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Biomedical subjects

Y Joulin

Publications and source records attributed to Y Joulin.

17 recordsLinked to original sources
PubMed2001

Effects of BP 2-94, a selective H(3)-receptor agonist, on blood flow and vascular permeability of the rat mandibular incisor pulp.

Pulpal blood-flow changes were monitored by laser Doppler flowmetry after electrical stimulation of the mandibular incisor. Stimuli of 10 s (50 microA, 2 ms, 20 Hz) were applied to the incisors of untreated animals and longer stimulations (5 min) were applied in animals treated with the alpha-blocker phenoxybenzamine. Changes in vascular permeability in the dental pulp were measured by Evans blue extravasation following resection of the superior cervical ganglion. In these groups, a selective agonist of H(3) receptors, BP2-94 (1.5 and 15 mg/kg), and an H(3)-antagonist ciproxifan (1 mg/kg) were administered. The effects of these drugs were compared with those obtained from animals treated only with the vehicle (methylcellulose 1%). Basal pulpal blood-flow was not affected significantly by BP2-94 or ciproxifan. The vasoconstriction induced in the group of intact rats by electrical stimulation of 10 s is decreased in amplitude and duration at the higher dose of BP2-94 by 58 and 40%, respectively (P<0.05, n=5). In the sympathectomized animals, plasma extravasation was significantly increased at 15 mg/kg BP2-94 (+100%, P<0.01, n=5). These results suggest that H(3) receptors may participate in the regulation of changes in vessel contraction and permeability provoked by electrical stimulation of the dental pulp. However, the non-selective effects of the H(3) agonists reacting on adrenergic sites and H(1) receptors could explain a part of the results.

Animals↗
PubMed1999

In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-alpha-methyl-histamine and its prodrug BP 2.94 in the dog.

1. The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog. 2. Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1-4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-alpha-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP). 3. Cardiac sympathetic stimulation induced a noradrenaline release into the coronary sinus along with a tachycardia and an increase in left ventricular pressure and contractility without changes in mean arterial pressure. Intravenous administration of H3-receptor agonists significantly decreased noradrenaline release by the heart (R-HA at 2 micromol kg(-1) h(-1): +77 +/- 25 vs +405 +/- 82; BP 2.94 at 1 mg kg(-1): +12 +/- 11 vs +330 +/- 100 pg ml(-1) in control conditions, P < or = 0.05), and increases in heart rate (R-HA at 2 micromol kg(-1) h(-1): +26 +/- 8 vs +65 +/- 10 and BP 2.94 at 1 mg kg(-1): +30 +/- 8 vs 75 +/- 6 beats min(-1), in control conditions P < or = 0.05), left ventricular pressure, and contractility. Treatment with SC 359 (1 mg kg(-1)) a selective H3-antagonist, reversed the effects of H3-receptor agonists. Treatment with R-HA at 2 micromol kg(-1) h(-1) and BP 2.94 at 1 mg kg(-1) tended to decrease, while that with SC 359 significantly increased basal heart rate (from 111 +/- 3 to 130 +/- 5 beats min(-1), P < or = 0.001). 4. Functional H3-receptors are present on sympathetic nerve endings in the dog heart. Their stimulation by R-alpha-methyl-histamine or BP 2.94 can inhibit noradrenaline release by the heart and its associated haemodynamic effects.

Animals↗
PubMed1999

Effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet.

METHODS: The effects of 4 days of oral administration of different doses of two drugs, an enkephalinase inhibitor (the antisecretory agent, racecadotril) and a mu-receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. RESULTS: The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5)--nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. CONCLUSIONS: In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

Animals↗
PubMed1997

Reciprocal interactions between intralaminar and lateral thalamic nuclei in rats.

Reciprocal interactions between intralaminar thalamic nuclei (ncl. centralis lateralis, CL, and ncl. parafascicularis, Pf), the pretectal area (Pt) and lateral thalamic nuclei (ventrobasal complex, VB, ncl. anterior ventralis, AV, and ncl. ventralis anterior, VA) have been observed in ketamine-anaesthetized rats. Extracellular single unit activity has been recorded after single electrical stimuli. Electrical stimulation of the VB evoked a short latency orthodromic response followed by a pause in spontaneous activity in neurones of medial thalamic nuclei. Lateral thalamic neurones responded to electrical stimulation of the intralaminar nuclei or the pretectal area with the same pattern of response. Striatal, sensorimotor cortical or peripheral electrical stimulation also evoked similar responses. The pauses in spontaneous activity were shown to be the result of inhibition since the responsiveness of the intralaminar nuclei or the lateral thalamic neurones to all inputs was abolished or reduced after a conditioning electrical single-shock stimulation in the VB or in the intralaminar nuclei, respectively. The two components of the response were of a different origin, since most of the short latency responses disappeared after medullary, upper cervical sections or large decortications, while the inhibitions persisted. These inhibitions were shown to be of thalamic origin since their duration was decreased after extensive decortications increased after medullary section. It is concluded that the neuroneal properties studied in this report are probably broadly represented throughout the thalamus and that thalamic neurones are under inhibitory control elicited by afferent volleys. This inhibitory control includes a relay in the nucleus reticularis thalami (nRT). The mechanisms of sensory interaction can be purely thalamic, but they can be modulated by suprathalamic and/or mesencephalic loops.

Animals↗
PubMed1997

Abnormal neuroneal activities in intralaminar thalamic nuclei following chronic lesions of nucleus reticularis thalami in rats.

Extracellular single unit activity in the intralaminar thalamic nuclei (ncl. centralis lateralis, CL, n = 77 and ncl. parafascicularis, Pf, n = 163) and in the pretectal area (Pt, n = 75) was examined following chronic electrolytic lesions of the nucleus reticularis thalami (nRT) in ketamine-anaesthetized rats after single electrical stimuli to the ventrobasal complex (VB). Extensive alterations of either the ongoing ("spontaneous") activity or the pattern of VB evoked responses were observed. Four major changes were observed in the activity of these intralaminar or pretectal neurones: 1) many neurones were silent, two times more frequently than in a parallel study with control intact rats; 2) the firing pattern of all the other neurones was in the form of tonic (stationary-like) discharge, without burst discharges as previously described in intact animals. They were ranked into classes according to their spontaneous discharge: class I, silent (no resting discharge) 12%, class II (1-15 Hz), 54 % and class III (> 16 Hz), 34%. Class III neurones were never found in intact rats; 3) electrical stimulation of the VB evoked a short latency orthodromic excitatory response in these neurones but this response was not followed by any slowing or depression of the spontaneous activity in more than 40% of recorded cells. When it occurred, this pause was shorter than that always observed in intact rats by more than 35% and longer in 7% of the responsive cells. All these changes were correlated with the extent of damage to the ipsilateral nRT; 4) VB stimulation evoked prolonged excitatory responses lasting more than 150 ms in 13% of the responsive cells, and nRT stimulation led to a short latency response followed by a pause of activity. These findings suggest that the nRT is involved in sensory integration and modulation.

Animals↗
PubMed1994

Effects of bradykinin B2 receptor antagonism on the hypotensive effects of ACE inhibition.

1. The aim of this study was to determine the participation of endogenous bradykinin (BK) in the antihypertensive effects of the angiotensin converting enzyme inhibitor (ACEI), perindoprilat, in the spontaneously hypertensive rat (SHR) on different salt diets. 2. Conscious SHRs receiving either a low or a high NaCl diet were used in order to evaluate the respective roles of angiotensin II suppression and bradykinin stimulation in the acute hypotensive effects of perindoprilat. Two different B2 receptor antagonists (B 4146 and Hoe 140) were used after bolus administration of 7 mg kg-1 of the ACEI, perindoprilat. In separate animals, Hoe 140 was administered before the injection of perindoprilat. In other experiments, the effects of Hoe 140 on the hypotensive effects of the calcium antagonist, nicardipine, were tested. 3. The different NaCl diets had no effect on baseline blood pressure. Hoe 140 injection before ACE inhibition did not modify blood pressure. Perindoprilat caused more marked hypotension in the low salt-fed rats than in the high salt animals (P < 0.01). Administration of Hoe 140 or B4146 after perindoprilat significantly reduced the antihypertensive effects of perindoprilat in the different groups, but this effect was more pronounced in high salt-fed rats. However, in SHRs receiving Hoe 140 before perindoprilat, the antihypertensive effect of perindoprilat was completely abolished in both high or low salt diet rats. In separate experiments we confirmed that Hoe 140 did not affect the hypotensive efficacy of the calcium antagonist, nicardipine. 4. Our study shows that inhibition of endogenous bradykinin degradation participates in the acute antihypertensive effects of perindoprilat in SHRs. The role of bradykinin is more pronounced following exposure to a high salt diet i.e., when the renin-angiotensin system is suppressed. Blockade of bradykinin B2 receptors by Hoe 140 before administration of perindoprilat completely abolished the hypotensive effect of perindoprilat suggesting an increased role of bradykinin in the onset of hypotensive action of ACE inhibitors. However, the exact mechanism of this interaction remains unclear.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Inhibitory effect of trimetazidine on thrombin-induced aggregation and calcium entry into human platelets.

The antiaggregatory properties of trimetazidine were investigated further by analyzing its effects on cytosolic calcium and proton concentrations, well-known regulators of platelet reactivity. Aggregatory responses of washed platelets were assessed by turbidometry, and cytosolic Ca2+ concentration ([Ca2+]i) and pH (pHi) were determined by their respective fluorescent probes: Fura-2 and BCECF. Preincubation with trimetazidine dose-dependently inhibited platelet aggregation induced by 0.05 U/ml thrombin (p < 0.001). At concentrations < or = 1 mM, trimetazidine did not affect the resting [Ca2+]i value but slightly alkalinized the cytosol by 0.05 +/- 0.03 pH units (p < 0.02, n = 11). In platelets stimulated by 0.05 U/ml thrombin, 0.1 mM trimetazidine did not modify pHi variations but decreased [Ca2+]i variations (p < 0.003, n = 16), blunting by 28 +/- 6% the transient peak of [Ca2+]i (p < 0.006) and decreasing by 6 +/- 2% the equilibrium value (p < 0.005). These inhibitory effects were inversely dependent on thrombin concentrations (p < 0.004, n = 21) and were abolished in the virtual absence of external Ca2+. Trimetazidine therefore attenuates the Ca2+ influx evoked by thrombin, thereby limiting Ca2+ accumulation in stimulated platelets. Such a protective effect may participate in the antiaggregatory properties of trimetazidine.

Blood Platelets↗
PubMed1993

Acute membrane effects of trimetazidine in human platelets.

The mechanisms by which trimetazidine (1-[2,3,4-trimethoxybenzyl]-piperazine) exerts its cytoprotective action have not been identified. This study was designed to investigate in human platelets and erythrocyte ghosts a possible perturbation of membrane dynamics by trimetazidine. Its effects on the steady-state anisotropies of two fluorescent probes, trimethylamino-diphenyl-hexatriene (TMA-DPH) and diphenylhexatriene (DPH) were compared. The effects on the aggregatory responses to collagen and ADP, and on platelet cAMP content were also investigated. In platelets, trimetazidine dose-dependently raised TMA-DPH anisotropy but not that of DPH. It reduced cAMP content (in the presence of Ro 15-2041, a phosphodiesterase inhibitor) and the aggregation responses to collagen and ADP. This suggests that trimetazidine decreases the 'fluidity' of the outer part of the plasma membrane, the adenylyl cyclase activity and some steps involved in platelet activation. In erythrocyte ghosts, the fluorescence anisotropy of TMA-DPH was not modified by trimetazidine. The membrane effects reported here could participate in the protection of cell metabolism afforded by a long-term treatment with trimetazidine.

Adenosine Diphosphate↗
PubMed1992

Fate of isopropyl-iodoamphetamine (IMP) in rat liver microsomes.

Para-iodoamphetamines are currently used in nuclear medicine to detect brain perfusion abnormalities with tomoscintigraphy. Little is known about their metabolism pathways in rat and humans. N-isopropyl-125I-iodoamphetamine (IMP) interactions were studied with rat liver microsomes. The first dealkylated metabolite (IAMP) at low concentration gave a type I binding complex then, with a high concentration, a very stable type II complex with oxidized cytochrome P-450 FeIII. In contrast, IMP only gave a type I binding complex in the absence of NADPH. In the presence of NADPH, IAMP and IMP produced 455 nm absorbing complexes, which were enhanced when phenobarbital-treated rat liver microsomes were used. During in vitro metabolic activation, covalent binding of IMP and IAMP on rat liver microsomal proteins was observed. This process was mixed function oxidase (MFO) dependent. The covalent binding level was higher with IAMP and was not affected by flavine oxidase inhibitors. These results confirm the interaction of IMP and IAMP with microsome proteins and cytochrome P-450 and suggest that an N-oxidation of IMP occurs after N-dealkylation. As cytochrome P-450 and dealkylated IMP (IAMP) were found in brain, cerebral metabolism in brain and evolution of activity biodistribution with the course of time can be suggested.

Amphetamines↗
PubMed1990

In vitro covalent binding of new brain tracer, para-125I-amphetamine, to rat liver and lung microsomes.

p-125I-amphetamine (I-Amp) is retained significantly in liver and lung during brain tomoscintigraphy. To attempt to explain this clinical observation, we have investigated the interaction of I-Amp with rat liver and lung microsomal proteins. Studies using spectral shift technique indicate that low concentration of I-Amp gives a type I complex and high concentration appears very stable type II complex with cytochrome P-450 Fe III. In the presence of NADPH, I-Amp gives rise to a 455 nm absorbing complex with similar properties to the Fe-RNO complexes. This complex formation was greatly enhanced with phenobarbital treated liver microsomes. The in vitro binding study shows that I-Amp and/or its metabolites was covalently bound to macromolecules in the presence of the molecular oxygen and NADPH-generating system. Incubation in the presence of glutathione, cystein and radical scavengers decreases binding. Mixed function oxydase (MFO) inhibitors diminish the amount of covalent binding and alter the extent of metabolite formation. The total covalent binding level increased with liver microsomes from PB pretreated rats as it was observed with the 455nm complex formation. The radioactivity distribution on microsomal proteins was examinated with SDS polyacrylamide gel electrophoresis and autoradiography. This experiment proves that the radiolabelled compounds are bound on the cytochrome P-450. The radioactivity bound increased when the PB induced rat liver microsomes were used. All these results indicate that I-Amp was activated by an oxydative process dependent on the MFO system which suggests a N-oxydation of I-Amp and the formation of reactive entities which covalently bind to proteins.

Amphetamine↗
PubMed1987

Interactions of phenylalkylamines with human lung membrane and microsome preparation.

Lipophilic amines are recognized as important tracers for brain imaging. Their pulmonary accumulation was a drawback for optimal concentration in the brain. We used IMP, HIPDM, IP, amphetamine derivatives to determine the relation between structure and accumulation in the lung. The incubation of phenylalkylamines in competition with 3H-Imipramine, for human lung membrane and microsomes was performed and led to the extraction of a competitive constant (KI). The results showed that the compounds can be classified in order of their decreasing affinity: Iodoamphetamine, iodoisopropylamphetamine, dimethyliodophentermine, hydroxyiodobenzyl propane diamine (HIPDM), isopropylamphetamine and amphetamine. Iodine set in the para position of the ring seemed to increase the affinity of phenylalkylamines for the lung. Adjunction of isopropyl or methyl groups to the lateral chain decreased this affinity.

Amines↗
PubMed1987

Amines for brain tomoscintigraphy.

Amines like N-isopropyl-p-123I-iodoamphetamine (IMP) and hydroxy 123I-iodobenzyl propyl diamine (HIPDM) associated with brain tomoscintigraphy have proved their worth for detecting ischaemic abnormalities. Even though the chemistry of their metabolism and their biodistribution are not fully understood, their application in the study of parenchymal impairment in stroke and reversible ischaemia yields additional information compared to the other methods of imaging like CT or MRI. The concept of a steady state in brain with a wash in/wash out model has been considered especially with IMP, to explain the evolution of the activity pattern with time when comparing early and delayed images. (This review leads to foresee the prognosis of of ischaemic diseases when redistribution is taken into account.)

Amphetamines↗