Length as a factor in excitation-contraction coupling in heart muscle: an investigation of mechanical transients in strontium-mediated contractions. Sr-mediated contractions have been used to provide an analogue of the normal twitch contraction but with a plateau phase of steady-state activity. An abrupt change of load during the plateau induced an isotonic oscillatory response whose frequency was generally related to the length at which it occurred but could be independently increased by adrenaline or caffeine. The response was not specific for Sr, being seen also in Sr- or Ca-activated K-contractures. The isotonic oscillatory response was less damped than the corresponding isometric transient, and spontaneous isotonic oscillation often occurred following the initial shortening phase, suggesting that the change in length rather than the change in load was the causal perturbation. In cat but not frog preparations a second slower oscillation, also influenced by adrenaline, could be induced. Analysis of velocity--length relations indicates that the isotonic oscillations observed during the plateau phase are analogous to the velocity transients previously described in twitch contractions, but then only in three states characterized implicitly by a relatively poor capacity for internal sequestration. These findings provide evidence that length influences the level of activation of the contractile proteins during shortening in heart muscle, probably through changing Sr/Ca availability.


Sarcomere dynamics in intact cardiac muscle. Elastic properties, length-tension relations, and some characteristics of unloaded shortening were measured at the sarcomere level in rat papillary muscles. Muscle length during contraction was controlled by a servo system, while instantaneous sarcomere length was measured with a light diffraction technique. Muscles quick-released to zero load recoiled by 6% of their length; of this, sarcomere shortening amounted to only 1.6%, the remainder of the series elastic recoil occurring outside the striated region of the muscle, i.e. at the damaged ends of the specimen adjacent to the mounting clips. The length-tension relation was obtained with the sarcomere length maintained constant during contraction. Peak isometric tension increased linearly with sarcomere length from 1.6 to 2.1 mum; but between 2.1 and 2.3 mum tension appeared to be constant. The velocity of sarcomere shortening in an unloaded contraction bore a functional relation to sarcomere length which was similar to that of isometric tension. Both isometric tension and velocity of unloaded shortening reached their peak values relatively early in the contractile cycle.


Physiological pump loading of isolated cardiac muscle. Cat papillary muscles were subjected to a continuously changing load, resulting from an analysis of the left ventricle as a muscle pump system. The papillary muscle was assumed to be part of a circumferential bundle of muscle fibers of a simplified ejecting ventricle. The load included the pressure--stress relationship of this ventricle and the peripheral vascular load with its inertial, resistive and capacitive components. When this loading function was imposed on a shortening muscle through an electronic feedback circuit, the time course of force development and the velocity versus force plots closely resembled data obtained in the intact heart. Analysis of mechanical work (delta 1 X f) and power (V X f) and their respective time course permitted distinction between changes of contractile performance due to (1) positive or negative inotropic interventions, (2) altered hypothetical ventricular dimensions and changed preload, and (3) the long-term load-dependent memory of cardiac muscle.


Preload, afterload, and the role of afterload mismatch in the descending limb of cardiac function. Ventricular function can be analyzed from measures of the ejecting phase of contraction (e.g. velocity and extent of wall shortening) in terms of the appropriateness of the matching between afterload and the level of inotropic state, as modulated by the preload. In the normal heart, under controlled conditions an afterload mismatch can be readily induced if the preload is not allowed to compensate for an increased afterload, or if the limit of the Frank--Starling reserve has been reached. In the conscious animal and in man, measures such as the mean velocity of fiber shortening (VCF, corrected for heart size) are relatively constant in the basal state, and when the normal left ventricle adapts successfully over several weeks to sustained experimental volume or pressure overload, the ejection phase measures remain normal per unit of muscle. However, if the inotropic state is considerably reduced, a mismatch between afterload and contractility (reduced VCF) will be evident in the basal state even when the afterload is normal. Failure to maintain normal ejection indices under conditions of acute or chronic mechanical overload can be explained in terms of an excessive afterload relative to the degree of hypertrophy, the level of inotropic state, and the Frank--Starling rereserve. The concept of afterload mismatch is illustrated by experimental data and used as a basis for characterizing responses to afterload changes in the clinical setting.


The physics of left ventricular ejection and its implications for muscle mechanics. The ejection stage of the left ventricle of the heart is analyzed using the proper form of Newton's Second Law of Motion and a simple cylindrical ventricular model. The Laplace relation is then used to calculate the dynamic relationship between force, velocity and acceleration in an average, circumferential, equitorial myocardial wall fiber, yielding: Fm=Fa + Cacf + Dvcf2 where Fm is the force in the fiber, Fa the fiber force that would be required to match aortic pressure, acf the acceleration and vcf the velocity of shortening of the fiber. C is a constant, and D is a geometrical parameter that varies smoothly with time. The significance of the above equation is discussed both in terms of muscle function (total muscular force) and pump function afterload Fa and the differential force, Fm - Fa): The afterload component Fa provides the pressure head needed to force the blood through the capillaries (Poiseuille flow) and varies with time in accordance with the impedance of the vascular system (auxotonic loading). The differential component force Fm - Fa provides the ventricular impulse needed to overcome the inertia of the system due to (1) the mass of the blood, (2) the geometrical constriction of the outflow tract as one moves downstream (Bernoulli effect), and (2) the moving ventricular walls. Analysis of this sort should help in attempting to separate the intrinsic properties of cardiac muscle and the pump function of the intact heart. The important role that isolated muscle experiments can play in this effort is discussed.


Left ventricle as a compression pump.

Left ventricle as a compression pump. Pressure-volume relationship of the left ventricle at endsystole was studied in three different series of experiment on the dog. Intraventricular pressure was measured with a miniature gauge at the apex. Intraventricular volume was accurately measured by three different methods: (1) plethysmographically with a cardiometer cup, (2) with an intraventricular balloon and a volumetric cylinder, and (3) with the same balloon and areciprocal pump which could clamp the endsystolic volume. We found consistently that as long as the contractile state was stable the endayatolic pressure-volume relationship curve was largely independent of the loading conditions such as enddiastolic volume and ventricular afterload pressure and also of whether the mode of contraction was isovolumic, auxobaric or physiologically ejecting. When the endsystolic pressure was kept unchanged in the ventricle with a stable contractile state, the intraventricular volume decreased to the same volume as given by the endsystolic pressure-volume relationship and the afterload pressure. When the endsystolic volume was maintained constant, the ventricle developed at the end of systole almost the same pressure as that predicted from the same endsystolic pressure-volume relationship. The endsystolic pressure-volume relationship, therefore, uniquely characterizes the degree of ventricular compression under a given contractile state.


On the question of tachyphylaxis to isoproterenol in guinea pigs. Isoproterenol (4 mug/kg, i.m.) decreased mortality of conscious guinea pigs to histamine, when histamine was injected 8 min after a single dose. But, when guinea pigs were injected with isoproterenol or saline every 20 min for 5 hr, followed by a histamine challenge 8 (or 120) min later, there was no difference in mortality between the two groups. This failure of repeated doses of isoproterenol to protect guinea pigs (from effects of histamine) may be related to its cardiovascular effects, since control blood pressure decreased significantly more in the isoproterenol group than in the saline group. This hypothesis was supported by the observation that histamine-induced mortality was significantly increased in guinea pigs treated with a vasodilator (minoxidil), whose blood pressure decreased to the same level (54 +/- 5 mm Hg) as that observed after repeated doses of isoproterenol. Tachyphylaxis to heart rate or blood pressure responses of isoproterenol was not observed. 10 repeated additions of isoproterenol to spontaneously beating atria or tracheal strips did not show any tachyphylaxis, nor did 15-20 additions of isoproterenol to perfused lungs.


Catecholamine release by intracerebral perfusion of 6-hydroxydopamine and desipramine. The rate of catecholamine release at perfusion sites in the diencephalon of the unanesthetized rat during the perfusion of a solution of 6-hydroxydopamine (6-OHDA) or desipramine (DMI). Endogenous stores of norepinephrine (NE) and dopamine (DA) were first tagged by the cerebral microinjection of 14C- or 3H-labelled NE or DA. After successive control perfusates were collected with a push-pull cannula system, 6-OHDA, in a concentration of 5.0, 0.5, or 0.1 mg/ml, was perfused at 20-23 mul/min through a site in the rat'e brain. The compound induced a dose-related release of both NE and DA. In control experiments, 6-OHDA exerted a non-specific releasing effect on 3H-inulin which was not dose dependent. In addition, DMI, an NE reuptake inhibitor in a concentration of 10.0, 2.0 or 0.5 mg/ml, was perfused through 23 sites in the brain following the injection of labelled NE. DMI enhanced the recovery of NE in the push-pull effluent at the 10.0 mg/ml concentration only. However, an augmented efflux of 3H-inulin was also observed during the perfusion of the highest concentration of DMI. These results support the view that 6-OHDA releases catecholamines from endogenous storage sites, but also indicate a strong non-specific releasing action of this compound possibly at extracellular or non-catecholaminergic loci.


Evaluation of the antinociceptive effects of 4, alpha-dimethyl-m-tyramine (H 77/77) in the rat. 4, alpha-Dimethyl-m-tyramine (H 77/77) has been shown to induce dose dependently antinociceptive activity against 3 parameters: (1) the motor (M), (2) the vocalisation during stimulation (V) and (3) the vocalisation after withdrawal of stimulation (VA) responses. The effect of H 77/77 upon the V and VA pain responses was abolished or reduced by prior treatment with phenoxybenzamine, chlorpromazine, H 44/68, FLA 63, reserpine and protriptyline, and was potentiated by atropine sulphate. It is suggested that H 77/77 may exert is inhibitory effect on painful stimulation predominantly by inhibiting spinal sensory input.


Gastric acid stimulating action of cysteamine in the rat. Cysteamine was previously found to produce duodenal ulcers in rats. In the present study, the effect of cysteamine on gastric secretion was studied. Cysteamine administered by a parenteral or intraduodenal route induced a marked and sustained increase in gastric secretion in conscious and in anesthetized rats. The response to cysteamine or its metabolite, cystamine, appeared gradually and the maximum response was observed in 2 or 3 hr after the administration. The response to cysteamine was completely inhibited by vagotomy and inhibited dose-dependently by atropine methylbromide or hexamethonium. Cysteamine stimulated gastric acid secretion in conscious rats with chronic gastric fistula but not in rats with denervated gastric pouch. Tissue histamine levels in the gastric mucosa, abdominal muscle and whole blood were not affected by cysteamine. These results suggest that a cholinergic mechanism is involved in the gastric secretion induced by cysteamine.


The effects of holothurin A on the resting membrane potential and conductance of squid axon. The effects of a marine toxin, holothurin A, on the electrical properties of squid axon membranes were studied. External application of holothurin A to the intact axon produced an irreversible depolarization of the membrane to nearly zero potential. Internal perfusion of squid axon with holothurin A produced a biphasic depolarization of the membrane. The time course of the depolarization was much shorter with internal application than with external application. The holothurin A-induced depolarization was partially reversed either by reduction of the external sodium concentration to 1 mM or by removal of sodium from both external and internal solutions. The results demonstrate an increase in resting sodium permeability as one of the mechanisms underlying the depolarization by holothurin A. However, external application of tetrodotoxin had no effect on the membrane depolarization. Increase of the resting permeability to potassium is suggested as the additional mechanism of depolarization. A model is developed which predicts this anomalous depolarization.


Effects of morphine and barbiturate on the SI and SII potentials evoked by tooth pulp stimulation of rats. The effects of morphine and barbiturate on the evoked potentials recorded from the primary and secondary somatic sensory areas of rats were investigated. The electric stimulation of contra- and ipsilateral tooth pulp (CTP and ITP) was used. The afferent impulse from dental pulp projected to the sensory face areas I and II (SI and SII). Morphine in doses of 2.5-10 mg/kg definitely inhibited SI and SII potentials evoked by CTP stimulation. Morphine also inhibited SII potentials evoked by ITP stimulation, while it rather enhanced SI potentials evoked by ITP stimulation. Pentobarbital sodium in doses of 4-16 mg/kg tended to inhibit SI potentials, but showed no effect or rather an enhancement on SII potentials evoked by CTP stimulation. Pentobarbital sodium enhanced SI and SII potentials evoked by ITP stimulation. In a large dose of 32 mg/kg, pentobarbital sodium inhibited SI and SII potentials evoked by ITP and CTP stimulations. The results suggest that SII is more closely related to the analgesia due to morphine than is SI.


Inhibition and potentiation of apomorphine-induced hypermotility in rats by neuroleptics. The effect of apomorphine (ap) was investigated in rats kept in a familiar cage; 0.25-5 mg/kg s.c. produced a short-lasting, abnormal hypermotility consisting mainly of locomotion and sniffing without grooming. Ap was administered to rate pretreated s.c. with various drugs. Ap hypermotility was antagonized by 12 neuroleptics from different chemical groups. The ap inhibitory effect of 5 neuroleptics was decreased when the interval between pretreatment and ap administration was increased from 0.5 to 4 hr. Clozapine was the only neuroleptic showing no inhibition but potentiation at 4 hr. Mepazine, a phenothiazine lacking antipsychotic effects, as well as the NA receptor blockers aceperone and phenoxybenzamine, did not inhibit ap hypermotility. Ap was also given 24 hr after haloperidol and clozapine. At this time both neuroleptics showed ap potentiation. The ap inhibition and potentiation after a single administration of the neuroleptics is presumable due to selective blockade and subsequent supersensitivity of some DA receptors.


Effect of intracerebroventricular 5,6-dihydroxytryptamine on blood pressure of spontaneously hypertensive rats. The effects of intracerebroventricular injections of 5,6-DHT on the development and maintenance of hypertension in spontaneously hypertensive rats has been investigated. 5,6-DHT, injected into 6 week old rats, retarded the development of hypertension for at least 6 weeks; this effect was not accompanied by inhibition of the pressor response produced by stimulation of the total peripheral sympathetic outflow. 5,6-DHT, injected into 14-15 week old rats with established hypertension, produced a short-lived fall in blood pressure. These findings suggest that central 5-HT neurones are involved in the development of hypertension in spontaneously hypertensive rats.


Separation of inhibiting and stimulating effects of morphine on self-stimulation behaviour by intracerebral microinjections. The effects on self-stimulation behaviour of 5 mug morphine HCl applied into the ventricular system and into different areas throughout the brain were studied. Injections into the ventricular system and in areas intermediate between the posterior hypothalamus and the periaqueductal grey matter had biphasic effects: an inhibition followed by an excitation. Injections into the posterior hypothalamus resulted in increased self-stimulation whereas injections into the periaqueductal grey matter and into the locus coeruleus were only inhibiting.


Centrally mediated antihypertensive and bradycardic effects of methysergide in spontaneously hypertensive rats. Methysergide caused dose-dependent reductions in systolic blood pressure and heart rate of unanesthetized SHR, whereas cyproheptadine was ineffective. In pithed SHR pretreated with methysergide or cyproheptadine, pressor responses to 5-HT were abolished. Responses to sympathetic nerve stimulation were unaltered by methysergide, whereas cyproheptadine slightly reduced them. Both drugs enhanced pressor responses to norepinephrine. Failure to identify a peripheral mechanism for the antihypertensive action of methysergide suggests that the effect may be centrally mediated but not reliant upon serotonin receptor blockade.


Behavioural, electrocortical and body temperature effects of cholera toxin. In young chicks intrahypothalamic infusion of cholera toxin produced a dramatic and dose-dependent increase in motor activity. Similar effects were also obtained in adult fowls after injection of cholera toxin into the third cerebral ventricle, the hypothalamus or the paleostriatum augmentatum. Electrocortical changes consisted of a slight desynchronization during the hypermotor activity and were preceded, when the highest intraventricular doses were used, by a short period of slower frequency and higher amplitude potentials. Intraventricular and intrahypothalamic but not intrastriatal injection of cholera toxin produced a typical biphasic hyperthermic response.


Alpha-noradrenergic modulation of hypothalamic self-stimulation: studies employing clonidine, 1-phenylephrine and alpha-methyl-p-tyrosine. An alpha-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the alpha-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral alpha-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an alpha-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission.


Prevention and reversal of tolerance to barbiturates by intraventricular injection of hemicholinium-3. Intracerebroventricular (i.c.v.) injection of phenobarbital, 800 mug, or intraperitoneal (i.p.) injection of hexobarbital, 100 mg/kg, into rats resulted in a loss of righting reflex lasting 15.4 +/- 0.2 min and 20.7 +/- 0.7 min, respectively. A 40-60% reduction in this response was obtained following administration of phenobarbital either i.c.v. (800 mug 4 times daily) or i.p. (80 mg/kg/day) for 4 days. Although these treatments also increased hepatic mixed function oxidase activity, this enzyme induction was shown to be unrelated to the development of tolerance to loss of righting reflex. I.c.v. injection of hemicholinium-3 (HC-3) in doses which reduce brain acetylcholine levels (4-20 mug) profoundly affected tolerance to the central depressant effect of the barbiturates. Thus, depending upon the time of administration, HC-3 either retarded or prevented development of this tolerance. Moreover, if tolerance was allowed to progress normally, administration of HC-3 on day 4 or 5 returned the duration of the loss of righting reflex toward normal values. HC-3 did not influence either the duration of this response in non-tolerant rats or the induction of the hepatic mixed function oxidase activity. These results suggest that brain ACh plays an important role in the development and maintenance of tolerance to the central depressant effects of barbiturates.


The effects of chronic reserpine treatment on the contractile activity of the isolated vas deferens of the guinea pig. Chronic reserpine treatment of guinea pigs during 5 days (1 mg/kg/day) induces postjunctional supersensitivity in the isolated vas deferens. It has been previously proposed that postjunctional supersensitivity occurs as a result of an ionic and/or membrane mechanism. Contrasting with previous observations in vascular smooth muscle the present results demonstrate that chronic reserpine treatment did not increase the sensitivity of the depolarized vas deferens to calcium. Experiments on drug responsiveness show that the supersensitive depolarized tissues have a greater and slower rate of loss of responsiveness than do control vasa deferentia. However, in a Ca2+-free Krebs solution responsiveness of supersensitive vasa deferentia did not differ from that of control tissues. These findings suggest that, in the guinea-pig vas deferens, reserpine-induced supersensitivity could be at least partially dependent on the increased availability of a calcium store(s) probably located at the cell membrane and/or cytoplasmic compartments.


DPAVP: a vasopressin analog with selective microvascular and RES actions for the treatment of circulatory shock in rats. The present study indicates that: (a) local administration of low concentrations of an analog of vasopressin, 1-deamino-[2-phenylalanine, 8-arginine]-vasopressin (DPAVP), constricts venules in the rat splanchnic terminal vascular bed of normal animals, unlike that seen for catecholamines; (b) maximal concentrations of DPAVP narrow but do not occlude both arterioles and venules: (c) microscopic muscular venules (31-39 mu i.d.) do not narrow more than 20% in response to the vasopressin analog DPAVP; and (d) terminal arterioles (17-23 mu i.d.) do not narrow more than 50% in response to DPAVP. Systemic administration of DPAVP to rats subjected to hemorrhage or bowel ischemia shock more than doubles survival rates over control rats receiving Ringer solution. Infusion of DPAVP produces a dose-dependent effect on arterial blood pressure, microscopic capacitance vessels, large arterioles and small arteries. In addition, i.v. administration of DPAVP: (a) returns arterial hematocrit towards normal after shock; and (b) regenerates and sustains vasomotion and venular tone, decreases microvascular hyperreactivity characteristic of shock syndromes, restores constricted arteriolar lumen sizes towards normal, predisposes to a splanchnic microbed virtually free of stasis, petechiae and leukocytic sticking, and restores capillary perfusion and outflow to near-normal. Further, DPAVP effectively restores the early reticuloendothelial system (RES) phagocytic depression, characteristic of shock syndromes, to normal; the latter eventuating in RES hyper-phagocytic activity. These findings indicate it is possible to synthesize vasoactive molecules which: (a) exert selective microvascular and RES phagocytic effects; and (b) are highly beneficial in the therapy of low-flow states, at least in rats.


BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride), a new inhibitor of dopamine-beta-hydroxylase with antihypertensive activity. BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride) was found to inhibit dopamine-beta-hydroxylase in vitro and in vivo and to have antihypertensive activity. The effect on dopamine-beta-hydroxylase in vitro was shown by inhibition of the conversion of phenylethylamine to phenylethanolamine, using enzyme extracted from rat adrenals. In vivo, BRL 8242 inhibited 3H-noradrenaline but not 3H-dopamine biosynthesis from 3H-L-dopa in rat brain. Furthermore, the compound lowered endogenous noradrenaline levels in both rat brain and heart whilst increasing the concentration of brain dopamine. In both metacorticoid hypertensive and normotensive rats, BRL 8242 lowered blood pressure. This response was dose related and correlated well with the reduction of endogenous noradrenaline in the tissues examined. It is therefore suggested that the inhibition of dopamine-beta-hydroxylase by BRL 8242 may account for its blood pressure lowering activity.


Placental transfer of central nervous system depressants in sheep. Continuous monitoring of the foetal electrocorticogram, eye movements and heart rate in ewes during the last month of gestation showed rapid placental transfer from the mother to the foetus of phenothiazine derivatives (acepromazine maleate), short-acting barbiturates (thiopental sodium) and narcotic analgesics (meperidine). Acepromazine and thiopental partially disrupted the foetal sleep cycle by synchronization of the ECoG for 1-2 h but increased the heart rate for 2-3 h. The effects of meperidine were similar but lasted only 5-10 min for the ECoG and less than 0.5 h for the heart rate.


Intragastric NaHCO3 perfusion and vagal-induced ulcer formation in the rat stomach. The effects of electrical vagal stimulation on gastric acid output and ulcer formation were studied in rats intragastrically perfused with saline or NaHCO3 solutions. Vagal stimulation produced a 100% incidence of glandular lesions and a significant increase in total acid output in saline-perfused stomachs. Antacid perfusion failed to prevent ulcer formation despite complete neutralization of the increased acid output. It is considered that vagal-induced gastric glandular lesions are not acid dependent.


Dopamine metabolism in the nucleus accumbens: the effect of clozapine. Dopamine metabolism in the nucleus accumbens of the rat was studied by gas chromatographic quantitation of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The ratio of DOPAC/HVA in the nucleus accumbens was significantly greater than the same ratio in the striatum. Dose-response curves for the increase in DOPAC and HVA in the nucleus accumbens and striatum 2 h after clozapine were generated. The effect of clozapine on dopamine metabolism was similar in both structures.


Calcium influx and postjunctional supersensitivity in guinea pig aortic strips. Both reserpine and 6-hydroxydopamine (6-OHDA) pretreatment potentiated the sensitivity of guinea pig aortic strips to norepinephrine (NE), barium, methoxamine and potassium indicating postjunctional supersensitivity. However, cocaine treatmetn only potentiated the NE response indicating prejunctional supersensitivity. 6-OHDA and reserpine-induced supersensitivity but not cocaine-induced supersensitivity was accompanied by an increase in 45Ca influx.


Caffeine and KC1 contracture in cat myocardium. Caffeine increases the force of contracture induced in cat myocardium by exposure to 140 mM KC1 in isotonic Tyrode solution. The effect of caffeine does not require prior exposure to the drug, develops rapidly, and is partially antagonized by procaine but not by verapamil. These results suggest that caffeine acts on depolarized sarcolemma to release a sarcolemmal calcium pool.


Quantitative comparison of the analgesic and anti-inflammatory activities of aspirin, phenacetin and acetaminophen in rodents. The mild analgesic activities of aspirin, phenacetin and acetaminophen have been compared in the trypsin, kaolin and carrageenan hyperalgesic assays as well as in the acetic acid writhing test. The trypsin and kaolin hyperalgesic assays were designed to be unaffected by drugs with anti-inflammatory activity. Aspirin and acetaminophen were inactive in these two tests at dose levels devoid of side effects. Phenacetin was active in the trypsin and kaolin assays with oral ED50's of 114 +/- 36.2 and 107 +/- 11.5 mg/kg, respectively. Non-steroidal anti-inflammatory drugs as well as phenacetin and acetaminophen were active in the acetic acid writhing and carrageenan hyperalgesic assays. This led to evaluation of phenacetin and acetaminophen as anti-inflammatory agents. Both of these latter drugs were active in the carrageenan pleurisy and adjuvant arthritis models of inflammation. In all studies phenacetin was equipotent to or more potent than acetaminophen. The data suggest that the analgesia produced by aspirin and acetaminophen results from their anti-inflammatory activity whereas the analgesia produced by phenacetin has two components, one dependent on and one independent of anti-inflammatory activity.


Modification by manganese ions and verapamil of the responses of the atrioventricular node to norepinephrine. In isolated and cross-circulated canine A-V node preparations single injections of Mn2+ (1-30 mumol) and verapamil (0.3-10 nmol) into the posterior septal artery (PSA) caused a dose-dependent increase in the A-V conduction time and, in large doses, produced A-V conduction block. The A-V conduction time increased by Mn2+ and verapamil is resotred by 1-norepinephrine (1-NE) injected into the PSA. The A-V nodal tachycardia induced by 1-NE is suppressed by Mn2+ but not by verapamil. These indicate the following: (1) the slow Ca2+ channel plays an important role in A-V conduction; (2) the positive dromotropic response of the A-V node to 1-NE may have some relations to the Ca2+ channel; (3) the A-V nodal tachycardia induced by 1-NE may be mediated by the Ca2+ channel. Possible causes which produced differences between Mn2+ and verapamil in the effects in antagonizing the 1-NE-induced A-V nodal tachycardia are discussed.


The electrodermal response as a model for central sympathetic reactivity: the action of clonidine. Electrodermal responses (EDR) were evoked centrally by stimulation of reactive loci in the posterior hypothalamus and peripherally by stimulation of the distal portion of the sectioned median or ulnar nerve. Moderate doses of clonidine (3-30 mug/kg, i.v.) reduced the amplitude of the centrally evoked EDR while having no effect on the peripherally evoked responses. This central action of clonidine occurred concomitantly with the clonidine-induced bradycardia and hypotension. Administration of clonidine shifted the centrally evoked EDR frequency-response curve to the right in a dose related manner at 3, 10 and 30 mu/kg, i.v. 1 mug/kg was without effect on these responses. This central depressant action of clonidine was partially reversed following administration of yohimbine (0.5-1.0 mug/kg, i.v.). These results suggest that clonidine inhibits central reactivity in this sympathetic-cholinergic system in a manner analogous to its action on other sympathetic systems, and that a central adrenergic inhibitory mechanism may be involved.


A double fatality with children due to fumigated wheat. Two children, four and two years old, played on top of wheat, that had been fumigated with malathion, pyrethrum and phosphine. Both died within 18 hours. Because after the autopsy, death could not be attributed to any organic or violent cause, a toxicological analysis was carried out. No drugs, except alcohol, was detected. Those results were attributed to hydrolysis of malathion, yielding two molecules of ethanol. As this was an indirect proof of malathion ingestion, it was assumed that phosphine had been ingested as well and that consequently this was the cause of death, because it is much more toxic than malathion and because it was continuously generated from not completely dissolved aluminiumphosphide tablets, while the children were still playing.


[Determination of lead by atomic absorption spectrophotometry with regard to toxicology research]. The toxicity of lead in the human environment is acquiring a growing interest which lead us to choose a quick, precise, sensitive and specific method able to perform number of measurements. Thanks to the survey consisting in a dosage of lead by atomic-absorption spectrometric, we are able to confirm the advantages and superiority of such a method and to employ it for the toxicologic research of lead in food, water, industrial atmosphere, and biological liquids.


[Toxic effects of methoxy-ethyl-mercury in the quail: influence of fasting]. Quails fed methoxy-ethyl-mercury-treated wheat (20 ppm of Hg) during 10 or 20 days, have been submitted to a three-day fasting following contamination. The test proved to be lethal for a number of intoxicated animals but not for controls. Mercury clearance was modified by anorexia; following fasting, there was a redistribution of the metal, with high concentrations in the liver and kidneys. According to the results of a blood survey uric acid, urea and T. G. O. levels appeared to be the most altered parameters. Transient high blood uric acid levels in intoxicated and anorectic animals could be attributed to kidney dysfunctioning. A possible effect of methoxy-ethyl-mercury on neoglycogenesis was discussed.


Toxicological studies of photosensitizer agents and photodegradable polyolefins. The authors report the results of a series of toxicological tests conducted on plastic materials (polyethylene) activated with tetraphenylbutadiene (TPB) an additive recently proposed as a sensitizer capable of photodegrading plastic materials. The toxic effects of polyethylene, TPB, and TPB's degradation products were investigated in rabbits, mice and rats. The studies revealed these products to possess a very low toxicity.


Behavioural repertory of cats without cerebral cortex from infancy. Bilateral removal of the cerebral cortex was made in cats neonatally. Spontaneous and imposed behaviour was studied while they were growing up and after they had become adult. Special emphasis was put on the utilization of visual cues and on learning. The cats ate, drank and groomed themselves adequately. Adequate maternal and female sexual behaviour was observed. They utilized the visual and haptic senses with respect to external space. Two cats were trained to perform visual discrimination if a T-maze. The adequacy of the behaviour of these cats is compared to that of animals with similar lesions made at maturity.


Early versus late visual cortex lesions: effects on receptive fields in cat superior colliculus. Cats that sustain lesions of the visual cortex early in life appear to perform certain visual discrimination tasks better than those operated as adults. This study sought to determine whether this recovery is visual capacities was accompanied by reorganization of single cell responses at the level of the superior colliculus. Areas 17 and 18 were ablated in adult cats and in kittens at various times during the neonatal period. Responses of units in superior colliculus ipsilateral to the lesion were recorded following a prolonged recovery period. Following cortical lesions, collicular units rarely exhibited direction selectivity, binocularity was reduced in the majority of animals, and the ocular dominance distribution was biased toward the contralateral eye. The reduction of direction selectivity and binocularity were unrelated to the animal's age at operation.


Recovery of function in cat visual cortex following prolonged deprivation. Evidence that there is a critical period during which response characteristics of neurons in visual cortex of the cat may be influenced has been provided in several studied, which suggest that the period of influence is restricted to the first few months of life. Using a somewhat different experimental procedure, we have obtained evidence that cortical units retain plasticity long after the end of this period has passed. In our procedure prolonged visual deprivation was followed by exposure in a normal visual environment. The animals were maintained throughout the first year of life either in total darkness or in an enclosure illuminated intermittently by a strobe light. Following the period of deprivation, electrophysiologic recordings were taken from some of these animals. The remaining cats were permitted 6-12 months in a normally-illuminated environment prior to recording. Cats of the same age reared from birth in a normally lit environment were also recorded. Cortical neurons in cats deprived of any normal visual experience rarely show orientation selective responses. In animals allowed subsequent normal visual experience about one-half of the units studied exhibited this property. This level of response specificity is intermediate between that of normally-reared and recently-deprived animals. While most cortical units in normally-reared cats exhibited direction selectivity, this property is rarely observed in the "recovery" cats. A number of unit types which are rarely observed in either normal or totally deprived animals were encountered in cats that had normal exposure following prolonged deprivation. A convergent strabismus was observed, in contrast with the divergent strabismus often shown by cats immediately following prolonged visual deprivation. This shows that ocular alignment as well as cortical unit properties can remain plastic in the adult.


Effects of serial lesions of somatosensory cortex and further neodecortication on retention of a rough-smooth discrimination in rats. Five groups of rats with bilateral lesions of the somatosensory cortex and one of animals sustained only sham operations were tested for retention of a rough-smooth discrimination. Two of the lesion groups had sequential unilateral ablations, in one case with interoperative testing, and three groups had one-stage bilateral lesions. The two groups of animals with serial lesions did not differ from each other or from sham operates in relearning the task. RAts with one-stage lesions and preoperative overtraining also performed well, but the other one-stage groups showed deficits relative to control and serial lesion groups. In the second experiment the sham operated rats from Experiment 1 experiences lesions anterior and posterior to the somatosensory zones. These lesions did not affect retention. Somatosensory cortex then was ablated in one operation and severe performance decrements were seen. Removal of additional neocortex in a sample of animals that had relearned the discrimination after one-stage somatosensory cortex lesions (Exp. 1) also affected retention. In contrast, retention was not impaired on some of the measures in those animals that originally had two-stage ablations. The findings from these two experiments show that some ablation effects can be circumvented with overtraining or serial lesion techniques. The data also indicate that non-somatosensory cortex may play a role in recovery after somatic cortex lesions, but that the substrates underlying recovery might not be the same after one-stage and two-stage ablations.


Isolation of sodium-complexing polypeptides from mammalian blood and cardiac muscle. Two distinct polypeptides have been isolated from rat heart and ox blood. They are both found to be effective in forming complexes with sodium ions, and it is suggested that they may have a function in stabilizing sodium ion activity.


Is there a recycling of hydroxyproline?

Is there a recycling of hydroxyproline? Rats can produce glycine from hydroxyproline and vice versa. After the injection, hydroxyproline is rapidly converted into glycine and then incorporated into collagen. Later the labelled amino acids in collagen are hydroxyproline, proline, serine, threonine, alanine, and glutamic acid. We suppose that all these labelled amino acids come from glycine.


Zeitgeber induced modulation of activity patterns in nocturnal mammals (Chiroptera). Changing the L:D intensity ratio of a synchronizing dark regime leads to characteristic modulations of the activity pattern of Chiroptera species. These modulations fit the predictions of WEVER'S oscillator model.


The effect of continuous exposure to low frequency electric fields on three generations of mice: a pilot study. Mice were allowed to mate, gestate, deliver and rear their offspring for 3 successive generations while being continuously exposed to 60 Hz electric fields. Mice exposed to vertical electric fields exhibited decreased body weights at 35 days postpartum and increased mortality rates for 3 successive generations. Mice exposed to horizontal electric fields exhibited decreased body weights for 2 successive generations.


Comparison of the effects of illumination on the melanophores of intact and eyestalkless fiddler crabs, Uca pugilator, and inhibition of the primary response by cytochalasin B. Approximately 100 times more illumination is required to produce pigment dispersion in the melanophores of eyestalkless fiddler crabs (Uca pugilator) than in the melanophores of intact crabs. The pigment in melanophores of isolated legs will normally disperse in response to irradiation, but this response is inhibited by cytochalasin B.


The influence of cobalt on the endoplasmatic reticulum of the horse bean (vicia faba l.). The exogeneous application of cobalt induces the differentiation of membrane complexes of the endoplasmic reticulum. After longer acting of cobalt these membranes are dilated and later destroyed. This fact can manifest itself also in some disturbances of the cell division.


Degradation of phenylalanine in the presence of hydrogen peroxide. UV-irradiation of phenylalanine by 253.7 nm light in the presence of hydrogen peroxide formed 5 ninhydrin reactive products and ammonia. Four of them were identified as aspartic acid, serine, alanine and lysine.


Noise and "pedagogic efficiency" in school activities. A group of 8 pupils born in 1962 and a group of 8 future teachers between 25 and 40 years of age, were submitted in 1975 to two types of tests in the presence of environment noises at various levels (45 to 75 dBa), in order to assess the influence of this nuisance on the pedagogic efficiency. The results show a nocivity threshold for the pupils at around 55 dBA and for the teachers at aroung 65 dBA. Furthermore, backward pupils suffer more in this context from the interference of noise than the advanced ones.


Effect of ascorbic acid on pigmentation of toad (Bufo melanostictus). Administration of ascorbic acid in toad during breeding season results an increase in melanin pigments in skin, liver and vocal sac.


Locomotory energetics in a marsupial (Antechinomys spenceri) and a rodent (Notomys alexis). Steady state oxygen consumption was compared in a rodent Notomys alexis and a marsupial Antechinomys spenceri. The marsupial was found to diverge from predicted eutherian energic patterns. N. alexis appears to use energy storage as a significant part of the step cycle before becoming bipedal. Aerobic scope and heat storage during running are similar in both species.


Slow current changes underlying square shaped potential waves in warmed Aplysia neurones. On warming, the regularly firing L11 neurone of Aplysia turns into a bursting-type neurone. The bursts of spikes are produced by slow square waves which can also be obtained at room temperature by adding TTX or Co++. Experiments with slow ramp voltage clamp show that warming induces a negative slope (or negative resistance) on the current-voltage characteristic and very slow current variations (r = 10 to 50 sec) in response to potential changes. The square waves are explained by these two phenomena.


Neural serotonin receptors in active and hibernating helicid snails (Helix lucorum). In hibernating snails Helix lucorum, the effect of 5-HT on neurons of an identified group is mainly hyperpolarization associated with a conzation conductance increase, while, inactive snails, the effect is de polarization decrease of the membrane conductance.


A simple approach to the toad's (Bufo melanostictus) nerve muscle preparation. A simple and modified dorsal approach method has been made in the toad's (Bufo melanostictus) sciatic gastrocnemius nerve-muscle preparation. This method incurs less blood loss, time consumption, nerve damage and visceral spoil compared to conventional ventral approach method.


Gibberellin and nucleic acid metabolism during Zea mays fertilization. Either by direct GA supply or by release of glycosidic bound GA, pollination causes partial opening of double-stranded DNA in somatic maize kernel tissues, as evidenced by increased Tm profiles. This phenomenon is associated with enhanced RNA and prtein production.


Effects of deneravation and decentralization upon taste buds. Denervation of vallate papillae results in failure of tactile and gustatory reception at a time when impulse conduction in the distal stump of the glossopharyngeal nerve is still unimpaired; delay of receptor deficit depends on axon length between receptor and axotomy sites; taste buds disappear by 10 days. Decentralization, through intracranial rhizotomy, does not modify lingual receptors structure or function.


Is beta-(4-chlorophenyl)-GABA a specific antagonist of substance P on cerebral cortical neurons? Beta-(4-chlorophenyl)-GABA (Baclofen, Lioresal) antagonized the excitant actions of acetylcholine and substance P to comparable extents. L-glutamate-induced excitation was affected to a lesser extent. These findings do not support the suggestion that beta-(4-chlorophenyl)-GABA is a specific substance P antagonist.


A new wave (2nd c-wave) on corneoretinal potential. The 2nd c-wave is a new wave of corneoretinal potential which is an on-response with a long latency (65-98 sec), and appears following the end of the c-wave of ERG. It suggested that the 2nd c-wave is based on the tail of the late receptor potential of the retina.


Interaction between two identified cells in the visceral ganglion of the snail, Helix pomatia. An interneurone, making excitatory synaptic connections with a second neurone has been identified in the brain of Helix pomatia. The results suggest that the connection is monosynaptic.


Ultrastructural changes in the dorsal root ganglia evoked by thalidomide in rabbits. Administration of the teratogenic drug thalidomide to pregnant does produces ultrastructural changes in foetal ganglion cells, Schwann cells and axons in the posterior root ganglia corresponding to forelimb segments deformed by the orug. Ultrastructural changes in ganglia appear on the 13th day of gestation, i.e., preceding the appearance of limb malformation.


Antischistosomal and some toxicological properties of a nitrodiphenylaminoisothiocyanate (C 9333-Go/CGP 4540). A procedure to enhance the schistosomicidal effectiveness in vivo of an isothiocyanate derivative and some of its antischistosomal properties are reported. Determinations of the effects of this compound on tissue thiol levels and on highly sensitivity bacterial tester strains have indicated that its mutagenic potential is of a low order and that the latter is decreased further after reduction of the host's intestinal bacterial flora.


Beta-blockade of morphine-induced hyperlactacidemia in rabbits. In morphinized rabbits blood lactate levels are elevated. Hyperlactacidemia persists after cessation of morphine injections. This morphine-induced lactate accumulation is completely abolished by simultaneous propranolol treatment. Phentolamine does not modify the action of morphine.


Frescon: neurophysiological action of a molluscicide. The molluscidice N-trityl morpholine (Frescon) has an unusual effect on the central nervous system of a freshwater snail. Nerve impulses become grouped into spontaneous "bursts", with many cells firing synchronously. This may result from interference with inhibitory processes.


Drug interactions in intestinal absorption of 3H-digitoxin in rats. The absorption of 3H-digitoxin from perfused rat small intestine was inhibited by probenecid (1.0 x 10-2 M), ethacrynic acid (0.5 x 10-3 M), and mersalyl (8.0 x 10-3 M) indicating that digitoxin absorption is at least partly an active process.


The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats. The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.


Differential effects of ethanol on prostaglandin responses of arterial and venous smooth muscles. The present results, using isolated rat aortic strips and portal vein segments, demonstrate that ethanol, depending upon concentration, can either enhance or attenuate the contractile actions of PGF2alpha on at least 2 different types of vascular smooth muscle. At the very least, the present findings question that the use of ethanol as a solvent when investigating the contractile actions of PG molecules on smooth muscles.


Phenobarbital and SKF-525A on vinblastine and vincristine toxicity in mice. The effect of SKF-525A and phenobarbital on the LD50 values of vinblastine and vincristine suggests that the toxicity of these agents in mice does not arise from a toxic metabolite.


Elevation of serum xanthine oxidase following halothane anesthesia in the rat. Halothan anesthesia was found to be hapatotoxic in the rat, as demonstrated by a significant elevation of serum xanthine oxidase (SXO) level. SXO appeared to be more sensitive marker of liver damage than serum glutamic oxalacetic transaminase. SXO was found to be elevated also following exposure to relative hypoxia.


Formation of lipoperoxide in the retina of rabbit exposed to high concentration of oxygen. When rabbit was exposed to high concentrations of oxygen, lipoperoxide in the retina was increased at 12 h of the exposure, after which period amplitude of electro-retinogram decreased. The degeneration was observed in the visual cell layer of the retina of the exposed animal. The exposure increased lipoperoxide in isolated retina. These data show the intervention of lipoperoxide in retinal degeneration by exposure to high concentration of oxygen.


Laminar Acetylcholinesterase localization in the optic tectum of five seawater teleosts. The histochemical localization of acetylcholinesterase in the optic tectum of seawater teleosts shows a characteristic laminar distribution which parallels the histological structure of the nervous centre. Significant differences have been observed between Gobius and the other 4 species of teleosts examined. It seems likely that cholinergic mechanisms play an important role in the function of teleost optic tectum.


Lipid and phospholipid content and fatty acid composition of the chick lung during embryonic development. The evolution of total phospholipid, phosphatidylcholine and phosphatidylethanolamine content of chick lung during embryonic development is in good agreement with morphological data. Saturated fatty acids are predominant. A sex-linked difference is observed in the evolution of phosphatidylcholine.


Abnormal mitochondria in retinoblastoma. In examination of six retinoblastoma tumor specimens, bizzare mitochondria were often found. Some are irregular forms with focal expansion and constrictions. Occasionally, a portion of the mitochondria forms rings. Branching mitochondria are also seen. Other striking features of the mitochondria from tumor cells are the alternation of cristae. Dense bodies are also occasionally observed within the mitochondria. Morphological modifications of the mitochondria may be as results of pathological conditions of the tumor cells.


Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum. Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.


Alpha-tocopherol: its inhibition on human platelet aggregation. Alpha-tocopherol inhibits human platelet aggregation induced by arachidonate sodium, collagen, epinephrine, adenosine diphosphate or thrombin - arachidonate sodium being the most susceptible. The second phase of the biphasic platelet aggregation induced by epinephrine or adenosine diphosphate is preferentially inhibited.


Effect of dipyridamole on human platelet phospholipids. The effect of dipyridamole on platelet phospholipids has been studied. After the platelet incubation with dipyridamole, a 38% reduction in the concentration of the sphingomyelin and a 21% increase in phosphatidyl choline were produced.


Time function of corticosteroid levels in the blood plasma of rats under the influence of 222Rn inhalation. The time function of cortocosteroid level in plasma of rats under two different 222Rn concentrations was investigated. Both curves show a maximum after 8h. Whereas the higher activity of 222Rn produces a second maximum after 5 days, the lower activity reaches its second maximum not before 9 days. From both time functions, a two-step mechanism in the intracellular control can be concluded.


Histamine as an extremely potent releaser of vasopressin in the rat. Intraperitoneal and intraventricualr injection of histamine induces a very fast and high elevation of vasopressin in rat plasma as determined by radioimmunoassay. The effects are dose and time related. The intraventricular injection is more effective with regard to time and dose than the intraperitoneal injection.


Successive clutches induced by surgical excision of post-ovulatory oocytes in the lizard Cnemidophorus uniparens. 19 animals had eggs excised from the oviducts soon after ovulation. Number of clutches was nearly tripled in excised animals as compared to controls. An influence of eggs in the oviduct on number of clutches is suggested and may indicate a neuronal link between oviduct and hypothalamus.


Precocious puberty in rats induced by hypothalamic lesions: a comparison of platinum and stainless steel electrodes. Precocious sexual maturation was induced in immature female rats by 2 types of unilateral hypothalamic lesions. Stainless steel electrodes produced smaller tissue defects but proved more efficient than platinum electrodes.


A simple system for mechanical and electrical recordings from frog nerve-muscle preparation. A device is described which can be used for simultaneous measurement of the muscle action potential and the contraction of the frog gastrocnemius nerve-muscle preparation. The apparatus is characterized by ease of construction, good accuracy and reliability.


Brain chopping: a new method for the rapid removal of newborn rat brain. A new multi-bladed air-driven guillotine is described. This device removes newborn rat heads and slices them into several thin wafers, which facilitates freezing and permits easy regional dissection.


Technical note about simultaneous recording of oxygen partial pressure and neuronal activity in cat cortex. A method is described for simultaneous measurements of pO2 and action potentials with microelectrodes using prefabricated gold wires. The construction and measuring with such gold electrodes is easier than with traditionally used platinum electrodes. Single electrodes recording is done with a specially adapted electronic circuit, allowing the separation of both signals (pO2 and action potentials. A measurement in cat brain illustrates this procedure.


Holding plastic-embedded specimens for sectioning in a rotary microtome. Three methods are evaluated for holding capsules of plastic-embedded tissue for rotary microtomy. Use of a V-block is rapid but deforms the capsule. Gluing the capsule to a supporting block is useful for reorientation of the capsule but otherwise time consuming. adapter is easy to use, does not deform the tissue, and is the preferred method for routine microtomy.


A new technique for dissociation of hair follicles into single cells. A method is described for the complete dissociation of mouse hair follicles into a suspension of single cells suitable for cell culture. Dermal tissue containing hair follicles is digested sequentially with trypsin and chondroitinase ABC under mild conditions.


[Pharmacological properties of the methylamide of N-(4-antipyril)-oxaminic acid (oxapyrine)]. Comparative results of a pharmacological study on amidopyrine and a new original drug--N-(4-antipyril)-oxaminic methylamide are reported. Investigations conducted on animals showed the anodyne action of amidopyrine to manifest itself in toxic doses. This drug has a direct depressing effect on an isolated heart, a length of the intestine and the uretus of test animals. When employed in experimental conditions N-(4-antipyril) oxaminic methylamide displayed a much greater analgesic action that did amidipyrine. The drug has low toxicity both with its single and systemic introduction for a period of 60 days and it produces no inhibitory effect on isolated smooth muscle organs. It is concluded that the advantages of the newly synthetized agent come as a result of purposefully made structural changes in the formula, viz by introduction of a hydrazine group and of an oxaminic radical in the side chain.


[Toxicity of etmozine, a new antiarrhythmic agent]. In tests set up on albino rats, guinea pigs and dogs chronic toxicity of aetmozine--a new antiarrhythmic drug used enterally in a dose of 35 mg/kg for periods of 1.3 and 6 months was studied. With different follow-up periods aetmozine was found not to lower the weight gain of the animals, nor to have any adverse effect on the blood and act as a local irritant. Histopathological changes occurring in the internal organs of the animals are of a reversible nature. Single oral administrations of the drug in a dose of 300 mg/kg at different terms of pregnancy did not produce any embryotoxic or teratogenous effects in rats.


[Cardiovascular effects of diazepam and chlordiazepoxide in experiments on non-narcotized animals]. Tests staged on non-anesthetized cats demonstrated that the symptoms of the inhibited behaviour of the animals following introduction of diazepam and chlordiazepoxide are attended by hypertension, tachycardia and an increased intensity of pressor vasomotor reflexes. Urethan and chlorasole lessened the intensity of the activating effect of the tranquilizers on the central component of the sympathetic nervous system tonicity.


[Effect of thyrocalcitonin on the recovery processes in adrenaline lesion of the myocardium]. Administration of thyrocalcitonine (TCT) in doses of 0.1 and 1 Un/kg for 14 days prevented the development of myocarditis in rats receiving epinephrine (3 mg/kg) for 4 days reduced the death rate among the animals, increased their body weight and normalized the electrolytes composition in the heart. Given in a dose of 10 Un/kg the drug produced a less pronounced positive effect on the study values in the animals with experimentally-produced epinephrine lesion of the heart. According to the authors this may be occasioned by an intensified secretion of the parathyroid hormone in response to a multiple introduction of large TCT doses to the animals.


[Effect of pyridinolcarbamate (parmidine) on some bradykinin effects]. The influence of pyridinolcarbamate (parmidine) on raising the tonicity of bronchial and intestinal muscles in guinea pigs, and also on the edema of the paw in rats, induced with bradykinin was studied. Parmidin displays a specific antibradykinin activity and mitigates the effects of bradykinin in all the objects under investigation, without exercising any influence on the spasmogenic action of histamine, serotonin and acetylcholine.


[Action of some pyrazolone derivatives on thrombocyte aggregation]. The influence of four agents--pyrazolidinedione derivatives on the ADP-induced aggregation and activity of glycolytic enzymes--glyceraldehydrophosphate dehydrogenase and lactate dehydrogenase (GAPD, LDG) and of the anatomic oxidation enzyme--glucose-6-phosphate dehydrogenase (G-6-PD) was studied. The substances known by a conventional designation of MYaK-38, No-13 and No-2 are shown to display an antiaggregational action. Amidopyrine was found to depress the adhesive capacity of blood platelets, to activate GAPD and LDG and to lower the activity of G-6-PD.


[Antiviral inhibitor induction under the influence of some anti-inflammatory agents]. An investigation into the effect produced by a series of acyl-derivatives of pyrasolone and salicytates on the generation of antiviral inhibitors (AVI) to the RNA and DNA-carrying viruses in the tissue cultures and chick embryos ascertained the active AVI inhibitors to be derivatives of 4-amino- and 4-methylaminoantipyrine, acylated with higher fatty and substituted benzoic acids.


[Effect of different doses of tetramethylthiuram disulfide on the enzyme-forming function of the small intestine]. The effect of tetramethylthiuramdisulphide on the activity of the small intestine mucosa in rats was studied. When administered in different doses the compound was found to bring about, in the main, a fall of the monoglyceride-lipase and dipeptidase and a rise of the invertase alkaline-phosphatase and amylolytic activity. A protracted introduction of the compound brings down the weight of the small intestine mucosa. One month after stoppage of the drug's administration in a dose of 1/50 DL50 practised for 6 months and 15 days following its single introduction in a dose of 1/3 DL50 the enzymatic and the weight of the intestinal mucosa returned back to normal.


[Effectiveness of sodium selenite in experimental liver dystrophy]. The effect of sodium selenite on the cholepoietic function of the liver in rats with acute dystrophy induced by carbon tetrachloride was studied. When used in doses of 1 and 10 gamma/100 g the drug was found to normalize the intensity of bile secretion, synthesis and secretion of bile acids and that of bilirubin, as well as excretion of cholesterol. This was attended by a rise of the cholate-cholesterol ratio.


[Is liver microsomal enzyme induction the cause of tolerance to barbiturates?]. In 12, 24 and 48 hours after a single injection of phenobarbital, barbital-sodium and pentabarbital-sodium in doses of 80 175 an 40 mg/kg respectively an increased synthesis of protein in the cell-free protein-synthetizing system and a rise in the level of cytochromes b5 and P-450 in the liver microsomes of female rats were noted. The maximal changes were registered following introduction of phenobarbital the inducing capacity of barbital-sodium and pentabarbital-sodium twice as low. With chronic introduction of the drugs the tolerance with respect to all of them develops at an equal rate, which excludes the dependence of this phenomenon upon the induction of microsomal metabolizing enzymes of the liver.


[Effect of retabolil and thyrocalcitonin on mineral metabolism in the bones of rats following a fracture of the lower jaw]. In tests conducted with 65 male-rats of the Wistar line, aged 2-3 months subject to studies was the effect of retabolil (RB) and thyrocalcitonine (TCT) on the mineral metabolism in the osseous tissue following fracture of the lower jaw. The per cent of the Ca45 isotope incorporation in the injured and unaffected (contralateral) sections of the jaw and also in the thigh bones, lying far away from the site of the injury, was determined in dynamics. The agents RB and TCT, displaying different modes of action, produce a similarly oriented effect, viz. accelerated mineralization of the osseous tissue, which is evident from an increased incorporation of the Ca45 isotope in the fracture area during the first post-traumatic week, followed by declining incorporation on the 14-28th day.


Antiinflammatory activity of two phenylindandione derivatives. 2-5-Dibromo-2-(beta-naphtyl)indan-1,3-dione (43/63) and 4-bromo-2-phenylindan-1,3-dione (43/13) are two interesting members of a series of "indandione" derivatives which possess an antiinflammatory activity (in the following tests: carrageenin induced rat hind paw edema, cotton pellets granuloma and chronic adjuvant arthritis). The two drugs are devoided of anticoagulant activity and their antiinflammatory effect is not adrenalmediated.


[Allergenic action of armin].

[Allergenic action of armin]. The allergic effect of armine--ethyl paranitrophenyl ether of the ethylpohosphinic acid--was studied. Armine was injected subcutaneously in doses of 0.1, 0.01, 0.005 and 0.0005 mg/kg to guinea pigs 5-6 times at intervals of 2-3 days. The challenging introduction of armine in a dose equalling the sensitizing one produced an anaphylactic shock in a group of animals sensitized with single doses of 0.005 and 0.0005 mg/kg. The allergic nature of these reactions was also confirmed by a large number of positive results secondary to immunological tests preceding the challenging dose, viz. by degranulation of mast cells, agglomeration of leucocytes and passive skin anaphylaxis.


[New chloro derivatives of benzothiopyrano indoles and quinolines]. Some chloro derivatives of the carcinogenic [1]benzothiopyrano[4,3-b] indoles and 6H[1] benzothiopyrano[4,3-b] quinolines have been synthesized from 7- and 8-chlorothiochroman-4-one. Mass spectral data of these compounds are comparated with those of benzothiopyranoindole. Biological tests for carcinogenic activity are in progress.


[Comparative evaluation of the toxicity of potassium hydrocarbonate and potassium chloride]. The potassium hydrocarbonate and potassium chloride toxicity was compared in experiments on 113 albino rats. The death following introduction of maximal amounts of potassium chloride was noted to supervene earlier than it did in animals receiving equivalent doses of potassium hydrocarbonate. Simultaneous introduction of sodium hydrocarbonate lowered the toxicity of both potassium hydrocarbonate and chloride. Morphological investigations revealed that toxic doses of potassium hydrocarbonate bring about shifts in the carbohydrate and lipids metabolism. Some mechanisms behind the action produced potassium chloride and hydrocarbonate are discussed.


Radiopaque contrast media. XXXV - Physical properties of iopronic acid, a new oral cholecystographic agent. Some physical properties of iopronic acid a new oral cholecystographic agent are reported. Determined are U.V., I.R., N.M.R. and mass spectra, X-Ray powder diffraction melting point and DTA, solubility, acidity constant and partition coefficient.


[Dynamics of some carbohydrate metabolic indices in the liver and the alcohol concentration in it depending on the time of day of its administration]. The liver glycogen and sugar levels in intact rats are shown to experience diuranal variations with a maximum at 3-9 and minimum at 15-21 hours. Intragastric administration of ethanol in a dose of 1.5 ml/100 g produced an abrupt fall of the glycogen content in the liver of rats in 3.12 and maximally after a lapse of 6 hours, this being followed by a drop in the amount of sugar in 12 hours. The decline in the level of metabolites at different periods of the day (3, 9, 15 and 21 hr) was dissimilar. The lethality among the animals and concentration of the alcohol in the liver 3 and 6 hours following the action of alcohol at the hours of the day under study correlated and were inversely proportional to the sugar and glycogen content of the same hours of the day.


Synthesis of (+/-)-8,12-trans-delta5-en-cis-11-KETO-14,15-trans-en-16-R,S-hydroxyprostanoic acid methyl ester. The synthesis of (+/-)-8,12-trans-delta5-en-cis-11-keto-14,15-trans-en-16-R,S-hydroxyprostanoic acid methyl ester (XIII) from 2-allyl-2-cyclopentenone (I) is described. The key products are the conjugate enone (IX) or the acetylenic secondary alcohol (X) derived from 2-propargyl-2-cyclopentenone (II).


Synthesis of new derivatives of the 4,5-diphenyloxazole series. In continuation of earlier studies carried out in the field of 2-amino- and 2-aminoalkyl-4,5-diphenyloxazoles, some of which had shown anti-inflammatory, analgesic and platelet antiaggregating properties, a series of 2-alkylthio-4,5-diphenyloxazoles was prepared.


Synthesis of (+/-)-8,12-trans-delta5-en-cis-9-KETO-14,15-en-trans-16-R,S-hydroxyprostanoic acid methyl ester. A new synthesis of (+/-)-8,12-trans-delta5-en-cis-9-keto-14,15-en-trans-16-R,S-hydroxyprostanoic acid methyl ester (VII) from 2-allyl-2-cyclopentenone (I) is described, for which a lateral chain link process, opposite to that previously reported (4), is adopted.


The effect of portacaval transposition of hepatic cholesterol-7alpha-hydroxylase activity in the rat. Portacaval anastomosis in the rat results in an increase in the activity of the liver microsomal cholesterol-7alpha-hydroxylase enzyme system. The increase in the activity of this oxygenase occurs despite a decrease in the total amount of cytochrome p450 in the liver microsomes after portacaval anastomosis. It is possible to increase further the activity of the cholesterol-7alpha-hydroxylase enzyme in these portacaval shunted animals by feeding them on a diet containing a bile salt sequestering agent. This suggests that one of the factors influencing the activity of the liver microsomal cholesterol-7alpha-hydroxylase enzyme may be the concentration of bile salts reaching the liver from the blood plasma. Portacaval anastomosis in the rat tended to achieve a small decrease in the plasma cholesterol concentration.


Proteins dealing with N-ethylmaleimide inhibition of pig heart mitochondrial phosphate transport system. Our data clearly demonstrate that protective effect of phosphate and protective effect of mersalyl against NEM-inhibition of phosphate transport act at the level of two kinds of proteins. (1)Two major components are phosphate and nigericin NEM sensitive. According to our previous data [13] it has been also demonstrated that these two proteins components are valinomycin NEM sensitive (results not shown here) suggesting a relationship between these proteins and the energy linked proton translocation process. Relationships between these proteins and the phosphate translocation process are not evident and are under further investigations. (2) Two other insoluble major components localised at the level of the subparticular fraction are mersalyl NEM sensitive. We can suggest that these proteins are implicated in the translocation of phosphate in pig heart mitochondria.


Respiratory rhythmicity in the cat.

Respiratory rhythmicity in the cat. Brain stem respiratory neuron activity in the cat was studied in relation to efferent outflow (phrenic discharge) under the influence of several forcing inputs: 1) CO2 tension: hypocapnia produces disappearance of firing in some neurons, and conversion of respiratory-modulated to continuous (tonic) firing in others. 2) Lung inflation: during the Bruer-Hering reflex, some neurons have "classical" responses and others have "paradoxical" responses (i.e., opposite in direction to peripheral discharge). 3) Electrical stimulation: stimulus trains to the pneumotaxic center region (rostral lateral pons) produce phase-switching, whose threshold is: a) sharp (indicating action of positive-feedback mechanisms), and b) dependent on timing of stimulus delivery (indicating continuous excitability changes during each respiratory phase). Auto- and crosscorrelation analysis revealed the existence of short-term interactions between: a) medullary inspiratory (I) neurons and phrenic motoneurons; b) pairs of medullary I neurons; c) medullary I neurons and expiratory (E) neurons. A model of the respiratory oscillator is presented, in which the processes of conversion of tonic to phasic activity and switching of the respiratory phases are explained by recurrent excitatory and inhibitory loops.


Neuronal control of respiration in decapod crustacea. Respiratory exchange in decapod crustacea requires the coordinated activity of the heart and the scaphognathites, appendages which ventilate the gills. There is common central nervous system neuronal modulation of both autogenically active systems as well as direct neuronal communication between both systems. The heart and scaphognathites also respond directly to oxygen tension. The neuronal control of the scaphognathites also respond directly to oxygen tension. The neuronal control of the scaphognathites is analyzed at several levels. Particular attention is directed toward the means by which the innately organized and stereotyped motor pattern for forward beating can be altered to produce reversed beating. The importance of sensory feedback in maintaining normal rates of scaphognathite beating is noted. And the phenomenon of bilateral coordination between the morphologically independent scaphognathites is described. Several different models of parts of the over-all scaphognathite neuronal circuitry are presented for heuristic purposes.


Sensory and central nervous control of gill ventilation in Limulus. The gills of Limulus are ventilated by a metachronal rhythm of movements of five pairs of gill plates. A gill plate is promoted and remoted by action of alternating nerve impulse bursts to antagonist promotor and remotor muscles. The motor output pattern is centrally generated, requiring no sensory feedback. Intracellularly recorded rhythmic activity of respiratory motoneurons consists of cyclic depolarization and spiking, and repolarization. The repolarizations have reversal potentials that indicate that motoneuron burst terminations result from synaptic inhibition. Intracellular and antidromic stimulation of motoneurons has little effect on other motoneurons. This apparent lack of interaction between motoneurons indicates that the central respiratory pattern is generated at interneuronal levels. Proprioceptive reflexes are present; they play little role in modulating the centrally generated motor pattern, but they are capable of partially entraining the rhythm when all gill plates are cycled at frequencies near the respiratory rate. Respiratory rate in intact animals is proportional to the ambient oxygen content, respiration ceasing in an anoxic environment. This oxygen dependence may result from sensory input from external oxygen receptors located in the cuticle between the coxae of the walking legs and within the lamellas of the book gills. The intercoxal units are inhibited by anoxia. Three classes of units are recorded from the gills: units excited by oxygen, units inhibited by oxygen, and units whose mechanosensitivity is oxygen dependent. These external oxygen receptors may modulate ventilation via command fibers present in the ventral nerve cord.


Intrauterine gonadal development.

Intrauterine gonadal development. This review article summarizes the intrauterine gonadal development and differentiation of both male and female human embryos and fetuses. It describes in detail (1) the organization of the indifferent gonad and its seeding by the extra-gonadal germ cells, (2) the development of the duct systems before sex differentiation, and (3) the controlling mechanism of differentiation of the ovaries and testes. Timetable for the development of the human male and female reproductive systems have been compiled from the literature.


Cytologic features of oocytes in the adult human ovary. A broad survey of the cytologic features of follicular oocytes from sections of adult ovaries from donors with normal menstrual cycles, from patients with polycystic ovarian disease, and from patients treated with estrogen and progesterone for gynecologic disorders with no apparent ovarian pathology has been made in this study. On the basis of light microscopic observations, four basic types of oocytes could be recognized: (1) oocytes with nuclei containing diffused or filamentous chromatin, (2) oocytes with metaphase I chromosomes or an extruded polar body, (3) oocytes with nuclei possessing massive clumps of chromatin frequently associated with the nucleolus, and (4) degenerating oocytes with no distinguishing cytologic features. The numbers of oocytes in these different groups varied with the reproductive state of the donors: 34 to 35% were type 1 during proliferative and secretory phases; mature oocytes type 2 were 3.3%, and were found only during the late proliferative phase; and 41 to 46% were type 3 during both phases of the menstrucal cycle. Large numbers of oocytes from polycystic ovaries (77%) and from ovaries of patients treated with steroids (86%) were degenerating and frequently contained massive clumps of chromatin material associated with the nucleolus.


The LEM device in an immediate postpartum contraception program. Experience with the LEM intrauterine device in an immediate postpartum program at the Jose Fabella Memorial Hospital, Manila, Philippines, is reported. During a 6-month period, the LEM was inserted in 1359 women immediately after normal term deliveries. The early expulsion rate was high, but removals for bleeding or pain were minimal. Pregnancy rates during the second 6 months of use were higher than those reported previously for postpartum insertions of the LEM device.


The effect of D-norgestrel, 30 micrograms, on the oral glucose tolerance test, including insulin levels, in Thai women. The effect of D-norgestrel, 30 mug, on the oral glucose tolerance test was studied in 49 Thai women. There was a significant elevation of the blood glucose level at 60 minutes during the test in women who had taken D-norgestrel for 6 and 12 months. Insulin levels in the blood were significantly elevated over control levels in both groups of women at 90, 120, 150, and 180 minutes during the test. There was no difference in the results obtained at 6 months and 12 months. There was also no significant difference in the fasting blood glucose or insulin levels in the three groups of women. The results indicate that D-norestrel at a daily dose of 30 mug has an effect on carbohydrate metabolism in Thai women.


Artificial insemination donor: clinical and psychologic aspects. Forty-four sterile sterile couples in whom the main cause of infertility was the male factor were investigated. Artificial insemination donor (AID) was performed, timed according to the basal body temperature chart. It was found that it is important to match not only the physical appearance of the couple to that of the donor but also the blood group of at least one of the future parents. Patients were interviewed by a psychologist in order to define their marital relationship, their attitude toward the infertility, their feelings about AID in comparison to adoption, their attitude toward the donor and pregnancy, and their attitude toward their physician. The role of the psycholgist in AID treatment was found to be important for careful selection of cases. He can also guide and prepare these couples to face family life in the future.


A new method for evaluating cervical penetrability using daily aspirated and stored cervical mucus. Cervical mucus samples from 33 women undergoing fertility work-up and married to normospermic husbands were aspirated daily with a tuberculin syringe during the periovulatory period. Samples were transferred to polyethylene tubing, sealed, and stored at 4 degrees C for 7 to 14 days. In vitro sperm penetration tests were performed in each case, using only one sample of husband's semen with all of the mucus samples that were collected during one cycle. Preliminary studies with 50 samples of cervical mucus taken at random showed that no difference in physicochemical and penetrability properties existed between fresh mucus and mucus stored for 10 to 14 days. Very often the optimal penetrability of the cervical mucus occurred on unpredictable days. In contrast, many tests performed on days which would have been predetermined for in vivo postocital tests were poor; consequently, those in vivo tests would have been falsely interpreted as negative. This new test using daily aspirated and stored mucus, which is simple to perform, is valuable mainly because it may eliminate the false negative results of other penetration tests. In this way the diagnosis of a truly hostile cervix may be more accurate.


Studies on the physiology and biochemistry of mammalian epididymis: effect of flutamide, a nonsteroidal antiandrogen, on the epididymis of the rat. The effect of flutamide (Sch 13521; 4'-nitro-3'-trifluoromethylisobutyranilide), a nonsteroidal antiandrogen, on male rat genital organs was studied. Administered at a dose of 25 mg/kg body weight daily for 30 days, flutamide caused a significant increase in the weight of the testis but had no effect on spermatogenesis and Leydig cell morphology. The secretory activity of the epididymis, as evidenced by the level of glycerylphosphoryl-choline and sialic acid, either remained unaffected or was stimulated. There was a significant decrease in seminal vesicle and ventral prostate weight and in the fructose content of the coagulating gland. The anti-androgen at the dose used did not affect the fertility of the rats. The significance of these findings is viewed in relation to the hypothesis of a differential threshold requirement of androgen for the epididymis and the accessory sex glands. The potentiality of antiandrogens as extragonadal antifertility agents in the male is discussed.


Artificial insemination using homologous semen: a review of 158 cases. One hundred fifty-eight women underwent artificial insemination with homologous semen (AIH) in an attempt to achieve conception. Only 15 (9.5%) were successful. Women with anatomical abnormalities were not excluded from the study and they were less successful than the normal women, but results were disappointing in both groups. The most frequently recorded indication for AIH was decreased density or motility of the husband's sperm, but pregnancy occurred in only 2 of the 48 cases in which sperm count was consistently less than 50 X 10(6)/ml and in only 3 of the 63 cases in which sperm motility was consistently less than 60%. When several semen analyses revealed considerable fluctuation in semen quality, the chances for impregnation by natural means appeared to be greater than the likelihood of success with AIH. The procedure does not seem to compensate for diminished count or motility, does not seem to be of particular value in cases of unexplained infertility, and appears to be indicated only in very special cases, if at all.


Pituitary-testicular axis in patients on lithium therapy. Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were studied in 10 patients undergoing lithium therapy. Testosterone levels were below the normal range in 7 of the 10 patients. FSH levels were high in two patients and LH levels were high in one. The effects of lithium on the pituitary-testicular axis are discussed.


A method for collecting motile spermatozoa from human semen. Spermatozoa migrate rapidly into a diluent brought into contact with semen. When this process was used to collect sperm in a diluent contained in Pasteur pipettes that were dipped into semen for 1 hour, concentrations of spermatozoa ranging from 0.6 to 5.7 X 10(6) cells/ml were obtained. This method yielded sperm suspensions free of seminal plasma and populations of spermatozoa that had increased motility ratings compared with the original semen. In contrast, removal of the seminal plasma by a procedure involving three dilutions and two gentle centrifugations resulted in a decrease in the average motility ratings. Determinations were made of the electrolyte, energy substrate, and trace element content of preovulatory human tubal fluid. A sperm diluent having an electrolyte composition similar to that of tubal fluid was formulated and used for collecting spermatozoa. Population of spermatozoa that migrated from semen into this diluent had significantly greater mean velocities than sperm in the semen. Moreover, the diluent proved to be a favourable medium for significantly delaying the deterioration of sperm progression over a 24-hour period.


Round-headed human spermatozoa.

Round-headed human spermatozoa. Ultrastructural investigation of two cases of round-headed spermatozoa from human ejaculates revealed the existence of two different pathomorphogenetic types. Case 1 represented round-headed spermatozoa of the Schirren and Holstein type caused by loss of the abnormally formed acrosome during spermiogenesis and the missing nuclear transformation. In case 2 a primary maturing inhibition was responsible for the round-headed feature of the spermatozoa; the normally flattened, conical nucleus and acrosomal cap were surrounded by huge droplets of ample cytoplasm. Secondary degenerative changes contributed to the decreased motility of these round-headed spermatozoa. Therapeutic trials for this oligospermic patient showed that an increase in cell count to values in the low-normal range and a drastic reduction in the percentage of round-headed cells (from 80% to 47%) could be achieved. The Schirren and Holstein type, however, must be regarded as absolutely infertile due to the absence of an acrosome and its intrinsic enzymes.


The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of "subclinical" varicocele. The accuracy of scrotal thermography as a diagnostic method to confirm or detect spermatic venous reflux in patients with palpable and subclinical varicocele, respectively, was evaluated. In all, 118 scrotal thermograms were performed in 110 patients, and the results were compared with the findings by selective retrograde venography of the internal spermatic vein whenever required. Normal thermograms were recorded in 23 oligospermic men without varicocele. Of 39 patients with palpable varicocele, 37 had abnormal thermograms; normal recordings occurred in 2 patients with associated unilateral testicular atrophy. Among 36 men suspected of having subclinical varicocele, 19 had abnormal thermograms and 16 presented reflux on the venogram. Venography was performed in 5 of the remaining 17 men with normal thermograms; only 1 had reflux. Screening for varicocele by means of scrotal thermography thus revealed reflux in 16 of 36 patients with unexplained infertility. Postoperative thermograms were disturbed in 6 of 20 cases, 5 of which presented reflux. Only 1 of 14 postoperative patients with normal thermograms underwent venography, and no reflux was demonstrable. Both the difference in temperature between the affected and contralateral hemiscrotum and the area of hyperthermia were significantly greater in patients with grades II and III varicocele, compared with those with subclinical and grade I varicocele. It is concluded that scrotal thermography is a valuable screening method for the detection of spermatic venous reflux. The technique allows selection of patients to be subjected to retrograde venography.


Characterization of phosphoglycerate kinase from human spermatozoa. We have confirmed the presence of a unique electrophoretic isoenzyme of phosphoglycerate kinase (PGK) in homogenate extracts of human sperm. No genetic variation was found in 30 individual specimens tested. However, immunologic neutralization studies indicate that the sperm PGK is different from red cell PGK.


Purification and characterization of a sperm-coating antigen from human seminal plasma. A sperm-coating antigen has been purified from human seminal plasma by a combination of fractionation methods including ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl cellulose ion-exchange chromatography. The purified antigen was demonstrated to be immunologically identical sperm-coating antigen, not derived from blood serum but having immunologically cross-relating antigens in milk and saliva, and a glycoprotein with a molecular weight of approximately 33,000. The purpose of purifying this antigen was discussed.


Effects of progesterone on labeling of soluble proteins and glycoproteins in rabbit endometrium. An in vitro test system was used to study in vivo effects of progesterone on synthesis and secretion of total proteins and glycoproteins in rabbit endometrium. Endometrial explants incubated in Eagle's minimal essential medium containing radioactive leucine and N-acetylglucosamine were found to synthesize soluble proteins readily, including glycoproteins. Furthermore, significant amounts of newly synthesized proteins, including blastokinin, were released by the tissues into the incubation medium. In addition, in vitro synthesis and release of labeled proteins by estrogen-primed endometrial tissue (E-primed tissue) was significantly enhanced by exposure of the tissues to progesterone in vivo. Double-labeling studies demonstrated qualitative as well as quantitative differences in peptide synthesis between E-primed tissues and E-primed, progesterone-treated tissues. Progesterone also stimulated both the synthesis and the release of glycoprotein by E-primed tissues. These studies, therefore, suggest that progesterone regulates qualitatively and quantitatively the synthesis and secretion of total proteins, including glyco-proteins, in rabbit endometrium.


[Concentration of urea in blood and organs during muscular activity]. Muscular activity increases the content of urea in blood, liver, and muscles equally. The urea content in the kidney, however, either decreases or does not change at all, increasing only after an exhausting work or during the rest. The amount of protein in the diet influences upon the urea quantity in the organism, but the level of it's change under the action of muscular activity remains practically identical in the regime of the different protein nutrition. The activity of arginase in the liver and muscles is equally changed with the changes of the urea content in the blood and tissues.


[Heat content of the body as a basic parameter of thermoregulation]. With the aid of thermometry and calorimetry, the role of the organism's heat degree for the vasomotor response of the ear skin was studied in the rabbit. The calorimetric temperature was constant (19-21 degrees C) throughout the experiment. The heat threshold varied from 86 cal/kg to 320 cal/kg, depending on the different initial heat degrees in the animal. The increase in the organism's heat degree is concluded to be the main mechanism for initiation of the heat loss responses.


[Osmo- and ionic liver receptors].

[Osmo- and ionic liver receptors]. Role of the liver receptors in osmo- and ionic homeostasis regulation was studied in unanesthetized dogs. The presence of selective sodium-and potassium-sensitive receptors was shown in the liver receptor field. Stimulation of the ionic receptors evokes ADH-induced antidiuretic and specific ionuretic renal response. Impulses depressing diuresis were found to spread mainly in the posterior roots of the spinal cord, while those changing the ion excretion - in the n. vagi.


[The role of several brain stem structures in activation of the neocortex and motor reflexes in chronically premesencephalic cats]. Chronic experiments were carried out in 18 cats. After premesencephalic section of the brain-stem, the neocortex can be activated both spontaneously and in response to the posterior hypothalamus or the forepaw skin stimulation. After bilateral lesions in the posterior hypothalamus, neither spontaneous nor the forepaw-skin stimulation-produced activation of the neocortex, was observed. Excitation of the mesencephalic RF is accompanied by activation of motor reflexes. A conclusion was made that the posterior hypothalamus, independently of the mesencephalic RF, is capable of activating the neocortex, while the mesencephalic RF, independently of the rostral structures, is responsible for the motor reflex activation.


[The effect of low-frequency electric stimulation of the caudate nucleus on the electrical activity of the cortex and on the sleep-wakefulness cycle]. In cats, the effect of low-frequency electric stimulation of the caudate nucleus on electric activity of neo- and archipaleocortex and on wakefulness-sleep cycle, was studied. The data obtained suggest: 1) at threshold and suprathreshold single electric shocks applied to the caudate nucleus they evoked potential occurs more readily in the sensorimotor area of the neocortex than in the dorsal hippocampus. At 2-6/sec stimulation the evoked potentials in the hippocampus are facilitated and become very stable, whereas in the sensorimotor cortex the most obvious responses occur at the 6-8/sec frequency. However, the evoked potentials are variable in the sensorimotor cortex, and at prolonged 8-12/sec stimulation spindle activity soon develops; 2) behavioral correlate of the synchronized activity in the neo- and archipaleocortical structures during low-frequency stimulation of the caudate nucleus, may involve development of drowsiness with the cessation of stimulation, however, both the EEG and behavioral signs of the drowsiness disappear. The onset of drowsiness following withdrawal of the caudate stimulation, is a rare phenomenon only occurring because of an occasional coincidence of the stimulation with the spontaneous onset of natural sleep; 3) low-frequency caudate stimulation entailing the ECoG synchronization does not cause the transition of paradoxical phase into the slow-wave phase of sleep, and as soon as the stimulation ceases its normal structure recovers. However, if the stimulation of the caudate nucleus is repeated several times in one paradoxical phase, this would shorten the subsequent slow-wave phase and accelerate the onset of the next paradoxical phase; 4) prolonged low-frequency stimulation of the caudate nucleus causing the ECoG synchronization results in a considerable change of wakefulness-sleep cycle in the post-stimulation period: a decrease in the total time of slow-wave sleep due to shortening of its different phases, and an increase in the total amount of paradoxical sleep because of the onset of its phases is rendered more frequent. This effect is more obvious in the first half of the 8-hr cycle.


[Changes in the activity of the cat sensomotor cortex under heterosensory stimulation]. In immobilized cats, the sensorymotor neurons were shown, in the course of habituation to the rhythmic light stimulation (1/sec), to start responding to stimuli of other modalities (somatic) when the latter were presented during the functional recovery cycle following the light stimulation. The habituation to the light stimuli did not occur when they were followed by a somatic stimulus with 100-300 msec delay. The data obtained seem to reflect the reconstruction occurring in the functional state of the sensory system.


[The effect of hippocampal stimulation on the evoked electrical activity of different brain structures]. The functional relationships of the dorsal and ventral hippocampus and entorhinal area were studied in cats. The dorsal hippocampus was shown to suppress the electric activity and evoked responses to entorhinal stimulation in the ventral hippocampus and other structures. The dorsal hippocampus inhibits evoked responses to skin stimulation in entorhinal area and ventral hippocampus. The ventral hippocampus produced opposite effects. The functional differences of the dorsal and ventral hippocampus suggest different connections with entorhinal area.


[The interaction of symmetrical cortical descending influences on lumbar motoneurons]. Postsynaptic potentials (PSPs) of the cat motoneurons elicited by stimulation of contralateral and ipsilateral motor cortex, and their changes during combination of both kinds of stimulation were studied with use of the intracellular recording technique. For elicitation of ipsilateral PSPs, the cortex stimulation of greater intensity was needed as compared with contralateral activation. The ipsilateral synaptic reactions had a longer latency and time of segmental delay than the contralateral ones. Conditioning stimulation of the ipsilateral cortex exerted an inhibitory effect upon contralateral cortically evoked EPSP and IPSP of motoneurons and upon potential recorded at the spinal cord surface. Suppression of conditioned PSPs occurred without changes of their sign or pattern in most cases. The data obtained suggest that inhibitory interaction of cortically evoked descending activities involves segmentary inhibitory interneurons and is realized at an interneuronal level and/or at the membrane of the motoneurons.


[An analysis of EEG rhythm changes following micropolarization of several brain structures]. With the aid of the EEG special statistical analysis, micropolarization of the temporal cortex of hypothalamus was shown to entail abrupt alterations of the theta-, alpha-, and beta-rhythms in the temporal and motor cortex, hypothalamus, and the midbrain RF. The changes of the biorhythms (their correlation, thresholds of occurring, connection of the local and distant shifts) are regarded as reflecting some fine regulation of the structures' functional condition as well as mutual influences of the cortex and the deep brain structures which tell on modulation of mnemic processes.