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Biomedical subjects

M Delhaye

Publications and source records attributed to M Delhaye.

At least 73 records · Page 4Linked to original sources

A comparison between muscarinic receptor occupancy, adenylate cyclase inhibition, and inotropic response in human heart.

Binding to muscarinic receptors was compared with adenylate cyclase inhibition in membranes derived from human heart auricles, and with inhibition of the contraction of auricular muscle fibers. In the absence of GTP, agonists recognized two classes of receptors both of which bound antagonists with the same affinity. In the presence of GTP, both classes of receptors for agonists were converted into a single low affinity state. Carbachol and oxotremorine inhibited adenylate cyclase activity by 43%, pilocarpine being less efficient (-28%). The 3 agonists exerted similar inhibitory effects on the inotropic response, in 7 out of 9 preparations of electrically- and norepinephrine-stimulated fibers. Dose-effect curves suggested that spareness (or an amplification mechanism) was implicated in the occupancy of low affinity binding sites by carbachol and oxotremorine (but not by the partial agonist pilocarpine) and the resulting inhibition of both adenylate cyclase activity and contractile force.

Adenylyl Cyclase Inhibitors↗

In vitro effect of thyroid hormones on lipolysis of rat fat cells during aging.

The in vitro effect of triiodothyronine (T3) 10(-5) M upon lipolysis was studied on white fat cells isolated from 1.5-6- and 30-month-old rats. We couldn't see any consistent effect of this hormone upon the basal lipolysis. We observed a T3 effect on epinephrine-stimulated lipolysis on the three groups of animals. After 1 h of incubation the increase of glycerol release varies with the dose of epinephrine; after 3 h the T3 effect persisted only in the 6-month and 30-month groups.

Adipose Tissue↗

Effects of full and partial beta-adrenergic agonists and antagonists on human lung adenylate cyclase.

The beta-adrenergic stimulation of adenylate cyclase in membranes from human lung was compared to that of adenylate cyclase in membranes with a majority of beta 2-adrenergic receptors (from rat lung) and in membranes with a homogeneous population of beta 2-adrenergic receptors (from rat erythrocytes and reticulocytes). In terms of adenylate cyclase stimulation, three full agonists (isoproterenol, epinephrine and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol and zinterol), and four antagonists (propranolol, metoprolol, atenolol and practolol) were tested. The potency (Kact or Ki) of the eleven beta-adrenergic agents, and the Hill coefficient (of 1) for the four antagonists tested indicated that the activation of human lung adenylate cyclase occurred through receptors of the beta 2-subtype only. Partial beta-adrenergic agonists were efficiently discriminated by the human lung preparation, as shown by distinct intrinsic activities. The mediocre efficacy and the relatively low potency of all beta-adrenergic agonists on adenylate cyclase suggested a relatively low density of beta 2-adrenergic receptors, as compared to the enzyme density.

Adenylyl Cyclase Inhibitors↗

The human heart beta-adrenergic receptors. I. Heterogeneity of the binding sites: presence of 50% beta 1- and 50% beta 2-adrenergic receptors.

Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 microM GTP and of increasing concentrations of four nonselective agonists giving a Hill coefficient of 1 (isoproterenol, salbutamol, fenoterol, and epinephrine), of two nonselective antagonists giving a Hill coefficient of 1 (pindolol and propranolol), and of a series of selective drugs giving a Hill coefficient of 0.60-0.72 that included three beta 1-selective antagonists (practolol, metoprolol, and atenolol) and two beta 2- selective agonists (procaterol and zinterol). KD values for all drugs were compatible with the coexistence in membranes from human auricles of beta 1- and beta 2-adrenergic receptors, the relative proportions of receptors of each subclass being approximately the same.

Adrenergic beta-Agonists↗

The human heart beta-adrenergic receptors. II. Coupling of beta 2-adrenergic receptors with the adenylate cyclase system.

The beta-adrenergic stimulation of adenylate cyclase in membranes from human auricles, ventricles, and fetal heart was compared with the binding properties of beta-adrenergic receptors in human auricles. In terms of adenylate cyclase activation, three full agonists (isoproterenol, epinephrine, and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol, and zinterol), and four antagonists (propranolol, metoprolol, atenolol, and practolol) were tested. The beta-adrenergic activation of adenylate cyclase in membranes from rat heart (with a majority of beta 1-adrenergic receptors), rat erythrocytes, and rat reticulocytes (with a homogeneous population of beta 2-adrenergic receptors) served as reference. The reactivity of human heart adenylate cyclase, estimated by the Kact or Ki values of 11 beta-adrenergic agents, indicated that the activation of this enzyme occurred through receptors of the beta 2-subtype only. Receptors of the beta 1-subtype (50% of the total population) were not coupled to the enzyme.

Adenylyl Cyclases↗

Effects of PHI on vasoactive intestinal peptide receptors and adenylate cyclase activity in lung membranes. A comparison in man, rat, mouse and guinea pig.

The presence of receptors, recognized by vasoactive intestinal peptide (VIP) as well as by PHI (a peptide with N-terminal histidine and C-terminal isoleucine amide), was documented in lung membranes from rat, mouse, guinea pig and man by the ability of these receptors, once occupied, to stimulate adenylate cyclase. In lung membranes from rat, mouse and guinea pig, the capacity of VIP, PHI and secretin to stimulate the enzyme and the potency of the same peptides to compete with 125I-VIP for binding to VIP receptors were similar, the affinity decreasing in the order: VIP greater than PHI greater than secretin. In addition, dose-effect curves were compatible with the coexistence of high-affinity and low-affinity VIP receptors, in the four animal species considered. If PHI was able to recognize all VIP receptors it could not, however, discriminate the subclasses of VIP receptors.

Adenylyl Cyclases↗

Characterization of the VIP- and secretin-stimulated adenylate cyclase system from human lung.

The response of a crude particulate adenylate cyclase preparation from surgically removed human lung to guanine nucleotides, sodium fluoride, beta-adrenergic agonists, prostaglandins, vasoactive intestinal peptide (VIP), secretin, and [Val5]secretin was investigated. The enzyme activity increased 5, 10, and 9-fold, respectively, with GTP, Gpp(NH)p, and sodium fluoride. This activity was stimulated (in the presence as well as in the absence of added GTP) by D,L-isoproterenol, L-epinephrine and L-norepinephrine, the relative potency of these agonists being compatible with the existence of beta-adrenoceptors of the beta2 subtype. Prostaglandins E1 and E2, but not PGF1alpha and PGF2alpha, stimulated the enzyme, PGE1 being at least 10 times more potent than PGE2. The biphasic pattern of stimulation of the same adenylate cyclase activity by VIP suggested the presence of high- and low-affinity VIP receptors coupled to the enzyme. This stimulation by VIP was not inhibited by secretin-(7-27). The stimulation of adenylate cyclase by secretin and [Val5]secretin was also biphasic, suggesting the coexistence of high- and low-affinity secretin receptors. Secretin-(7-27) was able to inhibit completely the secretin stimulation acting through high-affinity secretin receptors but exerted no effect on the stimulation operating through low-affinity secretin receptors, which might indicate that the latter receptors were in fact "VIP-preferring receptors". [Val5]secretin was also used to differentiate these peptide receptors, since its properties were more VIP-like than those of secretin.

Adenylyl Cyclases↗

Comparison of VIP-secretin receptors in rat and human lung.

The binding of 125I-VIP (Vasoactive Intestinal Peptide) to a crude particulate fraction from a rat lung was reversible and 125-I-VIP dissociation was accelerated by guanine triphosphate nucleotides. The relative potency of VIP and related peptides to compete with 125-VIP for binding was similar to their ability to stimulate adenylate cyclase in the same preparation. Dose-effect curves were compatible with the existence of two classes of VIP-receptors: a high-affinity type with equal affinity for VIP and [Val5] secretin, and a low-affinity type with affinity decreasing in the order VIP greater than [Val5] secretin greater than secretin. The response of a crude particulate adenylate cyclase preparation from human lung was also investigated. The biphasic pattern of adenylate cyclase stimulation by VIP suggested the presence of high- and low-affinity VIP receptors coupled to the enzyme. In addition, the stimulation of adenylate cyclase by secretin and [Val5] secretin was also biphasic, suggesting the coexistence of high- and low-affinity secretin receptors, Secretin (7-27) inhibited completely the secretin-stimulated activity operating through high-affinity secretion receptors, so that these receptors appear to be genuine secretin-preferring receptors.

Adenylyl Cyclases↗

[Introduction to Raman spectrometry].

The frequency shift observed when light is scattered by molecules is called Raman effect. Raman spectroscopy like infrared spectroscopy is a method of studying molecular vibrations. The two methods are complementary, they both give much informations about the structure of molecules and crystals, the nature of chemical bonds and intermolecular interactions. Infrared absorption is allowed if the vibration is accompanied by a variation of electric dipole moment, however Raman scattering will only be observed if a variation of molecular polarizability appears during the vibration. Symetry properties of molecules of crystals lead to the determination of the number of normal vibrational modes and their Raman or infrared activity. The discovery of Laser light source has permitted a great development of Raman instrumentation. Raman spectrometers can easily record the whole spectrum of molecular vibrations (0-4000 cm-1) of samples in solid, liquid or gazeous state. Very small quantities of material are required (several milligrams). Aqueous solutions are easily investigated. Owing to the easy exploration of the low frequency range by modern spectrometers, new areas are opened in the study of the solid state and polymeric chains. Resonance Raman effect allows the spectra of very dilute solutions to be obtained. With the development of rapid scanning systems and electro-optical spectrometers, study of transients species is now possible. Among the physical analysis methods, Raman spectroscopy is now more and more used, and this technic has already been successfully used in numerous biological and biochemical problems.

Crystallography↗

Resonance Raman spectroscopic studies of the interactions between trypsin and a competitive inhibitor.

Raman spectroscopy was used to study the interactions between bovine trypsin and a competitive inhibitor. For this purpose, a chromophoric substrate analogue, 4-amidino-4'-dimethylamine azobenzene, was synthesized. This compound competitively inhibits the enzyme with a 1:1 stoichiometry and an inhibition constant Ki of 2.3 muM at pH 6.08 and 15 degrees. Resonance Raman spectra in aqueous solution of free or enzyme-bound inhibitor were analyzed. The main spectral changes observed upon enzyme-inhibitor complex formation were changes in the relative intensities of four bands (1171, 1206, 1315, 1608 cm-1) while no large frequency shifts occurred. The binding of the inhibitor molecule to the enzyme did not induce a twisting of the phenyl groups around the N=N bond. Some modifications of the band widths are interpreted in terms of a restriction of rotational motions in the inhibitor molecule. The possible involvement of specific interactions between trypsin and the benzamidinium ion part of the inhibitor molecule is discussed.

Azo Compounds↗

Vasoactive intestinal peptide (VIP) and peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) stimulate adenylate cyclase activity in human heart membranes.

The presence of receptors, recognized by Vasoactive Intestinal Peptide (VIP) and Peptide having N-terminal Histidine and C-terminal Isoleucine amide (PHI), was documented in membranes from human right auricle and left ventricular cardiac muscle by the ability of these peptides to stimulate adenylate cyclase. The capacity of VIP and PHI to activate the enzyme was comparable, in auricle as well as ventricle membranes, the affinity of the system being moderately higher for VIP than for PHI. In auricles, dose-effect curves appeared compatible with the coexistence of high-affinity and low-affinity VIP receptors. PHI could not, however, discriminate these subclasses of VIP receptors.

Adenylyl Cyclases↗

Plasma and erythrocyte essential fatty acids during total parenteral nutrition in infants: effects of a cutaneous supply.

In order to prevent essential fatty acid (EFA) deficiency induced by fat-free total parenteral nutrition (TPN), 10 infants on TPN were rubbed three times daily for 20 days using oenethera oil (80% EFA). Total EFA amount provided cutaneously was 1900 mg/kg/d. Plasma and red blood cells phospholipids were determined on days 1 and 20 in these 10 treated and six untreated infants on TPN and compared with those of normal control infants. On day 1, plasma nonessential FA including 20:3 n-9(p less than 0.01) were increased in both TPN groups while 18:2 n-6 and 18:3 n-3 (p less than 0.001 and p less than 0.01) were decreased. On the 20th day, EFA deficiency had worsened with a decrease in plasma level of 20:4 n-6 (p less than 0.02) and a higher than normal triene/tetraene ratio : 3.4 +/- 1.1 and 2.3 +/- 0.6 vs 0.1 +/- 0.1 (p less than 0.02). As for red blood cells phospholipids, 16:0 was increased and 18:2 n-6 and 20:3 n-6 were decreased (p less than 0.05) on day 1. On day 20, these FA were more abnormal while 20:3 n-9 became significantly increased (p less than 0.05). No difference was observed between the TPN groups at any time. These results show that cutaneous application of large amounts of EFA-rich oil is unable to prevent or cure TPN induced EFA deficiency.

Absorption↗

Hepatocellular carcinoma: surgical treatment and prognostic variables in 56 patients.

BACKGROUND/AIMS: Partial hepatectomy (PH) or total hepatectomy and orthotopic liver transplantation (OLT) may be curative in selected patients treated for hepatocellular carcinoma (HCC). The analysis of clinical series may help in the choice of the more appropriate treatment. METHODOLOGY: During the past 11 years, 40 patients with HCC were treated by PH and 16 patients underwent total hepatectomy and OLT. Selection criteria for transplantation were the liver function and the tumor resectability. RESULTS: The actuarial 1-, 3- and 5-year survival rates were 67%, 34% and 18%, respectively, after PH and 62%, 54% and 54% after OLT. The only prognostic factor after PH was the tumor extension to a single or both lobes. Patients with associated cirrhosis had significantly more post-operative complications, but a comparable long-term survival. The proliferative cell nuclear antigen labeling index (PCNA-LI), evaluated on tumoral tissue in 16 patients, showed that an index <30% indicates a better prognosis for HCC developing in non-cirrhotic liver. CONCLUSIONS: For patients carefully pre-operatively evaluated, the presence of an associated cirrhosis does not seem to modify the long-term survival after PH, and OLT may offer more than 50% 5-year survival. A PCNA-LI <30% appears to be a good prognostic factor in patients without cirrhosis.

Actuarial Analysis↗

Endoscopic stenting for biliary strictures.

A consensus is growing among units that have an experience in both endoscopic and percutaneous stenting techniques that the endoscopic approach of malignant biliary strictures is more comfortable for the patient and provides less complications. This article describes endoscopic biliary drainage in different malignant stenosis of the bile ducts and delineates the respective indications of percutaneous and endoscopic techniques together with the possible combination of these two methods in selected cases. It also tackles the question of the medical surgical approach of the patients, which might, thanks to a better selection, reduce the morbidity and mortality associated with surgery. The indications of biliary stenting in benign strictures, namely post operative or chronic pancreatitis associated biliary stenoses, are also discussed. Recently, new materials became available for endoscopic and percutaneous biliary drainage, and particularly metallic self expanding stents which might provide a better palliation among these patients. If these stents fulfill their promise on longer follow-up, they may replace the conventional stenting devices.

Biliary Tract Neoplasms↗

Endoscopic treatment of esophagogastric varices.

We report our current management of variceal bleeding with endoscopic sclerotherapy. We emphasize the importance of resuscitation and of recording at time zero and within the first 72 hours clinical and laboratory indicators, as these influence the management of these patients. Primary sclerotherapy using Histoacryl for active bleeding and Ethoxysclerol for recent bleeding should be performed as soon as the patient is stable hemodynamically. As we have identified factors related to the severity of hemorrhage and of liver failure degree which can predict early failure of sclerotherapy, patients presenting with these findings should be, in the future, referred quickly toward alternative therapies among which non-surgical intrahepatic shunt appears a promising modality.

Cyanoacrylates↗

Treatment of peptic ulcer severe bleeding.

The success of a defined management policy op peptic ulcer haemorrhage which incorporates endoscopic therapeutic intervention depends on the early identification of a high risk group of patients and a high risk group of ulcers. The high risk group of patients consists of those likely to experience further bleeding on the basis of clinical prognostic indicators: shock and severe anaemia on admission and the pattern of bleeding; or tolerate rebleeding and emergency surgery poorly: patients over 60 years and those with associated disease. UGI endoscopy should be performed early (within 6-12 hours) in this group in order to identify the bleeding point and provide prognostic information regarding the risk of further haemorrhage. Peptic ulcers with major stigmata of recent bleeding (spurting or non-bleeding visible vessel) have high risk of rebleeding, the risk is even greater when major stigmata of recent haemorrhage (SRH) are associated with shock on admission. Patients with such ulcers should be monitored intensively and receive endoscopic haemostatic treatment in order to terminate active haemorrhage or prevent rebleeding thereby avoiding the need for emergency surgery with its attendant morbidity and mortality. Patients with ulcers with minor or no SRH have a very low risk of rebleeding and don't require intensive monitoring or endoscopic treatment and can be discharged from hospital early. Ulcers which cannot be completely characterized have an intermediate risk of rebleeding and should be managed as high risk lesions. Secondary to the anatomy of the visible vessel any haemostatic endoscopic treatment should be applied around, but avoiding, the sentinel clot. Well-designed randomized controlled trials of endoscopic haemostatic treatment of peptic ulcer haemorrhage in which stratification of risk was based on the SRH, have demonstrated for non-bleeding vessel a significant reduction in rebleeding and in emergency surgery, for spurting bleeding benefit was found only for the rebleeding risk. No advantage was demonstrated in each group of patients in term of mortality. Such studies also demonstrate the superiority of the Nd:YAG laser over the Argon laser. Perforation is a rare complication of Nd:YAG laser photocoagulation (less than 1%). Precipitation or aggravation of arterial haemorrhage during treatment of a visible vessel, as a result of a direct hit, is a more frequent complication (0-29%). Further laser treatment is successful in terminating 75% of these induced bleeds, the remainder requiring surgery. Preinjection of the ulcer with adrenaline does not appear to prevent this complication.(ABSTRACT TRUNCATED AT 400 WORDS)

Gastroscopy↗

Clinical significance of pancreas divisum.

Pancreas divisum (PD), a congenital anatomic variant consisting of a separate pancreatic ductal system, is diagnosed in nearly 10% of patients for whom a successful pancreatogram was obtained. The relationship between PD and pancreatic disease is discussed since 1976. Some authors, reporting a higher incidence of pancreatitis in patients having two separate pancreatic ducts, proposed the concept of relative outflow obstruction of pancreatic juice through the accessory papilla. Based on the literature data and on our own experience, this review asserts that there is no definite evidence for PD being associated with a significantly risk of idiopathic pancreatitis. Discrepancies between epidemiological series could be explained by selection biases leading to an apparent association of PD and pancreatitis. An objective assessment of accessory papilla stenosis in patients with PD is not clearly available to give consistent results. Although controversies persist with regard to the actual abnormality of PD and the presence of stenosis into the accessory papilla, several endoscopic and/or surgical procedures have been proposed in an attempt to correct what is thought to be a stenosis of the orifice of the dorsal duct. More than 300 patients have been treated until now with variable and unpredictable results, these treatments are not devoid of complications. We conclude that PD should be considered as a frequent coincidental anatomic variant having no clinical significance in the great majority of patients and not requiring systematic further therapy.

Ampulla of Vater↗