Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide

Summary The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30±15 (SD) % when the SCT was given once weekly and by 39±11% (P<0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline: creatinine ratios. The parenteral SCT reduced the AP by 33±23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone.     

Pharmacological characterization of mitogen-activated protein kinase activation by recombinant human 5-HT<Subscript>2C</Subscript>, 5-HT<Subscript>2A</Subscript>, and 5-HT<Subscript>2B</Subscript> receptors

The type 2 serotonin (5-HT₂) receptor subfamily is known to couple to phosphoinositide hydrolysis (PI) and the subsequent mobilization of intracellular Ca²⁺, as well as the release of arachidonic acid (AA). Less is known of 5-HT₂-mediated activation of the mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK1/2) signaling. The present study measured the relative efficacies and potencies of 5-HT agonists to activate ERK2 in non-neuronal cells expressing recombinant human 5-HT_2A, 5-HT_2B, and 5-HT_2C(ISV) receptors. 5-HT agonists stimulated ERK2 activity via all three 5-HT₂ subtypes. There were no meaningful differences in the potencies or relative efficacies of these agonists to affect ERK2 activity vs. PI accumulation or Ca²⁺ mobilization, suggesting that these pathways may be sequentially linked. Indeed, ERK2 activity was very sensitive to PKC inhibition and calcium chelation and insensitive to tyrosine kinase and PI-3-kinase inhibition. 5-HT₂ receptors efficiently couple to MAPK activation via sequential PI hydrolysis, and Ca²⁺ mobilization. This profile differs from reports of “agonist-directed trafficking of receptor stimulus” between PI/Ca²⁺ and AA pathways activated by 5-HT₂ receptors.     

常规剂量三氧化二砷对心脏功能影响的临床和实验研究

目的　研究常规剂量的三氧化二砷 (As2 O3)对急性早幼粒细胞白血病 (APL)患者心脏功能的影响。方法　通过对患者基础心率和心电图的动态观察 ,膜片钳技术对豚鼠心肌细胞用药前后动作电位和电流的监测 ,激光共聚焦技术对用药前后豚鼠心肌细胞内钙的测定 ,分析As2 O3对APL患者心脏功能影响的可能机制。结果　常规剂量的As2 O3静脉给药第 1～ 2周 ,5 2 .5 %～ 35 .0 %的APL患者产生不同程度的心脏不良反应 ,心电图上QT间期延长等。膜片钳监测显示 1,2 ,5 μmol LAs2 O3使豚鼠心肌细胞动作电位时程从 (5 6 3.0± 5 5 .8)ms分别延长到 (737.7± 131.7)ms、(84 2 .4± 115 .6 )ms和 (110 3.2± 96 .3)ms (P值分别 <0 .0 5 ,0 .0 1,0 .0 1) ,使L 型钙电流增加。激光共聚焦检测结果显示 ,1,2 ,5 μmol LAs2 O3使心肌细胞内钙增加 ,并可以被钙通道阻滞剂阻断。结论　常规剂量的As2 O3可使部分APL患者出现一过性心动过速、QT间期延长等不良反应。As2 O3对心脏功能的影响可能是通过影响心肌离子通道和细胞内钙来实现的。     

福州地区小儿锌铜铁钙营养状况临床流行病学调查

目的　探讨福州地区小儿锌、铜、铁、钙的营养状况及其影响因素。方法　采用原子吸收分光光度法对福州地区 80 3 5名小儿发中的锌、铜、铁及钙含量进行了测定 ;并采用SPSS软件包对发锌、铜、铁及钙含量与小儿年龄、性别、测定季节及不同年代之间的关系进行多因变量线性模型的方差分析。结果　福州地区小儿发锌、铜、铁、钙值分别为 ( x±s,μg/g) :112 9± 2 9 7、 7 70± 2 46、 45 88± 6 75、 448 7± 91 0。发锌含量受到年龄 ,头发中铜、铁、钙含量、测定年代的影响 ;发铁含量受到性别、年龄 ,头发中锌、钙含量、测定年代的影响 ;只有发锌含量和测定年代影响小儿发铜含量。发钙含量则受到年龄 ,头发中锌、铁含量、测定年代的影响。随着年代发展 ,发钙含量逐渐升高外 ,小儿头发中铜、铁含量逐步下降 ;发锌含量自 1993年起有所上升 ,在 1999～ 2 0 0 0年又开始下降。结论　福州地区小儿锌、铜、铁、钙营养状况仍处于一个较低水平 ,提倡平衡膳食 ,提高和改善小儿时期这些微量元素的营养状况仍是小儿时期最主要的健康问题之一     

钙离子选择性电极测定奶粉中钙的方法探讨

[目的 ]　探索用钙离子选择性电极测定奶粉中钙含量方法的可行性。　 [方法 ]　摸索钙离子选择性电极测定奶粉中钙的实验条件和干扰物对测定结果的影响。　 [结果 ]　经准确度和精密度测试 ,相对误差为 -3 .2 8%～4.10 %,相对标准差为 2 .6%。　 [结论 ]　该法用于奶粉中钙测定是可行的 ,不仅简化了操作程序而且也缩短了检测时间     

豚鼠心脏氧反常损伤机制及药物保护

本文在离体灌流豚鼠心脏模型上研究了氧反常损伤的机制。结果表明：缺氧４０ｍｉｎ时，心肌钠，钾－三磷酸腺苷酶（Ｎａ~＋，Ｋ~－ＡＴＰａｓｅ）活性下降２４％（Ｐ＜０．０５），钙（Ｃａ~（２＋））含量升高２８％（Ｐ＜０．０５），丙二醛（ＭＤＡ）含量无明显变化。复氧２ｍｉｎ时，Ｎａ＋，Ｋ＋－ＡＴＰａｓｅ活性下降４８％，与缺氧４０ｍｉｎ相比有显著差异，Ｃａ~（２＋）和ＭＤＡ含量分别增加９０％和４３％；复氧２０ｍｉｎ时，Ｎａ~＋，Ｋ~＋－ＡＴＰａｓｅ活性下降７２％，Ｃａ~（２＋）和ＭＤＡ含量分别增加７．２倍和３．７倍。复氧２０～３０ｓ即有·ＯＨ和Ｏ－２产生，在复氧３ｍｉｎ时达高峰。结果提示，氧自由基可能是氧反常损伤的初始原因；小壁胺（３μＭ）和地尔硫（３μＭ）能不同程度地减轻氧反常损伤。     

苯丙氨酸对自发性高血压大鼠血管平滑肌细胞内钙的影响

目的 探索苯丙氨酸对自发性高血压大鼠血管平滑肌细胞内钙的影响，方法 将ＳＨＲ和ＷＫＹ的血管平滑肌细胞在不同浓度苯丙酸培养液中培养一定时间后，加入（＾４５ＣａＣｌ２）温育一定时间后，测定进入细胞内（＾４５Ｃａ＾２＋）的量；而后将在不同浓度苯丙氨酸培养液中培养一定时间后的ＳＨＲ和ＷＫＹ的血管平滑肌细胞同ＰＳＳ液温育，采用Ｆｕｒａ－２／ＡＭ荧光指示剂测定不同浓度苯丙氨酸对细胞内游离Ｃａ＾２＋的影响。结果     

Alkylamides that produce tingling paresthesia activate tactile and thermal trigeminal neurons

Alkylamides isolated from the fruit of Xanthoxylum, Szechuan pepper, produce a strong tingling sensation in the mouth. In order to determine the peripheral basis of this sensation, extracellular nerve recordings were obtained from the lingual nerve of rats. The primary pungent compound, hydroxy-alpha-sanshool (HO-alpha-S), altered the levels of spontaneous activity in cool-sensitive fibers as well as inducing activity in tactile fibers, cold nociceptors and silent fibers that were insensitive to innocuous thermal or tactile stimuli. Moreover, tactile or thermal sensitivity was induced in fibers that were initially insensitive to touch or cooling. The neuronal distribution of sensitivities to capsaicin and to HO-alpha-S indicate that this compound affects neurons mediating innocuous sensations. HO-alpha-S may be useful as a model stimulus for studies of paresthesia.     

丁烯酸内酯对心肌细胞Ca^2＋通道的阻滞作用

采用贴附式膜片钳技术，在培养的Ｗｉｓｔａｒ大鼠单个心肌细胞上记录丁烯酸内酯对Ｂ，Ｌ，Ｔ３型Ｃａ２＋通道单通道电活动的影响。结果表明，丁烯酸内酯浓度为３００ｍｇ·Ｌ－１时，心肌细胞Ｂ，Ｌ，Ｔ３型Ｃａ２＋通道均受到明显的阻滞，其阻滞作用表现在使Ｂ，Ｌ，Ｔ３型Ｃａ２＋通道的开放时间分别缩短４６６％，５０５％和１５３％，关闭时间分别延长３０５％，３２２％和３２８％，使通道的开放概率分别下降５６８％，６１５％和３５０％。而对流过Ｂ，Ｌ，Ｔ３型Ｃａ２＋通道的Ｂａ２＋流幅值均无明显影响。