Cefoxitin is a new semisynthetic cephamycin derivative with broad bactericidal activities. In order to determine the extent of the transplacental transfer of cefoxitin, 35 pregnant women received 1 Gm cefoxitin intramuscularly 15 to 180 minutes before normal or Caesarean delivery. Cefoxitin was measured microbiologically in maternal blood (multiple-time samples), umbilical blood (one-time sample), and amniotic fluid in the cases of Caesarean sections. The mammary excretion of cefoxitin injected at the same dose was investigated by measuring cefoxitin in the milk of 16 nursing mothers. In the maternal blood, a peak plasma level of approximately 25 microgram/ml was reached 30 minutes after the 1-Gm intramuscular injection. A clear-cut passage of cefoxitin in the umbilical cord blood was demonstrated. In the fetal blood, a peak level of 15 microgram/ml was obtained 45 minutes after the injection. No cefoxitin was detectable in any of the milk samples from 30 minutes to 24 hours after the 1-Gm intramuscular injection.

Adolescent↗

PubMedDate not supplied

Evidence for a non-GABAergic action of quaternary salts of bicuculline on dopaminergic neurones.

Intracellular recordings were made from neurones, presumed to be dopaminergic, in the rat midbrain slice preparation. Bicuculline methiodide (BMI) and methochloride (BMC) reversibly blocked the slow, apamin-sensitive component of the afterhyperpolarization in these cells. The IC50 for this effect was about 26 microM. In comparison, BMC antagonized the input resistance decrease evoked by muscimol (3 microM) with an IC50 of 7 microM. The base of bicuculline was less potent in blocking the slow afterhyperpolarization. SR95531 (2-[carboxy-3'-propyl]-3-amino-6-paramethoxy-phenyl-pyridaziniu m bromide), another competitive GABA(A) antagonist, and picrotoxin, a non-competitive GABA(A) antagonist, also blocked the action of muscimol (IC50s: 2 and 12 microM respectively), but had no effect on the afterhyperpolarization at a concentration of up to 100 microM. Moreover, 100 microM SR95531 did not affect the blockade of the afterhyperpolarization by BMC. This blockade persisted in the presence of tetrodotoxin and was apparently not due to a reduction of calcium entry, suggesting that it involved a direct action on the channels which mediate this afterhyperpolarization. These results strongly suggest that quaternary salts of bicuculline act on more than one target in the central nervous system. Thus, the involvement of GABA(A) receptors in a given effect cannot be proven solely on the basis of its blockade by these agents.

Animals↗

PubMedDate not supplied

[Correlation between epileptogenic nature of a lesional focus and presence of "activated astrocytes". Human and animal investigation (author's transl)].

Histoenzymologic analysis of human and animal epileptogenic foci has shown enzymatic changes in certain reactive astrocytes. Histochemical examination of these astrocytes in animals has led to clear differentiation between the classic, perilesional reactive astrocyte, constituting a medium for cicatrical glioses and the reactive astrocyte present in experimental epileptogenic foci. We have called the latter the "activated astrocyte". Analysis of 154 human cerebral tumours revealed activated astrocytes in the cortex of all patients with epileptic antecedents. No epileptic attacks were observed in patients where the cortex was invaded by the tumour but no activated astrocytes were present. Analysis of ten cases of non tumoral focal epilepsy confirmed the presence of activated astrocytes in the focus in all cases where the scar was resected surgically. The production of epileptogenic foci in animals shows the close relation between activated astrocytes and the epileptogenic focus. It even seems that the enzymatic changes in the astrocytes precedes the first electrical signs. The authors arguse against the hypothesis that the activated astrocytes are the result of attacks. Until the morphological criteria of the epilectic neuron have been defined the activated astrocyte constitutes the only morphological evidence of the epileptogenic focus.

Animals↗

PubMedDate not supplied

[Electrophysiological aspects of the properties of potentially addictive drugs].

Considerable progress has been made during the last ten years in the study of the mechanism of action of addictive drugs. In this text, data concerning endogenous opioids and opiates are described. After a brief summary of the physiology of brain opioid systems, the various electrophysiological effects of these substances in the mammalian central nervous system are described. Finally, we summarize some experimental data allowing a better understanding of the development of tolerance and dependence to opiates in the rat.

Amino Acid Sequence↗

PubMedDate not supplied

[Piracetam: effect on posthypoxic inhibition of dopamine and acetylcholine release of striatum sections of the rat].

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Acetylcholine↗

PubMedDate not supplied

Pharmacological properties of (N-dicyclopropylmethyl) amino-2-oxazoline (S 3341), an alpha-2 adrenoceptor agonist.

Pharmacological actions of (N-dicyclopropylmethyl)-amino-2-oxazoline (S 3341), an agonist of alpha-2 adrenoceptors, were examined in acute animal studies. In the normotensive anaesthetized dog S 3341 (0.3 mg/kg, i.v.) produced an initial transient increase followed by a marked, prolonged fall in mean arterial pressure (MAP) of 20 mmHg. Central actions of S 3341 were demonstrated by administration of low doses into the vertebral artery of the anaesthetized dog. A rapid and marked fall in MAP resulted which was antagonised by piperoxan. Splanchnic discharges were strongly decreased following S 3341 i.v. administration, suggesting a centrally mediated diminution of sympathetic tone. Peripheral actions of S 3341 were observed in the pithed rat where a dose-dependent increase in MAP was noted which was somewhat antagonised by prazosin and largely by prazosin plus yohimbine. S 3341 reduced hypertension and tachycardia due to stimulation of the sympathetic outflow in the pithed rat, an effect also antagonised by piperoxan. These effects were more marked and prolonged than those of clonidine. S 3341 reduced the tachycardia resulting from stimulation of the cardioaccelerator nerve in the anaesthetized, spinalised and bilateraly vagotomised dog, this effect was reversed by piperoxan. S 3341 did no change the tachycardia induced by noradrenaline or tyramine. Plasma renin activity was significantly decreased after S 3341 treatment in dogs on low normal or high sodium diets. In rats S 3341 decreased the rate of discharge of noradrenergic cells located in the locus coeruleus which are believed to be involved in wake/sleep mechanisms. This depression was 63 times less than that of clonidine. At effective hypotensive doses S 3341 produced no sedation (i.e. loss of righting reflex) in 2 day old chicks. In addition the sedative action of clonidine was inhibited by S 3341 pretreatment. In the mouse tail flick model, the antinociceptive effects of S 3341 were 45 times less than those of clonidine. S 3341, an oxazoline derivative, appears to have haemodynamic effects similar to those of other agonists of central alpha-2 adrenoceptors but with fewer side-effects, and therefore could be of interest an as antihypertensive agent.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

[Sulmazole: a new positive inotropic agent].

Sulmazol (AR-L 115 BS) is a new positive inotropic agent with arterial and venous vasodilator properties. The authors studied the effects of a 24 hours intravenous infusion (an injection of 0.5 mg/kg over 1 minute, followed by an infusion of 1.4 mg/min) on the major haemodynamic parameters of 17 patients with heart failure: 10 patients with chronic decompensation (group I) and 7 patients with heart failure as a result of acute myocardial infraction (group II). The haemodynamic criteria of inclusion were a cardiac index less than or equal to 2.5 l/min/m2 and a pulmonary capillary pressure greater than or equal to 18 mm Hg. After 6 hr of the infusion, the cardiac index increased in both groups (45%, p less than 0.001 and 40%, p less than 0.001 respectively); the pulmonary capillary pressure decreased (32%, p less than 0.001 and 30%, p less than 0.001) and the right atrial pressure decreased (51%, p less than 0.005 and 31%, NS). The total systemic resistance was also decreased (32%, p less than 0.001 and 34%, p less than 0.001), but there was no significant change in the systolic blood pressure. The heart rate increased only in group II (17%, p less than 0.001). These beneficial hemodynamic effects lasted for the 24 hours of the infusion. Sulmazol was therefore found to be very effective in the treatment of acute and chronic heart failure; its long term tolerance still needs to be demonstrated.

Aged↗