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Biomedical subjects

T Richard

Publications and source records attributed to T Richard.

At least 19 recordsLinked to original sources
PubMed2006

Recognition characters in peptide-polyphenol complex formation.

Dietary polyphenols have received attention for their anti-oxidative, anti-carcinogenic and anti-neurodegenerative effects. Polyphenols bind to proteins leading to the formation of soluble or insoluble protein-polyphenol complexes which could significantly influence their biological activities. NMR and molecular modeling studies were performed to investigate the influence of the bulk, flexibility and hydrophobicity of polyphenols on the association with bradykinin, the peptide model. Our results show that the strength of the interactions could be positively correlated with polyphenol hydrophobicity and a comparison between pentagalloylglucose and vescalagin indicated that flexibility might play a positive role in the interaction with peptides and proteins.

Biphenyl Compounds↗
PubMed2005

Role of peptide primary sequence in polyphenol-protein recognition: an example with neurotensin.

Polyphenols are known for their impact on health and one of their major properties is the formation of complexes with proteins. To investigate the involvement of polyphenol-protein complexes in health, the interactions between bioactive polyphenols and neurotensin were examined by structural NMR and molecular modeling. Neurotensin is a linear bioactive tridecapeptide and polyphenols seem to affect the NT metabolism. We studied the polyphenols resveratrol and its glucoside the piceid in order to observe the possible role of glucose group and the penta-O-galloyl-D-glucopyranose (PGG). NMR data and molecular modeling showed that interaction occurred with the three polyphenols involving hydrophobic stacking and hydrogen bonds. Moreover, the peptide primary sequence plays a role in the specificity of complex formation.

Amino Acid Sequence↗
PubMed2003

Is the C-terminal region of bradykinin the binding site of polyphenols?

Bradykinin is a bioactive hormone involved in a variety of physiological processes. In various solvents, this peptide adopts beta-turn structures. The C-terminal turn is a structural feature for the receptor affinity of agonists and antagonists while the N-terminal turn might be important for antagonistic activities. Polyphenols like dimeric proanthocyanidin B3 interact with the peptide. Thus to investigate the effects of polyphenols on bradykinin activity and structure, we studied the interaction in the structuring solvent DMSO which can be a close mimic of aqueous physiological environments like receptor-binding sites. Bradykinin alone presented a folded structure with two turns. B3 interacted with the peptide C-terminus and involved the loss of the bend structure of this region, while the N-terminus turn was maintained. Numerous studies have shown that polyphenolic molecules can act upon various biological targets, and the formation of this type of complex might be one of the possible modes of action.

Anthocyanins↗
PubMed2003

Second malignancies following adjuvant chemotherapy: 6-year results from a Belgian randomized study comparing cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with an anthracycline-based regimen in adjuvant treatment of node-positive breast cancer patients.

BACKGROUND: Alkylating agents and topoisomerase-II inhibitors have been associated with the occurrence of secondary leukemias and myelodysplastic syndromes in breast cancer patients treated with adjuvant chemotherapy. Conversely, data on the occurrence of second solid malignancies in this setting are scarce. PATIENTS AND METHODS: This study retrospectively evaluates the occurrence of second hematological and solid malignancies in the context of a prospective multicenter phase III trial comparing epirubicin-cyclophosphamide at intermediate doses (EC), or at full doses (HEC), with classical cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in 777 patients with early breast cancer. RESULTS: At a median follow-up of 73 months, the following 8-year actuarial rates of second solid primaries were observed: CMF 5.5% [95% confidence interval (CI) 1.5% to 9.5%], EC 4.1% (95% CI 0.1% to 8.1%), and HEC 7.2% (95% CI 3.2% to 11.2%) (P = 0.79 by log rank test). Three secondary acute myeloid leukemias (AML) were reported, all in the HEC arm (incidence = 1.2%, 95% CI 0.0% to 2.5%), which by a three arm comparison allows us to conclude that HEC is statistically different (borderline significance) from CMF and EC (P = 0.05). CONCLUSIONS: HEC, as delivered in this trial, cannot be recommended in clinical practice because of the lack of superiority over classic CMF and because of the increased risk of AML observed in this arm. Prolongation of conventional anthracycline-based treatment beyond the current standard of four to six cycles is not recommended in clinical practice.

Adult↗
PubMed2003

[Aneurysm of the persistent sciatic artery].

The authors report a case of persistent sciatic artery presenting with limb ischemia and pulsatile mass in the buttock treated only by femoro tibio peroneal by pass graft since follow up helical CTA at six months showed spontaneous aneurysmal exclusion by thrombosis of the persistent sciatic artery above the aneurysm. Review of the literature confirms the rarity of this anomaly, which is frequently associated with aneurysmal transformation and its specific inherent complications. It is treated by femoro popliteal shunt with endovascular embolization.

Aneurysm↗
PubMed2002

A new B-chain mutant of insulin: comparison with the insulin crystal structure and role of sulfonate groups in the B-chain structure.

The solution structure of a new B-chain mutant of bovine insulin, in which the cysteines B7 and B19 are replaced by two serines, has been determined by circular dichroism, 2D-NMR and molecular modeling. This structure is compared with that of the oxidized B-chain of bovine insulin [Hawkins et al. (1995) Int. J. Peptide Protein Res.46, 424-433]. Circular dichroism spectroscopy showed in particular that a higher percentage of helical secondary structure for the B-chain mutant is estimated in trifluoroethanol solution in comparison with the oxidized B-chain. 2D-NMR experiments confirmed, among multiple conformations, that the B-chain mutant presents defined secondary structures such as a alpha-helix between residues B9 and B19, and a beta-turn between amino acids B20 and B23 in aqueous trifluoroethanol. The 3D structures, which are consistent with NMR data and were obtained using a simulated annealing protocol, showed that the tertiary structure of the B-chain mutant is better resolved and is more in agreement with the insulin crystal structure than the oxidized B-chain structure described by Hawkins et al. An explanation could be the presence of two sulfonate groups in the oxidized insulin B-chain. Either by their charges and/or their size, such chemical groups could play a destructuring effect and thus could favor peptide flexibility and conformational averaging. Thus, this study provides new insights on the folding of isolated B-chains.

Amino Acid Sequence↗
PubMed2001

Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol present in wine, which has been reported to have anti-inflammatory, anti-platelet, and anti-carcinogenic effects. The glucuronidation of this compound and that of the cis-isomer also naturally present, has been investigated in human liver microsomes. Both isomers were actively glucuronidated. The reaction led to the formation of two glucuronides (3-O- and 4'-O-glucuronides), whose structure was characterized by LC-MS and proton NMR. Glucuronidation was regio- and stereoselective. It occurred at a faster rate with the cis-isomer and preferred the 3-position on both isomers. In addition, the glucuronidation of resveratrol was tested using several recombinant UDP-glucuronosyltransferase (UGT) isoforms. The reaction was catalyzed by UGT of the family 1A (UGT1A1, 1A6, 1A7, 1A9, 1A10). The bilirubin conjugating UGT1A1 was mainly involved in the 3-O-glucuronidation of trans-resveratrol, whereas the phenol conjugating UGT1A6 activity was restricted to cis-resveratrol. The UGT1A9 and 1A10 were active toward both isomers. The activity supported by UGT2B7 and UGT2B15 was very low and restricted to cis-resveratrol. UGT1A3, 1A4, 2B4, and 2B11 were unable to form resveratrol glucuronides.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

NMR and simulated annealing investigations of bradykinin in presence of polyphenols.

Epidemiological studies have shown that the incidence of some cardiovascular degenerative diseases appears to be lower in populations with regular but moderate drinking of red wine rich in polyphenols. One of the most important properties of polyphenols is to form complexes with proteins. The linear nonapeptide hormone bradykinin (H-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9-OH) is involved in a variety of physiological processes such as the cardiovascular processes. Thus, the goal of this work was to study the effects of tannins on the peptide structure by NMR investigations and molecular modeling. The results of these investigations show that in the presence of catechin, the peptide conformation is not affected and is in a random coil structure. On the contrary, the peptide structure is modified by the addition of dimeric proanthocyanidin B3 (catechin 4alpha-->8 catechin). The dimer leads to the formation of a large flexible turn between the 6-9 residues. Thus, the biological activities of bradykinin in the presence of polyphenols could be affected.

Anthocyanins↗
PubMed2001

[Percutaneous treatment of a common iliac aneurysm extending to the hypogastric artery with embolization and a covered endoprosthesis].

A case of iliac aneurysm treated percutaneously by endovascular stent graft (Wallgraft - Boston) and transcatheter embolization of internal iliac artery in order to prevent retrograde filling of the aneurysm from the patent hypogastric artery is presented. The initial radiographic evaluation included arteriography, and 2D and 3D spiral CT angiograms. This enabled analysis of the extent of mural thrombus, flow direction, as well as selection of stent graft and coil size. The procedure of embolization and implantation was technically uneventful. Post procedure 3D CT and arteriography demonstrated exclusion of the aneurysm, and return to a normal flow pattern. Follow-up at 6 and 12 months confirmed the stability of the results. Percutaneous treatment of common iliac artery aneurysms involving the hypogastric artery can be performed easily, especially in elderly patients. 3D CT is essential in assessing the endo and extra luminal characteristics of the aneurysm to insure optimal results and to detect complications.

Aged↗
PubMed1997

Neutrophil-mediated damage to vascular endothelium in the spontaneously hypertensive rat.

Lysis of aortic endothelial cells (EC) by neutrophils from spontaneously hypertensive rats (SHR) was investigated using a nonradioactive cytotoxicity assay. Interleukin-1-activated EC, but not unstimulated EC, were effective target cells for lysis by SHR neutrophils. Supernatants from activated neutrophil did not exert a cytotoxic effect on EC. Inhibitors of reactive oxygen species did not affect the cytotoxicity of neutrophils on EC. In contrast, inhibitors of serine protease and elastase markedly inhibited the cytotoxicity of neutrophils on EC. Antibodies against the endothelial cell surface ligands ICAM-1 (CD54) and E-selectin (CD62E) inhibited the adhesion and cytotoxicity of activated neutrophils on EC. The cytotoxicity of neutrophils required direct cell-to-cell contact because separating them with a microporous membrane abrogated the neutrophil-mediated cytotoxic activity. These results demonstrate that SHR neutrophils possess potent cytotoxicity against cytokine-activated EC. Neutrophil-mediated damage of EC could contribute to organ damage in hypertension under conditions of local or systemic activation of neutrophils.

Animals↗
PubMed1997

Characterization of arterial antigens using arterial antigen-reactive T cell clones from spontaneously hypertensive rats.

We have previously demonstrated that arterial antigens derived from the aorta of spontaneously hypertensive rats (SHRs) stimulate arterial antigen-reactive T cell clones established from the spleens of SHR to proliferate and release cytokines. To identify immunogenic protein components associated with the arterial wall, arterial antigen-reactive T cell clones were tested against arterial antigens separated by SDS-PAGE and transferred to nitrocellulose. The greatest T cell reactivity was obtained with protein bands of molecular weight 66 kDa, 50 kDa, and 45 kDa. T cell clones reactive against the 50 and 45 kDa antigens from gels failed to respond to proteins of other molecular weight (M(r)) separated under reducing or nonreducing conditions, suggesting that these molecules are not subunits of larger proteins and may represent monomeric antigens polymerized into the arterial wall. These data suggest that certain epitopes of arterial wall antigens are immunogenic. T cells activated with these immunogenic epitopes could initiate or perpetuate vasculitis in the arteries of hypertensive rats.

Animals↗
PubMed1990

[Potassium cyanide poisoning treated with hydroxocobalamin].

A fifteen-year-old girl, with a clean medical history, was admitted to the intensive care unit 90 minutes after ingestion of 2.5 g potassium cyanide. She had typical signs of severe cyanide poisoning including deep coma, circulatory failure, and major metabolic acidosis. Gastric lavage and antidotal treatment with 4 g hydroxocobalamin and 8 g sodium hyposulfite was administered without delay together with supportive treatment consisting of mechanical ventilation with FIO2, blood alkalinisation and administration of beta-stimulants. These measures led to a rapid clinical improvement. The ventilatory support was discontinued after 24 hours and the patient left the intensive care unit on the fourth day with only slightly impaired mental status. She survived despite a very high blood cyanide concentration (494 mumol.l-1 on admission) probably because of the rapid symptomatic and antidotal treatment.

Acidosis↗
PubMed1989

Preoperative spinal cord arteriography in aneurysmal disease of the descending thoracic and thoracoabdominal aorta: preliminary results in 45 patients.

Between 1985 and 1988 45 patients with descending thoracic or thoracoabdominal aortic aneurysms underwent selective arteriography of the intercostal and lumbar arteries to delineate preoperatively the artery of Adamkiewicz and the thoracic radicular artery. Identification of these vessels failed in five patients (11%), was considered complete in 31 patients (69%) and incomplete in nine (20%). Selective arteriography classified these patients into four groups: groups A and B--the artery of Adamkiewicz arose respectively above and below the zone of operation; group C--the artery arose directly from the segment to be operated; and group D--origin could not be determined. All 30 patients in group C underwent a spinal cord revascularization procedure (complete in 20 cases, incomplete in 10). Spinal cord complications occurred in 9/45 patients (20%). No spinal cord complications occurred in groups A and B; their incidence was 5% in group C when revascularization was complete, and 50% when revascularization was incomplete; and 60% had complications in group D (p less than 0.01). Spinal cord complications were more frequent (p less than 0.05) when the artery of Adamkiewicz arose from an intercostal or lumbar artery obliterated at its aortic origin but filled through collaterals or when spinal cord circulation was interrupted for more than 45 minutes. This study confirms the importance of preserving arterial supply to the spinal cord during repair of descending thoracic and thoracoabdominal aneurysms. The information obtained from spinal cord arteriography allows the prediction of complications and informs the choice of the appropriate surgical technique.

Adult↗