BACKGROUND & AIMS: :The immune cell products interleukins 1 alpha and -beta, which stimulate osteoclast activity in vitro, are among the most potent bone resorbing factors so far described. Although it appears likely that these cytokines are involved in regulation of trabecular bone turnover, nothing is known of their effects on extracellular fluid calcium concentration. In this report, we show the effects of 72-hr subcutaneous infusions of interleukins 1 alpha and -beta on plasma calcium and bone morphology in mice. Both interleukins 1 caused a marked dose-dependent increase in the plasma calcium. In higher doses, which cause the animals to die, the plasma calcium fell preterminally. Quantitative histomorphometry of bone sections showed evidence of increased numbers of osteoclasts and bone resorption surfaces. The effects were similar to those obtained with infusions of parathyroid hormone. These data suggest that in addition to its potential influence on trabecular bone volume, interleukin 1 may also modulate extracellular fluid calcium homeostasis under conditions in which it is produced excessively.

背景与目标： 免疫细胞产物白细胞介素1α和-β在体外刺激破骨细胞活性，是迄今为止描述的最有效的骨吸收因子之一。尽管这些细胞因子似乎参与了小梁骨周转的调节，但尚不清楚它们对细胞外液钙浓度的影响。在此报告中，我们显示了白细胞介素1α和-β皮下输注72小时对小鼠血浆钙和骨形态的影响。两种白介素1均引起血浆钙的显着剂量依赖性增加。高剂量会导致动物死亡，血浆钙会先期下降。骨切片的定量组织形态计量学显示出破骨细胞和骨吸收表面数量增加的证据。效果类似于输注甲状旁腺激素所获得的效果。这些数据表明，白细胞介素1除了对小梁骨体积的潜在影响外，在其产生过多的条件下，白细胞介素1还可能调节细胞外液钙稳态。

BACKGROUND & AIMS: CONTEXT:The autosomal dominantly inherited condition familial hypocalciuric hypercalcemia (FHH) is characterized by elevated plasma calcium levels, relative or absolute hypocalciuria, and normal to moderately elevated plasma PTH. The condition is difficult to distinguish clinically from primary hyperparathyroidism and is caused by inactivating mutations in the calcium sensing receptor (CASR) gene. OBJECTIVE:We sought to define the mutation spectrum of the CASR gene in a Danish FHH population and to establish genotype-phenotype relationships regarding the different mutations. DESIGN AND PARTICIPANTS:A total of 213 subjects clinically suspected to have FHH, and 121 subjects enrolled as part of a family-screening program were studied. Genotype-phenotype relationships were established in 66 mutation-positive index patients and family members. MAIN OUTCOME MEASURES:We determined CASR gene mutations, and correlating levels of plasma calcium (albumin corrected), ionized calcium (pH 7.4), and PTH were measured. RESULTS:We identified 22 different mutations in 39 FHH families. We evaluated data on circulating calcium and PTH for 11 different mutations, representing a spectrum of clinical phenotypes, ranging from calcium concentrations moderately above the upper reference limit, to calcium levels more than 20% above the upper reference limit. Furthermore, the mean plasma PTH concentration was within the normal range in eight of 11 studied mutations, but mild to moderately elevated in families with the mutations p.C582Y, p.C582F, and p.G553R. CONCLUSIONS:The present data add 19 novel mutations to the catalog of inactivating CASR mutations and illustrate a variety of biochemical phenotypes in patients with the molecular genetic diagnosis FHH.

背景与目标： 背景：常染色体显性遗传性家族性低钙血症性高钙血症（FHH）的特征是血浆钙水平升高，相对或绝对低钙血症以及血浆PTH正常至中度升高。这种病很难在临床上与原发性甲状旁腺功能亢进区分开来，并且是由钙感应受体（CASR）基因的失活引起的。
目的：我们试图确定丹麦FHH人群中CASR基因的突变谱，并建立有关不同突变的基因型-表型关系。
设计和参与者：共研究了213名临床怀疑患有FHH的受试者，并纳入了121个作为家庭筛查计划一部分的受试者。基因型与表型之间的关系建立了66突变阳性指数患者和家庭成员。
主要观察指标：我们确定了CASR基因突变，并测定了血浆钙（白蛋白校正），离子钙（pH 7.4）和PTH的相关水平。
结果：我们在39个FHH家族中鉴定出22个不同的突变。我们评估了11种不同突变的循环钙和PTH数据，这些突变代表了一系列临床表型，范围从钙浓度适度高于参考上限，到钙水平高于参考上限超过20％。此外，平均血浆PTH浓度在11个研究突变中的8个处于正常范围内，但在突变p.C582Y，p.C582F和p.G553R的家庭中轻度至中度升高。
结论：目前的数据在失活的CASR突变目录中增加了19种新的突变，并说明了分子遗传学诊断为FHH的患者的各种生化表型。

BACKGROUND & AIMS: :At the end of assessment of an hypercalcemia with acute renal failure in a seventy year-old man, is discovered a tumorlike muscular sarcoidosis of both thighs whose steroid treatment quickly proves effective. Rarity of such forms urges us to report this observation which allows to remind that, in case of a suggestive picture of sarcoidosis, it is necessary to look minutely for any muscular abnormality.

背景与目标： ：在对一名70岁男性的急性肾功能衰竭高钙血症的评估结束时，发现两条大腿都出现了类似肿瘤的肌肉结节病，其类固醇治疗很快被证明是有效的。这种形式的稀疏性促使我们报告这一观察结果，这提醒我们，在结节病的提示性图像中，有必要仔细检查任何肌肉异常。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :The finding of persistent hypercalcemia suggests doing other medical tests to find the cause. Familial hypocalciuric hypercalcemia is usually benign and it requires no treatment. It is important to do CASR gene sequencing to avoid unnecessary treatments. We report a 12-year-old child, asymptomatic, with calcemia between 11.4 and 12.2 mg/dl. His father and two brothers presented asymptomatic hypercalcemia. The blood test with magnesium, phosphorus, 25(OH)Vit D was normal, remarkable normal parathyroid hormone for the level of hypercalcemia. Urinary calcium/creatinine ratio was 0,11 mg/dl and 24-hour urinary calcium was 1,8 mg/kg per day. Abdominal and parathyroid ecography, long bone radiographs and densitometry were normal. Genetic study showed a mutation, c.1651A>G, in exon 6 of the calciumsensing receptor gene, confirmed in father and brothers, too. :La presencia de hipercalcemia mantenida obliga a realizar pruebas complementarias para determinar su origen. Es benigna y, generalmente, no requiere tratamiento. La secuenciación del gen CaSR confirma el diagnóstico y evita tratamientos innecesarios. Se presenta a un niño de 12 años, asintomático, con hipercalcemia persistente entre 11,4 y 12,2 mg/dl. El padre y dos hermanos tenían hipercalcemia asintomática. El análisis de laboratorio mostró valores de magnesio, fósforo y vitamina D normales y de hormona paratiroidea llamativamente normal para el valor de la hipercalcemia. Indice de calcio/creatinina urinario: 0,11 mg/mg; y calciuria de 24 h: 1,8 mg/kg/día. Ecografía abdominal, paratiroides, radiografías de huesos largos y densitometría ósea, normales. El estudio genético mostró mutación en exón 6 (c.1651A>G) del gen CaSR (en heterocigosis), confirmada en el padre y los hermanos.

背景与目标： ：持续高钙血症的发现建议做其他医学检查以找出原因。家族性低钙血症性高钙血症通常是良性的，不需要治疗。进行CASR基因测序很重要，以避免不必要的治疗。我们报告了一个12岁的儿童，无症状，血钙在11.4至12.2 mg / dl之间。他的父亲和两个兄弟表现出无症状的高钙血症。镁，磷，25（OH）Vit D的血液检查正常，对于高钙血症水平，甲状旁腺激素明显正常。尿钙/肌酐比率为0.11 mg / dl，每天24小时尿钙为1.8 mg / kg。腹部和甲状旁腺造影，长骨X光片和光密度测定正常。遗传研究表明，钙敏感受体基因第6外显子的一个突变c.1651A> G也已在父亲和兄弟俩中得到证实。
：预防性的先天性颅骨钙过多症：确诊为原发性前列腺癌。 es benigna y，generalmente，无需tratamiento。 CaSR的确凿性确证了无可辩驳的证明和证据。daccess-ods.un.org daccess-ods.un.org连续12个月，每天12毫克，1,2毫克/分升持续性骨钙血症。 El padre y dos hermanosteníanhipercalcemiaasintomática。实验室最严重的精神病，正常的维生素D和激素性副甲状腺功能亢进。尿cal指数：0.11 mg / mg;产后24小时：1.8 mg / kg /día。腹部，腹部，腹腔，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部，腹部有明显的辐射。在第6册（c.1651A> G）上进行了基因突变（encictciosis），确认了帕尔兹·洛斯·赫曼诺斯的一切。

BACKGROUND & AIMS: :Hypercalcemia occurring in a patient with an islet cell carcinoma of the pancreas suggests the diagnosis of Multiple Endocrine Neoplasia Type I and associated hyperparathyroidism. We describe a patient with an islet cell carcinoma and hypercalcemia in whom low concentrations of PTH, the absence of skeletal metastases, hypophosphatemia, and elevated nephrogenous cAMP alternatively suggested the syndrome of humoral hypercalcemia of malignancy. The peptide PTHrP was measured in the patient's serum during the course of therapy by an immunoradiometric assay directed toward the midportion of the molecule. Hypercalcemia was treated with an investigational aminobisphosphonate. The concentration of PTHrP[56-86] increased over time and fell after the patient received chemotherapy directed toward the islet cell tumor.

背景与目标： 胰岛细胞癌患者中发生的高钙血症提示诊断为I型多发性内分泌肿瘤和相关的甲状旁腺功能亢进。我们描述了患有胰岛细胞癌和高钙血症的患者，其中低浓度的PTH，不存在骨骼转移，低血磷症和肾源性cAMP升高提示恶性体液高钙血症综合征。在治疗过程中，通过针对分子中部的免疫放射分析法测定了患者血清中的PTHrP肽。高血钙症是通过研究用氨基双膦酸盐治疗的。患者接受针对胰岛细胞瘤的化疗后，PTHrP [56-86]的浓度随时间增加而下降。

BACKGROUND & AIMS: :Humoral hypercalcemia of malignancy is a common metabolic disturbance associated with solid tumors, but it also occurs in lymphoma patients. Among these, low grade B-cell lymphoma accounts for only few cases, in which secretion of parathyroid hormone-related protein (PTHrP) remains even exceptional. We report the very rare case of a patient with a CLL type low grade leukemic B-cell lymphoma showing PTHrP-related hypercalcemia without evidence of bone lesions. Using immunohistochemistry, we demonstrate the cytoplasmic expression of PTHrP by the lymphoma cells in the bone marrow obtained at the onset of hypercalcemia. We postulate a pathogenetic role of leukemic cell production and secretion of PTHrP in hypercalcemia in low grade leukemic B-cell lymphoma.

背景与目标： ：恶性肿瘤的体液高钙血症是与实体瘤相关的常见代谢紊乱，但它也发生在淋巴瘤患者中。其中，低度B细胞淋巴瘤仅占少数病例，其中甲状旁腺激素相关蛋白（PTHrP）的分泌甚至异常。我们报道了CLL型低级白血病B细胞淋巴瘤患者的罕见病例，显示PTHrP相关的高钙血症而没有骨病变的证据。使用免疫组织化学，我们证明高钙血症发作时获得的骨髓中的淋巴瘤细胞的PTHrP的细胞质表达。我们推测白血病细胞的产生和PTHrP分泌在低度白血病B细胞淋巴瘤高钙血症中的致病作用。

BACKGROUND & AIMS: :A number of factors have been proposed as potential mediators of the syndrome of humoral hypercalcemia of malignancy (HHM), but to date no firm cause-and-effect relationship has been established. We attempted to establish such a relationship by determining whether the presence or absence of adenylate cyclase-stimulating activity (ACSA) in the media of cultured tumor cells predicted the occurrence of the syndrome of HHM when these cell lines were grown in nude mice in vivo. Conditioned media from 35 human renal carcinoma cell lines were surveyed for ACSA in the PTH-sensitive rat osteosarcoma 17/2.8 cell assay. 12 lines were positive (mean, 13.7-fold stimulation, range, 3.0 to 44.0), and 23 lines were negative (mean, 1.2-fold stimulation, range, 0.9 to 1.5). We were successful in establishing five of the positive and six of the negative lines in three to five nude mice per line. Mice implanted with the positive lines uniformly became hypercalcemic (mean serum calcium, 15.8 mg/dl), whereas mice implanted with the negative lines uniformly remained normocalcemic (mean serum calcium, 9.5 mg/dl), in spite of comparable mean tumor size. Acid-urea tumor extracts from each of four hypercalcemic animals contained potent in vitro ACSA (mean, 15.9-fold stimulation), while 5/5 extracts from normocalcemic animals did not (mean, 1.4-fold stimulation). Our study demonstrates that in this model system in vitro ACSA is a reliable predictive marker for HHM in vivo. Whether the protein responsible for this activity is also the mediator of the bone resorption seen in HHM remains to be demonstrated.

背景与目标： ：已提出许多因素作为恶性体液性高钙血症综合征（HHM）的潜在介体，但迄今为止，尚未建立牢固的因果关系。我们试图通过确定培养的肿瘤细胞培养基中腺苷酸环化酶刺激活性（ACSA）的存在与否来预测当这些细胞系在裸鼠体内生长时HHM综合征的发生，从而建立这种关系。在PTH敏感的大鼠骨肉瘤17 / 2.8细胞分析中，对来自35种人肾癌细胞系的条件培养基的ACSA进行了调查。 12线阳性（平均13.7倍刺激，范围3.0至44.0），23线阴性（平均1.2倍刺激，范围0.9至1.5）。我们成功地在每行三到五只裸鼠中建立了五个阳性线和六个阴性线。植入阳性线的小鼠均匀地变成高钙血症（平均血清钙，15.8 mg / dl），而植入阴性线的小鼠均匀地保持正常血钙性（平均血清钙，9.5 mg / dl），尽管平均肿瘤大小相当。来自四只高钙血症动物中每只的酸性尿素肿瘤提取物均含有有效的体外ACSA（平均刺激15.9倍），而来自正常高钙血症动物的5/5提取物则没有（平均1.4倍刺激）。我们的研究表明，在体外该模型系统中，ACSA是体内HHM的可靠预测标记。在HHM中所见，负责这种活性的蛋白质是否也是骨吸收的介体，尚待证实。

BACKGROUND & AIMS: :Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.

背景与目标： ：在正常受试者的基线状态期间以及在通过盐水和钙输注改变其血清钙浓度的过程中，确定了适合血清钙浓度的尿环AMP（UcAMP）。将其与UcAMP在76例高钙血症患者和5例低钙血症患者中进行了比较。在56例原发性甲状旁腺功能亢进患者中，有54例UcAMP的血钙浓度过高，其中2例有肾功能衰竭。在四名患有维生素D中毒，结节病，乳碱综合征和噻嗪类引起的高钙血症的患者中，以及在五名由于甲状旁腺功能低下引起的低钙血症的患者中，UcAMP的血清钙浓度适当较低。在16例非甲状旁腺肿瘤患者中，有10例的UcAMP水平过高，提示异位甲状旁腺激素（PTH）介导的高钙血症，而6例的UcAMP水平较低，表明其高钙血症是由于除PTH以外的溶骨因子引起的。 UcAMP，血清钙浓度和羧基末端免疫反应性PTH之间的相关性表明，随机UcAMP是循环的生物活性PTH的敏感准确反映。如果有足够的肾功能（血清肌酐浓度低于2.0 mg / dl），则随机表示为mumol / g肌酐并根据血清钙浓度进行分析的UcAMP会完全分离PTH和非PTH介导的高钙血症患者。

BACKGROUND & AIMS: :Hypercalcemia in accelerated phase of chronic myelogenous leukemia (CML) is very rare. Its pathogenesis is considered humoral hypercalcemia of malignancies mediated by parathyroid hormone-related protein (PTHrP). In severe hypercalcemia, calcifications in kidneys, skin, vessels, heart, and stomach may occur. Our two cases were admitted because of severe hypercalcemia in accelerated phase of CML. On Tc-99m methylene diphosphonate (MDP) bone scintigraphies, a marked tracer accumulation was seen in the lung, heart, stomach and kidney. We report increased tracer accumulation of multiple organs on Tc-99m MDP bone scintigraphy in two rare hypercalcemic patients with CML.

背景与目标： ：慢性粒细胞性白血病（CML）加速期的高钙血症非常罕见。其发病机理被认为是由甲状旁腺激素相关蛋白（PTHrP）介导的恶性体液性高钙血症。在严重的高钙血症中，可能会在肾脏，皮肤，血管，心脏和胃中发生钙化。我们的两个病例是由于CML加速期严重的高钙血症而入院的。在Tc-99m二磷酸二甲酯（MDP）骨显像仪上，在肺，心脏，胃和肾脏中发现了明显的示踪剂蓄积。我们报告了两名罕见的高钙血症伴CML患者在Tc-99m MDP骨闪烁显像仪上多个器官的示踪剂积累增加。

BACKGROUND & AIMS: :Hypercalcemia with concomitant elevation of serum parathyroid hormone (PTH) and PTH-related protein (PTHrP) levels was found in a patient with advanced gastric carcinoma and multiple liver metastases. The most common features are hypercalcemia associated with hypersecretion of PTHrP and physiological suppression of PTH secretion in the syndrome of humoral hypercalcemia of malignancy (HHM). Although we initially made a diagnosis of primary hyperparathyroidism concomitant with HHM due to gastric cancer, diagnostic imaging studies, such as echography, CT, sestamibi scintigraphy, and autopsy findings, did not reveal evidence of any parathyroid tumors or ectopic parathyroid glands in the mediastinum. Both primary and metastatic tumor cells showed positive staining with PTH-specific antibody as well as PTHrP-specific antibody on immunohistochemical examination. PTH concentration in the cytosolic fraction of the metastatic tumor was elevated compared to that from a control patient with no calcium metabolic disorders in vitro. These findings indicated that PTH secreted ectopically by gastric cancer cells, not by parathyroid glands, caused hypercalcemia in this patient. To our knowledge, this is the first case report of PTH-secreting gastric carcinoma cells. We report the case and a review of the previous reported PTH-secreting non-parathyroid tumors along with the mechanisms of secretion.

背景与目标： ：患有晚期胃癌和多发肝转移的患者发现高钙血症并伴有血清甲状旁腺激素（PTH）和PTH相关蛋白（PTHrP）升高。在恶性体液性高钙血症（HHM）综合征中，最常见的特征是与PTHrP过度分泌相关的高钙血症和PTH分泌的生理抑制。尽管我们最初诊断出因胃癌而伴有HHM的原发性甲状旁腺功能亢进症，但影像学检查（如回波描记术，CT，司他他比闪烁显像和尸检结果）并未显示出纵隔中有任何甲状旁腺肿瘤或异位甲状旁腺的证据。在免疫组织化学检查中，原发性和转移性肿瘤细胞均显示PTH特异性抗体和PTHrP特异性抗体呈阳性染色。与没有钙代谢异常的对照组患者相比，转移性肿瘤的胞质部分中的PTH浓度升高。这些发现表明，胃癌细胞而不是甲状旁腺分泌的异位PTH引起该患者高钙血症。据我们所知，这是分泌PTH的胃癌细胞的首例报道。我们报告该病例，并对先前报道的分泌PTH的非甲状旁腺肿瘤及其分泌机制进行了回顾。

BACKGROUND & AIMS: Cancers from patients with tumor-induced hypercalcemia usually produce a circulating factor that mimics the parathyroid hormone activity, termed parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia appears to be high in patients with squamous cell carcinoma of the esophagus, and the presence of parathyroid hormone-related protein have been shown in some primary esophageal cancers. In the present study, we have investigated the presence of parathyroid hormone-related protein in a patient with metastasized squamous cell carcinoma of the esophagus complicated with tumor-induced hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA was investigated by reverse transcriptase-polymerase chain reaction and S1 nuclease assay. Both messenger RNA and protein were detected in hepatic metastases, whereas normal esophageal mucosa and primary cancer did not express detectable protein or messenger RNA using the S1 nuclease assay. Reverse transcriptase-polymerase chain reaction was positive in all these tissues, including normal esophageal mucosa. In conclusion, the present case suggests that tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be caused by parathyroid hormone-related protein mostly released by liver metastases.

背景与目标： 患有肿瘤引起的高钙血症患者的癌症通常会产生一种模仿甲状旁腺激素活性的循环因子，称为甲状旁腺激素相关蛋白。食道鳞状细胞癌患者中肿瘤引起的高钙血症的发生率似乎很高，并且在一些原发性食道癌中已显示甲状旁腺激素相关蛋白的存在。在本研究中，我们调查了食管转移性鳞状细胞癌并发肿瘤引起的高钙血症的患者中甲状旁腺激素相关蛋白的存在。通过免疫组织化学搜索蛋白质，并通过逆转录酶-聚合酶链反应和S1核酸酶分析研究信使RNA。在肝转移中检测到信使RNA和蛋白，而正常食管粘膜和原发性癌症未通过S1核酸酶分析表达可检测的蛋白或信使RNA。在所有这些组织中，包括正常的食管粘膜，逆转录酶-聚合酶链反应均为阳性。总之，本案表明，食管鳞状细胞癌引起的肿瘤引起的高钙血症可能是由大部分由肝转移释放的甲状旁腺激素相关蛋白引起的。

BACKGROUND & AIMS: :Parathyroid hormone-like adenylate cyclase-stimulating proteins (hACSPs) have been implicated as one of the calcemic, bone-resorbing agents in patients with humoral hypercalcemia of malignancy. We report the synthesis of an amino-terminal hACSP fragment, Tyr36 hACSP (1-36) amide. The synthetic hACSP is a potent agonist of renal membrane adenylate cyclase (Km, 1.7 X 10(-10)) and of bone cell adenylate cyclase (Km 1 X 10(-9)M). It is a potent bone-resorbing agent in vitro, stimulating 45Ca release from fetal rat long bones at a concentration of 10(-9) M. When infused via osmotic minipumps into rats, it is also a potent calcemic factor in vivo, inducing a rise in serum calcium from (mean +/- SD) 10.6 +/- 0.6 to 19.7 +/- 3.2 mg/dl when infused at 1.4 micrograms/h and from 9.9 +/- 0.7 to 11.4 +/- 1.2 mg/dl when infused at 0.14 micrograms/h. These findings indicate that biologically active hACSP fragments can be synthesized. One such synthetic peptide possesses the in vitro and in vivo bioactivities demonstrated in native, tumor-derived hACSPs. It is also a potent calcemic, bone-resorbing agent.

背景与目标： ：甲状旁腺激素样腺苷酸环化酶刺激蛋白（hACSPs）已被认为是恶性体液性高钙血症患者的钙化，骨吸收剂之一。我们报告了氨基末端hACSP片段，Tyr36 hACSP（1-36）酰胺的合成。合成的hACSP是肾膜腺苷酸环化酶（Km，1.7 X 10（-10））和骨细胞腺苷酸环化酶（Km 1 X 10（-9）M）的有效激动剂。它是一种有效的骨吸收剂，在体外以10（-9）M的浓度刺激胎儿长骨中45Ca的释放。当通过渗透性微型泵注入大鼠体内时，它也是一种有效的钙化因子，可在体内诱导钙的释放。当以1.4微克/小时注入时，血清钙从（平均值/-标准差）从10.6 /-0.6增至19.7 /-3.2 mg / dl，当以0.14微克/小时注入时从9.9 /-0.7至11.4 /-1.2 mg / dl H。这些发现表明可以合成具有生物活性的hACSP片段。一种这样的合成肽具有在天然的，肿瘤来源的hACSP中证明的体外和体内生物活性。它也是强效的钙化，骨吸收剂。

BACKGROUND & AIMS: :Patients on hemodialysis may develop severe and symptomatic hypercalcemia if skeletal buffering is ineffective. We report a case of persistent hypercalcemia with apparent extrarenal vitamin D synthesis. Associated aluminium intoxication was suggested on desferrioxamine challenge and adynamic uremic osteodystrophy confirmed on bone biopsy. Plasma calcitriol did not suppress with corticosteroids but did with ketoconazole. No other evidence for underlying granulomatous disease was found. We discuss our approach to less usual causes of hypercalcemia, and emphasise the pitfalls associated with factitious disorders.

背景与目标： ：如果骨骼缓冲无效，则血液透析患者可能会出现严重的症状性高钙血症。我们报告一例持续的高钙血症，伴有明显的肾外维生素D合成。建议在去铁胺攻击中伴有铝中毒，并在骨活检中证实无动力尿毒症骨营养不良。血浆骨化三醇对皮质类固醇激素无抑制作用，但对酮康唑有抑制作用。没有发现其他潜在肉芽肿疾病的证据。我们讨论了减少高钙血症的常见原因的方法，并强调了与人为疾病相关的陷阱。

BACKGROUND & AIMS: BACKGROUND:Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS:CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS:The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION:Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

背景与目标： 背景：以前，膳食补充富含欧米伽3脂肪酸二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）的亮氨酸和鱼油可降低C26荷瘤小鼠恶病质相关的结局。为了进一步探讨相关的过程和机制，我们研究了血浆Ca2水平的变化，甲状旁腺激素相关蛋白（PTHrP）的参与及其与环氧合酶2（COX-2）的可能相互作用。
方法：对CD2F1小鼠皮下接种C26腺癌细胞或进行假手术，分为：（1）对照组，（2）荷瘤对照组和（3）接受实验饮食的荷瘤小鼠。 20天后，确定身体和器官的质量以及血浆总Ca2水平。此外，在培养的C26细胞中研究了DHA，EPA和亮氨酸对PTHrP产生的影响。
结果：亮氨酸和鱼油的组合减少了肿瘤相关的高钙血症。血浆Ca2水平与car体质量和多个器官质量负相关。在体外，DHA能够减少C26细胞产生的PTHrP。结果表明，该效应独立于COX-2抑制而发生。
结论：我们的结果表明，可通过富含亮氨酸和鱼油的营养干预措施来改善与癌症相关的高钙血症。鱼油的作用可能与DHA诱导的肿瘤引起的PTHrP排泄减少有关。