Activities of aspartate and alanine aminotransferases and alkaline phosphatase in sera of healthy subjects.

The activities of serum aspartate aminotransferase (EC 2.6.1.1, L-aspartate: 2-oxoglutartate aminotransferase, ASAT) and alanine aminotransferase (EC 2.6.1.2, L-alanine: 2-oxoglutarate aminotransferase, ALAT) were determined in the sera of 1484 apparently healthy subjects using kinetic methods according to the Scandinavian recommendation (33). In the adult sera the mean activity of ASAT was 21.4     

ICU危重病患者血清酶活性与病情的关系

目的探讨ICU危重病患者 5种血清酶活性的变化及其与病情及预后的关系。方法检测 1 32例危重病患者血清ALT、AST、LDH、AKP、GGT的酶活性 ,其中合并多功能器官障碍综合征 (MODS)患者 60例 ,死亡 2 0例 ,并以 1 0 0例健康体检者作为正常对照组。结果危重病组ALT、AST、LDH、AKP、GGT明显高于正常对照组 (P <0 .0 1 ) ;MODS组与非MODS组 5种酶相比较 ,有显著性差异 ;死亡组又明显高于存活组 (P <0 .0 1 )。结论血清酶活性既可反映ICU危重病患者的病情及预后 ,又是早期判断MODS的重要指标。     

Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study

OBJECTIVE: To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes. RESEARCH DESIGN AND METHODS: From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT). RESULTS: At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations. CONCLUSIONS: Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.     

Hepatic safety of erythromycin acistrate in 1549 patients with respiratory tract or skin infections.

Erythromycin acistrate is a new 2'-acetyl esther prodrug of erythromycin, whose structure resembles that of erythromycin estolate. However, in toxicological studies, it does not have the problems of hepatotoxicity. To assess its effects on hepatic functions in clinical practice, the liver parameters of patients with respiratory tract or skin infections were monitored during therapy. In total 1549 patients were treated for 7-14 days. In addition, 127 patients with suspected viral infections served as controls. There were no significant differences in serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (gamma-GT) or alkaline phosphatase (APHOS) values between the erythromycin acistrate or control groups at the beginning or end of therapy. ASAT values increased moderately in 2.4% and clearly in 0.3% of patients treated, but also decreased in 2.0%. ALAT values were moderately increased in 9.9%, clearly increased in 0.6% and normalized in 3.5% of the patients. gamma-GT values increased moderately in 3.5% and and clearly in 0.3%, but decreased to normal in 3.3% of the patients. APHOS was moderately elevated in 1.0% of the patients and normalized in 1.3%. The correlation of changes between the different liver enzymes was poor. Only ten patients (0.6%) had two or more clearly elevated liver enzyme values by the end of the therapy, of whom five had increased liver enzyme activities before the treatment, two had underlying disease explaining the changes and in only three patients out of 1549 (0.2%) could hepatic changes be attributed to erythromycin acistrate therapy. These changes were reversible. The results demonstrate the hepatic safety of erythromycin acistrate in clinical practice. Concomitant food intake did not affect the safety profile.     

Effects of storage time and temperature on urinary enzymes.

We measured three renal tubular brush-border enzymes (lactate dehydrogenase, LDH, EC 1.1.1.27; gamma-glutamyltransferase, GGT, EC 2.3.2.2; and alkaline phosphatase, AP, EC 3.1.3.1) in morning urine samples from 48 healthy subjects to check whether different storage times and temperatures could modify enzyme concentrations. Short-term (24 h) storage time at room temperature or 4 degree C does not affect urinary enzyme activity. A few days of freezing, at -20 or -70 degrees C, dramatically lowers LDH and AP values; GGT is partially preserved only at -70 degrees C, if the sample has been previously centrifuged. Urinary enzymes investigated in this study are extremely labile at low temperatures.     

Are increases in thyroxin-binding globulin in patients with acute hepatitis ascribable to synthesis by regenerating hepatocytes?

We describe a case of liver cirrhosis lacking the expected increase in serum thyroxin (T4)-binding globulin (TBG) despite abrupt, severe increases in aspartate and alanine aminotransferases (ASAT and ALAT) in serum. Sequential change in serum T4, triiodothyronine (T3), and TBG concentrations were also measured retrospectively in serum of 10 hospitalized patients with acute viral hepatitis. Although their mean T4 and TBG concentrations significantly exceeded those in 40 normal subjects (P less than 0.002 and P less than 0.001, respectively), these values were within the normal reference intervals in five patients. ASAT and ALAT concentrations were not significantly different in patients with increased TBG and patients with normal TBG, whereas mean concentrations of serum albumin and cholinesterase and mean prothrombin times (in percent) in the former group were significantly higher than those in the latter group (P less than 0.05, P less than 0.05, and P less than 0.001, respectively). For 60 samples with increased ASAT and ALAT, TBG and albumin or cholinesterase correlated significantly (r = 0.49, P less than 0.001 and r = 0.50, P less than 0.001, respectively), but not TBG and ASAT or ALAT. Collectively, these results suggest that the increase in serum TBG in acute hepatitis may reflect its synthesis in regenerating hepatocytes rather than a simple leakage from damaged hepatocytes.     

Enhanced cardiac enzyme profile

A protocol for an enhanced Cardiac Enzyme Profile is proposed based on an admission, or initial, serum specimen and a second specimen 16 hours after onset of symptoms as minimal baseline serum samples in order to accomplish several simultaneous goals: 1. Detecting CK2MB at its average peak for maximal assurance of diagnosis when release is small and for prognosis in all cases of increased serum CK2MB 2. Detection of laboratory evidence of myocardial injury when admission is delayed after onset by the collection of an admission sample for declining CK2MB, and for assays of other enzymes with longer time curves after myocardial injury such as LD isoenzymes and ASAT/ALAT activities and ratio 3. Establishment of decision limits and criteria for the determination of laboratory evidence of myocardial injury 4. Providing cost-effective procedures other than limitation of the number of samples; these include establishing thresholds and criteria for total CK, total LD, and ASAT so that isoenzymes and ALAT are only performed when thresholds are exceeded and criteria are met; performing only CK and, if the threshold is exceeded, CK isoenzymes on the 16-hour sample; collecting additional samples after the first two only when indicated by positive or suspicious (borderline) results and only on routine morning or afternoon rounds rather than specifically timed specimens (except in cases involving thrombolytic therapy); and termination of the protocol once peak positive CK2MB activity and requisite diagnostic consensus confirmation (such as positive LD isoenzymes) is obtained whether or not thrombolytic therapy is involved. Tissue localization of the enzymes has been outlined in some detail with particular reference to the amount of CK2MB in skeletal muscle. Pathophysiological factors discussed in more depth in a previous article have been amplified here with particular reference to the role of increased synthesis as a response to myocardial injury by surrounding prehypertrophic and hypertrophic myocardium as a possible major source of increased serum enzymes in myocardial infarction. ASAT and especially the ASAT/ALAT ratio are useful tests in the protocol, particularly in cases tested late after onset of symptoms when CK2MB has declined into the borderline or usual range, and ASAT/ALAT may be helpful in evaluating LD isoenzyme results. Codes for interpretive comments are provided to serve as guidelines.     

Altered gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase serum activities in long-term anticonvulsive therapy--comparison of diphenylhydantoin and carbamazepine

In 110 patients receiving a long-term anticonvulsant monotherapy with Diphenylhydantoin (DPH) and Carbamazepine (CBZ) the serum activities of gamma-GT, ASAT, ALAT, and AP were examined retrospectively. Elevated serum levels of enzymes were seen predominantly concerning gamma-GT and AP. 91% resp. 39% of patients receiving DPH-therapy showed increased gamma-GT resp. AP-levels compared to 64% and 14% of gamma-GT and AP-elevations by CBZ-treatment. All enzymes evaluated were more often and higher elevated by DPH than CBZ. Frequency and extent of increased activity of gamma-GT were highly related to daily dosage in both preparations. The proportion of pathological enzyme levels was associated with age in DPH and CBZ as well but not found to be significant. Sex differences in the frequency of increased enzyme activities could not be demonstrated. The results are discussed in the context of induction of cytochrome P-450-system.     

胆碱酯酶活性检验在脂肪肝中的应用

目的通过检测、分析脂肪肝患者血清中胆碱酯酶（CHE）、丙氨酸氨基转移酶（ALT）、γ-谷氨酰转移酶（GGT）及血脂的含量变化,证实CHE在脂肪肝诊断中的应用价值。方法在健康组与脂肪肝组中测定CHE浓度及ALT、天门冬氨酸氨基转移酶（AST）、GGT等酶类活力及对总胆固醇（TC）、三酰甘油（TG）进行了测定,并对结果进行统计学分析。结果脂肪肝患者CHE活性上升最显著（P＜0.001）,TC、TG也明显增高（P＜0.01）。结论提示CHE是常规生化指标中测定脂肪肝最敏感的检测项目,联合检测CHE活性及相关项目对脂肪肝的诊断有重要临床价值。     

Does haemoconcentration account for the changes in serum enzyme activities following haemodialysis?

We have estimated serum lactate dehydrogenase and isoenzymes, alkaline phosphatase, aspartate aminotransferase, amylase, creatine kinase, urea, creatinine and albumin on 29 patients with end-stage renal failure, before and after regular maintenance haemodialysis. All enzymes except serum aspartate aminotransferase, creatine kinase and LDH₁ were significantly increased (0.01 >P > 0.001 or P < 0.001) following dialysis. Because of the significant changes in serum albumin (P < 0.001) following dialysis, correction was made to all post-dialysis enzyme activities for the degree of haemoconcentration. When corrected no changes occurred in any of these enzyme activities following haemodialysis. We have also confirmed that in vitro dialysis of a predialysis serum does not alter the LDH isoenzyme activities, when corrections are made for changes in albumin concentration.     

血清γ谷氨酰转肽酶与BMI的相关性研究

目的：探讨血清γ-谷氨酰转肽酶（GGT）与BMI水平的关系。方法采用横断面研究法对某轻体力劳动单位职工进行问卷调查、体格检查、生化检测等,对资料完整的172名职工的数据进行分析,比较不同BMI水平、不同性别及不同GGT水平组别间一般资料的差异,采用单因素方差分析、Pearson相关分析及多元逐步回归分析探讨GGT与BMI的相关性。结果体质量过低组、正常体质量组、超体质量组、肥胖组4组间GGT水平比较差异有统计学意义（P＜0.05）;男性4个GGT四分位组间BMI、腹围、心率、舒张压、ALT、AST、碱性磷酸酶（ALP）比较差异有统计学意义（P＜0.05）;女性4个GGT四分位组间ALT、AST、ALP、HDL-C、甘油三酯比较差异有统计学意义（P＜0.05）;Pearson 相关分析显示,男性组 GGT 水平与 BMI、腹围、心率、肝右斜径、ALT、AST、ALP呈正相关,女性组GGT水平与BMI、腹围、收缩压、舒张压、ALT、AST、ALP、血肌酐、甘油三酯呈正相关,与HDL-C呈负相关。多元逐步回归分析提示GGT可以显著影响BMI及腹围;调整了性别、年龄、GGT、肝右斜径、ALT、AST、ALP、血肌酐、HDL-C、LDL-C、甘油三酯、空腹血糖等指标之后,GGT与BMI独立相关。结论血清GGT水平的上升与BMI水平存在显著且独立的相关性。     

Enzyme catalytic concentrations in human plasma after a marathon

Blood was obtained from 11 males participating in the Berlin marathon 1986, directly before and after the marathon, and on the three following days. Several observations were made: a) catalytic concentrations (activity) of creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) increased directly after the marathon or on the three following days; b) Cholinesterase (CHE), amylase (AML) and gamma glutamyltransferase (GGT) decreased directly after the marathon; c) the time course of AP and LDH isoenzyme activity after the race indicated an elimination from plasma to lower values than those originally observed before the run.     

Predictive value of serum enzyme determinations in acute myocardial infarction

The prognostic significance of serum enzyme measurements in acute myocardial infarction was studied in 146 patients hospitalized shortly after the attack. Creatine kinase (CK), CK-MB, aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH) were serially determined every four hours during the first three days following admission.Peak enzyme levels correlated well with the cumulated CK release (r = 0.95, 0.74, 0.70 for CK, ASAT and LDH respectively). Among all enzyme measurements, LDH levels determined when CK reached its peak value provided the best discrimination between acute phase survivors (15 days) and non-survivors. LDH was also the best measurement for identifying patients with ventricular impairment. LDH and ASAT peak levels were more powerful predictors of the patient's risk than CK peak levels. CK levels determined later in the course of myocardial infarction were more discriminant, indicating prolonged CK elevation in non-survivors. There was no significant difference in CK-MB levels, nor in cumulated CK-MB amounts for survivors and non-survivors.It is concluded that serum LDH activity is a better predictor of the short term evolution of myocardial infarction than CK levels or infarct size estimations from serial CK determinations.     

Lipid- and lipoprotein values in octo- and nonagenarians free from overt degenerative arterial disease

To investigate the reason for the increased activities of gamma-glutamyltransferase in the serum of renal transplant recipients, the activity of this enzyme was determined together with the alanine aminotransferase and alkaline phosphatase activity in serum (as an index of liver damage) and the urinary excretion of D-glucaric acid (as an index of microsomal enzyme induction) in 63 renal transplant recipients. Forty-one patients had increased activities of gamma-glutamyltransferase. Increased D-glucaric acid excretion was found only in ten patients having elevated alanine aminotransferase and/or alkaline phosphatase in seven cases and gamma-glutamyltransferase in eight cases. Therefore, the increased gamma-glutamyltransferase activities in renal transplant recipients can be primarily considered as a consequence of hepatobiliary dysfunction and not of enzyme induction.     

Collagen glucosyltransferase activity in human serum

Collagen glucosyltransferase activity was demonstrated in human serum. The assay used for this enzyme was shown to be specific, whereas attempts to measure collagen galactosyltransferase activity were unsuccessful. It is suggested that most of the serum collagen glucosyltransferase activity originates from the extravascular tissue, although it is possible that some is derived from the platelets.The activity of collagen glucosyltransferase in serum varied somewhat with age, the mean value in newborn infants being about 30 per cent higher than the level in adult subjects.In a randomly selected group of 50 hospitalized patients with various diseases, serum collagen glucosyltransferase activity was found to be elevated in 12 cases. The activities of reference enzymes (mainly aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) were elevated in 10 of these 12 patients and in three additional patients within the group. However, collagen glucosyltransferase activity showed no clear linear correlation with the activities of the reference enzymes within this group of 15 patients with elevated enzyme activities, the correlation being highest in the case of aspartate aminotransferase activity (r = +0.56, P < 0.05). In two patients collagen glucosyltransferase activity was elevated but all reference enzyme activities were normal, this pattern being possibly caused by damage concentrated in the connective tissue.The measurement of collagen glucosyltransferase activity in serum may prove useful in studying destructive diseases affecting the collagen-producing tissues.     

Comparison of ASAT, CK, CK-MB, and LD for the estimation of acute myocardial infarct size in man

The purpose of this study was to set up a simple and reliable procedure for estimating acute myocardial infarct (AMI) size by measuring serum enzymes in a few daily blood samples. Peak enzyme values and estimated infarct size from one, two, or three daily samples of aspartate aminotransferase (ASAT), creatine kinase (CK), CK-MB, and lactate dehydrogenase (LD) were compared with the extent of myocardial necrosis measured at autopsy in 22 patients who died from AMI. The correlation between the extent of the necrosis measured and peak serum enzymes from one daily blood sample was highest for CK-MB (r = 0.78) and LD (r = 0.73) compared to CK (r = 0.68) and ASAT (r = 0.67). To obtain a significant correlation, however, two patients had to be excluded from the ASAT and LD analyses. No significant improvement was obtained by more frequent blood sampling. Estimation of infarct size did not improve the correlation significantly for any enzyme, although the coefficient of correlation for CK-MB increased slightly (r = 0.83). Serum CK-MB determination provides a semiquantitative estimate of infarct size, but the other enzymes may give erroneous estimates owing to lesser cardiospecificity.     

Hepatotoxicity of oral and intravenous voriconazole in relation to cytochrome P450 polymorphisms

OBJECTIVES: Voriconazole, like all other antifungals of the azole group, is potentially hepatotoxic. A large interpatient variability of liver enzyme elevations during oral or intravenous (iv) voriconazole administration is observed. This interpatient variability may be explained by differences in voriconazole metabolism because of cytochrome P450 polymorphisms. We examined the relationship between cytochrome P450 polymorphisms and hepatotoxicity in immunocompromised patients predominantly receiving oral formulations of voriconazole. METHODS: In a single institution retrospective study of 86 immunocompromised patients receiving oral (n = 74) or iv (n = 12) voriconazole, we studied the influence of cytochrome P450 polymorphisms (CYP2C19, CYP2C9 and CYP3A5) on the maximum bilirubin and serum liver enzyme levels [alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), serum aspartate aminotransferase and serum alanine aminotransferase] and their respective common toxicity criteria scores (CTC-scores). RESULTS: Median serum bilirubin as well as the level of all other liver enzymes increased during voriconazole treatment. A decline in CTC-score was observed in zero (0%) to six (7%) patients; an increase in CTC-score was demonstrated in 36 (42%) to 54 (63%) patients. No statistically significant differences in maximum value or maximum increase of liver enzymes or CTC-score in relation to cytochrome P450 polymorphisms were observed. Only a trend towards higher maximum CTC-score of GGT for wild-type of CYP2C9 was observed (P = 0.046). CONCLUSIONS: No significant relationship between CYP2C9, CYP2C19 or CYP3A5 polymorphisms and serum liver enzyme levels was observed in patients treated with voriconazole.     

高功率脉冲微波对心肌酶谱的影响

目的研究高功率脉冲微波( high power pulse microwave ,HPPM)辐照对心肌酶谱的影响. 方法以实验犬 30只和离体培养原代乳鼠心肌细胞为对象,检测 HPPM辐照后不同时间点动物血清和细胞培养液中天门冬氨酸氨基转移酶、乳酸脱氢酶、乳酸脱氢酶同工酶、肌酸激酶、肌酸激酶同工酶、羟丁酸脱氢酶和碱性磷酸酶活性的变化. 结果HPPM辐照后,出现以酶活性显著降低为主的心肌酶谱紊乱.实验犬以肌酸激酶的变化最为敏感,于辐照后 6 h～ 1个月 [辐照后 6, 24 h,3 d,1, 2周, 1个月实验犬的肌酸激酶分别为( 796.9± 756.70) ,(287.8± 274.87),(367.2± 241.16),(324.4± 128.81),(336.5± 152.36),(257.5± 105.86),(165.8± 99.00) mmol/L]一直显著降低( t=2.67～ 4.77,P< 0.01);细胞培养液心肌酶多于辐照后 0～ 1 h下降到最低水平, 24 h时大多恢复到正常水平, 48 h时酶活性出现显著性增高. 结论HPPM辐照可明显影响实验动物和心肌细胞的心肌酶活性.     

Standardization of clinical enzyme analysis using frozen human serum pools with values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures

Variation in clinical enzyme analysis, particularly across different measuring systems and laboratories, represents a critical but long-lasting problem in diagnosis. Calibrators with traceability and commutability are imminently needed to harmonize analysis in laboratory medicine. Fresh frozen human serum pools were assigned values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK) and lactate dehydrogenase (LDH) by six laboratories with established International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures. These serum pools were then used across 76 laboratories as a calibrator in the analysis of five enzymes. Bias and imprecision in the measurement of the five enzymes tested were significantly reduced by using the value-assigned serum in analytical systems with open and single-point calibration. The median (interquartile range) of the relative biases of ALT, AST, GGT, CK and LDH were 2.0% (0.6–3.4%), 0.8% (?0.8–2.3%), 1.0% (?0.5–2.0%), 0.2% (?0.3–1.0%) and 0.2% (?0.9–1.1%), respectively. Before calibration, the interlaboratory coefficients of variation (CVs) in the analysis of patient serum samples were 8.0–8.2%, 7.3–8.5%, 8.1–8.7%, 5.1–5.9% and 5.8–6.4% for ALT, AST, GGT, CK and LDH, respectively; after calibration, the CVs decreased to 2.7–3.3%, 3.0–3.6%, 1.6–2.1%, 1.8–1.9% and 3.3–3.5%, respectively. The results suggest that the use of fresh frozen serum pools significantly improved the comparability of test results in analytical systems with open and single-point calibration.     

Biochemical changes in liver, kidney and blood associated with common bile duct ligation

Common bile duct ligation (CBDL) in rats was used to induce liver disease and secondary kidney damage. The biochemical changes in the liver, kidney and plasma were studied at 3, 6, 10 and 21 days post CBDL. The observed alterations climaxed at the 6th day following ligation. Renal, activities of aldolase (ALD), lactic dehydrogenase (LDH), isocitric dehydrogenase (ICDH), sorbitol dehydrogenase (SDH), and alkaline phosphatase (ALP), were lowered in CBDL rats. Further, microsomal Na,K-ATPase and Mg-ATPase and mitochondrial oxidative-phosphorylation were inhibited. In the liver from CBDL rats the activities of aspartate aminotransferase (AST), Mg-ATPase and ALP were elevated, while SDH, ALD, malic dehydrogenase (MDH), LDH, malic enzyme (ME) and Na,K-ATPase were lowered. Plasma enzymes, AST, ALP, MDH, LDH, ALD, acid phosphatase (ACP) and ICDH and the metabolites bile acids, bilirubin, creatinine and urea were elevated. Addition of bile acids or bilirubin at concentrations comparable to those found in the plasma of CBDL rats, to the reaction mixture of the various enzymes strongly inhibited most, particularly mitochondrial oxidative phosphorylation. High concentrations of these substances in the blood may explain the development of renal failure during liver disease and its reversibility when liver function returns to normal.