Biomedical subjects

Michel Nguyen

Publications and source records attributed to Michel Nguyen.

7 recordsLinked to original sources

PubMed2006

Delays to reperfusion therapy in acute ST-segment elevation myocardial infarction: results from the AMI-QUEBEC Study.

BACKGROUND: Through the AMI-QUEBEC Study we sought to describe delays to reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) and to identify factors associated with prolonged delays. METHODS: We reviewed the charts of all consecutive patients with STEMI admitted to 17 hospitals in the province of Quebec in 2003 to obtain data on the time from presentation to reperfusion therapy. Data were available for 1189 (83.0%) of 1432 patients. RESULTS: The median delay to reperfusion therapy was 32 minutes (first and third quartile [Q1, Q3] 20, 49) for 535 patients who received fibrinolytic therapy, 109 minutes (Q1, Q3 79, 150) for 455 patients who underwent primary percutaneous coronary intervention (PCI) at the initial hospital of presentation and 142 minutes (Q1, Q3 115, 194) for 199 patients who underwent primary PCI after an interhospital transfer. Patients who presented outside daytime working hours, those who received primary PCI and those who required interhospital transfer for primary PCI were less likely to receive reperfusion therapy within current recommended times (odds ratios [ORs] 0.49, 0.56 and 0.15, respectively). Increased age was associated with prolonged delays only among patients who received fibrinolytic therapy (OR for each 10-year increase in age 0.95, 95% credible interval [CrI] 0.93-0.99 for fibrinolytic therapy and 0.99, 95% CrI 0.95-1.05, for primary PCI). INTERPRETATION: In 2003, many patients with STEMI in Quebec were not treated within the recommended times. Delays may be reduced by reorganizing pre-and in-hospital care for patients with STEMI to expedite delivery of reperfusion therapy.

Age Factors↗

PubMed2006

Same-day transfer of patients with unstable angina and non-ST segment elevation myocardial infarction back to their referring hospital after angioplasty.

BACKGROUND: Recent evidence has shown the advantages of an early invasive strategy for patients with high-risk unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI). However, the number of beds available for postangioplasty monitoring limits the use of this approach at the Centre hospitalier universitaire de Sherbrooke (Fleurimont, Quebec). OBJECTIVES: To study the safety of a protocol allowing the same-day return of patients with UA or NSTEMI to their referring hospital after angioplasty at the Centre hospitalier universitaire de Sherbrooke. METHODS: From June 2001 to June 2003, of the 532 patients with UA and NSTEMI who underwent percutaneous coronary intervention with planned same-day transfer back to their referring hospital, 419 consecutive patients who were eligible to return the same day were prospectively followed for 24 h. RESULTS: Stents were used in 94.7% of patients and platelet glycoprotein IIb/IIIa receptor antagonists were used in 34.8% of patients. For 85% of patients, the femoral artery was used as the access route for percutaneous coronary intervention. The mean time that patients stayed in the hospital after angioplasty before returning to their referring centres was 4.4 h. No deaths, life-threatening arrhythmias or urgent revascularizations were reported during the 24 h postangioplasty follow-up period, but one patient had a major bleeding complication. During the study period, the mean angioplasty waiting time decreased from 5.7 days to 2.1 days. CONCLUSIONS: The protocol evaluated in the present article is safe. It frees more beds, thus reducing the waiting list and allowing patients with high-risk acute coronary syndromes without ST segment elevation from community hospitals to benefit from the advantages of an early invasive strategy.

Adult↗

PubMed2004

In vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein reductase MabA by isoniazid.

The first-line specific antituberculous drug isoniazid inhibits the fatty acid elongation system (FAS) FAS-II involved in the biosynthesis of mycolic acids, which are major lipids of the mycobacterial envelope. The MabA protein that catalyzes the second step of the FAS-II elongation cycle is structurally and functionally related to the in vivo target of isoniazid, InhA, an NADH-dependent enoyl-acyl carrier protein reductase. The present work shows that the NADPH-dependent beta-ketoacyl reduction activity of MabA is efficiently inhibited by isoniazid in vitro by a mechanism similar to that by which isoniazid inhibits InhA activity. It involves the formation of a covalent adduct between Mn(III)-activated isoniazid and the MabA cofactor. Liquid chromatography-mass spectrometry analyses revealed that the isonicotinoyl-NADP adduct has multiple chemical forms in dynamic equilibrium. Both kinetic experiments with isolated forms and purification of the enzyme-ligand complex strongly suggested that the molecules active against MabA activity are the oxidized derivative and a major cyclic form. Spectrofluorimetry showed that the adduct binds to the MabA active site. Modeling of the MabA-adduct complex predicted an interaction between the isonicotinoyl moiety of the inhibitor and Tyr185. This hypothesis was supported by the fact that a higher 50% inhibitory concentration of the adduct was measured for MabA Y185L than for the wild-type enzyme, while both proteins presented similar affinities for NADP(+). The crystal structure of MabA Y185L that was solved showed that the substitution of Tyr185 induced no significant conformational change. The description of the first inhibitor of the beta-ketoacyl reduction step of fatty acid biosynthesis should help in the design of new antituberculous drugs efficient against multidrug-resistant tubercle bacilli.

Acyl Carrier Protein↗

PubMed2003

1H and 13C NMR characterization of hemiamidal isoniazid-NAD(H) adducts as possible inhibitors of InhA reductase of Mycobacterium tuberculosis.

Isoniazid (INH) is easily oxidized with manganese(III) pyrophosphate, a chemical model of the KatG protein involved in activation of INH inside the bacteria Mycobacterium tuberculosis. Performed in the presence of NAD(+), this oxidation generates a family of isomeric INH-NAD(H) adducts, which have been shown to be effective inhibitors of InhA, an enzyme essential in mycolic acid biosynthesis. In this work, we fully characterized by (1)H and (13)C NMR spectroscopy four main species of INH-NAD(H) adducts that coexist in solution. Two of them are open diastereoisomers consisting of the covalent attachment of the isonicotinoyl radical at position four of the nicotinamide coenzyme. The other two result from a cyclization involving the amide group from the nicotinamide and the carbonyl group from the isonicotinoyl radical to give diastereoisomeric hemiamidals. Although an INH-NAD(H) adduct with a 4S configuration has been characterized within the active site of InhA from Xray crystallography and this bound adduct interpreted as an open form (Rozwarski et al., Science 1998, 279, 98-102), it is legitimate to raise the question about the effective active form(s), open or cyclic, of INH-NAD(H) adduct(s). Is there a single active form or are several forms able to inhibit the InhA activity with different levels of inhibitory potency?

Bacterial Proteins↗

PubMed2002

The relationship of intracoronary stent placement following thrombolytic therapy to tissue level perfusion.

BACKGROUND: Stenting has been shown to improve lumen diameters and thereby improve epicardial blood flow, but the impact of stent placement on tissue level perfusion has not been well characterized. METHODS: Data were drawn from the LIMIT trial of rhuMAb CD18 (anti WBC antibody) in acute myocardial infarction (AMI). Adjunctive/rescue stenting was performed at the discretion of the investigator. The TIMI Myocardial Perfusion Grade (TMPG) was assessed and digital subtraction angiography (DSA) was used to quantify brightness of the myocardial blush. RESULTS: TIMI 3 flow was 54.2% (64/118) before stent placement, and improved to 87.2% (102/117, p < 0.001) following stent placement. Likewise, Corrected TIMI Frame Counts (CTFCs) improved from medians of 37.6 to 21 (p < 0.001). By DSA, the rate of growth in brightness also tended to be greater after stenting (2.3 +/- 0.4 Gray/sec, n = 54 vs 3.1 +/- 0.3, n = 54, p = 0.07). The incidence of TMPG 0 decreased following stent placement (25.2% (29/118) vs 14.3% (16/118), p = 0.03) and the incidence of a stain in the myocardium (TMPG 1) increased (13.5% (16/118) vs 28.6% (34/118), p = 0.004). CONCLUSION: Adjunctive stenting following thrombolytic administration in AMI improves epicardial TIMI 3 flow and TIMI frame counts as well as dye inflow into the myocardium: TMPG 0 is reduced and myocardial blush measured quantitatively by DSA tends to be brighter. However, more TMPG 1 or dye staining was present on next injection, suggesting dye outflow may be impaired.

Blood Flow Velocity↗

PubMed2002

Mn(III) pyrophosphate as an efficient tool for studying the mode of action of isoniazid on the InhA protein of Mycobacterium tuberculosis.

The antituberculosis drug isoniazid (INH) is quickly oxidized by stoichiometric amounts of manganese(III) pyrophosphate. In the presence of nicotinamide coenzymes (NAD+, NADH, nicotinamide mononucleotide [NMN+]) and nicotinic acid adenine dinucleotide (DNAD+), INH oxidation produced the formation of INH-coenzyme adducts in addition to known biologically inactive products (isonicotinic acid, isonicotinamide, and isonicotinaldehyde). A pool of INH-NAD(H) adducts preformed in solution allowed the rapid and strong inhibition of in vitro activity of the enoyl-acyl carrier protein reductase InhA, an INH target in the biosynthetic pathway of mycolic acids: the inhibition was 90 or 60% when the adducts were formed in the presence of NAD+ or NADH, respectively. Under similar conditions, no inhibitory activity of INH-NMN(H) and INH-DNAD(H) adducts was detected. When an isolated pool of 100 nM INH-NAD(H) adducts was first incubated with InhA, the enzyme activity was inhibited by 80%; when present in excess, both NADH and decenoyl-coenzyme A are able to prevent this phenomenon. InhA inhibition by several types of INH-coenzyme adducts coexisting in solution is discussed in relation with the structure of the coenzyme, the stereochemistry of the adducts, and their existence as both open and cyclic forms. Thus, manganese(III) pyrophosphate appears to be an efficient and convenient alternative oxidant to mimic the activity of the Mycobacterium tuberculosis KatG catalase-peroxidase and will be useful for further mechanistic studies of INH activation and for structural investigations of reactive INH species in order to promote the design of new inhibitors of InhA as potential antituberculous drugs.

Antitubercular Agents↗

PubMedDate not supplied

Microstructured liposome array.

Conversion of a DNA chip to a nanocapsule array was performed by grafting on a liposome an oligonucleotide complementary to an oligonucleotide bound to the array. Each liposome may be loaded by a soluble molecule or may present a hydrophobic or amphiphilic molecule inserted in its wall. To detect liposomes on the chip, we used fluorescent dyes encapsulated in the liposome internal volume or fluorescent lipids. We observed that an oligonucleotide-grafted liposome containing a defined dye specifically accumulated on the area where its complementary oligonucleotide had been spotted on the array. The virtually unlimited amount of addresses allows the specific binding of large amounts of liposomes in one single batch.

Liposomes↗