骨质疏松症大鼠血液中碱性磷酸酶来源方式探讨

目的探讨骨质疏松症大鼠的血液碱性磷酸酶（ALP）的来源方式。方法 40只4个月龄雌性SD大鼠,分为两组,模型组和假手术组（对照组）,模型组进行双侧卵巢摘除,对照组只打开腹腔。实验动物颈椎脱臼处死后,取股骨,去尽肌肉与结缔组织,截取相应的骨组织浸入4%多聚甲醛中固定3 d,然后浸入4%EDTA溶液中,室温脱钙4周,每周换液1次。采用原位杂交和免疫组化法分别检测骨组织中ALP表达情况。结果对照组骨组织中的ALP蛋白及ALP mRNA表达含量均明显高于模型组,P均〈0.01。结论骨质疏松症大鼠血液中的ALP主要来源于成骨细胞破坏;骨组织ALP水平可作为其他细胞向成骨细胞分化的一个鉴定指标。     

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.     

Associations of serum alkaline phosphatase with metabolic syndrome and mortality

Background

Recent data suggest that elevated serum alkaline phosphatase levels are associated with increased mortality, but the mechanisms for this association are unknown. As metabolic syndrome is associated with higher serum alkaline phosphatase levels, we examined the joint association of mortality with metabolic syndrome and serum alkaline phosphatase levels in the US general population.

Methods

Retrospective observational study of 15,234 adult participants in the National Health and Nutrition Examination Survey III. Multivariable Cox regression analyses were used to jointly relate mortality risk to serum alkaline phosphatase and indicators of metabolic syndrome.

Results

Prevalence of metabolic syndrome was 14% to 41% among patients in lowest and higher quartiles, respectively, for baseline serum alkaline phosphatase. The mortality hazard ratio for each doubling of serum alkaline phosphatase was 1.52 (95% confidence interval [CI], 1.35–1.72) adjusting only for demographic factors, and 1.37 (95% CI, 1.21–1.56) adjusting for both demographic and metabolic syndrome factors in the full cohort, and was 1.83 (95% CI, 1.36–2.46) adjusting for demographic factors in the subgroup without any of the component conditions of metabolic syndrome.

Conclusions

In the US general population, higher levels of serum alkaline phosphatase is a predictor of mortality independent of the baseline prevalence of metabolic syndrome. Further studies are warranted to unravel the mechanisms of this association.     

Verapamil increases serum alkaline phosphatase in hypertensive patients

In rats, verapamil decreases intestinal absorption of calcium, increases serum parathyroid hormone (PTH), and induces osteopenia. In this prospective study, verapamil 80-120 mg three times daily was given for 2 months to 20 patients with hypertension, and the effects on calcium homeostasis were recorded. This dose of verapamil significantly reduced supine systolic and diastolic blood pressure (+/- SD) from 158/100 +/- 9/8 mmHg to 146/89 +/- 14/8 mmHg (P = 0.001). Serum alkaline phosphatase (ALP) increased significantly from 2.77 +/- 1.06 mu kat l-1 to 3.19 +/- 1.22 mu kat l-1 (P = 0.004), and isoenzymes of ALP of skeletal origin appeared after verapamil treatment. The excretion of sodium in the urine increased (Na/creatinine ratio 8.95 +/- 6.01 before and 13.16 +/- 8.26 after verapamil; P = 0.04), while the excretion of calcium, phosphate and potassium was not changed. PTH was slightly increased at the end of verapamil treatment (1.09 +/- 0.54 vs. 0.98 +/- 0.74 microgram l-1; P = 0.07), and s-1,25(OH)2D3 was also somewhat increased (22.3 +/- 14.4 vs. 17.6 +/- 4.9 ng l-1; P = 0.26). Serum Ca was not affected by verapamil (before verapamil 2.43 +/- 0.11 mmol l-1, after verapamil 2.40 +/- 0.12 mmol l-1; P = 0.28). The increase in serum ALP demonstrates that verapamil affects bone cell metabolism in man. This effect could be secondary to the enhancement of PTH secretion.     

Elevated serum alkaline phosphatase levels in a renal transplant patient precede colitis

An asymptomatic, but highly significant, rise in serum alkaline phosphatase (AP) levels developed in a renal transplant recipient. Investigations ruled out bony or hepatobiliary disease. Subsequent diarrhea and weight loss led to a diagnosis of cytomegalovirus (CMV) colitis, which was confirmed with a positive CMV pp65 antigenemia test and an endoscopic finding of multiple colonic erosions. Intravenous ganciclovir led to complete patient recovery and a swift reduction of serum AP levels to normal. Normally, intestinal AP isoenzymes are cleared quickly from the circulation. However, acute bowel diseases, especially when inflammatory in origin, can produce high serum AP levels. In this presented patient, the rise in serum AP levels preceded symptomatic manifestations of CMV colitis, and fell with successful therapy. Acute CMV disease in solid organ transplant recipients is common, can take many shapes, and needs to be diagnosed quickly. An unexplained rise in serum AP levels should lead to a search for inflammatory bowel disease, specifically CMV colitis, in transplanted patients.     

永嘉县氟中毒未成年人血清碱性磷酸酶水平的变化情况分析

目的探讨永嘉县氟中毒未成年人血清碱性磷酸酶水平的变化情况。方法选择2012年4月至2013年4月永嘉县入院检查诊断为氟中毒的未成年人共67例作为氟中毒组,按照1∶1对照方案选择同年龄、同性别的入院体检的健康儿童67例作为对照组,比较2组受试者血清碱性磷酸酶的水平。结果不同年龄阶段氟中毒儿童血清碱性磷酸酶水平均显著高于对照组儿童（P〈0.05）;将ALP〉500 U/L作为异常,本研究共检出异常者8例,其中氟中毒组检出异常7例,异常率为10.45%,对照组检出异常1例,检出异常率为1.49%,2组比较,差异具有统计学意义（P〈0.05）。结论氟中毒儿童其血清碱性磷酸酶活性有所增加,血清碱性磷酸酶升高对儿童氟中毒所致骨损伤具有着重要的意义。     

Leukocyte alkaline phosphatase in cancer patients

Summary Leukocyte alkaline phosphatase (LAP) activity in peripheral blood was determined in 113 patients with non-metastatic malignancies, 36 patients with metastatic spread, and 22 individuals who served as controls. The LAP score of the non-metastatic cancer patients was significantly higher (p<0.001) than the controls, and the score of the metastatic group was further increased significantly as compared to both control (p<0.001) and nonmetastatic groups (p<0.001).The results of this survey suggest that the level of LAP score in peripheral blood might be used to differentiate between non-metastatic and metastatic disease and might serve as an aid in prognosis of the patients.     

Elevated serum alkaline phosphatase as a predictor of cognitive impairment in patients with acute ischaemic stroke: A retrospective cohort study

BackgroundIn the present study, we assessed the relationship between serum alkaline phosphatase (ALP) levels and cognitive function changes in acute ischaemic stroke patients.MethodsWe retrospectively collected the demographic data and clinical information from the medical records of patients after the onset of ischaemic stroke. We used the Chinese version of the Mini-Mental State Examination to assess cognitive function. Mixed linear and logistic regression models adjusted for several factors were used to explore the relationship between ALP and cognitive impairment.ResultsA total of 1019 patients were included in the analysis, including 523 poststroke patients with cognitive impairment (PSCI) and 496 patients with non-PSCI. The incidence of poststroke cognitive impairment was 51.3 %. The serum ALP level in the PSCI group was significantly higher than that in the non-PSCI group (86.5 ± 18.9 U/L vs 68.6 ± 15.5 U/L, P < 0.001). The mixed linear model fully adjusted for all variables indicated that the ALP level was positively associated with cognitive impairment (based on the Mini-mental State Examination score) decline, with changes from -0.54 to -0.16 per unit increase in ALP. The logistic regression revealed that the odds of cognitive impairment increased by 42 % when the ALP concentration increased by one U/L (odds ratio (OR) = 1.42, 95 %CI: 1.17−3.09, P = 0.012). The spline regression model further confirmed the dose-response relationships between ALP levels and three-month cognitive impairment (P for nonlinear trend = 0.012).ConclusionThe present study revealed that relatively high serum ALP levels at baseline might be an independent risk factor for cognitive impairment in patients with acute ischaemic stroke.     

Antigenicity of adult Schistosoma mansoni alkaline phosphatase

Antibodies to the alkaline phosphatase (AP) of Schistosoma mansoni in infected human and mice sera were evaluated by a direct solid-phase AP immunoadsorption assay (APIA) and by Western blot and immunostaining. APIA consisted of (a) solid-phase capture of immunoglobulins from infected human or mice, (b) immunoadsorption of the enzyme antigen by the antibodies, and (c) detection of the enzymatic activity. By this procedure the appearance of the anti-AP response in mice was detected around 50 days post-infection; this response was not specific for an AP of a given schistosome strain and it was not induced by an autoimmunity phenomenon. Fourteen out of 15 sera from infected people tested by APIA showed a clear antibody response against this enzyme. Immunoblots in non-reducing conditions supported APIA results indicating that the parasite AP was specifically recognized by the antibodies present in infected human and mice sera. These results suggest the possible usefulness of the schistosome AP as a marker for S. mansoni infection.     

Neutrophil alkaline phosphatase levels after induction of hypersegmented neutrophil release into blood of the rat

Summary Hypersegmentation of nuclei was induced in rat circulating neutrophils after cyclophosphamide (CY) administration and neutrophil alkaline phosphatase (NAP) activity was measured. It was shown that changes in NAP levels and segmentation of neutrophil nuclei were parallel. Relationship between age of neutrophils and NAP levels is discussed.     

Neonatal androgenization: effects of responsiveness of ovarian alkaline phosphatase to gonadotropins.

Five-day-old female mice were injected subcutaneously with 100 mug of testosterone benzoate in oil, or with oil only. At various ages thereafter, they received either 5 I.U. human chorionic gonadotropin (hCG) per 10 g body weight or saline only, and were killed 24 h later. Alkaline phosphatase activity was measured in whole ovarian homogenates. Neonatal androgenization failed to affect the early phases of ovarian responsiveness, but selectively abolished both the normal rise in alkaline phosphatase which precedes the onset of puberty and the responsiveness of the enzyme to hCG stimulation at this time.     

Mechanism of action of 1,25-dihydroxyvitamin D3-induced stimulation of alkaline phosphatase in cultured osteoblast-like cells

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates the alkaline phosphatase of rat and human osteoblast-like cells in culture. Here the mechanism of this effect was investigated using the rat osteogenic sarcoma cell line ROS 17/2-8. We found that 50% maximum alkaline phosphatase stimulation is elicited by 1,25(OH)2D3 at 7 X 10(-10) M. The concentration of serum in the culture medium influences inversely the effective 1,25(OH)2D3 concentration. Increased alkaline phosphatase appears after a lag period of cell exposure to 1,25(OH)2D3 which is between 8 and 24 h; during 96 h culture in the presence of 1,25(OH)2D3 the enzyme activity continues to rise. Cycloheximide (0.1-1 micrograms/ml) added in the cultures for 3 days or actinomycin-D (1-30 ng/ml) added for 24 h inhibit the 1,25(OH)2D3 effect on alkaline phosphatase in a dose-dependent fashion; withdrawal of cycloheximide restores the responsiveness of cells to 1,25(OH)2D3 completely, but withdrawal of actinomycin-D restores cell responsiveness only partially. These findings suggest that 1,25(OH)2D3-induced stimulation of alkaline phosphatase in the osteoblast-like cells involves genome activation and de novo protein synthesis.     

肾脏病患者碱性磷酸酶及同工酶的检测及分析

目的　探讨碱性磷酸酶(ALP)及同工酶与肾脏疾病的关系。方法　1997 -03 ~2003 -05黑龙江省医院用自动生化分析仪测定43例肾脏病患者ALP浓度,聚丙烯酰胺凝胶圆盘电泳及扫描定量测定ALP同工酶浓度。结果　按肾脏病理改变分为肾小球损伤组、肾小管损伤组和重度弥漫病变组。尿液总ALP肾小球损伤组和肾小管损伤组与对照组比较差异有极显著性(P<0 .001),组织非特异型ALP同工酶与正常对照组比较差异有极显著性(P<0. 001);尿液小肠型ALP同工酶肾小管损伤组与正常对照组和肾小球损伤组比较差异有极显著性(P<0. 001)。严重病变组尿液总ALP及同工酶与正常对照组比较差异无显著性(P>0. 05 )。结论　尿液ALP同工酶可以作为肾脏不同部位损伤的指标。     

实验性牙周炎大鼠牙龈组织中碱性磷酸酶水平变化及意义

目的观察碱性磷酸酶（ALP）水平变化在牙周炎发病中的作用。方法选用40只健康SD大鼠随机分为对照组和观察组各20只,观察组建立牙周炎模型,对照组常规饲养;分别于造模术后4周和8周各处死20只,采用酶标仪测定牙龈组织中ALP水平,观察牙槽骨吸收情况及牙周组织学改变。结果造模术后4周和8周时观察组牙龈组织中ALP水平均明显高于对照组（P〈0．01）,且术后8周高于4周（P〈0．01）;观察组有明显牙槽骨吸收及牙周组织炎症细胞浸润,对照组则无。结论ALP水平变化可能在牙周炎发病过程中起重要作用。     

Elevated serum alkaline phosphatase correlates with postoperative cognitive dysfunction: A retrospective cohort study based on STROBE statement

Little is known about the association between serum alkaline phosphatase (ALP) levels and postoperative cognitive dysfunction (POCD) after general anesthesia. Thus, we investigated the association of serum ALP levels with POCD in patients who underwent surgery with general anesthesia in a retrospective cohort study. We retrospectively collected data from patients who underwent surgery with general anesthesia between May 2016 and June 2020. Serum ALP activity was detected using a p-nitrophenyl phosphate assay. Pre-and postoperative cognitive function were evaluated using the Chinese version of the Mini-Mental State Examination. Univariate and multivariate logistic regression were used to explore the effect of ALP on cognitive function. The incidence of POCD was 13.5%. Compared with the control group, the POCD group had higher ALP levels. The neuropsychological test results suggested that the scores of most items were lower in the POCD group than in the non-POCD group. Univariate logistic regression indicated that increased ALP levels were significantly associated with cognitive dysfunction (odds ratio = 1.15, 95% confidence interval: 1.13–1.18, P = .000). Multivariate regression showed that elevated ALP was still associated with POCD after adjusting for confounding factors (odds ratio = 1.16, 95% confidence interval: 1.13–1.18, P = .000). The spline regression model indicated the dose–response associations between ALP level and POCD risk (P for nonlinear trend < .001). Our study indicated that elevated serum ALP was an independent predictive factor of POCD at the 3-month follow-up. The occurrence of POCD could be associated with inflammatory status.     

血清ALP、GGT水平对射频消融术治疗原发性肝癌患者预后的影响

目的探讨治疗前血清ALP、GGT水平对射频消融术治疗原发性肝癌患者预后的影响。方法收集2010年10月-2015年6月吉林大学第一医院肿瘤中心收治的165例经病理或临床确诊为原发性肝癌并接受射频消融治疗的患者术前的临床资料。计数资料组间比较采用χ~2检验,采用Kaplan-Meier法及Cox回归分析治疗前血清ALP、GGT水平与患者总生存期、无进展生存期及临床特点的关系。结果治疗前血清ALP正常(≤135 U/L)及异常(135 U/L)患者的1年生存率分别为91%和79%,2年生存率分别为90%和68%,5年生存率分别为35%和18%,两组差异有统计学意义(P=0.01);治疗前血清GGT正常(≤45 U/L)及异常(45 U/L)患者的1年生存率分别为95%和87%,2年生存率分别为85%和71%,5年生存率分别为37%和21%,两组差异有统计学意义(P0.001)。治疗前血清ALP[风险比(HR)=1.766,95%可信区间(95%CI):1.068~2.921,P=0.027]及GGT(HR=2.312,95%CI:1.367~3.912,P=0.002)与原发性肝癌患者射频消融术后的总生存期密切相关,是其独立预后影响因素。治疗前血清ALP正常及异常患者的1年无进展生存率分别为72%和50%,2年无进展生存率分别为52%和21%,5年无进展生存率分别为14%和3%,两组差异有统计学意义(P0.001);治疗前血清GGT正常及异常患者的1年无进展生存率分别为81%和56%,2年无进展生存率分别为62%和35%,5年无进展生存率分别为18%和7%,两组差异有统计学意义(P0.001)。治疗前血清ALP(HR=1.653,95%CI:1.001~2.729,P=0.049)及GGT水平(HR=1.949,95%CI:1.296~2.930,P=0.001)与原发性肝癌患者射频消融术后的无进展生存期密切相关。在ALP异常患者中,男性患者比例高,肝功能Child-Pugh分级差,腹水发生率高;GGT异常患者中,肝功能Child-Pugh分级差,肿瘤分期晚,肿瘤≥5 cm患者比例高,肝性脑病发生率高。结论治疗前血清ALP、GGT水平可用于预测原发性肝癌患者射频消融术后的预后,二者对原发性肝癌患者射频治疗后的远期生存具有一定的指导意义。     

Assessment of alkaline phosphatase on the surface membrane of neutrophils by immunofluorescence

Expression of alkaline phosphatase (ALP) on the surface membrane of neutrophils (mNAP) was studied by immunofluorescence using an anti-ALP monoclonal antibody. Fluorescent intensity distribution of mNAP was analyzed using FACS (fluorescence-activated cell sorter). The mean fluorescent intensity (MFI) of the mNAP in this assay was well correlated with the neutrophil ALP (NAP) score demonstrated cytochemically (r = 0.832). mNAP levels in various hematological disorders were evaluated by % mNAP⁺ cells and MFI. The levels in aplastic anemia and polycythemia vera were significantly higher, and in chronic myelocytic leukemia and paroxysmal nocturnal hemoglobinuria (PNH), the levels were significantly lower compared with the levels in healthy volunteers. Two-color immunofluorescence with anti-ALP and anti-CD16 showed that the PNH clone was essentially negative for mNAP, whereas residual normal neutrophils (CD16⁺) had levels slightly higher than those in normal individuals. Highly reproducible results were obtained in the blood samples which were stored at 4°C for at least 24 hr without any treatment prior to immunofluorescent staining. No degradation of fluorescent intensity was seen 4 days after staining and fixation. The mNAP assay is simple, without subjective evaluation for quantification, and is useful for differential diagnosis of hematological disorders. Am. J. Hematol. 60:12–18, 1999. © 1999 Wiley-Liss, Inc.