Autoradiographic localization of H1-histamine receptors in brain using 3H-mepyramine: preliminary studies.

3H-Mepyramine (3H-MEP) binds to slide-mounted tissue sections with characteristics indicating the labelling of a H1-histamine receptor. It is saturable (Bmax 12 pg/g tissue), of a high affinity (KD 0.5 mM) and possesses a drug specificity similar to that observed for H1 receptors in a variety of systems. In agreement with other biochemical studies, the association constant and the number of binding sites appear lower in the rat than in the guinea pig. Once the optimal conditions for labelling the receptors were found in the biochemical studies, tissue sections were prepared for autoradiographic studies. The receptor density varied markedly in the different brain regions. For example, there was a high density of H1 receptors in the molecular layer of the guinea pig cerebellum. In the guinea pig hippocampal formation, the highest densities were found in the molecular layer of the dentate gyrus while lower levels were found in the dendritic fields of the pyramidal cells. Significant densities of receptors were found in other areas of the rat and guinea pig brain as well.


Presynaptic inhibition by ergotamine of the responses to cardioaccelerator nerve stimulations in the cat.

The effects of ergotamine on the tachycardia elicited by postganglionic stimulation of the cardioaccelerator nerve have been investigated in both intact and spinal (desmethylimipramine-pretreated) cats. Ergotamine (2.5--20 microgram kg-1) selectively antagonized the response to low-frequency (0.3--3 Hz) stimulation. The responses elicited by stimulation of the nerve with higher frequencies (greater than 10 Hz) either remained unaltered or were facilitatated by the drug. Pretreatment of the cats with pimozide (0.2 mg kg-1) completely antagonized the inhibitory effects of ergotamine on the sympathetic neuron. Although phentolamine (0.5 mg kg-1) did appear to attenuate the effects of ergotamine, the changes were, however, not statistically significant. Since the drug did not reduce the cardiac effects of isoprenaline or tyramine, it is concluded that ergotamine interferes with the release of noradrenaline from the cardioaccelerator nerve, mainly by stimulating the presynaptic dopaminergic receptors. This effect may be an important mechanism by which the drug causes bradycardia in almost all species regardless of the blood pressure response.


Rat and human cardiac monoamine oxidase: a comparison with other tissues.

Experiments were made to test the proposal that rat heart mitochondrial monoamine oxidase (MAO) differs from that in certain other organs. Using kynuramine as the substrate, cardiac MAO of rats was compared with that in the vas deferens and liver. While the relative proportions of type A and B MAO varied between the three tissues, the sensitivity of the MAO types to preferential inhibitors, mixed substrate interactions and apparent Km determinations failed to reveal differences. Human atria contained mostly type B MAO, but the properties of the A and B types were not radically different from those found in rat tissues. No clorgyline-resistant MAO activity was detected with kynuramine, either in the rat or human tissues. Differences in rat heart MAO seem to be exposed by some substrates but not others, such as kynuramine.


Enhancement by elevated external potassium of the maximal responses to acetylcholine and norepinephrine in the rat vas deferens.

In the rat vas deferens, the maximal response to acetylcholine increased almost linearly as a function of external potassium concentration, [K+]0. The magnitudes of the maximal responses in 10, 15 and 20 mM [K+]0 were 128, 155 and 184% of the maximal response in 6 mM [K+]0, respectively. The response to carbachol also increased in 20 mM [K+]0 to almost the same extent. The enhancement of the norepinephrine response was observed only in 20 mM [K+]0; its magnitude was only 125%. The increase in [K+]0 from 6 to 20 mM did not affect the sensitivity (expressed as the geometric mean ED50) either to norepinephrine or to acetylcholine. Denervation of the postganglionic nerves to the vas deferens did not affect the enhancement of the maximal responses in 20 mM [K+]0, indicating that the release of neuronal transmitters may not be involved.


Effects of antidepressants and anticholinergics in a mouse "behavioral despair" test.

A new "behavioral despair" test previously asserted to be selectively sensitive to antidepressant treatments was examined for specificity. The results of the present study demonstrate that, in addition to antidepressants, agents with anticholinergic properties such as scopolamine, danitracin, benactyzine, benztropin, clozapine and cyproheptadine also reduce immobility in this test. These results indicate that the swim test in mice cannot be considered selectively sensitive to antidepressants.


Differential effects of triton X-100 on benzodiazepine and GABA binding in a frozen-thawed synaptosomal fraction of rat brain.

The effect of Triton X-100 on 3H-GABA and 3H-diazepam binding was measured in a frozen-thawed synaptosomal fraction of rat brain. Specific binding activity (amount bound per mg protein) of both ligands was increased by the treatment. Diazepam binding capacity in the pellet was progressively decreased, while GABA binding was increased, then decreased by increasing Triton X-100. Diazepam binding affinity was unchanged, while GABA binding affinity increased. Triton X-100 appears to preferentially solubilize benzodiazepine binding sites, indicating GABA and benzodiazepine binding sites are on separate macromolecules.


The triple effect induced by delta 9-tetrahydrocannabinol on the rat blood pressure.

The intravenous injection of delta 9-tetrahydrocannabinol (2-10 mg/kg) produced dose-related changes in the rat blood pressure. Three effects were detected: (1) an immediate and short-lasting hypotension related to bradycardia, blocked after atropine, vagotomy hexamethonium and pithing; (2) A rise in blood pressure 30 seconds after injection, insensitive to yohimbine, hexamethonium, pithing and reserpine treatment; (3) a slow and persistent hypotension, 5 min later, insensitive to atropine and vagotomy but inhibited by hexamethonium, pithing and reserpine treatment. It was concluded that intravenous injection of THC in rats may induce vagal stimulation and hypotension. This effect was reversed and followed by hypertension due to direct vasoconstriction not dependent on sympathetic activity. After this action a central decrease in sympathetic tonus led to a persistent hypotension an effect which is commonly reported for mammals.


Release of radioactive purines from cat nictitating membrane labeled with 3H-adenine.

Cat nictitating membranes were incubated with 1-2 x 10(-7) M 3H-adenine or 3H-adenosine for 1 h. A tissuebath ratio of about 15 was found for both compounds in intact and denervated membranes. In intact nictitating membranes sympathetic nerve stimulation (4 Hz, 5 min) caused a net release of purines (0.66 +/- 17% of the tissue content), which was reduced by alpha-blockade. Noradrenaline (1-3 microM) or tyramine 60 microM), which produced the same contractile response as did nerve stimulation, increased purine release to the same extent as did nerve stimulation. The effect of either agent was reduced or abolished by phentolamine. Purine release could also be induced by acetylcholine and ATP. This release was not altered after surgical denervation. There was an excellent correlation between the contractile response and the purine release induced by nerve stimulation, noradrenaline, tyramine and acetylcholine. However, ATP caused a larger release of 3H-purines than expected from the contractile responses, possibly indicating displacement. The results indicate that most if not all of the 3H-purines released by nerve stimulation in the cat nictitating membrane are derived from postjunctional elements.


Repeated administration of 5-methoxy-N,N-dimethyltryptamine to male rats potentiates stimulation of prolactin secretion by serotonin agonists.

Repeated administration of 5-methoxy-N,N-dimethyltryptamine (5MeODMT, 5 mg/kg, a serotonin agonist, every 3 h for a total of 4 injections) potentiated its prolactin (PRL)-releasing effect and that of two other serotonin agonists, quipazine and N,N-dimethyltryptamine. This pretreatment schedule had no effect on PRL response to anti-dopaminergic drugs. The onset of enhanced PRL response to serotonin agonists was gradual and appears to be due to sensitization of the serotonergic mechanism involved in the regulation of PRL secretion. The possible mechanisms underlying this phenomenon are discussed.


A comparison of changes in atropine-induced tachycardia and atropine concentration in conscious dogs.

In the conscious dog, after intravenous injection of 0.2 mg/kg 3H-labelled atropine the progressive decrease of the heart rate was well correlated with the disappearance of atropine from the blood. But, with atropine infusion (0.2 mg/kg/h) the tachycardia decreased progressively in spite of an increase in the blood concentration of atropine. Differences appeared between the normal animals or those pretreated with propranolol or reserpine, and the animals which had undergone bilateral thoracic sympathectomy. In the stellectomized animals atropine induced a smaller but much more lasting cardiac acceleration than under the other experimental conditions. It seems that only peripheral factors are involved in the complex interactions between the adrenergic and cholinergic nervous systems at the sinus node level.


Autoanalgesia: acquisition, blockade and relationship to opiate binding.

Acquisition of autoanalgesia (behaviorally activated antinociception) was assessed across 7 consecutive days by shocking rats 10 sec after the determination of their tail-flick latencies. Thus the effect of conditioned fear on antinociception was being investigated, since each shock preceded the subsequent tail-flick test by 24 h. Autoanalgesia was acquired by the second fear-conditioning trial. Although pretreatment with naltrexone or diazepam had no effect, spinal cord transection at the thoracic level effectively obviated autoanalgesia. Investigations of opiate and opioid binding indicated significantly less binding in the fear-conditioned rats as well as an inverse relationship between binding and antinociception. These changes in binding are suggestive of partial mediation of autoanalgesia by an endogenous opiate peptide that is released by the fear-conditioning procedure.


Tricyclic antidepressant radioreceptor assay.

A radioreceptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [3H]-3-quinuclidinyl benzilate (3H-QNB) for binding to muscarinic cholinergic receptors in rat brain membranes. The assay is sensitive, in that in can detect, for example, 2 ng/ml nortriptyline in plasma. Seven plasma samples from depressed patients treated with nortriptyline were assayed with the radioreceptor and gas liquid chromatographic methods, and the results from these two methods were almost identical. This assay should be used cautiously, if at all, in patients treated with other drugs that have potent anticholinergic effects.


THIP and isoguvacine are partial agonists of GABA-stimulated benzodiazepine receptor binding.

The effects of THIP and isoguvacine on 3H-flunitrazepam binding to washed membranes prepared from the cerebral cortex of adult rats have been examined. THIP, which has only minimal stimulatory effects on benzodiazepine (BZ) receptor binding, has been found to inhibit the stimulation induced by small concentrations (2 microM) of exogenous GABA. While isoguvacine stimulates BZ receptor binding, although to a smaller extent than GABA, it also antagonizes the stimulation of BZ receptor binding induced by GABA. Thus THIP and isoguvacine exhibit the properties of a partial agonist of GABA-stimulated BZ receptor binding.


Endogenous prostaglandins modulate adrenal catecholamine secretion.

Adrenal catecholamine secretion induced by haemorrhage in the cat was increased by administration of indomethacin to intact or to bilaterally nephrectomized animals. Infusion of PGE2 (but not of PGF2 alpha) suppressed the increased catecholamine secretion caused by indomethacin.


Vasoactive intestinal peptide inhibits release of somatostatin from hypothalamus in vitro.

The effect of vasoactive intestinal peptide (VIP) was studied on the release of somatostatin (SRIF) from slices of several regions of the rat brain in vitro. VIP induced a dose-dependent inhibition of SRIF release from mediobasal hypothalamic slices but did not interfere with SRIF release from preoptic area, amygdala or cortex. VIP inhibition had an apparent affinity: Kd = 6.8 +/- 3.9 x 10(-11) M. Secretin had a similar effect but at 600-fold higher concentrations (Kd secretin = 4.2 +/- 0.6 x 10(-8) M). Gucagon was ineffective in concentrations ranging from 10(-10) M to 10(-7) M. The data are consistent with a role of VIP in the hypothalamic control of growth hormone secretion.


Paracetamol potentiates acetylsalicylate in inhibiting prostaglandin synthesis.

Lower concentrations of paracetamol stimulated, but a higher concentration inhibited prostaglandin synthesis by bull seminal vesicle homogenate in the absence of added co-factors. Admixed with acetylsalicylate or indomethacin, paracetamol strongly potentiated the inhibition of prostaglandin synthesis in vesicle homogenate, and weakly potentiated inhibition in rat gastric fundus strip. We propose that, by acting as a phenolic co-factor, paracetamol stimulates prostaglandin synthesis and thus renders the cyclo-oxygenase more vulnerable to acetylsalicylate or indomethacin.


Frequency-dependent effects of the pyrethroid insecticide decamethrin in frog myelinated nerve fibres.

The pyrethroid insecticide decamethrin (10(-6) M) caused a frequency-dependent depression of the action potential in frog myelinated nerve fibres which was associated with a progressive membrane depolarisation brought about by summation of depolarising after-potentials. Voltage clamp experiments with single nodes of Ranvier showed that this afterpotential was most probably due to a long-lasting prolongation of the transient increase in sodium permeability of the membrane. The results indicate that decamethrin, like the other pyrethroids, specifically affects the sodium channels of the nerve membrane.


In vivo evidence of partial agonist activity exerted by purported 5-hydroxytryptamine antagonists.

Using a food-reinforced two-lever operant method, rats (n = 9) were trained to discriminate 0.16 mg/kg LSD from saline. Tests for stimulus generalization in rats so trained indicated that the purported 5-HT antagonists cyproheptadine (1.25 and 10 mg/kg), methysergide (0.16 to 10 mg/kg) and mianserin (2.5 to 40 mg/kg) produced partial generalization with LSD. The hallucinogens mescaline (5 to 40 mg/kg) and quipazine (1.25 to 5 mg/kg) were also generalized with LSD. The data suggest that cyproheptadine, methysergide and mianserin may produce partial agonist effects in addition to their antagonist action at central 5-HT receptor sites.


Nociceptive threshold after neonatal capsaicin treatment.

The nociceptive threshold as determined by the reaction time in the hot-plate and tail-flick tests was measured 3 to 4 months after pretreatment of young rats with capsaicin (50 mg kg-1 s.c.). The reaction time in the tail-flick test was prolonged in rats pretreated with capsaicin on the 2nd day of life. Capsaicin pretreatment up to the 10th day of life also resulted in a prolonged reaction time in the hot-plate test whereas capsaicin pretreatment after the 10th day of life was without effect. The elevation of the nociceptive threshold after neonatal capsaicin pretreatment most likely follows from degeneration of afferent nerve fibres activated by noxious stimuli.


Anticholinergic behavioral effect of phencyclidine.

Phencyclidine (PCP) impaired spatial alternation performance in rats. This effects was mimicked by antimuscarinic anticholinergics (scopolamine, atropine) and PCP derivatives (ketamine, cyclohexamine) but not by a variety of other agents. Muscarinic cholinergic agonists antagonized PCP. Impairment of spatial alteration performance by PCP appears to be mediated, at least in part, by and anticholinergic action; this is the first instance of a behavioral effect of PCP that can be largely attributed to a specific mechanism.


Effect of methadone and morphine on serotonin uptake in rat periaqueductal gray slices.

In vitro effects of d,l-methadone and morphine on [3H]serotonin (3H-5-HT) uptake in rat periaqueductal gray (PAG) slices were investigated. Only methadone had a significant inhibitory effect on 3H-5-HT uptake which was significantly enhanced by naloxone. The systemic administration of methadone did not affect 3H-5-HT uptake in vitro. These data further weaken the possible relationship between narcotic analgesia and blockade of the 5-HT reuptake mechanism.


Oral motor performance following central dopamine receptor blockade.

Oral motor responses were recorded in water-deprived rats receiving injections of spiroperidol, the dopamine blocker, into the nucleus accumbens and caudate nucleus. Spiroperidol injected into the nucleus accumbens resulted in dose dependent decreases in lap volume and tongue extension. Injections of spiroperidol into adjacent sites or into the caudate nucleus did not significantly reduce lap volume even with an 8 fold larger dose administered into the caudate. These observations implicate the mesolimbic dopaminergic projections to the nucleus acumbens in oral motor responses and indicate the need for systematic comparisons of the contributions of mesolimbic and nigrostriatal dopaminergic systems to ingestive behaviors.


Depressant effects of phenoxygenzamine on potassium contracture in cat ventricular muscle.

Phenoxybenzamine has been shown to have a depressant action on K+-depolarization contracture in cat ventricular muscle. In the present study, we show that this depressant action is specific for phenoxybenzamine and occurs in the presence of beta-adrenergic receptor blockade with nadolol. K+-contracture is not depressed by phentolamine nor augmented by phenylephrine. Thus, the depressant action of phenoxybenzamine is not mediated by its effects on cardiac adrenergic receptors.


Enhanced analgesic effects of stress following chronic administration of naltrexone in rats.

Chronic administration of the long acting opiate antagonist naltrexone potentiated the analgesic effects of foot-shock stress in the hot-plate test in rats. No changes in pain responsiveness were noted in naltrexone-treated rats that were not subjected to the foot-shock treatment. The results suggest that chronic opiate receptor may lead to the development of supersensitivity in endogenous opiate systems that mediate the analgesic effects of stress.


Cross-tolerance between ethanol and morphine with respect to their hypothermic effects.

Daily administration of ethanol (10-12 g/kg) to rats in a liquid diet resulted in tolerance to the hypothermic effects of ethanol. The rats also developed cross-tolerance to the hypothermic effect of morphine (15 and 30 mg/kg), whereas no cross-tolerance to the hyperthermic effect of morphine (5 mg/kg) was seen. Administration of morphine (30 mg/kg i.p.) for 3 days resulted in tolerance to morphine hypothermia and also cross-tolerance to ethanol-induced hypothermia. These studies fit with our hypothesis that tolerance and cross-tolerance among drugs develop to drug effects rather than to the drug per se. Therefore drugs sharing a common effect, even by different mechanisms, might show cross-tolerance for that effect.


Morphine no longer blocks gastrointestinal transit but retains antinociceptive action in diallylnormorphine-pretreated rats.

Diallylnormorphine (DANM) the quaternary N-allyl derivative of nalorphine, administered to rats, 8 mg/kg i.p., 20 min before i.v. injection of the potent opiate buprenorphine (1 microgram/kg, tritrium-labeled), reduced in vivo binding of the latter (63% of controls at 30 min) in small intestine longitudinal muscle including myenteric plexus, but not in cerebrum. Naloxone, 1 mg/kg s.c., had the same effect of buprenorphine binding in the two sites (52 and 54% of controls respectively). The marked slowing in the transit of a forced charcoal meal through the small intestine of rats given 10 mg/kg morphine, i.v. was prevented to comparable extents by DANM and naloxone; the latter also abolished the delay in hot plate reaction induced in these animals by morphine which, however, retained considerable antinociceptive effect in DANM-pretreated rats.


The effect of muscimol on hippocampal pyramidal cells.

The effects of muscimol on rabbit hippocampal pyramidal cell firing were studied and compared after iontophoretic, topical, and intravenous administration of the drug. All modes of application resulted in a bicuculline-sensitive, strychnine-insensitive, depression of the monosynaptically activated population spike evoked by micro-stimulation of the contralateral hippocampal field. These findings indicate that systemically administered muscimol selectively activates hippocampal GABA receptors suggesting that this compound may be useful for studying limbic system physiology.


Suppression of 3H-lysine incorporation into the vascular non-collagenous protein in rats treated with estradiol-17 beta.

The in vivo incorporation of 3H-lysine into non-collagenous protein of the heart, aorta and mesenteric arteries was measured in castrated or non-castrated male young rats given hormone treatment once daily for 14 consecutive days. In rats given estradiol-17 beta (50 micrograms), a significant reduction of blood pressure was noted at 7 and 8 weeks of age. The lysine incorporation into non-collagenous protein was markedly decreased in mesenteric arteries and to a lesser extent in the aorta of rats treated with estradiol-17 beta (50 micrograms). The decline in blood pressure concomitant with the reduction of lysine incorporation into non-collagenous protein of the same vessels was of similar magnitude in castrated, testosterone (50 micrograms) plus estradiol-17 beta (50 micrograms)-treated rats as compared with that in castrated testosterone-treated (50 micrograms) animals. Despite the variety of hormone treatments, the incorporation of 3H-lysine into non-collagenous protein of heart was similar for all the rats examined. It is suggested that the suppressive effect of estradiol-17 beta on biosynthesis of vascular non-collagenous protein, especially in small arteries, plays an important role in lowering the blood pressure of young male rats.


Effects of clonidine on the lumbar sympathetic pathways to the large intestine and urinary bladder of the cat.

The effects of clonidine on lumbar sympathetic outflow to the colon and urinary bladder were examined by recording drug-induced changes in spontaneous postganglionic firing and spinal viscero-sympathetic reflexes in the lumbar colonic and hypogastric nerves of the cat. Clonidine in doses between 2--40 micrograms/kg produced a dose dependent depression of spontaneous and evoked discharges in efferents of the hypogastric nerve but did not alter activity in the lumbar colonic nerves. Clonidine also reduced arterial blood pressure and spontaneous firing in the renal nerves. These data coupled with previous observations in this laboratory indicate that spinal sympathetic pathways can exhibit a considerable variation in the sensitivity to the depressant actions of clonidine. This variation in sensitivity may reflect the relative importance of noradrenergic inhibitory mechanisms in the respective pathways.


Effects of barbiturate anesthetics and ketamine on the force-frequency relation of cardiac muscle.

The effects of ketamine and barbiturates (pentobarbital, thiopental, methohexital) were studied in an isolated rabbit Langendorff preparation. All agents tested depressed contractility. Ketamine, as well as the lipophilic barbiturates (thiopental, methohexital), caused a relatively greater depression at higher pacing rates such that the force-frequency relation was reversed. Pentobarbital did not reverse Bowditch. The effects of barbiturates on Bowditch correlated directly with lipid solubility, suggesting that their rate-related effects are due to perturbation of the membrane lipid bilayer. Disruption of hydrogen bands between polar membrane components may also be involved. The time course of the effect of thipental at high pacing rates was slower, both in onset and recovery, than at low rates. At a pacing rate of 1 Hz, maximal depression of contraction developed within 5 min. However, at 2.5 Hz, contractility continued to decline for up to 30 min. After 5 min of perfusion with thiopental, Bowditch was still positive, but by 30 min it was reversed. These temporal differences in thipental effects suggest that different mechanisms may dominate in the support of contractility at different ranges of heart rate.


Convulsant and anticonvulsant actions in DBA/2 mice of compounds blocking the reuptake of GABA.

Compounds blocking the uptake of GABA into neurons or glia have been injected intracerebroventricularly (icv) or intraperitoneally (ip) in DBA/2 mice, age 21-28 days. Protection against audiogenic seizures was seen 30 min after the icv injection of (+)-2,4-diaminobutyric acid (0.5-2.0 mumoles), (+/-)-nipecotic acid (1.6-3.2 mumoles), (+)-ethyl nipecotate (0.4-0.8 mumoles), (-)-piperazic acid (4 mumoles) and putrescine (2 mumoles) or the ip injection of (+)-2,4-diaminobutyric acid (4-8 mmoles/kg and (+)-ethyl nipecotate (0.24-0.32 mmoles/kg). Of these ethyl nipecotate and nipecotic acid were the most effective anticonvulsants icv, but nipecotic acid was ineffective ip. Limb myoclonus and other epileptic manifestations (rearing, wild running, tonic clonic seizures) occurred in the absence of auditory stimulation after (+)-2,4-diaminobutyric acid (0.5-2.0 mumoles), (+/-)-cis-3-aminocyclohexane carboxylic acid (3.2-6.4 mumoles) and putrescine (2 mumoles). beta-Alanine (2-4 mumoles, icv) depressed respiration but did not protect against audiogenic seizures or induce myoclonus.


Enhancement of reflex vagal bradycardia following intracerebroventricular administration of methysergide in cats.

Metehysergide in total doses of 100, 200 and 400 micrograms injected into the fourth cerebral ventricle of cats potentiated the reflex bradycardic responses which were evoked by i.v. pressor doses of norepinephrine. Methysergide (400 micrograms) injected i.v., or intracerebroventricularly in vagotomized cats did not affect the reflex bradycardia. These results suggest that the enhancement of reflex vagal activation is due to an action of methysergide in the central nervous system. Intracerebroventricular methysergide significantly reduced the resting arterial pressure and heart rate, while i.v. administration caused only significant bradycardia. Carotid occlusion responses were depressed following both i.v. and intracerebroventricular methysergide. The magnitude of reductions in arterial pressure and heart rate following the injection of methysergide into the fourth cerebral ventricle were the same in vagotomized cats and in intact vagus preparations. It is suggested that depression of cardiovascular function is due to a central action of methysergide and is mediated by reduction in sympathetic outflow.


Separation of normal human bone marrow cells by counterflow centrifugal elutriation. I. Morphological analysis and subfractionation of neutrophilic granulocytes.

We have used counterflow centrifugal elutriation to separate the nucleated cells of normal human bone marrow into their major morphologically identifiable cellular components. Human bone marrow cells were separated simultaneously into the major cell types--lymphocytes, monocytes, granulocytes, and erythroid precursors. Significant concentration of bone marrow cell types could be achieved, including myeloblasts (x 25), promyelocytes (x 43), early myelocytes ( x 22), late myelocytes (x 17), metamyelocytes (x 6), eosinophils (x 40), basophils (x 55), erythroblasts (x 35), monocytes (x 40), and plasma cells (x 35). Cell loss is minimal (85% recovery of input) and random, and cell viability, as measured by trypan blue staining, is high (greater than 95%). Factors interfering with separation are also described: a low loading flow rate, the presence of an excess of mature red cells, and the absence of fetal calf serum resulted in poor cell recovery and viability. The use of heparin as the anticoagulant resulted in cell loss, decrease in cell viability, and an ineffective separation. Separation of cells from normal bone marrow by centrifugal elutriation should facilitate the study of bone marrow cell interactions and the purification of individual types of bone marrow cells.


The dynamics of red cell chimaerism in histoincompatible parabiosed mice.

A new technique for the quantitation of isoenzymes was applied to assess the proportions of red cells in the circulation of parabiosed mice. Two parent-F1 hybrid combinations showing phosphoglucose isomerase polymorphism were examined at successive stages of parabiosis and after separation. Once red cell populations became mixed, 3 days after union, the ratio of red cell phenotypes was never significantly different from one partner to the other, although parental red cells became predominant after about 20 days. However, F1 hybrid red cells could always be detected. After separation of parabiosed mice there was a return to the original composition although this took longer than would be expected on the basis of reported red cell life span. Packed cell volume measurements indicated that a parental polycythaemia and F1 hybrid anaemia developed in one strain combination but not in the other. Evidence was adduced to support the hypothesis of a difference in red cell flux being responsible for the generation of this polycythaemia-anaemia.


Quantitative and qualitative changes in the mitochondria in hepatocytes during postnatal development of male rats.

The volume density of mitochondria increases during postnatal development of the hepatocytes of male rats (test ages: 0 [birth], 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th, 21st, 28th day and 2nd, 3rd, 4th, 5th and 6th month) from 0.165 at birth to 0.236 on the 14th day, after which it decreases to 0.139 until the 6th month. At the same time the absolute volume of the mitochondria of the hepatocytes increases from 728.8 micrometer 3 at birth to 1225.5 micrometer 3 on the 14th day and reaches a maximum of 2102.3 micrometer 3 at the end of the 2nd month. The number of mitochondria per hepatocyte is 204 at birth. It increases continuously and reaches 2199 at the end of the 6th month. The volume of the average mitochondrion on the other hand diminishes during postnatal development from 3.83 micrometer 3 at birth to 0.64 micrometer 3 towards the end of the 6th month. Transverse divisions of mitochondria, budding of parts of mitochondria, autophagocytotic processes and degenerative changes can be observed throughout this period.


Image processing in pathology. IX. A new morphometry system and its application on gangliocytes of the nucleus olivaris.

This paper describes a new software system for automatic image processing in pathology. The system is based on the hardware NU2/ODD/PDP8 and the thereby yielded results. The effectiveness of the system esp. its velocity has been essentially improved by a significant modification of the primary data sampling and by the new implementation of feature determination. The first application of this new system concerns age-dependent alterations of the gangliocytes in the nucleus olivaris.


Effect of potential cytostatic and immune modulating chemicals on the plasma membrane of red blood cells (RBC) as revealed by osmotic hemolysis, cell electrophoresis and scanning electron microscopy (SEM).

The influence on red blood cells (RBC) of two cancerostatic-(ZIMET 3106 and ZIMET 3393) and two immunomodulating agents (ZIMET 3164 and ZIMET 86/76) administered subcutaneously, or intraperitoneally in case of the radiolabelled N-mustard compounds, to mice, was studied by means of measurements of the radiolabelled compounds in blood, by cell electrophoresis, filipin-induced hemolysis of pretreated RBC and by scanning electronmicroscopy. The portion of doses applied which binds to RBC-surface decreases in the sequence of ZIMET 3106, ZIMET 3164, ZIMET 3393 and ZIMET 86/76. However, the highest reduction of the electrophoretic mobility and protection from filipin-induced hemolysis of pretreated RBC was found with ZIMET 3164. In both tests ZIMET 86/76 proved to be ineffective. These findings are in good agreement with the modifications demonstrated in pretreated RBC after filipin-induced hemolysis by means of SEM. The results presented point to a N-mustard specific interaction between the cholesterol of the membrane and/or other membrane constituents. However, these fundamental differences found in binding affinity, surface-charges and membrane interactions caused by the chemically similar compounds cannot be attributed merely to the N-mustard group.


Tumors of the rat kidney induced by nitrosourea compounds.

Apart from other lesions, 51 renal neoplasms were induced in rats by administration of methylethy-, dimethyl- and phenylmethylnitrosourea. 3 tumors originated from the renal pelvis and were classified as transitional cell papilloma (1) or transitional cell carcinoma (2). 48 neoplasms were considered as "mesenchymal tumors". These growths were regarded as rat kidney specific tumors. They display a wide spectrum of histological structures: spindle  cells which are capable to differentiate into smooth muscle cells, fibroblasts, angioblasts, fat cells, and even into cartilage thus forming the typical microscopical features which are completed by the tendency of mesenchymal cells to swirl around preexisting renal tubules in several closely investing layers. As the cell of origin is not yet established the term "mesenchymal tumor" seems to be the most suitable one. There is no basis for classifying these tumor as nephroblastomas and the two entities should be strictly separated.


Lung alterations in newborn rabbits after maternal thrombin-shock. II. Lung phospholipids.

Alterations of the lung- and lung lavage fluid-phospholipids (PL's) after a maternal thrombin-shock have been studied in 1 and 5 h old newborn rabbits delivered at days 28 and 30 of gestation. In lung wash the amount of PL increases during the period of gestation and during the first hours of life. In asphyxiated mature animals the PL-content is statistically significantly decreased. The very low PL-content of the lung wash in premature born animals is not affected by asphyxia. The amount of phosphatidyl choline (PC) as a percentage of total PL is unchanged in all animals studied. The PL and PC content in the lung tissue follows the same developmental pattern but the differences are not statistically significant. Changes in the lung weight/body weight (LW/BW)--ratio after asphyxia show a disturbed development of the newborn lung, too.


Hypotonic unmasking of erythrocyte receptor sites.

The study reports on plasmalemmal perturbation of erythrocytes under osmotic stress. In comparison with isotonic human erythrocytes a 10 minutes incubation in 150 mosm sodium cacodylate pH 7.4 at 20 degrees C results in an increase of the anti AH P binding rate by a factor of two. 0.1 M N-acetyl galactosamine inhibits the binding of anti-AH P of both isotonic and hypotonic red cells. Contrary to isotonic mouse erythrocytes the agglutination with peritoneal murine leukocytes of hypotonic red cells is greatly enhanced provided the erythrocytes have been incubated in autologous serum. The findings are considered evidence of the unmasking of binding sites due to nonspecific rearrangement of membrane constituents.


Quantitative stereological studies on the mechanism of immunosuppressive effect of nitrogen mustards of benzimidazole derivatives: the role of polymorphonuclear leukocytes and mononuclear phagocytes.

The effect on antigen uptake and digestion in macrophages and polymorphonuclear leukocytes (PMNL) of 2 compounds of a series of benzimidazole nitrogen mustard derivatives has been investigated by ultrastructural quantitative stereological techniques in order to enlighten some mechanisms of the immunosuppressive effect of especially one of the chemicals. One compound, ZIMET 3393 (Cytostasan), is a powerful cancerostatic with only moderate immunosuppressive side effects while ZIMET 3164 proved an effective immunosuppressant with low cytostatic action. Results of a recent study (FRITSCH and GOTHE 1979) have lent support to the hypothesis that immunosuppression can be induced by an inhibition of antigen processing by macrophages through a membrane-stabilizing effect of the chemicals under investigation. It can be shown in the present study that in the case of ZIMET 3164 an increased competitive antigen phagocytosis and digestion takes place in PMNL. This alternative pathway of antigen processing is suggested to be ineffective with respect to enhancement of immune responses compared with that through macrophages, thus providing an additional possible mechanism of chemical immunosuppression.


Influence of cycloheximide on normal and induced delta-aminolevulinic acid synthetase (aminoketone synthesis) of rat liver in vivo and in vitro.

2 and 5 mg/kg cycloheximide given i.p. 30 minutes prior to the inducer allylisopropylacetamide (AIA) diminished or prevented the enhancement of delta-aminolevulinic acid synthetase (ALAS) activity in newborn rats. In adult rats the small AIA effect 24 hours after pretreatment was enhanced by 2 mg/kg cycloheximide i.p., when the inhibitor was injected 2 hours prior to the inducer. The basic aminoketone synthesis was inhibited by cycloheximide alone. 150-600 microgram/ml cycloheximide had no effect on the aminoketone synthesis of rat liver slices in vitro during 4 hours of incubation. The in vitro induction by 0.6 mg/ml AIA was enhanced by cycloheximide, if the inducer was added 1 hour after preincubation with cycloheximide. It is supposed, that the cytoplasmically localized precursor-ALAS is activated at the beginning of the induction process prior to the initiation of de novo enzyme synthesis, at least in vitro.


Stimulation of kidney function in rats of different ages injured by nephrotoxic agents.

Intensity and duration of nephrotoxic effects can be characterized by measurement of renal p-aminohippurate (PAH) excretion. Single administration of potassium dichromate or glycerol is followed by a marked decrease of renal PAH excretion in dependence on the time after the administration as well as on the dosage used. Both agents are without effect in young rats with an immature tubular transport system for organic anions. As observed previously in rats with intact kidney function, renal PAH excretion can also be stimulated in rats with potassium dichromate or glycerol induced kidney damage. Stimulation of renal PAH excretion is possible in injured rats by repeated administrations of PAH and cyclopenthiazide, respectively. Exactly, the duration of injury is shortened whereas the intensity of the nephrotoxic effect is not changed. However, this effect depends on the age of rats as well as on the nephrotoxic agent administered.


Influence of porcine corpus luteum extract on DNA synthesis and proliferation of cultivated fibroblasts and endothelial cells.

The angiogenic activity in corpus luteum (corpus luteum angiogenesis factor--CLAP) reported first by us in 1977 was enriched by ammonium sulfate precipitation and further purified by ion exchange chromatography. Extracts produced in this way from corpora lutea of cyclus synchronized pigs have proven effective to stimulate DNA synthesis and proliferation of both calf aorta endothelial cells and primary mouse embryo fibroblasts cultivated either under optimal or suboptimal (depletion) conditions. The mitogenic action of these extracts has been found to be dose-dependent and similar to that of bovine brain extract produced according to the preparation method published by GOSPODAROWICZ.


Comparison of protein and DNA synthesis assays of guinea pig spleen lymphocytes after stimulation with influenza virus antigen and phytohemagglutinin.

Two in vitro-methods for demonstration of cell-mediated immune response are compared: Protein and DNA synthesis for detection of in vitro influenza virus antigen- and mitogen-induced lymphocyte stimulation. Guinea pig spleen lymphocytes sensitized with influenza virus antigen were tested in a microadaptation of the lymphocyte transformation test using 14C- or 3H-leucine and 3H-thymidine. As a positive control for T-cell stimulation PHA-induced lymphocyte stimulation was measured. The following results were obtained: 1. Kinetics of the incorporation of 14C-leucine and 3H-thymidine in lymphocytes incubated with optimal and suboptimal PHA-doses respectively are quantitatively similar but different in time. 2. The results of the protein- and DNA-synthesis stimulation assays were correlated against influenza virus antigens, this could not be described by the comparison of cellular and single humoral parameters. 3. The administration of influenza virus antigens in CFA induced a more intensive cell-mediated reaction than injections of antigens in aqueous suspensions, but the results of both methods of CMI were correlated. 4. The optimal CMI under the experimental conditions described is induced by an administration of 30 to 50 microgram virus protein per animal and by a combined intramuscular--intraperitoneal immunization procedure. 5. The measurement of the early stimulation of protein synthesis in the PSS-test is substantially more rapid than for the classical LTT.


Studies on the quantification of local tissue injury following intramuscular injection of aqueous solutions. VIII. The local lesion after application of turimycin in different preparations.

The increase in drug concentration in aqueous solutions is not responded to by a comparable enlargement of volume of necrosis after intramuscular injection. After application of TURIMYCIN the lesion is more voluminous than those caused by penicillin, lower than those following OTESOLUT and nearly equal to those caused by 5% WOFAPYRIN (phenylbutazone + aminophenazone 1:1).


Post mortem changes in adenylate cyclase activity in rat brain striatum.

Adenylate cyclase activity in rat striatum decreased post mortem. Half-lives were about 2.7 h at 22 degrees C, 72 h at 4 degrees C. Differences in stability after death of adenylate cyclase in human brain and rat striatum, and possible heterogenity of the enzyme, are briefly discussed.


Biotransformation of polyprenols by the larvae of Pieris rapae crucivora.

The biotransformation of cleomeprenols-1-3H by the larvae of Pieris rapae crucivora Boisduval has been investigated. It was found that cleomeprenols fed to the larvae are transformed into long chain fatty acid esters that are excreted in the feces.


Triglyceride metabolism in Ephestia cautella pupae exposed to carbon dioxide.

The triglyceride content of Ephestia cautella pupae exposed to increased carbon dioxide atmospheres at low relative humidity was not markedly affected. There was a significant increase in weight loss of pupae exposed to low relative humidity. Results indicate that for E. cautella, metabolic water formation by fat utilization can hardly regulate water exigencies for the pupae and cannot fully compensate for water losses in high carbon dioxide atmospheres.


Ascorbic acid biosynthesis in the mammalian kidney.

The egg-laying mammals (Prototheria) synthesize L-ascorbic acid only in kidney, as is characteristic of reptiles. Bandicoots (Marsupialia) synthesize it in both kidney and liver. 2 other species of marsupials (kangaroos) synthesize it primarily in liver, but some individuals also synthesize in kidney.


A thin-layer chromatographic assay for measuring pineal hydroxyindole-O-methyltransferase activity.

A thin-layer chromatographic procedure for measuring pineal HIOMT activity is described, based on the methylation of NAS to melatonin. The method enables simple and accurate determination in small aliquots from a single pineal organ homogenate.


Serum cholesterol levels in a Nigerian population sample.

Serum cholesterol was determined in 104 healthy Nigerians (57 males and 47 females). The average cholesterol concentration was 187 +/- 72.8 mg/100 ml (mean +/- SD) with a range of 60-480 mg/100 ml. Cholesterol levels were higher in males than in females and increased with age. Distribution of cholesterol level was generally skew to the left.


The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat.

The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH3) and VII (R-COCH3). Hydrolysis of the epoxides produces the male antifertility agents alpha-chlorohydrin (IX, X-Cl) and alpha-bromohydrin (IX, X-Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.


Karyology of the primitive salamanders, family Hynobiidae.

Karyotypes have been studied in 3 species of Hynobius and in 1 species each of the remaining genera of Hynobiids (Ranodon, Batrachuperus, Salamandrella and Onychodactylus). All species have large diploid numbers, between 56 and 66, and asymmetrical and bimodal karyotypes. DNA contents (2C) were found to vary between 33 and 51 pg. Determination was not possible in Onychodactylus where higher values may be suspected. Some of the karyotypes investigated are similar to those of Cryptobranchids. Phylogenetic implications are discussed.


Cytogenetics of South American akodont rodents (Cricetidae). V. Segregation of chromosome No. 1 polymorphism in Akodon molinae.

Akodon molinae is polymorphic with 2n=42, 43, 44, where the metacentric autosome No. 1 is homologous to 2 acrocentrics 1a and 1b. Matings between 2n=43 heterozygotes 1/1a, 1b gave a surplus of 1/1 offspring, a moderate reduction of heterozygous and a strong reduction of homozygous 1a, 1b/1a, 1b offspring. The latter type also has a highly reduced fertility.


Instances of sex inversion in the domesticated swordtail, Xiphophorus helleri Heckel (Pisces, Osteichthyes).

3 protogynous hermaphrodites were found in a domesticated strain of Xiphophorus helleri, confirming much doubted observations by older authors. It therefore seems that sex determination may vary between strains, certain strains being strictly gonochoristic but others being capable of true hermaphroditism.


A genetic study of intergradation between Mytilus edulis and Mytilus galloprovincialis.

A study of geographic variation at 2 diagnostic allozyme loci in the mussels Mytilus edultis and M. galloprovincialis reveals considerable spatial variation, both in allele frequencies and in the extent of intergradation.


Role of oxygen radicals scavenging enzymes in the protoporphyrin induced photohemolysis.

Inhibition of superoxide dismutase by diethyldithiocarbamate or cyanide increases the rate of red blood cells lysis after irradiation in the presence of protoporphyrin IX. Catalase activity, which is decreased during the photohemolytic process, appears to be not essential for the lytic event. No relationship between catalase activity and hemolysis rate was found. Superoxide dismutase appears to prevent only in part catalase inactivation by singlet oxygen.


Inhibitory effect of beta-ecdysone on protein synthesis by blowfly fat body in vitro.

Synthesis of blow fly calliphorin and other blood proteins by larval fat body in organ culture is inhibited by beta-ecdysone. The findings suggest a novel function for the hormone.


The sterols of the khapra beetle, Trogoderma granarium Everts.

The khapra beetle, Trogoderma granarium Everts, does not dealkylate and convert dietary C28- or C29-Phytosterols to C27-sterols such as cholesterol. There is, however, an increase in the concentration of cholesterol and campesterol in its tissues relative to the dietary concentrations of these sterols, presumably as a result of selective uptake.


External nares and olfactory perception.

Lower vertebrates have more widely separated external nares than higher forms and are thus better adapted to utilize olfactory tropotaxis, or stereolfaction, than higher vertebrates which, on account of their flexible necks, must utilize klinotaxis. Snakes and tubenosed bats break the rule on account of their specialized life styles.


Mitosis in the haemocytes of Sarcophaga ruficornis (Diptera).

Among the haemocytes of Sarcophaga ruficornis, only the prohaemocytes divide. Injection of phytohaemagglutinin-P induces 100% prohaemocytes to undergo mitosis but does not induce mitosis in other cells. Mitotic stages other than the prophase are apparently very short lived.


4,5,6,7-Tetrahydro-7-oxobenzo[b]thien-4-ylurea; Sulbenox1, a novel animal growth stimulant.

The title compound, a metabolite of 4,5,6,7-tetrahydrobenzo[b]thien-4-ylurea, was synthesized and found to be an effective growth promoter in sheep, mice, and rats. In sheep it gave over a 6-week growth period at 15 and 60 ppm in the diet an economically and statistically significant growth response.


On the significance of the rostral process of bipolar neurosecretory cells in the caudal neurosecretory system of certain catfishes.

Neurosecretory substance has been identified in the rostral process of bipolar neurosecretory cells of the caudal neurosecretory system in 4 Indian catfishes, using acid violet stain. The role of the rostral process in the transmission of the neurosecretory substance is discussed.


The effects of legume seed extracts on plant virus infection.

Extracts from the seeds of 15 species of legume inhibited the infection of plants by viruses. Extracts could be divided into those with marked inhibitory activity reducible on heating and those with less marked inhibitory activity which increased on heating. Evidence is given is given to suggest that seed extracts contain both virus inhibitors and augmenters and that the inhibitors are high molecular weight proteins possibly related to lectins.


Base pairing in messenger RNA's for small peptides.

Longest runs of Watson-Crick pairing in hypothetical m-RNA's for a number of natural peptides were no greater than those in the hypothetical m-RNA's for a large number of randomized amino acid sequences from these peptides. This shown that even if base-pairing in m-RNA were a biological requirement, it would little constrain the amino acid sequence.


Lemming cycles in captivity.

2 freely growing confined populations of Norwegian lemmings displayed population peaks and declines which were similar to natural populations. In most other studies of confined populations of rodents, the number of animals stabilized and maintained fairly constant numbers. Juvenile mortality and reduced pregnancy rate contributed to the decline.


Potassium uptake by cold-resistant mouse L cells stored at low temperature.

Adaptation of a cultured mouse L cell population to 4 degrees C increased the survival of the cells and induced the uptake of potassium from the medium at this temperature.


The effect of lidocaine on the secretion induced by cholera toxin in the cat small intestine.

The intraluminal administration of lidocaine, a local anaesthetic agent, inhibits the net loss of fluid into the intestinal lumen produced by cholera toxin in the cat. It is suggested that the activation of a nervous reflex is involved in the pathogenesis of cholera.


The excretion of urea by the larvae of Spodoptera mauritia Boisd. (Noctuidae: Lepidoptera) during development.

The concentration of urea in the excreta of the 6th instar larvae of Spodoptera mauritia varies from 4.017 +/- 0.541 to 31.052 +/- 1.193 mumoles/g dry excreta (mean +/- SE). The observation confirms that urea excreted is of metabolic origin.


Haloperidol produces hypothermic effects in rats.

Intraperitoneal administration of either haloperidol or chlorpromazine produced hypothermia both in the cold (8 degrees C) and at room temperature (22 degrees C). The hypothermia was brought about both by a decrease in metabolic heat production and an increase in the cutaneous temperature of tail and foot skin. However, at a higher temperature (29 degrees C), there were no changes in rectal temperature and other thermoregulatory responses.


Ca2+-binding to erythrocyte membrane of hypertensive men and rats: effects of acetylcholine and eserine.

Both acetylcholine and eserine affect Ca2+-binding to mammalian erythrocyte membranes. Differences in Ca2+-binding between normotensive and hypertensive groups (human as well as rats) was found under eserine influence.


Effect of theophylline and triiodothyronine on some early estrogenic responses in the rat uterus.

Theophylline increases and triodothyronine decreases uterine edema induced by physiological doses of estradiol-17 beta. Both of them decrease estrogen-induced uterine eosinophilia and the number of blood eosinophils, suggesting an explanation for the results in the uterus.


The pharmacological relevance of vital staining with neutral red.

The uptake of neutral red into the renin-containing juxtaglomerular granules does not inhibit the release of renin either in basal or in stimulated states of renin secretion. The vasodilating effect of neutral red may be due to a nonspecific binding to noradrenaline-receptors in the vascular smooth muscle cells.


Skeletal muscle capillary densities during reactive hyperemia.

Reactive hyperemia was induced in hindlimbs of rats by occlusion of the femoral artery. Using fluorescein dye as a peripheral vascular marker, we observed that there was an increase in the number of flowing capillaries supplying the muscle fibres following release of the occlusion. The results indicate that the number of flowing capillaries is not dependent on the duration of occlusion (2-10 min).


Eyelid closure causes myopia in humans.

Humans with unilateral ptosis are more myopic in the closed eye than in the normal eye. The effect seems unrelated to visual loss. In pairs of humans ranked for sleep and myopia, the more myopic tends to sleep the more. We conclude that eyelid closure causes myopia.


Features of intracellular calcium distribution in the adipose tissue of spontaneously hypertensive rats (SHR).

The in vitro study of the kinetics of 45Ca efflux from adipose tissue of rats reveals 3 pools of exchangeable calcium. Calcium content in the intracellular pools of adipose tissue of spontaneously hypertensive rats is increased as compared to that in normotensive controls.


Plasma branched-chain amino acids in cold- and heat-acclimatised rats.

The concentrations of plasma branched-chain amino acids, valine, isoleucine and leucine, were significantly elevated in cold-acclimatised rats, while these values were significantly reduced in heat-acclimatised rats, in both 2-week and 4-week temperature acclimatisation.


Effect of para-methoxyphenylethylamine on chronic stress-induced hypertension in the rat.

This report presents data showing that par-methoxyphenylethylamine is effective in both preventing and reversing chronic stress-induced hypertension in the rat.


Effect of reserpine on the larval-pupal moult of the wax moth Galleria mellonella L. (Lepidoptera).

Significant retardation of G. mellonella development was induced by reserpine injected to the last instar larvae in doses having a long-lasting effect on the neurosecretory system.


Atypical mast cell degranulation and focal hydropic degeneration of venular endothelium in diffuse fibrosing alveolitis.

Atypical scroll-like and tubular degranulation of mast cells closely associated with focal endothelial hydropic degeneration is reported in human lung from 4 patients with diffuse fibrosing alveolitis in which the predominant abnormality was hyperplasia and desquamation of type 2 pneumocytes.


DPH-induced macrocytosis in the 14-day rat foetus.

Phenytoin injected in the pregnant rat induces in the 14-day-old foetus macrocytosis of the primitive red blood cells which is sometimes linked with limb haemorrhages. The action of the drug is possibly the result of a blood circulation disturbance.


Inhibitory effect of atropine on the isoprenaline-induced increase in vasopressin plasma concentration in rats.

The isoprenaline-induced increase in plasma levels of vasopressin in conscious rats was reduced by intravenous and intracerebroventricular applications of atropine. It is concluded that central neurons with muscarinic receptors contribute to the isoprenaline-induced vasopressin release.


A study of vasoactive intestinal polypeptide (VIP) stimulated intestinal fluid secretion in rat and its inhibition by indomethacin.

4 groups of rats were studied under anaesthesia to assess the effect of VIP and the influence of the prostaglandin synthetase inhibitor indomethacin in isolated bowel loops. VIP produced a highly significant increase in the luminal fluid content and this was completely inhibited by addition of indomethacin.


A quantitative study of the catecholamine-fluorescence in the ganglion paracervicale uteri of the rat.

In the ganglion paracervicale uteri of the rat, there are principle neurons which are able to take up offered catecholamines. Normally there is an inverse relationship between their size and their mean catecholamine-fluorescence. A comparison with the catecholamine-fluorescence of depleted and repleted adrenergic perikarya in the ganglion cervicale superius is made.


Lymph node metastases of EMT6 tumour in nude mice.

Metastatic axillary lymph nodes following the injection of EMT6 tumour cells were observed in athymic nude mice, more often in female animals, and had a rapid growth rate. These metastases did not develop in syngeneic hosts. The latency of their appearance was inversely related to the number of injected cells.


Inhibition by tryptophan of nucleolar RNA synthesis in salivary gland nuclei of Chironomus thummi.

Tryptophan, but not glutamine and lysine, inhibits the incorporation of 3H-uridine into nucleoli of explanted salivary glands by about 60%. In isolated nuclei also, the nucleolar incorporation of 3H-uridine triphosphate is reduced to about 50% by tryptophan. It is concluded that tryptophan acts directly at the nuclear level and the possible mechanisms.


Microperoxisomes in steroidogenic cells of the rat ovary: interstitial, thecal and luteal cells.

Microperoxisomes are present in luteal, interstitial and thecal cells. They are in close relation with smooth endoplasmic reticulum and lipids. Their probable role in steroid biosynthesis is discussed.


Effects of low temperatures on survival of frozen-thawed mouse embryos.

Almost no damage to mouse morulae was observed between 0 and -40 degrees C, and freezing damage to embryos in DMSO, glycerol or ethylene glycol occurred after exposure to -60, -50 or -50 degrees C, respectively. Cooling embryos in DMSO or glycerol to temperatures below -50 to -60 degrees C increased freezing damage. To the contrary, in the presence of ethylene glycol, no more damage occurred after exposure to temperatures below -50 degrees C.


Cyclosporins: immunosuppressive agents with antitumor activity.

Initial screening of the 2 recently developed immunosuppressive agents, cyclosporin A and cyclosporin C, in 11 murine transplantable neoplasms revealed significant increase of lifespan with long-term survivors after i.p. injection to the ascites tumors, Taper liver, Sarcoma 180J and Ehrlich.


The effects of decreased glucose concentrations on the in vitro development of the post-blastocyst mouse embryo in a fetal calf serum- or bovine serum albumin-supplemented medium.

Decreasing the glucose concentration from 1.0 mg/ml to 0.25 mg/ml has no detrimental effects on post-blastocyst embryo development when either dialyzed fetal calf serum serum (20%) or bovine serum albumin (4.0 mg/ml) is used to supplement Eagle's Basal Medium (BME). Development is reduced in both serum- and BSA-supplemented BME devoid of glucose in comparison to glucose controls. Serum-supplemented media support better overall development than BSA-supplemented media.


Effect of human seminal plasma on tumour-associated immunity in prostatic cancer. A preliminary report.

Evidence of significant suppression of tumour-associated immunity in patients with prostatic cancer by human seminal plasma (HuSPl) has been observed. Collation of the immunosuppressive property of HuSPl in this and previous studies, together with recent studies demonstrating experimental induction of prostatic cancer by spermatozoa and the relationship of prostatic cancer to sexual activity are suggestive of an etiologic role for SPl in prostatic cancer.


Release of gastrointestinal hormones following an oral water load.

The ingestion of 2 different water loads (7.5 and 15 ml/kg) by healthy subjects stimulated the release of plasma motilin, gastrin, pancreatic polypeptide and VIP. Atropine was found to block the release of PP but not the other hormones.


Seasonal variations in vasopressin secretion in rats.

Plasma vasopressin concentrations and vasopressin content in neurohypophysis in rats show seasonal variations; namely, high in summer and low in winter.


Calcitonin: effect on protein synthesis in different rat tissues.

Protein synthesis was inhibited in the pancreas whereas it was enhanced in the kidney and intestine (jejunum-ileum) after a single injection of porcine calcitonin (20 MRC units/kg b.wt). The incorporation of [3H]leucine into total protein in the brain, heart, liver and stomach did not change after the hormone treatment.


Variations of the labelling index in vitro of rat mammary gland in pregnancy and early lactation.

The labelling index of rat mammary gland during oestrus, pregnancy and early lactation was studied in vitro. The implications concerning the existence of a critical cell division are discussed.


Photoperiodic effects in the Djungarian hamster: one minute of light during darktime mimics influence of long photoperiods on testicular recrudescence, body weight and pelage colour.

In male Djungarian hamsters (Phodopus sungorus) short photoperiods (L/D 8/16) with additional 1- or 5-min light-pulses 8 h after light-off were as effective as long photoperiods (L/D 16/8) in stimulating testicular recrudescence, increase in body weight and moult into summer pelage. The results are discussed with regard to the hypothesis that the pattern of melatonin release from the pineal gland is important in mediating photoperiodic effects in mammals.


Endocrine control of lysosomal alterations in rat liver during the perinatal period.

Within hours of birth, some physical properties of liver lysosomes are modified. These alterations, which may be related to the autophagic vacuoles formation known to occur during this period, were inhibited by insulin administration. Glucagon, a potent inducer of autophagy in adult rat liver, did not anticipate this process in fetal liver. Our results suggest that the decrease of plasma insulin immediately after birth is an important factor in the development of hepatic autophagy.


Acupuncture points and cutaneous nerves.

In view of the number of workers who have confirmed the presence of cutaneous nerves beneath acupuncture points, a plea is made not to dismiss them too lightly or hastily at this point in the search for the mechanisms of acupuncture.


Hemopoietic stem growth on a capillary stage.

A hollow fibre capillary stage was used for the maintenance and renewal of hemopoietic stem cells in extra corporeal conditions. The partial success of this technique is due to the preservation of cell-cell contacts and interactions within the tissue sections.


New aporphine alkaloids of Ocotea minarum.

Fourteen aporphine alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea minarum Nees (Mez). The known alkaloids were identified through their physico-chemical properties as: leucoxylonine (VII), dicentrine (IV), ocoteine (V), leucoxine (VI), ocopodine (VIII), predicentrine (IX), dicentrinone (XIV) and thalicminine (XV). Six new aporphine alkaloids were also isolated: ocotominarine (I), ocominarine (III), nor-leucoxylonine (XI), iso-oconovine (xii), 4-hydroxydicentrine (XIII) and ocominarone (XVI). Their structures were determined using spectroscopic methods and chemical correlations.


[Clathrates of unsaturated hydroxamic acids with antifungal acitivity].

Urea complexes of 10-undecen-hydroxamic acid (III) and trans-2-dodecen-hydroxamic acid (IV) were prepared with the aim of testing antifungal activity. No significant difference of activity between the complexes and corresponding hydroxamic acids was demonstrated.


[Cardiovascular effect of 1,2,4-benzothiadiazine-1,1-dioxide derivatives. VIII].

A series of carboxy- and carbomethoxyalkyl derivatives of 3-amino-1,2,4-benzothiaidazin-1,1-dioxide either substituted or unsubstituted in the benzene ring [compounds (I leads to XVIII)] was prepared and tested for cardiovascular activity. It was found that the introduction of a carboxy-or carbalkoxy-group in the omega position of 3-alkylamino derivatives of 1,2,4-benzothiadiazine-1,1-dioxide usually causes marked decrease or abolition of the cardiovascular activity shown by the parent compounds. The negative effect on the pressor trace (hypotension and increase in differential pressure) is more frequent and significant than that on bradycardial activity.


4-Demethoxy-4-alkoxydaunorubicins.

The synthesis and the antitumor activities of a group of 4-demethoxy-4-alkoxydaunorubicins (VIII) are reported. The new compounds were found to have an activity equal or superior to that of daunorubicin, at somewhat higher doses.


[Theophylline 7-substitutes. III. Arylderivatives].

Some 7-aryltheophyllines were prepared and pharmacologically screened. They showed low toxicity, sedative properties and, in some cases, anticonvulsant activity.


[Condensation of 3-phenyl-5-aminopyrazolo with acylpyruvic and ethoxymethylenacetic esters].

The synthesis of ethyl 2-phenyl-7-alkyl (or 7-phenyl)pyrazolo[1,5-a]pyrimidine-5-carboxylate and ethyl 2-phenyl-7-alkyl (or 7-phenyl)pyrazolo[1.5-a]pyrimidine-6-carboxylate are reported. Decarboxylation of the acids, obtained by hydrolysis of the above esters, yields the same compounds. N.M.R. data on the reduction products of the ethyl 6-carboxylate confirm all the assigned structures.


Doxorubicin 14-ethers.

The synthesis and the antitumor activities of a group of doxorubicin (adriamycin) 14-ethers are reported. The new compounds were found to have an activity similar to that of daunorubicin, at somewhat higher doses, but inferior to that of doxorubicin.


[Research on agents with antineoplastic activity. LXIII. Anthramycin and analogous compounds. X. Synthesis of 11-phenyl-5H-pyrrolo[2,1-c] [1,4] benzodiazepine derivatives].

Reaction between arolychlorides and 1-(2-aminobenzyl)-2-cyanopyrrole afforded the corresponding aroylamides, which were transformed by intramolecular cyclization into 11-aryl-3-cyano-5H-pyrrolo[2,1-c] [1,4] benzodiazepines. Hydrolysis of cyanoderivatives furnished the corresponding amides or acids depending on the reaction conditions. Decarboxylation and reduction of some derivatives to afford 11-aryl-5H-pyrrolo[2,1-c] [1,4] benzodiazepines and 11-aryl-3-cyano-10,11-dihydro-5H-pyrrolo[2,1-c] [1,4] benzodiazepines are described.


Quantitating ruminal turnover.

Basic principles of in vivo kinetics are reviewed as they apply to the digestive process in ruminants. Emphasis is on application and limitations of techniques for measuring ruminal turnover of undigested feed residues. This turnover can best be measured by using feed particles whose organic constituent(s) contain uniform concentrations of an isotope. Alternatively, rare earths remain attached to feed residues throughout the digestive tract and can also be used. Appropriate application of mathematical methods must consider ingestaflow as a multicompartment process.


Influence of ruminal turnover on site and extent of digestion.

Ruminal turnover rate plays a major role in ruminant nutrition. Theoretical considerations have been developed and several excellent models are available. Newer methods in marker technology offer opportunity for collection of accurate data. Few good studies have been published. This paper covers the above considerations and gives a critical evaluation of some published data. Increased ruminal turnover of liquid alters ruminal fermentation toward more acetate, butyrate and methane and less propionate. It also results in a greater rate of passage of small feed particles of any type. The effect on total digestion depends on feed composition and physical form. Total fiber digestion is usually reduced. Ruminal liquid turnover is increased by increased level of intake, addition of coarse fiber to rations, and osmotically active agents. It is reduced by some mineral complexes and monensin, and by reducing average particle size. Solid turnover rate is increased by reduced particle size and by several factors that influence liquid turnover. The rate of particle size reduction to a critical size is important in any description of solid turnover rate. Literature data that relate to ruminal turnover and in vivo digestion are discussed.


Intracellular ion activities in Necturus proximal tubule.

Ion-sensitive microelectrodes were used to measure the intracellular activities of Na, K, and Cl in proximal tubules of the perfused Necturus kidney. Cell Cl was 2-3 times higher than the value predicted for passive distribution during perfusion with normal Ringer; intracellular Na was far below the level for passive distribution. Cell Na and Cl fell to very low values when the lumen was NaCl-free. Cl entry into the tubule cell from the lumen required luminal Na. Na entered the cell across the luminal membrane both by diffusion and by coupled movement with Cl.


Electrochemical potentials in frog skin: inferences for electrical and mechanistic models.

To evaluate possible mechanisms of transport at apical and basolateral barriers of Na transporting cells of epithelia, it is necessary to know the difference of electrochemical potentials at each barrier. A reevaluation in light of new data of intracellular voltages of frog skin leads to fundamental questions concerning the origin of the voltages at both inner and outer barriers of this tissue. Whereas the inner barrier is highly selective for K, confirming the observations of Koefoed-Johnsen and Ussing, the voltage across the inner barrier, Vi, especially in the absence of transepithelial Na transport, may be greater than the Nernst equilibrium potential for K estimated from the maximum values of intracellular [K] reported in the literature. Consequently, it is proposed that the Na:K pumps may, under some conditions, behave not only as a Na:K exchange pump but also as a cation extrusion pump for K especially when intracellular [Na] falls to low levels. In order to explain the relationship between Na entry and the voltage at the outer barrier, it is proposed that the conductance of the outer barrier is voltage dependent, in line with previous observations of the nonlinear electrical behavior of the apical barrier of Na transporting cells. Thus, the outer barrier may behave as a simple voltage independent resistor with a Thévenin electromotive force of zero at negative intracellular voltages despite the existence of a chemical potential for Na at this barrier.


Inhibitors of renin and their utility in physiologic studies.

The enzyme renin is the initiator of a series of steps that ultimately leads to the generation of angiotensin II, a potent pressor peptide that also has both a direct and indirect role in renal sodium conservation. Renin's action on its protein substrate, angiotensinogen, is inhibited by specific antibody, a peptide produced by actinomyces, pepstatin and its derivatives, and by peptide analogs of a segment of the endogenous substrate. These inhibitors vary considerably in specificity, inhibitory constant, and utility for in vivo studies.


Surgical treatment of endometriosis in the infertile female: a modified approach.

Two groups of infertile women underwent conservative surgery for endometriosis, group I (107 patients) prior to 1970 and group II (138 patients) after 1970. To determine whether modifications to the surgical approach after 1970 further increased the likelihood of conception, postoperative pregnancy rates were examined. The data suggest that postoperative pregnancy rates can be improved by (1) removal rather than "repair" of diseased adnexa if the involvement is unilateral and (2) leaving diseased areas undisturbed where excision or cauterization may predispose to the development of postoperative ovarian and/or tubal adhesions. The current surgical technique (used for group II) is described in detail.


Relationship of weight to successful induction of ovulation with clomiphene citrate.

Over a 6 1/2-year period, 117 patients who were anovulatory, euthyroid, and estrogen-primed were treated with clomiphene citrate. Graduated doses from 50 mg to 250 mg daily for 5 days were used to induce ovulation. Of 62 patients who completed treatment, 50 ovulated and 12 did not. Several factors, including age, duration of infertility, weight, previous menstrual history, previous pregnancy history, and previous use of oral contraceptives, were investigated to determine conditions which might influence response. Only weight was found to be significantly different between responders and nonresponders. Furthermore, there was a linear relationship between body weight and dose of clomiphene required to induce ovulation. The ovulation rate for those completing therapy was 81% with a pregnancy rate of 76% of the total and 94% of those ovulating. Population homogeneity with anovulation as the major cause of infertility appears to be the most plausible explanation for the high pregnancy rate.


Ovarian implantation into the uterus (Estes operation): clinical and experimental evaluation.

Ovairan implantation into the uterus was performed in 27 women, none of whom conceived during the 4- to 6-year follow-up period. Bypassing the fallopian tube may, in itself, explain the disappointing results of this procedure in our series as well as in those reported in the literature. Experimental ovarian implantation into the uterus of rats supplied information regarding additional factors underlying the low success rate of this operation. It is concluded that this surgical intervention has been made superfluous in view of the poor results and the modern methods for extracorporal fertilization at present being developed.


Sperm penetration in vitro: correlations between parameters of sperm quality and the penetration capactiy.

A nonlinear regression analysis was used in order to fit a logistic model to 200 runs of human ejaculated spermatozoa penetrating cervical mucus of good quality. The data revealed excellent correlation between the number of sperm penetrating (sigma penetration, SP) and the motility (r = 0.776) and vitality (r = 0.534) of the spermatozoa. The percentage of abnormal spermatozoa found in the ejaculate was negatively correlated (r = -0.649), while sperm concentration showed a poor correlation with SP (r = 0.327). Furthermore, concentration was shown to have no effect in samples containing over 5 million sperm/ml. The conclusion of this study is that the two major parameters of sperm quality determining the capacity of spermatozoa to penetrate cervical mucus are motility and the presence of normal forms of spermatozoa.


Seminal plasma concentration of glycerylphosphorylcholine before and after vasectomy and vas reanastomosis.

The concentration of glycerylphosphorylcholine (GPC) was determined in semen obtained from normal fertile, vasectomized, and vas-reanastomosed subjects. Concentrations of GPC were markedly lower in the semen of vasectomized men. GPC levels observed in vas-reanastomosed subjects were similar to those found in normal fertile men. Vasectomy may not affect GPC synthesis significantly.


Egg transport in the rabbit oviduct following ampullary resection and microsurgical end-to-end anastomosis.

Surgical alteration of rabbit oviducts was employed to investigate the mechanisms of ovum transport. Resection of a 5- to 10-mm segment of midampulla was followed by microsurgical end-to-end anastomosis. One to two months later, direct observations were made, in situ, of ampullary egg transport. Stained cumulus masses were transported normally to the site of anastomosis: two-thirds of those studied were delayed at that point for an average of 2 1/2 minutes. Normal transport then resumed and continued to the ampullo-isthmic junction. In all but one instance, blockage of muscular activity with isoproterenol prevented transport beyond the anastomosis site, demonstrating the presence of an obstacle to ciliary transport. These studies reveal an important facilitative role for muscle in improving the reliability of ampullary egg transport. Considering species differences in egg transport mechanisms, it is suggested that ampullary-ampullary anastomosis in women might have a poor prognosis for re-establishing fertility.


Eelectron microscopic examination of the rabbit oviductal ampulla following microsurgical end-to-end anastomosis.

The endosalpinx of both normal and microsurgically reconstructed ampullae in rabbit oviducts was examined by scanning and transmission electron microscopy following ovum transport studies. Tall, longitudinal mucusal folds ran continuously throughout the lumina of normal ampullae and were clearly interrupted at the incision site in the reconstructed oviducts. In both normal and surgically repaired tubes the endosalpinx was covered with long, slender cilia and bulbous processes of secretory cells with microvillous surfaces. Intracellular examination of these epithelial cells suggested no abnormal structure or function. These observations indicate that the epithelium on the severed ends of the endosalpinx healed completely within 1 month following ampullary anastomosis. Since no luminal obstruction was observed, the interruption and misalignment of the mucosal folds appear to be the cause of the impaired ciliary transport of cumulus masses observed in these oviducts. When species differences in tubal structure and function are considered, it appears likely that ampullary-ampullary anastomosis could hinder egg transport and fertility in women.


Evidence for a human chorionic gonadotropin-like material in the rabbit blastocyst.

Extracts from (1) 300 day 6 rabbit blastocysts, (2) 300 day 2 unfertilized ova, and (3) uteri from the nonpregnant does were analyzed in the following assays in order to determine the presence of a chorionic gonadotropin: (1) in vitro bioassay for testosterone production by decapsulated rat testes, (2) in vitro bioassay for progesterone production by porcine granulosa cells, (3) in vitro determination of adenylyl cyclase-stimulating activity in rabbit Graafian follicles, (4) gel filtration in a Sephadex G-150 column and assay of the elutions in a radioimmunoassay (RIA) specific for the beta-subunit of human chorionic gonadotropin (hCG), (5) parallelism with hCG standard preparations in beta-hCG RIA, and (6) concanavalin A-column chromatography. The rabbit blastocyst extracts showed an hCG-like material in all of the systems tested. None of the other two extracts presented hCG-like activity in any of the assay. The immunoreactive material in the beta-hCG RIA of the blastocyst extracts after gel filtration presented a profile different from that of pure hCG; this may represent heterogeneity due to a species difference or a slightly different molecular weight. These results confirmed previous findings of several investigators and those from our laboratory in that the preimplanted rabbit embryo contains a gonadotropin with characteristics similar to hCG.


[Analysis of species specific acoustic signals in the mesencephalic, diencephalic, and neostriatal structures of the brain].

In chronic experiments, the neuronal activity in structures of the auditory analyzer was studied during perception of species-specific signals in the chicken. The majority of the neostriatum cells responded to territorial vocalizations of the rooster and to squeaking of the chicken; in the midbrain structures the maximal responses occurred to signals of distress and alarm. The greatest number of cells responded most obviously to the cardinal component of the chicken vocalization spectrum.


[Impulse synchronization in the mechanisms of adaptive plasticity of neuronal populations of the posterior hypothalamus].

An increase in the firing rate induced minimization of the reward (a weak electrical skin stimulation) and altered the neuronal activity patterns in the posterior hypothalamus. The estimation of the expected random coincidence functions between the two neuronal activity trains belonging to adjacent cells showed the synchronization both in high- and low-frequency ranges. In the process of adaptive alterations of the neuronal activity, fluctuations of the expected randon coincidence coefficients occurred.


[Adaptive modification of neurophysiologic and vegetative processes during positive food and negative taste autoreinforcement].

A certain rhythm in brain activity of the cat was reinforced with milk in one series of feedback experiments, and with KCl solution--in another series. The 1st series feedback augmented the rhythm, particularly in the 12--15 Hz range, in the sensory--motor area. Obvious minimization of the rhyth m occurred in the 2nd series within the range of 4--7 Hz only, and negative reinforcement of the 12--15 Hz rhythm in these series induced neurosis. The vegetative activity estimated by the cardio--interval dynamics, was regarded as the correlate of emotional tension induced by biologically significant effect.


[Influence of the brain stem reticular formation on seizure activity in the cerebral cortex].

Activation of the mesencephalic RF facilitates triggering of paroxysmal potentials and augments existing epileptic activity. Stimulation of nucleus reticularis pontis caudalis inhibits triggering of epileptic discharges. The microelectrode studies corroborated these data. The desynchronization elicited by the mesencephalic RF seems to be mostly activating, whereas desynchronization elicited by the nucleus reticularis pontis caudalis--mostly inhibitory.


[Slow potentials of the receptive field of the ciliary body and their relationship to regulation of intraocular pressure].

Spontaneous slow potentials with amplitude ranging from 25 mcV to 1.3 mV and wave duration from 600 to 6000 msec was recorded in the receptive area of the ciliary body. The same potentials persisted even 15--20 min after the death of animal in the enucleative eye as well as in the isolated preparation of the ciliary body with sclera. The rise of the intraocular pressure up to 30--35 mm Hg augments the potentials whereas further rise up to 45 mm Hg and more suppresses them. Electrostimulation acts in a similar way: square pulses of 25 mcV augment the potentials' amplitude whereas the 250 mcV pulses reduce it.


[Changes in the spike activity of vagus nerves following stimulation of the anticlotting system].

In rabbits, changes of electrical activity of the n. vagus liver branches were studied during i. v. administration of thrombin and perfusion of the isolated carotid sinus, during the reflex response of the anticoagulating blood system. The efferent vagus activity raised to the maximal level within 3--10 min after i. v. administration or after perfusion, coinciding in time with the maximal effect of the hypocoagulation. The augmentation of the activity depended on amount of thrombin. The similarity of effects of the perfusion and i. v. thrombin suggests the same efferents for the reflex response of the anticoagulating blood system passing through the vagus.


[Effect of cerebral blood supply disorders on certain aspects of metabolism].

Bilateral ligation of common carotid arteries sharply decreases volume blood flow and oxygen consumption in the cortex, in diencephalon and midbrain whereas inducing no changes in the cerebellum and medulla oblongata. The same is true for intensity of metabolism of both total and separate fractions of phospholipids. This suggests that the changes of phospholipid metabolism in neural tissue depend on the degree of its blood supply disturbance and duration of the ischemia.


[Effect of hypoxia on the contractile activity of smooth muscle cells of the thoracic lymphatic duct].

Hypoxia (95% N2; 5% CO2) led to complete or partial inhibition of spontaneous contractile activity of isolated segment of the rat thoracic lymphatic duct, PO2 of perfused solution being 5--10 mm Hg. Reoxygenation restored rhythmical although more frequent contractions of the smooth muscle cells. Excitability of cells membrane tested with KCl, BaCl2, and noradrenaline during hypoxic period proved lower during this decreased PO2. Preliminary depolarization with KCl, BaCl2, and noradrenaline of cells membrane delayed the inhibition of contractile activity during hypoxia. Compared with the portal vein, lymphatic duct revealed a greater resistance to hypoxia. The hypoxia seems to affect first the smooth muscle cell membrane which leads to modification of the contraction character.


[Concentration and rate of depletion of glycogen in fast and slow rat muscles].

Glycogen content of the fast m. tibialis anterior at rest is higher than in the slow m. soleus: 0.650 +/- 0.030 and 0.540 +/- 0.029 g/100 muscle wet weight, resp. A considerable glycogen breakdown occurs in both muscles in alternative regimen of 5-sec tetanic contraction and 5-sec rest. The rate of depletion is maximal during the first 10-min contraction, then it slows down abruptly to an approximately constant level during the further 30-min contaction. Linear correlation exists between the rate of glycogen depletion and glycogen content at rest, the correlation being especially high in the m. tibialis anterior. The rate of correlation increases with prolongation of stimulation in both muscles. The degree of glycogen depletion and the depletion rate are higher in the m. tibialis anterior than in the m. soleus. The relation is independent of glycogen content in the muscles at rest.


[Role of changes in the body's heat content during the development of thermoregulatory responses].

Summation of temperature signals from different body parts was shown to occur in the temperature homeostasis maintenance, as revealed by the value delta to average . m . c, where delta to average--increment of the body average temperature, m--body mass, c--body specific heat. Raise of the rabbit heat condition by 245.9 +/- 35.8 cal/kg at ambient temperature 19-21 degrees C induces ear vasodilatation which is the thermoregulatory response aimed at the heat loss. Dropy of the rabbit heat condition by 266.9 +/- 21.5 cal/kg at ambient temperature 28-30 degrees C induces ear vasoconstriction. The heat condition seems to the object of regulation in the organism thermoregulation system.


[Nonspecific sensory and endocrine thermoregulatory mechanisms during acute cooling of the body].

Involvement of the midbrain RF into the thermoregulatory response follows excitation of anterior and posterior hypothalamic thermoregulatory centers and afferentation from thermoreceptors and other sensitive structures mainly during the "transitory" stages of the cooling process in cats and albino rats. Endocrinal shifts (hypothalamo-hypophyseal-adrenal, thyroid, and enterochromaffine systems) typical for stress response in 3-hr cooling, developed, strictly parallel to changes of thermoregulatory parameters; no such parallelism occurred in prolonged cooling (up to 30 days). Selective suppression of the endocrinal stress response to acute cooling by means of blocking the transport of hypothalamic neurosecret entailed diminishing of the adaptive thermoregulatory shifts. The unspecific sensory-endocrinal (stress) mechanism of thermoregulation seems to be adequate to acute cooling when specific responses of acclimation to prolonged cooling cannot be actualized.


[Changes in the efficiency coefficient of the heart and diaphragm during cold adaptation].

The heart and diaphragm efficiency seems to be an actively regulated variable. It alters in prolonged adaptation (raises in adaptation to hypoxia; diminishes in cold adaptation which means an increase in heat production per unit of muscle's contractile activity). Enhancement of noradrenaline calorigenic effect on skeletal muscles during cold adaptation is corroborated in an isolated diaphragm. Diminishing of the heart and diaphragm efficiency in thyrotoxicosis suggests participation of thyroid hormones in formation of adaptive decrease of muscular contraction efficiency in cold adaptation. The heart efficiency raises in hypothermia and, probably, in limitation of the myocardium oxygen supply. Possible mechanisms of changes of muscular contraction efficiency are discussed.


[Analysis of reflex thermoregulatory reactions induced by thermal stimulation of the trigeminal zone].

In anesthetized rabbits, the activity of thermoreceptors, the neuronal activity in the preoptic area of hypothalamus (POAH), and the efferent outflow in sympathetic fibres of the auricular nerve were studied during thermal stimulation of the skin innervated by the trigeminal nerve. Among 79 receptors 8 responded to warming of the skin and 38 responded to cooling with the maximal activity at the skin temperature 22-21 degrees C. The activity of 46 POAH neurons out of 94 correlated with the skin temperature: 34 neurons increased the frequency of firing during cooling and 12 during warming. The firing rate in the sympathetic ganglion cells and postganglionic fibers increased by 50-100% during cooling causing vasoconstriction of the rabbit's ear, while warming of the receptive zone reduced the activity by 56-48% or abolished it, leading to vasodilatation.


[Certain quantitative patterns in the control of cutaneous blood flow during thermoregulatory reactions].

The total blood flow of rabbit's ear was inversely proportional to ambient temperature when the hypothalamic temperature was by 1 +/- 1.5 degrees C higher than normal due to ambient temperature raise from 15 degrees to 35 degrees C. The data obtained corroborate the viewpoint that the blood flow regulation not only controls heat loss by the rabbit ear, but also stabilizes the temperature of venous blood flow in the ear, when the ambient temperature varies in wide range.


[Seasonal features of body temperature and vascular thermoregulatory responses in rabbits].

Seasonal changes of body temperature, heart and respiratory rate were studied in rabbits with thermocouples indwelled into the anterior hypothalamus. Temperature of skin of dorsal part of body and inner temperature (rectal and hypothalamic) were much higher in spring. Hypothalamic temperature was significantly lower than rectal temperature and respiratory rate was at its highest level in summer. Absolute threshold temperature for activation of heat dissipation was higher in summer than in winter.


[Changes in brain temperature in dogs while running].

Brain temperatures in different sites, rectal, aortal temperatures, and ventilation rate were measured in 3 dogs during treadmill running at 90 m/min, ambient temperature being 19-24 degrees C. External sites of the brain had a higher temperature than internal ones. Approximately the same temperature gradient was observed both during the exercise and at resting. Rectal temperature raised to a higher value than brain and aortal temperatures. Exercise had no effect on temperature threshold for panting.


[A comparison between the effects of angiotensin II and angiotensin III injected into the third cerebral ventricle on vasopressin secretion in conscious rats (author's transl)].

As the greater part of the immunoreactive angiotensin II in cerebrospinal fluid has been suggested to be angiotensin III, a comparison was made between the effects on vasopressin release of angiotensin II and angiotensin III administered into the third cerebral ventricle in conscious male rats. The blood samples were collected 90 seconds after the injection of angiotensin II or angiotensin III by means of decapitation. Plasma vasopressin (microU/ml) extracted and determined by radioimmunoassay were 2.3 +/- 0.8, 6.7 +/- 5.0, 14.0 +/- 2.2, 16.3 +/- 4.3 and 20.7 +/- 2.5 (mean +/- SEM), respectively following the injection of 0, 10, 25, 50 and 100ng of angiotensin II. The increases in plasma vasopressin produced by angiotensin II 25, 50 and 100ng were statistically significant (p less than 0.05). On the other hand, plasma vasopressin following the injection of 22.7 and 45.4ng of angiotensin III, which are equimolar to 25 and 50ng of angiotensin II each, were 14.9 +/- 2.7 and 16.3 +/- 5.6, respectively. No significant difference was found between the effect on plasma vasopressin of angiotensin II and that of angiotensin III at the dose level of 24.3 or 48.6 p. mol. These data indicate that angiotensin III is equipotent to angiotensin II in terms of vasopressin release when administered into the third cerebral ventricle. The possible role of angiotensin III in the brain on vasopressin secretion is discussed.


[The high pressure liquid chromatography of corticoids. II. Analysis of synthetic corticoids in blood and urine (author's transl)].

The high pressure liquid chromatographic (HPLC) technique was developed to separate and quantitate the synthetic corticosteroids (s-CS) which are widely used clinically. 1) 12 kinds of s-CS in alcoholic solvent and 2) some of their metabolites in the plasma and urine of healthy subjects with oral administration of s-CS were investigated for the preliminary work. The results are summarized as follows: 1) Cortisol sodium phosphate, Dexamethasone 21, disodium phosphate, Paramethasone acetate, Cortisol acetate, Cortisone acetate, Methylprednisolone acetate, Prednisone, Dexamethasone, 9 alpha-fluorocortisol, Betamethasone, Triamcinolone, and Prednisolone in ethanol were clearly separated by HPLC from Cortisol (F). In the suitable condition of the HPLC (LC-2 type) with a Zorbax SIL column, organic solvent (cyclohexane:dichloromethane:ethanol = 9:4:1)-carrier mobile phases and UV detector, the retention time of each s-CS was obviously different from that of F. The calibration curve was obtained in a linear line with regards to each s-CS. The mean recovery was 97.6% and the coefficient of variation were 1.6 (intraassay) and 7.2 (interassay)%. The sensitivity of the steroid determination was 200pg order. 2) The serial changes in plasma concentrations of s-CS; CS-metabolites and endogenous F were shown in 3 healthy males and 2 females following oral administration of the s-CS. The separated metabolites in number and quality depended on the kind of s-CS. Prednisone and other kinds of the acidified products were separated from prednisolone in the plasma and urinary samples of the healthy subjects as well as Addisonian patients. In conclusion, the HPLC method is useful for the separation and quantitation of the UV-absorbing CS of human plasma and urine. The obtained chromatograms may be an indication of the metabolic state of the subject with treatment of s-CS.


Some roots of preference: roles, activities and familial values.

This paper examines some of the connecting links between modernization in a developing society, particularly urbanization and increased education for women, and preferences for number of children. Using 1973 Taiwan data, preferences for smaller families are found to be consistently related to modern attitudes and behavior in the three domains examined: intrafamilial husband-wife role relationships, extrafamilial activities of the wife, and familial and religious values relating the family to the larger institutional setting. Modernization of these attitudes, behaviors, and values has an impact on reproductive goals independent of their association with structural variables. The wife's outside activities and exposure to modern influences through the mass media are especially important linkages, having a particularly strong mediating effect in the education effect on preferences. Intrafamilial relations appear to be of less importance. Modernization of familial and religious values mediates between urbanization and family size preferences. The measure of preference used is a scale value which has been found in other research to be more predictive of reproductive behavior than the conventional single-valued statement of number of children wanted. As the level of contraceptive use rises in developing societies, family size preferences increasingly become a factor in birth rates, and understanding the sources of change in these preferences takes on added importance. The policy implications of these findings are discussed.


The earnings of men and remarriage.

Focusing on the effects of men's earnings, this paper analyzes remarriage. Previous empirical research has not established what theoretical aspects of men's earnings are important. Here, data for Wisconsin high school graduates that include male respondents' Social Security earnings history are analyzed. The results indicate that absolute earnings, earnings instability, and earnings relative to peers have minimal effects on a man's probability of remarriage, but that permanent income positively affects remarriage. However, studies of marital disruption often find permanent income is not as important as relative earnings measures. Concluding remarks speculate about the meaning of these contrasting findings for the economics of marriage.


Patterns of suburban population growth, 1970--75.

Population redistribution within U.S. suburban rings between 1970 and 1975 was characterized by frequent population declines for individual suburbs. On the whole, recent spatial patterns of suburban population decline are similar in nature, if not overall levels, to those found in the 1950s and 1960s. Population decline is greatest in the inner suburbs, and is also evident, to some extent, in the most peripheral suburbs. Patterns for all metropolitan areas mask clear variation among metropolitan areas. This variation is related to metropolitan age or historical period of development.