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Biomedical subjects

Bernard Meunier

Publications and source records attributed to Bernard Meunier.

At least 19 recordsLinked to original sources
PubMed2026

Risk factors associated with urinary tract infection within 4 days of male rectal cancer surgery in the era of enhanced recovery after surgery (ERAS) programs.

BACKGROUND: Bladder drainage is systematically used in rectal cancer surgery in male patients, even in the era of enhanced recovery after surgery (ERAS). However, little data is available on risk factors for urinary tract infection (UTI). Identifying the risk factors associated with UTI within 4 days of male rectal cancer surgery in an ERAS program could support more individualized decision-making. METHODS: We used data from the GRECCAR 10 randomized clinical trial, a comparison of outcomes of transurethral catheterization (TUC) or suprapubic catheterization (SPC). 240 patients were randomized, 209 retained in the study (TUC n = 99; SPC n = 109). Univariate and multivariate logistic regression post-hoc study analyses were performed to assess association between potential predictive factors and UTI within 30 days after surgery. RESULTS: Out of 208 patients (median age 64.5 years), 19 (9.1%) had UTI, 26 (12.5%) had bacteriuria and 145 (69.7%) had pyuria. Univariate analysis identified age ≥ 65 years (OR = 3.08 [1.07-8.89]; p = 0.038), hypertension (OR = 3.65 [1.23-10.84]; p = 0.020) and ASA score ≥ 3 (OR = 4.15 [1.53-11.2]; p = 0.005) as risk factors for UTI until POD4. Multivariate analysis identified ASA score ≥ 3 with a risk of UTI. CONCLUSION: Regarding male rectal cancer surgery, our study shows that nearly 1 in 10 patients had UTI within 4 days. An ASA score ≥ 3 is an independent risk factor linked to UTI. Identifying this risk factor for UTI is necessary to advise patients, support a tailored decision-making process, and prevent these complications.

Humans↗
PubMed2006

Influence of chelators and iron ions on the production and degradation of H2O2 by beta-amyloid-copper complexes.

beta-Amyloid peptide (Abeta) 1-42, involved in the pathogenesis of Alzheimer's disease, binds copper ions to form AbetaxCu(n) complexes that are able to generate H(2)O(2) in the presence of a reductant and O(2). The production of H(2)O(2) can be stopped with chelators. More reactive than H(2)O(2) itself, hydroxyl radicals HO() (generated when a reduced redox active metal complex interacts with H(2)O(2)) are also probably involved in the oxidative stress that creates brain damage during the disease. We report in the present work a method to monitor the effect of chelating agents on the production of hydrogen peroxide by metallo-amyloid peptides. The addition of H(2)O(2) associated to a pre-incubation step between ascorbate and AbetaxCu(n) allows to study the formation of H(2)O(2) but also, at the same time, its transformation by the copper complexes. AbetaxCu(n) peptides produce but do not efficiently degrade H(2)O(2). The reported analytic method, associated to precipitation experiments of copper-containing amyloid peptides, allows to study the inhibition of H(2)O(2) production by chelators. The action of a ligand such as EDTA is probably due to the removal of the copper ions from AbetaxCu(n), whereas bidentate ligands such as 8-hydroxyquinolines probably act via the formation of ternary complexes with AbetaxCu(n). The redox activity of these bidentate ligands can be modulated by the incorporation or the modification of substituents on the quinoline heterocycle.

Amyloid beta-Peptides↗
PubMed2006

Guanine oxidation: one- and two-electron reactions.

Guanine bases in DNA are the most sensitive to oxidation. A lot of effort has been devoted to the understanding of the chemical modifications of guanine under different oxidizing conditions, the final goal being to know which lesions in DNA can be expected in vivo and their biological consequences. This article analyses the mechanisms underlying guanine oxidation by the comparison between one- and two-electron transfer processes. The different oxidants used in vitro give complementary answers. This overview presents a choice of some key intermediates and the predictive description of G-oxidation products that can be generated from these intermediates depending on the reaction conditions.

Electron Transport↗
PubMed2006

Synthesis of new macrocyclic chiral manganese(III) Schiff bases as catalysts for asymmetric epoxidation.

We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III) salen complexes. The developed reaction pathway allows the modulation of the different key groups, namely, the chiral diimine, the bulky substituents in positions 3 and 3', and the linker used in the macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available structural variations. The catalytic properties of the catalysts (5 mol %) were improved for the asymmetric epoxidation of 2,2'-dimethylchromene with NaOCl or H2O2 as oxygen atom donor. A large range of enantiomeric excesses was obtained (ee values from 30% to 96%), depending on the features and the stability of the complexes. The most efficient catalyst, in terms of stereoinduction (ee value = 96%), contains a diiminocyclohexyl moiety, ethyl groups in positions 3 and 3', and a short polyether junction arm.

Catalysis↗
PubMed2006

Guanine oxidation by electron transfer: one- versus two-electron oxidation mechanism.

The degeneracy of the guanine radical cation, which is formed in DNA by oxidation of guanine by electron transfer, was studied by a detailed analysis of the oxidation products of guanine on oligonucleotide duplexes and by labeling experiments. It was shown that imidazolone, the major product of guanine oxidation, is formed through a one-electron oxidation process and incorporates one oxygen atom from O2. The formation of 8-oxo-7,8-dihydroguanine by a two-electron oxidation process was a minor pathway. The two-electron oxidation mechanism was also evidenced by the formation of a tris(hydroxymethyl)aminomethane adduct.

Chromatography, High Pressure Liquid↗
PubMed2005

The first chemical synthesis of the core structure of the benzoylhydrazine-NAD adduct, a competitive inhibitor of the Mycobacterium tuberculosis enoyl reductase.

[reaction: see text] An isoniazid-NAD adduct has been recently proposed as the ultimate metabolite responsible for the antituberculous activity of isoniazid (INH). Its structure results from binding of the isonicotinoyl radical at C4 position of the nicotinamide ring of NAD with further possible and debated cyclization to form a cyclic hemiamidal derivative. Replacing the pyridine cycle of INH in INH-NAD adduct by a phenyl cycle (BH-NAD adduct) was shown previously to still retain the activity. On these bases, the core structure (4-benzoyl-1,4-dihydronicotinamide ribonucleoside) of the BH-NAD adduct and a series of analogues have been synthesized by using 3,4-pyridinedicarboximide as starting material. Depending on the nature of the substituent (pyridine or aryl) and on the oxidized or the reduced state of the nicotinamide nucleus, they were found either in a cyclized hemiamidal or an opened form or were shown to exist in equilibrium under cyclized or opened forms. Although none of these compounds could significantly inhibit activity of the InhA or MabA reductases (two possible targets of isoniazid), they represent attractive targets to develop potential second-generation inhibitors, including the total chemical synthesis of the bioactive BH-NAD adduct.

Antitubercular Agents↗
PubMed2005

[Liver transplantation for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.

Carcinoma, Hepatocellular↗
PubMed2005

Mechanistic studies on DNA damage by minor groove binding copper-phenanthroline conjugates.

Copper-phenanthroline complexes oxidatively damage and cleave nucleic acids. Copper bis-phenanthroline and copper complexes of mono- and bis-phenanthroline conjugates are used as research tools for studying nucleic acid structure and binding interactions. The mechanism of DNA oxidation and cleavage by these complexes was examined using two copper-phenanthroline conjugates of the sequence-specific binding molecule, distamycin. The complexes contained either one or two phenanthroline units that were bonded to the DNA-binding domain through a linker via the 3-position of the copper ligand. A duplex containing independently generated 2-deoxyribonolactone facilitated kinetic analysis of DNA cleavage. Oxidation rate constants were highly dependent upon the ligand environment but rate constants describing elimination of the alkali-labile 2-deoxyribonolactone intermediate were not. Rate constants describing DNA cleavage induced by each molecule were 11-54 times larger than the respective oxidation rate constants. The experiments indicate that DNA cleavage resulting from beta-elimination of 2-deoxyribonolactone by copper-phenanthroline complexes is a general mechanism utilized by this family of molecules. In addition, the experiments confirm that DNA damage mediated by mono- and bis-phenanthroline copper complexes proceeds through distinct species, albeit with similar outcomes.

Binding Sites↗
PubMed2005

The antimalarial drug artemisinin alkylates heme in infected mice.

Heme alkylation by the antimalarial drug artemisinin is reported in vivo, within infected mice that have been treated at pharmacologically relevant doses. Adducts resulting from the alkylation of heme by the drug were characterized in the spleen of treated mice, and their glucuroconjugated derivatives were present in the urine. Because these heme-artemisinin adducts were not observed in noninfected mice, this report confirms that the alkylating activity of this antimalarial drug is related to the presence of the parasite in infected animals. The identification of heme-artemisinin adducts in mice should be considered as the signature of the alkylation capacity of artemisinin in vivo.

Alkylation↗
PubMed2005

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

Oxidative activation of the antituberculous drug isoniazid (INH) in the presence of the NADH cofactor gives a pool of INH-NAD adducts proposed to be involved in the mechanism of action of this drug through inhibition of the reductase InhA. Among these adducts and besides dihydropyridine derivatives, two pyridinium-type isoniazid-NAD adducts were shown to be formed in solution and have been fully characterized by 1H/13C NMR and MS. One of them results from the oxidation of dihydropyridine-type INH-NAD adducts. The spectral data strongly support its existence under two epimeric structures. These epimers arise from a cyclization process between the carboxamide group and the ketone function with the creation of a new chiral center at C-7. The second pyridinium-type adduct was formed in acidic solution by dehydration of the cyclized dihydropyridine-type INH-NAD adducts and also exists as a cyclized structure. Both of these pyridinium-type compounds were inactive as inhibitors of InhA activity and can be considered as deactivated species.

Anti-Bacterial Agents↗
PubMed2005

Studies on the 4-benzoylpyridine-3-carboxamide entity as a fragment model of the Isoniazid-NAD adduct.

An ortho-metallation-electrophilic substitution sequence was employed as a key step to build the 4-benzoylpyridine framework. It was found that 4-benzoylpyridine-3-carboxamide and an N-pyridyl alkylated derivative both exist in a unique cyclized hemiamidal structure, not in the usually expected keto-amide open form. These structures represent fragment models of the Isoniazid-NAD adducts involved in the mechanism of action of the antituberculous drug Isoniazid.

Crystallography, X-Ray↗
PubMed2005

Porphyrin derivatives for telomere binding and telomerase inhibition.

The capacity of G-quadruplex ligands to stabilize four-stranded DNA makes them able to inhibit telomerase, which is involved in tumour cell proliferation. A series of cationic metalloporphyrin derivatives was prepared by making variations on a meso-tetrakis(4-N-methyl-pyridiniumyl)porphyrin skeleton (TMPyP). The DNA binding properties of nickel(II) and manganese(III) porphyrins were studied by surface plasmon resonance, and the capacity of the nickel porphyrins to inhibit telomerase was tested in a TRAP assay. The nature of the metal influences the kinetics (the process is faster for Ni than for Mn) and the mode of interaction (stacking or external binding). The chemical alterations did not lead to increased telomerase inhibition. The best selectivity for G-quadruplex DNA was observed for Mn-TMPyP, which has a tenfold preference for quadruplex over duplex.

DNA↗
PubMed2005

Cytostatic activity of 1,10-phenanthroline derivatives generated by the clip-phen strategy.

The cytostatic activities of a series of twelve 1,10-phenanthroline (Phen) derivatives and of their copper complexes were studied on L1210 murine leukemia cells. Large increases in the biological activity were observed for compounds of the 3-Clip-Phen series, in which two Phen moieties were bridged at their C3 positions by an alkoxy linker, the 3-pentyl-Clip-Phen derivative showing an IC(50) value of 130 nM while Phen shows an IC(50) value of 2500 nM under the same conditions. IC(50) values seemed to be modulated not only by the position, the nature, and the length of the linker of Clip-Phen but also by hydrophobicity. Since copper complexes of Phen are chemical nucleases and nucleic acids are thus a potential target for these compounds, the corresponding copper complexes were also studied. Copper complexation of the 3-Clip-Phen ligands did not increase their biological activities. Attempts to vectorize 3-Clip-Phen derivatives with a DNA binder such as spermine or with a cell-penetration peptide failed to increase their biological activity relative to the original 3-Clip-Phen series.

Animals↗
PubMed2005

Heme alkylation by artesunic acid and trioxaquine DU1301, two antimalarial trioxanes.

The sesquiterpene Artemisinin, an antimalarial drug that is effective against multidrug-resistant Plasmodium falciparum strains, contains a 1,2,4-trioxane, and the endoperoxide function plays a key role in its biological activity. However, its poor solubility means that hemisynthetic derivatives, such as artesunic acid, are preferred for drugs. The reductive activation of the peroxide function of artemisinin by iron(II)-heme produces heme derivatives that are alkylated at meso positions by a C-centered radical derived from artemisinin. We checked if the alkylating ability of trioxane-based drugs toward heme, which might be related to its parasiticidal activity, is a general feature by comparing the chemical reactivity toward heme of the clinically relevant derivative artesunic acid and DU1301, a drug of the trioxaquine family, that is active against P. falciparum. Both artesunic acid and trioxaquine DU1301 efficiently alkylated the heme macrocycle after activation of their peroxide function by the iron(II) of heme itself and thus gave rise to covalently coupled heme-drug products. This heme-drug adduct formation might be related to the high antimalarial activity of DU1301.

Alkylation↗
PubMed2005

Use of short duplexes for the analysis of the sequence-dependent cleavage of DNA by a chemical nuclease, a manganese porphyrin.

A manganese porphyrin, manganese(III)-bis(aqua)-meso-tetrakis(4-N-methylpyridiniumyl)porphyrin, in the presence of KHSO5 is able to perform deoxyribose or guanine oxidation depending on its mode of interaction with DNA. These two reactions involve an oxygen-atom transfer or an electron transfer, respectively. The oxidative reactivity of the manganese-oxo porphyrin was compared on short oligonucleotide duplexes of different sequences. The major mechanism of DNA damage is due to deoxyribose hydroxylation at a site of strong interaction, an (A.T)3 sequence. Guanine oxidation by electron transfer was found not to be competitive with this major mechanism. It was found that a single intrastrand guanine was three orders of magnitude less reactive than an (A.T)3 sequence. The reactivity of a 5'-GG sequence was found to be intermediate and was estimated to be two orders of magnitude less than that of an (A.T)3 site. Short oligonucleotide duplexes, as double-stranded-DNA models, proved to be convenient tools for the study of the comparative reactivity of this reagent toward different sequences of DNA. However, they showed a particular reactivity at their terminal base pairs (the "end effect") that biased their modeling capacity for double-helix-DNA models.

Base Sequence↗
PubMed2005

Accuracy of preoperative imaging methods in a retrospective series of 14 patients with operated intraductal papillary mucinous tumors of the pancreas.

UNLABELLED: Accuracy of preoperative imaging methods for the diagnosis of intraductal papillary mucinous tumor of the pancreas (IPMT) is not well known. AIMS: To compare diagnostic accuracy of various preoperative imaging methods with pathology data following surgical resection. PATIENTS AND METHODS: Fourteen consecutive patients underwent pancreatic surgical resection for IPMT between January 1988 and May 2002. Imaging methods included endoscopic retrograde cholangiopancreatography and/or magnetic resonance cholangiopancreatography and/or endoscopic ultrasonography. Results of preoperative morphological examinations were compared with histopathological findings from surgical specimens. RESULTS: IPMT was located to the pancreatic head or body in 72% of patients and involved the main pancreatic duct (MPD) in 79% of cases Carcinoma was diagnosed in 35% of the cases. Sensitivity of imaging methods varied from 64 to 80% to accurately locate the tumor and from 73 to 80% in distinguishing between types involving the MPD or the accessory ducts. Planned surgical resection based on preoperative imagery correlated with final surgery in 57% of the patients. Histological study of whole pancreas specimens revealed lesions in undilated ducts, and also dilated ducts without histological lesions. CONCLUSION: The sensitivity of preoperative imaging methods is moderate in defining intraductal extension of IPMT. Duct dilatation is not predictive of histological involvement by tumors and ducts may be pathological without dilatation.

Aged↗