Identification of biomarker panels as predictors of severity in coronary artery disease.

Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo-CII and CIII and Apo-E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP-3 and MMP-9, TIMP-1 and TIMP-2, Apo-CII, Apo-CIII and Apo-E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP-3 and MMP-9 plasma levels in CAD patients were significantly increased (P < 0.001) compared to controls (3.54- and 3.81-fold, respectively). Furthermore, these increments are modulated by CAD severity as well as for Apo-CII and Apo-CIII levels (P < 0.001). TIMPs levels were decreased in CAD versus controls (P < 0.001) and in inverse correlation to MMPs. Standard ROC curve approach showed the importance of panels of biomarkers, including MMP-3, MMP-9, TIMP-1, TIMP-2, Apo-CII and Apo-CIII, for disease aggravation diagnosis. A high area under curve (AUC) value (0.995) was reached for the association of MMP-9, TIMP-2 and Apo-CIII. The unbalance between MMPs and TIMPs in vascular wall and dyslipidaemia creates favourable conditions for plaque disruption. Our study suggests that the combination of MMP-9, TIMP-2 and Apo-CIII values ('CAD aggravation panel') characterizes the severity of CAD, that is electrophysiological state, number of involved vessels, stent disposal and type of stent.

Successful switch from insulin to oral sulfonylurea therapy in HNF1A-MODY Tunisian patient with the P291fsinsC mutation.

The hot spot mutation P291fsinsC was identified for the first time in a 26 years old Tunisian woman. The low serum level of high C-reactive protein was helpful to target the HNF1A gene. Due to the molecular diagnosis, the change from insulin to sulfonylurea therapy was performed successfully.

Gaucher Disease: Clinical, Biological and Therapeutic Aspects.

We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective function of the catabolic enzyme ß-glucocerebrosidase (GBA), leading to an accumulation of its substrate, glucocerebroside. Clinical signs and symptoms include neurological dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia and thrombocytopenia. Enzyme replacement therapy with recombinant GBA is the mainstay of treatment for GD, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.

Clinical utility of serum cystatin C in predicting coronary artery disease in patients without chronic kidney disease.

BACKGROUND: Cystatin C has been proposed as a novel marker of renal function and predictor of cardiovascular risk. The aim of this study was to investigate the role of cystatin C level as a predictor of cardiovascular events in patients with coronary artery disease (CAD). METHODS: Three hundred and five coronary artery patients were included in this study. Serum cystatin C levels, high-sensitive C-reactive protein (hs-CRP), and oxidative stress were measured. Estimated glomerular filtration rate (eGFR) and the CAD severity score were calculated. RESULTS: Cystatin C was correlated with the CAD severity score (r = 0.631, P < 0.0001) and was significantly elevated in the CAD severity score >50. Every 0.1 mg/l increase in cystatin C, 2 mg/l increase in hs-CRP, 0.2 mmol/l decrease in high-density lipoprotein cholesterol, 13.7 ml/min decrease in eGFR, and 1.51 µmol/l increase in homocysteine caused a 34, 12, 5, and 22% increase in the risk of having CAD, respectively. CONCLUSION: Cystatin C could be a useful laboratory biochemical marker in predicting the severity of CAD. Cystatin C is associated with biochemical atherosclerosis markers such as CRP and homocysteine.

Brain MRI and biological diagnosis in five Tunisians MLD patients.

Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA). we studied 5/200 cases of MLD and clearly distinguished three clinical forms. One of them presented the juvenile form; two presented the late infantile form; and two other presented the adult form. The Magnetic Resonance Imaging (MRI) of these patients showed a diffuse, bilateral and symmetrical demyelination. The biochemical diagnosis of MLD patients evidencing the low activity of ASA and sulfatide accumulation. PATIENTS AND METHODS: We studied 5/200 MLD patients addressed to us for behavioral abnormalities and progressive mental deterioration. All of them were diagnosed at first by brain MRI evidencing a bilateral demyelination, then the measurement of ASA activity using P-nitrocathecol sulfate as substrate, finally the sulfatiduria was performed using thin-layer chromatography using alpha-naphtol reagent. RESULTS: In this study, from 200 patients presenting behavioral abnormalities and a progressive mental deterioration, we reported just 2 patients were diagnosed as late-infantile form of MLD. Only1 case presented as the juvenile form; and 2 patients with the adult-type of MLD. The brain magnetic resonance imaging (MRI) of all patients showed characteristic lesions of MLD with extensive demyelination. Biochemical investigations of these patients detected a low level of ASA activity at 0°C and 37°C; the excess of sulfatide in sulfatiduria. CONCLUSION: MRI is required to orient the diagnosis of MLD patients; the latter must be confirmed by the biochemical investigations which is based on the measurement of ASA activity and the excess of sulfatide showed in the sulfatiduria. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1791578262610232.

Real time PCR for fast detection of the angiotensinogen polymorphisms.

OBJECTIVE: to develop a rapid and reliable real-time PCR to detect polymorphisms of angiotensinogen (AGT), to compare the two methods of MS-PCR (Mutagenically Separated PCR) and real-time PCR to determine three polymorphisms of the angiotensinogen gene M235T, the A (-6) G and A (-20) C. METHODS: the method of real-time PCR was developed on the PLC Roche LightCycler1 with SYBR Green I. We used two sense primers and a primer nonsense. Detection of polymorphisms of angiotensinogen gene was performed by comparing the melting curves. RESULTS: the DNA samples were analyzed by two methods: real-time PCR and MS-PCR. In our study, no differences were found between the two techniques. DISCUSSION: The real-time PCR is a rapid and reliable method for detecting gene polymorphisms on the AGT M235T, the A (-6) G and A (-20) C. CONCLUSION: this method of real-time PCR is a reliable genetic test, which is fast and cheap and can be used in practice to study particular polymorphisms of AGT gene associated with cardiovascular disease.

Correlation of oxidative stress parameters and inflammatory markers in tunisian coronary artery disease patients.

INTRODUCTION: Oxidative stress is now recognized as being the cause and the consequence of cardiovascular diseases. OBJECTIVE: The role that oxidative stress parameters and inflammatory markers may play in diabetes and related cardiovascular disease (CVD) among Tunisian coronary diabetic patients. PATIENTS AND METHODS: We measured the erythrocyte glutathione peroxidase (GPX), the superoxide dismutase (SOD) activities and the plasmatic total antioxidant status (TAS) concentration by colorimetric methods, the hs-CRP by immunonephelometry assays. RESULTS: TAS and GPX were significantly decreased among patients compared to the controls (1.14 ± 0.28 mmol/l vs 1.55 ± 0.35 mmol/l; 59.32 ± 10.72 U/gHb vs 149.19 ± 30.95 U/gHb). For the diabetic patients, TAS is correlated positively with hs-CRP (r=0.01, p<10(-3)). At the not diabetic subjects, TAS is correlated negatively with the hsCRP. CONCLUSION: Determination of antioxidative defense markers contributes to understanding the effect of stress oxidative on the development and the prevention of cardiovascular disease.

Evaluation of oxidative stress among coronary diabetics patients.

OBJECTIVES: Determination of the superoxide dismutase (SOD), glutathione peroxidase (GPX) and the total antioxidant status (TAS) and evaluation of inflammation by the use of high sensitivity C reactive protein (hs-CRP) among Tunisian coronary diabetic patients. MATERIALS AND METHODS: We measured the erythrocyte GPX activity and the plasmatic TAS concentration by colorimetric methods, the apolipoproteins [ApoA1, ApoB], hs-CRP and the fibrinogen by immunonephelometry assays. RESULTS: TAS and GPX were significantly decreased among patients compared to the controls [TAS: 1,14 +/- 0,28 mmol/l vs 1,55 +/- 0,35 mmol/l, GPX: 59,32 +/- 10,72 U/gHb vs 149,19 +/- 30,95 U/gHb]. For the coronary diabetic patients, the TAS is correlated positively with hs-CRP [r= 0,01, p<10(-3)]. Pearson's correlation shows a significantly positive correlation between GPX and TAS among all patients. CONCLUSIONS: Determination of antioxidative defense markers contributes to understanding the effect of stress oxidative on the development, prevention and therapy of cardiovascular disease. (www.actabiomedica.it).

[Metachromatic leucodystrophy. Clinical, biological, and therapeutic aspects]. / La leucodystrophie métachromatique Aspects clinique, biologique et thérapeutique.

Scholz's disease or metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency in arylsulfatase A (ARSA: EC 3.1.6.8). This enzyme is responsible for the degradation of sulfatides commonly called cerebroside-3-sulfate or 3-O-sulfogalactosylcéramide in galactocérébroside and sulfate. The success of hydrolysis of these sphingolipids by ARSA necessarily depends on the presence of saposine B forms a complex with the substrate. The pathological accumulation of sulfatides in the nervous system (myelin, neurons and glial cells) results most often neurological, mental retardation, nervous disorders, blindness. The metachromatic granules accumulated in the central nervous system and peripheral compounds are highly toxic. These are at high levels in the urine of patients affected by the MLD. Arylsulfatase A activity is collapsed in these patients. Unfortunately, the value of enzyme activity is not a predictor of clinical severity of the neuropathology. In contrast, the study of the gene that codes for the ARSA is seen as a way to diagnose the simplest and most reliable of the disease to avoid misdiagnosis due to the presence of pseudodeficit. The conventional therapeutic approaches are essentially symptomatic. They were made in order to restore the enzyme activity of arylsulfatase A and prevent the progression of the pathological accumulation of sulfatides and consequently reduce morbidity associated with MLD.