Search PubMed⌕ Search

Biomedical subjects

P Marchand

Publications and source records attributed to P Marchand.

At least 19 recordsLinked to original sources
PubMed2004

[Laparoscopy under local anaesthesia and hypnoanaesthesia about 35 cholecystectomies and 15 inguinal hernia repair].

OBJECTIVE: To present hypnosedation and the feasibility of this technique performed for laparoscopic procedure. STUDY DESIGN: Retrospective and descriptive study of feasibility. PATIENTS AND METHODS: Hypnosis can significantly reduce intraoperative requirements of intravenous sedation for surgery under local anaesthesia. Modifications of surgical procedure: laparoscopic surgery under local anaesthesia and hypnosis is performed using a subcutaneous lifting of anterior abdominal wall. Insufflation is only use to push out smoke. If patient or surgical uncomfort happens, moral contract with patient includes convert to general anaesthesia. RESULTS: We performed 35 cholecystectomies; 13 needed convert to general anaesthesia, mainly for peritoneal pain induced by CO(2) insufflation; 22 procedures were completed with patients' satisfaction. Upon 15-hernia repairs, only one patient needed convert to general anaesthesia, for dissection difficulty. CONCLUSION: Probably hypnosis can't be extent to intraperitoneal laparoscopic procedures. On the other hand interest of hypnosis performed for extraperitoneal laparoscopic hernia repair must be explore.

Adult↗
PubMed2002

[Hypnosis for treatment of nausea and vomiting: it works!].

We report a case of uncontrollable vomits in 76-year-old patient, for which hypnosis was effective. Described vomits became initiated by administration of morphine per os, lasted three months and stood up to usual medication as well attempts of nutrition by ballasted micro-tube. Somatic etiology search was unsucceSsful; the growing significance of hypnosis in the field of anesthesia led to use relational and oriented solution therapy. The situation was rapidly and constantly solved.

Aged↗
PubMed2001

Synthesis and pharmacological evaluation of (indol-3-yl)alkylamides as potent analgesic agents.

A series of (indol-3-yl)alkylamides was synthesized and evaluated for analgesic activity. Two N-(pyridin-4-yl)acetamides, compounds 24 and 25, bearing benzyl or 4-fluorobenzyl moieties in 1-position of indole ring exhibited promising analgesic properties (ED50 = 8.1 and 11 mg/kg p.o., respectively), being as potent as the reference drugs flupirtine (CAS 56995-20-1), ibuprofen (CAS 15687-27-1) and diclofenac (CAS 15307-86-5). The two test compounds were tested for their anti-inflammatory activity by carrageenin-induced edema in rat paw test. 4-Fluorobenzyl derivative 25 whose ID50 was 0.085 +/- 0.021 mmol/kg was selected as a lead compound for further pharmacomodulation.

Alkanes↗
PubMed2000

The first asymmetric synthesis of alpha-sulfanylphosphonates.

[reaction: see text] Diastereoselectivity of up to 88% was achieved for the synthesis of an alpha-mercapto gamma-unsaturated phosphonate using the readily available chiral dimenthylphosphonyl ester group and a carbanionic [2,3]-sigmatropic rearrangement. Absolute configuration of the newly formed chiral center of this nonracemic thiol was determined, and the corresponding phosphono thiolane and thiolane S-oxide were also stereoselectively prepared.

Anti-Infective Agents↗
PubMed2000

Selective inhibition of monocyte chemoattractant protein-1 gene expression in human embryonal kidney cells by specific triple helix-forming oligonucleotides.

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is expressed by a variety of tissue cells in response to inflammatory stimuli, such as IL-1beta, TNF-alpha, and IFN-gamma. A major function of MCP-1 is the recruitment and activation of monocytes and T lymphocytes. Overexpression of MCP-1 has been implicated in a number of diseases, including glomerulonephritis and rheumatoid arthritis, indicating that the modulation of MCP-1 activity and/or expression is a desired therapeutic strategy. In the present study, our aim was to test whether the MCP-1 expression could be inhibited at the transcriptional level using triple helix-forming oligonucleotides (TFOs). We designed a TFO targeted to the SP-1 binding site in the human MCP-1 gene promoter. Gel mobility shift assays demonstrated that the phosphodiester TFO formed a sequence-specific triplex with its dsDNA target with an EC50 of approximately 1.9 x 10(-7) M. The corresponding phosphorothioated oligonucleotide was also effective in this assay with an 8-fold higher EC50 value. Binding of the TFO to the target DNA prevented the binding of rSP-1 and of nuclear proteins in vitro. The TFO could also partially inhibit endogenous MCP-1 gene expression in cultured human embryonic kidney cells. Treatment of TNF-alpha-stimulated human embryonic kidney 293 cells with the TFO inhibited the secretion of MCP-1 in a dose-dependent manner (up to 45% at 5 microM oligonucleotide). The inhibition of MCP secretion was caused at the level of gene transcription, because MCP-1 mRNA levels in oligonucleotide-treated cells were also decreased by approximately 40%.

Binding, Competitive↗
PubMed2000

Ultra trace detection of a wide range of anabolic steroids in meat by gas chromatography coupled to mass spectrometry.

The control on use of anabolic agents in meat producing animals is generally based on urine, faeces or hair analysis. This exercise, which is usually performed in slaughterhouses or on farms, is not relevant to imported carcasses or retail meat. A single sensitive method for a wide range of anabolic steroids was developed. After extraction of the lyophilised meat, enzymatic hydrolysis was used for deconjugation. Solid-phase extraction on a polymeric stationary phase was performed prior to hydrolysis of ester residues under alkaline conditions. Liquid-liquid partitioning was used to separate the analytes into two main categories: phenol containing molecules, such as phenolic steroids, resorcylic acid lactones and stilbenes, and delta4-3-one containing molecules, such as most androgens and progestagens. Solid-phase extraction on silica columns was performed before applying a specific derivatisation for each compound sub-group. The combination of high-resolution chromatography with a quadrupole mass spectrometer permitted detection of 23 steroids in the 5-100 ng/kg range. Ion chromatograms for residue positive samples are shown and discussed.

Anabolic Agents↗
PubMed2000

[Digestive hemorrhage originated elsewhere].

We report the case of splenic subcapsular haematoma, that happens to a woman after three months. Breaking and fistulation of the splenic haematoma into the gastric cavity and its subsequent evacuation made it first identify as digestive haemorrhage.

Diagnosis, Differential↗
PubMed1999

New selective nonsteroidal aromatase inhibitors: synthesis and inhibitory activity of 2,3 or 5-(alpha-azolylbenzyl)-1H-indoles.

Six azolyl substituted indoles were synthesized and tested for their activity to inhibit two P450 enzymes: P450 arom and P450 17a. It was observed that the introduction of alpha-imidazolylbenzyl chain at carbon 3 or 5 on indole nucleus led to very active molecules. Compounds 22, 23 and especially 33 demonstrate very high potential against P450 arom. Under our assay conditions of high substrate concentration the IC50 are 0.057, 0.0785 and 0.041 microM, respectively. These compounds are moderate inhibitors against P450 17alpha.

Aromatase Inhibitors↗
PubMed1998

[Diaphragmatic or juxtadiaphragmatic schwannoma?].

The authors report one case of schwannoma of diaphragmatic topography. This lesion is exceptional and, to our knowledge, only seven cases have been published in the literature. The first diagnosis was a suprarenal tumour. Magnetic resonance imaging provided more detail about the juxta diaphragmatic topography of the tumour, which was subsequently confirmed by surgery. The diagnosis of benign schwannoma was made at the pathological and immuno-histochemical examination of the specimen. The schwannoma corresponded to the type B of the classification of Antoni. Pathogeny and origin of the tumour are discussed. The sympathetic nervous para-vertebral system, the phrenic or intercostal nerves could be the origin of the tumour. In the eight cases reported, the tumoural removal was performed through thoracotomy (n = 5) or laparotomy (n = 3). The preoperative exact location of the juxta diaphragmatic tumours remains difficult to specify.

Adult↗
PubMed1998

N-methyl-N-alkylsilyltrifluoroacetamide-I2 as a new derivatization reagent for anabolic steroid control.

Analytical methods for the control of growth promoters have to be specific and sensitive. At low concentration levels, it is difficult to identify some molecules unambiguously even with the improved performance of analytical methods. GC-MS analysis of 17 beta-trenbolone and its major metabolite, 17 alpha-trenbolone, is a good example. A new derivatization agent has been developed which is based on silylation of the 3- and 17-oxygenated functions and nucleophilic substitution in the 4-position. The structure of the derivatized products was demonstrated using a simple model, cyclohex-2-en-1-one, by NMR and MS spectrometry. In contrast to data found in the literature, this derivative permitted specific mass spectra for trenbolone, sensitive signals for high mass ions and reproducible gas chromatograms to be obtained. The addition of an N(CH3)COCF3 radical to the steroid nucles allowed highly specific detection in GC-high resolution MS even following extraction from complex matrices; sensitive responses were also observed in the negative chemical ionization mode. Moreover, there are significant differences in the electron ionization mass spectra of the two stereoisomers, 17 alpha- and 17 beta-trenbolone. These preliminary results and those obtained for androsta-1,4-dien-3-one and pregna-4,6-dien-3-one indicate useful advances for the determination of steroids and potential applications for metabolism studies on such compounds.

Anabolic Agents↗
PubMed1997

Synthesis and in vitro evaluation of 3-(1-azolylmethyl)-1H-indoles and 3-(1-azolyl-1-phenylmethyl)-1H-indoles as inhibitors of P450 arom.

In the challenge to develop potent inhibitors of aromatase for reducing the levels of estrogens, we found that azolyl-substituted indoles inhibit aromatase activity, 3-(1-Azolylmethyl)-1H-indoles 9-15 and 3-(1-azolyl-1-phenylmethyl)-1H-indoles 22-25 were prepared, and tested on their ability to inhibit P450 arom. Analysis of the inhibitory effect exerted by several derivatives (11, 12, 22, and 23) on microsomal aromatase in vitro activity indicates that azolyl-substituted indoles containing an imidazole moiety are more potent inhibitors than triazole derivatives. In the first series, the introduction of the N-benzyl moiety has been found to enhance the inhibitory profile of these 3-(1-azolylmethyl)-1H-indole derivatives. The corresponding 4-fluoro derivative 12 displays the highest inhibitory activity (IC50 = 0.0718 microM) of all investigated compounds; thus, 12 is 258 times as potent as aminoglutethimide (AG). The presence of a chloro grouping in para position of the phenyl ring in compounds 22 and 24 exerts a positive effect only in the triazol-l-yl sub-series: compound 25 is 4-fold more potent than 24.

Aromatase Inhibitors↗
PubMed1997

Recombinant human 92-kDa type IV collagenase/gelatinase from baculovirus-infected insect cells: expression, purification, and characterization.

Human 92-kDa type IV collagenase/gelatinase (MMP9) has been expressed in insect cells and secreted into the cell medium via a baculovirus expression system. The expression level of the proenzyme from Trichoplusia ni cells was estimated to be > = 300 mg/L of cell medium. The recombinant protein was purified in a single step using heparin-affinity chromatography with an overall yield of ca. 70%. The purified zymogen could be activated in vitro using 4-aminophenylmercuric acetate to yield an active protease. Kinetic analysis of the activated recombinant enzyme demonstrates that this material is comparable to activated MMP9 from natural human sources. The recombinant enzyme provides a useful source of protein for a variety of biochemical and biophysical studies aimed at elucidating the structure and function of human MMP9.

Amino Acid Sequence↗
PubMed1996

Cysteine mutations in the MAM domain result in monomeric meprin and alter stability and activity of the proteinase.

Meprins are oligomeric, glycosylated cell surface or secreted metalloendopeptidases that are composed of multidomain disulfide-linked subunits. To investigate whether subunit oligomerization is critical for intracellular transport or for the enzymatic and/or physical properties of the proteinase, specific cysteine residues were mutated, and the mutants were expressed in 293 cells. Mutation of mouse meprin alpha Cys-320 to Ala in the MAM domain (an extracellular domain found in meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu) resulted in expression of a monomeric form of meprin, as determined by SDS-polyacrylamide gel electrophoresis and nondenaturing gel electrophoresis. The monomeric subunits were considerably more vulnerable to proteolytic degradation and heat inactivation in vitro compared with the oligomeric form of the enzyme. Proteolytic activity of the monomeric meprin using a bradykinin analog or aminobenzoyl-Ala-Ala-Phe-p-nitroanilide as substrate was similar to that of disulfide-linked oligomeric meprin; however, activity against azocasein was markedly decreased. Mutation of another cysteine residue in the MAM domain (C289A), predicted to be involved in intrasubunit disulfide bridging, resulted in disulfide-linked oligomers and monomers. These results indicated that this mutant was capable of forming intersubunit disulfide bonds but less efficiently than wild-type meprin subunits. Mutant C289A also retained activity toward peptides but not the protein substrate and was more vulnerable to proteolytic degradation and heat inactivation compared with the wild-type enzyme. Both Cys mutants were expressed and secreted into the medium at levels comparable with the wild type and had slightly altered glycosylation. This work indicates that 1) Cys-320 of mouse meprin alpha is most likely responsible for the covalent interactions of the subunits; 2) covalent dimerization of subunits is not essential for efficient biosynthesis, trafficking, or posttranslational processing of the secreted protease; and 3) mutations in the MAM domain affect noncovalent interactions of the subunits and the stability and activity of the protease domain, indicating that domain-domain interactions are critical for structure and function of the enzyme.

Animals↗
PubMed1995

COOH-terminal proteolytic processing of secreted and membrane forms of the alpha subunit of the metalloprotease meprin A. Requirement of the I domain for processing in the endoplasmic reticulum.

Cell surface isoforms of meprin A (EC 3.4.24.18) from mice and rats contain beta subunits that are type I integral membrane proteins and alpha subunits that are disulfide-linked to or noncovalently associated with membrane-anchored meprin subunits. Both alpha and beta subunits are synthesized with COOH-terminal domains predicted to be cytoplasmic, transmembrane, and epidermal growth factor-like; these domains are retained in beta subunits but are removed from alpha during maturation. The present studies establish that an inserted 56-amino acid domain (the "I" domain), present in alpha but not in beta, is necessary and sufficient for COOH-terminal proteolytic processing of the alpha subunit. This was demonstrated by expression of mutant meprin subunits (deletion mutants, chimeric alpha beta subunits, and beta mutants containing the I domain) in COS-1 cells. Mutations of two common processing sites present in the I domain (a dibasic site and a furin site) did not prevent COOH-terminal proteolytic processing, indicating that the proteases responsible for cleavage are distinct from those having these specificities. Deletion of the I domain from the alpha subunit resulted in accumulation of unprocessed subunits in a preGolgi compartment. Furthermore, COOH-terminal proteolytic processing of wild-type alpha subunits occurred before acquisition of endoglycosidase H resistance. Pulse-chase experiments and expression of an alpha subunit transcript containing a c-myc epitope tag, confirmed that proteolytic processing at the COOH terminus occurs in the endoplasmic reticulum. This work identifies the region of the alpha subunit that is essential for COOH-terminal processing and demonstrates that the differential processing of the evolutionarily-related subunits of meprin A that results in a structurally unique tetrameric protease begins in the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed1995

[Major liver injury. Role of preoperative transcutaneous endoluminal aortic clamping].

Severe contusion of the liver (type V in the Moore and Flint classification) still has a very poor prognosis. Exsanguination may lead to cardiac arrest when the abdomen is opened. Three patients with major liver injury were treated after percutaneous intra-aortic balloon occlusion and complete vascular exclusion of the liver. Two patients survived and one died due to complications resulting from lung trauma. The aorta was occluded with a balloon catheter inserted via the femoral route. The hepatic vascular exclusion was performed surgically after resuscitation had reestablished a satisfactory haemodynamic situation. Liver resection could then be performed under safe conditions. Aortic occlusion is a simple procedure with minimal disadvantages which could improve prognosis of major liver contusion by reducing the rate of intra-operative death.

Aorta↗
PubMed1995

Disruption of murine Hexa gene leads to enzymatic deficiency and to neuronal lysosomal storage, similar to that observed in Tay-Sachs disease.

Tay-Sachs disease is an autosomal recessive lysosomal storage disease caused by beta-hexosaminidase A deficiency and leads to death in early childhood. The disease results from mutations in the HEXA gene, which codes for the alpha chain of beta-hexosaminidase. The castastrophic neurodegenerative progression of the disease is thought to be a consequence of massive neuronal accumulation of GM2 ganglioside and related glycolipids in the brain and nervous system of the patients. Fuller understanding of the pathogenesis and the development of therapeutic procedures have both suffered from the lack of an animal model. We have used gene targeting in embryonic stem (ES) cells to disrupt the mouse Hexa gene. Mice homozygous for the disrupted allele mimic several biochemical and histological features of human Tay-Sachs disease. Hexa-/- mice displayed a total deficiency of beta-hexosaminidase A activity, and membranous cytoplasmic inclusions typical of GM2 gangliosidoses were found in the cytoplasm of their neurons. However, while the number of storage neurons increased with age, it remained low compared with that found in human, and no apparent motor or behavioral disorders could be observed. This suggests that the presence of beta-hexosaminidase A is not an absolute requirement of ganglioside degradation in mice. These mice should help us to understand several aspects of the disease as well as the physiological functions of hexosaminidase in mice. They should also provide a valuable animal model in which to test new forms of therapy, and in particular gene delivery into the central nervous system.

Animals↗