RESUMEN
Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article we summarize our previously published research, which assessed the value of myocyte injury, vascular inflammation, hemostatic, and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, we measured heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein-A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT-proBNP, and peak cTnT were independent predictors of 1-year death/MI. Our research demonstrated that, in patients presenting within 4 hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification.
Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/metabolismo , Biomarcadores/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/metabolismo , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/mortalidad , Proteína C-Reactiva/metabolismo , Ligando de CD40/sangre , Dolor en el Pecho/etiología , Diagnóstico Precoz , Proteína 3 de Unión a Ácidos Grasos , Proteínas de Unión a Ácidos Grasos/sangre , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Glucógeno Fosforilasa de Forma Encefálica/sangre , Humanos , Metaloproteinasa 9 de la Matriz/sangre , Análisis Multivariante , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Peroxidasa/sangre , Valor Predictivo de las Pruebas , Proteína Plasmática A Asociada al Embarazo/metabolismo , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Troponina T/sangreRESUMEN
BACKGROUND: Reduced high-density lipoprotein cholesterol (HDL-C) concentration is considered to be an independent risk factor for cardiovascular morbidity and mortality. Fibrates are useful in managing dyslipidaemia; reports highlight an expected increase in HDL-C of 10-15% in conjunction with falls in plasma triglycerides of approximately 30%. Despite this, there are several reported cases of paradoxical decreases in HDL-C caused by fibrate treatment. AIM: To report the second largest observational study to date. METHODS: Fenofibrate use at a regional lipid clinic was associated with reductions in HDL-C in a considerable proportion of patients, necessitating cessation of the medication. In view of this, characteristics of the first 94 patients to be given fenofibrate were retrospectively analysed, and comparisons were made between those whose profiles responded as expected and those experiencing paradoxical decreases in HDL-C. RESULTS: 94 patients (57 male; mean (SD) age 52.5 (12.5) years; mean (SD) body mass index 28.9 (4.5) kg/m2) were assessed. After 8-12 weeks on daily fenofibrate (200 mg micronised or equivalent), 43 of the patients (46%) showed a paradoxical decrease in HDL-C (in nine the decrease was >50% from baseline). When responses to fenofibrate were compared against baseline variables, there were no significant differences between groups other than a higher baseline HDL-C (p = 0.045) in patients responding appropriately. CONCLUSIONS: Fenofibrate was associated with a reduction in HDL-C in almost half the patients studied. This is substantially more than in most studies reported to date. Other HDL-C-raising strategies need to be considered in these patients, and the mechanisms need to be explored.
Asunto(s)
HDL-Colesterol/sangre , Dislipidemias/sangre , Fenofibrato/efectos adversos , Hipolipemiantes/efectos adversos , Adulto , Anciano , Colesterol/sangre , Quimioterapia Combinada , Dislipidemias/tratamiento farmacológico , Femenino , Fenofibrato/uso terapéutico , Humanos , Hipolipemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Triglicéridos/sangreRESUMEN
BACKGROUND: Few studies have examined the effect of alcohol consumption on total homocysteine (tHcy) concentrations. AIM: To assess the effect of an 8-week intervention with vodka or red wine on plasma tHcy and B vitamin concentrations in healthy male volunteers. To assess the effect on tHcy according to methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. DESIGN AND METHODS: A randomized controlled crossover intervention study measuring tHcy and serum folate and vitamin B(12) concentrations was conducted in 78 male subjects (21-70 years). Following a 2-week washout period during which no alcohol was consumed, all subjects consumed 24 g alcohol (either 240 ml red wine or 80 ml vodka)/day for a 2-week period. Following a further 2-week washout, participants consumed the alternate intervention for 2 weeks. RESULTS: A significant increase in plasma tHcy was observed after the 2-week red wine intervention (5%, P = 0.03), and a non-significant increase in tHcy with vodka intervention (3%, P = 0.09). When the two interventions were compared, the change in tHcy did not differ between the vodka and red wine interventions (P = 0.57). There were significant decreases in serum vitamin B(12) and folate concentrations, and this decrease did not differ between interventions. The increase in tHcy observed in both interventions did not vary by MTHFR 677C>T genotype. CONCLUSION: A 2-week alcohol intervention resulted in a decrease in folate and vitamin B(12) status and an increase in plasma tHcy. The effect of alcohol intervention on tHcy, folate and vitamin B(12) concentrations did not differ between the red wine and vodka intervention groups.
Asunto(s)
Consumo de Bebidas Alcohólicas/metabolismo , Ácido Fólico/metabolismo , Homocisteína/metabolismo , Vitamina B 12/metabolismo , Adulto , Anciano , Estudios Cruzados , Genotipo , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/sangre , Persona de Mediana Edad , Adulto JovenRESUMEN
Amyloids are filamentous protein deposits ranging in size from nanometres to microns and composed of aggregated peptide beta-sheets formed from parallel or anti-parallel alignments of peptide beta-strands. Amyloid-forming proteins have attracted a great deal of recent attention because of their association with over 30 diseases, notably neurodegenerative conditions like Alzheimer's, Huntington's, Parkinson's, Creutzfeldt-Jacob and prion disorders, but also systemic diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease) and type II diabetes. These diseases are all thought to involve important conformational changes in proteins, sometimes termed misfolding, that usually produce beta-sheet structures with a strong tendency to aggregate into water-insoluble fibrous polymers. Reasons for such conformational changes in vivo are still unclear. Intermediate aggregated state(s), rather than precipitated insoluble polymeric aggregates, have recently been implicated in cellular toxicity and may be the source of aberrant pathology in amyloid diseases. Numerous in vitro studies of short and medium length peptides that form amyloids have provided some clues to amyloid formation, with an alpha-helix to beta-sheet folding transition sometimes implicated as an intermediary step leading to amyloid formation. More recently, quite a few non-pathological amyloidogenic proteins have also been identified and physiological properties have been ascribed, challenging previous implications that amyloids were always disease causing. This article summarises a great deal of current knowledge on the occurrence, structure, folding pathways, chemistry and biology associated with amyloidogenic peptides and proteins and highlights some key factors that have been found to influence amyloidogenesis.
Asunto(s)
Amiloide/química , Péptidos/química , Proteínas/química , Animales , Cisteína/química , Humanos , Concentración de Iones de Hidrógeno , Sustancias Macromoleculares , Modelos Moleculares , Conformación Molecular , Enfermedades Neurodegenerativas/metabolismo , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Electricidad EstáticaRESUMEN
Troponins T and I are highly sensitive markers of myocardial injury. However, non-cardiac disorders, such as pulmonary embolism, renal failure, subarachnoid haemorrhage, sepsis, eclampsia, chemotherapy, and inflammatory muscle conditions (dermatomyositis and polymyositis), can also result in raised serum troponin concentrations. This article describes two cases that occurred within a month of each other in Craigavon Area Hospital, whereby conditions unrelated to myocardial ischaemia resulted in raised concentrations of cardiac markers. The first patient, in retrospect, underwent unnecessary investigation as an inpatient in the cardiac ward. Experience gained from this case led to more appropriate consultation and management of the second patient.
Asunto(s)
Dermatomiositis/diagnóstico , Polimiositis/diagnóstico , Troponina T/sangre , Adulto , Biomarcadores/sangre , Forma MB de la Creatina-Quinasa/sangre , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Hepatoerythropoietic porphyria (HEP) is an uncommon inherited cutaneous porphyria, related to porphyria cutanea tarda, that results from severe uroporphyrinogen decarboxylase (UROD) deficiency. It is characterized clinically by the onset in early childhood of severe lesions on sun-exposed skin. We describe a man aged 38 years with an unusually mild form of the disease that started in his early teens. Our data confirm that homozygosity for the F46L mutation in the UROD gene causes a mild form of HEP and show that this genotype may be associated with a unique urinary porphyrin excretion pattern in which pentacarboxylic porphyrin predominates.
Asunto(s)
Mutación Missense , Porfiria Hepatoeritropoyética/genética , Porfirinas/orina , Uroporfirinógeno Descarboxilasa/genética , Adulto , Homocigoto , Humanos , MasculinoRESUMEN
The merits and limitations of traditional and new markers for alcohol abuse (and abstinence) are critically examined for detection and monitoring of alcoholics, hazardous drinkers and binge drinkers. The traditional markers discussed include gamma-glutamyltransferase (GGT), aspartate and alanine aminotransaminases (AST, ALT) and mean corpuscular volume (MCV); new markers include mitochondrial AST, carbohydrate-deficient transferrin (CDT), serum/urine 5-hydroxytryptophol, beta-hexosaminidase and acetaldehyde adducts. The strengths and weaknesses of several of the self-reporting screening questionnaires are also explored. No laboratory test is reliable enough on its own to support a diagnosis of alcoholism. Sensitivities and specificities vary considerably and depend on the population concerned. GGT continues to remain the test that combines greatest convenience and sensitivity: its diagnostic accuracy can be enhanced by combination with other traditional markers (AST, ALT, MCV). None of the newer markers offers significant advantage, although CDT seems to be better at monitoring patients for increased alcohol consumption or progress towards abstinence.
Asunto(s)
Alcoholismo/diagnóstico , Templanza , Transferrina/análogos & derivados , Acetaldehído/sangre , Alanina Transaminasa/sangre , Consumo de Bebidas Alcohólicas , Intoxicación Alcohólica/diagnóstico , Aspartato Aminotransferasas/sangre , Biomarcadores/análisis , Técnicas de Laboratorio Clínico , Índices de Eritrocitos , Etanol/análisis , Humanos , Hidroxitriptofol/análisis , Encuestas y Cuestionarios , Transferrina/análisis , beta-N-Acetilhexosaminidasas/sangre , gamma-Glutamiltransferasa/sangreRESUMEN
We examined the effect of halothane or isoflurane anaesthesia on hepatic function in 30 ASA I-III patients aged 18-70 yr undergoing lumbar discectomy. Hepatic function was assessed before anaesthesia, at the end of surgery, and at 3, 6, 24 and 48 h after surgery using routine enzyme tests of hepatic function and mitochondrial aspartate transaminase (mAST) activity. Although serum mAST activities increased after surgery in both groups of patients, these increases were statistically significantly greater in the group that received halothane. The groups were similar with regard to other tests of hepatic function. Calculation of the ratio of serum enzyme activities compared to baseline values suggested that mAST is a sensitive marker of anaesthetic-induced hepatic injury.
Asunto(s)
Anestésicos por Inhalación/farmacología , Aspartato Aminotransferasas/sangre , Halotano/farmacología , Isoflurano/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Adolescente , Adulto , Anciano , Aspartato Aminotransferasas/fisiología , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Mitocondrias Hepáticas/enzimología , Factores de TiempoRESUMEN
The reaction between aryl aldehydes, the macrocyclic ligand 6-methyl-1,4,8,11-tetraazacyclotetradecane-6-amine (L1), and NaBH3CN produces the corresponding benzyl-substituted ligands in good yield. Copper(II) complexes of the ligands derived from salicylaldehyde (L2), p-hydroxybenzaldehyde (L4), and p-carboxybenzaldehyde (L5) were structurally characterized: [CuL2](ClO4)2.3H2O (monoclinic, P2(1)/c, a = 11.915(6) A, b = 13.861(2) A, c = 17.065(8) A, beta = 102.14(2) degrees, Z = 4); [CuL4](ClO4)2 (monoclinic, P2(1)/n, a = 9.550(3) A, b = 17.977(2) A, c = 14.612(4) A, beta 96.76(1) degrees, Z = 4), and [CuL4](ClO4)2 (monoclinic, P2(1)/n, a = 9.286(2) A, b = 11.294(1) A, c = 23.609(8) A, beta 93.68(1) degrees, Z = 4). Conjugation of several CuII complexes to a protein (bovine serum albumin) has been pursued with a view to the application of these macrocycles as bifunctional chelating agents in radioimmunotherapy.
Asunto(s)
Compuestos Heterocíclicos/química , Radioinmunoterapia , Cristalografía por Rayos X , Modelos Moleculares , Proteínas/químicaRESUMEN
The reaction between alkyl or aryl aldehydes and macrocyclic ligands with pendant amine groups produced imidazolidine-containing bi- or tricyclic ligands. The copper complexes of three of these ligands were structurally characterized: [CuL3Cl].3H2O (triclinic, P1, a = 10.041(2) A, b = 10.172(1) A, c = 11.202(1) A, alpha = 92.07(1) degrees, beta = 96.76(2) degrees, gamma = 92.99(1) degrees, Z = 2), [Cu(H2L4)Cl]Cl.2H2O (monoclinic, P2(1)/n, a = 15.159(5) A, b = 10.645(1) A, c = 19.094(6) A, beta = 93.78(1) degrees, Z = 4), [CuL5].2H2O.NaNO3 (monoclinic, P2(1)/n, a = 10.649(8) A, b = 7.261(2) A, c = 15.25(1) A, beta = 94.77(4) degrees, Z = 2). The conformational rigidity and stereochemical activity of these macrocycles and their complexes are discussed in comparison with close analogues.
RESUMEN
Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy and this may include abnormalities in growth characteristics and the extracellular matrix. As the actual mechanisms by which glucose induces VSMC dysfunction remain unclear, the aim of this study was to assess the potential role of glucose-induced oxidative stress. Porcine aortic VSMCs were cultured for 10 days in either 5 mmol/l normal glucose or 25 mmol/l D-glucose (high glucose). There was evidence of oxidative stress as indicated by a 50% increase in intracellular malondialdehyde (p < 0.05), increased mRNA expression of CuZn superoxide dismutase and Mn superoxide dismutase (by 51% and 37% respectively, p < 0.01) and a 50% decrease in glutathione in 25 mmol/l D-glucose (p < 0.001). Growth was increased by 25.0% (p < 0.01). mRNA expression of extracellular matrix proteins (collagens I, III, IV and fibronectin) was not altered by high glucose in these experimental conditions. Repletion of glutathione with N-acetyl L-cysteine (1 mmol/l) in VSMC grown in high glucose was associated with reduction in malondialdehyde and restored growth to that of normal glucose. The water soluble analogue of vitamin E, Trolox (200 mumol/l), reduced malondialdehyde concentrations, but had no effect on glutathione depletion or the increased growth rate seen with high glucose. The addition of buthionine sulphoximine (10 mumol/l) to VSMC cultured in normal glucose reduced glutathione, increased malondialdehyde and increased growth to a similar extent as that found in high glucose alone. These results suggest that thiol status, rather than lipid peroxides, is a key factor in modulating VSMC growth and that mRNA expression of extracellular matrix proteins is not increased in VSMC under conditions of glucose-induced oxidative stress.
Asunto(s)
División Celular , Matriz Extracelular/metabolismo , Glucosa/farmacología , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Estrés Oxidativo , Animales , Antioxidantes/farmacología , Aorta , Apoptosis , Butionina Sulfoximina/farmacología , Células Cultivadas , Cromanos/farmacología , Inhibidores Enzimáticos/farmacología , Expresión Génica , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Malondialdehído/metabolismo , ARN Mensajero/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , PorcinosRESUMEN
Free radical-mediated damage to vascular cells may be involved in the pathogenesis of diabetic vasculopathy. The aim of this study was to compare the extent of glucose-induced oxidative stress in both vascular smooth muscle cells (VSMCs) and pericytes and the effect on antioxidant enzyme gene expression and activities. Porcine aortic VSMC and retinal pericytes were cultured in either 5 or 25 mmol/l glucose for 10 days. Intracellular malondialdehyde (MDA) was measured as a marker of peroxidative damage, and mRNA expression of CuZn-SOD, MnSOD, catalase, and glutathione peroxidase (GPX) were measured by Northern analysis. Glutathione (GSH) was also measured. There was a significant increase in MDA in VSMCs in 25 mmol/l glucose (1.34 +/- 0.11 vs. 1.88 +/- 0.24 nmol/mg protein, 5 vs. 25 mmol/l D-glucose, mean +/- SE, n = 15, P < 0.01), but not in pericytes (0.38 +/- 0.05 vs. 0.37 +/- 0.05 nmol/mg protein, n = 11). There was a significant decrease in GSH in both cell types (VSMC, 1.40 +/- 0.13 vs. 0.69 +/- 0.12 nmol/mg protein, n = 15, P < 0.001; pericytes, 1.97 +/- 0.17 vs. 0.94 +/- 0.16 nmol/mg protein, n = 11, P < 0.001). mRNA expression of CuZnSOD and MnSOD was increased only in VSMCs (by 58.5 +/- 8.1 and 41.0 +/- 6.9%, respectively, n = 8, P < 0.01). CuZnSOD protein was increased by approximately 120% (P < 0.00001). None of the antioxidant enzyme activities was altered between 5 and 25 mmol/l glucose in either cell type. Both MnSOD activities and GSH concentrations were higher in pericytes compared with VSMC under basal (5 mmol/l) conditions (P < 0.05 and P < 0.02, respectively). These results demonstrate glucose-induced reduction of GSH in both cells, but only in VSMC is there evidence of oxidant damage in the form of lipid peroxidation, implying significant differences in intracellular responses to glucose between contractile cells in the macro- and microvasculature.
Asunto(s)
Glucosa/farmacología , Músculo Liso Vascular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Retina/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Aorta/citología , Aorta/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Microcirculación/efectos de los fármacos , Músculo Liso Vascular/citología , Retina/citología , PorcinosRESUMEN
L-Dopa has long been the mainstay of therapy for Parkinson's disease but its long-term shortcomings, principally uncoordinated, spasmodic or irregular movements (dyskinesias) and fluctuating control of motor symptoms (on/off fluctuations), are well documented. The postulated neuroprotective properties of L-deprenyl, often used as an adjunct to L-dopa, are under scrutiny and doubts have also been raised regarding its safety. Alternative therapeutic approaches are clearly needed. In this review, Jim Hagan, Derek Middlemiss, Paul Sharpe and George Poste outline some new approaches to treatment, with an emphasis on novel, selective dopamine receptor agonists. In addition, Parkinson's disease is commonly thought to be caused by the neurotoxic effects of an unidentified agent but recent data indicate a greater genetic component than previously recognized. Developments in the genetics of Parkinson's disease may provide the key to the next generation of therapeutics.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Humanos , Enfermedad de Parkinson/fisiopatologíaRESUMEN
The International Spinal Research Trust (ISRT) has selected a sub-set of the key molecular and cellular events underlying spinal injury and nerve regeneration, to be focus of their funding and other means of research support. These priority targets are (i) to understand and to minimise the damage caused by spinal injury and the resulting inflammatory and fibrotic events, in order to prevent the establishment of a post-acute situation that is ill-placed for regeneration; and (ii) to understand and then to manipulate the integrated environment for regrowth that is created by the interplay of soluble and matrix- or membrane-associated factors, both trophic and inhibitory. Investigation and, ultimately, exploitation of these targets requires the development of standardised and representative animal models and the application of quantitative methods for assessing functional re-innervation. The ISRT will also sponsor the networking of different disciplines and technologies to apply the most productive skills to spinal repair.
Asunto(s)
Investigación , Traumatismos de la Médula Espinal/terapia , Humanos , Modelos Teóricos , Guías de Práctica Clínica como AsuntoRESUMEN
The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.
Asunto(s)
Antioxidantes/metabolismo , Ejercicio Físico/fisiología , Aptitud Física/fisiología , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Estudios Transversales , Femenino , Radicales Libres , Estado de Salud , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Irlanda del Norte , Factores Sexuales , Fumar/metabolismo , Estadísticas no ParamétricasRESUMEN
Excessive alcohol consumption is a major health problem in the UK leading to both serious morbidity and mortality. This study compared newer potential biochemical markers of excessive alcohol consumption [carbohydrate-deficient transferrin (CDT), mitochondrial AST (mAST) and alpha glutathione-s-transferase (alpha-GST)] with conventional markers (AST, ALT, GGT, MCV). Patients (n = 85) were enrolled in the study and subdivided into several groups on the basis of alcohol consumption. Patients with non-alcoholic liver disease (NALD) (n = 40) were also enrolled. All the markers, with the exception of the ratio mAST/total AST were significantly higher in heavy drinkers/alcoholics compared to teetotallers/social drinkers (p < 0.05). mAST and AST/ALT ratio were significantly higher in alcoholics compared to NALD (p < 0.01), whereas ALT was higher in the NALD group (p < 0.05). Multivariate discriminant function analysis (Wilks method) demonstrated that the logarithmic functions of AST/ALT ratio and mAST could correctly classify 87.9% of cases into either the alcoholic or NALD groups. ROC plot analysis showed that AST, mAST and GGT were the best markers at distinguishing heavy consumption of alcohol from lesser levels and that AST/ALT ratio and mAST were the best in distinguishing alcoholics from NALD. In conclusion, none of the newer biochemical markers, with the exception of mAST, offers any major advantage over the conventional markers.