甲状腺功能亢进症316例肝功能某些指标变化的分析

目的探讨甲状腺功能亢进症（甲亢）患者与肝功能的一些指标变化关系。方法对316例甲亢患者行甲功、肝功能检测,指标包括丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、谷胺酰转肽酶（GGT）、碱性磷酸酶（ALP）、血清总胆红素（TBL）;比较分析甲亢性肝功能损害和甲亢无肝功能损害两组之间的游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素（TSH）水平;并分析甲亢患者肝功能变化的情况。结果甲亢性肝损害组TSH、FT3、FT4比无肝损害甲亢组高（P〈0．05）,甲亢性肝功能损害时主要以ALP、ALT、AST的异常增高为主;并且FT3、FT4分别与ALP、ALT、AST存在正相关关系,P〈0．05。结论甲亢性肝功能损害（特别是ALP变化）与甲状腺激素水平有密切关系,能否用ALP来协助甲亢诊断和治疗观察值得探讨。     

不同甲状腺功能状态对人体血清瘦素水平的影响

目的　研究不同甲状腺功能状态(甲亢、甲减及正常)对人体血清瘦素水平的影响。方法　选取甲亢患者53例(男15,女38),甲减患者48例(男15,女33)和正常对照51例(男15,女36),抽取静脉血测瘦素水平。结果　各组瘦素水平皆与BMI呈强的正相关(P＜0.01),且女性瘦素水平显著比男性高。甲亢患者无论性别,其瘦素水平〔男性(1.2±0.8)μg/L;女性(4.0±2.2)μg/L〕都较正常人〔男性(3.7±2.0)μg/L;女性(7.3±3.0)μg/L〕低(男性P＜0.01,女性P＜0.001);而甲减患者女性瘦素水平〔(5.1±4.1)μg/L〕较正常女性〔(7.3±3.0)μg/L〕低(P＜0.001),男性瘦素水平〔(3.8±2.7)μg/L〕与正常男性〔(3.7±2.0)μg/L〕相比差异无显著性(P=0.09)。结论　生理浓度的甲状腺激素水平可能是人体产生足够的瘦素、从而维持人体正常能量代谢平衡的一个重要因素。     

老年脑卒中患者肢体瘫痪后骨和钙代谢的变化

目的探讨老年脑卒中患者肢体瘫痪对其骨、钙代谢的影响。方法对发病3天以内入院的170例急性期老年脑卒中患者,其中脑梗死患者114例,脑出血患者56例。分别于发病3天内及发病1年后测定血钙(Ca)、碱性磷酸酶(ALP)、骨钙素(BGP)、甲状旁腺激素(PTH)、尿羟脯氨酸(HOP)、尿肌酐(Cr)。结果患者发病3天内血ALP(83.9±25.3)U/L,BGP(9.98±2.91)μg/L,Ca(2.36±0.15)mmol/L,PTH(25.2±14.8)ng/L,尿HOP/Cr(0.64±0.31);1年后患者血ALP(104.20±16.6)U/L,BGP(11.76±1.54)μg/L,Ca(2.48±0.16)mmol/L,PTH(37.0±15.7)ng/L,尿HOP/Cr(0.77±0.42)。发病1年后患者血BGP、ALP,Ca,PTH及尿HOP/Cr比值均明显升高(P均<0.01)。结论老年脑卒中患者肢体瘫痪后骨、钙代谢明显异常。     

氟剂对成骨细胞成骨功能表达的影响

目的　从不同剂量氟化钠 (NaF)对大鼠成骨细胞 (OB)功能表达的影响 ,研究氟剂促进成骨作用的机制及剂量效应关系。方法　经酶消化法从新生 2 4hSpregne Dawley (SD)种乳鼠头盖骨分离得到的成骨细胞。在 10 -7～ 5× 10 -4mol/LNaF中培养。用生化法测定细胞碱性磷酸酶 (ALP)活性 ,用放射免疫法测定培养液中骨钙素 (OC)含量。结果　NaF对细胞ALP活性的影响呈双向 ,即低浓度NaF(10 -7～ 10 -5mol/L)增加ALP活性 ,高浓度NaF (10 -4～ 5× 10 -4mol/L)则抑制ALP活性 ;对骨钙素产生和分泌的影响则呈单向 ,即各浓度NaF均刺激细胞骨钙素分泌 ,并与氟剂剂量呈正相关 ,其中 5× 10 -4mol/L组骨钙素水平最高 ,与对照组相比增加 6 7 14 % (P <0 0 5 )。结论　适量氟剂能增加成骨细胞ALP的活性及骨钙素的产生 ,促进成骨细胞的骨形成功能 ,但有效剂量范围狭窄     

投氟不同时间大鼠血清氧化应激和碱性磷酸酶活性的变化研究

目的 观察过量氟处理的大鼠在不同时间内氧化应激态与碱性磷酸酶(ALP)活性的变化.方法 24只Wistar大鼠,按体质量随机分成对照组、高氟组,每组12只.对照组大鼠饮用自来水(氟化钠<1 mg/L),高氟组大鼠饮用自来水中加入剂量为221 ms/L的氟化钠.实验期间动物自由进食、饮水,每周测体质量1次.实验时间分别为l、4、 8、 12周.通过生化方法检测大鼠血清丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、尿酸和ALP活性.结果 投氟与时间两因素对ALP活性影响有交互作用(F=4.690,P<0.05).投氟1周与12周大鼠血清的ALP活性[(19.29±3.69)、(15.72±0.79)kU/L]较对照组[(14.08±1.99)、(12.91±3.97)kU/L]明显升高(P均<0.05);投氟1周和4周大鼠血清MDA[(13.37±4.38)、(11.82±2.08)μmol/L]较对照组[(8.75±3.24)、(7.42±2.62)μmol/L]明显增高(P均<0.05);高氟组SOD、GPx与对照组比较,差异无统计学意义(P均>0.05);投氟1、4周大鼠血清尿酸[(89.53±13.21)、(88.47±19.78)μmol/L]较对照组[(77.79±11.43)、(65.42±13.42)μmol/L]明显增高(P均<0.05),而投氟8、12周大鼠尿酸[(67.21±9.44)、(73.95±9.52)μmol/L]低于对照组[(77.79±11.43)、(65.42±13.42)μmol/L,P均<0.05].结论 投与过量氟大鼠的ALP活性变化具有一定的时间依赖性;而投氟刺激大鼠氧化应激水平增强,这种刺激与投氟时间没有明显关联.     

洛伐他汀对成骨细胞骨形态发生蛋白2表达及碱性磷酸酶活性的影响

目的　观察洛伐他汀对成骨细胞骨形态发生蛋白 2 (BMP 2 )表达及碱性磷酸酶 (ALP)活性的影响 ,初步探讨洛伐他汀刺激成骨细胞的作用机制。　方法　体外培养成年小鼠的成骨细胞 ,对照组不用洛伐他汀 ,实验组以不同浓度 (0 2、0 5、1 0 μmol L)的洛伐他汀作用 72h后行细胞BMP 2免疫细胞化学染色、ALP染色及细胞ALP比活性测定。　结果　洛伐他汀作用 72h后 ,细胞ALP染色增强 ,胞浆内BMP 2表达水平增高 ,并随洛伐他汀浓度的增加而增加 ;对照组的成骨细胞几乎无BMP 2的表达。对照组ALP比活性为 (70 5 5 6± 171 4 0 )U·g- 1 ·L- 1 ,实验组洛伐他汀不同浓度组分别为 (716 39± 2 94 6 1)U·g- 1 ·L- 1 、(84 9 70± 2 30 0 9)U·g- 1 ·L- 1 、(983 4 8± 2 0 8 35 )U·g- 1 ·L- 1 ,其中 1 0μmol L组与对照组细胞ALP活性的差异有显著性 (P <0 0 5 )。　 结论　洛伐他汀的成骨作用与其促进成骨细胞BMP 2的高表达、引起细胞自分泌或旁分泌BMP 2增多、细胞ALP活性增高有关。     

原发性胆汁性肝硬化31例临床分析

目的　对原发性胆汁性肝硬化患者的临床特征进行回顾性分析 ,以提高对该病诊治的认识。方法　分析 31例原发性胆汁性肝硬化患者的一般资料、临床表现、生化、免疫学及病理学等改变。结果　本组患者中女性 2 5例 ,确诊时的平均年龄为 (4 9.2± 10 .7)岁。症状以黄疸最为多见 (74 .2 % ) ,其次为皮肤瘙痒 (5 1.6 % )和乏力 (32 .3% ) ,3例患者 (9.7% )合并腹水。所有患者血清碱性磷酸酶、γ 谷氨酰转肽酶及胆红素水平明显升高 [分别为 (388.9± 2 77.5 )U/L、(381.6± 2 13.2 )U/L和 (176 .4± 176 .1) μmol/L],血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)水平呈轻至中度升高 [分别为(79.7± 4 6 .3)U/L及 (119.8± 6 1.2 )U/L],患者血清IgM升高 (3.0± 1.9)g/L ,行线粒体抗体检查者92 % (2 3/ 2 5 )阳性 ,6 1.3%患者熊去氧胆酸治疗短期内显示一定疗效。结论　原发性胆汁性肝硬化主要累及中年女性 ,血清碱性磷酸酶及γ 谷氨酰转肽酶水平升高、抗线粒体抗体阳性、血清IgM升高有助于诊断本病 ,肝活检病理学检查有助于进一步确诊及组织学分期     

碱性成纤维细胞生长因子诱导老年大鼠心肌细胞保护及其机制研究

目的　探讨碱性成纤维细胞生长因子（bFGF）对老年大鼠心肌细胞缺氧/复氧（H/R）损伤的影响及其保护机制。　方法　在分离的老年大鼠心肌细胞H/R模型上,观察bFGF预孵育对H/R后心肌细胞乳酸脱氢酶（LDH）漏出、ATP含量和细胞存活率的影响,并采用滤纸法测定心肌细胞外信号调节激酶(ERKs)活性的变化。　结果　bFGF激活ERKs,并呈剂量依赖性减轻H/R所致心肌细胞损伤,表现为细胞存活率〔bFGF10ng组(70.0±4.6)%,H/R组(53.0±4.5)%,P＜0.01〕和细胞内ATP含量〔bFGF10ng组(23.1±2.3)nmol/106细胞,H/R组(12.3±2.1)nmol/106细胞,P＜0.01〕升高,细胞浆酶LDH漏出〔bFGF10ng组（257.3±51.0）U/L,H/R组（372.5±69.2）U/L,P＜0.05〕减少;ERKs上游激酶抑制剂PD098059完全消除上述保护作用〔PD098059组细胞存活率（57.0±5.8）%,ATP含量（15.1±2.6）nmol/106细胞,培养液中LDH活性（325.5±59.0）U/L,与bFGF10ng组比较均为P＜0.01〕。　结论　bFGF可以提高老年大鼠心肌细胞对于缺氧的耐受性,其保护机制涉及ERKs的活化。     

自身免疫性甲状腺疾病患者血清纤维化指标观察

目的 观察自身免疫性甲状腺疾病(AITD)患者血清Ⅲ型前胶原(PCⅢ)和透明质酸(HA)水平.探讨其临床意义.方法 按甲状腺功能将114例AITD患者分为3组:①Graves病甲状腺功能亢进(简称甲亢)组(38例),②桥本甲状腺炎甲状腺功能低下(简称甲低)组(35例),③桥本甲状腺炎亚临床甲状腺功能低下(简称哑甲低)组(41例),另设40例健康人作为对照组.用免疫化学发光法检测以上各组人群血清游离三碘甲腺原氨酸(FT3),游离甲状腺素(FT4),超敏促甲状腺激素(sTSH)水平.用酶联免疫吸附试验(ELISA)检测血清PCⅢ水平,用放射免疫分析法(RIA)检测血清HA水平.结果 甲亢组血清FT3,FT4水平[(18.35±6.19),(76.28±23.49)pmol/L]明显高于对照组[(4.75±0.31),(16.12±3.27)pmol/L],sTSH水平[(0.15±0.07)mU/L]明显低于对照组[(3.78±0.15)mU/L],差异均有统计学意义(P＜0.01),甲低组FT3,FT4水平[(3.36±0.26),(6.37±2.19)pmol/L]均低于对照组(P＜0.05),sTSH[(44.58±13.29)mU/L]明显高于对照组(P＜0.01),亚甲低组FT3,FT4水平[(4.86±0.45),(15.26±2.78)pmol/L]与对照组比较,差异无统计学意义(P＞0.05),sTSH[(14.26±4.73)mU/L]明显高丁对照组(P＜0.01).甲亢组血清PCⅢ水平[(4.63±1.22)μg/L]明显高于甲低组[(3.64±1.12)μg/L],亚甲低组[(3.54±1.17)μg/L],对照组[(3.56±1.07)μg/L],组问两两比较差异有统计学意义(P＜0.05),而甲低组,哑甲低组,对照组PCⅢ水平任意两组间比较,差异均无统计学意义(P＞0.05),甲低组血清HA水平[(31.13±10.28)μg/L]高于甲亢组[(22.24±7.22)μg/L],亚甲低组[(22.43 4-7.99)μg/L]和对照组[(23.09±9.19)μg/L],组间两两比较差异均有统计学意义(P＜0.05),而甲低组,亚甲低组,对照组HA水平任意两组比较,差异均无统计学意义(P＞0.05).结论 在排除肝纤维化等病变的情况下,检测甲亢患者血清PCⅢ,对了解早期的心肌纤维化有重要意义,对病程较长的甲亢患者,血清HA,PCⅢ的榆测可作为早期发现肝损伤和纤维化的参考依据.     

甲状腺机能亢进症患者部分骨代谢生化指标的变化及分析

目的　查明甲状腺机能亢进症患者血清骨钙素 (BGP)、碱性磷酸酶 (AL P)及尿羟脯氨酸 (HOP) ,观察其变化并进行分析。方法　以 30例甲亢患者及 15例正常人为研究对象 ,测定 BGP、AL P、尿 HOP等指标。结果　甲亢患者血清 BGP(11.18± 4.74) ng/ m l和尿 HOP(2 4.32± 11.2 1) mg/ g.Cr均高于正常对照组 (P <0 .0 5)。结论　骨吸收增加和骨形成相对降低可能为甲亢患者骨代谢异常发生的主要原因     

Leukocyte alkaline phosphatase: another organ-specific alkaline phosphatase

We have used enzyme specific inhibitors and heat inactivation to distinguish Leukocyte alkaline phosphate (LAP) from other organ-specific alkaline phosphatases as well as to compare LAP from normal granulocytes and leukemic cells with elevated LAP. The heat inactivation and inhibition curves of LAP are quite different from those of other organ-specific alkaline phosphatases. The inhibition curves and heat inactivation characteristics of LAP from normal granulocytes and that obtained from chronic granulocytic leukemia (CGL) blast phase cells with elevated LAP are identical. These data suggest that LAP is distinct from other organ-specific alkaline phosphatases, particularly placental alkaline phosphatase. We also conclude that the LAP present in cells with elevated levels is very similar or identical to that of normal granulocytes.     

Electrophoretic separation of alkaline phosphatase isoenzymes compared with alkaline phosphatase and gamma-glutamyltransferase in hepatobiliary diseases

Electrophoretic separation of serum alkaline phosphatase fractions and measurement of serum alkaline phosphatase and serum gamma-glutamyltransferase were carried out in 82 consecutive patients with suspected hepatobiliary disease to investigate the usefulness of the three tests in distinguishing between parenchymatous hepatic disease and occlusive hepatobiliary disease. It was concluded that measurement of total serum alkaline phosphatase was superior to the two other tests.     

Leukocyte alkaline phosphatase.

In summary, LAP is an intriguing enzyme and its control is related to pituitary-adrenal function. A review of the changes in LAP activity which occur in some physiological conditions and in disease states has been presented. The function of LAP, however, is unknown. Table I summarizes those conditions in which the LAP is consistently altered enough so to help in the diagnosis of the disorder. Of prime importance is the differentiation of CML from a leukemoid reaction or agnogenic myeloid metaplasia with a leukocytosis. However, in no instance is the LAP value alone diagnostic of any disease. It remains a laboratory test to be utilized in conjunction with all other available clinical data.     

Phosphotyrosine and phosphoprotein phosphatase activity of alkaline phosphatase in mineralizing cartilage

We used embryonic skeletal cartilage known to have high levels of alkaline phosphatase activity to determine whether growing cartilage has phosphotyrosine phosphatase activity and phosphotyrosinyl histone phosphatase activity at physiologic pH. Embryonic chick pelvic cartilage and fetal pig scapular growth-plate cartilage were assayed using phosphotyrosine as substrate at pH 7.5 and the amount of tyrosine generated measured. Both cartilage models had Km for phosphotyrosine between 6 to 24 mus mol/L. Phosphotyrosine phosphatase activity correlated with alkaline phosphatase activity as assessed by (1) distribution of histologic staining for alkaline phosphatase within the cartilages, (2) hormonal stimulation of cartilage alkaline phosphatase activity in vitro, (3) comparison of alkaline phosphatase and phosphotyrosine phosphatase activities in the presence of known inhibitors (vanadate, levamisole, homoarginine, and zinc), and (4) assaying chick epiphyseal cartilage alkaline phosphatase purified to homogeneity for phosphotyrosine phosphatase activity. Areas of cartilage with elevated alkaline phosphatase activity also had raised phosphotyrosine phosphatase activity. Triiodothyronine, a known stimulator of cartilage alkaline phosphatase, increased chick cartilage alkaline phosphatase activity 88% and phosphotyrosine phosphatase activity 106%, and stimulated porcine growth-plate cartilage alkaline phosphatase activity 91% and phosphotyrosine phosphatase activity 145% after 3 days of in vitro incubation. Each of the inhibitors block alkaline phosphatase and phosphotyrosine phosphatase activities. The purified alkaline phosphatase had a Km for phosphotyrosine of 18 mus mol/L and Vmax of 5700 nmol tyrosine/mg protein/h, which is well over 1000-fold higher than the phosphotyrosine phosphatase activity found in the above preparations of pelvic and scapular cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Perspectives on alkaline phosphatase isoenzymes

Since 1959, electrophoretic technics have ushered in the era of isoenzymes with a proliferation of methods and new findings. This is an attempt to develop a perspective on alkaline phosphatase isoenzymes from both fundamental and applied points of view.Thus, in addition to the bone source, isoenzymes of alkaline phosphatase from liver, intestine and placenta have now been found to contribute importantly to the serum, either individually, or in combination. It is now possible to distinguish each of these from the others in mixtures and to quantitate them by either a combination of specific inhibitors and heat inactivation or urea denaturation or by the employment of a variety of electrophoretic technics in which isoenzyme bands can be identified by their sensitivity to specific inhibitors or their reactivity to specific anti-serums.Particularly helpful in the fractionation of these isoenzymes has been the use of organ-specific inhibitors such as L-phenylalanine and L-homoarginine. In turn, their study has provided new insights into the mechanism of uncompetitive inhibition.The appearance of new forms of alkaline phosphatase during development and an appreciation of developmental control mechanisms has been paralleled by hormone enhancement of activity in cells (HeLa) growing in culture. The role of alkaline phosphatase in fat absorption and in placental function has now become a subject of interest, and the interrelationship with genetic factors such as blood groups has been recognized. The appearance of new forms during development is now accepted.The classic question of whether or not the liver is able to generate a major contribution of alkaline phosphatase to the circulation is still being investigated.Finally, an exciting direction is the study of the recently discovered placental forms of alkaline phosphatase in the tumor tissue, body fluids and serum of certain cancer patients. From the clinical point of view, tumor alkaline phosphatase may explain certain hyperphosphatasemias in problems of differential diagnosis, and from the biological perspective, this phenomenon can be studied profitably as an example of embryonic gene activation in cancer.     

Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase.

A cDNA clone for human adult intestinal alkaline phosphatase (ALP) [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] was isolated from a lambda gt11 expression library. The cDNA insert of this clone is 2513 base pairs in length and contains an open reading frame that encodes a 528-amino acid polypeptide. This deduced polypeptide contains the first 40 amino acids of human intestinal ALP, as determined by direct protein sequencing. Intestinal ALP shows 86.5% amino acid identity to placental (type 1) ALP and 56.6% amino acid identity to liver/bone/kidney ALP. In the 3'-untranslated regions, intestinal and placental ALP cDNAs are 73.5% identical (excluding gaps). The evolution of this multigene enzyme family is discussed.     

Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets

Objective: Serum alkaline phosphatase (ALP) levels show great variation with age and sex in children and adolescents. Additionally, different buffers used even in the same method cause variable results. This detail is not usually taken into account in the evaluation. We aimed to study pediatric age- and sex-specific reference ranges for ALP by colorimetric assay using p-nitrophenyl phosphate as substrate and diethanolamine as buffer and also to compare the ALP levels in patients with different types of rickets. Methods: 1741 healthy children and adolescents (904 girls) were included in the study for normative data. 77 different ALP measurements from 38 nutritional rickets (NR), 7 vitamin D-dependent rickets (VDDR) and 8 hypophosphatemic rickets (HR) patients were included. Results: Reference values for ALP were constructed. ALP levels demonstrated a tetraphasic course with two peaks at infancy and puberty. There was no difference in ALP levels between boys and girls until puberty. However, higher ALP levels were noted at 10-11 years in girls (p=0.02) and at 12-13, 14-15, 16-17 years in boys (p<0.001). ALP levels start to decline after age 12 and 14 in girls and boys, respectively. Serum ALP levels were highest in the VDDR group and lowest in the HR group (median z-score values in HR, VDDR and NR were 3.6, 10.4 and 6.5, respectively; p<0.001). Similarly, plasma parathormone(PTH) levels ranged from highest to lowest in the VDDR, NR and HR groups (median values: 525, 237 and 98 pg/mL, respectively; p<0.001). Conclusions: This normative data will provide a basis for better evaluation of ALP levels determined by the described method. Furthermore, use of z-scores gives a more precise assessment of changes in ALP levels in rickets and other bone disorders. Conflict of interest:None declared.