Pharmacokinetics of fluoride in man after single and multiple oral doses. The doses of fluoride (F) recommended in the literature for caries prevention and for the treatment of osteoporosis vary. This partly reflects inadequate knowledge of F pharmacokinetics. In the present study various single and multiple oral doses of F were given to eight volunteers, who had a strictly controlled F intake in the diet. The resulting plasma and parotid saliva concentrations as well as urinary output of F were measured. The plasma data fitted a two-compartment open model with a beta-slope half-life ranging between 2 and 9 h. Plasma clearance was 0.15+/-0.02 (SD) liter/kg/h. Data from the highest dose (10 mg) were fitted to both two- and three-compartment models, and there was no significant difference between them. Multiple doses of F 3.0 Or 4.5 mg yielded steady state concentrations ranging from 54 to 145 ng/ml. About 50 per cent of the given dose was recovered in the urine, which is indicative of considerable accumulation in the body. The saliva F/plasma F concentration ratio was 0.64 with a coefficient of variation of 5%.


Immunological properties of two related fragments from human and equine growth hormones. The immunological properties of a synthetic human growth hormone fragment comprising the amino acids 73 through 128 and of the homologous natural horse growth fragment formed by amino acids 73 through 123, have been comparatively studied. Antisera obtained in rabbits inoculated with the native human hormone or with the fragments, were used. By hemagglutination experiments both fragments have the same reactivity toward the anti-human growth hormone serum, but complement fixation curves detect the existence of at least two populations of antibodies presumably originated against the sequence 73-128 of human growth hormone. Of these, only one of the corresponding antigenic areas is present in the homologous region of equine growth hormone. The known cross-reactivity detected between both hormones is thus partially explained.


Identification of the effector cells in human blood displaying spontaneous cytotoxicity to chicken erythrocytes. By combining velocity and linear density fractionations as well as target cell rosetting techniques we have isolated and morphologically identified the human effector cell type responsible for spontaneous, trypsin-augmentable cytotoxicity against chicken red cells and human myeloma cell line targets. This cell is a large lymphoid cell with strong alpha-naphthyl esterase activity concentrated in a limited area in the cytoplasm usually at the indentation site of a slightly reniform nucleus. Cells with this morphology also formed plaques on chicken erythrocyte monolayers. The cell is nonphagocytic and nonadherent, it carries Fc receptors but no complement receptors on its surface, and shows a weak affinity to sheep red blood cells (SRBC). The frequency of these cells based on morphological analysis is 3 x 10(4)--6 x 10(4)/ml in normal human blood. This cell shows similarities (surface Ig-, Fc+, C3-) with the human natural killer (NK) cells lytic to hematopoetic target cell lines but differs in that the cytotoxicity is augmentable by trypsin and the affinity to SRBC is lower. Therefore, we postulate that these two killer populations represent different subpopulations of human NK cells.


Autoagglutinin produced by organ fragment cultures of mouse spleen. Mouse spleen fragment microcultures produced a heat-labile substance which agglutinated syngeneic erythrocytes. The substance reacted with an antigen present on some strains of mouse erythrocytes and on rat erythrocytes, but absent from other strains of mouse erythrocytes and from guinea pig, rabbit or sheep erythrocytes. Agglutination was inhibited by antisera to mouse immunoglobulins except for antisera specific to mouse IgM which enhanced agglutination. The agglutinin sedimented with 19 S Ig on ultracentrifugation and was destroyed by pretreatment with mercaptoethanol. Using a rosette assay increased numbers of cells, specifically binding syngeneic erythrocytes by means of a surface Ig receptor were demonstrated in spleen fragment microcultures. It is considered that the agglutinin is a noncomplement-activating IgM autoantibody and that the precursors of the cells producing the autoantibody are detected by the rosette assay.


Natriuretic and phosphaturic response to diuretics after parathyroidectomy in dogs. Intact and acutely parathyroidectomized (TPTX) dogs were studied during hydropenia, volume expansion (VE), volume expansion plus ethacrynic acid (EA), and volume expansion plus acetazolamide (AZ). In intact dogs, VE produced marked increases in both Na+ and phosphate (Pi) excretion; in TPTX dogs, Na+ excretion increased but phosphaturia was minimal. Addition of EA increased Na+ but not Pi excretion in both groups. Discontinuing EA and substituting AZ in intact dogs produced a marked increase in Pi excretion compared to both VE and VE + EA. In TPTX dogs, AZ failed to increase Pi excretion compared to VE alone. The results suggest that increased distal Pi absorption in acutely TPTX dogs is not associated with NaCl reabsorption in the thick ascending loop of Henle or may occur at an alternative nephron site. Furthermore, the increased distal Pi reabsorptive capacity revealed by TPTX can overcome the increased distal Pi delivery produced by the superimposition of AZ on VE.


An evaluation of the coronary constriction following propranolol. This study attempts to determine whether a direct coronary vasoconstriction follows beta blockade with propranolol. Coronary blood flow was varied with the aid of a pump. When myocardial contractile force was plotted as a function of coronary blood flow a characteristic biphasic curve resulted. Autoperfusion without the pump resulted in a flow rate which fell on the knee of that curve. Any direct vasomotion therefore should shift that autoperfused flow rate off of that knee. When propranolol was given intravenously at 0.5 mg/kg a new contractile force--flow curve resulted but the autoperfused coronary blood flow remained at the knee of the curve. Since these data indicate that coronary flow fell precisely in proportion to myocardial metabolism it is concluded that all coronary vasoconstriction following propranolol is secondary to changes in metabolism.


Effect of prolonged treatment with adrenergic neuron blocking drugs on sympathoadrenal reactivity in rats. The effects of repeated high doses of the adrenergic neuron blocking drug guanethidine or a hexahydropyrazinoindole compound (2-guanyl-1,2,3,10,10a, hexahydro-1,2,a-pyrazinoindole, EMD 21192) (30 mg/kg i.p., 21.5 mg/kg i.p. respectively, equimolar doses) on sympathoadrenal activity were investigated in normotensive adult rats. During treatment for 5 weeks with either guanethidine or EMD 21192 the systemic blood pressure fell steadily. Noradrenaline content in the heart and vas deferens were decreased markedly by guanethidine and to a much less degree by EMD 21192. EMD 21192 markedly lowers the catecholamine content of the adrenal medulla, presumably as a result of inhibition of dopamine-beta-hydroxylase. The plasma catecholamine concentrations reflected the different sites of action of the drugs in the sympathoadrenal system, i.e. guanethidine mainly reduced circulating norepinephrine and dopamine-beta-hydroxylase by more than 50%, whereas EMD 21192 decreased considerably by the total catecholamines (mainly epinephrine) without altering significantly in the plasma norepinephrine. Disappearance or reduction of fluorescent nerve endings in the iris and the heart and a decrease of the intensity of fluorescence in chromaffin cells of the adrenal gland caused by the drugs were consistent with the biochemical alteration. Whereas the repeated doses of guanethidine caused degeneration of sympathetic nerves, destruction of adrenergic neurons was not found after prolonged treatment with EMD 21192.


3H-metaraminol releasing action of mescaline from rat hypothalamus in vitro. The amine releasing action of mescaline was investigated in rat isolated hypothalamus labeled with 3H-metaraminol. Mescaline had no effect on the uptake of 3H-metaraminol but produced its release in a concentration-related manner. 4 x 10(-4) M mescaline, which produced submaximal effects was used for subsequent experiments. 3 x 10(-5) M cocaine had no effect on the 3H-metaraminol releasing action of mescaline. Mescaline was fully effective in Ca2+-free medium while 6 x 10(-2) M KCl was ineffective. 3 x 10(-7) M tetrodotoxin or 6 x 10(-5) M lidocaine partially blocked mescaline-induced release but substantially or completely blocked 3 x 10(-2) M KCl-induced release. Prior exposure of hypothalamus to 3 x 10(-4) M tyramine reduced the releasing action of mescaline. Thus, mescaline appears to release 3H-metaraminol both by Ca2+-independent (tyramine-like) and Ca2+-dependent (lidocaine-sensitive) mechanisms. 3 x 10(-4) M tyramine and 6 x 10(-2) M KCl released 14C from control hypothalamus labelled with 14C-mescaline, but not from reserpinized hypothalamus. The amounts of 14C recovered in 14C-mescaline labeled control and reserpinized hypothalamus at the end of 50 min of efflux were similar suggesting a poor retention of 14C-mescaline by storage particles.


Inability of naloxone to change brain morphine levels in tolerant mice. The effect of naloxone on brain morphine concentrations was measured in naive and morphine-dependent mice using radioimmunoassay and gas-liquid chromatography. No displacement of morphine from the brain by naloxone could be observed in naive mice acutely injected with morphine or in pellet-implanted mice at increasing intervals after removal of the morphine pellets. The suggestion of a change in affinity of opiate receptors during the development of tolerance/dependence, which had been made on the basis of the displacement of morphine by naloxone found by other workers, is thus not supported by the present results.


Direct or indirect action of histamine on dopamine metabolism in the rat striatum? Intraventricular administration of 500 microgram of 2-pyridylethylamine, an agonist of the histamine (Hi) H1-receptor, produced a 20% increase of striatal HVA in the rat while the Hi H2-receptor agonist 4-methylhistamine had no influence on HVA and DOPAC levels. L-Histidine (1.5 g/kg) or amodiaquine (60 mg/kg) given i.p. increased HVA and DOPAC levels to the same extent as did pyridylethylamine. Histidine combined with tremorine had an additive effect with respect to the increase of DA acidic metabolites while mepyramine slightly attenuated the tremorine-induced rise of HVA.


Increased dopamine release from rat striatal slices by inhibitors of GABA-aminotransferase. The effects were examined of two inhibitors of GABA-aminotransferase, amino-oxyacetic acid (AOAA) and RMI-71645-16, on depolarization-induced (30 mM K+) dopamine (DA) release from rat striatal slices. When added to the medium, these drugs increased the release of radiolabeled DA, either accumulated by high-affinity uptake or synthesized from 14C-tyrosine. AOAA did not modify the release of 14C-acetylcholine from striatal slices or 3H-noradrenaline from cortical slices. Moreover, 3H-DA release from substantia nigra was not affected. The data suggest the possibility that the effects of GABA-T inhibitors on striatal DA release are mediated by intrinsic GABA-ergic neurons.


Biphasic nature of the effects of delta9-tetrahydrocannabinol on body temperature and brain amines of the rat. The effects of i.v. injected delta9-tetrahydrocannabinol (delta9-THC) on behaviour, body temperature and levels of brain monoamines, measured spectrophotofluorimetrically, of the rat were determined. Doses of delta9-THC in the range of 0.05--5.0 mg/kg produced biphasic changes in behaviour, body temperature and levels of 5-hydroxyindoleacetic acid (5-HIAA). The whole brain levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were not altered by delta9-THC. The subjective behavioural biphasic responses did not appear to be dose related, whereas the biphasic changes in body temperature and brain levels of 5-HIAA were dose-related. Low doses of delta9-THC (0.05 and 0.1 mg/kg) caused hyperthermia, while doses of 1.0, 2.0 and 5.0 mg/kg induced hypothermia. On the other hand, 0.05 mg/kg delta9-THC significantly reduced, whereas doses of 1.0, 2.0 and 5.0 mg/kg significantly increased the 5-HIAA levels in a dose-related manner. It is concluded that an inverse relationship exists between delta9-THC-induced changes in body temperature and alterations in brain 5-HIAA levels.


The interaction between noradrenaline and 5-hydroxytryptamine in the isolated perfused rat hindlimb. The vascular response to bolus injections of 5-hydroxytryptamine (5HT) over the range 0.01-10.0 microgram was measured in isolated perfused rat hindlimbs. The hindlimb vasculature displayed a vasoconstrictor response to 5HT, which was potentiated by the addition of 0.01 microgram/ml noradrenaline (NA) to the perfusate at all doses tested. The response to 5HT was also enhanced by the monoamine oxidase (MAO) inhibitor, tranylcypromine (0.05 mg/ml), suggesting that MAO located in the vascular wall is involved in the termination of the response to 5HT in the peripheral circulation. MAO inhibition abolishes the potentiation of 5HT by NA, indicating that this potentiation results from competition for MAO by both amines, leaving more amine intact to activate membrane receptors. Corticosterone (0.01 mg/ml), catecholamine extraneuronal uptake inhibitor, did not alter the response to 5HT, nor the increase of this response by NA, it thus appears that 5HT and NA have different membrane transport systems in the peripheral vasculature.


Adrenergic regulation of the plasma levels of purine metabolites in the rat. The effects of i.v. infusions of catecholamines on the plasma levels of uric acid and allantoin were investigated in the conscious rat. Isoproterenol and epinephrine, in this decreasing order of potency, remarkably elevated both uric and allantoin levels. Norepinephrine did not affect these purine metabolite levels. These effects of isoproterenol and epinephrine were completely abolished by propranolol. Phentolamine, on the contrary, slightly potentiated the effects of epinephrine. In contrast to i.v. fusion, s.c. injection of epinephrine had no effect, but, after prior treatment of animals with phentolamine, elicited striking increases in the plasma purine metabolite levels. Catecholamines thus caused hyperuricemia with a rise in plasma allantoin, both effects being mediated via beta-adrenoceptors and alpha-adrenergic mechanism sometimes functions in such a manner as to mask or inhibit this beta-mediated response.


Biphasic effects of amphetamine on striatal dopamine dynamics. S(+)-Amphetamine (AMPH) was administered to rats over the dose range 0.15-10.0 mg/kg (1.74(3)mumoles/kg) at various times before sacrifice. 15 min before sacrifice rats received an intraventricular injection of 3H-tyrosine, and the accumulation of striatal 3H-dopamine (DA) was assessed as an index of striatal DA formation and utilization. 3H-DA formation exhibited a biphasic dose response to AMPH. At 16 and 31 min after AMPH administration, 3H-DA accumulation increased linearly in response to AMPH to a maximal rate of 200% of control values at 1.0 mg/kg, then declined to less than 50% of control values at AMPH doses of 5 and 10 mg/kg. As a function of time, low doses of AMPH (to 2.0 mg/kg)) only increased 3H-DA accumulation, whereas high doses of AMPH (greater than 2.5 mg/kg) only decreased 3H-DA accumulation. All doses of AMPH increased endogenous levels of striatal DA. The data are discussed in terms of compensatory adaptive mechanisms of the nigrostriatal dopaminergic pathway.


Evidence for an inhibitory action of methyldopa on spinal sympathetic reflexes. The antihypertensive activity of methyldopa is mediated primarily by effects on the central nervous system. A number of centrally acting hypotensive substances has recently been shown to depress spinal pathways and reflexes as well as inhibiting supraspinal areas. The present series of experiments evaluated the potential influence of methyldopa on spinal mechanisms. Stimulation of an intercostal nerve evoked a two-component response (early and late) in the splanchnic nerve of anesthetized cats. The "late" phase involves supraspinal neurons, whereas, the "early" component involves only spinal pathways. The i.v. administration of 100 mg/kg of methyldopa reduced systemic blood pressure and both components of the evoked potential progressively. These experiments indicate that methyldopa exerts an effect of spinal sympathetic mechanisms which may contribute to the antihypertensive response to the compound.


Effect of pancuronium bromide on the adrenergic reactivity of the isolated rat vas deferens. Pancuronium bromide (10(-7) to 10(-4) M) failed to produce contraction of the isolated rat vas deferens. Also, no contractions were seen when the animals were pretreated with an MAO inhibitor (iproniazid 80 mg/kg, p.o.). On the other hand, pancuronium bromide (10(-6) to 10(-4) M) produced 1.62- to 2.65-fold increases in the sensitivity of the vas deferens to noradrenaline. This rules out an indirect adrenergic effect in this preparation and suggests an inhibitory effect on catecholamine uptake.


Conversion between configurational states of the muscarinic receptor in rat brain. Reductive alkylation of neural membranes by N-ethyl maleimide (NEM) converts muscarinic acetylcholine receptors from a state of low to high affinity for receptor agonists. Interactions of muscarinic antagonists with the receptor are unaffected by this treatment. Muscarinic receptors from the rat telencephalon in the high agonist affinity state are increased from 34.2 to 53.4% of the total receptor population and the Ki for carbamylcholine inhibition of 3-quinuclidinyl benzilate binding is decreased from 1.2 X 10(-4) to 6.9 X 10(-5) M by NEM treatment.


Involvement of central GABA receptors in the regulation of blood pressure and heart rate of anesthetized cats. Intracerebroventricular (i.c.c.) injections of muscimol (0.03-3 microgram/kg) and GABA (30-1000 microgram/kg) caused dose-related reductions in blood pressure and heart rate of anesthetized cats whereas glycine (30-3000 microgram/kg) was much less effective. I.v. administration of muscimol or GABA had little or no effect. Renal sympathetic nerve discharge was also reduced by central GABA receptor stimulation. The effects of both muscimol and GABA were reversed by either picrotoxin or bicuculline administered intravenously. The results suggest an important role for GABA receptors in the central regulation of blood pressure and heart rate.


An effect of beta-melanocyte stimulating hormone (beta-MSH) on alpha-motoneurones of cat spinal cord. Actions of beta-MSH and of melatonin on the recovery cycle of single spinal neurones were studied in the decerebrate-spinal cat. beta-MSH facilitated the rate of post-excitation recovery of alpha-motoneurones and some internuncial neurones, and melatonin inhibited the rate of post-excitation recovery. These observations provide additional evidence that beta-MSH functions in the nervous system as a modulator, and may help explain actions of beta-MSH in modifying acquisition of conditioned avoidance responses as well as its interaction with drugs such as morphine.


Effect of intracerebroventricular administration of morphine upon intestinal motility in rat and its antagonism with naloxone. Morphine, intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) administered to rats, inhibited intestinal propulsion as tested by a charcoal meal. Such an inhibition was shown to be linearly related to the log of administered doses for both routes of administration and the two linear regressions are parallel, so that morphine was calculated to be 206 times more potent when administered i.c.v. than i.p. A dose of morphine fully active by the i.c.v. route was completely inactive when injected by the i.v., i.p., i.m. and s.c. routes. Naloxone, administered i.c.v., blocked the antipropulsive effect of morphine i.c.v. or i.p. The pA2 of naloxone versus morphine, both administered i.c.v. was determined and calculated to be 7.14 (6.76-7.62).


A pharmacologic comparison of 3,4-methylenedioxyamphetamine and LSD in the chronic spinal dog. MDA (2.0 and 2.2 mg/kg) was compared to LSD (10 microgram/kg) and d-amphetamine (3.2 mg/kg) in single dose, antagonism, cross tolerance and appetite suppression studies. In single doses MDA specifically resembled d-amphetamine by producing marked mydriasis, nictitating membrane retraction, stereotypy and darting eye movements and LSD by markedly facilitating the flex or reflex, producing continuous stepping, whining and eye tracking movements. LSD and MDA increased respiration, body temperature and the latency of the skin twitch reflex and produced behavioral arousal. Cyproheptadine antagonized the effects of LSD but was ineffective against MDA. Phenoxybenzamine antagonized the respiratory, pupillary and hyperthermic effects of MDA and the respiratory effect of LSD. Chlorpromazine antagonized many of the effects of LSD and MDA. Spinal dogs were made tolerant to the behavioral and physiologic effects of LSD. Cross tolerance developed to some but not all of the effects of MDA. In intact dogs MDA was 1/10 as potent as d-amphetamine in suppressing appetite. It is concluded that MDA has properties resembling both LSD and amphetamine.


Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration. Repeated treatment with haloperidol and sulpiride induced tolerance to the increases in homovanillic and dihydroxyphenyl acetic acids in the striatum, nucleus accumbens, tuberculum olfactorium and frontal cortex of the rat. The threshold dose inducing this effect appeared to be lower in the striatum than in the limbic regions. Similar results were found in the frontal cortex by measuring dopamine utilization. Moreover, tolerance developed earlier in the striatum than in the limbic areas. The possible reasons are discussed for the differential development of tolerance in the various DA areas investigated.


3H-Spiroperidol labels dopamine receptors in pituitary and brain. 3H-Spiroperidol of high specific radioactivity labels dopamine receptors in membranes of bovine caudate nucleus and anterior pituitary. The saturation and kinetic properties of 3H-spiroperidol binding are similar in the two tissues. In both caudate and pituitary 3H-spiroperidol displays very high affinity with a dissociation constant of 0.2-0.3 nM. The relative potencies of numerous dopamine agonists and antagonists in competing for 3H-spiroperidol binding are closely similar in anterior pituitary and caudate.


Anticonvulsant action of thiabendazole.

Anticonvulsant action of thiabendazole. Thiabendazole was found to be specifically effective against maximal electroshock seizures in albino rats. It produced a significant dose-dependent decrease in the duration of the tonic extensor phase of hind legs. The ED50 was similar for oral or s.c. administration. PTZ-induced convulsions were unaffected by lower doses but aggravated by the higher dose studied.


Selective inhibition of noradrenaline and serotonin uptake by C 49802-B-Ba and CGP 6085 A. The effects of two new compounds, 1-(1-methylamino-2-hydroxy-3-propyl)-dibenzo[b,e]bicyclo[2,2,2]octadiene-HCl (C 49802-B-Ba) and 4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl (CGP 6085 A), on noradrenaline (NA) and serotonin (5-HT) uptake were investigated in different test systems, CGP 6085 A is a very potent and selective inhibitor of 5-HT uptake in rat brain (ED50 1-4 mg/kg p.o., depending on test system). Doses up to 1000 mg/kg p.o. did not inhibit NA uptake. C 49802-B-Ba is a potent and selective inhibitor of NA uptake in rat brain (ED50 5-10 mg/kg p.o. depending on test system) and heart (ED50 1.5 mg/kg p.o.). At 300 mg/kg p.o., this compound caused no inhibition of 5-HT uptake.


[Maintenance of mice in automatic rearing system. I. Rearing tests with ICR mice (author's transl)]. Female ICR:JCL mice were reared in wire-mesh cages with nozzles for automatic water supply on a battery with an automatic washing system, and the evaluation of this system was made in comparison with the conventional feeding system with water bottles, alumite cages and changes of the bedding. In weight gains, feed intakes, water consumption, leucocyte and erythrocyte counts, hematocrit values or vaious organ weights during the period from 3 to 14 weeks of age, animals maintained by the automatic rearing system showed no significant difference as compared with those maintained by the conventional system, providing evidence for a conspicuous labor saving with the automatic control system.


[Artificial insemination in the mouse with special reference to the effect of sperm numbers on the conception rate and litter size (author's transl)]. Mature female mice (ICR-JCL), 8 to 12 weeks of age, were artificially inseminated at 8:30-9:30 a. m. on the day of estrus vaginal smear (about 3-7 hr after ovulation) with 3.18 X 10(6), 1.83 X 10(6) and 1.15 X 10(6) sperms from four, two and one cauda epididymidis, respectively, of adult males which were suspended in 50 microliter of a modified Krebs-Ringer-bicarbonate solution and incubated at 37 degrees C was under 5% CO2 in air for an hour. Immediately after insemination, pseudopregnancy induced by an artificial penis and a vaginal tampon. Out of 13 females inseminated with 3.18 X 10(6) sperms, 9 females showed placental signs and 8 of them gave birth to the mean 10.5+/-2.20 (M+/-S.D.) young at term. Four of 13 females having received 1.83 X 10(6) sperms became pregnant giving birth to the mean 4.3+/-2.1 (M+/-S.D.) young at term. On the other hand, 5 out of 6 females failed to become pregnant following insemination with 1.15 X 10(6) sperms, and only one showed a placental sign and gave birth to twelve young at term. It is concluded that the conception rate and litter size are both dependent on the number of sperms inseminated and that more than 3 X 10(6) sperms are necessary to get the conception rate and the litter size comparable to those in natural mating.


[Fluctuation and distribution of animal room temperature and the temperature in cages (author's transl)]. The temperature of various positions in an occupied animal room (mice, rats) including inside of cages were measured using a 50 channels thermal data recorder (step time 0.5 sec, 5 min intermittent through 24 hr and continuous) in a summer day. Any short periodical fluctuation of room temperature had practically no influence on the inside temperature of plastic cages. Against small diurnal fluctuations, stable vertical gradients (about 1 degree C between tops and bottoms of racks) were observed among one hour averages of room air temperatures. Air temperature in the cage fluctuated in larger scale. (up to 3 degrees C) For controlling animal room temperature, each of short periodical fractuation, diurnal change and spasal distribution should be separately concerrned.


[Simplified methods in sampling and shipping of individual sera from mice and rats for serological checking of infections (author's transl)]. The usefulness of simplified techniques in sampling of individual mouse and rat sera and their shipping in wet state for serological checking of infections were described.


Analysis of receptor mechanisms involved in the hemopoietic effects of androgens: use of the Tfm mutant. The insensitivity of Tfm mutant mice to androgens is due to a greatly diminished ability to bind 5alpha-dihydrotestosterone to androgen-binding receptors in the cytoplasm of target tissues. Testosterone stimulates hemopoiesis through several mechanisms. The Tfm mutant mouse was used in an attempt to delineate hemopoietic effects of androgens that are mediated by androgen-binding receptors from those that require other cellular mechanisms. Mice of the Tfm mutant and related (androgen-binding) genotypes were treated with multiple doses of 5alpha-dihydrotestosterone (5alpha-DHT). The Tfm mutant was not stimulated to incorporate 59Fe, suggesting that androgen-binding receptors mediate this hemopoietic action of 5alpha-DHT. In contrast, the mutation did not block the ability of a single dose of 5alpha-DHT to increase the absolute number of committed granulocyte/macrophage precursors (CFU-C) in the femurs of mutant mice. The latter finding suggests that androgen-binding receptors are not involved in the mechanisms that lead to amplification of the CFU-C population by 5alpha-DHT. Tfm mutant mice respond to nonandrogenic stimuli of erythropoiesis. These findings emphasize the specificity of the diminished ability of the Tfm mutant mouse to respond erythropoietically to androgen. Accordingly, the Tfm mutant mouse appears to be a useful analytical tool for studying mechanisms underlying the hematopoietic effects of testosterone and related steroids.


Phagocytosis of 'old' red blood cells by macrophages from syngeneic mice in vitro. We have studied in vitro the interaction of peritoneal macrophages with 'old' and 'young' RBC, as well as with enzymatically treated 'old' and 'young' RBC from syngeneic mice. 'Old' RBC were recognized and phagocytized by macrophages, whereas 'young' RBC were not. Neuraminidase treatment of both 'young' and 'old' RBC had little effect on the extent of phagocytosis. Trypsin treatment, on the other hand, markedly reduced the phagocytosis of 'old' RBC and had no effect on the phagocytosis of 'young' RBC. The level of phagocytosis of 'old' RBC by macrophages from mineral-oil treated mouse peritoneal cavities was roughly half that of macrophages from untreated mice. It is postualted that 'old' RBC could be recognized due to the presence of cytophilic antibodies on the surface of the macrophages. The specificity of these hypothetical cytophilic antibodies is believed to be directed towards sites which are absent or shielded in 'young' RBC, and exposed in 'old' RBC. Trypsin treatment of 'old' RBC appears to remove these antigenic sites from the 'old' RBC. The lower level of phagocytosis of 'old' RBC by mineral-oil induced macrophages could be due to the previous phagocytic activity of these cells, and their relatively uncoated, newly form plasma membrane, lacking cytophilic antibodies. In support of this hypothesis, we have demonstrated that trypsin treatment of macrophages resulted in a markedly decreased phagocytosis of 'old' RBC.


Effect of a low dose of vincristine on platelet production in mice. The effect of a single low dose (0.1 mg/kg) of vincristine (VCR) on platelet production was investigated in C57B1 mice. A parallel increase of circulating platelets and (75Se)-selenomethionine (Se-Met) uptake was observed. The total megakaryocyte count decreased insignificantly 6 hours after VCR injection, followed by an increase after 18 hours. Plasma taken from mice 24 hours after VCR injection was tested for thrombopoietic activity. The post-VCR plasma caused a significant thrombocytosis, increased Se-Met uptake and increased protein synthesis of the platelets, indicating an active overproduction of platelets. These results suggest that the thrombocytosis induced by a low dose of VCR is mediated by a thrombopoietin-like substance.


Oxymetholone and erythropoiesis: failure to detect an effect in fetal mouse liver cell cultures. Oxymetholone, a steroid of proven clinical value in the treatment of refractory anemia, was without effect on endogenous or erythropoietin-mediated heme synthesis in fetal mouse liver cell cultures. This conclusion applied both when the cells were exposed to oxymetholone prior to culturing with erythropoietin and when the steroid was present in the cultures simultaneously with erythropoietin. Unlike those steroids having a direct effect on erythroid cells, oxymetholone also failed to increase the proportion of erythropoietin responsive cells in DNA synthesis. The relevance of these observations to the therapeutic benefit of oxymetholone is discussed. While the possibility that oxymetholone has to be metabolized to an active form cannot be excluded, the results suggest that oxymetholone does not seem to be erythropoietically active by a direct effect on erythroid cells. The fact that it is a successful therapeutic agent in some patients with aplastic anemia may be due to its proven ability to increase endogenous erythropoietin levels or to reduce ineffective erythropoiesis.


The adaptation of a reflex response to the ongoing phase of locomotion in fish. The reflex response to stimulation of the tail fin has been studied in the swimming fish, by bilateral electromyographical (EMG) recordings in several segments along the body. The response varies with the phase of swimming. When the muscles on one side (segment) are active, a large response will occur on this side but no response on the contralateral side at the same level. When the other side becomes active an identical stimulus will cause an activation of this side but no response on the previously active side. When the movements were filmed a powerful mechanical effect was demonstrated with an augmentation of the ongoing movement, that would result in an instantaneous increase in speed. The stimulus causes in addition a shortening of the duration of the swimming cycle and its components. Most of the results were obtained on spinal dogfish, which also exhibits spontaneous locomotion after a spinal transection. Mainly electrical bipolar stimulation of the tail fin was used. Identical stimuli applied in different phases on an ongoing movement, thus give a reflex response that changes dramatically with the phase of the movement. This phase dependent reflex reversal is functionally meaningful; it is fast and due to spinal mechanisms.


Receptive field types of area 18 neurones in the cat. In cats, 131 area 18 units with receptive fields 10-50 degrees from the visual axis, were recorded and tested with moving stimuli. These stimuli included light slits, dark bars, single edges, gratings and a random square pattern. 94% of the units were responsive to visual motion. 106 neurones could be classified by a screening procedure based on responses to a moving standard grating and a moving random square pattern. When testing with moving stimuli, the criteria for distinguishing between simple and complex cells in area 17 (Pettigrew et al., 1968; Bishopel al., 1971a,b, 1973 Goodwin and Henry, 1975, Sherman et al., 1976) also apply to area 18 neurones. No tests with stationary stimuli were made in distinguishing simple from complex cells. In addition to simple (50%) and complex (18%) cells, area 18 contains other cell types as hypercomplex cells (11%), cells with a radially symmetric RF (6%) and amplitude specific cells (10%). Six cells (5%) were unclassified. A special battery of tests was designed to study the RF of the very sophisticated amplitude specific cells. Their RF appears to consist of a discharge region preceded by a trigger area and of two flanking inhibitory regions.


Influence of movement parameters on area 18 neurones in the cat. In cats, 107 area 18 neurones with identified FR type, 10-50 degrees from the visual axis, were tested for the influence of direction, velocity and amplitude of movement. These three parameters are believed to be the primary parameters of a movement analysing system. 94% of the neurones were influenced by the direction of movement, all of them by the angular velocity and 16% by the amplitude of movement. For each of the primary parameters, tuning curves were established. Angular velocity influenced not only the response magnitude but also the response latency and the direction bias. By preparing response amplitude functions at different velocities the influence of movement duration was ruled out. The association of functional properties and RF organization suggests a model of information processing in area 18 of the cat.


A cerebellar projection onto the pontine nuclei in the albino rat. Following removal of a significant part of the dentate nucleus and most of the interpositus nucleus in the rat cerebellum degenerated cerebellopontine fibres are shown to end in three fairly restricted regions in the contralateral pontine gray: in the paramedian position, in the middle and in the lateral third. The three regions are arranged in rostro-caudal longitudinal columns in the caudal three-quarters of the pons and these columns are continuous with one another by regions of scattered degeneration. The fibres appear to end in relation to distal dendrites of the pontine cells.


Nuclear enlargement and DNA synthesis in mouse epidermis treated with carcinogen and promotor. An autoradiographic investigation was made into the causes of nuclear size increase observed in the mouse epidermis within a few days of topical benzpyrene treatment. The effects of croton oil pretreatment of posttreatment in combination with benzpyrene were examined to see what effect a growth stimulus had on this response. The degree of nuclear size increase induced in the epidermis suggested that some ploidy level increase resulted from combined croton oil and benzpyrene treatment and evidence was found of a G2 block occurring in association with this. Enhancement of nuclear size increase by croton oil highlighted the importance of a growth stimulus in carcinogen induced nuclear enlargement and the implications of this are discussed. Disappearance of enlarged nuclei was seen when mice were kept for 5 days after combined croton oil and benzpyrene treatment in spite of a reduced cell loss compared with croton oil treatment alone.


Electronmicroscopical investigations of the effects of heparin upon the structural elements of the rat glomerulus. In this study the ultrastructure of the renal glomeruli was investigated 30 minutes after the intraperitoneal administration of heparin. It was observed that the matrix and fibrillary structure became more abundant in the mesangial cells and also in the epicytes; it was noted that the Golgi apparatus was active and the granular endoplasmic reticulum was very enlarged, partially containing structures of a particular shape. Furthermore, there was a general thickening and a dense accumulation of matter in the basement membrane. It was thought that this was due to the migration of structural elements of the mesangial cells and epicytes to the basement membrane and not because of heparin storage. Therefore we have postulated that these structural changes observed in the glomeruli were not associated with the extrarenal effects (antiinflammatory; anticoagulating and anticomplementary activities) of heparin but that they could be related to its cyto-hormonal action upon the epicytes and mesangial cells.


Rheological studies of matrix--special reference on the mobility of leucocytes in relation to the rheological characters of experimental matrix. The rheological characteristics of a model matrix, consisting of Bacto-agar, were correlated with the ability of the matrix to permit cellular penetration, using a rheolometer and the agar bullet method. The most important rheologic characteristic that affected cellular mobility was found to be the viscosity rate. A viscosity rate under 1,000 X 10(4) dyne sec/cm2 was needed to permit cellular mobility.


Qualitative and quantitative changes in the ultrastructure of the dog heart after temporary ischaemia and coronary reperfusion. A total ischaemia of one area of the myocardium was produced by ligature of a coronary artery in dogs. After 30 min, 1 hr, 2 hrs, and 4 hrs the ligature was loosened and the artery was for 1--2 hrs reperfused up to 4--7 days. At the end of the ischaemia and after reperfusion the ultrastructure of the myocardium was qualitatively and morphometrically investigated. The findings concerned: loss of glycogen (partly glycogen accumulation), mitochondrial swellings and fusions and development of megamitochondria, loss of cristae, rupture of the mitochondrial outer membranes, relaxation or supercontraction of the myofibrils, vesicular and vacuolar changes of the sarcoplasmic reticulum, oedema of the sarcoplasm, rupture of the sarcolemma. No significant differences of the quantitative parameters could be observed during the ischaemia from 30 min to 4 hrs: myofibrils 53.65--59.74%, mitochondria 26.51--33.59%, sarcoplasm 8.22--11.86%, sarcoplasmic reticulum 1.41--2.63%, lipofuscin 0.05--0.87%, lipids 0.01--0.10%. In comparing the data of the single animals we could determine significant differences between some parameters at the ends of the ischaemic phase and of the reperfusion phase, but as far as the findings are concerned both increases and decreases could be observed. The investigations show that the limit of the reversibility of damages in myocardial cells is about 45 min; in special cases a longer survival time may be taken into account. Reperfusion has different, though not always positive, effects.


Ultrastructure of the human antral G cells during fasting. The ultrastructure of the human antral G cells was examined in gastrobiopsies of 7 healthy volunteers fasting 24 to 240 hours. In contrast to the animals gastric C cells during fasting, the dissolution of the substance of gastrin granules (but not emiocytosis of granules) was observed in the human antral G cells during long fasting. The authors consider the possibility of artificially inducing the dissolution of the substance of the granules only the technique of gastrobiopsy itself.


Influence of starving on the rat gastric mucosa -- light and electron microscopical findings. The histology and ultrastructure of the rat gastric mucosa were investigated during 168 hours of starvation. An increased desquamation of individual foveolar cells was found. In the preserved cells of the foveolae, the content of the PAS positive mucosubstances did not change during starvation, and no changes took place in the appearance and in the amount of the mucous granules at the electron microscopic investigation. The number of lipid droplets increased in the mucous foveolar cells within 24 and 48 hours. During starvation the mitochondria (mainly in the parietal cells) were enlarged and contained rare mitochondrial cristae. Some mitochondria were distintegrated and removed by lysosomes. The number of lysosomes (mainly cytosergresomes) was markedly increased n parietal cells. A collapse of the intracellular canaliculi occurred as well as a narrowing in the tubulovesicular profiles. In chief cells the profiles of the granular endoplasmic reticulum and Golgi apparatus were reduced. It was shown that the ultrastructural changes induced by starvation can be interpreted functionally in changed histochemical parameters of the gastric mucosa.


Heart infarction-like effect induced by natural catecholamines in vitro. Isolated rat hearts were perfused using retrograde technique under constant perfusion pressure or under constant coronary flow. The addition of L-epinephrine or L-nor-epinephrine (1 microgram per ml) into the perfusion medium for one hour caused visible and irreversible morphological changes. They became apparent usually after 4 hours of perfusion in the form of small, pale, opaque spots of streaks gradually enlarging on the surface or on the transverse section of myocardium. Light microscope and electron microscope examination showed the disintegration process analogous to myocardial infarction but lacking the infiltration with blood elements. The structural changes were preceeded by increased release of lactate dehydrogenase into the effluent, the most characteristic metabolic change a accompanying myocardial injury. Although the underlying mechanism of cardiotoxic action catecholamines remains to be clarified, several factors under consideration could be eliminated like hyperlipidemia, thrombogenic process or reduced total coronary inflow rate.


[Serological and histological investigations as well as studies on changed food uptake during adrenaline application by intraperitoneal depot capsule]. The authors have developed a method for long-term permanent application of water soluble substances by a intraperitoneal depot capsule [KLINGENBERG et al., Exp. Path. 13, 302-311 (1977)]. The present study deals with the effects on the liver and several metabolic processes induced by continuous long-term adrenaline application by means of such a depot capsule.


Sex differences in renal damage induced in the mouse by Amanita virosa. The sensitivity of male and female mice to Amanita virosa was compared. Dried, homogenized mushroom was given orally by stomach tubing at doses of 100, 200, 400 and 800 mg dried mushroom/kg body weight. Both in males and in females, the kidneys were the only organs showing macroscopical changes. The dose of 100 mg/kg caused renal damage in females, whereas in males the first signs of kidney damage were seen at the dose of 400 mg/kg. The renal lesions observed in the males were located in the cortex, while in the females they were limited to the outer stripe of the outer medullary zone. Testectomy diminished the nephrotoxicity of A. virosa in male mice and caused changes in the localization of renal lesions.


Vascular chronic-fibrosing pancreatitis of the rat after 5/6-nephrectomy. The pancreases of 77 uremic rats of a Wistar strain were investigated light-microscopically in groups of 5 animals at 11 different times between one day and ten weeks after 5/6-nephrectomy. The serum concentration of urea reached a maximum mean value of 375 mg% after three days; during the stage of chronic uremia the mean value was found to be 175 mg%. The blood pressure increased in the third week after 5/6-nephrectomy and reached in the course of the experiment values of up to 200 mm Hg and more. Histologically, after an initial acute interstitial pancreatitis with focal dystrophies of the exocrine parenchyma which was virtually cured by the 14th day of the experiment, an increasing proliferative-exudative and granulomatous vasculopathy appeared at the end of the third week. This was followed by a perivascular transmitted chronic-fibrosing pancreatitis which may be regarded as a model of vascularly induced pancreatitis. Early damage by uremia and initial pancreatitis, the rapidly developing hypertension and allergical and autoallergical reactions are discussed as aetiological complex for the vascular alterations. The typical findings of the uremic pancreatopathy, well-known in human pathology, are not reproducible.


Metabolism in porifera. VII. Conversion of [7,7-3H2]-fucosterol into calysterol by the sponge Calyx niceaensis. The sponge Calyx niceaensis metabolizes administered [7,7--(3)H2]-fucosterol to produce labelled calysterol, the principal sterol component of the sponge, possessing the unique feature of a cyclopropene ring bridging C23,24.


Electron microscopic study of infantile renal biopsy specimens. Out of 54 open renal biopsies performed on children, 17 were selected and studied not only by light microscopy but also by electron microscopy. Statistical-mathematical analysis of basement membrane thickness-measurements was carried out. It is concluded that electron microscopic investigation of the renal biopsy material is required in selected cases involving diagnostic or therapeutic problems. In nephrotic syndrome it may help above all to separate minimal changes from early forms or glomerular lesion of the focal sclerosing type. Electron microscopy can also be useful in any of the mono- and oligosymptomatic renal diseases. In those cases only electron microscopy makes it possible to provide exact morphological diagnosis which is necessary to the proper therapy.


Completion of the natural groups of ergot alkaloids: syntheses and pharmacological profiles of beta-ergosine and beta-ergoptine. The syntheses and pharmacological potencies of beta-ergosine and beta-ergoptine, the missing links in the natural groups of ergot peptide alkaloids are described.


New tigliane and daphnane derivatives from Pimelea prostrata and Pimelea simplex. From the methanol extract of Pimelea prostrata, prostratin (I) and 2 autoxidation products have been isolated. They are tigliane derivatives and relatively nonirritant on the mouse ear. The irritant pimelea factor P5 (IIa) also with a tigliane skeleton and related to mancinellin (IIb), as well as the irritant diterpene ester pimelea factor P1 (IIa, simplexin) with daphnane skeleton, were found to be present in both P. prostrata and P. simplex. Further the irritant homologue of simplexin, pimela factor IIIb was detected in P. prostrata. Some biogenetic consequences of these findings are discussed.


Procainized murine macrophages fail in the agglutination of opsonized isologous erythrocytes. Murine peritoneal macrophages exhibit numerous slender microvilli and several invaginations of the cell membrane. By treatment with isotonic 2.10(-2) M procain-PBS the surface of macrophages is smoothed significantly. Isolated macrophages agglutinate opsonized isologous erythrocytes. Procainizing of macrophages inhibits this agglutination. The finding provides evidence for typing of macrophage receptors whether or not sensitive to procain treatment.


Methionine metabolism in apple tissue.

Methionine metabolism in apple tissue. A metabolic intermediate isolated from apple tissue fed either methionine or 5'-methylthioadenosine has been tentatively identified as a methionine-pyridoxal Schiff base. The formation of this compound is discussed in relation to ethylene biosynthesis.


Identification of thromboxane B2 in guinea-pig uterine homogenates. On the basis of gas chromatographic and mass spectrometric evidence, thromboxane B2 has been identified in incubates of homogenised guinea-pig uterus.


[Analysis of a population of Cannabis sativa L. originating from Mexico and cultivated in France (author's transl)]. Cannabinoid content of a population of Cannabis sativa L. originating from Mexico and cultivated in France is studied. The statistical analysis of results shows how difficult it is to obtain homogenous and representative samples. This problem is correlated to genetic heterogeneity of seeds.


Synthesis and some characteristics of [13C]-specially enriched tetragastrin and the related compound. [13C]-enriched tetragastrin and the related compound were synthesized in solution. Conversion of S-[13C]methylated tetragastrin to the enriched tetragastrin gave 10.5 ppm upfield chemical shift of Cepsilon resonance. The potency of the synthetic tetragastrin to stimulate gastric acid secretion was virtually identical with that of pentagastrin (ICI).


Red cell metabolism in red and grey kangaroos. Glucose utilization, lactate production and glutathione regeneration were measured in the red blood cells of 2 species of Australian Marsupials, Eastern grey Kangaroo (Macropus gigantus) and red kangaroo (Macropus rufus), and were found to be significantly lower in the red blood cells from grey than that of red kangaroos.


[Peroxidase isoenzymes in cress seedlings (Lepidium sativum L.) and their inhibition by silybin, silydianin and silychristin]. Seedlings of Lepidium sativum L. contain 4 peroxidase isoenzymes. Their de-novo-synthesis is significantly depressed in the presence of 3.10(-3) moles/1 silybin, silydianin and silychristin in the incubation medium respectively.


Cytosine deaminase: structural modifications studies. Structural modification studies have been shown that a cysteine, a histidine and possibly an arginine residue are involved in the catalytic process. The enzyme gave a single band on polyacrylamide gel electrophoresis, and the amino acid analysis showed it to contain a high proportion of hydrophobic residues, which was in agreement with the chemical modification results.


A highly active glutathione peroxidase in red blood cells of normal and acatalasemic mice. The activities of catalase (E.C.1.11.1.6) and glutathione peroxidase (E.C.1.11.1.9) were compared in red blood cells from humans, ducks and normal and acatalasemic mice. In the cells from both strains of mice, an equally high activity of GSH-Px was found which could be inhibited completely by iodoacetate but was not sensitive to N-ethylmaleimide.


Metabolic energy requirements during teleost melanophore adaptations. Inhibition of oxidative phosphorylation by 2,4-dinitrophenol or sodium cyanide promotes complete melanosome aggregation in teleost melanophores. This aggregation is not promoted via the alpha-sympathetic receptor sites because it occurs in the presence of tolazoline hydrochloride, an alpha-receptor blocking agent. Interpretation of these results suggests metabolic energy release is required in the centrifugal direction only.


The effects of chronic peroxide intake on the peroxide metabolism enzyme activities of rat organs. In rats receiving a dilute aqueous solution of hydrogen peroxide for a prolonged period, the activity of the peroxide metabolising enzymes, i.e. superoxide dismutase, peroxidase and catalase, is significantly increased in most tissues.


Variation of glutamate decarboxylase activity and gamma-amino butyric acid content of wheat embryos during ripening of seeds. GAD activity and gamma-ABA content of wheat embryos at 7 ripening stages were verified with the aim of studying the metabolic activity of embryo during dehydration and quiescence of caryopsis. Data showed that in the early stage of ripening GAD activity is very low, increases rapidly at dough-stage, remaining constant up to waxy-stage, and decreases in the last fully-ripe embryos. gamma-ABA content appears to be roughly parallel to the variations of GAD activity.


On the phospholipids of adult Ancylostoma caninum. The phospholipid composition of Ancylostoma caninum has been examined. Phospholipids amounted to 0.9% of the wet weight of the parasite. Ethanolamine and choline containing lipids comprised about 76% of the total phospholipids. Lysolecithin, sphingomyelin, phosphatidyl inositol and phosphatidyl serine were present in minor amounts. Cerebrosides and sulfatides were also identified.


Suppression and enhancement of humoral immune response to Toxoplasma gondii by passive antibody. Anti-toxoplasma antibodies administered passively to mice may lead to suppression of enhancement (reported for the first time with Protozoan parasites) of subsequent antibody response when these animals are later infected with Toxoplasma gondii. The outcome is dependent on infecting strain of Toxoplasma and the antigen-antibody ratio.


Villus growth and cell replacement in the small intestine of the neonatal pig. Cells produced in the crypts of newborn pig ileum migrate onto villi during development. There is little or no corresponding loss of cells from villus tips during the first week of postnatal life. Villus growth during this period is largely responsible for the slow rate of cellular renewal seen to take place.


Effect of histones from brain on DNA-synthesis in vitro. The results of these experiments demonstrate that histones from brain inhibit the replication of DNA in vitro. A similar effect is observed with polylysine or polyarginine. The reversion of inhibition by polyglutamic acid or acidic proteins is completed in all cases except when the DNA is previously complexed with histones, polyarginine or polylysine. This suggest that histones masking of DNA towards the polymerases involves electrostatic forces.


Satellite heterophagosomes.

Satellite heterophagosomes. An incidental observation made during a recent ultrastructural study shows that after ingestion of an erythrocyte by a Kupffer  cell surface budding occurred from the heterophagosome leading to the formation of smaller satellite or daughter heterophagosomes. It is suggested that an entire erythrocyte may be too large to digest in a single heterolysosome and that fragmentation into smaller units facilitates digestion by bringing about better contact between the enzymes and substrates.


Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit. The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.


Postnatal development of adrenergic and cholinergic sensitivity in the isolated rat atria. The sensitivity to adrenergic drugs in isolated rat atria increased with the postnatal development. The cholinergic chronotropic sensitivity did not further change after birth.


Changes of hormonal status in young mice by restricted caloric diet. Relation to lifespan extension. Preliminary results. The maintainance of mice on a reduced caloric diet for 6 weeks starting from weaning time produces persistent changes in their hormonal status as reflected by differences in blood levels of gonadal and adrenal steroids. The changes might express a permanently different hypothalamic regulation. This might account for a prolongation of their life span.


The effect of dehydration on the neurohypophyseal blood flow in rats with hereditary diabetes insipidus. Neurohypophyseal blood flow increases in water-deprived rats. This increase is independent of vasopressin release, since it occurs even in rats with hereditary defect of hypothalamic vasopressin synthesis.


Vitamin C and gallstone formation: a preliminary report. Gallstone formation in hypovitaminotic C guinea-pig fed a high cholesterol diet was associated with qualitative changes in the gallbladder bile, namely, a high cholesterol concentration, a lowered bile acid content and diminished phospholipid-to-cholesterol and bile acid-to-cholesterol ratio.


Influence of metiamide and atropine on pepsinogen secretion in the conscious rat. Activity of peptic cells is influenced directly by cholinolytic or cholinergic agents. Histamine H2-antagonists influence the activity of the chief cells through changes of acidity of gastric juice.


The levels of metallothionein-like proteins in animal tissues. The level of metallothionein-like proteins was determined in different tissues of 6 animal species. The highest concentrations were found in pig and rat tissues. The organs richest in metallothionein-like proteins included: kidneys (101-305 microgram/g), intestine (127-257 microgram/g) and liver (54-496 microgram/g).


Central effect of 5,8,11,14-eicosatetraenoic acid (arachidonic acid) on the temperature in the conscious rabbit. Hyperthermia induced by arachidonic acid in rabbit was attenuated by phenoxybenzamine, cyproheptadine and indomethacin. The reduction in arachidonic acid hyperthermia, after 6-OH-DA and the failure of PCPA to reduce this rise, indicates the involvement of noradrenaline in arachidonic acid hyperthermia.


Chlorinated benzene induction of hepatic porphyria. 1,4-Dichlorobenzene and 1,2,4-trichlorobenzene were compared with hexachlorobenzene which is known to cause porphyria. Although hexachlorobenzene administration resulted in a manyfold increase in liver porphyrin levels and urinary excretion of porphyrins, the lesser chlorinated compounds did not do so.


The opposed influences of beta-adrenergic stimulation and adenosine on the frequency-force relationship of isolated left atria of guinea-pigs. The normal frequency-force relationship of left guinea-pig atria can be largely suspended when strong beta-adrenergic stimulation by orciprenaline is antagonized by the negative inotropic effect of adenosine, so that contraction amplitude is nearly equal at an intermediate level over a wide range of stimulation rates. Curves obtained with new method for recording continuous frequency-force loops are presented.


Interaction between aldosterone and renomedullary prostaglandins. Competitive action between aspirin and spironolactone. Aldosterone injected i.m. decreased the release of renomedullary PGEs and the index (urinary Na/K ratio) in conscious normotensive intact and adrenalectomized rats. Coadministration of spironolactone increased the release of PGEs as well as the index (urinary Na/K ratio). The effect of spironolactone was partly inhibited by aspirin injected in a ratio 5:1 (aspirin:spironolactone), and effect which could be reversed by the infusion of a synthetic prostaglandin (PGA2) in a subhypotensive dose.


The effect of methaqualone on prenatal development in the rat. Methaqualone treatment of pregnant rats in doses of 100-200 mg/kg day produces resorption and a series of anomalies whose incidence increases with the dose-level employed.


Precocious retina development caused by receptor cell independent light effect. In the retina of the mouth-brooding teleost Tilapia leucosticta, light causes and accelerated development of ganglion cells. This effect is presumably not mediated by receptor and interneuronal cells.


Histochemical and ultrastructural modifications of mice endometrium, vagina and pituitary following zeranol treatment. The histochemical and ultrastructural changes produced by zeranol treatment on the endometrium and the gonadotropic FSH cells of the adenohypophysis have been investigated in mice at the prepuberal and virginal stages. Modifications similar to those induced by estrogen treatment were observed. It is concluded that both estrogens and zeranol share the same activity on the tissues examined.


A morphometric study of nuclei, nucleoli and nuclear bodies in goitres and papillary thyroid carcinomas. Significant positive correlations were found between the nuclear surface-to-volume ratio and the volumetric density of nucleoli, as well as between the volumetric density of nucleoli and the volumetric and numerical densities of complex nuclear bodies in goitres and papillary thyroid carcinomas.


Association of asymmetric unit membrane plaque formation in the urinary bladder of adult humans with therapeutic radiation. Asymmetric unit membrane (AUM) is a component of the luminal membrane of urinary bladder in many species. In normal human adults it is inconspicuous, but it becomes prominent following incidental exposure to therapeutic irradiation.


Gliogenesis during embryonic development in the rat. With the aid of thymidine-H3 autoradiography gliogenesis in the rat brain was seen to start during embryonic stages, which might continue into the postnatal stages of development. Gliogenesis followed a caudo-rostral gradient closely following neurogenesis. Ependymogenesis was found to occur in parallel with gliogenesis.


Comparison of native and microwave irradiated DNA. Chemical changes induced in the testicular DNA of irradiated Swiss male mice are described. Parameters quantified were hyperchromocity and melting temperature. The data supports the possibility that microwave causes strand separation.


Differences in cytochalasin D-induced surface alterations between chronic lymphocytic leukaemic and normal lymphocytes. Cytochalasin D (CD) causes an unusual surface alteration in normal lymphocytes consisting of the formation of focal irregular club-shaped cell processes. Lymphocytes from chronic lymphocytic leukaemic cases did not show this change on exposure to CD. There was either no surface change or, in some cases, clear double-membrane lined vesicles were formed and appeared to be discharged from the cell. This difference in response may be related to the changes in cell membranes known to occur in malignant transformation.


The immunopotentiating effect of thiosulphate in vivo. Sodium thiosulphate injected i.v. into mice causes a marked increase in concentration of several serum proteins, particularly immunoglobulins. When given together with antigen, it significantly potentiates the T-dependent humoral responses.


Methemoglobin in hypoxic rats.

Methemoglobin in hypoxic rats. Methemoglobin levels have been found to vary with altitude and to shift the hemoglobin-oxygen dissociation curve. In this study, hematocrits and methemoglobin levels were monitored in rats exposed to hypoxia (420 torr absolute) for various intervals. Hematocrits gradually increased throughout the period of hypoxia, while methemoglobin levels rose by 12 h, peaked at 24 h and returned to control level by day 6. These data, in the context of other work, suggest that increased methemoglobin is important in acclimation to hypoxia.


Radioimmunoassay of some hormones simultaneously measured in serum and breast cyst fluid. Blood and breast cyst fluid were drawn simultaneously for hormonal determination. There was no difference between serum and cyst fluid values of PRL and TSH. A significant difference was noted for LH (p less than 0.01) and FSH (p less than 0.05), serum concentrations being higher than cyst fluid concentrations.


Production of porcine antibodies with high specificity to [8-D-arginine] deamino-vasopressin (dDAVP). The development of a specific radioimmunoassay for [8-D-arginine] deamino-vasopressin (dDAVP) is described.


Divorce therapy: an in-depth survey of therapists' views. In-depth interviews were conducted with 21 highly experienced therapists on the criteria of a constructive divorce, the obstacles to achieving such a divorce, and the strategies and tactics of divorce therapy. The primary criterion of a constructive divorce was the successful completion of the process of psychic separation and the protection of the welfare of minor children. Therapy may focus on the decision to get divorced and/or the negotiation of the terms of a divorce settlement. Three types of therapeutic strategies were identified: reflexive intervention by which the therapist orients himself to the marital problems and attempts to gain the trust and confidence of the partners; contextual interventions by which he tries to promote a climate conducive to decision-making; and substantive interventions intended to produce resolution on terms the therapist has come to believe are inevitable or necessary. The nascent state of divorce therapy as an area of therapeutic specialization is noted. The problem of diagnostic criteria for divorce, the relationship between therapists and lawyers, the nature and consequence of therapist impartiality, and the degree to which therapists should mediate the terms of divorce are considered central issues meriting further study.


Family rituals a powerful tool in family therapy. The use of systemic models in family therapy obliged our team to devise therapeutic tasks involving the entire family. Among these, one was found to be extremely effective: the prescribing of a family ritual. This article gives details of on such example aimed at the destruction of a myth that had been created by three generations of a family. In order that the reader may have a adequate understanding of this ritual, were shall fully describe the story of the family and of the transgenerational evolution of this myth. In the description of the treatment of the family, certain errors were made by the therapists that will come to light-errors that, as usual, were far more instructive than the actual successes. Eventually, it was the very understanding of these errors and their repercussions that led us to the successful prescription of the ritual. Finally, detailed analysis of the substance and aim of the ritual will illustrate and explain exactly what we mean by the term ritual.


A systems theory approach to a case of anorexia nervosa. Systems theory views mental and psychosomatic illness as the natural consequences of a dysfunctional human interactional group. The symptom chosen is affected by the symptom carrier's age, sex, and unique individual characteristics. However, the reason the symptom develops and is maintained is to be found in the system(s) of which the symptom carrier is a part. A human system consist of two or more individuals who have an ongoing, often goal-directed, relationship with each other. The most important human system today is undoubtedly the family. The welfare of the individual is usually related to membership in a vital, well-adjusted family. A dysfunctional family easily becomes dependent on mental or behavioral deviations in one of its members as a means of preventing disintegration. We hope this article's description of a typical treatment situation will demonstrate how a systems theory approach differs from other forms of family therapy in its evaluations and techniques.


Parental focus of attention in a videotape feedback task as a function of hypothesized risk for offspring schizophrenia. The families of 29 disturbed but nonpsychotic adolescents were observed in a structured task in which they discussed their reactions to viewing themselves interacting on videotape. Measures derived from the Singer-Wynne concenpt of transactional style deviance were applied to the parental behaviors and related to prior assessments of parental communication disorder based on individual parental TAT protocols. The results confirm the Singer-Wynne hypothesis of the cross-situational stability of transactional style deviance. The most striking finding, however, is that an index of positive focusing behavior differentiates more strongly parents of adolescents hypothesized to be at varying leves of risk for schizophrenia than does the measure of transactional style deviance.


Family therapy training for paraprofessionals in a community mental health center. An ecologically oriented family therapy training program is advocated for teaching paraprofessionals to work with high-risk clients in a community mental health setting. The context of training as well as the particular abilities and needs of beginning paraprofessional family therapists are explored in order to design a flexible and effective program in the face of limited resources. This paper describes a variety of educational and supervisory formats such as group supervision, peer supervision, and live supervision. The usefulness of these of different models in facilitating skill development and growth in paraprofessionals is evaluated. Recommendations are made to trainers concerning problems encountered in teaching paraprofessionals and in implementing family systems training in community mental health centers.


On the reclaiming of denied affects in family therapy. A central developmental task of the family is to help its members develop the capacity to cope with the grief attendant on separation and loss. In order to work through such feelings, each member must first be able to acknowledge the affect as present, internal, and belonging to the self. Depending on the degree of intrapsychic differentiation, and the dread of abandonment, family members may seek to avoid awareness of such feelings within themselves. The disclaimed emotions remain powerful unconscious motivators of behavior, exerting their influence despite their denial. Some typical clinical illustrations of this are provided. Excerpts from conjoint family therapy are then presented to illustrate the therapeutic interventions made in assisting a family to acknowledge denied grief over the separation of one of its members along with unspoken tender feelings within the family. This paper affirms the continued relevance of a psychodynamic, interpretative approach for families struggling with unresolved grief.


The effects of family presence and brief family intervention on global outcome for hospitalized schizophrenic patients. Virtually all modern inpatient psychiatric units operate on the assumptions that family presence, when the identified patient has schizophrenia, does affect outcome and that adding brief family intervention to the treatment prescription will enhance hospital and posthospital outcome. Often the family intervention is believed not adequate in terms of duration or frequency or quality (since trainees are the family therapists), given the standards of some experienced family clinicians. This report addresses these issues by comparing outcome measures for hospitalized patients with schizophrenia by (a) presence of a family and (b) amount and/or kind of family intervention. Most importantly, we wished to learn if global outcome would show change by virtue of family therapy (within the constraints imposed by the above limitations of family intervention).


Factors influencing indomethacin toxicity in the rat. The influence of various experimental conditions, such as nature of the diet, feeding schedule, sex and castration on indomethacin toxicity in the rat has been determined. In general, the following conclusions can be drawn: a) Independently of feeding schedule, sex or castration, indomethacin is significantly more toxic in animals on regular (RD) than in those on fat-free diet (FFD). b) Regardless of sex or castration, fasting significantly reduces indomethacin toxicity in RD fed animals. c) With the exception of RD unfasted animals, indomethacin is significantly more toxic in males than in females. d) Incidence and degree of intestinal ulceration are not sex dependent. e) Independently of the kind of diet and of the feeding schedule, castration reduces indomethacin toxicity in males but does not modify it in females. These findings are discussed.


New curare alkaloids. II. New bisbenzylisoquinoline alkaloids from Abuta grisebachii (Menispermaceae). From Abuta grisebachii Triana & Planchon, Menispermacea used by Sanama tribe for the preparation of curare, five bisbenzylisoquinoline alkaloids have been isolated; four of them are tertiary (peinamine and three new alkaloids, 7-O-demethylpeinamine, N-methyl,7-O-demethylpeinamine and macolidine) and one is a new quaternary alkaloid called macoline. Their structures have been elucidated on the basis of chemical reactions and spectroscopic data.


1,3-dicyclohexyl-5-alkyl-5-aminomethylbarbituric acids as potential antiinflammatory agents. The synthesis and the structure of 1,3-dicyclohexyl-5-alkyl-5-aminomethylbarbituric acids, obtained by the Mannich reaction, are described. Some of the obtained compounds showed a strong antiinflammatory activity in biological tests.


[Insulin-poietic effect of pentagastrin after beta-adrenergic block in the anesthesized dog]. Infusion of pentagastrin (5-G) into the femoral vein of anaesthesized dogs, in doses of 0.20 microgram/kg/min for 30 minutes, causes a prompt and significant increase in plasma IRI. The insulin-secretory effect of the peptide was not affected by 0.5 mg/kg i.v. of propranolol (a beta-adrenergic blocking agent) or by 1.3 mg/kg i.v. of practolol (a selective beta1-adrenergic blocking agent). These results show that the action of 5-G on the pancreatic beta-cells could be not related to the beta-adrenergic system.


[Oposite effects of audiogenic stress on the liver and adrenal dehydrogenase of the HMP shunt]. The effects of audiogenic stress (92 dB at 2000 Hz) on the liver and adrenal levels of glucose-6-phosphate-dehydrogenase (G6-PD) and 6-phosphogluconate-dehydrogenase (6-PGD) were studied in adult male rats. Blood glucose and liver glycogen were also measured. In liver of stressed rats the levels of glycogen, G6-PD and 6-PGD were lower in comparison with controls. On the contrary, a significant increase of the measured enzymatic activities was shown in the adrenals. The mechanism and biological meaning of such modifications are discussed.


Preparation and characterization of the sulfamethoxazole-trimethoprim 1:1 molecular compound. Physico-chemical properties of sulfamethoxazole-trimethoprim 1:1 molecular compound were investigated by DSC, X-ray diffraction patterns and I.R. spectroscopy. The phase diagram of the binary system was drawn and the possible nature of bonding between the components was briefly discussed.


[Direct effect of reserpine. II. Response of the rat vas deferens to calcium]. It has been shown that reserpine competitively antagonises the response of the isolated rat vas deferens to Ca2+. It has also been shown that reserpine does not modify uptake of Ca2+ from the external medium. On the basis of the results obtained and bearing in mind the uncoupling effect of reserpine on oxidative phosphorylation, it is suggested that reserpine owes its "direct" action to reduced availability of Ca2+ for contraction due to metabolic block.


The use of gonadotropins for the induction of ovulation in women with polycystic ovarian disease. Ten infertile patients with polycystic ovarian disease were treated with 18 cycles of "pure" human pituitary follicle-stimulating hormone (HP-FSH) and 10 cycles of human menopausal gonadotropin (HMG) consisting of FSH and luteinizing hormone (LH) in a 1:1 ratio. Human chorionic gonadotropin was used to trigger ovulation when optimal follicular development was achieved as judged by urinary estrogen determinations. Of the 18 cycles utilizing HP-FSH, 14 were presumptively ovulatory, 2 were conceptual, and in 5 cycles ovarian enlargement was noted. Of the 10 HMG cycles, none was ovulatory, no conceptions resulted, and 6 instances of hyperstimulation were noted. Pretreatment serum LH levels were significantly higher than normal follicular phase values. These observations suggest that endogenous LH levels in patients with polycystic ovaries are quite adequate for follicular development so that the administration of exogenous LH is unwarranted. Furthermore, the data suggest that HP-FSH or low-LH-containing HMG may prove to be an additional safe and effective nonsurgical treatment modality for patients who are anovulatory because of polycystic ovaries.


Medroxyprogesterone acetate for the evaluation of hypertestosteronism in hirsute women. Twenty-three women with moderately elevated plasma testosterone levels (77 to 240 ng/dl) received 10 mg of medroxyprogesterone acetate (MPA) orally, three times daily, for 3 months or more. The testosterone levels were reduced to normal (less than 70 ng/dl) in 21 patients, suppressed partially in 1 patient, and unchanged in 1 patient. The removal of an ovarian teratoma normalized the testosterone level in the patient whose levels had failed to suppress with MPA. On therapy, the mean plasma testosterone concentration decreased 60%, apparent free testosterone decreased 31%, and dihydrotesterone decreased 34% (P less than 0.001, P = 0.05, and P = 0.01, respectively). A small decrease in the testosterone-binding capacity did not reach statistical significance. Experience with this simple trial suggests that extensive diagnostic testing may not be required in women with hirsutism and moderately elevated testosterone levels.


The cervical factor in infertility: diagnosis and treatment. One hundred and fourteen women with an abnormal fractional postcoital test (PCT) and no other demonstrable cause of female infertility were included in this study. By utilizing the results of the postcoital test, it was possible to divide the patients into three major groups: (1) those with anatomical cervical defect, (2) those with abnormal cervical mucus, and (3) those with an abnormal PCT and normal cervical mucus. In the latter group the abnormality was due to either an abnormal male factor or an undetermined factor. The treatment used in all cases was either steroidal (diethylstibestrol) or mechanical (cervical cup insemination). In 53 of the patients there was an improvement in the PCT as a direct result of therapy. Twenty-three of these patients became pregnant--a pregnancy rate of 43%. Of the entire group of 110 patients (excluding 4 patients whose husbands had azoospermia), only 21% became pregnant. Of the 57 patients who failed to respond to therapy, 41 have been followed for 1 year, and only 2 pregnancies have been noted without therapy. No correlation was found between an abnormal PCT and the immunologic factor.


Inhibition of sperm migration through cervical mucus in vitro. The effectiveness of inhibiting bovine sperm migration through cervical mucus in vitro by prior treatment of semen with 45 to 150 micrograms of soybean trypsin inhibitor, univalent (papain-digested, nonagglutinating) and bivalent (undigested) rabbit anti-bovine sperm immunoglobulin, and heat-treated heifer serum was studied. Sperm head-to-head agglutination resulted from treatment of semen with bivalent immune antibody and heat-treated heifer serum. Migration through cervical mucus was inhibited only by treatment resulting in spermagglutination. It is postulated that in vivo inhibition of sperm migration may be influenced by secretory immunoglobulins from the cervix.


The new improved silastic band for ligation of fallopian tubes. Twelve different sizes of elastic bands were tried in animal experimentation for tubal sterilization. Reversible sterilization was not successful in any of the animals after removal of the various-sized bands. A new elastic Silastic band is reported which is larger and wider than those previously described. Over a 4-year period, no serious complications have been reported and extremely low pregnancy rates have been achieved by utilizing the new, wider bands and our applicators for human sterilization.


Frequency distribution of sperm counts in fertile and infertile males. In this study the frequency distribution of sperm counts and total sperm counts from more than 4000 allegedly fertile males were compared with those of husbands in 1000 infertile couples. Significant differences were observed only at the lower end of the scale (sperm counts below 10 million/ml and total sperm counts below 25 million/ejaculate). Frequency distributions of sperm counts above 10 million/ml or total sperm counts above 25 million/ejaculate revealed little difference between the fertile and infertile groups. These data suggest that, unless other parameters are found to be abnormal, sperm counts and total sperm counts above 10 million/ml and 25 million/ejaculate, respectively, probably are not major factors in a couple's infertility.


Relation between indices of semen analysis and pregnancy rate in infertile couples. Both partners of 198 consecutive infertile couples were evaluated. Studies in the female included clinical evaluation of ovulation for a minimum of two menstrual cycles, investigation of tubal patency, and evaluation of sperm survival in cervical mucus. Six semen specimens were analyzed from each male. Laparoscopy, scrotal exploration, and testicular biopsies were performed as required. Where indicated, the female was treated intensively. The only therapy offered to the males was ligation of varicoceles, if present. The couples were grouped on the basis of sperm counts, total sperm counts, motile sperm counts, and total motile sperm counts, and the incidence of pregnancy was computed. Pregnancy rates of approximately 50% occurred in couples where sperm counts or total sperm counts were in the range of 5 to 60 million/ml or 25 to 200 million/ejaculate, respectively. When sperm counts were over 60 million/ml or total sperm counts over 200 million/ejaculate, pregnancy rates increased to above 70%. These observations emphasize the importance of considering infertility as a problem of a couple rather than as a specific disorder of one of the partners. These data also demonstrate a lack of direct correlation between sperm density in the ranges of 5 to 60 million/ml and pregnancy rates in couples where the wife is treated intensively.


Levels of L-carnitine and L-O-acetylcarnitine in normal and infertile human semen: a lower level of L-O-acetycarnitine in infertile semen. The level of total L-carnitine was determined in normal human seminal plasma and sperm. Most of the L-carnitine is concentrated in the seminal plasma and its level is about 10 times higher than that in blood plasma. About 50% of total L-carnitine in normal human seminal plasma exists in the form of acetylcarnitine. Similar studies were also carried out in oligospermic and azoospermic human seminal plasma. The level of L-O-acetylcarnitine in both types of infertile samples is significantly lower than that in normal samples. On the other hand, the level of free L-carnitine is the same in fertile and infertile seminal plasma.


Turbidimetric analysis of human sperm motility. A turbidimetric method has been developed for determining rapidly the fraction of sperm in human ejaculates which show the most vigorous motility. The method is based on the fact that sperm cells so endowed will be the first to swim upward into clear medium from a concentrated cell suspension at the bottom of an optical cuvette. This results in a time-dependent increase in turbidity in the medium which is recorded spectrophotometrically as an increase in absorbance. The determination requires 10 minutes and yields both the fraction of rapidly moving sperm, FRM, and their average velocity, VRM. Examination of 25 samples yielded FRM values of 10% or lower, whereas values for VRM averaged about 100 microns/second. These vigorously motile cells may be the best candidates for fertilization, and samples with a high fraction of such cells should have high fertilizing capacity. It is suggested that this simple turbidimetric test be used in evaluation of human semen as a possible indicator of fertilizing capacity.


Fundamental comments on cell polarography according to Velazquez and Rosado. Some fundamental comments are made on cell polarography according to Velázquez and Rosado (Fertil Steril 23:562, 1972). The results which they have obtained cannot be reliable because fundamental mistakes are made against the principles of the electroanalytic techniques used. We comment upon the conductometry, the amperometric titrations, and the alternating-current polarography as carried out by Velázquez and Rosado.


Proteins of human vaginal fluid.

Proteins of human vaginal fluid. Proteins of vaginal fluid from normal and hysterectomized women were identified and compared with those of cervical mucus. Albumin, alpha1-antitrypsin, alpha2-haptoglobin, alpha2-macroglobulin, beta-lipoprotein, orosomucoid, ceruloplasmin, gamma chains, gamma G. K. (Bence Jones), and immunoglobulins G, A, and M were present in both vaginal fluid and cervical mucus. Fibrin and C-reactive protein were not found in the vaginal fluid but were identified in cervical mucus. alpha2-Haptoglobin, alpha2-macroglobulin, beta-lipoprotein, orosomucoid, and immunoglobulin M were absent in the vaginal fluid of hysterectomized women, indicating that their presence in the vaginal secretion of normal women may be due to contamination from cervical mucus.


The effect of aminopterin-induced folic acid deficiency on spermatogenesis. Folic acid deficiency was produced by injecting aminopterin into adult male albino rats, resulting in inhibition of spermatogenesis. Bone marrow smears were studied to serve as an index of folic acid deficiency; however, changes in spermatogenesis were noticed earlier than the bone marrow changes. Meiotic division was affected more than mitotic division. The nuclei of spermatogenic cells showed degenerative changes. Chromosomal abnormalities, chiefly sticky chromosomes, were noticed in squashed preparations of seminiferous tubules.


Pharmacologic modification of the time course of ovum transport in guinea pigs. Various agents were examined for their effects on ovum transport in the guinea pig. Estrogen significantly accelerated ovum transport in this species. The experiments further demonstrated that estrogen did not act by inducing prostaglandin synthesis, nor by altering plasma progesterone levels. The estrogen-induced acceleration was significantly antagonized by tamoxifen, an antiestrogen that acts by interfering with estrogen receptor synthesis. Cycloheximide also antagonized the effects of estrogen on ovum transport. These data suggest that the modification of ovum transport by estrogen is due to the entrance of estrogen into the nuclei of target cells, and subsequent protein synthesis. Although we assume that this action occurs at the level of the oviduct, our experiments do not prove this assumption.


A comparison of leukocyte alkaline phosphatase and plasma estradiol measurements in the monitoring of clomiphene and gonadotropin therapy. Leukocyte alkaline phosphatase (LAP) and plasma estradiol (E2) were measured in 56 infertile women treated with clomiphene citrate and human chorionic gonadotropin (hCG) and in 21 infertile women treated with human menopausal gonadotropin (hMG) and hCG. Plasma LAP scores were found to correlate significantly with plasma E2 levels in both clomiphene- and hMG-stimulated patients, reflecting the depdence of LAP on the level of circulating plasma estrogens. However, the plasma LAP score failed to distinguish the difference between normal stimulated and hyperstimulated cycles following hMG administration. We conclude that plasma LAP measurements have little value in monitoring ovulation induction therapy.


Hemorrhage induced by intrauterine devices: control by local proteinase inhibition. The intrauterine application of proteinase inhibitors, tranexaminc acid and the pancreatic trypsin inhibitor (Trasylol), reduces or eliminates menorrhagia and intermenstrual bleeding (spotting) produced by an intrauterine device (IUD). A decrease in pain and vaginal (cervical) discharge is also frequently observed. A single application is usually sufficient, more than three never being required. The effect lasts for an average of three cycles. In addition to the clinical use of these agents for the treatment of uterine hemorrhage, the slow release of proteinase inhibitors from an IUD may well be useful in minimizing its side effects without interfering with its contraceptive activity.


[Effect of GABA and phenybut on the neuronal activity of the cortex and potentials of the spinal roots]. The effects of GABA AND PHENYBUT (BEta-phenyl-gamma-aminobutyric acid) on the dorsal (DRP) and ventral (VPR) root potentials were studied in the isolated frog spinal cord. The direct action of these agents on the neuronal membranes was studied by means of the microiontophoretic method in the cat cerebral cortex. Phenybut, like GABA, SUPPRESSES DRP and VRP at the spinal cord level, but it prolongs the duration of DRP and VRP rising phase and at the same time depresses the VR reflexes. Phenybut microiontophoretic application does not considerably affect the neuronal activity whereas GABA exerts an obvious inhibitory action. Differences in the mechanisms of GABA and phenybut actions on the c. n. s. elements are discussed.


[Relationship between blood flow in the motor cortex and neuronal and total bioelectrical activity of the rabbit brain]. In unrestrained rabbits, the local blood flow (LBF), the unit activity in the motor cortex, the EEG, and the EMG of forelimbs were simultaneously recorded during different kinds of stimulation. The EEG arousal response and the increase in the firing rate of unspecific neurons were only followed by the increase in the LBF on adequate stimulation or movement, whereas on inadequate stimulation it was the decrease in the LBF. With the specific neurons, the increase or decrease in their firing rate corresponded either to enhancement or to reduction of the LBF on adequate and inadequate stimulation. The above correlations were only revealed at the normal functional state of the cerebral cortex. The energy expenditure of specific neurons is suggested to be the main factor in the mechanism for the LBF control.


[Electrophysiologic characteristics of the inhibitory neuromuscular synapses of the crayfish with different rhythms of activity]. By means of intracellular recording, the IPSP's parameters and the characteristics of inhibitory neuromuscular transmission in the dactylopod-opener muscle, were studied at different rhythms of activity. The presynaptic character of the high-frequency (pessimal) blockade of inhibitory system was shown. Transformation of the stimulation rhythm was correlated with the drop in the velocity of conduction along the inhibitory axon and/or its branches. At high-frequency stimulation, the mean quantae content of IPSP's on the potentiation plateau prior to transformation was lower than at lower frequencies. No signs of the depletion of the mediator store was revealed during the high-frequency activity. The mechanism of the inhibitory mediator secretion seems to be more reliable than the function of conduction of the presynaptic neural impulse.


[Adaptational characteristics of muscle stretch receptors of the dynamic type]. In cats with deefferented m. triceps, some stretch receptors of the dynamic type were shown to adapt rapidly after stretching of the muscle and keeping it at the new length, whereas other receptors revealed rapid and slow components of the adaptation. The units with different kinds of adaptation coexist in the same muscle, their afferents being related mainly to the group I, although overlapping with the group II afferents does exist. The above differences are revealed at high values of the muscle initial stretch. It seems that the adaptation slow component is based on a mechanical factor depending on the viscous-elastic properties of the tissue in the area of sensitive nerve terminals.


[Activation mechanisms of the contractile cells of cerebral arteries and veins]. In isolated strips of internal carotid artery and middle cerebral artery in humans, spontaneous electric and contractile activities were revealed. Low (35 degrees C) and high (40--41 degrees C) temperatures inhibited the development of spontaneous contractions. Under depolarization of the cells' membranes by potassium ions, no development of spontaneous electric or contractile waves occurred, while contractions of the tonic type were observed in arterial preparations. No spontaneous contractions were found in the cerebral veins.


[Morphologic basis for the common action of the nervous and hormonal control of gastric activity]. In adult dogs and white Wistar rats, relationships between the automonic nerve endings, mucosal endocrine cells, mast cells, and blood capillaries in the gastric wall were studied with the aid of electron microscopy. A close association of 3 components of the regulatory mechanisms: neural, hormonal, and humoral, in the form of the triad comprising endocrine cells, autonomic nerve endings, and blood capillaries, was revealed, with no true synapses between them. Accumulations of the granules of the endocrine cells, synaptic vesicles of the autonomic nerves, and the pinocytose vesicles of the capillary endothelium were seen at inner surface of the cells' membranes which is the morphological indication of the physiological function. The data obtained suggest that the interaction between the 3 above components is realised through the diffuse synapses, and indicate that the interstitium of the digestive tract wall is the area of integration of the neural and the hormonal links of neuro-homoral visceral reflexes.


[Influence of adaptation of hypoxia on the relationship between tissue respiration, temperature and oxygen tension in vitro]. The effect of adaptation to hypoxia on rat tissue respiration at different pO2 and temperature in vitro was studied. The temperature coefficient Q10 and the Michaelis constant Km for oxygen were estimated. The tissue sensitivity to low pO2 and low temperature obviously decreased while the tissue affinity for oxygen and the direct temperature dependence on Km increased in animals adapted to hypoxia. A functional interrelationship between adaptational changes of Q10 and Km of tissue respiration in different organs was revealed. The data obtained suggest participation of cellular oxidation changes in adaptive increase of oxygen affinity.


[The mechanism of follicle growth. II. The mode of action of the follicle-stimulating hormone (FSH) on follicle growth (author's transl)]. The mode of action of the follicle-stimulating hormone (FSH) on ovarian follicle growth was studied in hypophysectomized rats using the histologic, autoradiographic and histochemical techniques. The follicle growth was stimulated by the administration of both FSH and estrogen. The histologic finding of the follicle growth induced by the two hormones was different. Namely, after the administration of FSH, the theca layer was thick, but after the administration of estrogen, it was thin. 3H-thymidine and 3H-leucine were used to investigate cell division in a growing follicle. The uptake of 3H-thymidine and 3H-leucine by the theca layer was enhanced remarkably by FSH. On the other hand, the uptake of 3H-thymidine by the granulosa layer was enhanced by FSH or estrogen, while the grain count of granulosa cells was increased only by the administration of estrogen. Moreover, the administration of FSH resulted in an increase of the enzyme activity of glucose-6-phosphate dehydrogenase (G-6-PD), DELTA5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) and alkaline phosphatase (ALPase) in the theca layer. Furthermore, the administration of FSH caused an increase in the serum estradiol and estriol of rats, whereas the administration of estrogen did not. It seems possible, therefore, that FSH stimulated proliferation of theca cells and produced estrogen. The results suggest that the estrogen produced by the theca cells might stimulate proliferation of granulosa cells; consequently, follicle growth might be induced.


High performance liquid chromatographic determination of dothiepin and northiaden in human plasma and serum. A method has been developed for the separation and measurement of dothiepin and the N-demethyl metabolites, northiaden, in human plasma or serum by high performance liquid chromatography. The method uses a structurally-related drug, amitriptyline, as an internal standard and provides a limit of detection of about 10 ng/ml for each component. At a concentration of 20 ng/ml, northiaden and dothiepin could be measured with +/-11% and +/- 6% of the mean respectively and at 200 ng/ml within +/-3% and 1% of the mean. The method has been applied to the analysis of serum from patients undergoing dothiepin therapy.


Steady-state serum concentrations of dothiepin and northiaden after two dosage regimens of dothiepin hydrochloride (Prothiaden). Five healthy volunteers took part in a crossover study which examined the serum concentrations of dothiepin and northiaden after a 25 mg three times a day and a 75 mg once a day dosage regimen of Prothiaden. The inter-individual variation of serum levels was large after either schedule which is to be expected with this group of drugs. The minimum steady-state level of dothiepin tended to be lower after the single daily dose, but the differences were small and not statistically significant. The approximate maximum steady-state levels of dothiepin showed large intra-and inter-subject variation and no obvious trend. The values of the desmethylated metabolite, norhiaden, tended to follow the dothiepin concentrations but were lower than the parent drug. Average steady-state levels tended, with one exception, to be very similar after both regimens with no evidence with no evidence fo any trend when comparing the two regiments. The study showed that the two regimens yielded similar steady-state serum concentrations both of drug and metabolite but inter-individual differences were large.