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Biomedical subjects

B Vacher

Publications and source records attributed to B Vacher.

At least 19 recordsLinked to original sources
PubMed2005

Conformational analysis and crystal structure of {[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt.

{[1-(3-Chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt (C(20)H(22)ClF(2)N(3)O, C(4)H(4)O(4)) (1) was synthesized and characterized by the complete (1)H, (13)C and (19)F NMR analyses. The conformation of the piperidin ring, in the solution state, was particularly studied from the coupling constants determined by recording a double-quantum filtered COSY experiment in phase-sensitive mode. (1)H NMR line-shape analysis was used, at temperatures varying between -5 and +60 degrees C, to determine the enthalpy of activation of the rotational barrier around the CN bond. Compound 1 crystallizes in the triclinic space group P1 with a=8.517(3) Angstrom, b=12.384(2) Angstrom, c=12.472(3) Angstrom, alpha=70.88(2) degrees, beta=82.04(2) degrees, gamma=83.58(2) degrees. The results strongly indicate that the solid and solution conformations are similar. Thermal stability and phases transitions were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore polymorphism screening was studied from recrystallization of 1 performed in seven solvents and by slurry conversion in water. The X-ray powder diffraction (XRPD) and differential scanning calorimetry results suggested that 1 crystallizes into one crystalline form which melts at 157 degrees C (DeltaH=132 J g(-1)).

Calorimetry, Differential Scanning↗
PubMed2003

[Spontaneous splenic rupture: report of three new cases and review of the literature].

This study reports 3 new cases of spontaneous (or atraumatic) splenic rupture of the spleen, including two with massive hemoperitoneum and one with a secondary rupture of splenic infarct, and reviews the literature about this rare disease. These spontaneous ruptures are rare and potentially fatal. They result from infectious diseases (mainly mononucleosis and and paludism) and hematological diseases (mainly malignant hemopathies) in more than 50% of cases. Mortality is close to 20%, and includes some deaths occurring before diagnosis was established and postoperatives deaths, which can result from delayed management and bad general condition of the patients. Splenectomy is usually mandatory. Non-surgical treatment can be indicated only in young and stable patients.

Diagnosis, Differential↗
PubMed2002

Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia.

We report the discovery of F 13640 and evidence suggesting this agent to produce powerful, broad-spectrum analgesia by novel molecular and neuroadaptative mechanisms. F 13640 stimulates G(alphaomicron) protein coupling to 5-HT(1A) receptors to an extent unprecedented by selective, non-native 5-HT(1A) ligands. Fifteen minutes after its injection in normal rats, F 13640 (0.01-2.5 mg/kg) decreases the vocalization threshold to paw pressure; 15 min upon injection in rats that are exposed to formalin-induced tonic nociception, F 13640 inhibits pain behavior. The initial hyperalgesia induced by 0.63 mg/kg F 13640 was followed, 8 hrs later, by paradoxical hypo-algesia; 5 mg/kg of morphine produces the opposite effects (i.e., hypo-algesia followed by hyper-algesia). Repeated F 13640 injections cause an increase in the basal vocalization threshold and a reduction of F 13640-produced hyperalgesia; in these conditions, morphine causes basal hyperalgesia and antinociceptive tolerance. Continuous two-week infusion of F 13640 (0.63 mg/day) exerts little effect on the threshold in normal rats, but markedly reduces analgesic self-administration in arthritic rats. F 13640 infusion also decreases allodynic responses to tactile and thermal stimulations in rats sustaining spinal cord or sciatic nerve injury. In these models of chronic nociceptive and neuropathic pain, the analgesia afforded by F 13640 consistently surpasses that of morphine (5 mg/day), imipramine (2.5 mg/day), ketamine (20 mg/day) and gabapentin (10 mg/day). Very-high-efficacy 5-HT(1A) receptor activation constitutes a novel mechanism of central analgesia that grows rather than decays with chronicity, that is amplified by nociceptive stimulation, and that may uniquely relieve persistent nociceptive and neuropathic pains.

Acetates↗
PubMed2001

5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential.

To examine further the hypothesis that the magnitude of the intrinsic activity of agonists at 5-HT1A receptors determines the magnitude of their psychotropic activity, we studied the relationship between the maximal receptor activation produced by various 5-HT1A receptor ligands and their antidepressant-like effects (i.e., decreased immobility in the forced swimming test in rats). Using three different in vitro assays suitable to measure differences among high, intermediate, and low efficacy 5-HT1A receptor agonists, ligands were identified with intrinsic activities ranging from low-negative (i.e., the inverse agonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide (WAY 100635)) to high-positive (i.e., 3-chloro-4-fluorophenyl-(4-fluoro-4-[[(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl]-piperidin-1-yl-methanone (F 13714)). In addition, novel compounds with intermediate intrinsic activity, like buspirone, but with high selectivity for 5-HT1A receptors, unlike buspirone, were identified. The maximal effects of the 5-HT1A receptor ligands in the forced swimming test correlated positively (rS=0.91, P<0.005) with the rank order of their intrinsic activity at 5-HT1A receptors. This relationship constitutes evidence that the magnitude of the psychotropic activity of 5-HT1A receptor ligands is a positive function of their intrinsic activity at the receptor, and suggests that F 13714, which had maximal effects in the forced swimming test significantly larger than any of the other compounds examined here, did so because of its higher intrinsic activity at 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Novel derivatives of 2-pyridinemethylamine as selective, potent, and orally active agonists at 5-HT1A receptors.

The aim of this work was to improve the oral bioavailability of a recently discovered, novel structural class of 5-HT1A receptor agonists: aryl-{[4-(6-R-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1 -yl-metha none. Incorporation of a fluorine atom in the beta-position to the amino function in the side chain led to analogues that exhibited, in general, enhanced and long-lasting 5-HT1A agonist activity in rats after oral administration. Location of the fluorine atom at the C-4 position of the piperidine ring was the most favorable, and among the various substituents tested, the ability of the fluorine was unique in improving the oral activity of this family of ligands. Thus, the derivatives 39, 46, and 61 bound with higher affinity and selectivity to 5-HT1A receptors (versus dopaminergic D2 and adrenergic alpha1 receptors) and displayed more potent 5-HT1A agonist activity in vitro and in vivo than their C-4 desfluoro analogues. To examine the relationship between the conformation of the pharmacophore and the level of agonistic activity of this type of ligand, we synthesized a series of 3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-(H or CH3)-6-R-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl-+ ++methanone derivatives and found that the combination of a 5-methyl and a 6-methylamino substituent on the pyridine ring synergistically affected their 5-HT1A agonist properties. Thus, the 3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-6-methylamino-pyridin- 2-ylmethyl)-amino]-methyl}-piperidin-1-yl-methanone 40 behaved as a more potent 5-HT1A receptor agonist in vitro and in vivo than its 5-unsubstituted analogue 38. The antidepressant potential of the lead compounds 40, 45, and 54 was examined by means of the forced swimming test (FST) in rats. The results indicated that, after a single oral administration, these compounds inhibited immobility in the FST more potently and more extensively than the clinically used antidepressant imipramine. Thus, 40, 45, and 54 are potent, orally active 5-HT1A receptor agonists with marked antidepressant potential.

Administration, Oral↗
PubMed1998

Design and synthesis of a series of 6-substituted-2-pyridinylmethylamine derivatives as novel, high-affinity, selective agonists at 5-HT1A receptors.

A search for novel, selective agonists with high intrinsic activity at the 5-HT1A subtype of serotonin (5-HT) receptors was undertaken. Mechanistic and thermodynamic considerations led to the design of 6-substituted-2-pyridinylmethylamine as a potential 5-HT1A pharmacophore. Various adducts derived from the 6-substituted-2-pyridinylmethylamine moiety were tested for their affinity at 5-HT1A, alpha1-adrenergic, and D2-dopaminergic receptors. Compounds with high affinity for 5-HT1A receptors (pKi >/= 8) were examined for agonist properties by measuring their ability to inhibit forskolin-stimulated cAMP production in HA7 cells (i.e., HeLa cells permanently transfected with the h5-HT1A receptor gene and expressing the h5-HT1A receptor protein). Several compounds of the type aryl¿4-[(6-substituted-pyridin-2-ylmethylamino)methyl]piperidin -1-yl¿ methanone had nanomolar affinity for 5-HT1A binding sites and were more than 500-fold selective with respect to alpha1 and D2 sites. Importantly, their 5-HT1A agonist properties were demonstrated in HA7 cells where they behaved as potent inhibitors of cAMP accumulation. In particular, (3, 4-dichlorophenyl)¿4-[(6-oxazol-5-ylpyridin-2-ylmethylamin o)methyl]pip eridin-1-yl¿methanone (70) and (3, 4-dichlorophenyl)¿4-[(6-azetidinopyridin-2-ylmethylamino)met hyl]piper idin-1-yl¿methanone (36) appeared to be more potent than, and at least as efficacious as, the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT. SAR studies revealed that the pyridine nitrogen atom and the nature and the position of the substituents on the pyridine ring were critically involved in the ability of the compounds to recognize and activate 5-HT1A receptors. Structural modifications of the nonpharmacophoric part of the molecule showed, however, that the entire structure was required for affinity at 5-HT1A binding sites.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Adhesion-related glycocalyx study: quantitative approach with imaging-spectrum in the energy filtering transmission electron microscope (EFTEM).

Large polysaccharide molecules composing the glycocalyx have been shown to prevent cell adhesion. However, this process was not observed microscopically. Terbium labeling, combined with a new quantitative imaging method based on electron energy loss spectroscopy, allowed specific glycocalyx staining with excellent contrast. Image analysis enabled us to compare glycocalyx structure in free membrane areas and contacts between monocytic cells and bound erythrocytes. Apparent glycocalyx thickness, in contact areas, was half of the sum of glycocalyx thicknesses in free areas without label density increase. Ultrastructural immunogold localization of CD43 molecules, a major component of glycocalyx, was also demonstrated to be excluded from contact areas during adhesion. Thus, both approaches strongly suggest that some glycocalyx elements must exit from contact to allow binding of adhesion molecules.

Antigens, CD↗
PubMed1998

Characterization of nanophase Al-oxide/Al powders by electron energy-loss spectroscopy.

Al nanoparticles were prepared by the inert gas condensation method. After passivation with oxygen and air exposure we obtained a powdered sample of an Al-oxide/Al nanocomposite material. In the present paper we describe the use of the electron energy-loss spectroscopy (EELS) technique in a transmission electron microscope to characterize such nanostructured powders compared with a microcrystalline commercial aluminium foil. Energy-filtered images showed the presence of an alumina overlayer of approximately 4 nm covering the aluminium nanoparticles (23 nm in diameter). EELS analysis enabled us to determine the total amount of Al2O3 and metallic Al and the structure of the alumina passivation overlayer in the sample. In particular, the extended energy-loss fine structure analysis of the data showed a major presence of Al tetrahedrally coordinated with oxygen in the alumina passivation layer of Al nanoparticles instead of the octahedral coordination found for a conventional Al foil. This surprising effect has been attributed to the nanoscopic character of the grains. The analysis of the electron-loss near-edge structure also determines the presence of a certain degree of aggregation in this kind of powdered sample as result of the coalescence of the nanocrystalline grains. The procedure presented here may have the potential to solve other problems during characterization of nanostructured materials.

Journal Article↗
PubMed1997

[Laparoscopy-assisted colonic polypectomy or how to be helped by laparoscopy to prevent colectomy in benign colonic polyps considered to be unresectable by colonoscopy].

The aim of this study was to prospectively evaluate the role of laparoscopic surgery in all patients presenting with colonic polyps. From April 1994 to April 1996, 16 consecutive patients were treated. The laparoscopy starts the procedure, then a colonoscopy easily and rapidly locates the colonic lesion. Under laparoscopic supervision a new snare polypectomy is often possible. If polypectomy remains impossible, a mini-laparotomy is performed above the polyp and allows polypectomy by extra-peritoneal colotomy. In one case, the polyp was not found on colonoscopy. Colonoscopic polypectomy was possible in 6 cases (40%), and 9 mini-laparotomies were necessary (60%). No colectomy was performed. The final histologic result showed two Dukes A carcinomas justifying secondary wide colectomy. Laparoscopy-assisted polypectomy is a safe and efficient procedure, allows complete excision of polyps and may avoid a colonic resection.

Aged↗
PubMed1995

Immune-complex glomerulonephritis associated with Staphylococcus aureus infection of a totally implantable venous device.

We report a previously unrecognized complication of totally implanted subcutaneous ports. A patient with a totally implantable central venous device developed a septic syndrome. Blood and injection-reservoir cultures grew Staphylococcus aureus. There was no evidence of endocarditis. The port was removed but acute oliguric renal failure developed. A percutaneous renal biopsy showed acute diffuse proliferative glomerulonephritis. There was no extracapillary crescent. On immunofluorescence study, capillary wall granular deposits stained brightly for IgG and C3. These findings were thought to be consistent with infection-associated immune-complex glomerulonephritis.

Aged↗
PubMed1994

Curative resection for left colonic carcinoma: hemicolectomy vs. segmental colectomy. A prospective, controlled, multicenter trial. French Association for Surgical Research.

PURPOSE: This study was developed to compare median and actuarial survival after left hemicolectomy vs. left segmental colectomy. METHODS: Between January 1980 and January 1985, 270 consecutive patients (133 males and 137 females; mean age, 64 +/- 12 (range, 18-91) years with left colonic carcinoma located between the left third of the transverse colon and (but not, including) the colorectal juncture were randomly allotted to undergo either left hemicolectomy or left segmental colectomy. Left hemicolectomy removed the entire left colon along with the origin of the inferior mesenteric artery and the dependent lymphatic territory. Left segmental colectomy removed a more restricted segment of the colon and left the origin of the inferior mesenteric artery unmolested. RESULTS: After elimination of 10 patients for protocol violation, 131 patients with left hemicolectomy and 129 with left segmental colectomy were analyzed. Both groups were similar with regard to preoperative risk factors (age, sex, obesity, weight loss, anemia, diabetes, cirrhosis, kidney failure, steroid therapy or radiation therapy performed for any cause other than cancer), pathology findings (size, degree of differentiation, Dukes stage, invasion of lymph nodes at the origin of the inferior mesenteric artery), and associated lesions. Only the length of tumor-free margins of colon removed was significantly longer in left hemicolectomy. The number of early postoperative abdominal and extra-abdominal complications was similar in both groups. Overall, early postoperative mortality was 4 percent higher, but not significantly in left hemicolectomy (eight deaths, 6 percent) than in left segmental colectomy (three deaths, 2 percent). Median survival was 10 years and nearly equivalent in both groups. The two actuarial survival curves were similar. Bowel movement frequency was significantly increased after left hemicolectomy during the first postoperative year. Our results suggest that survival after left segmental colectomy is equivalent to that of left hemicolectomy. Notwithstanding the observation of other carcinologic rules, left segmental colectomy rather than left hemicolectomy may theoretically be performed under laparoscopy without compromising the carcinologic outcome.

Adenocarcinoma↗
PubMed1992

[A direct approach and a crease-resistant prosthesis: two simplifications of subperitoneal hernioplasty].

With experience of six already known techniques, the authors have developed a personal procedure combining three main principles: 1) large and direct exposure of the preperitoneal space, 2) the mesh, supple but not soft, needing no fixation, 3) outline of this mesh adapted to the concave shape of the pelvic wall, and avoiding the risk of a ventral hernia. The original points of this technique are the following: approach along the lateral border of the rectus muscle through its sheath, the initial exposure of the iliopsoas muscle and retropubic space, and the cutting of the mesh extending far beyond the borders of the inguinal and femoral orifices, with a flap reinforcing the posterior aspect of the rectus muscle. One hundred and two consecutive patients (173 hernias, 48 recurrences) were operated upon, and all but two were followed for a mean period of 36.8 months. Morbidity was low, with no prosthesis infection, and there was no recurrence or incisional hernia. The authors emphasize the simplicity and the rapidity of this technique, without advocating it as a routine operation, since it carries, like all prosthetic techniques, the potential for sepsis and preperitoneal fibrosis.

Adult↗
PubMed1990

[Colorectal preparation for excision surgery. Development after 4 randomized multicenter studies].

1,265 patients having elective surgery with colectomy for cancer or sigmoiditis have been included in four successive randomized multidepartmental studies in order to define the most effective preparation, reducing the rate of postoperative infections, and the shortest one. The first study included 202 patients divided up into 2 groups, and compared a three-day conventional preparation (CP) (low-residue diet, laxatives and enemas) with a total digestive irrigation (TDI) (9 liters in 6 h) with Mannitol. Both preparations were associated with a three-day preoperative antibiotic therapy with Neomycin and Tetracyclin. Intolerance to TDI (50% of cases) and the greater number of fistulae with this method lead to preferring CP. The second study (326 patients in 4 groups) compared on one hand, a CP with the single absorption of a sachet of Sennosides or 2 liters of 10% Mannitol, and on the other hand, the preoperative antibiotic treatment utilizing Neomycin or Tetracyclin over three days with a 24-hour treatment with Metronidazole. Its conclusions are that the absorption of Sennosides is better tolerated than Mannitol and significantly more effective than the CP. There is no significant difference between the antibiotic therapy over three days and that over 24 h. The third study (335 patients in 4 groups) compared on one hand, lukewarm water enemas to enemas with iodinated polyvidone diluted to 5%, and on the other hand an antibiotic therapy utilizing Metronidazole on the day before, the same day and the three following surgery with a 24-hour antibiotic therapy utilizing Metronidazole (1.5 g) and/or Cefotaxime (4 g) on the same day as the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1985

[Surgical resection of hepatocellular carcinoma. Retrospective study of 42 cases].

We studied the results 42 liver resections performed for hepatocellular carcinoma. Thirty-three patients underwent major liver resections. Hepatocellular carcinomas were associated with cirrhosis in 30.9 p. 100 of cases. The overall operative mortality was 24.3 p. 100: 60 p. 100 in patients with cirrhosis who underwent major liver resections and 12.5 p. 100 in patients with cirrhosis undergoing limited resections. The overall 5-year survival rate was 14.8 p. 100; the 5-year survival rate in patients with hepatocellular carcinoma without cirrhosis was 20 p. 100 whereas no patient with associated cirrhosis of the liver survived at 3 years. We conclude that surgical resection of hepatocellular carcinoma must be performed whenever possible: a limited resection should be done if the tumor is small, especially in patients with cirrhosis; a major liver resection must be proposed when the tumor is large and if the remaining liver parenchyma is normal.

Carcinoma, Hepatocellular↗