Mechanism of lymphocyte activation: the binding of phytohemagglutinin to the lymphocyte surface.

The dynamics of phytohemagglutinin (PHA)-lymphocyte interaction was studied using 125I-labeled PHA (leucoagglutinin) and pig mesenteric lymph node lymphocytes that had been depleted of erythrocytes, dead cells, adherent cells and immunoglobulin-bearing cells. Evidence was obtained that PHA stimulated the majority of the lymphocytes to transform. Binding of PHA at 37 degrees C was fairly rapid (rate constant for association: 2.6 X 10(5) M-1 sec-1), saturable, reversible and specifically inhibited by N-acetylgalactosamine (Kdiss: 3 X 10(-4) M) and unlabeled PHA. A Scatchard plot was curvilinear and gave evidence for 3.6 X 10(5) binding sites per cell comprising 8.7% of high affinity sites (Kdiss: 3.7 X 10(-9) M) and 91.3% of lower affinity (Kdiss: 1.4 X 10(-7) M). About 20% of the sites were occupied under culture conditions giving maximal transformation. Alternative explanations for the curvilinear plot included negative cooperative interactions and/or increase in affinity through multivalent interaction. Negative cooperativity was supported by the demonstration that free PHA promoted the dissociation of bound PHA. Binding was not affected by metabolic inhibitors, and binding to purified lymphocyte plasma membrane resembled that to whole cells. These results suggested that PHA binding to whole lymphocytes was not grossly influenced by "capping", endocytosis and shedding.


Evidence for suppressor cells in Lewis rats' experimental allergic encephalomyelitis.

In this work we demonstrate a suppressive activity on the induction of experimental allergic encephalomyelitis (EAE) in Lewis rats, transferable to syngeneic animals, challenged with encephalitogenic mixture (myelin basic protein, complete Freud's adjuvant plus Bordetella pertussis organisms) 24 h later. This activity is probably effected by T cells and not by (an) inhibitory serum factor(s). The induction of this specific protection could be due to the penetration of the myelin basic protein antigen into the thymus where we first found suppressive cells. From the thymus, suppressor cells could then emigrate to spleen (on day 15) and to nondraining lymph nodes (on day 17). In the course of normal EAE in Lewis rats and especially at the time of self cure, this suppression is not demonstrated, but possible.


Inhibition of lymphocyte proliferation by factor(s) produced by Schistosoma mansoni.

Normal spleen cells of CBA mice or Fischer rats were cultured with mitogens or allogeneic cells, together with various substances of Schistosoma mansoni origin, and thymidine uptake was measured. The proliferation (DNA synthesis) of normal lymphocytes was inhibited by the incubation product of the parasite as well as by cell-free supernatant of schistosome culture. Inhibition was obtained only when active materials were added at the beginning of the culture. Both T and B cell proliferation were inhibited. The inhibitory activity found in cell-free supernatant suggested the release by the parasite of some factor(s) interfering with lymphocyte proliferation. Moreover, serum from rats infected by S. mansoni inhibited lymphocyte proliferation also. The inhibitor(s) appeared heat resistant, dialyzable and of low molecular weight (500-1000). Incubation of normal spleen cells with S. mansoni inhibitor(s) did not enhance the release of nonspecific suppressor cell factor. The inhibition of product(s) released by the parasite could explain part of the immunosuppression status found in schistosomiasis.


Anticholinesterase and antiacetylcholine activity of 1-phenylcyclohexylamine derivatives.

The antiacetylcholine and anticholinesterase potencies of four 1-phenylcyclohexylamine derivatives were estimated by measuring their antagonism to the contractile response of smooth and striated muscles and their inhibition of cholinesterase activity. In addition, their affinities towards the central muscarinic receptor from mouse brain homogenate were determined by competition experiments in vitro. Relative to atropine, these drugs exerted mild antimuscarinic activity in both isolated smooth muscle and in the competition experiments. On the other hand, they were found to exert antinicotinic potencies equal to that of d-tubocurarine in the striated muscle. The concentration of (3H)-phencyclidine taken up by mouse brain in vivo could be correlated with its dissociation constants from the central muscarinic binding sites, as well as with the Ki values for acetylcholinesterase inhibition, both determined in vitro. Since these drugs have a similar rigid spatial molecular structure, it is proposed that the variations in the potency of their cholinergic interactions stemmed mainly from the structural changes in the region of the 'cationic head'.


A slow-release silicone pellet for chronic amphetamine administration.

A slow release amphetamine pellet consisting of a silicone capsule containing d-amphetamine base in polyethylene glycol is described. When implanted s.c. in rats this pellet produces brain levels initially comparable to an i.p. dose of 2 mg/kg of d-amphetamine sulfate; these levels gradually fall but appreciable amphetamine remains present in the brain for over 10 days. Rats implanted with these pellets exhibit sustained motor stereotypies and constant hyperactivity in stabilimeters for 2-3 days. Four days after implantation activity declines to near control levels even though amphetamine is still present in the brain. During this later stage rats show exaggerated startle responses and resist handling. This pellet is a unique tool for the study of the behavioral and physiological effects of prolonged amphetamine intoxication.


The stability of synthetic substance P in blood.

Experiments with synthetic substance P incubated in whole blood show that apart from a moderate loss of activity immediately on exposure of the peptide to whole blood, it is inactivated slowly in this tissue, approximately 25% of control activity remaining after 30 min incubation. Incubation with plasma did not result in the degradation of substance P. The attenuation of substance P activity in blood may be due to enzymatic destruction within erythrocytes.


Cooperative effects of hemicholinium-3 on high-affinity choline uptake by rat diaphragm.

Choline uptake in the end-plate rich area of rat diaphragm is saturable between 0.7 and 16 micron. This choline uptake obeys hyperbolic kinetics and indicates the presence of high-affinity carrier with Km values of 11.8 and 13.2 micron and Vmax values of 37 and 31 nmol choline/h/g tissue respectively. In the presence of hemicholinium-3 the carrier shows sigmoidal kinetics, and hemicholinium-3 is apparently a cooperative effector of choline uptake. The carrier is more calcium than sodium dependent.


Presynaptic dopamine receptors as mediators of dopamine-induced inhibition of neurogenic vasoconstriction.

I.v. infusion of dopamine (10 microgram/kg/min) caused significant attenuation of renal vasoconstrictor responses to sympathetic nerve stimulation in pentobarbital-anesthetized dogs, whereas renal vasoconstrictor responses to exogenously administered norepinephrine were unaffected. Desipramine treatment significantly potentiated the inhibitory effect of dopamine on neurogenic vasoconstriction. Pretreatment with pimozide, a dopamine receptor blocking agent, prevented the inhibitory influence of dopamine on renal sympathetic nerve function. These results demonstrate that dopamine can inhibit neurogenic vasoconstriction by activating presynaptic dopamine receptors present on renal sympathetic nerves.


Naloxone-reversible peripheral electroanalgesia in intact and spinal rats.

Peripheral electrical stimulation of the rat produced a "dose-dependent" analgesia both in intact and in spinal animals. Naloxone, a narcotic antagonist, almost completely reversed this analgesia. It is felt that peripheral electroanalgesia acts via the release of endogenous narcotic-like substances, the enkephalins, at spinal and supraspinal centres.


Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of gamma-acetylenic gaba and gamma-vinyl GABA, two irreversible GABA-T inhibitors.

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of GABA-transaminase, produce marked and sustained elevations in mouse brain GABA concentrations and protect DBA/2 mice against audiogenically induced seizures in a similar dose and time-dependent manner. The acetylenic analog also inhibits GAD activity while the vinyl compound has minimal activity against this enzyme. The increase in brain GABA concentrations induced by these compounds correlates well with attenuation of audiogenic seizure intensity (r = 0.991 and 0.962 for gamma-acetylenic and gamma-vinyl GABA respectively) and with degree of seizure protection (r = 0.974 and 0.834). Seizure intensity is reduced by 50% when brain GABA is increased to 265% and 264% of control values by the two inhibitors and seizure incidence is halved at 322% and 324%. Thus, audiogenic seizure protection in genetically susceptible mice is apparently a function of whole brain GABA concentrations.


Studies on the capacity of mazindol and dita to act as uptake inhibitors or releasing agents for 3H-biogenic amines in rat brain tissue slices.

The effects of the anorexic and stimulant agents mazindol and dita on 3H-biogenic amine uptake and release were determined. Mazindol and dita were very potent inhibitors of 3H-norepinephrine uptake into rat brain occipital cortex slices with ED50 values (point of 50% inhibition of uptake) of 1.5 X 10(-9) M and 3.2 X 10(-9) M, respectively. Mazindol (ED50 of 2.8 X 10(-7) M) and dita (ED50 value of 8.5 X 10(-7) M) were also potent inhibitors of 3H-dopamine uptake into rat neostriatal slices and of 3H-serotonin uptake into whole brain slices (ED50 values of 5.5 X 10(-7) M and 5.1 X 10(-7) M for mazindol and dita respectively). Both compounds proved however to be extremely weak releasing agents for the 3H-biogenic amines in the respective brain areas. The effects of mazindol and dita on uptake may help to explain some of their pharmacological properties.


Cardiovascular effects of synthetic substance P in several species.

In dogs anaesthetised with chloralose, infusion of synthetic substance P into the femoral artery caused marked elevation of femoral arterial blood flow which was well sustained during the infusion period. Doses less than 59 fmol/kg/min increased femoral arterial flow only, but larger doses caused transient hypotension accompanied by tachycardia. The administration of substance P by i.v. and intravertebral (i.vert.) arterial routes caused hypotension and tachycardia of similar pattern and magnitude to those produced by intrafemoral (i.f.) arterial infusion of equivalent doses. I.v. injection of substance P into rats and rabbits caused qualitatively similar cardiovascular effects to those in dogs, but higher doses were required for threshold responses. Substance P had little effect on the spontaneously beating isolated guinea-pig heart. Like many other vasodilator substances in vivo, substance P caused constriction of the isolated perfused ear vein from the rabbit. The results suggest that the major cardiovascular effect of synthetic substance P is vasodilatation and that a direct action on vascular smooth muscle is involved.


Effects of diuretics on thyroid function of guinea pigs.

Uptake of radioiodide by the isolated thyroid and serum concentrations of thyroxine (T4) and tri-iodothyronine (T3) were determined in guinea pigs pretreated with ethacrynic acid (20 mg/kg), furosemide (40 mg/kg) or hydrochlorothiazide (40 mg/kg). It was found that both ethacrynic acid and furosemide suppressed the 131I uptake by the isolated thyroid tissues. In addition, thyroid weight and serum T3 concentration were lower in ethacrynic acid-treated animals. It seems that some diuretics, particularly ethacrynic acid, depressed the function of thyroidal follicular cells.


Effects of prostaglandin E1 and indomethacin on the stimulation-evoked overflow of 3H-noradrenaline from guinea-pig taenia.

Prostaglandin E1 (5.8 X 10(-8) M) markedly and reversibly reduced the stimulation-evoked overflow of total tritium, while it had no effects on basal outflow. Indomethacin (8.4 X 10(-6) M) increased the stimulation-evoked overflow of total tritium at low frequencies (2--5 HZ), while it had no effect at high frequencies of stimulation (more than 10 HZ). It was concluded that endogenous prostaglandin E1 also plays a regulatory role in adrenergic inhibitory neurotransmission by inhibiting the noradrenaline release from adrenergic nerve terminals of the guinea-pig taenia caecum.


The effect of verapamil on intestinal calcium transport.

Verapamil (1.5 mM) completely inhibits active calcium transport by everted rat duodenum sacs and depresses oxygen consumption by duodenal rings. Increasing the Ca2+ concentration in the incubation medium from 0.4 mM 5.0 mM reverses the inhibition of oxygen consumption by verapamil but is without effect on the extent of inhibition of calcium active transport.


Evidence for a nicotinic receptor in the sinus node.

The sinus node of the guinea pig was perfused in vitro and potassium uptake was studied in the absence and in the presence of several nicotinic agonists and antagonists. The following results were obtained: (1) the decrease in K uptake caused by a low (10(-9)M) concentration of acetylcholine was changed to an increase when acetylcholine was given in the presence of nicotinic blockade; (2) a small concentration (10(-10)M) of atropine potentiated the decrease in K uptake induced by a low concentration of acetylcholine and 10(-8)M atropine abolished it: (3) a small concentration of nicotine (10(-10)M) decreased K uptake; (4) 1,1-dimethyl-4-phenylpiperazinium (DMPP) did not modify K uptake; (5) the lack of effect of DMPP was not affected by hexamethonium; (6) trimethylphenylammonium (TMPA) decreased K uptake; and (7) the inhibitory effect of TMPA was abolished by decamethonium. It is concluded that a nicotinic receptor in the sinus node mediates the inhibitory action of a low concentration of acetylcholine on K uptake.


Potentiating effect of (+)-sotalol and deoxysotalol on prostaglandin-evoked contractions of the isolated rat uterus.

The effect of (+)-sotalol and deoxysotalol on prostaglandin (PGF2a and 15-methyl PGF2alpha)-evoked contractions was studied using the isolated rat uterus. After control responses to prostaglandins had been obtained the uterus was exposed to the nutrient fluid containing 10 microgram/ml of (+)-sotalol, deoxysotalol or (--) sotalol. 30 min later the responses to prostaglandins were again recorded. Both (+)-sotalol and deoxysotalol potentiated PGF2alpha as well as 15-methyl PGF2alpha-induced contractions. (--)-Sotalol did not potentiate the PGF2alpha-evoked contractions of the isolated rat uterus. The possible clinical significance of the results is discussed.


Responsiveness of the guinea-pig vas deferens to phenylephrine and norepinephrine in vivo.

A method is described for the study of guinea-pig vas deferens in vivo response to phenylephrine and norepinephrine. Tissue sensitivity to both agonists did not differ in vivo but the maximum response to phenylephrine was smaller. Responsiveness to norepinephrine was depressed in vitro after in vivo experiments. No such effect was observed for phenylephrine. This method allowed the comparison of the responsiveness of the guinea-pig vas deferens to adrenoceptor agonists in vivo and in vitro.


Central cardiovascular effects of morphinomimetic peptides in dogs.

Morphinomimetic peptides were injected into the cisterna magna of chloralosed dogs. Methionine enkepalin (500 microgram/kg i.c.) was found ineffective but beta-endorphin (50 microgram/kg i.c.) induced an initial and transient increase in blood pressure and heart rate followed by a delayed hypotension and bradycardia. The synthetic pentapeptides, [d-ala2]met-enkephalin (500 microgram/kg i.c.), [d-ala2]met-enkephalinamide 500 microgram/kg i.c.) also induced a marked hypotensive, bradycardic and sympatho-inhibitory effect. High doses of naloxone (100 microgram/kg i.v.) were required to antagonize these effects transiently.


[Adrenaline application by intraperitoneal depot capsule -- effects in the heart (author's transl)].

An intraperitoneal depot capsule was developed to improve the hitherto used in vivo test methods for chronic action of water soluble substances (repeated injections or permanent infusion which immobilizes the experimental animals). The capsule allows free movement of the animal and guarantees long-term continuous output of the substance. The effectiveness of the capsule was examined using adrenaline as test substance. In these experiments the maximum period of effectiveness and the consequences of permanent occupation of the receptors due to continued supply of adrenaline were studied.


Electron microscopic investigations of intracytoplasmic A particles in mouse mammary tumours.

Mouse mammary tumour cells were investigated with special regard to intracytoplasmic A particles using ultrahistochemical techniques, especially for the detection of DNA. The findings are discussed in connection with biochemical and immunological results, previously reported by several groups.


Histological and histochemical studies on the rat brain under conditions of carbon disulfide intoxication.

The brains of 35 male Wistar rats weighing 250 g were histologically and histochemically examined after a chronic intoxication due to five-month exposure to carbon disulfide. Morphologically, myelin sheath disruptions within the longitudinal tract systems of the spinal cord, destructions of individual ganglion cells in all brain regions and elective parenchyma necroses in the frontal and parietal cerebral cortices were found. The histochemical assays for enzyme activities of monoamine oxidase, ATPase, glucose 6-phosphatase, acetylcholine esterase and succinic dehydrogenase in the entire central nervous system revealed values identical to those obtained for control animals. Only succinic dehydrogenase and acetylcholine esterase revealed focal reduction in activities within the elective parenchyma necroses. After twenty-week duration of experiments a moderate decrease in activities of arylsulfatases and glutamic dehydrogenase in the entire central nervous system was found. Eventual causes responsible for these changes are discussed.


[Aspartate aminotransferase activities in renal tissue during experimental and human chronic pyelonephritis].

This study belongs to a series of comparative biochemical and semiquantitative-histological investigations in renal tissue fractions of pyelonephritis patients (human PN) and of different types of experimental pyelonephritis (experimental PN). The experiments aim at more detailed knowledge on the interrelationship of intermediary cell metabolism and histopathological changes during the different phases of human and experimental PN. The results concerning acid and alkaline phosphatase activities as well as concerning glutaminase I and glutamic dehydrogenase activities were earlier reported (Exp. Path. vols. 8, 9, 10 and 12). In the present study the author has analyzed the activities of aspartate aminotransferase (E.C.2.6.1.1. AspAT) the synonym of which is glutamic oxaloacetic transaminase (GOT).


[Synthesis and properties of bromocriptine (author's transl)].

The bromination of alpha-ergokryptine, a genuine ergot alkaloid of the peptide type, in position 2 of the indol nucleus to 2-bromo-alpha-ergokryptine is described. Its transformation to the methanesulfonate led to the prolactin inhibitor bromocriptine-methanesulfonate, Parlodel.


Inhibitory effect of antiproteoglycan serum on the biosynthesis of proteochondroitin sulfate in calf rib cartilage in vitro.

Incubation of calf rib cartilage slices with antiproteoglycan serum elevates CO2-production, but inhibits biosynthesis of proteochondroitinsulfate and of total protein. Absorbing antiserum with proteoglycan abolishes these effects.


The hemolytic activity of heterocyclic n-alkyl amine oxides.

The N-alkyl derivatives of morpholine-, pyrrolidine-, piperidine- and perhydroasepine-N-oxides caused the rapid, temperature-dependent, hemolysis of human red blood cells. The most hemolytic were the amine oxides with alkyl groups having 14-18 carbon atoms.


[Silymarin--an inhibitor of horseradish peroxidase (author's transl)].

Silybin and silychristin non-competitively inhibit the horseradish peroxidase in vitro. Silydianin on the other hand is a competitive inhibitor of the enzyme.


Isotopic composition of cattle pancreatic stones: biological and geochemical implications.

Latitudinal variations of the O18/O16-ratios of carbonate and phosphate of cattle pancreatic stones parallel a similar pattern of oxygen isotope values in rain water. C13/C12-ratios were virtually identical for the 7 cases studied. Isotopic measurements of mammalian hard tissues may be used for studying short-term climatic variations through Quaternary.


On the in vitro behaviour of mouse submaxillary gland cells. II. Metabolic differences between male and female C3H mice.

Submaxillary gland cells from female C3H mice were isolated, cultivated in vitro and their metabolic properties compared with those of male derived cells. From the results it can be concluded that these cells retain their metabolic differences when grown in vitro.


Effects of hypo- and hyperthyroidism on the activity of cystathionase in mammalian parenchymatous organs during early development.

In rats after neonatal thyroid destriction, cystathionae in liver and pancreas increased, but the enzyme activity in kidneys decreased. Substitution with thyroxine corrected these changes. Excess of thyroxine, too, had an effect on tissue cystathionase.


The alteration of the functional properties of human haemoglobin by spectrin.

Kinetic investigation by means of stopped flow techniques showed the rate of deoxygenation of haemoglobin to be slower in the presence of spectrin. At pH 7.15, the kinetic constant was 27.2 sec-1 in presence of spectrin instead of 34.3 sec-1 for haemoglobin alone. Also, equilibrium studies have revealed that the oxygen pressure for half-saturated haemoglobin decreased when spectrin was added to the reaction medium. At pH 7.35, the log (pO2)1/2 was 0.88 for haemoglobin in presence of spectrin instead of 0.93 for haemoglobin alone. From these results, an interaction between spectrin and haemoglobin may be suspected.


Central tyramine prevents hypertension in uninephrectomized DOCA-saline treated rats.

Prevention of high blood pressure in uninephrectomized, DOCA-saline treated rats was observed after treatment with central tyramine precursors. We suggest that the high blood pressure is either due to relative lack of tyrosine, which might be caused by the hyperactivity of tyrosine hydroxylase, or to hypoactivity of the decarboxylase: in both cases the result is diminished tyramine synthesis.


Activity tests of alcohol dehydrogenases in wheat, rye and triticale.

The relative band staining intensities of ADH isoenzymes in wheat and triticale suggest alloploid genome interactions. Rye ADH is scarecely affected by anti-wheat-ADH. Despite the evolutionary divergence of their Adh genes, ADH monomers of wheat and rye form enzymatically active heterodimers in triticale.


Interorder transfer of mycoplasmalike microorganisms between Drosophila paulistorum and Ephestia kühniella. II. Numbers of MLO and sterility.

A successful attempt was made to culture the mycoplasmalike microorganism causing semispecific hybrid male sterility in Drosophila paulistorum utilizing Ephestia kühniella as the intermediate host. Data gleaned from this passage indicates that the induction of sterility depends upon the quality not the quantity of infectious intracellular symbionts.


Demonstration of lateral asymmetry in G-banded mouse embryo chromosomes.

Cells obtained from 10-day mouse embryos were cultured for 3 h in medium containing colcemid. Chromosome preparations were subjected to G-banding in either calcium-magnesium free Hank's solution or the ASG method. From one to several occurrences of lateral asymmetry (unequal banding of sister chromatids) were observed in the majority of karytotypes analyzed.


Inheritable precocious opening of the vagina in laboratory rats exposed to 300 R and 200 R of X-rays on day 6 of their intrauterine life.

A highly significant inheritable advancement in opening of the vagina in laboratory rats has been induced by the X-ray application to pregnant females of different filial generations origination from the X-irradiated FO embryos. The reaction to X-rays has so far been followed through 9 filial generations.


[Squamous metaplasia of human mammary epithelium in long-term organ culture].

Squamous metaplasia of the mammary epithelium was observed in human breast tissue maintained in long-term organ culture. The phenomenon occurred only in the synthetic medium 199 with Earle's salts. Insulin and/or glucose enrichment enhanced its occurrence.


Effect of indole-3-acetic acid on the kinetics of horseradish peroxidase catalyzed scopoletin oxidation.

The kinetics of horseradish peroxidase catalyzed of scopoletin oxidation were observed to be sigmoidal. The apparent KmS for scopoletin is 0.9 mM. Inhibition of scopoletin oxidation by indole-3-acetic acid (IAA) appears to be non competitive. Non competitive inhibition by IAA suggests a more significant role of the peroxidase protein matrix in regulating the activity of the heme moiety.


Biochemical studies on peptide alkaloids: induction of ion selective mitochondrial swelling.

The effect of frangulanine, a cyclopeptide alkaloid isolated from Hovenia dulcis Thunb., on mitochondrial swelling was studied. Frangulanine induced mitochondrial swelling in 0.15 M KCl solution at the concentration of 6.5 muM. The alkaloid showed ion selectivity on the induction of mitochondrial swelling. Upon addition of frangulanine, mitochondria underwent swelling in 0.15 M KCl or RbCl solution but in neither NaCl nor LiCl solution.


Effect of botulinum toxin on the choline acetyltransferase activity in salivary glands of cats.

The choline acetyltransferase activity of submandibular glands that had previously received a retrograde injection of botulinum toxin via their ducts was found to be markedly lower than in the untreated contralateral glands. In the parotid glands exposed to the same treatment the activity of this enzyme was less affected.


Reproductive consequences of mega vitamin E supplements in female rats.

Female rats fed 0, 25, 2500 and 10,000 IU vitamin E/kg diet for 3 months were examined for reproductive performance. On 10,000 IU vitamin E/kg diet, the fertility of inseminated rats was significantly reduced as compared to rats given normal or nutritional levels of vitamin E.


On the mechanism of the amphetamine induced vasodilation at the rat's cerebral cortex.

Cerebral cortical blood flow was measured with the hydrogen clearance technique. It was found that the increase in CoBF induced by amphetamine is blocked by atropine or chlorpromazine.


Are there 2 cholinergic thermoregulatory centres in rats?

An attempt was made to replicate the conflicting previous reports of hypo- and hyperthermic effects of intrahypothalamically administered carbachol. Despite using the same coordinates, injection parameters, and strain of rats reported by others, only hypothermia was conclusively demonstrated. It was concluded that the cholinergic system mediates heat loss mechanisms in rats.


Demonstration of microtubule independent protein secretion from rat liver.

The induced secretion of rat liver microsomal-beta-glucuronidase into serum is, unlike other proteins secreted from liver, not dependent upon an intact microtubule apparatus.


Offset-induced audiogenic seizures.

A relatively stereotyped seizure reaction can be triggered by the "offset" of an intense bell sound in C57BL/6J mice. Susceptibility to this offset-induced audiogenic seizure was found to depend upon the age of the animals tested (higher in older mice) and the duration of the noise exposure (more effective with longer exposure).


Contribution of diffusive pathway in intestinal absorption of glucose in rat under normal feeding condition.

Luminal concentration of glucose determined by a specific enzymatic method was about 50 mM after meal in rat jejunum. The diffusive pathway was suggested to have an important role in intestinal absorption of glucose.


Experimental hydrocephalus following mechanical increment of intraventricular pulse pressure.

Experimental hydrocephalus has been induced in lambs by artificial increase of the amplitude of intraventricular cerebrospinal fluid (CSF) oscillations related to arterial pulsations, without concomitant changes of the mean CSF-pressure. The characteristics of this hydrocephalus demonstrate that the intraventricular CSF-pulsations can play a role in the genesis of ventricular dilation. Such a method may be used to produce an original model of hydrocephalus independent of changes of CSF-circulation or absorption.


False interpretation of membrane transport data due to osmotic volume changes of cells.

It is shown theoretically that in a nonsaturable transport system across a cell membrane, the kinetical analysis yields (erroneously) apparent saturation kinetics if osmotic volume changes of the cell occur and not taken into acount. Experimentally this is illustrated for the case of exit of glycerol from beff erythrocytes.


Does the long term wear of contact lenses produce a loss of corneal sensitivity?

Corneal sensitivity was measured with the Cochet-Bonnet aesthesiometer in a control group of 42 people and in 82 people who had worn hard contact lenses for various amounts of years. Corneal sensitivity was found to diminish significantly after a few years of wear, thus placing the wearer at some risk.


The perirenal venous arch of the rat: its functional significance.

A functional and morphological study of the perirenal venous arch of the rat has been carried out. The various drainage possibilities of this arch through its multiple collaterals are demonstrated. Venous renal blood can reach the adrenal gland via the perirenal arch. The endocrine interactions between these organs are discussed.


Monosynaptic inhibition of thalamic neurons produced by stimulation of the substantia nigra.

Electric stimulation to the substantia nigra (Pars reticulata) produced a monosynaptic inhibition of the neurons of the ventromedial nucleus of the thalamus in anesthetized cats.


Localization of a new neuroleptic in the pituitary gland of the rat.

The 14C-labelled, substituted benzamide neuroleptic Tiapride has been found to accumulate transiently in the pituitary gland of the rat following a single dose, and a prolonged retention of the drug was observed in the pars intermedia.


Methadone and brain development.

The effect of maternally administered methadone hydrochloride (5 mg/kg) on brain development of offspring treated during gestation and/or lactation was studied in 21-day-old rats. Animals treated during gestation or lactation were the most severely affected, with reductions in brain weights (12% and 30%, respectively), and DNA values (50% and 34%, respectively) observed.


Direct toxic effect of isoproterenol on cultured cardiac muscle cells.

Isoproterenol at relatively high doses (2.5 mg/ml) has a marked toxic effect on rat heart muscle cells cultivated in vitro. This effect is not prevented by propranolol and therefore is not mediated by beta adrenergic receptors.


Effect of clonidine on the noradrenergic cyclic AMP generating system in the limbic forebrain and on medial forebrain bundle self-stimulation behavior.

The present results show that clonidine does not mimic the agonist action of norepinephrine (NE) on the noradrenergic cyclic AMP generating system of the limbic forebrain, but antagonizes the stimulatory effect of NE while not influencing the action of isoprenaline. In self-stimulation behavior, clonidine decreases responding and blocks the facilitation caused by d-amphetamine.


Ultrastructural changes in dog thyroid follicular cells elicit by concanavalin A in vitro.

Dog thyroid follicular cells exposed to concanavalin A (Con A) in vitro showed changes in cell shape, induction of colloid droplets and alterations in the distribution of microvilli. Cells exposed to Con A plus suboptimal concentrations of TSH (thyroid stimulating hormone) showed pseudopods and their cytoplasm was virtually occupied with colloid droplets. This findings suggest that Con A potentiated pseudopod and colloid droplet formation induced by TSH.


Role of the pituitary in cyproheptadine-induced pancreatic beta-cell toxicity.

Hypophysectomized rats given cyproheptadine (40 mg/kg) for 10 days exhibited a loss of pancreatic immunoreactive insulin and ultrastructural changes in the cytoplasm of beta-cells. Sham-operated animals given cyproheptadine showed identical changes in pancreatic beta-cells except that cytoplasmic involvement progressed to the formation of large vacuoles. The pituitary is not directly involved with the cyproheptadine-induced depletion of pancreatic insulin but plays a role in the formation of large cytoplasmic vacuoles.


In situ noradrenaline-induced stimulation of dog thyrotrophic secretion.

Anterior pituitary microinfusions of noradrenaline in the dog causes a significant release of TSH while adrenaline and dopamine do not.


Effect of a sesquiterpene from Aristolochia indica Linn. on fertility in female mice.

A sesquiterpene isolated from the roots of Aristolochia indica (Linn.) was found to exert 100% interceptive activity and 91.7% anti-implantation activity in mice at a single oral dose of 100 mg/kg b. wt. No toxic effect was found at the dose levels used.


A centrally induced vasodepressor response after intravenous administration of whole venom of Naja mossambica pallida in cats.

Naja mossambica pallida venom administered i.v. (200 microgram/kg) produces an initial brief fall in blood pressure, due to a direct myocardial depressant effect, and a sustained fall due to central depressant effect.


Comparison of human adult and fetal hemoglobin: aminophenol-induced methemoglobin formation.

Human fetal hemoglobin was more susceptible to methemoglobin formation in the presence of aminophenols than was adult hemoglobin. This was due to the intrinsic properties of the proteins rather than the presence of methemoglobin reductases.


Differences in cerebral morphology in 2 stocks of mutant mice heterozygous for the loop-tail (Lp)-gene.

Adult loop-tail heterozygotes (Lp/+) from a stock of Lp-mice which consistently fail to show head wobbling exhibit normal brain morphology with respect to size and shape of lateral ventricles and nearby nuclei. Loop-tail heterozygotes from a head wobbling stock of Lp-mice show enlargement and deformity of the lateral ventricles.


A quantitative analysis of plasma osmotic pressure during metamorphosis of the bullfrog, Rana catesbeiana.

The plasma constituents contributing to osmotic pressure are, in decreasing order: Na+, Cl-, HCO3-, K+, glucose, amino acids, urea and protein. Plasma osmotic pressure increases from 180 mmoles/1 to 200 mmoles/1 throughout development.


Development of intratesticular implants of rat pituitary primordia.

Intratesticular grafts of pituitary primordia from 11-13-day-old rat embryos developed in 6 weeks into round nodules approximately 1 mm in diameter. The nodules were principally composed of well differentiated glandular and nervous tissues.


[Interkinetic nuclear migration in nasal placode of chick embryo].

Cells of nasal placode of chick embryos were studied with thymidine H3 and autoradiography. Our results shown, that the nuclei in the nasal placode synthesize DNA in the outer zone, then migrate toward the inner zone to undergo division and subsequently return to the outer zone.


Effect of propylthiouracil on intestinal tumor formation by azoxymethane in rats.

Treatment with propylthiouracil (PTU) resulted in a significant decrease in azoxymethane-induced intestinal tumors, total concentration of fecal bile acids as well as the fecal neutral steroids, cholesterol and coprostanol. Thus, a hypothyroid state induced by PTU treatment may affect intestinal carcinogenesis in this animal model by lowering the concentration of fecal bile acids and neutral steroids.


Changes in the thermal denaturation profiles of DNA from different developmental stages of the newt Triturus vulgaris.

The melting profiles of DNA samples from the early gastrula and early neurula of Triturus vulgaris are essentially the same, whereas DNA from mid to late gastrula possesses higher Tm values and shows a deviation from the regular sigmoidal shape at temperatures above Tm. The plot on normal probability paper indicates a second DNA fraction which melts at higher temperatures and, consequently, it has a higher GC-content than the bulk of DNA. These facts confirm our idea that differential DNA replication occurs during gastrulation.


Mitogenic action of neuraminidase.

A new effect of NCV on lymphocytes is demonstrated. This property is the capacity to act as a mitogen in and of itself. The possible mechanisms of this phenomenon are discussed.


Changes in rate of methemoglobin reduction and oxygen affinity of erythrocytes incubated with inosine, pyruvate and phosphate.

Incubation of human erythrocytes with inosine, pyruvate and phosphate increases several fold the ferrihemoglobin reductase activity, the values of which, however, depend on the age of blood (by 6 to 2 times with respect to the normal value of fresh blood).


Electrical stimulation induces clot retraction after previous in vitro platelet aggregation.

The spontaneous clot retraction of platelet-rich plasma is inhibited by previous in vitro ADP-induced platelet aggregation. The electrical stimulation of the clot always restores a maximal clot retraction, even after a prolonged previous in vitro platelet aggregation.


Leukocyte mobilization by epinephrine and hydrocortisone in patients with chronic renal failure.

The mobilization of WBC from the bone marrow, as judged from hydrocortisone-induced leucocytosis, is markedly impaired in dialyzed and nondialyzed uremic patients. The release of WBC from the marginal pool by epinephrine was found to be normal.


A lectin in Nemopanthus mucronatus to papain treated porcine erythrocytes.

Extracts of the mountain holly, Nemopanthus mucronatus, contained an agglutinin to papain treated porcine erythrocytes but not untreated or neuraminidase treated cells. Human erythrocytes similarly treated did not react.


Effect of estrogens on LH- and FSH-levels in prepuberal male and female androgenized rats.

This paper has demonstrated that neonatal androgenization increases in prepuberal male and female rats the FSH-levels without changes in LH, indicating that the sexual differences in the control of FSH is a relevant process that takes place during the differentiation of the hypothalamus.


Radioprotective effects of cyproterone acetate.

The pretreatment of irradiated mice by cyproterone acetate had a better radioprotective effect in comparison with orchidectomy, although the weight of the thymus was lower in the cyproterone acetate group. The radioprotective mechanisms involved in both cases were discussed.


Effect of propranolol on various parameters of estrogen stimulation in the rat uterus.

Pretreatment with propranolol does not modify the estrogen-induced uterine eosinophilia, the water imbibition effect, nor the increase in uterine RNA and protein content. This confirms the independence of these parameters from the estrogen-induced early increase in uterine cAMP, since, when observed, the latter is suppressed by propranolol pretreatment.


Salivary gland enlargement as a test for a new way of permanent isoproterenol application.

Low doses of isoproterenol, given permanently by a new application-method, show the same effects on salivary-gland enlargement of rats throughout approx. 6 days than 10fold higher concentrations given by previous workers as single daily injections.


Androgenic properties of gibberellic acid in the chick comb bioassay.

Gibberellic acid stimulates the growth of the comb in the male chicks, but is ineffective in females. Estrogen prevents gibberellin-induced stimulation.


Absence of beta-exotoxin in Thuricide preparations.

The biological insecticide Thuricide is produced from B. thuringiensis, Berliner, var. kurstaki (serotype 3a, 3b), a bacterial strain which does not synthesize exotoxin. Thus, our product is devoid of any C-mitotic or mutagenic potentiality such as is to be found in exotoxin.


Possibility of using 131I-albumin as a marker for the estimations of microbial protein synthesis rates in the rumen.

Total microbial protein synthesis rates in the rumen of buffaloes were estimated by isotope dilution technique, using 131I-albumin treated with tannic acid as a marker. The animals were fed groundnut cake treated with formaldehyde to meet 50% of their digestible crude protein (DCP) requirement and 2.5% urea molasses mixture was given to meet the remaining requirement of DCP. Wheat straw was fed as the basal roughage. The total average microbial protein synthesis was 58.14 g/day.


[Effect of chronic ethanol consumption on the thyroxine hydroxylase activity of various brain structures in rats].

The effect of chronic (8-week long) 5 percent-ethanol consumption on the activity of tyrosine hydroxylase on the rat brain hypothalamus, striatum and midbrain was studied. In rats with strong ethanol prefence the enzyme activity was found to increase by 65-86 percent in the hypothalamus and to diminish by 52-68 percent and 29-68 percent in the midbrain and striatum, respectively. In rats with weak ethanol preference the enzyme activity in the brain striatum and midbrain remained unchanged, while in the hypothalamus it decreased by 25-40 percent. Chronic ethanol consumption had no effect on the inhibition of the enzyme activity neither by dopamine (8.0 X10(-4)M), nor tyrosine (in an inhibitory concentration of 3.7X(10(-4)M).


[Central action of a new cholinesterase reactivator, diethyxime].

In anesthetized cats, whose peripheral muscarinic-cholinorecptors are blocked by m-cholinolytics (benzilyl choline) failing to penetrate into the brain, the cholinesterases reactivator diethyxime debars the centrally caused fall of the arterial pressure produced by armine, an inhibitor of cholinesterases readily gaining access into the brain. Diethyxime is also capable of abolishing the depression of the phrenic nerve action potentials produced by armine. Dipyroxime-a quaternary diethyxime analogue and also a quaternary cholinesterase reactivator fails to produce such an effect.


[Effect of novocaine incorporation into the structure of a water-soluble polymer on its pharmacological activity].

The topically anesthesizing action and acute toxicity of two polymetric derivatives of novocaine-celnovocaine and polynovocaine No 5 (PN-5) were studied. The polymeric derivatives differ in the orientation of the novocaine molecule with respect to the macro-molecule of the water-soluble polymer-the modified cellulose. In celnovocaine novocaine joins the macromolecule through the intermediary of diethylamino-ethanol nitrogen and in PN-5-through the intermediary of paraaminobenzoic acid nitrogen. The ratio of the polymer-carrier (mol. weight 20 000-26 000) to novocaine is 1:1. The chemical bonding between novacaine and modified cellulose potentiates ad prolongs the infiltrative and terminal anesthesia, without changing (PN-5) or lowering  (celnovocaine) the toxicity. The extent to which the action and duration of the effect, as well as changes in the toxicity depend upon the orientation of the novocaine molecule relative to the water-soluble polymer molecule.


[Action of isolanide in acute cardiac insufficiency in rats].

Acute teste staged on rats showed low doses of the cardiac glycoside isolanide to bring down the level of total lipids, cholesterol and beta-lipoproteins, without causing any changes in the content of NAD, adenyl nucleotides, non-esterified fatty acids (NEFA) and of phospholipids in themyocardium. Large doses of the drug uniformly reduce the content of all the co-enzymes fractions, the amount of ARP, ADP, cholesterol, beta-lipoproteins and the raise the level of total lipids, phospholipids and NEFA. In cases of acute cardiac insufficiency the drug produces a normalizing action on the co-enzymes and adenyl nucleotides content and reduces that of beta-lipoproteins and cholesterol. It appears that a definite part in the mechanism of the isolanide action plays its influence on the level of nucotinamide co-enzymes, adenyl nucleotides and lipids.


[Effect of mercazolyl on the course of isadrin lesions of the heart].

Tests conducted on rats established the prophylactic administration of mercazolil to produce a beneficial influence on the course of experimental isadrine-induced heart affections Administration of mercazolil concurrently with isadrine, on the contrary, tends to aggravate the course of the pathological process.


[Effect of obsidan on the systemic hemodynamics of dogs in ontogeny].

Investigations on dogs of different age have brought evidence that intravenous administration of 2 mg/kg of obsidan (propranolol hydrochloride) causes in 18-22-day old puppies a fall of arterial pressure due to a reduced cardiac ejection with little changing total vascular peripheral resistance. The frequency of the rhythm and conduction in the heart are slowed down. In dogs aged 3-5 years the arterial pressure remains unchanged, since the diminution of the cardiac output is attended by a greater vascular resistance.


[Fibrinolysis in the blood of animals exposed to the chronic per os use of a heparin-urea complex].

When given per os a complex heparin-urea produces in the organism an intensive anticoagulant and fibrinolytic background which makes itself manifest in 1 hour time and continues to exist for as long as 16 hours after the last (10th) introduction. Upon abolishing the intake of the complex the study figures for the coagulation, anticoagulation and fibrinolytic activity return back to their physiological level. Introduction per os of the complex heparin-urea did not cause any changes in the tissues of the liver, heart, lungs, spleen and kidneys, while administration by the same route of an equivalent amount of urea caused mainly an increased non-fermentative fibrinolysis in the kidneys.


[Effect of histamine and nicotine on carbohydrate metabolic indices and the catecholamine balance in the vascular wall].

In experiments on cats subject to study was the effect of histamine and nicotine used in different doses on the level of "key" metabolites of the carbohydrate metabolism and on the catecholamines balance in the wall of vessels of different functional purpose at the instant of the maximum, bioelectric and motor response to a vasomotor agent. It was shown that the vasodilation phase observed after introduction of the mediatory type drugs was attended by activation of the carbohydrate metabolism this proving the energy-dependence of the relaxation process. The presence of variously oriented and differently marked changes in the content of the carbohydrate metabolites in vessels vessels of diverse functional purpose made it possible to classify the vessels according to the type of metabolism, which coincides with their functional purpose.


[Comparative evaluation of the action of clofeline and isoglaucon on the eye].

In experiments on rabbits it was found that the developed clofelin eyedrops in the shape of 0.125, 0.25 and 0.5 percent solutions with a rated storage time of 2 years display a hypotensive action. The fall of the intra-ocular pressure following instillation of the drug may be put down to the inhibition of the sympathetic nervous system coming as a result of the central action, as well as to the local alpha-adrenomimetic effect that brings with it a diminished secretion and improved outflow of the aqueous humor. A comparison of the effects produced by clofelin and isoglaucon on the intraocular pressure, hydro- and hemodynamics of the eyes did not reveal any essential differences between these drugs.


[Study of the action of x-ray contrast substances on the respiratory chain of rat liver mitochondria].

Subject to study was the influence of roentgen-contrast media on the respiration and linked with it phosphorylation in the mitochondria of the rats' liver. Triotrast, cardiotrast, bilignost and endografin are shown to produce no effect on the oxidative phosphorylation in concentrations that can be built up following their administration "in vivo", but inhibit the respiratory mitochondrial chain. Triombrin, urotrast and iodamide have no effect on the mitochondria.


[Synthesis of n-hexanoylmethylene triphenylphosphorane].

An efficient synthesis of n.hexanoylmethylenetriphenylphosphorane (II), a fundamental intermediate for obtaining prostanoic products, is described. The crucial intermediate in the synthesis is the 2-keto-n.heptyltriphenylphosphonium chloride (VII), which is prepared via a very precise procedure.


[Mechanism of the anti-inflammatory action of immunodepressants].

The effectiveness of immunodepressants in lingering exudative processes, their inhibitory action in the proliferative phase of inflammation, depression of the phagocytic activity of leucocytes, as well as suppressive influence on the development of a toxic pulmonary edema and upon generalized anaphylaction reaction was demonstrated in tests staged on rats and mice. The antiphlogistic action of immunodepressants was not abolished during the first hours after their administration by specific metabolites, but was suppressed at the peak of the cytostatic effect together with the latter. The phlogolytic effect was not mediated through the hypophysis-adrenal system and did not include the lienic factor.


[Effect of drug preparation combinations on intrauterine development].

On the 13th day of pregnancy chloridine (50 mg/kg) or 6-mercaptopurine (60 mg/kg) was administered to rats. Thirty minutes before this the anomals received insulin (40 IU/kg), pentoxyl (100 mg/kg), ethonium (15 mg/kg), dimexide (5500 mg/kg), or magnesium sulphate (250 mg/kg). Oi the 20th day of preganancy the animals were sacrificed. While chloridine and 6-mercaptopurine caused abnormal development in all live embryos, their damaging (teratogenic and embryolethal) and action was sharply reduced when teratogens were used in combination with other drugs. The author feels that the normalizing effect of the study agents is due to the influence of these compounds on the functioning of the lysosome-segregational system.


Alkaloids of Ocotea brachybotra.

Aporphine, proaporphine and morphinane alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea brachybotra (Meiss.) Mez. The known alkaloids were identified through their physico-chemical properties as: (I) (+/-)-glaziovine, (II) dicentrine, (III) ocopodine, (IV) cassynthicine, (V) predicentrine, (VI) leucoxine, (IX) sinacutine and (X) pallidine. The structure of (VI) leucoxine was confirmed by a detailed analysis of the N.M.R. spectra recorded in various conditions. New morphinane alkaloids, (XI) ocobotrine and (XII) 14-espisinomenine, having the unusual B/C-trans configuration were also isolated. Their structures were determined using spectroscopic methods and chemical correlations.


[Changes in the quantity of nucleic acids in the liver and kidneys of rats with experimental lead poisoning].

In the liver and kidneys of 125 control and test albino rats poisoned perorally daily with different doses of neutral lead acetate for 1, 3, 5, 10, 20, 30 and 45 days the RNA and DNA contest was measured. A statistically significant increase of nucleic acids was registered in both organs, earlier and stronger pronouced in the liver than in the kidneys. The amount of DNA changed quicker than that of DNA. In all the groups of animals the rise in the content was proportional to the introduced amount of lead (20, 40 and 100 mg/kg body weight). Following poisoning with 20 mg/kg of lead acetate the DNA and RNA accretion (statistically significant) remained after the 10th day roughly the same till the 45th day. The main reason for the DNA increment in the study organs seems to be an intensive synthesis, the rise of RNA is due to an inhibited activity of ribonuclease.


[Synthesis of 2,3-diazaphenothiazines. XIII. Dialkylaminoalkylic derivatives of 7-acetylamino-2H-pyridazino(4,5-b) (1,4)benzothiazin-1 (1OH)one and of the isomer of 7-acetylamino-3H-pyridazino(4,5-b) (1,4)benzothiazin-4 (1OH)-one].

Some derivatives of 7-acetylamino-2H-pyridazino [4,5-b] [1,4] benzothiazin-1 (1OH)-one (VI a...d) and of 7-acetylamino-3H-pyridazino [4,5-b] [1,4]benzothiazin-4 (1OH)-one (X a...d) substituted in the 2 and 3 positions with dialkylaminoalkyl groups are described. The compounds were subjected to pharmacological screening.


[Effect of a number of sulfur-containing radioprotective agents on the evacuatory function of the stomach in mice].

Tests staged on mongrel albino mice demonstrated that sulphur-containing radioprotectors used in doses two orders below those exercising a radioprotective action with their peroral administration are apt to significantly modify the evacuative function of the stomach. This properties of the sulphur-containing radioprotectors depends upon their chemical structure. A particularly strong influence on the evacuative function of the stomach in mice exerts cystamine dichlorohydrate, aminoalkylamino-alkylthiophosphates and mercaptoamidines. This property is less pronounced in cystaphos and cysteamine chlorhydrate. The least effect on the delayed evacuation was found in cysteamine bitartrate and in the disodium salt-4, 4(1)-trithiobis (butane-sulphonate). These data allow it to explain the specificity of the toxic and radioprotective action produced by diverse drugs with their peroral administration.


[Synthesis and preliminary pharmacological characteristics of various derivatives of 1,2,5-oxadiazole (furazan)].

The synthesis, the chemical properties, the acute toxicity, the action of frog flexor reflex of 4-methylfurazan-3-N-methylcarboxamide (II), 4-methylfurazan-3-N-isopropylcarboxamide (III), 3-methyl-4-morpholinocarbonylfurazan (IV), 3-methyl-4-pyrrolidinocarbonylfurazan (V), 3-amino-4-methylfurazan (VI), 3-acetylamino-4-methylfurazan (VII), are reported. LD50 decrease in the following order: (VI), (II), (IV), (III), (VII), (V). All compounds, except (VII), depressed frog flexor reflexes.


Reaction of dichloroketene and sulfene with N,N-disubstituted 6-aminomethylene-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones. Synthesis of 5H-benzo(5,6)cyclohepta(2,1-b)pyran and 5H-benzo(5,6)cyclohepta(1,2-e)-1,2-oxathiin derivatives.

The 1,4-cycloaddition of dichloroketene to N,N-disubstituted 6-aminomethylene-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones afforded N,N-disubstituted 4-amino-3,3-dichloro-3,4,10,11-tetrahydro-5H-benzo[5,6]cyclohepta[2,1-b]pyran-2-ones only in the case of full or partial aromatic N-substitution. The relative adducts gave N,N-disubstituted 4-amino-3-chloro-10,11-dihydro-5H-benzo[5,6]cyclohepta[2,1-b]pyran-2-ones by dehydrochlorination. The 1,4-cycloaddition with sulfene occurred readily in the case of both aliphatic and aromatic N-substitution to give N,N-disubstituted 4-amino-3,4,10,11-tetrahydro-5H-benzo[5,6]cyclohepta[1,2-e]-1,2-oxathiin-2,2-dioxides. These compounds, as well as the pyran derivatives, can be considered as linear heterocyclic analogues of the Amitriptyline ring system.


[Preparation and study of phytotoxicity of N-arylalkyl substituted amides. I. Benzylamides].

A series of N-benzyl substituted amides (substances I-CV) have been prepared and tested for phytotoxicity. Preliminary tests were carried out on various common plants using both pre- and post-emergence tests at doses of 6 kg/ha. Further tests using doses of 4 and 2 kg/ha were carried out on the most interesting compounds. Some of the compounds tested showed marked phytotoxic activity. This activity appears clearly different as regards mechanism from that of homologous anilides. The amides studied appear to be quite inactive as inhibitors of the Hill reaction.


Radiopaque contrast media. XLIV - Preclinical studies with a new nonionic contrast agent.

L-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophthalic acid di-(1,3-dihydroxy-2-propylamide), abbreviated Iopamidol, a new non-ionic water soluble contrast agent for angiography, myelography, ventriculography and for contrast reinforced computer-assisted axial tomography is described. Extensive preclinical testing showed favorable physico-chemical features of the new compound, low systemic toxicity, excellent cardiovascular and renal tolerability, very mild effects on the blood-brain barrier and on nervous tissue.


Pregnancy following the "insensitive ovary syndrome".

A patient in whom the "insensitive ovary syndrome" was followed by a successful pregnancy is reported and discussed. Conception occurred while this patient was receiving estrogen therapy. The marked differences in her ovarian responsivity to endogenous and exogenous gonadotropin stimulation remain enigmatic.


Microscopic vasectomy reversal.

More than 300 patients undergoing microscopic vasovasostomy have been carefully studied in an effort to determine the factors which affect the recovery of fertility after an accurate microscopic reanastomosis. The over-all pregnancy rate in an unselected group of early patients was 71%. Recovery of fertility correlated with the return of normal sperm counts and with the quality of seminal fluid in the vas deferens on the testicular side of the obstruction at the time of vasovasostomy. The three most important factors influencing return of fertility after vasovasostomy are (1) a meticulous microscopic technique for reconnection, (2) the duration of time the vas deferens has been obstructed, and (3) the presence of absence of a sperm granuloma at the site of the vasectomy, venting the long-term pressure buildup which otherwise would occur. The presence of a sperm granuloma at the vasectomy site generally ensured the presence of good quality sperm in the vas fluid at the time of vasovasostomy and the recovery of a good sperm count postoperatively. If all three of these factors are favorable, vasectomy should be reversible for most patients.


Clomiphene citrate in the management of male hypofertility: predictors for treatment selection.

All males treated with long-term, low-dose clomiphene citrate retrospectively were categorized as having pregerminal, primary germinal, or postgerminal hypofertility and their response to treatment was observed. Among couples in which no female factor could be identified and the husband was categorized as demonstrating pregerminal hypofertility, a pregnancy rate of 42% was established after treatment.


Artificial donor insemination with frozen human semen.

This study describes the experience with artificial donor insemination (AID) using frozen semen in 227 women who began therapy in 1974 and were followed until March 31, 1976. Ninety-one women (40%) conceived during this period. Sixty-five women (37.9%) failed to continue treatment after three or fewer cycles; follow-up on these patients was incomplete and it is presumed that most did not conceive. The cumulative pregnancy rate was 56.5% among women who persisted in AID for four or more cycles. Additional causes for infertility were found in 53 women. Excluding these, the pregnancy rate was 67.4% for apparently fertile women who had had four or more cycles of AID. Fifty-eight per cent of conceptions occurred within the first three cycles and eighty-five per cent within the first six cycles. The pregnancy rate was not significantly affected by age, occupation, cigarette smoking, or prior fertility. The large number of dropouts after a few cycles of AID suggests a need for intensive and continuous educational, emotional, and psychologic support.


Antigenicity of frozen and fresh spermatozoa.

Since cryopreservation of spermatozoa causes surface changes, we tested whether specific antigens associated with the plasmalemma might be dislodged or destroyed during freezing. When we compared the use of frozen sperm with the use of fresh sperm in indirect immunofluorescence tests for antisperm antibodies, we found changes in antigenicity. There was a decrease in antigenicity of the acrosomal region, and antigenicity of the sperm tail was increased with the addition of 10% glycerol, with or without cryopreservation. These results suggest that women who are infertile and, as demonstrated by immunofluorescence, have antibodies to sperm may be aided by artificial insemination with the husband's cryopreserved sperm.


Modification of germinal epithelium ischemia by perfusion.

Three groups of dogs underwent testicular ischemia for a 3-hour period. Group I (10 animals) was not subsequently perfused. Group II (10 animals) underwent subsequent perfusion by a new in vivo reversible method via the internal spermatic artery with heparinized saline. Group III (5 animals) underwent perfusion with Sacks' solution. At 3 weeks' time the histology of the testes of the three groups was compared. Group I showed a 75.5% decrease in the germinal epithelium. Group II showed a 21.4% decrease. Group III showed a 31.8% decrease. The survival rate of the germinal epithelium in the two perfused groups was significantly improved (P less than 0.01).


[Transcallosal modulation of a focus of maximal activity in the motor cortex].

In acute experiments on cats, when recording EPs from 170 symmetrical points of the motor cortex, callosal influence on the maximal activity focus (MAF) was studied in conditions of stimulation of the sciatic nerves with different stimuli. After callosal transection, weak stimuli enlarged the MAF, strong one-narrowed it. The transcallosal modulation in intact brain is supposed to aid to delineate the MAF in the motor cortex and to exaggerate the differences between MAFs occurring at stimulation with different stimuli.


[Nature of the hig-frequency (pessimal) block in the excitatory neuromuscular synapses of cray fish].

The characteristics of the excitatory neuromuscular transmission of the crayfish claw opener were studied with intracellular recording during high frequency stimulation . The high frequency block was of the presynaptic origin. The appearance of failures of transmission was correlated with the decrease of the conduction velocity in the axon and/or its branches. At the high rates of stimulation before the failures of transmission, the mean quantum content of the polysynaptic EPSPs on the plateau of potentiation was lower than that at the lower rates. There were no signs of the transmitter store depletion during high frequency stimulation. The stability of transmitter secretion mechanism is concluded to be higher than that of the nerve conduction.


[Mechanisms of release of adrenaline and noradrenaline from the caudal mesenteric ganglion of dogs].

Adrenaline (A) and noradrenaline (N) release from the caudal mesenteric ganglion (CMG) during preganglionic nerve stimulation is due to acetylcholine action on N--and M-cholinoreceptors of ganglion's adrenergic structures (GAS) and probably, primarily on SIF--cells, whereas during peripheral reflexes of CMG it is related to the excitation of noncholinergic afferent neurons which affect the corresponding receptors of GAS. A and N release is inhibited via M-receptors. There is a complex relationship between receptor fields of GAS. Hemicholinium as well as N--cholinoblocking agents, during first minutes of their application to the ganglion elicit A and N release both before and after preganglionic fiber degeneration, which indicates their postsynaptic effect on the cholinoreceptors. Changes in A and N in the ganglion during peripheral reflexes are increased after prolonged action of hemicholinium and chronic decentralisation of CMG.


[Comparative characteristics of changes in the diameters of microvessels and blood flow within them during systemic shifts in hemodynamics].

In anesthetized cats, with the aid of the method of television line single out, the diameters of mesenteric microvessels and their blood flow were studied. The diameter of the flow in arterioles and venules was shown to undergo greater changes than the diameter of the microvessels proper, although a close correlation was revealed between both parameters. The above differences of the changes of diameters are more obvious during dilatory responses. The changes depend on the initial caliber of the arterioles and venules.


[Sike activity of low-threshold stretch receptors in the lungs of cats under dynamic conditions].

The disharge frequency at the end of inspiration was by 13--19% higher and during expiration--by 18--20% lower than at the corresponding lung volume under static conditions. The influence of dynamic factor on impulse activity of low-threshold pulmonary stretch receptors was relatively weak ("volume receptors"). Afferent output from pulmonary stretch receptors during inspiration is 8 times as great as at the expiratory phase. During inspiratory efforts after tracheal occlusion the afferent output was 2 times, and during expiratory phase--1.5 times as great as the afferent output during expiration before the occlusion. The dynamic lowering of discharge frequency in fibers o pulmonary stretch receptors aid to the shortening of expiratory phase.


In vitro suppression of macrophage spreading caused by supernatants of tumour, thymus, and lymph node cells.

Peritoneal macrophages washed out from C3Hf/Bu mice were cultivated in medium 199 supplemented with 35% foetal calf serum. If the pH of the medium was adjusted to 7.2, there were 70% spread macrophages after six hours of incubation at 37 degrees C. We investigated the effect of tumour cells on macrophage spreading. Supernatants from cell cultures of a fibro-sarcoma of C57BL mice and lymphoma of C3Hf/Bu mice were used to determine the number of spread macrophages after 6 hours of culture in these supernatants. Supernatants from cell cultures of the kidney, thymus and lymph nodes of normal C57BL or C3Hf/Bu mice and peritoneal cells of normal C3Hf/Bu mice in medium 199 alone served as control. We observed that supernatants from both allogeneic and syngeneic tumour cell cultures reduced significantly the percentage of spread macrophages in comparison with the percentage of spread macrophages found in the kidney culture supernatants. However, a similar spreading inhibition was caused also by supernatants from the thymus and lymph node cell cultures. In these experiments we confirmed the earlier observations that tumour cells can suppress the activation of macrophages, and we also pointed to the possibility that this effect is not specific only for malignant tissues.


Attempts to characterize cellular mechanisms of immunologic tolerance to HSA in chickens.

Partial suppression of antibody formation in neonatally induced tolerance to HSA as observed during immunization at 6 weeks of age or at a later time, is caused mainly by a rapid escape from tolerance. The following findings support this view: 1. After immunization at 4 weeks of age with a larger dose of HSA, which elicits detectable circulating antibody formation in all control birds, anti-HSA antibodies cannot be demonstrated in a large majority of tolerant chickens. 2. Surgical bursectomy performed in tolerant birds on the day of hatching or 7 or 11 days after hatching increases considerably the degree of suppression of anti-HSA antibody formation and slows down the return of reactivity to HSA. These findings suggest that new immunocompetent cells originating in the bursa are responsible for escape from tolerance in this experimental system. The existence of suppressor cells in birds tolerant to HSA was not demonstrated by the transfers of spleen cell mixtures from immune and tolerant donors to young, irradiated recipients.


Nucleoli in human pseudostratified columnar epithelium cells. (Microscopic classification of nucleoli).

The human pseudostratified epithelium was investigated to provide more information on the incidence of main nucleolar types in its epithelial cells. The compact nucleoli or nucleoli with nucleolonemas investigated by light microscopy were usually present in epithelial cells with highly basophilic cytoplasm. The absence of these nucleoli and the presence of ring-shaped nucleoli and/or micronucleoli (reflecting the decrease or inhibition of the RNA synthesis) were observed in epithelial cells which were characterized by the diminished or disappeared basophilic properties of the cytoplasm. These observations indicating the gradual inhibition of the nucleolar (ribosomal) RNA suggest that similar maturation processes may occur in investigated human pseudostratified columnar epithelium which are known for cell lines of the mesenchymal origin.


Latex particle adherence (LPA) test for identification of adherent and non-adherent leucocytes.

A new simple and rapid in vitro test is proposed for identification of adherent and non-adherent leucocyte subpopulations. The test based on adherence of latex (polystyrene) particles to the cell surface utilizes latex particle suspension commercially available for routine examination of the rheumatoid factor in blood of patients with progressive rheumatoid arthritis.


Binding of bull seminal ribonuclease (AS RNase) to human tumour tissues.

Homogenates of human carcinomas of the intestine, stomach, skin, ovary and penis absorbed AS RNase more intensively than the corresponding normal tissues.


[Malignant tumors of internal organs and dermatoses].

According to the author there are five possible kinds of relationship between visceral neoplasmas and diseases of the skin. 1. Instances in which neoplasma induces dermatosis (the so-called paraneoplastic diseases). 2. Instances in which defective immune mechanism or long-lasting immune suppression promote the development of neoplasma as well as of skin diseases due to microorganism and viruses. 3. Instances in which the tumor and dermatosis are associated without causal relationship. 4. Cases of malignant lymphoma arising from neoplastic  proliferation of the cells of the reticulohistiocytic system involving visceral organs and the skin. 5. Skin metastases of internal neoplastic processes.


[The Goltz-Gorlin syndrome].

The above described genodermatosis with its abundant symptomatology (ocular, dermatic, dental and bone changes) can be classified as Goltz-Gorlin Syndrom. It is believed that this case has a priority in the anomaly of the lycrymal organs which has not been described yet in the accessible literature.


[Cellular and humoral immune reactions in fungus allergy].

Cellular and humoral immune reactions upon the polysaccharide preparations of trichophyton-rubrum-cultures have been proved in the most of 185 examined patients. Quantitative and qualitative specific changes of the cells connected with their sensibilization, could be observed in the early period of trichophyton-rubrum-mycosis, in the course of the further development of the disease we also saw an accumulation of circulatory antibodies. Humoral reactions have become predominant. The peculiarity of humoral and cellular mycotic allergy may be responsible to a great extent for the polymorphism of the clinical symptoms of the disease, is persistent course and resistibility to the treatment.


[Skin vasoconstriction effect of contact antiphlogistics].

Five contact antiphlogistics were evaluated and compared to hydrocortisone by the human skin vasoconstriction assay in 20 volunteers. The test concentrations ranged from 10(-2) to 10(-6) w/w; the duration of occlusive application was 16 h. The substances could be ranked as follows in ascending order of activity (index values in relation to hydrocortisone).


Age-related changes in the reducible cross-links of human dermis collagen.

Samples of normal human dermis of different ages are reduced with tritiated sodium borohydride and changes of major reducible cross-links are compared as a function of chronological age. While lysinorleucine practically remains constant, reduced desmosine changes slightly, hydroxylysinoroleucine and dihydroxylysinonorleucine display a marked decrease with age. An unknown compound is shown to increase with aging. The data suggest a correlation between the change of aldimine cross-links and the structural and/or biochemical changes occurring with increase in age.


Hyperkeratotic form of porokeratosis Mibelli.

A case with a hyperkeratotic form of porokeratosis Mibelli is reported. The clinical characteristics were a nonfamilial occurrence, hyperkeratotic verrucous plaques with an erythema and a segmental distribution. The histopathology showed cornoid lamellae and additional atypical findings. By electron microscopic study Civatte bodies and other degenerated epidermal cells were clarified.


Photochemotherapy in treatment of psoriatic variants.

Our procedure for treating psoriatic variants--psoriasis pustulosa generalisata (PPG) and psoriasis erythrodermica (PE)--was based on the following points: (a) to quickly obtain a good tolerance level to photochemotherapy (PUVA) by applying corticosteroids and/or methotrexate (MX); (b) to discontinue the application of systemic drugs with the help of photochemotherapy, and (c) to maintain the improved condition by applying radiation in gradually prolonged intervals, thus enabling the biologic forces of the organism to participate, undisturbed by drugs, in the healing process. In some PE cases, sole PUVA therapy was sufficient, while in others small doses of MX were added to maintain the improved condition. In PPG, skin manifestations completely disappeared and general symptoms were calmed in the first application of this combined therapeutic procedure. However, in the later relapses PUVA had little share in such a combined treatment.


The relationship of amniotic fluid insulin levels and the lecithin-sphingomyelin ratio.

Amniotic fluid insulin levels and the lecithin-sphingomyelin ratio were determined in 62 samples of 33 insulin-dependent diabetic patients from the 29th to the 44th week of gestation inclusive and in 42 samples of 38 gestational diabetic patients from the 35th to the 43rd week of gestation inclusive. (Gestational age was measured by ultrasonography.) The level of insulin in the amniotic fluid did not appear to affect the lecithin-sphingomyelin ratio.


Fetal movements recorder, use and indications.

A new device for recording fetal movements is presented. This device is composed of 2 sensors, incorporating a highly sensitive piezoelectric material. It is sensitive to rapid straining forces such as fetal movements and relatively insensitive to steady, slow movements such as uterine contractions and maternal respiratory movements. In this study of 20 women, the sensors were placed on 2 different zones of the abdomen, usually above the umbilicus. There was a good correlation between fetal movements recorded by the device and those felt by the patients. Seventy percent of all observed fetal movements recorded by the device were registered simultaneously by the women. The device recorded 90.4 percent and the women recorded 79.7 percent of all such movements.


The testicular feminization syndrome: a report of two cases.

Two cases of complete testicular feminization syndrome are presented. The relevant clinical features and laboratory findings are summarized. Some interesting aspects of this syndrome are surveyed.


Hemodynamic effects of oral contraceptives during exercise.

The effects of a combined oral contraceptive pill on female hemodynamics during exercise were studied in 14 young, healthy women. The increase in blood volume, stroke volume, and cardiac output during exercise was significantly greater during combined oral contraceptive therapy than when the patients were not taking the pill. The use of combined oral contraceptive pills may be advantageous to the physical fitness of female athletes.


Secondary liposarcoma of the ovary.

This report is the first description of a secondary ovarian liposarcoma. The primary growth was in the mediastinum. The growth rate of the ovarian tumor was very rapid, but the patient died of cardiopulmonary causes. The mode of spread is discussed, and it probably occurred by transcelomic migration and surface implantation.


Psychological sequelae of sterilization in women in Singapore.

The Chinese in Singapore erroneously believe that there is an association between sterilization and castration. This belief has led to deep-seated fears that sterilization may result in obesity, physical weakness, and impairment of sexual function. Beginning in 1969, Singapore authorities introduced increasingly stronger social policies to help reduce family size. Subsequently, there was a large increase in the number of tubal ligations. It was initially thought that this might result in a high incidence of psychological sequelae. A study of 150 women who had had culdoscopic ligations showed that 6.3 percent were dissatisfied at the end of 2 years. Women with fewer than 4 children and those with fewer than 2 sons tended to be more dissatisfied with sterilization.


Amniotic fluid embolism: a review of the literature with two case reports.

Amniotic fluid embolism (AFE) is a rare but dramatic obstetric complication. In this study, the pathogenesis of AFE and the disorders of coagulation and fibrinolysis and postmortem gross pathologic and histologic findings resulting from it are reviewed. The 2 case histories examined in this report exemplify different clinical courses of amniotic fluid embolism. In the first case, there was a predominant activation of the coagulation system, with a fatal outcome. In the second case, generalized fibrinolysis dominated, and the woman survived. Finally, the authors wish to emphasize that the administration of fibrinogen is an incorrect approach to the management of this syndrome. A combination of Macrodex and heparin might be effective in preventing the formation of microthrombi, but increased fibrinolysis has to be treated by a sufficiently high dose of fibrinolytic inhibitors.


Carcinoma of the cervix uteri in Ibadan: coital characteristics.

Carcinoma of the cervix uteri has been found to be the most common female malignancy in Ibadan, excluding the reticuloendothelial tumors. In a study to investigate associated etiological factors in this environment, it was demonstrated that certain coital characteristics of women with cervical cancer can be identified. These were a common denominator which could explain the frequency of the disease among some categories of patients who engage in early sexual practice, have intercourse frequently and with multiple partners, and have many pregnancies. Support was given to the view that a sexually transmitted factor might be important in the cause of carcinoma of the cervix.


Changes in menstrual cycle length and regularity after use of oral contraceptives.

This is an analysis of changes in menstrual cycle length and regularity occurring for a group of 211 women who had discontinued use of oral contraceptives. The analysis is based on prospectively recorded histories from the Menstruation and Reproduction History Program. Post-pill menstrual cycle length and regularity are compared with pre-pill averages. In the first post-pill cycle, there was an average increase of 6 days in cycle length. In subsequent cycles, however, cycle length and regularity were comparable to pre-pill norms in most cases.


The benefit of lactation amenorrhea as a contraceptive.

A group of 148 lactating women who delivered normally at El-Galaa Hospital, Cairo, were followed up monthly for 1 year to study the pattern of lactation amenorrhea, the return of menstruation and ovulation, and the incidence of pregnancy. By the end of the sixth week postpartum, only 1.3 percent of the women had begun menstruating; the percentage gradually increased to 60.2 percent by the end of the first year. The amount of blood loss and the duration of menstruation increased gradually until the fourth postpartum menstrual period. Ovulation had occurred in 58.1 percent and pregnancy in 26.1 percent of all cases at the end of the 12th postpartum month. Among menstruating, lactating mothers, ovulation occurred in 86.5 percent and pregnancy in 32.6 percent, while in amenorrheic, lactating mothers only 6.1 percent had become pregnant at 1 year postpartum.


Perspectives in evaluating the safety and effectiveness of steroidal contraceptives in different parts of the world.

While differences in acceptability of steroidal contraceptives from nation to nation are generally recognized, variations in safety and effectiveness have been given little attention. Cardiovascular hazards such as thromboembolic disease, myocardial infarction, and stroke, which create such concern in developed countries, may be insignificant problems in other parts of the world where these diseases are rare in women of reproductive age. On the other hand, the influence of nutritional deficiencies, anemia, intestinal parasitism, malaria, and other widespread health problems on the effects and/or metabolism of steroids, which may be of major concern in developing countries, is just coming under study. Side effects also vary greatly among religiously and ethnically different populations, and significant differences in pregnancy protection and bleeding patterns among different populations have been reported-even with injectables. It is, therefore, important to examine and define intergroup differences and especially to recognize that safety concerns in one geographic setting cannot be automatically assumed to apply equally in other areas.


Medicated intrauterine devices to improve bleeding events.

In an attempt to find an IUD that will cause a minimum amount of blood loss, while continuing to be effective and easily retained, we are studying 4 medicated IUDs: a copper-bearing Lipps Loop, a Copper-T-200, a progesterone-releasing U-coil, and a tranexamic-acid-releasing Lippes Loop. Inert devices of the same shape and size are used as controls. This is a comparison of the findings on menstrual blood loss and loss and changes in bleeding patterns for patients using the plain and copper-bearing Lippes Loops. Preliminary results for the progesterone-bearing U-coil and the tranexamic-acid-releasing Lippes Loop are also given, but studies of these devices are not yet complete.


IUD insertions by midwives: five years' experience in Santiago, Chile.

This report includes data on insertions of Lippes Loop D, Copper-7, and Copper-T intrauterine devices (IUDs) performed by certified nurse-midwives and physicians with comparable levels of training and experience in inserting IUDs. Net 1-year pregnancy, expulsion, and removal rates were used to compare the experiences of the 2 groups. There were no significant differences between the groups in most of the event rates or in the overall method discontinuation rates. The authors conclude that, with adequate training and experience, nurse-midwives can provide this family planning service with no additional risk to patients.


Induction of abortion with 15(S)-15-methyl PGF2alpha (Tham) vaginal suppositories.

The repeated administration of vaginal suppositories containing 1 mg 15(S)-15 methyl PGF2alpha (Tham) sucessfully induced abortions in 60 of 62 patients. Among patients who successfully aborted, the mean abortion time was 19.0 hours. The mean abortion time was not related to gestational age or parity. Sixty (96.8 precent) aborted within 48 hours, and 53 (85.5 percent) aborted within 24 hours. Gastrointestinal side effects occurred for 33.9 percent of the patients. Diarrhea was the most frequent side effect. The abortion was complete for 40.3 percent of the patients.


Response to prolactin and ovarian steroids of normal mammary epithelial cell cultures.

Mouse mammary epithelial cells in confluent primary monolayer cultures retain responsiveness to the specific hormones that induce mammary growth in vivo. Simultaneous stimulation by prolactin, progesterone and estrogen, in the presence of 5 percent fetal calf serum, is required to induce an increase in both thymidine uptake into DNA and in cell replication (as judged by mitotic indexes) over the hormone-free control. This increase in mitogenic response could not be elicited in either mouse fibroblasts or in mouse mammary tumor cells, the latter known to be hormone insensitive.


Binding of [3H]tamoxifen in rat uterine cytosols: a comparison of swinging bucket and vertical tube rotor sucrose density gradient analysis.

The interaction of the antioestrogen tamoxifen with rat uterine oestrogen receptor has been studied using swinging bucket and vertical tube rotor techniques of sucrose density gradient analysis. Tamoxifen inhibits the binding of [3H]oestradiol to the 8S oestrogen receptor protein whereas using the swinging bucket rotor technique of sucrose density gradient analysis [3H]-tamoxifen appears to bind to an oestradiol specific protein which sediments at 4-5S. In contrast, using rapid sucrose density gradient analysis with a vertical tube rotor [3H]tamoxifen shows oestrogen specific binding in the 8S region. It is suggested that conventional techniques of sucrose density gradient analysis are unsuited for the investigation of the low affinity ligand interactions with oestrogen receptor proteins since rapid dissociation of complexes can result in ligand binding to nonreceptor proteins.


Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens.

Metabolic transformations of progesterone in cultures of granulosa cells from immature hypophysectomized rats treated with diethylstilbestrol were studied in relation to the synergistic action of exogenous androgen and FSH on progestin (progesterone and 20alpha-dihydroprogesterone) accumulation. Androstenedione (Ad; 10 ng/ml) enhanced the sensitivity of rat granulosa cells to this steroidogenic action of FSH, lowering the threshold of the response from greater than 4 ng/ml (FSH alone) to 0.8 ng/ml in the presence of Ad. A synergistic effect with FSH was also shown by various 5alpha-androstane derivatives. They were, however, less effective than the parent delta4-3 keto androstenes. Progesterone underwent extensive 5alpha-reduction during culture, leading to accumulation of endogenous 5alpha-pregnane compounds, and to transformation of labelled progesterone into 5 alpha-reduced radiometabolites. These compounds corresponded in gas-liquid and thin-layer chromatographic behaviour to 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha,20alpha-diol. The rate of 5alpha-reduction of progestins was not affected by the presence of exogenous Ad (1 microgram/ml), ruling out the possibility that the effect of androgen on progestin accumulation depends on competitive inhibition of 5alpha-reductase. An involvement of androgen of thecal origin in the enhancement of the sensitivity of the FSH-responsive mechanism in granulosa cells is suggested.


Nuclear translocation of the estradiol receptor: partial inhibition by ethidium bromide.

Ethidium bromide (EB), an intercalating drug, has been shown to prevent the in vitro interaction of the estrogen receptor (R) with DNA (André et al., 1976). We have now studied the effect of this drug on the nuclear translocation of R in order to determine whether DNA integrity is needed for this translocation. In a cell-free reconstituted system made of purified nuclei and cytosol, the pretreatment of nuclei by EB prevented approximately half of the R nuclear translocation, but was unable to extract more than 17% of the E2-R previously translocated. A series of indirect evidences suggests that EB inhibits the nuclear translocation of R by interacting with nuclear DNA. The degree of the inhibition was related to the amount of drug bound to nuclei and was in agreement with the degree of ultrastructural modifications of chromatin. R was not irreversibly altered by the drug. The EB inhibition was only observed with DNA-containing particles and with estrogen receptor able to bind to DNA. In surviving uteri the drug also inhibited the R nuclear translocation. These resuts indicate two types of nuclear translocation of R, one sensitive and the other resistant to EB, and suggest that DNA is required for the EB-sensitive translocation.


In vitro synthesis of rat testicular androgen-binding protein (ABP).

Testicular tissue from immature and adult rats shows in vitro synthesis of androgen-binding protein (ABP). The ABP synthesis is dependent on a complete tissue culture medium, the incubation temperature and the age of the rats. ABP synthesis is inhibited at 0 degrees C or in the presence of cycloheximide, puromycin or sodium fluoride. Immature (17-25-day-old rat) testes showed a higher rate of ABP synthesis per 100 mg tissue than adult rat testes during 'baseline' conditions (no additions to the medium). Addition of NIH-FSH-S10 or testosterone to the medium increases the production of ABP by the testicular minces. The in vitro techniques have proved to be useful for studies of direct hormonal influence on the Sertoli cell protein synthesis.


[A semi-automatic system for the analysis of ecocardiographic tracings (author's transl)].

A semi-automatic system is described for analysis of echocardiographic traces of the left ventricle. Filtering interpolating and averaging processes are discussed and the overall accuracy evaluated. The program is able to calculate ventricular indexes (strake volume, ejection fraction, circumferential velocity of fiber shortening), continuous functions (istantaneous ventricular diameter and volume, wall thickness, velocity of cavity compression and dilation) and, correlating the echo data with pressure values, circumferential stresss and ventricular compliance. Pressure is obtained along the ejection phase only from the carotidal pulse calibrated by means of the brachial pressure values. Advantages and limits of the method are discussed.


[The antiarrhythmic effects of verapamil in acute myocardial infarction. Considerations on the possible action mechanism (author's transl)].

In 12 patients affected by acute myocardial infarction complicated only by ventricular extrasystoles, verapamil was highly effective in the control of the arrhythmias. This result is in agreement with the experimental finding that ischemia inactivates partially or totally early Na+ inward currents, so that fast fibers become slow fibers. The efficacy of verapamil stresses the importance of these fibers which have acquired a slow response in the genesis of arrhythmias due to acute coronary attacks and opens interesting therapeutical prospects.


[Hyperglycemia in acute myocardial infarction (author's transl)].

50 non-diabetic patients, less then 70 y.o. and with fasting blood sugar (FBS) subsequently proved to be normal, consecutively admitted to the Coronary Care Unit by the 10th hour of acute myocardial infarction (AMI), have been studied. Blood sugar (BS) and white blood cell count (WBC) on admission and serum CPK every four hour until the 36th hour, have been determined. Oral glucose tolerance test (OGTT) has been performed at least one week later, when FBS has been determined. In 16 patients with normal OGTT the test has been repeated twice, 4 to 15 months later, before and after a cortisone load. Data have been statistically computed. Mean blood sugar on admission was significantly higher then mean FBS. No correlation was found between BS and WBC neither between BS and maximal CPK. No significant difference has been found between the mean BS on admission among 25 patients with normal OGTT and the one among the remaining 25 patients with abnormal OGTT. The OGTT was confirmed to be normal in the 16 patients belonging to the former group, who had the test repeated, with a single exception as far as the cortisone-OGTT is concerned. The above results are consistent with the opinion that the hyperglycemia usually observed during the first hours of AMI, is related to the acute medical stress and in no way indicates subclinical and/or latent diabetes.


[Effects of oxyfedrine on sino-atrial function and on conduction in patients with sinus node and/or atrial dysrhythmias (author's transl)].

The electrophysiological effects of Oxyfedrine on sino-atrial function and on A-V junctional and subjunctional conduction have been studied in 16 patients with sinus node and/or atrial dysrhythmias. The following effects have been observed: --a positive chronotropic effect on the sinus node; --an essentially indirect (rate-dependent) shortening of the Functional and Effective Refractory Periods (FRP and ERP) of the atria without variation of the Intra-Atrial Conduction Time (HRA-LRA). There was no significant shortening of the Maximal Atrial Latency (max AL), of the Corrected Sinus Node Recovery Time (CSNRT) and of the Sino-Atrial Conduction Time (SACT). The limits of Zones I, II, III of the sinus node response to atrial extra-stimuli were reduced with no significant change in their duration, expressed as percentage of the Sinus Cycle Length (SCL); --an improvement in the A-V junctional conduction (shortening of the A-H interval for comparable cycle lengths) due to a relatively shortened A-V junctional ERP. The use of the drug in patients with sinus bradycardia and/or atrial dysrhythmias and conduction disturbances, is proposed.


[Intraventricular conduction delays, ventricular pre-excitation and ventricular repolarization anomalies of familial character (author's transl)].

An examination is made on different members of a family in which, owing to hereditary transmission of dominant autosomal type, exist alterations that sometimes manifest with disorders of the intraventricular conduction, sometimes with more or less pronounced aspects of ventricular pre-excitation and some other time with anomalies of the ventricular repolarization phase. In examining the genealogical tree of the family, there are in the fourth generation five cases of short PQ-normal QRS syndrome and one case with ventricular repolarization anomalies; in the third generation six cases with left anterior hemiblock, one case with short PQ-normal QRS syndrome, one case with Wolff-Parkinson-White syndrome and three cases with ventricular repolarization anomalies; in the second generation three cases with bundle branch block associated with left anterior hemiblock. The clinical laboratory investigation permitted to exclude the presence of congenital or acquired heart diseases which, rather frequently are responsible for documented electrocardiographic anomalies; the morphology and cardiac volumetry, put in evidence by radiological examinations, remained within the limits of the normal.


[Congenital mitral valve malformations. Anatomical lesions and surgical treatment in paediatric age (author's transl)].

Congenital mitral valve malformations are diverse. When they present clinically in infancy medical treatment is often ineffective. Mitral valve replacement with prosthesis in children carries an high operative and postoperative risk. For these reasons the Authors have undertaken in 1972 a cooperative study which includes: 1) a surgical classification of the congenital mitral valve lesions; 2) a systematic attempt to repair the mitral valve. Over 43 observed cases, 18 have been operated upon. Eleven cases (61%) presented associated cardiac lesions. Hospital mortality was 16% (3 cases). There have been either mortality nor morbidity in the follow-up period. Eight cases have been recatheterized two years after the operation. The pulmonary artery pressure has significantly decreased and the mitral insufficiency disappeared almost completely. The classification, suggested by the Authors, is explained in details.


[Study of the precision and limitations in measuring left ventricular pressure and its first time-derivative (author's transl)].

The precision in measuring left ventricular pressure and its first time-derivative has been evaluated with the study of the physical caracteristics of a system currently used for pressure wave sampling. Besides the different catheters, the set-up tested consists of a nylon connector (110 cm) and of two three way stopcocks. Amplitude and phase response, from 1 to 60 Hz, have been obtained testing the system with sinusoidal pressure waves generated by an hydraulic oscillator. Despite mild differences dependent on the different catheters, the system amplifiers remarkably at frequencies above 5 Hz. Above this limit the harmonic content of the left ventricular pressure wave is negligible and can be ignored in defining the basic morphology and the absolute values of the curve. Similary, the amplification of these high frequency harmonics operated by the system does not affect appreciably pressure measurements. In the case of the pressure time-derivative the significant harmonic content is shifted toward higher frequencies. For this reason a reliable dp/dt cannot be obtained with this hydraulic set-up. A maximal hypothetic error, utilizing a Cook 5.2 F 105 cm catheter, of 8-9% and 28-31% has been estimated for pressure and time-derivative measurments respectively.


[The effort test in the diagnosis of typical stable effort angina (author's transl)].

Among 173 patients with typical effort angina (159 men and 14 women) which underwent exercise test and coronary angiography, significant stenosis (greater than or equal to 70%) of one or more of important coronary branches were present in 93,1% of the cases (96,3% among the males and 57% among the females). In the same group the exercise test sensitivity was 88,8%; when 3 coronary branches were involved the sensitivity rises to 94,3%. The 96,6% of patients with positive exercise test had coronary lesions too (true positives). We did not find any correspondence between the site of transient subendocardial ischemia occurred during the exercise test and coronary branch involved, when the stenosis was limited only one important coronary branch. Finally the researche of correlation between the entity of coronary disease (number of coronary vessels involved, entity of left ventricular contractility impairment) and behavior of patient during exercise test, evaluated with different parameters measured at the moment of stopping of exercise (heart rate and threshold work load, rate-pressure product, maximal downsloping of ST segment, different positivity criteria for exercise test) allowed us to show a good correlation only between the extent of coronary involvement and rate-pressure product or maximal downsloping of ST segment.