azure A, methylene blue, and brilliant cresyl blue. The granules were also demonstrated, but not as well, by thionin, neutral red, safranin O, toluylene blue, and acridine orange. Under the conditions of staining, the reserve zone matrix and the lower hypertrophic (calcifying) zone matrix stained, whereas the proliferative and upper hypertrophic zone matrix did not stain. Gallocyanin, crystal violet, basic fuchsin, azocarmine B, gallamine blue, and alcian blue either did not stain, or gave a different pattern of staining from that described above. It is suggested that the pK and molecular weight of the dyes are important, but not necessarily the only factors in determining the staining of the granules. The results indicate that there is a change in the metachromatic material (presumably proteinpolysaccharide) in both the matrix and cells of epiphyseal cartilage, which appears to be related to calcification.     

Histological abnormalities of the calcaneum in congenital talipes equinovarus

Six calcaneal fragments from patients aged 2, 3, 4, and 5 years with relapsed talipes, and two normal feet from a 40-week-old stillborn fetus were studied. All tissue was sectioned in the sagittal or coronal plane and stained using alcian blue and sirius red to distinguish cartilage and bone. Immunocytochemistry was performed to illustrate collagen types I and II. Within the clubfoot calcaneum, there were fewer chondrocytes and a diminished number of cartilage canals. Although a growth plate was present, the zones of differentiated chondrocytes were not apparent and the chondrocytes were smaller and flatter. The alcian blue staining within the spherical physis was paler than normal, suggesting that the amount of extracellular proteoglycans was reduced. Overall, the growth plate region of the talipes calcaneum resembled that of a permanent cartilage, like articular cartilage. Abnormalities were also seen in the ossification center. Cartilage spicules were rare, and developing bone frequently abutted directly onto the growth plate cartilage. The relative absence of a primary spongiosa suggested that the physis was virtually inactive and endochondral bone formation was retarded. These findings are consistent with the hypothesis that an intrinsic primary growth disorder causes the formation of a small hypoplastic bone and, subsequently, a smaller foot. Received: February 21, 2001 / Accepted: June 12, 2001     

Duration of increased mucosal permeability of the urinary bladder after acute overdistension: an experimental study in rats

The duration of damage to the mucosal barrier of the urinary bladder after overdistension was investigated in a rat model. Overdistension was induced for 3 h in 48 female Sprague-Dawley rats by forced diuresis and balloon obstruction of the bladder neck. In 24 rats 0.5 ml of 2% solution of Trypan blue in 0.9% NaCl solution was instilled into the bladder for 1 h at 0 h, 24 h, 48 h, 7 days and 21 days after overdistension. After dyeing, full-thickness samples were taken from the wall of the bladder dome and body immediately above the ureteral orifices for histological studies. Inflammatory reaction was investigated histologically without Trypan blue dyeing in 24 rats at 0 h, 24 h, 48 h, 7 days and 21 days after overdistension. At 0, 24 and 48 h after overdistension the bladder wall was deep blue throughout. The dome and body were similar. At 7 days there was only slight staining of the bladder surface urothelium and subjacent connective tissue, while at 21 days there was no longer any dye in the bladder wall or urothelium. Oedema reached its maximum at 48 h, and large numbers of inflammatory cells were seen in the submucosa at 48 h. These changes had normalized by 7 days. After overdistension urothelial integrity is destroyed for several days, making it possible for different substances in the urine to penetrate into the bladder wall. This renders questionable the use of bladder distension in the treatment of interstitial cystitis, as it may only increase leakage of the urothelium and accelerate inflammatory reaction in the bladder wall. However, in the present study of healthy rat bladders the integrity of the urothelium had recovered to a large extent after 1 week and completely after 3 weeks. Received: 21 April 1998 / Accepted: 22 January 1999     

Scanning Force Microscopy of the Fine Structure of Cartilage Irradiated with a CO2 Laser

. Alterations of the cartilage matrix structure under non-destructive laser irradiation have been investigated by scanning force microscopy. Porcine nasal septum cartilage was irradiated with a CO₂ laser with a power density of 50 W/cm² under two different time regimes: for 3 s and for 30 s. Short-time irradiation had little effect on the structure of the cartilage matrix. In comparison with non-irradiated cartilage, small channels of 100–400 nm in cross-section appeared. This observation gives evidence that the underlying mechanism of laser-induced stress relaxation of cartilage is based on short-time depolymerisation and subsequent re-formation of proteoglycan units. The 30 s laser treatment results in melting and denaturation of the matrix. For the first time, small crystals, 100–800 nm, were found on cut sections of the laser treated cartilage. The crystals mainly consist of resolvable sodium carbonate. Thus, they cannot be responsible for the formation of a stable cartilage configuration after laser treatment. Paper received 24 February 1998; accepted after revision 22 June 1999.     

Study on the pineal gland of ungulates]

Study of the pineal gland of 91 Ungulates belonging to 55 species shows the constant presence of calcarine concretions of various importance. These concretions develop in the walls of vessels that first undergo a preliminary transformation characterized by the presence of alcian blue or PAS positive substances. In nearly all cases, the presence of alcian blue positive cells with processes (distinct from mastocytes) can be found in the pineal gland of ungulates. These elements sometimes contain fine calcarine granulations that probably are the site of origin of acervuli. These observations were extended to several marsupials, carnivora, pinnipeda and perissodactyles.     

Paneth cell adenoma of the stomach

A case of Paneth cell adenoma of the stomach in a 75-year-old woman is reported. At histological examination, a tubular adenoma with low-grade (moderate) dysplasia was found. The dysplastic cells had distinct coarse cytoplasmic granules that stained red with eosin and PAS but were negative with alcian blue pH 2.5. The adenoma may have developed from paneth cells present in areas of preexisting intestinal metaplasia.     

软骨细胞外基质源性取向支架与骨髓基质干细胞体外软骨组织工程的初步研究

目的 制备关节软骨细胞外基质源性取向支架,观察其对体外培养的骨髓基质干细胞分布排列的影响,探索其用于修复关节软骨缺损的可行性.方法 收集天然猪关节软骨,在PBS溶液中超微湿法粉碎关节软骨,利用差速离心收集细胞外基质悬液;低温超速离心收集沉淀,制备成2%～3%悬液;采用定向结晶与冷冻干燥技术制备取向支架,应用紫外交联及碳化二亚胺交联.光学显微镜及扫描电镜观察支架的形态结构,冰冻切片后组织化学染色对支架进行定性分析;生物力学方法检测支架的力学特性.分离培养兔骨髓基质干细胞,PKH26标记,接种到支架上体外软骨诱导培养,倒置荧光显微镜及扫描电镜观察培养3 d内种子细胞在支架内的黏附、分布及排列方式.结果 制备的支架材料具有垂直取向排列的孔道结构,软骨细胞外基质特异性染色阳性,纵向压缩弹性模量为(2.02±0.02)MPa,横向压缩弹性模量为(0.264±0.16)MPa,具有各向异性的力学特点.体外培养显示骨髓基质干细胞广泛均匀地分布在支架内部,并且在支架材料表层呈平行排列,深层呈柱状排列,类似于天然软骨组织中细胞的排列方式.结论 以关节软骨细胞外基质材料制备的取向性组织工程支架,在生化组成和结构上仿生天然关节软骨细胞外基质,是一种较为理想的软骨组织工程支架.     

A comparative study of experimental and human pancreatic carcinoma with special reference to histochemical findings

This study was undertaken in order to histochemically investigate the mucoid substances (acid mucopolysaccharide and sialic acid) in experimental and human pancreatic carcinoma. The degree of alcian blue staining in the ductal and interstitial portions of the pancreas increased, especially in hamster tubular adenocarcinoma which had been induced by N-nitrobis (2-hydroxypropyl) amine. The pancreatic carcinoma of the rats, induced by di-methyl benz (α) anthracene, was usually poorly differentiated carcinoma, in which alcian blue and toluidine blue staining was high in the interstitial portion when compared with that of the hamster pancreatic carcinoma, which was usually well differentiated. The rates of enzyme digestion of acid mucopolysaccharide and sialic acid showed more prominently in the rat pancreatic carcinoma than in the hamster pancreatic carcinoma. Mucoid substances in the ductal portion of human pancreatic carcinoma revealed properties similar to those of hamster pancreatic carcinoma whereas those in the interstitial portion were similar to those of rat pancreatic carcinoma. These results suggested that mucoid substances, especially acid mucopolysaccharide, both in experimental and human pancreatic carcinomas, may play an important role in tumor growth.     

软骨脱细胞基质的研制及其力学性质分析

目的　猪CACM的制作及其力学特征的检测。方法　切取猪耳软骨 ,采取TritonX - 10 0、Tris -HCl液等 4步法制取脱细胞的猪耳CACM。采用光镜、透射电镜、扫描电镜等对结构进行检测 ,同时对CACM进行力学检测。结果　肉眼观察 ,CACM与软骨除颜色略白外无差别。组织学HE染色 ,细胞陷窝已无细胞结构 ,阿尔新兰染色呈淡染 ,阴性 ;透射电镜下CACM软骨陷窝内已无细胞结构 ,细胞膜、核器均已溶解 ;扫描电镜下CACM基质纤维成分与正常软骨基质的胶原纤维在形态上无差异 ;力学试验 ,最大拉伸强度 ,最大拉伸比 ,猪耳软骨与其脱细胞基质比较及其弹性模量无统计学意义。结论　经TritonX - 10 0为主的脱细胞处理方法可以脱去软骨的细胞成分 ,不改变软骨细胞基质的主要成分 ,不改变其原有力学性质     

骨髓基质干细胞复合改性的聚羟基丁酸-羟基异戊酯体外构建组织工程化软骨

目的 探讨应用骨髓基质干细胞(BMSCs)复合光接枝改性的聚羟基丁酸-羟基异戊酯(PHBV)构建组织工程化软骨的可行性. 方法 将3代绵羊骨髓基质细胞接种于光接枝改性的三维PHBV支架材料上,24 h后以成软骨诱导液培养,3周后,复合培养物行扫描电镜观察,组织学观察,测定糖胺聚糖(GAG)含量.并将复合物埋植于绵羊腹部皮下,4周后取出,行大体及组织学观察. 结果 经成软骨诱导后,扫描电镜下,BMSCs的突触逐渐变短,由长梭形向扁平形转变,分泌基质量亦明显增多.组织学观察见细胞支架复合物阿利新蓝、番红O、Ⅱ型胶原免疫组化染色均呈阳性.GAG含量测定示诱导3周后,细胞分泌的GAG量(1306.7±192.3)明显高于未经诱导的BMSCs(205.0±26.2)(P<0.001),但仍低于正常软骨细胞(1969.2±235.3)(P<0.001).复合物埋植于皮下4周后,其内炎症细胞浸润明显,但番红O、Ⅱ型胶原免疫组化染色均呈阳性. 结论 以BMSCs为种子细胞,复合改性的PHBV,可于体外构建出软骨样组织,但该组织的理化特点与正常软骨仍有差距.     

Ex vivo investigations of laser auricular cartilage reshaping with carbon dioxide spray cooling in a rabbit model

Laser cartilage reshaping (LCR) with cryogen spray cooling is a promising modality for producing cartilage shape change while reducing cutaneous thermal injury. However, LCR in thicker tissues, such as auricular cartilage, requires higher laser power, thus increasing cooling requirements. To eliminate the risks of freeze injury characteristic of high cryogen spray pulse rates, a carbon dioxide (CO₂) spray, which evaporates rapidly from the skin, has been proposed as the cooling medium. This study aims to identify parameter sets which produce clinically significant reshaping while producing minimal skin thermal injury in LCR with CO₂ spray cooling in ex vivo rabbit auricular cartilage. Excised whole rabbit ears were mechanically deformed around a cylindrical jig and irradiated with a 1.45-μm wavelength diode laser (fluence 12–14 J/cm² per pulse, four to six pulse cycles per irradiation site, five to six irradiation sites per row for four rows on each sample) with concomitant application of CO₂ spray (pulse duration 33–85 ms) to the skin surface. Bend angle measurements were performed before and after irradiation, and the change quantified. Surface temperature distributions were measured during irradiation/cooling. Maximum skin surface temperature ranged between 49.0 to 97.6 °C following four heating/cooling cycles. Significant reshaping was achieved with all laser dosimetry values with a 50–70 °C difference noted between controls (no cooling) and irradiated ears. Increasing cooling pulse duration yielded progressively improved gross skin protection during irradiation. CO₂ spray cooling may potentially serve as an alternative to traditional cryogen spray cooling in LCR and may be the preferred cooling medium for thicker tissues. Future studies evaluating preclinical efficacy in an in vivo rabbit model are in progress.     

Rapamycin retards growth and causes marked alterations in the growth plate of young rats

Rapamycin is a potent immunosuppressant with antitumoral properties widely used in the field of renal transplantation. To test the hypothesis that the antiproliferative and antiangiogenic activity of rapamycin interferes with the normal structure and function of growth plate and impairs longitudinal growth, 4-week-old male rats (n = 10/group) receiving 2 mg/kg per day of intraperitoneal rapamycin (RAPA) or vehicle (C) for 14 days were compared. Rapamycin markedly decreased bone longitudinal growth rate (94 ± 3 vs. 182 ± 3 μm/day), body weight gain (60.2 ± 1.4 vs. 113.6 ± 1.9 g), food intake (227.8 ± 2.6 vs. 287.5 ± 3.4 g), and food efficiency (0.26 ± 0.00 vs. 0.40 ± 0.01 g/g). Signs of altered cartilage formation such as reduced chondrocyte proliferation (bromodeoxiuridine-labeled cells 32.9 ± 1.4 vs. 45.2 ± 1.1%), disturbed maturation and hypertrophy (height of terminal chondrocytes 26 ± 0 vs. 29 ± 0 μm), and decreased cartilage resorption (18.7 ± 0.5 vs. 31.0 ± 0.8 tartrate-resistant phosphatase alkaline reactive cells per 100 terminal chondrocytes), together with morphological evidence of altered vascular invasion, were seen in the growth plate of RAPA animals. This study indicates that rapamycin can severely impair body growth in fast-growing rats and distort growth-plate structure and dynamics. These undesirable effects must be kept in mind when rapamycin is administered to children.