甲状旁腺瘤组织同种移植治疗甲状旁腺功能低下症初步报告

目的　为甲状旁腺移植的供体来源提供一种新途径。　方法　将甲状旁腺瘤组织用 6Gy60 钴照射后 ,切成 0 5mm× 0 5mm× 0 5mm～ 1 0mm× 1 0mm× 1 0mm薄片 ,植入裸鼠肾包膜下过渡 14d ,移植给甲状旁腺功能低下症患者 ,受者术前 1d及术后 14d服用环孢素A(5mg·kg 1·d 1) ,以后不用任何免疫抑制剂。术后观察临床症状、体征、治疗的钙剂及罗钙全剂量变化 ,检测血钙及血甲状旁腺激素 ,以确定移植效果。　结果　临床应用 5例 ,其中 3例术后不需静脉补钙 ,口服钙剂量及罗钙全剂量减少 ,血钙浓度基本恢复到正常值。　结论　甲状旁腺瘤组织为甲状旁腺移植提供了一种方便、易于获取的新的供体 ,且可移植给多个患者治疗。     

同种异种甲状旁腺移植治疗甲状旁腺机能减退性心肌病三例…

利用经培养的胎儿甲状旁腺（ＰＴＧ），对３例甲状旁腺机能减退性心肌病（ＨＯＰＴＣＰ）行ＴＰＧ移植治疗。供体为４－７个月水囊引产的死胎，在显微镜下将胎儿ＰＴＧ取出，４℃Ｈａｎｋ氏液漂洗，经培养５－８天后，在Ｂ型超声波引导下，一次性将６－１０个胎儿ＰＴＧ注入受者１侧肾包膜内。术后患者症状改善，随访年半均未复发，该方法简便易行，符合生理需要。     

同种异体甲状旁腺移植治疗甲状旁腺机能减退性心肌病三例报告

利用经培养的胎儿甲状旁腺（ＰＴＧ），对３例甲状旁腺机能减退性心肌病（ＨＯＰＴＣＰ）行ＰＴＧ移植治疗。供体为４～７个月水囊引产的死胎，在显微镜下将胎儿ＰＴＧ取出，４℃Ｈａｎｋ氏液漂洗，经培养５～８天后，在Ｂ型超声波引导下，一次性将６～１０个胎儿ＰＴＧ注入受者１侧肾包膜内。术后患者症状逐渐改善，随访１年半均未复发，该方法简便易行，符合生理需要。     

裸鼠过渡异体甲状旁腺移植的初步报道

目的探讨裸鼠过渡异体甲状旁腺移植的方法和效果。方法取即死亡尸甲状旁腺，经深低温、^60Co照射、裸鼠移植过渡等处理，治疗甲状旁腺功能低下症2例。结果裸鼠过渡期10～15d血清甲状旁腺分泌最高，其中1例症状消失，效果为优，1例症状部分消失，效果为良，结论裸鼠过渡异体甲状旁腺移植可以是治疗甲状旁腺功能低下症的的一种方法选择。     

先灌后切供体器官血管胚胎甲状腺及甲状旁腺移植（附六例…

为了缩短供体器官的热缺血时间，我们采用先全身冷灌注，后切取供体器官的方法，对６例甲状旁腺功能减退患者（其中２例还伴特发性甲状腺功能减退）行带血管的胚胎甲状腺－甲状旁腺移植，４例移植右侧，２例移植双侧。１例供胎还同时供胰腺移植给１例Ｉ型糖尿病患者。疗效１年内２例优，４例良；有５例随访８个月－４年，效果良好。胰腺移植后追踪观察２年，效果亦良好。作者认为先灌后切供体器官有以下优点。（１）尽量缩短热缺血时     

先灌后切供体器官带血管胚胎甲状腺及甲状旁腺移植（附六例报告）

为了缩短供体器官的热缺血时间，我们采用先全身冷灌注，后切取供体器官的方法，对６例甲状旁腺功能减退患者（其中２例还伴特发性甲状腺功能减退）行带血管的胚胎甲状腺－甲状旁腺移植，４例移植右侧，２例移植双侧。１例供胎还同时供胰腺移植给１例Ⅰ型糖尿病患者。疗效１年内２例优，４例良；有５例随访８个月～４年，效果良好。胰腺移植后追踪观察２年，效果亦良好。作者认为先灌后切供体器官有以下优点。（１）尽量缩短热缺血时间，保证器官功能；（２）可一供者供多个脏器，有助于解决大龄胚胎供者不足的问题；（３）切取时从容不迫，不易损伤供体器官。     

先灌后切供器官胚胎甲状旁腺移植二例报告

报道2例胚胎甲状旁腺移植术采用先低温灌注,然后切取脏器的方法,缩短了热缺血时间,临床效果满意。     

胚胎多脏器联合切取供胰及甲状腺—甲状旁腺(附1例报告)

介绍胚胎先灌后切多脏器联合切取供带血管胰及甲状腺—甲状旁腺移植的１例经验。作者认为此法可避免热缺血损害，并能同时提供多个脏器，优于常规的先切后灌法，从而为解决大龄胎尸供者缺乏的矛盾提供了一条新途经。     

人胚甲状旁腺细胞移植治疗甲状旁腺功能低下症

目的　探讨人胚甲状旁腺细胞移植治疗甲状旁腺功能减退症的临床意义。　方法　将培养的人胚甲状旁腺细胞在B超引导下移植到 6例甲状旁腺功能减退症患者的肾周围脂脂囊中。应用放射免疫方法测定患者术前、术后血中甲状旁腺激素 (PTH)及钙水平 ,并进行自身对照 ,对疗效进行评价。　结果　 6例患者在接受人胚甲状旁腺细胞移植前 ,血钙及PTH平均水平分别为 (1 6 3±0 12 )mmol/L及 (1 36± 0 2 1)ng/L ;接受移植 3d后分别为 (1 77± 0 2 2 )mmol/L及 (9 5 3± 2 2 1)ng/L ,两者差异有显著性意义 (P <0 0 1) ;6d后达正常水平 ,临床症状逐渐减轻至消失 ;术后观察 9～ 12个月病情保持稳定。　结论　培养的人胚甲状旁腺细胞肾周围脂肪囊内移植是治疗甲状旁腺功能减退症的一种较理想的新方法     

Compensatory parathyroid hypertrophy after hemiparathyroidectomy in rats feeding a low calcium diet

Summary The functional and anatomic compensatory response of the parathyroid gland was examined in hemiparathyroidectomized (HPTx) rats whose parathyroid hormone (PTH) secretion was stimulated by a low calcium diet. These responses were compared with those observed in the thyroid gland of hemithyroidectomized (HTx) rats. Rats kept on a low calcium diet for 10 days were subjected to HPTx, HTx, or sham operations. Throughout the experiment (up to 28 days after surgery), serum calcium levels of HPTx rats were lower than the basal, with Δ values (mg/dl, mean±SEM) of −0.66±0.17 and −0.84±0.17, (P<0.05) 3 and 28 days after surgery, respectively. Serum PTH decreased significantly from 7 to 21 days after HPTx, reaching normality at day 28 after surgery. In HTx rats, serum thyroxine (T4) levels diminished significantly 7 days after surgery, and attained normality thereafter. The mitotic index (number of metaphases/1,000 cells) in parathyroid glands of colchicine-treated HPTx rats increased significantly in comparison to sham-operated controls, when examined 2 or 40 days after surgery. The mitotic index of thyroid follicular cells was significantly higher than that of their respective controls, 2 but not 40 days after HTx. These results indicate that after HPTx, a delayed compensatory response is found when the animals are kept under a low calcium diet. Parathyroid response is both delayed and of a minor degree compared to that found in the thyroid gland after HTx.     

Time-related changes in the ultrastructure of osteoclasts after injection of parathyroid hormone in young rats

Summary The effects of parathyroid hormone (PTH) on the size of the osteoclasts, nuclei, ruffled borders, and clear zones in long bones of thyroparathyroidectomized (TPTX) rats were quantitated as a function of time. These data were compared with the number of osteoclasts in the bone and with plasma calcium levels. A significant increase in the average size of the ruffled borders was demonstrated 30 min after injection of 50 U of purified bovine PTH, and of the clear zones 30–90 min after PTH. This was followed at 90 min by an increase in the average size of the cells. The sizes of ruffled borders and clear zones dropped sharply to control levels after 6 h, whereas the size of the cells remained elevated up to 12 h and returned to control values at 24 h. Plasma calcium levels were increased, but not significantly, between 30 min and 6 h. An increase in the number of osteoclasts was significant after 12 h. Removal of the parathyroid glands did not diminish the normal activity of osteoclasts. In animals with intact glands injection of 50 U of PTH did not cause a significant change in cell size or resorbing apparatus. It is concluded that PTH acts to rapidly stimulate the bone resorptive activity of osteoclasts and to cause a delayed increase in their number.     

甲状旁腺素对人肾小管上皮细胞细胞外基质合成与降解的影响

Objective To investigate the effects of parathyroid hormone (PTH) on the synthesis and secretion of collagen Ⅲ and fibronectin (FN), and the expressions of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in cultured human renal tubular epithelial cells (HK-2).Methods HK-2 cells were cultured in DMEM-F12 medium supplemented with 5% FBS. Cells were exposed to different concentrations of PTH (0, 10-12, 10-11, 10-10, 10-9, 10-8 mol/L) for 48 h, or 10-8 mol/L PTH at different time (0, 12, 24, 48, 72 h). The gene expressions of collagen Ⅲ,FN, PAI-1, MMP-1, and TIMP-1 were detected by semi-quantitative RT-PCR. The protein expression of collagen Ⅲ was detected by Western blotting. The level of FN in the supernatant was assayed by enzyme linked immunosorbent assay (ELISA). Results PTH increased gene expressions of collagen Ⅲ, FN, PAI-1 and TIMP-1 in a dose- and time-dependent manner, but decreased MMP-1 gene expression. Then the ratio of MMP-1/TIMP-1 was decreased. PTH increased the collagen Ⅲ protein expression in cultured HK-2 cells and the level of FN in the supernatant of cultured HK-2 cells in a dose- and time-dependent manner. Conclusion PTH can up-regulate PAI-1, TIMP-1 gene expressions, and down-regulate MMP-1 gene expression,resulting in elevation of extracellular matrix (ECM) synthesis and reductim of degradation.     

甲状旁腺素对人肾小管上皮细胞细胞外基质合成与降解的影响

Objective To investigate the effects of parathyroid hormone (PTH) on the synthesis and secretion of collagen Ⅲ and fibronectin (FN), and the expressions of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in cultured human renal tubular epithelial cells (HK-2).Methods HK-2 cells were cultured in DMEM-F12 medium supplemented with 5% FBS. Cells were exposed to different concentrations of PTH (0, 10-12, 10-11, 10-10, 10-9, 10-8 mol/L) for 48 h, or 10-8 mol/L PTH at different time (0, 12, 24, 48, 72 h). The gene expressions of collagen Ⅲ,FN, PAI-1, MMP-1, and TIMP-1 were detected by semi-quantitative RT-PCR. The protein expression of collagen Ⅲ was detected by Western blotting. The level of FN in the supernatant was assayed by enzyme linked immunosorbent assay (ELISA). Results PTH increased gene expressions of collagen Ⅲ, FN, PAI-1 and TIMP-1 in a dose- and time-dependent manner, but decreased MMP-1 gene expression. Then the ratio of MMP-1/TIMP-1 was decreased. PTH increased the collagen Ⅲ protein expression in cultured HK-2 cells and the level of FN in the supernatant of cultured HK-2 cells in a dose- and time-dependent manner. Conclusion PTH can up-regulate PAI-1, TIMP-1 gene expressions, and down-regulate MMP-1 gene expression,resulting in elevation of extracellular matrix (ECM) synthesis and reductim of degradation.     

The experimental induction of parathyroid hyperplasia in rats,and the use of toluidine blue O forin vivo identification of parathyroid tissue

An experiment was designed to compare the degree of parathyroid hyperplasia induced in rats by subtotal nephrectomy and by oral phosphate administration singly or in combination. The greatest degree of parathyroid hyperplasia was×4.49 and was seen in the rats with both subtotal nephrectomy and oral phosphate administration. Over the 77-day period of the experiment, subtotal nephrectomy alone did not produce a significant increase in the size of the glands, whereas phosphate fed to otherwise normal rats did produce a significant increase.Toluidine blue was given intravenously before killing the rats and was found to stain the hyperplastic glands in the same way that it stains normal and adenomatous glands. Staining was found to be satisfactory for identification purposes in both the normal and in the hyperplastic glands with 5 mg/kg body weight. A greater depth of staining was given by 10 mg/kg body weight.

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Zusammenfassung Es wurde ein Experiment an Ratten durchgeführt, um den Grad der Parathyreoidea-Hyperplasie anhand folgender Punkte zu vergleichen: subtotale Nephrektomie, orale Phosphatverabreichung oder eine Kombination von beiden. Die maximale Parathyreoidea-Hyperplasie war 4,49mal größer als bei den Kontrollen und wurde bei Ratten mit subtotaler Nephrektomie und mit oraler Phosphatverabreichung festgestellt.Während der 77 Tage des Experimentes erzeugte subtotale Nephrektomie allein keine bedeutende Zunahme der Drüsengröße; Phosphat hingegen, welches im übrigen normalen Ratten verfüttert wurde, bewirkte eine bedeutende Zunahme.Toluidinblau wurde den Ratten intravenös injiziert, bevor sie getötet wurden; es färbte die hyperplastischen Drüsen ebenso befriedigend wie normale und adenomatöse Drüsen. Die Färbung war mit 5 mg/kg Körpergewicht befriedigend zur Identifizierung der normalen wie der hyperplastischen Drüsen. Eine tiefere Färbung wurde mit 10 mg/kg Körpergewicht erreicht.

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Résumé Le degré d'hyperplasie parathyroidïenne a été étudié chez le Rat après néphrectomie subtotale, après administration buccale de phosphate ou par combinaison des deux. Le degré le plus élevé d'hyperplasie parathyroidïenne est de ×4.49 et a été observé chez le rat après néphrectomie sub-totale et administration buccale de phosphate.Au cours des77 jours d'expérience, la néphrectomie sub-totale ne produit pas une augmentation significative de la taille des glandes, alors que le phosphate, mélangé à l'alimentation de rats normaux, produit une augmentation significative.Le bleu de toluidine, administré par voie intra-veineuse avant le sacrifice des rats, colore les glandes hyperplasiques de la même façon qu'il colore les glandes normales et adénomateuses. La coloration s'avère intéressante pour l'identification des glandes normales et hyperplasiques à la concentration de 5 mg/kg de poids corporel. Une coloration plus intense est obtenue avec 10 mg/kg de poids corporel.

     

Stimulation of alkaline phosphatase activity in cultured neonatal mouse calvarial bone cells by parathyroid hormone

Summary The effect of parathyroid hormone (PTH) on alkaline phosphatase activity was examined in confluent, serum-free primary cultures of neonatal mouse calvarial cells. It was found that synthetic bPTH-(1-34) caused an increase in the specific activity of skeletal alkaline phosphatase isoenzyme by 18 hours. Between 10 and 500 ng/ml, the mganitude of the change was directly related to peptide concentration. The change occurred in the absence of any effect on cell number, total cell protein, or DNA and was not the result of an effect on either proliferation or survival of a specific cell population. Results of histochemical studies indicate that bPTH-(1-34) caused an increase in the proportion of cells containing enzyme activity. The response was duplicated by intact bPTH-(1-84) and DBcAMP, but not by oxidized bPTH-(1-34) or insulin and did not require prostaglandin synthesis or hydroxylation of 25-hydroxyvitamin D₃. These results demonstrate that bPTH has a direct effect on osteoblast maturationin vitro, that the effect is specific for PTH, and suggest that it is mediated by cAMP.     

大鼠甲状旁腺细胞经培养后再移植的实验研究

目的　研究大鼠甲状旁腺细胞经培养后再移植对其存活的影响。方法　将经胶原酶和胰蛋白酶消化的甲状旁腺细胞培养后再行移植 ,观察移植物的存活情况 ,并对移植物做透射电镜观察。结果　新鲜甲状旁腺移植组平均存活期为 (9.2 5± 3.4 5 )d ;甲状旁腺细胞培养后移植 ,移植物的存活时间为 (46 .2 5± 7.4 4 )d ,明显延长(P<0 .0 1) ,在 5 0d观察期内 ,8只鼠中有 6只的血清钙及PTH值持续在正常范围内。移植物内可见完整的甲状旁腺细胞 ,其内见丰富的粗面内质网、杆状的线粒体及分泌颗粒。结论　大鼠甲状旁腺细胞经培养后再移植可以延长移植物的存活时间 ,是治疗甲状旁腺功能低下症的一条有效途径。     

Inhibition of parathyroid hormone-stimulated resorption in cultured fetal rat long bones by the main metabolites of ipriflavone

Ipriflavone is an isoflavone derivative used in the prevention and treatment of postmenopausal and senile osteoporosis in humans. To assess the potential contribution of the mainin vivo ipriflavone metabolites (M1, M2, M3, and M5) on the pharmacological properties of the drug, we investigated their effect on osteoclastic resorption induced by the well-known stimulator of bone resorption bovine parathyroid hormone fragment 1–34 (bPTH 1–34). The study was carried out using fetal rat long bones in stationary cultures. The amount of osteoclastic resorption was determined by assaying for 5 days the release from bones in the media of previously incorporated⁴⁵Ca. All metabolites were effective at inhibiting osteoclastic resorption. Maximal potency was shown by M3, characterized by a significant effect at 10 μM (P<0.01) and by an IC₅₀ value of 17 μM. M2 was about threefold less potent than M3 (IC₅₀=46 μM). M1 and m5 were the least active compounds with an IC₅₀ value of 117 and 200 μM, respectively. The present evidence indicates that metabolites of ipriflavone, in particular M3 and M2, inhibit bPTH 1–34-induced bone resorption in fetal rat long bones. Accordingly, they may play an important role in the pharmacological effects of the drug.