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Biomedical subjects

C Marchand

Publications and source records attributed to C Marchand.

At least 37 records · Page 2Linked to original sources
PubMed2000

Retroviral integrase inhibitors year 2000: update and perspectives.

HIV-1 integrase is an essential enzyme for retroviral replication and a rational target for the design of anti-AIDS drugs. A number of inhibitors have been reported in the past 8 years. This review focuses on the recent developments in the past 2 years. There are now several inhibitors with known sites of actions and antiviral activity. The challenge is to convert these leads into drugs that will selectively target integrase in vivo, and can be added to our antiviral armamentarium.

Anti-HIV Agents↗
PubMed2000

Emergency interruption of the inferior vena cava: a debatable issue.

In spite of improvements in the diagnosis and treatment of thromboembolic disease, pulmonary embolism continues to be a major cause of morbidity and mortality. Anticoagulation remains the preferred therapy for deep venous thrombosis; however, this form of treatment is either ineffective or contraindicated for some patients. For these patients, partial interruption of the inferior vena cava via percutaneous filter placement has become the procedure of choice to protect against fatal pulmonary embolism. We described in this paper results obtained with the available permanent filters and complications of these filters described in the literature. We highlighted the interest of temporary filters in patients whose thromboembolic risk is temporary, finally we insist on recognised indications for vena cava filters when anticoagulation is contraindicated or ineffective.

Contraindications↗
PubMed2000

Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters.

The antiviral activity of L-chicoric acid against HIV-1 has been attributed previously to the inhibition of HIV-1 integration. This conclusion was based on the inhibition of integrase activity in enzymatic assays and the isolation of a resistant HIV strain with a mutation (G140S) in the integrase gene. Here we show that the primary antiviral target of L-CA and its analogs in cell culture is viral entry. L- and D-chicoric acid (L-CA and D-CA) and their respective tetra-acetyl esters inhibit the replication of HIV-1 (III(B) and NL4.3) and HIV-2 (ROD) in MT-4 cells at a 50% effective concentration (EC(50)) ranging from 1.7 to 70.6 microM. In a time-of-addition experiment, L-CA, D-CA, L-CATA, and D-CATA were found to interfere with an early event in the viral replication cycle. Moreover, L-CA, D-CA, and their analogs did not inhibit the replication of virus strains that were resistant toward polyanionic and polycationic compounds at subtoxic concentrations. Furthermore, HIV-1 strains resistant to L-CA and D-CA were selected in the presence of L-CA and D-CA, respectively. Mutations were found in the V2, V3, and V4 loop region of the envelope glycoprotein gp120 of the L-CA and D-CA-resistant NL4.3 strains that were not present in the wild-type NL4.3 strain. Recombination of the gp120 gene of the L-CA and D-CA resistant strain in a NL4.3 wild-type molecular clone fully rescued the phenotypic resistance toward L-CA and D-CA. No significant mutations were detected in the integrase gene of the drug-resistant virus strains. Although inhibition of HIV integrase activity by L-CA and its derivatives was confirmed in an oligonucleotide-driven assay, integrase carrying the G140S mutation was inhibited to the same extent as the wild-type integrase.

Anti-HIV Agents↗
PubMed1999

Interleukin 1beta mediates the effect of high D-glucose on the secretion of TNF-alpha by mouse uterine epithelial cells.

Previous observations have shown that tumour necrosis factor alpha (TNF-alpha) synthesis is increased in the uterus of diabetic rats and that the epithelial layer lining the uterine lumen is the major site of TNF-alpha over-production. In the present study, TNF-alpha secretion was found to be stimulated by high D-glucose levels in primary cultures of mouse uterine luminal cells but not in cultures of the mouse uterine epithelial WEG-1 cell line. Experiments were performed to investigate the possibility that non-epithelial cells may mediate the influence of high D-glucose on TNF-alpha production by uterine epithelial cells. Immunocytochemical analysis revealed the reproducible presence of a small proportion of macrophages in primary cultures. Macrophages of the RAW 264.7 cell line were found to secrete more interleukin (IL)-1beta (but not TNF-alpha) when cultured in high D-glucose. TNF-alpha production in WEG-1 cells was increased upon exposure to IL-1beta and both protein kinase-C and tyrosine kinase pathways appeared to be involved in TNF-alpha stimulation. Addition of IL-1 receptor antagonist to primary cultures partially abrogated the effect of high D-glucose. Since WEG-1 cells do not produce IL-1beta, the data lend support to the hypothesis that uterine epithelial cells synthesize high levels of TNF-alpha in response to hyperglycaemia via an increase in IL-1beta secretion by stromal macrophages.

Animals↗
PubMed1999

Design of a triple-helix-specific cleaving reagent.

BACKGROUND: Double-helical DNA can be recognized sequence specifically by oligonucleotides that bind in the major groove, forming a local triple helix. Triplex-forming oligonucleotides are new tools in molecular and cellular biology and their development as gene-targeting drugs is under intensive study. Intramolecular triple-helical structures (H-DNA) are expected to play an important role in the control of gene expression. There are currently no good probes available for investigating triple-helical structures. We previously reported that a pentacyclic benzoquinoquinoxaline derivative (BQQ) can strongly stabilize triple helices. RESULTS: We have designed and synthesized the first triple-helix-specific DNA cleaving reagent by covalently attaching BQQ to ethylenediaminetetraacetic acid (EDTA). The intercalative binding of BQQ should position EDTA in the minor groove of the triple helix. In the presence of Fe(2+) and a reducing agent, the BQQ-EDTA conjugate can selectively cleave an 80 base pair (bp) DNA fragment at the site where an oligonucleotide binds to form a local triple helix. The selectivity of the BQQ-EDTA conjugate for a triplex structure was sufficiently high to induce oligonucleotide-directed DNA cleavage at a single site on a 2718 bp plasmid DNA. CONCLUSIONS: This new class of structure-directed DNA cleaving reagents could be useful for cleaving DNA at specific sequences in the presence of a site-specific, triple-helix-forming oligonucleotide and also for investigating triple-helical structures, such as H-DNA, which could play an important role in the control of gene expression in vivo.

Base Pairing↗
PubMed1999

[Carotid surgery under loco-regional anesthesia. Early results of 100 recent cases].

A prospective single-centre study was performed to evaluate the safety and efficacy of carotid revascularisation under local anesthesia. Between November 1, 1996 and March 30, 1998, 92 patients underwent surgery for 100 carotid artery stenoses under local cervical block anesthesia. Fifty-eight stenoses were asymptomatic and 42 were symptomatic. Duplex ultrasound scanning showed a tight (n = 17) or very tight carotid artery stenosis (n = 83); angiography showed 19 contralateral carotid artery stenosis and 30 hemodynamically significant stenosis of vertebral and/or subclavian arteries. Cerebral Magnetic Resonance Imaging (MRI) (N = 87) with circle of Willis Magnetic Resonance Angiogram (MRA) (n = 83) detected 29 ischemic defects (33%). Fifteen ischemic defects were found in 58 asymptomatic patients (26%). Circle of Willis was incomplete in 41%. Anesthesia was performed using superficial cervical block (n = 100). Endarterectomy was the most commonly used revascularisation technique in 86 cases with 5 eversion endarterectomies; carotid vein or prosthetic graft was used in 14%. In this study, there was no mortality, and no cardiac or neurologic complications, during the first postoperative month. Twelve patients experienced neurologic intolerance to carotid clamping. This clamping-related ischemia required 4 shunts. All patients with clamping intolerance had a good clinical outcome after revascularisation with no objective or MRI sequelae. Incomplete circle of Willis on MRA was a significant predictive test of clamping intolerance (p < 0.0001). Carotid artery surgery under local anesthesia reduces the cumulative mortality and morbidity rate (TCMM) to a very low level: 0% in this study. These recent results are the modern reference for current carotid artery surgery evaluation.

Adult↗
PubMed1998

Optimization of alternate-strand triple helix formation at the 5'CpG3' and 5'GpC3' junction steps.

Oligonucleotide-directed triple helix formation normally requires a long tract of oligopyrimidine.oligopurine sequence. This limitation can be partially overcome by alternate-strand triple helix (or switch triple helix) formation which enables recognition of alternating oligopurine/oligopyrimidine sequences. The present work is devoted to the optimization of switch triple helix formation at the 5'CpG3' and 5'GpC3' junction steps by combination of base triplets in Hoogsteen and in reverse Hoogsteen configurations. Rational design by molecular mechanics was first carried out to study the geometrical constraints at different junction steps and to propose a "switch code" which would optimize the interactions at junctions. These predictions were further checked and validated experimentally by gel retardation and DNase I footprinting assays. It was shown that the choice of an appropriate linker nucleotide in the switching third strand plays an important role in the interaction between oligonucleotides and alternating oligopurine/oligopyrimidine target sequences at different junctions: (i) the addition of a cytosine at the junction level in the oligonucleotide optimizes the crossover at the 5'CpG3' junction, whereas (ii) the best crossover at the 5'GpC3' junction step is achieved without any additional nucleotide. These results provide a useful guideline to extend double-stranded DNA sequence recognition by switch triple helix formation.

Base Composition↗
PubMed1997

[Relationship between iron status and diet in 410 hyperlipidemic patients].

In order to examine the influence of a low-fat diet on iron status, we carried out a study which involved 410 out-patients with hyperlipidaemia, i.e. 256 men and 154 women. Serum iron was positively correlated with protein intake (p = 0.11; p < 0.05) and transferrin saturation was inversely correlated with fat intake (p = - 0.12; p < 0.05). A positive iron balance (serum iron > 27 mumol/l and transferrin saturation > 45%) was found in 1.6% of the male subjects, a frequency which could be explained by the presence of the hemochromatosis genes. A negative iron balance (serum iron < 10 mumol/l and tranferrin saturation < 15%) was found in 13.7% for women aged 21-49 yr, 3.7% for women aged 50-77 yr and 3.5% for men aged 21-77 yr. We found no association between low-fat diet and iron deficiency. Men with iron deficiency had 12% decrease in total calorie intake compared to the Recommended Dietary Allowance. Our results do not provide evidence that hypolipidemic diet is associated with a high frequency of iron deficiency.

Adult↗
PubMed1996

Stabilization of triple helical DNA by a benzopyridoquinoxaline intercalator.

Biophysical, footprinting, and chemical probing experiments are described which characterize the triple helix-stabilizing effects of a benzo[f]pyridoquinoxaline derivative BfPQ-4,3 structurally related to the previously reported benzo[f]pyridoindole compound BePI [Mergny et al. (1992) Science 256, 1681-1684]. Two parallel triple helix model systems have been investigated; one in which the third strand matched perfectly a 27 base pair purine-pyrimidine motif in target DNA and another in which the third strand was one nucleotide longer, i.e., a 28-mer. In the latter system, the pairing of the (Y)28 third strand to the (Y.R)27 target induces the formation of a bulge containing at least one unpaired base, which can be evidenced by chemical probing experiments with osmium tetroxide. BPQ, which uinwinds a duplex DNA by 17 degrees as judged by viscometric experiments and otherwise behaves as a typical nonspecific intercalculating drug, promotes the formation of Y.R.Y parallel triple helix containing both T.A.T and C.G.C+ triplets. Both DNase I and MPE.FeII footprinting experiments concur that triplex formation with the target (Y.R)27 sequence can be detected in the presence of BPQ at about 10-fold lower oligonucleotide concentrations than are required to produce an equivalent footprint in the absence of the drug. In addition, BPQ will promote binding to the polypurine-polypyrimidine target sequence by the longer mismatched oligonucleotide, providing significant stabilization of the parallel bulge-containing(Y.R)27,(Y)28 triplex with nearly the same efficiency as the bulge-free (Y.R)27.(Y)28 triplex. Thus in vivo BPQ might enhance the formation of both undesired and desired DNA triplexes. By performing an MPE*FeII probing reaction with a 5'-32 P-labeled oligonucleotide third strand, we have obtained evidence that BPQ is actually bound to the triplex region and may distort in a sequence-specific fashion.

Base Sequence↗
PubMed1995

Localized chemical reactivity in double-stranded DNA associated with the intercalative binding of benzo[e]pyridoindole and benzo[g]pyridoindole triple-helix-stabilizing ligands.

Footprinting with methidiumpropyl-EDTA.FeII has been used to map the binding sites on duplex DNA of two closely related benzopyridoindole derivatives which selectively stabilize triple-helical DNA-oligonucleotide complexes. Both ligands bind to many sites, including certain oligopurine.oligopyrimidine tracts, with a weak preference for some (but not all) sequences rich in A.T base pairs. This indifference to primary sequence, with evidence of binding to the commonly disfavoured (A)n.(T)ntracts, may at least partially explain why the ligands stabilize triplex structures composed of T.A.T pairings. Neither 3-methoxy-7H-8-methyl-11- [(3'amino)propylamino]benzo[e]pyrido[4, 3-b]indole (BePI) nor 3- methoxy-7-[3'-diethylamino)propylamino]-10-methyl-11H- benzo[g]pyrido[4,3-b]indole (BgPI) affect the reaction of dimethyl sulphate or potassium tetrachloropalladinate with the N7 of purines in the major groove, but both enhance the reactivity of purines (mostly adenine residues) towards diethylpyrocarbonate, both proximal and distal to their identified binding sites. With potassium permanganate and osmium tetroxide/pyridine, probes for the accessibility of the 5,6 double bond of pyrimidine residues, BgPI has a more potent effect than BePI and, generally, the reaction with KMnO4 is more pronounced than that with OsO4. BgPI conspicuously potentiates the oxidation of pyrimidines in the triplet sequences 3'-ATA, 3'-GTA and 3'-GCA, whereas BePI enhances the reactivity of OsO4 towards thymine in sequences 3'-ATYR, with no effect on cytosine residues. Thus, despite their structural homology and common lack of specific sequence preferences, the two benzopyridoindole derivatives induce distinct conformational changes in duplex DNA, not just within the sites where footprints can be detected.

Animals↗
PubMed1995

Safety and feasibility of a self-monitored, home-based phase II exercise program for high risk patients after cardiac surgery.

OBJECTIVE: To determine the safety and effectiveness of a self-monitored, home-based phase II exercise program for high risk patients after cardiac surgery. METHODS: High risk patients were defined as those presenting with severe left ventricular dysfunction with an ejection fraction less than 35%, severe ventricular arrhythmias, incomplete revascularization, abnormal response to a standard walking test or significant (grade 3/4) valvular regurgitation persisting postoperatively. Eighty patients (mean age 58.5 +/- 8.9 years) were randomly assigned to two groups. The experimental group (n = 37) received a home program of aerobic training with an intensity gradually increasing from 1.5 to 4.0 multiples of resting oxygen consumption (METs). This program was started at discharge from the hospital and lasted eight weeks. The control group (n = 43) received general guidelines for progressive increase of their activity level. Functional capacity was measured at discharge by the 6 min walking test and between the sixth and eighth week following discharge by a symptom-limited exercise test, according to the Naughton protocol. RESULTS: No cardiovascular complications occurred during the training program. At the final evaluation, there was no significant difference between the experimental and control groups regarding aerobic capacity (5.1 +/- 1.8 versus 4.9 +/- 1.6 METs respectively, P = 0.61), nor peak rate-pressure product (22.8 +/- 4.9 versus 23.6 +/- 5.2 beats/min x mmHg x 10(3) respectively, P = 0.54).

Aged↗