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Biomedical subjects

G Peeters

Publications and source records attributed to G Peeters.

At least 19 recordsLinked to original sources

Interlimb coordination deficits in patients with Parkinson's disease during the production of two-joint oscillations in the sagittal plane.

Two-limb coordination patterns involving cyclical flexion-extension movements, performed in the same or in different directions, were studied in patients with Parkinson's disease and a group of elderly subjects. The three patterns referred to the homologous (both arms or legs), homolateral (right or left arm and leg), and heterolateral (right arm and left leg or vice versa) limb segment combinations that were performed in the sagittal plane from a seated position. Findings revealed that interlimb coordination deficits were evident in patients with Parkinson's disease. Moreover, mean cycle duration and its variability were increased, particularly during the production of nonhomologous limb movements in different directions. These temporal findings suggest that movement slowness was not a primary consequence of an intrinsic inability to move the limb segments at the required speed but rather reflected an intentional strategy to cope with the complexity of the coordination pattern. Finally, movement amplitude was substantially smaller and more variable in patients with Parkinson's disease, suggestive of hypometria during the production of these cyclical tasks.

Aged↗

Mechanism of action of OPC-8490 in human ventricular myocardium.

BACKGROUND: The quinolinone compounds OPC-8212 (vesnarinone), OPC-18790, and OPC-8490 are members of a family of unique positive inotropic compounds that have no positive chronotropic effects. In subjects with heart failure, the prototypic compound OPC-8212 may reduce morbidity and mortality at low doses but increase mortality at high doses. METHODS AND RESULTS: To further characterize the inotropic mechanism(s) of action of these compounds, we investigated the effects of OPC-8490, a water-soluble quinolinone, on the inotropic response, inhibition of phosphodiesterase (PDE), and action potential in human ventricular myocardial preparations. In isolated right ventricular trabeculae and membranes prepared from left ventricular myocardium, OPC-8490 produced dose-related positive inotropic effects, inhibited type III PDE activity, and prolonged action potential. Comparative experiments with other PDE inhibitors, sodium channel agonists, and potassium channel antagonists indicated that the positive inotropic effects are due to PDE inhibition, whereas the action potential effects of OPC-8490 are due to effects on ion channels. CONCLUSIONS: We conclude that OPC-8490 produces selective positive inotropic effects because of type III PDE inhibition combined with ion channel effects, with the latter property inhibiting the positive chronotropic response usually associated with agents that increase intracellular cAMP concentrations.

3',5'-Cyclic-AMP Phosphodiesterases↗

Relationship between numbers of alpha 2- and beta 2-adrenoceptors in teat tissue and blood cells and milkability of primiparous cows.

Milking characteristics were measured on 14 cows at morning milkings. After collection of blood, cows were slaughtered and teats were removed. beta 2-Adrenoceptors on teat tissue and lymphocyte membranes were identified by binding of [3H]dihydroalprenolol. For the determination of alpha 2-adrenoceptors on teat tissue and blood platelet membranes, [3H]rauwolscine was used. In teat tissue and blood cells, except for the amount of milk collected during the 3rd min, all other milking parameters were highly correlated with the ratio of beta 2-adrenoceptors to alpha 2-adrenoceptors. Good milkability appears to be associated with low ratio of beta 2-adrenoceptors to alpha 2-adrenoceptors densities in teat tissue, and a high ratio of beta 2- to alpha 2-adrenoceptors densities in blood cells. We postulated earlier that a low ratio of beta 2- to alpha 2-adrenoceptors in teat tissue of fast milking cows probably reflects changes of mainly prejunctional adrenoceptors. From our results on blood cells, we are now hypothesizing that in teat tissue prejunctional and extra junctional alpha 2- and beta 2-adrenoceptors might have been identified together, whereas alpha 2- and beta 2-adrenoceptors identified on blood platelets and lymphocytes, respectively, are reflecting by preference extra junctional adrenoceptors are activated primarily by circulating epinephrine. The high ratio of beta 2- to alpha 2-adrenoceptors observed in blood cells of fast milking cows might indicate a decreased vasomotor tone in the teat and an increased dilatation of the teat sphincter in these animals.

Animals↗

Comparison of the milk leakage potencies of adrenergic agonists in lactating cows.

The activities of epinephrine (2-6 micrograms) and of norepinephrine (20-60 micrograms) on the relaxation of teat sphincter muscles were compared by measuring milk leakage from the full udder of 5 lactating cows. Substances were injected into the external pudic artery after pretreatment with an alpha-adrenoceptor blocking agent (prazosin or phentolamine). Milk leakage was induced by creating a vacuum (-30 cm of water) in a plethysmographic chamber enclosing one teat and volumes of milk loss were measured every min. In a second series of experiments the activities of the beta 2-adrenoceptor selective agonist zinterol (0.5-2.5 micrograms) and of the nonselective beta-agonist isoproterenol (3-22.5 micrograms) on sphincter muscle relaxation were compared. Epinephrine was found to be more potent than norepinephrine in inducing relaxation of sphincter muscles. Zinterol was more active than isoproterenol. It is concluded that there is a predominance of beta 2-adrenoceptors in the teat sphincters.

Adrenergic alpha-Agonists↗

Effects of valerate and isobutyrate on fatty acid secretion by the isolated perfused mammary gland of the lactating goat.

The isolated mammary glands of six lactating goats were perfused with heparinized and oxygenated blood for 8 to 11 h. Adequate quantities of glucose, acetate and amino acids (including valine) were added to the perfusate. Either unlabelled valerate or unlabelled isobutyrate was added in excess to the perfusate of one gland, while the respective symmetrical gland was used as a control. After the administration of valerate, the proportions of the odd-numbered fatty acids (C11:0, C13:0, C15:0) in the milk fat, collected every hour during perfusion, rose progressively after 5 h until the end. The synthesis of milk fatty acids from valerate is discussed. After isobutyrate was added to the perfusate, isoC12:O, isoC14:0 and isoC16:0 in the milk fat increased as compared to the control. The effect of isobutyrate indicated that valine acted as a precursor of milk iso-branched fatty acids after its metabolisation to isobutyryl-CoA. During perfusion in the presence of the complete substrate mixture, the proportion of certain major milk fatty acids (C10:0, C12:0, C14:0 and C16:0) increased, whereas the proportion of C18:0 and C18:1 decreased. These effects have been ascribed to the presence of acetate and beta-hydroxybutyrate in the substrate mixture.

Animals↗

Double-blind comparison of ketanserin with placebo in patients with essential hypertension.

Two double-blind multicenter trials were performed to compare the antihypertensive action of ketanserin, at an oral dosage of 20 mg three times daily, with that of placebo over a period of four to six weeks. A subset of patients was treated in a crossover fashion for either four weeks (36 patients) or six weeks (24 patients). The patients had essential hypertension, with a diastolic blood pressure greater than or equal to 95 mmHg measured in sitting position at the end of a placebo run-in period of at least one week. In a first trial, 78 of 82 patients completed the four-week study period, where the mean drop of the systolic/diastolic blood pressure was -14/-12 mmHg in the ketanserin group (n = 32) versus -8/-5 mmHg in the placebo group (n = 46). This difference is statistically significant (p = 0.05/p less than 0.01). In 13 patients who after the initial ketanserin treatment were further treated with placebo in crossover for four weeks, the blood pressure rose slightly (+1/+3 mmHg). In the alternative group (n = 23), the blood pressure fell by -10/-7 mmHg after placebo and decreased further by -10/-8 mmHg after ketanserin. In a second trial, 24 patients completed a two by six week crossover treatment. In 12 patients assigned to the sequence placebo-ketanserin, there was a drop of the systolic/diastolic blood pressure by -7/-4 mmHg after placebo and an additional drop by -26/-10 mmHg after ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Relationship between milkability and adrenoceptor concentrations in teat tissue in primiparous cows.

Milking characteristics were measured on 19 primiparous cows of the Red Pied breed at morning milkings. Measurements included maximum and average rate of flow, yield of milk through the 1st, 2nd, and 3rd min, amount of milk through the first 2 and first 3 min of milking, and milking time. Subsequently cows were slaughtered and teats immediately removed. Adrenoceptors on membranes isolated from teat tissue were identified by radiolabeled antagonists: [3H]dihydroalprenolol for beta 2-adrenoceptors, [3H]rauwolscine for alpha 2-adrenoceptors, and [3H]prazosin for alpha 1-adrenoceptors. Measurements of milking characteristics were highly repeatable within cow. Cows showed five distinct and significantly different milk flow patterns, which were characteristic for fast (type I, II), relatively fast (type III), and slow (type IV, V) milking cows. Covariance analysis for the five different types revealed an average regression between alpha 2-adrenoceptor density and milking rate 1st min as well as between beta 2:alpha 2-adrenoceptor ratios and milking rate 2nd min and milking time. A hypothesis is presented to explain these observations. During milking, tone of efferent sympathetic nerves in the teat is low. This phenomenon is more pronounced in fast milking cows. The typical presynaptic adrenoceptor pattern in the teat of fast milkers (low beta 2:alpha 2-adrenoceptor ratio) results in a decline of norepinephrine release by feedback mechanisms.

Animals↗

A comparison of the binding characteristics of the alpha 2-adrenoceptor antagonists 3H-yohimbine and 3H-rauwolscine in bovine teat muscles.

3H-Yohimbine and 3H-rauwolscine, both potent and selective alpha 2-adrenergic antagonists, were used to identify alpha 2-adrenoceptors in smooth muscles of the cistern wall of teats of lactating cows. Binding of these radioligands was rapid and readily reversed by 10 microM phentolamine. Saturation experiments in the presence of 3H-yohimbine showed an equilibrium KD value of 6.23 +/- 0.74 nM and a maximum number of sites of 81 +/- 7 fmol/mg of membrane protein. In the presence of 3H-rauwolscine, however, a higher density of alpha 2-receptors (164 +/- 12 fmol/mg protein) with a KD of 6.16 +/- 0.64 nM was found. No cooperative interactions among both binding sites were observed. Both 3H-yohimbine and 3H-rauwolscine binding sites showed alpha 2-adrenergic specificity. On the basis of its higher affinity to the alpha 2-adrenoceptor sites, better ratio of specific to non-specific binding and for other reasons, 3H-rauwolscine appears to be the ligand of choice.

Adrenergic alpha-Agonists↗

Effect of serotonin on the motility of smooth muscles in teats of lactating cows.

The effects of serotonin, injected into one udder artery, on teat smooth muscle function were investigated in four lactating cows. Motility of longitudinal smooth muscles was recorded by a plethysmographic technique, and sphincter function by measuring milk leakage from the full udder. Serotonin (40, 120 and 360 micrograms) activated teat muscle tonicity and reduced the volume of milk leakage. The effects on longitudinal smooth muscles were reduced by mianserin and ketanserin (0.375, 1.5 and 6 mg) and by methysergide (1.5 mg). These blocking substances were also effective (0.2, 0.6 and 1.8 mg respectively) in antagonizing the inhibiting action of serotonin on milk leakage. It is suggested that serotonin effects are mediated by receptors of the S2-type.

Animals↗

Changes in the fatty acid composition of goat milk fat after a 48-hour fast.

Five lactating goats were milked twice daily. After a control period of 3 days, they were fasted for 48 hr. The milk was collected at each milking. At the end of the fasting period, milk yield fell to 28% and milk fat to 55% of the original yield. The percentage of milk fat increased. Generally, the relative concentrations of fatty acids with less than or equal to 16 carbons, containing even and odd-numbered straight-chain as well as monomethyl-substituted fatty acids of the milk fat, decreased significantly 24 hr after food was withheld. The decrease was most pronounced for the fatty acids with the shortest chain lengths. Longer-chain acids increased or did not change. Iso and anteiso-acids seemed to follow the same, although less pronounced trend, the effect being obvious after 48 hr of fasting. It is suggested that the decline in the proportions of fatty acids with less than or equal to 16 carbons was due to the inhibition of mammary gland synthesis. The increase in the proportions of longer-chain fatty acids was ascribed to adipose tissue lipolysis.

Animals↗

Homogeneity of beta-adrenoceptors on bovine teat muscles.

Bovine teat beta-adrenergic receptors were investigated with binding studies using 3H-dihydroalprenolol (DHA) as ligand. Inhibition of 3H-DHA-binding by beta 1-(betaxolol, atenolol, practolol) and beta 2-(zinterol, fenoterol, ICI 118551) selective drugs resulted in monophasic displacement curves with Hill coefficients close to 1.0. Computer assisted analysis of these curves did not reveal the presence of more than one class of binding sites. These data suggest that the beta-receptor sites present in bovine teat walls are of the beta 2-subclass.

Adrenergic beta-Antagonists↗

Identification and characterization of 3H-prazosin binding to alpha 1-adrenoceptors in bovine teat muscles.

The highly specific alpha 1-adrenoceptor antagonist 3H-prazosin was used to characterize alpha 1-adrenoceptors in smooth muscles of the cistern wall of teats of lactating cows. Binding was rapid, readily reversible, stereospecific and saturable. Scatchard analysis of saturation binding data on bovine teat membranes revealed that 3H-prazosin bound to a single class (Bmax = 128 +/- 13 fmol/mg of membrane protein) of noncooperative sites (Hill coefficient = 0.95 +/- 0.02) with high affinity (KD = 0.47 +/- 0.05 nM). Competition binding studies with 9 antagonists and 8 agonists, indicated that 3H-prazosin labeled the alpha 1-receptor.

Animals↗

Effect of prazosin on the function of the teat sphincter in lactating cows.

Oxytocin was infused for 60 min into the jugular vein of 8 lactating cows with full udders before milking. Under these circumstances milk loss occurred spontaneously in 3 cows and was evoked in 5 cows by reducing pressure around one teat (-30 cm water) using a plethysmographic chamber. Milk loss was measured continuously. The postsynaptic alpha-blocking agent prazosin ( PRZS ) injected either into the udder artery (2 or 5 mg) or into the jugular vein (200 mg) consistently induced a significant increase in milk leakage. It is suggested that PRZS effectively inhibits alpha-adrenoceptors in the teat sphincter muscles and thus promotes the action of beta-adrenoceptors, in this way inducing relaxation of the teat sphincter.

Animals↗

Identification of beta-adrenoceptors in bovine teat muscles by 3H-dihydroalprenolol binding.

beta-Adrenoceptors present in smooth muscles of the cistern wall of teats of lactating cows were identified and characterized by 3H-dihydroalprenolol (DHA) binding. Binding association and dissociation at 37 degrees C were very rapid (t1/2 amounting to 2 min and 1 min 30 sec respectively), stereospecific and saturable. By Scatchard analysis, the mean receptor density was 92 fmol of 3H-dihydroalprenolol bound/mg protein and the dissociation constant was 0.63 nM. The Hill number was 1.01. The order of potency of catecholamines for the binding was (-)-isoproterenol greater than (-)-epinephrine greater than (-)-norepinephrine, indicating a population of mainly beta 2-adrenoceptors. Potency series of 10 antagonists and 15 agonists, determined from binding-inhibition experiments, were composed.

Alprenolol↗

Action of epinephrine on the function of the teat sphincter in the lactating cow.

Under continuous IV infusion of oxytocin, milk leakage was elicited in 6 lactating cows with full udders by induction of a vacuum (-30 cm of water) around 1 mammary papilla (teat) with a plethysmographic apparatus. The volumes of milk loss were measured every minute. Epinephrine injected either into the jugular vein (20, 100, and 500 micrograms) or into the external pudic artery (1.5, 7.5, and 37.5 micrograms) induced an increase in milk leakage in 5 cows. This effect could be antagonized by the beta-blocking agent sotalol hydrochloride (0.5 to 4 mg) injected into the external pudic artery. In 1 cow, however, epinephrine given intra-arterially exerted a biphasic effect, small doses inducing stimulation, and large doses evoking inhibition of milk loss. The stimulating effects were blocked by sotalol (2 mg). The inhibiting effects were antagonized by the alpha-blocking agent prazosin (2 mg).

Animals↗

Metabolism of leucine by the isolated perfused goat udder.

Seven lactating goat mammary glands from 6 goats were perfused for several hours in the presence of [U-14C]L-leucine (4 experiments) or [2-3H; 1-14C]DL-leucine (3 experiments) and received adequate quantities of glucose, acetate and amino acids. Radioactivity in casein was mainly recovered in leucine and 90% of casein leucine was derived from free plasma leucine. About 64% of the leucine molecules were used for casein synthesis. Up to 12% of the molecules were channelled into lipid synthesis, while the remaining (up to 24%) were metabolized to CO2. From the 3H/14C ratio of casein and casein leucine, it was calculated that 70-80% of the leucine molecules were reversibly transaminated before their incorporation into milk protein. However, only 4-8% of the plasma leucine molecules were transaminated during passage through the udder. Different pools for oxidation and for protein synthesis may be present in the goat mammary gland.

Amino Acids↗