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Biomedical subjects

S Thorens

Publications and source records attributed to S Thorens.

17 recordsLinked to original sources
PubMed1999

Clara's birth.

Advocacy for homebirth is based on the strong assumption that birthing is a physiological process and does not require medical interventions unless things turn "wrong." Let us assume that something might always go wrong, for instance during Clara's birth when the placenta was still retained after three hours. What needs to be done? The moment the midwife entered the house she was endowed with a responsibility for any problem caused by her failure to give proper guidance. With this weight on her shoulder, and according to her training and experience, there was no other way for her than to suggest an intervention regarding the placenta. The two midwives, B, and C., might not agree on risk estimations, the nature of the intervention, whether it should be performed at home or in a hospital. The estimation of abnormalities, evaluation of risks and the procedures with which to handle them are the main practical difference between classic obstetrics and non-interventionist midwifery--by analogy, between allopathy and naturopathy. The rest (positive thinking) is basically literature. A delivery will not remain normal just because we decide it "must" be physiological. Dr. Barua, a professor of obstetrics in Pondicherry, pointed out that normal deliveries are rare--fewer than 10 percent in South India. What we have instead is either pathological or "natural" deliveries in which regenerative processes take care of abnormal situations. Unless she has developed sensitive hands, a birth assistant or midwife must rely on monitoring procedures to evaluate deviations from the normal process. Even with the greatest care, these procedures are intrusive in that they disconnect the parturient from her own sensations. While successful unattended homebirth stories emphasise the extraordinary power and sensitivity of a birthing woman, the whole dream seems to collapse in abnormal or pathological cases. It would have collapsed for Sonia as well, had she not discarded negative suggestions. Dependency on medical experts is an alienation by which the patient is forced to tolerate what is not tolerable to her at a precise moment. The trauma of medicalized birth is not surprisingly associated with rape. It remains that the leitmotif in homebirth literature is more "empowerment," self assertion, militancy for the freedom of choice and ownership of her own body, than "self reliance" which involves a long-term sensitisation. Even outstanding essays a advocating non-medicalized birth may contain a sentence with implicit fear talk defusing the argument. For instance: "And if need be, [the midwife] can transport you to the hospital if you truly need the help that only modern obstetrics can provide...."] The sentence may be countereffective to a reader who is insecure about homebirth. The problem lies in the proximity of "truly" and "only." It was indeed the writer's intention to emphasise "truly" with an interrogative connotation: "Are you sure you need it?" However, the effect is overruled by the assertive strength of "only." The reader's unconscious reading may be that, truly, she needs the help that only modern obstetrics can provide. This is an example of negative suggestions conveyed by confidence building talk about health and pregnancy. Another example was Denis and Sonia's obsession with the placenta retention problem that had been causally exposed by midwife B. Why should her empowerment end suddenly when there is a life threatening complication during the delivery? If the pregnant woman claims a fundamental right to choose her way of birthing in uncomplicated cases, she needs even more self determination when she is in real danger. This paradox is striking evidence that the common sense attitude toward danger is affected by the "allopathic mind." It sets up an insurmountable barrier between the physiological and the pathological, whereby symptoms are failures of the normal regenerative processes. Hence, testimonies of women feeling that their bodies "b

Female↗
PubMed1983

Does [3H]nifedipine label the calcium channel in rabbit myocardium?

The ionic and drug specificities of the [3H]nifedipine binding site in rabbit cardiac homogenates were investigated. Divalent cations inhibited specific [3H]nifedipine binding in the potency order: Ni+2 greater than Ca+2 greater than or equal to Mg+2. Monovalent cations did not affect binding. The inorganic calcium entry blocker La+3 (IC50 = 1.1 mM) was the most potent cation in inhibiting radioligand binding. Calcium entry blocking drugs of different chemical classes inhibited [3H]nifedipine binding, with a rank potency order of: nifedipine much greater than D600 = verapamil greater than tiapamil greater than cinnarizine = prenylamine. The same potency order was observed for these drugs in inducing negative inotropic activity of isolated, electrically stimulated rabbit papillary muscle. The stereoselectivity of verapamil and D600 ((-) much greater than (+) isomers) in depressing papillary muscle contractions was not seen in [3H]nifedipine competition experiments. This presents an obstacle to accepting the equivalence of the [3H]nifedipine binding site with the myocardial Ca+2 channel. It is, however, possible that the myocardial Ca+2 channel may be associated with multiple sites of action for calcium entry blockers.

Animals↗
PubMed1982

Characterization of [3H]nifedipine binding sites in rabbit myocardium.

A specific, high affinity (KD 1.8 nM) binding site for the calcium entry blocking drug [3H]nifedipine was identified in homogenates of rabbit myocardium. [3H]Nifedipine binding was rapid (t1/2 3 min) and reversible (t1/2 11 min). Calcium entry blockers with different chemical structures competed with [3H]nifedipine binding in the potency order: nifedipine much greater than D600 = verapamil greater than tiapamil greater than cinnarizine = prenylamine. Diltiazem and perhexiline did not significantly inhibit [3H]nifedipine binding. The potencies of these drugs to inhibit binding were similar to their abilities to depress contractions of the isolated rabbit papillary muscle. The stereoselectivity of D600 and verapamil ((-)-much greater than (+)-isomers) as inhibitors of papillary muscle contractions was not apparent in [3H]nifedipine competition experiments. The slopes of the concentration-inhibition curves for D600 and verapamil were significantly less than for nifedipine. It is concluded that [3H]nifedipine may be labelling part of the myocardial Ca2+ channel, and that verapamil-like substances and nifedipine differ in their mode of interaction with this binding site.

Animals↗
PubMed1982

Ca2+-dependent phosphorylation and Ca2+ uptake in membrane fractions of the mesenteric artery.

Ca2+-dependent phosphorylation of endogenous substrate proteins (mol. wt 30 800, 35 500, 38 600 and 53 200) is found in a membrane subcellular fraction from rabbit mesenteric arteries. Characteristics of 32P incorporation are suggestive of a phosphoester-type phosphorylation produced by a Ca2+-dependent protein kinase. Ca2+-dependent phosphorylation and Ca2+ uptake rate show comparable affinities for Ca2+ of 3.5 x 10(-7) M and 2.4 x 10(-7) M, respectively. The dependence of both phenomena on the MgATP concentration is also similar. Ca2+-dependent phosphorylation and Ca2+ uptake are inhibited by trifluoperazine with an IC50 of 3 x 10(-5) M and 5 x 10(-5) M, respectively. These results suggest that Ca2+ uptake might be modulated by a Ca2+-dependent protein kinase, which is possibly regulated by membrane-bound calmodulin. Endogenous Ca2+-dependent phosphorylation is stimulated up to 300% by the addition of boiled cytosol. This stimulation is due to phosphorylation of proteins of molecular weight 21 000 and 81 500 and is reversed by trifluoperazine. Since this stimulation cannot be mimicked by addition of calmodulin or phosphatidylserine, and since boiled cytosol does not stimulate Ca2+ uptake, it is proposed that an unknown cytosolic factor stimulates a second Ca2+ pump. Since cAMP-dependent protein kinase is shown to cause little phosphorylation and has no effect on Ca2+ uptake, it is concluded that a Ca2+-dependent rather than a cAMP-dependent protein kinase might modulate Ca2+ transport in vascular smooth muscle.

Adenosine Triphosphate↗
PubMed1981

Noradrenaline contractions in rabbit mesenteric arteries skinned with saponin.

1. In rings of small rabbit mesenteric arteries, noradrenaline induced oscillatory contractions. After depolarization with potassium, which produced in this preparation only a transient contraction, the arteries responded to noradrenaline with tonic contraction. 2. Artery rings, skinned for 6 min with saponin (0.5 mg/ml.), were highly sensitive to calcium (half-maximum contraction at 4 x 10(-7) M-Ca2+). In the skinned preparations, a contraction was still elicited by noradrenaline. 3. Treatment with saponin renders virtually all smooth muscle cells of the mesenteric artery preparation hyperpermeable as indicated by both physiological and morphological criteria. 4. While the Ca stores responsible for the noradrenaline-induced contraction of skinned arteries were depleted at a slow rate by 0.1 mM-EGTA, they were completely emptied by a 4 min exposure to 10 mM-EGTA. After release of intracellular Ca by noradrenaline, the Ca stores could be partially replenished by incubating the preparation in 10(-6) M-Ca2+ for 4 min. 5. Noradrenaline failed to contract skinned arteries after part of the intracellular Ca had been released by caffeine but not after Ca release by the ionophore X-537 A. 6. The mitochondrial uncoupler, carbonyl cyanide m-chlorophenylhydrazone, inhibited noradrenaline-induced contractions of skinned arteries. 7. Noradrenaline had no effect on 45Ca translocation in either membrane vesicles or mitochondria isolated from mesenteric arteries. 8. The present results show that in vascular smooth muscle a certain degree of structural integrity of the cell membrane, but not its selective permeability, is required for the coupling between alpha-adrenoceptors and Ca release from intracellular stores; the data also suggest that alpha-adrenoceptor stimulation results in release of Ca bound to the plasma membrane rather than indirect release of Ca accumulated in intracellular organelles.

Animals↗
PubMed1981

Tiapamil, a new calcium antagonist. 1. Demonstration of calcium antagonistic activity and related studies.

N-(3,4-Dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine-1,1,3,3-tetraoxide hydrochloride (tiapamil, Ro 11-1781), a new homoveratrylamine derivative, was studied under various experimental conditions which allow the recognition of calcium antagonistic activity, and compared with the reference calcium antagonist verapamil. Similar to verapamil, tiapamil inhibited in a concentration-dependent manner calcium-induced contractions in isolated, potassium-depolarized preparations of rat renal artery, dog coronary artery and rabbit main pulmonary artery. The inhibitory effects of tiapamil and verapamil were overcome by raising the calcium concentration of the bath fluid and a competitive antagonism between calcium ions and both compounds was found. In the rabbit main pulmonary artery both tiapamil and verapamil reduced 45Ca influx into the potassium-depolarized vascular smooth muscle cells. Calcium-mediated slowly rising potentials were evoked in partially depolarized guinea-pig papillary muscles by electrical stimulation in the presence of isoprenaline. Tiapamil, like verapamil, inhibited the slow potentials, an effect which was antagonized by elevation of the concentration of calcium or isoprenaline in the bath fluid. Both tiapamil and verapamil decreased contractile force in isolated guinea-pig atria and papillary muscles as well as in isolated cat hearts. In the last preparation the two compounds also reduced heart rate and increased coronary flow. These results characterize tiapamil as a calcium antagonist in both vascular smooth muscle and cardiac muscle. A comparison between tiapamil and verapamil indicated that both drugs are of approximately equal calcium antagonistic potency in coronary vascular smooth muscle, but verapamil is 5--10 times more potent in smooth muscle of other arterial beds and in cardiac muscle. Thus tiapamil appears to be a calcium antagonist with some preference for coronary vascular smooth muscle.

Anesthetics, Local↗
PubMed1980

Effects of tetraethylammonium chloride on contractile, membrane and cable properties of rabbit artery muscle.

1. Two types of effects of tetraethylammonium chloride (TEA) have been found in the smooth muscle cells of the rabbit main pulmonary artery. (a) With rapid onset of action TEA depolarizes the cell membrane, increases the membrane resistance, causes anomalous rectification and occasionally spike potentials in response to externally applied depolarizing current pulses and produces tonic contractions. (b) During prolonged (greater than 30 min) incubation in TEA phasic contractions develop progressively and the vascular strips respond to electrical stimulation with synchronized and powerful contractions. 2. There is a linear relationship between log concentration TEA and depolarization over the range of 10-100 mM-TEA. TEA (10 and 30 mM) raises the membrane resistance and decreases the core resistance. The latter effect appeared to develop more slowly than the former. 3. During short exposure to TEA part of the smooth muscle cells respond to depolarizing current pulses with spike potentials of variable amplitude and duration. These spikes are very sensitive to inhibition by verapamil or nickel chloride but are not affected by tetrodotoxin. The amplitude of electrotonic potentials, increased by TEA, is slightly further elevated by verapamil or nickle chloride. 4. TEA (10 mM) increases the mechanical response to low and intermediate potassium concentrations but has no effect on maximal contractions to high potassium. The slope of the line relating log potassium concentration to membrane potential is decreased by TEA. 5. TEA (10 mM) shifts the concentration response curve for the contractile effect of noradrenaline to the left and increases the maximum of noradrenaline-induced contractions. In the presence of TEA, noradrenaline reduces the membrane potential to markedly lower values than under control conditions. 6. It is concluded that the rapidly occurring effects of TEA on the vascular smooth muscle cells of the rabbit main pulmonary artery are a decrease in potassium and an increase in calcium conductance. The latter effect may be related to a blockade of potassium channels; however, we cannot rule out the possibility that TEA affects calcium conductance independent of its presumed action on potassium channels. The slowly developing effects of TEA may be ascribed to the formation of gap junctions and/or (less likely) to an intracellular accumulation of TEA.

Animals↗
PubMed1980

The effect of tetraethylammonium chloride on calcium fluxes in smooth muscle from rabbit main pulmonary artery.

1. In the first part of this investigation we studied the experimental conditions under which the 'lanthanum method' gives valid estimations of the changes in intracellular calcium induced by either tetraethylammonium chloride (TEA) or high K in the rabbit main pulmonary artery. Subsequently, the effect of TEA on Ca movements in this blood vessel was measured. 2. The uptake of 140La by the vascular tissue is time- and concentration-dependent; it is separated into an early and a late phase. La binds to at least two classes of extracellular sites with affinities of 0.06 and 4.76 M. 3. A 1 hr exposure of the vascular strips to a 1 mM-La solution appears to be a convenient treatment for removal of Ca from the extracellular space. Under these conditions (a) 45Ca efflux from an intracellular compartment loaded with Ca during exposure to TEA or K is virtually blocked, (b) there is no major penetration of La into the smooth muscle cells as revealed by electron microscopy, and (c) there is no change in the size of the extracellular space. 4. TEA increases in a concentration-dependent manner the La-resistant 45Ca content (maximum increase 0.18 m-mole 45Ca/kg wet weight in response to 70 mM-TEA). There is a linear relationship between log concentration TEA and 45Ca influx. 5. The calcium antagonist verapamil (10(-6) and 10(-5) M) inhibits the TEA-induced 45Ca influx. 6. The increase in 45Ca influx produced by K (20 or 30 mM) is markedly enhanced by TEA. 7. The noradrenaline-induced increase in 45Ca accumulation is not influenced by TEA. 8. 45Ca efflux from the La-resistant Ca space is increased by TEA both in the presence and in the absence of non-radioactive Ca in the medium. 9. It is concluded that TEA contracts the vascular smooth muscle cells of the rabbit main pulmonary artery by an increase in the Ca permeability of the cell membrane.

Animals↗
PubMed1979

Effects of some vasodilators on calcium translocation in intact and fractionated vascular smooth muscle.

The "lanthanum method" was used to measure the effects of vasodilators on the 45Ca influx induced in isolated strips of rabbit main pulmonary artery after replacement of NaCl by KCl in the bathing solution. Two Ca antagonists, verapamil and Ro 11-1781, produced dose-dependent inhibitions of 45Ca influx with IC50 values of 3 X 10(-7) and 4 X 10(-6)M, respectively. Papaverine was virtually equipotent with Ro 11-1781 (IC50 = 2 X 10(-6)M). High concentrations of diazoxide (10(-4) to 10(-3)M) and nitroglycerin (10(-3)M) were required to cause inhibitions which did not exceed 40%. While prazosin 3 X 10(-4)M stimulated 45Ca influx, sodium nitrite and sodium nitroprusside had no effect. A comparison of the effects of vasodilators on contraction and 45Ca influx indicated that, of the drugs studied, only Ca antagonists and papaverine may cause relaxation by interfering with Ca influx. While high concentrations (greater than 10(-4)M) of verapamil, papaverine and nitroglycerin produced an inhibition of 45Ca uptake by membrane fractions from rabbit aorta, the other vasodilators tested were inactive.

Animals↗
PubMed1978

Effects of adenosine 3' : 5'-monophosphate and guanosine 3' : 5'-monophosphate on calcium uptake and phosphorylation in membrane fractions of vascular smooth muscle.

The effects of adenosine 3' : 5'-monophosphate (cyclic AMP), guanosine 3' : 5'-monophosphate (cyclic GMP) and exogenous protein kinase on Ca uptake and membrane phosphorylation were studied in subcellular fractions of vascular smooth muscle from rabbit aorta. Two functionally distinct fractions were separated on a continuous sucrose gradient: a light fraction enriched in endoplasmic reticulum (fraction E) and a heavier fraction containing mainly plasma membranes (fraction P). While cyclic AMP and cyclic GMP had no effect on Ca uptake in the absence of oxalate, both cyclic nucleotides inhibited the rate of oxalate-activated Ca uptake when used at concentrations higher than 10(-5) M. The addition of bovine heart protein kinase to either fraction produced an increase in the rate of oxalate-activated Ca uptake which was further augmented by cyclic AMP. Cyclic GMP caused smaller stimulations of protein kinase-catalyzed Ca uptake than cyclic AMP. Mg-dependent phosphorylation, attributable to endogenous protein kinase(s), was inhibited in fraction E by low concentrations (10(-8) M) of both cyclic AMP and cyclic GMP. In fraction P, an inhibition by cyclic AMP occurred also at a concentration of 10(-8) M, while with cyclic AMP a concentration of 10(-5) M was required for a similar inhibition. Bovine heart protein kinase stimulated the phosphorylation of the membrane fractions much more than Ca uptake. In fraction E, in the presence of bovine protein kinase, both cyclic AMP and cyclic GMP stimulated phosphorylation up to 200%. Under these conditions, no stimulation was observed in fraction P. These results are compatible with the hypothesis that in vascular smooth muscle soluble rather than particulate protein kinases are involved in the regulation of intracellular Ca concentration.

Animals↗
PubMedDate not supplied

Studies on the mechanism of positive inotropic activity of Ro 13-6438, a structurally novel cardiotonic agent with vasodilating properties.

We investigated the possible mechanisms involved in the positive inotropic activity of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a structurally novel cardiotonic agent with vasodilating properties. The positive inotropic response to Ro 13-6438 of the isolated guinea pig papillary muscle was accompanied by inhibition of myocardial phosphodiesterase (PDE) activity and elevation of intracellular cyclic AMP (cAMP) levels Ro 13-6438 had no effect on Na+,K+-stimulated or Ca2+-stimulated ATPase activity and did not influence the rate of 45Ca uptake in cardiac membrane vesicles. Ro 13-6438 caused a concentration-dependent increase in the upstroke velocity, overshoot, and duration of slow action potentials evoked in partially depolarized papillary muscles. Pretreatment of guinea pigs with reserpine did not prevent the effects of Ro 13-6438 on slow action potentials, but slightly decreased its positive inotropic activity. The muscarinic agonist carbachol reversed the Ro 13-6438-induced enhancement of contractility and changes in the slow action potential in an atropine-sensitive manner. These results indicate that the positive inotropic effects of Ro 13-6438 are correlated with PDE inhibition, increased cAMP levels, and an increase of the slow action potential in ventricular myocardium. It is suggested that the elevated cAMP levels resulting from the Ro 13-6438-induced inhibition of PDE enhance the slow inward Ca2+ current.

3',5'-Cyclic-AMP Phosphodiesterases↗