Serum Enzyme Tests Research Articles

Anti-diabetic effect of <i>Eucalyptus camaldulensis</i> (Red gum) leaf-supplemented diet in streptozotocin-induced diabetic rats

Purpose: To investigate the potential anti-diabetic effect of supplementing a diet with Eucalyptus camaldulensis leaves in streptozotocin (STZ) induced Wistar rats. 
 Methods: Methanolic extract of E. camaldulensis was screened using gas chromatography-mass spectrometric analysis. After that, eighteen animals were separated into three groups: Group A served as control group. Group B, the diabetic control group, was induced with STZ, and Group C was induced with STZ and fed a 10 % E. camaldulensis leaf-supplemented diet for 14 days. Thereafter, rats were sacrificed, and fasting blood was collected for serum glucose, enzyme and protein activity tests. Organs were excised for biochemical and histological analysis. 
 Results: The GC-MS fingerprint identified 17 constituents, with 2-hydroxy carbazole being the most abundant. Rats on the E. camaldulensis leaf-based diet for 14 days exhibited a significant decrease (p < 0.05) in serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, albumin, total bilirubin, urea, and creatinine concentrations compared to diabetic controls. Insulin levels significantly increased (p < 0.05). Additionally, the E. camaldulensis diet led to a significant decrease in serum lipid profile levels but increased high-density lipoprotein cholesterol (HDL-C). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased significantly, while malondialdehyde levels decreased significantly (p < 0.05). Histopathology revealed positive effects on hepatocytes, acini, pancreatic duodenal lymphoid activation, islets of Langerhans resurgence, and normal kidneys. 
 Conclusion: Eucalyptus camaldulensis leaf-supplemented diet demonstrates anti-diabetic, hypolipidemic and antioxidant enzyme activities. Carbazole identified by GC-MS may be the potential anti-diabetic and hypolipidemic agent in E. camaldulensis leaf-based diet.

Multifunctional photo-responsive liposomes for tumor imaging and phototherapy to enhance the antitumor efficacy and reduce the hepatotoxicity of methotrexate

Methotrexate (MTX) is a chemotherapy drug widely applied in clinical treatment for various tumors. However, side effects caused by MTX greatly affect the therapeutic efficacy. Hence, photo-triggered release liposomes were constructed by amphiphilic photosensitizers ZnPc(PEG)4 and phospholipid materials DPPC to load MTX for improved antitumor effect. It was demonstrated that ZnPc(PEG)4 integrated into lipid layers endowed final product ZnPc(PEG)4:MTX@LiPOs improved stability. ZnPc(PEG)4:MTX@LiPOs was verified to have excellent characteristics in terms of photo-triggered release, ROS generation and heat production. In particular, cellular experiments indicated that ZnPc(PEG)4:MTX@LiPOs had synergistic cytotoxicity of phototherapy and chemotherapy. The cell uptake assay demonstrated that the internalization of MTX into tumor cells was significantly increased by the encapsulation of ZnPc(PEG)4@LiPOs. ZnPc(PEG)4:MTX@LiPOs was confirmed to possess excellent tumor targeting reflected in faster accumulation, higher drug level and longer retention at tumor sites than free ZnPc(PEG)4. In addition, ZnPc(PEG)4:MTX@LiPOs had significantly enhanced tumor inhibition rate. What's more, liver histopathology and serum enzyme tests indicated that ZnPc(PEG)4:MTX@LiPOs had distinctly reduced hepatotoxicity than MTX. The constructed liposomes with photo-triggered release can be applied to deliver other chemotherapy drugs for synergistic antitumor ability and reduced side effect.

Investigating Correlation of Lower Extremity Muscle Compartment Syndrome with Muscle Related Serum Enzyme Tests: Is any Reliable Biomarker?

Introduction Lower extremity trauma with producing acute Muscle Compartment Syndrome (MCS) is a known devastating complication require fast diagnosis and repair for precluding its debilitating outcome. The least result of progressive and insidious increased intra compartment pressure is relative

One-year Treatment of Morpholino Antisense Oligomer Improves Skeletal and Cardiac Muscle Functions in Dystrophic mdx Mice

Antisense therapy has been successful to skip targeted dystrophin exon with correction of frameshift and nonsense mutations of Duchenne muscular dystrophy (DMD). Systemic production of truncated but functional dystrophin proteins has been achieved in animal models. Furthermore, phase I/II clinical trials in United Kingdom and the Netherlands have demonstrated dystrophin induction by local and systemic administrations of antisense oligomers. However, long-term efficacy and potential toxicity remain to be determined. The present study examined 1-year systemic effect of phosphorodiamidate morpholino oligomers (PMO) treatment targeting mutated dystrophin exon 23 in mdx mice. PMO induced dystrophin expression dose-dependently and significantly improved skeletal muscle pathology and function with reduced creatine kinase (CK) levels by a regimen of 60 mg/kg biweekly administration. This regimen induced <2% dystrophin expression in the heart, but improved cardiac functions demonstrated by hemodynamics analysis. The results suggest that low levels of dystrophin induction may be able to provide detectable benefit to cardiac muscle with limited myopathy. Body weight, serum enzyme tests, and histology analysis showed no sign of toxicity in the mice treated with up to 1.5 g/kg PMO for 6 months. These results indicate that PMO could be used safely as effective drugs for long-term systemic treatment of DMD.

Aluminum‐mediated metabolic changes in rat serum and urine: A proton nuclear magnetic resonance study

The toxic effects of Al(3+) have been studied in 90-days AlCl(3) orally treated male albino rats (n = 7) using (1)H NMR spectroscopy-based metabolic profile of rat serum and urine, serum enzyme tests, behavioral impairment, and histopathology of kidney and liver. Metabolic profile of 90-days Al(3+)-treated rat sera showed significantly elevated levels of alanine, glutamine, beta-hydroxy-butyrate, and acetoacetate and significantly decreased level of acetone when compared with that of control rats. However, metabolic profile of 90-days Al(3+)-treated rat urine showed significantly decreased levels of citrate, creatinine, allantoin, trans-aconitate, and succinate and significantly increased level of acetate when compared to control rats. The overall perturbations observed in the metabolic profile of serum and urine demonstrate the impairment in the tricarboxylic acid cycle, liver and kidney metabolism, which was further reinstated by clinical chemistry and histopathological observations. Moreover, "in vivo" behavioral impairment has also been observed as the indication of aluminum neurotoxicity.

Assessing liver function

This is a review on the techniques for assessing liver function in critically ill patients. Actually, there is no ideal real-time and bedside technique for assessing liver function in critically ill patients. Though not allowing to differentiate between liver blood flow and cell function, dynamic tests, that is indocyanine green plasma disappearance rate and lidocaine metabolism (monoethylglycinxylidide test), are superior, however, to static tests. Recently, the indocyanine green plasma disappearance rate, which nowadays can be measured reliably by a transcutaneous system in critically ill patients, was confirmed to correlate well with indocyanine green clearance. In general, the indocyanine green plasma disappearance rate is superior to bilirubin, which is still used as a marker of liver function, and comparable or even superior to complex intensive care scoring systems in terms of outcome prediction. Furthermore, indocyanine green plasma disappearance rate is more sensitive than serum enzyme tests for assessing liver dysfunction and early improvement in the indocyanine green plasma disappearance rate after onset of septic shock is associated with better outcome. Since no ideal tool is currently available, dynamic tests such as indocyanine green plasma disappearance rate and monoethylglycinxylidide test may be recommended for assessing liver function in critically ill patients. The indocyanine green plasma disappearance rate has the advantage, however, of being measurable noninvasively at the bedside and providing results within a few minutes.

Hepatic Gene Expression Response to Acute Indomethacin Exposure

Rising morbidity and mortality related to the use of NSAIDs has led to the withdrawal of some of these agents and reconsideration of the adverse effects and usage paradigms of commonly available NSAIDs. Our objective in this study was to assay molecular indicators of acute hepatic injury associated with the administration of indomethacin, a prototypical NSAID, metabolized by the liver that undergoes enterohepatic circulation with associated gastrointestinal adverse effects. Analysis of gene expression, using high-throughput, ADME (absorption, distribution, metabolism, excretion)-specific microarrays, was performed on RNA extracted from the livers of control or indomethacin treated rats, in parallel with serum enzyme tests and histological analysis of paraffin-embedded liver specimens. Male Sprague-Dawley rats (n = 45) were administered intraperitoneal injections of indomethacin for 3 days at the recommended normal dose (6.7 mg/kg), indomethacin at a high dose (20 mg/kg) or vehicle alone (controls). Upon termination of the study on day 4, serum gamma-glutamyl transferase activity and alkaline phosphatase/alanine aminotransferase ratios were significantly elevated in both high- and normal-dose cohorts compared with vehicle-treated animals. Diffuse microvascular steatosis was present in hepatic serial sections obtained from all animals subjected to the high-dosage regimen. High-resolution microarray analysis (six replicates/gene/animal) identified 256 genes, after outlier removal, in 17 functional classifications that were significantly altered by the high, but not by the normal dosage. These included depression of 10 of 11 cytochrome P450 genes (2B3, 2C70, 1A2-P2, 4F1, 2E1, 3A1, 2F1, 3AP7, 2C11, phenobarb-inducible P6) and 7 of 9 genes involved in the response to reactive oxygen species (e.g. glutathione reductase, glutathione transferase, and superoxide dismutase). Of 16 genes associated with toxin removal, nine exhibited significantly decreased transcripts. There was a marked shift away from lipid metabolism (decreased expression of eight genes) towards glucose utilization associated with steatosis. Despite the compromise of detoxification programs and a shift in metabolic substrate utilization, a compensatory remodeling response was activated, including genes for metalloproteases (ADAM10, MMP10, MMP11), integrins (integrin alpha-1 and alpha-E1), and extracellular matrix molecules (platelet/endothelial cell adhesion molecule-1 and heparan sulfate proteoglycan, perlecan), as well as transcripts associated with cell proliferation. The expression levels of only five genes were significantly altered among animals receiving the normal indomethacin dosage. These data confirmed that even brief exposure to indomethacin altered serum enzymatic activities and that high levels significantly altered gene expression in the liver and hepatic histology (by interfering with the clearance of toxins and xenobiotic substrates) and the regulation of basal metabolism.

Targeting urokinase-type plasminogen activator receptor on human glioblastoma tumors with diphtheria toxin fusion protein DTAT.

The prognosis for patients with brain cancer is poor, and new therapies are urgently needed. Recombinant toxic proteins that specifically target tumor cells appear to be promising. Urokinase-type plasminogen activator (uPA) receptor (uPAR) is expressed on the surface of glioblastoma and some other tumor cells and endothelial cells. We synthesized a recombinant fusion protein, DTAT, which contains the catalytic portion of diphtheria toxin (DT) for cell killing fused to the noninternalizing amino-terminal (AT) fragment of uPA, and investigated its effectiveness in targeting uPAR-positive tumor cells. In vitro cytotoxicity of DTAT was measured by cell proliferation assays. For in vivo studies, athymic nude mice (four to five animals/group) bearing uPAR-expressing human glioblastoma (U118MG) cell-induced tumors were injected with DTAT or control protein. Tumor volume was assessed over time, and differences between treatments were analyzed by Student's t test. Effects of DTAT on body organ systems were evaluated in normal, tumor-free C57BL/6 mice histologically and functionally by serum enzyme tests. All statistical tests were two-sided. In vitro, DTAT was highly potent and selective in killing uPAR-expressing glioblastoma cells (U118MG, U373MG, and U87MG) and human umbilical vein endothelial cells. In vivo, compared with mice treated with control proteins, DTAT caused a statistically significant (P =.05) regression of small U118MG cell-induced tumors in all mice. Control fusion proteins that did not react with glioblastoma cells had no effect on tumor growth. DTAT given to tumor-free C57BL/6 mice had little effect on kidney, liver, heart, lung, and spleen histologies. Serum analysis in the same mice showed no elevation in blood urea nitrogen, indicating lack of effect on kidney function but a statistically significant (P =.046), albeit non-life-threatening, elevation in liver alanine aminotransferase levels. DTAT may have potential for intracranial glioblastoma therapy because of its ability to target tumor cells and tumor vasculature simultaneously and its apparent lack of systemic effects.

Hepatotoxicity in drug development: detection, significance and solutions

Despite considerable progress in the understanding of the mechanism of liver toxicity we are not yet able to design non-hepatotoxic molecules rationally. Also, there is no “universal” in vitro primary screening approach for early identification of hepatotoxic molecules. In most cases hepatotoxicity is detected at later stages of drug development in animal toxicity studies or clinical trials. Although the liver is the most common target organ for drug candidates in animal toxicity studies, hepatotoxicity rarely leads to cessation of drug development during the preclinical phase. Indeed, contrary to other target organs, liver toxicity is usually reversible and can be monitored in man by sensitive serum enzyme tests. Therefore in many cases a compound found hepatotoxic in an animal species will be tested in man for a definitive assessment of its hepatotoxic potential. Liver toxicity in man may be acceptable when a drug has major therapeutic potential. In this situation mechanistic studies are essential to assess the risk in man and in some cases to identify protective agents. When liver toxicity leads to project termination a secondary screening approach may be envisaged if biologically active analogs are available.

Biochemical tests in the diagnosis of chronic pancreatitis and in the evaluation of pancreatic insufficiency

Chronic pancreatitis (adults) and cystic fibrosis (children) are the most common diseases leading to exocrine pancreatic insufficiency that, when reduced to <5% of normal function, is characterised by steatorrhoea. The pathogenesis of the former condition is outlined, and recent concepts are emphasized. Biochemical tests to detect pancreatic insufficiency and to identify pancreatic disease as the cause of steatorrhea include: serum enzyme tests (lipase, amylase, trypsin); stool chymotrypsin; isotopic tests based upon the assimilation of [ 14C] lipids and starch or excretion of the isotope as breath CO 2, as well as the dual-labelled Schilling test; oral function tests utilising substrates hydrolysed by pancreatic enzymes such as benzoyl tyrosyl- p-aminobebzoic acid and fluorescein dilaurate; and duodenal intubation studies following meal-induced or hormonal stimulation of the pancreas. The rationale for these tests and the cumulative clinical experience of their utility are reviewed. A recommended diagnostic strategy is briefly presented. The role of various biochemical procedures to evaluate the efficacy of pancreatic enzyme replacement therapy is also described.

Differential Diagnosis of Patients with Abnormal Serum Creatine Kinase Isoenzymes

For the diagnosis of myocardial injury, particularly AMI, CK-MB has become the gold standard. Changing CK-MB activities in serially collected blood from patients with suggestive signs and symptoms of AMI is almost pathognomonic for infarction. Nevertheless, an increased CK-MB cannot be equated with AMI owing to the many other types of inflammatory, traumatic, and miscellaneous forms of injury to the heart and the trace activities of CK-MB in skeletal muscle. Other enzyme tests for AMI are less efficient. In order of decreasing efficiency, the tests are CK-MB, CK, LD1 greater than LD2 or LD1/LD2 greater than 0.76, AST and LD; the latter two tests are not cost effective and add little or nothing when results for CK-MB, CK, and LD isoenzymes are available. The value of the isoforms of CK-MM and CK-MB remains to be established. Early evidence suggests that they could be helpful in the diagnosis of AMI; however, owing to the greater technical difficulties in performing these tests, their use is necessarily more restricted. Enzyme testing on admission and then every 12 hours for 2 days is sufficient and effective in making the initial diagnosis. In patients presenting early after an attack, CK and CK-MB are often normal. Decisions on AMI cannot be made on blood tests collected in the emergency department. Clot-lysing agents like streptokinase, urokinase, and tPA have changed the therapy of AMI dramatically. Enzyme tests clearly separate patients with and without successful therapeutic or spontaneous reperfusion. With successful reperfusion, the uniform finding has been a "washout" phenomenon with significantly earlier peaking times for CK and CK-MB. The isoforms of CK and myoglobin give the earliest peaks after successful reperfusion. With faster turnaround times for these tests, they may become important tools in patient management.

Comparison of serum cardiac specific troponin-I with creatine kinase, creatine kinase-MB isoenzyme, tropomyosin, myoglobin and C-reactive protein release in marathon runners: cardiac or skeletal muscle trauma?

Problems arise in distinguishing skeletal from cardiac muscle trauma on the basis of serum enzyme tests following severe muscle exercise. The contributions of cardiac and skeletal sources have been assessed in eleven marathon runners by measuring pre- and post-race serum levels of cardiac-specific myofibrillar troponin-I together with total creatine kinase, creatine kinase-MB isoenzyme, myoglobin, myofibrillar tropomyosin and C-reactive protein. Total creatine kinase, creatine kinase-MB isoenzyme, tropomyosin and myoglobin were significantly elevated above pre-race levels in all runners between 1 h and 128 h post-race. Neither mean cardiac troponin-I nor C-reactive protein was elevated post-race. Nine out of sixty-three samples fulfilled conventional positive criteria for cardiac muscle damage on the basis of combined creatine kinase and creatine kinase-MB isoenzyme levels. Six runners had one or more positive samples. No samples had levels above twice the upper normal limit for either cardiac troponin-I or C-reactive protein. Correlation analysis of levels in each sample indicated skeletal and not cardiac muscle as the source of raised serum protein.

Effect of benzyl chloride on rat liver functions.

Benzyl chloride (BCL) is extensively used in industry for the manufacture of dyes, perfumes, and pharmaceutical products. A previous study from this laboratory revealed the presence of liver steatosis of the microvesicular type and central focal inflammation in rats following the inhalation of BCL. This study was conducted to investigate the hepatotoxicity of intravenous (iv) BCL in rat. BCL (250, 25, and 0 micrograms/kg) was administered (iv) to rats, and serum enzyme tests were used to evaluate hepatic injury. After 10 min from BCL administration, serum glutamic-pyruvic transaminase and lactic dehydrogenase activities were significantly increased compared to the control group, while the values returned to normal within 1 h from the administration of BCL. Also, ornithine carbamyltransferase enzyme activity was significantly increased and reached a maximum as early as 0.5 h from the administration of BCL. Hepatic excretory function was investigated by the clearance of bromosulfophthalein (BSP) after 0.5 and 24 h from the administration of BCL. The clearance of BSP in both treatments was significantly slower compared to control group throughout the 24 h studied. Furthermore, BCL significantly decreased liver and blood glutathione values. This study revealed that BCL has the potential to cause hepatomalfunction.

Routine serum enzyme tests in the diagnosis of acute myocardial infarction: Cost-effectiveness: Fisher ML, Keleman MH, Collins D, et al Arch Intern Med 143:1541–1543 Aug 1983

Routine serum enzyme tests in the diagnosis of acute myocardial infarction: Cost-effectiveness: Fisher ML, Keleman MH, Collins D, et al Arch Intern Med 143:1541–1543 Aug 1983

Frequency of myocardial injury after blunt chest trauma as evaluated by radionuclide angiography

Seventy-seven patients who had sustained multisystem trauma, including severe blunt chest injury, were prospectively evaluated to assess the frequency of associated traumatic myocardial injury. Traumatic injury to either the right or left ventricle was defined by the presence of discrete abnormalities of wall motion on electrocardiographically gated cardiac scintigraphy in patients without a clinical history of heart disease. Forty-two patients (55%) (Group 1) had focal abnormalities of wall motion; 27 involved the right ventricle, 7 the left ventricle, 7 were biventricular, and 1 involved only the septum. Both the right and left ventricular ejection fractions were significantly (p < 0.01) lower (31 ± 11% and 47 ± 14%, respectively) than those in the 35 traumatized patients without wall motion abnormalities on scintigraphy (Group 2) (49 ± 8% and 58 ± 11%, respectively). Repeat scintigraphic examination in 32 Group 1 patients at a time remote from initial injury showed improvement or resolution of previously defined focal wall motion abnormalities in 27 of 32 patients (84%). The electrocardiogram and serum enzyme tests were insensitive indexes of traumatic myocardial injury when defined by the scintigraphic abnormalities. Thus, severe blunt chest trauma results in a higher frequency of traumatic myocardial injury than heretofore recognized, and frequently involves the anteriorly situated right ventricle.

Routine Serum Enzyme Tests in the Diagnosis of Acute Myocardial Infarction

To determine the cost-effectiveness of routine use of serial SGOT, lactic dehydrogenase (LDH), and LDH isoenzyme determinations in patients with suspected acute myocardial infarction (AMI), 166 consecutive patients admitted to a coronary care unit were prospectively identified and clinical findings analyzed independently using predetermined criteria. Based on chest pain characteristics, ECG, and creatine kinase--MB (CK-MB) results, patients were placed in categories of definite AMI (31%), possible AMI (34%), or AMI excluded (36%). The SGOT and/or LDH patterns were considered positive (ie, suggestive of AMI) in 82% of the patients with definite AMI but only confirmed CK-MB results. Positive SGOT/LDH results yielded new clinically relevant information in only 14 patients (8%). Total charges for SGOT/LDH determinations in these 166 patients totaled $10,938 or approximately $780 for each additional clinically important positive result. When serial ECG and CK-MB results are available, routine serial SGOT/LDH determinations are not justified.

Routine serum enzyme tests in the diagnosis of acute myocardial infarction. Cost-effectiveness

Routine serum enzyme tests in the diagnosis of acute myocardial infarction. Cost-effectiveness

INFARCT AVID (HOT SPOT) MYOCARDIAL SCINTIGRAPHY

Infarct avid scintigraphy has emerged as a noninvasive method for determining the presence, location, and extent of myocardial necrosis secondary to infarction. In the future, it may replace studies such as serum enzyme tests, electrocardiography, and vector cardiography, all of which provide only indirect evidence of these parameters.

Myocardial scintigraphy with infarct-avid tracers

The scintigraphic appearance of infarcted myocardium as an area of increased activity has considerable appeal, since standard techniques, including serum enzyme tests, electrocardiography, and vectorcardiography, provide only indirect evidence of the presence, size, and location of infarcted myocardium. Although these techniques are usually accurate in detecting infarction, the availability of techniques to localize precisely the site of damaged myocardium and the extent of damage is limited. Radiopharmaceuticals that are extracted by normal myocardium, such as potassium and its analogues [1] and radiolabeled fatty acids [2], offer additional help by outlining poorly perfused tissue as regions of decreased tracer concentration in myocardial scans [3]. These radiopharmaceuticals, however, do not permit differentiation of acute infarction and fibrotic or previously infarcted tissue. To overcome these difficulties, investigators have sought agents that accumulate selectively in damaged myocardium.

Serum enzyme tests in diseases of the liver and biliary tree.

Eight serum enzyme tests were performed over a three-year period in 1,147 cases of patients with suspected hepatobiliary disease, of whom 580 had identifiable primary disease of the liver or biliary system. Individually, aminotransferase assays did not provide good discrimination among the various categories of hepatobiliary disease, but when expressed as a ratio a useful degree of discrimination was obtained. Isocitrate dehydrogenase, guanase and glutamate dehydrogenase alone were poor discriminants of the various disease categories studied; combination of the latter enzyme with the aminotransferases in various ratios did not achieve worthwhile improvement. Adenosine deaminase was normal in most patients with extrahepatic obstruction and abnormal in most patients with parenchymal hepatic disease, and is potentially a useful test additional to the aminotransferases in routine diagnosis. 5'-Nucleotidase was more sensitive and specific than alkaline phosphatase in diagnosing hepatobiliary disorders. Abnormalities of all these enzymes were encountered in patients who did not have hepatobiliary disease, most frequently among subjects with cancer, diabetes mellitus, and diseases of the respiratory and cardiovascular systems.