The integrative role of the intralaminar system of the thalamus in visual orientation and perception in the cat. Electrical stimulation with repetitive pulses (6/sec) was applied to the internal medullary lamina and produced tonic contraversive turning movements of eyes and head which were associated with recruiting responses in the visual cortex. Optical gratings of a spatial frequency of 0.5 c/deg which alternated with diffuse illumination of equal intensity were then presented to the animal during conjugated adversive eye movements induced by intralaminar stimulation with continuous sine-wave alternating currents of 5000 c.p.s. The head of the animal was fixed except for rotation in the horizontal plane. Prior to intralaminar stimulation it was turned in the direction opposite to the induced eye movements so that the animal always viewed the central area of the screen. The potential recorded in the visual cortex in response to the gratings consisted of an initial positive-negative potential of the order of 20 muV followed by later deflections of irregular shape. The size of this initial potential was measured during induced gazing and in the absence of intralaminar stimulation. A significantly greater potential in response to the gratings was found during gazing. Diminishing the visual acuity of the animal resulted in a marked decrease of the initial potential and in this condition very little increase was obtained during gazing. No enhancement of the potential was seen when stimulation was applied to other thalamic structures that yielded no visual orientation. It is concluded that perception of contrast is improved during visual orientation and that the effect is due to a concomitant activation of unspecific intralaminar afferents to the visual cortex.


Field potentials in the olfactory bulb of the rainbow trout (Salmo gairdneri): evidence for a dendrodendritic inhibitory pathway. Field potentials have been recorded from the olfactory bulb of the teleost fish, Salmo gairdneri. Stimulation of the olfactory nerve generates a complex wave pattern, which when recorded near the surface in the centre of the bulb consists of one positive and three negative components, P, N1, N2 and N3. The N1 has been attributed to depolarization of mitral cell dendrites, N2 to depolarization of the superficial dendrites of granules cells, and P to subsequent hyperpolarization of mitral cells. Possible origins of the N3 wave are discussed. Spikes from single units recorded in the mitral cell layer usually occur superimposed on the N1 wave, and single units recorded in the region of granule cells are usually found coincident with the trailling edge of the deep positive wave. With the exception of N3 the patterns of activity observed are very similar to previously published results obtained from other vertebrates. It is suggested that the dendrodendritic inhibitory pathway proposed for the mammalian olfactory bulb (Rall et al., 1966; Rall and Shepherd, 1968) is common to all vertebrates.


Spontaneous activity of single neurons in the olfactory bulb of the rainbow trout (Salmo gairdneri) and its modulation by olfactory stimulation with amino acids. Spontaneous action potentials recorded from 126 neurons in the olfactory bulb of Salmo gairdneri show a higher tendency towards bursting patterns of activity than those shown in previous reports about other fish. Granule cells and periglomerular cells are more likely to fire in bursts than mitral cells. Natural chemical stimulation of the olfactory mucosa with amino acid solutions produced a unique pattern of excitatory and inhibitory responses across all units. Chi-square values were calculated for stimulatory effectiveness between forty-five pairs of odours. L-serine and L-alanine consistently showed a high  degree of similarity with several other odours. The converse was true for GABA and L-histidine, although this pair had a high chi-square value when mutually compared. Enantiomeric pairs of amino acids were often found to have opposite stimulatory effects on bulbar units. These results are discussed in relation to the possible properties and configurations of odorant receptor sites for amino acids in the fish olfactory mucosa.


Maintained activity of cells in the three shrew's optic tract. The maintained activity of different types of ganglion cells in the tree shrew's retina has been investigated in darkness and different adaptation luminances, with particular reference to on-centre sustained and transient cells. The firing rate of on-centre sustained cells rises with increasing luminance up to 5.10(-2) W/m2 (human photopic equivalent 5.10(4) cd/m2) whereas, for on-centre transient cells no simple relationship between luminance and activity could be found. The ratio of mean and standard deviation (regularity) of the interval length of sustained cells increases with light intensity, while in most transient cells a constant ratio is observed. Various kinds of interval histograms are observed for sustained units: exponential, gamma, bimodal and other types. Transient cells tend to fire in bursts with correspondent biomodal interval histograms. The first order serial correlation coefficient is positive for the majority of sustained cells and negative for most transient cells. It is argued that the final statistical properties of the maintained activity of retinal ganglion cells are mainly determined by the retinal circuitry between photoreceptors and ganglion cells.


Effects of frontal eye field stimulation upon activities of the lateral geniculate body of the cat. Effects of electrical stimulation of the frontal eye field (FEF) upon activites of the lateral geniculate body (LG) were studied in encephale isole cats. In some experiments the effects were examined by recording field responses of the dorsal nucleus of LG (LGd) and the visual cortex (VC) to electrical stimulation of the optic chiasm (OX). Conditioning  repetitive stimulation of FEF exerted no significant effects on the r1 wave of LGd responses but had a facilitatory effect on the r2 wave. FEF-induced facilitation of VC responses was prominent in the late postsynaptic components. These effects had latencies of 50-100 msec and durations of 200-500 msec. Transection of the midbrain showed that most of the FEF-effect was not mediated via the brainstem reticular formation. Extracellular unitary recordings were made from 125 neurons, of which 91 were LGd neurons, 23 neurons of the caudal part of the thalamic reticular nucleus (TRc) and 11 neurons of the ventral nucleus of LG (LGv). In 30 to 87 LGd relay neurons FEF stimuli increased response probabilities to OX stimuli and their spontaneous discharges. These FEF-facilitated LGd neurons were distinguished from the non-affected ones in that the former had longer OX-latencies than the latter. The FEF-facilitated neurons probably correspond to "X" neurons of LGd. In 17 TRc neurons the effects were inhibitory. Their time courses were similar to those of the facilitation in the LGd relay neurons. Seven LGv neurons recieved facilitaroy effects from FEF. Among them 5 neurons showed short-latency (6.7-17 msec) responses to FEF single shocks. The FEF sites inducing conjugate lateral eye movements exerted stronger facilitatory effects than those inducing upward or centering eye movements did. It is suggested that the effects may subserve to cancel the inhibitory convergence onto X-cells just after saccadic eye movements so as to improve visual information transmission through LGd during the eye fixation.


Dynamic properties of excitation and two-tone inhibition in the cochlear nucleus studied using amplitude-modulated tones. The dynamic properties of excitation and two-tone inhibition in the cochlear nucleus were studied from extracellularly recorded unit responses to two simultaneously presented tones. One tone was presented at the unit's characteristic frequency, CF, the other at the unit's best inhibitory frequency, BIF. One or both of the tones were amplitude-modulated with pseudorandom noise. The system under study is in general nonlinear, but can be considered to function as a linear system for small changes in sound intensity around a certain operating point. The dynamic properties are likely to be different at different operating points. A suitable method for the study of dynamic properties of such a system employs tones that are amplitude-modulated with pseudorandom noise. In the present study, the dynamic properties were assessed by cross-correlating the unit discharge rate with the modulation. This was accomplished by computing the cross-covariance function between a period of noise and a period histogram of the discharges, the histogram being locked to the periodicity of the pseudorandom noise. In this way, it has been shown in previous works (Moller, 1973, 1974b), that the cross-covariance function is a valid approximation of the system's impulse response function at a certain sound intensity, provided the modulation is kept at a low value. In the present study the computed cross-covariance function is thus an approximation of the change in discharge rate of the cochlear nucleus units in response to a brief increase in stimulus intensity. As the response of the system under the given circumstances is approximately that of a linear system, the integrated cross-covariance is an approximation of the system's step response function, i.e the change in discharge rate that resulte from a hypothetical step increase in stimulus intensity. The results of the present study can be summarized as follows: 1. The impulse and step response functions computed from the responses to the modulated inhibitory tone of the great majority of units from which recording was made were found to be virtual mirror images of those obtained when the excitatory tone was modulated, the inhibitory response being somewhat smaller in amplitude than the excitatory. 2. When both tones were modulated simultaneously, the step response function was approximately the algebraic sum of the two responses obtained when the tones were modulated singly, further indicating that the system functions as a linear system when the stimulus amplitude is varied slightly around a certain operating point. 3. The shape of the cross-covariance functions is similar for all three stimulus situations, but varies with stimulus intensity and is different in different units. 4. The implication of the results is that the inhibition studied may either originate from the inhibition (suppression) seen in primary fibers or it may be the result of a true neural inhibition in the cochlear nucleus that occurs without any interneurons.


The lateral reticular nucleus in the cat. V. Does collateral activation from the dorsal spinocerebellar tract occur? 1. The assertion made by Burton, Bloedel and Gregory (1971) that neurones in the mLRN (major portion of lateral reticular nucleus comprising its parvi- and magnocellular parts) receive collateral excitation from the dorsal spinocerebellar tract (DSCT) has been tested. The activation of mLRN neurones on stimulation of limb nerves was studied in preparations with the spinal cord interrupted at C3 sparing only the dorsal part of the ipsilateral lateral funiculus (iDLF preparations), only the ipsilateral ventral quadrant (iVQ preparations), or only the ipsilateral lateral and ventral funiculi (iLFVF preparations). 2. In iDLF preparations (with the DSCT intact) stimulation of limb nerves evoked responses in only occasional mLRN neurones. These responses could be attributed to activation from some dorsally located fibres belonging to the bilateral ventral flexor reflex tract (bVFRT) and to activation from a previously unknown path activated after a long latency from ipsilateral forelimb and hindlimb afferents. 3. In iLFVF preparations (with the DSCT intact) and iVQ preparations (with the DSCT interrupted) most mLRN neurones responsed to limb nerve stimulation. The responses in two preparations were similar and could be attributed largely or exclusively to activation from the bVFRT. 4 It is concluded that the DSCT does not activate any major group of mLRN neurones.


Conduction velocity groupings among axons of cat retinal ganglion cells, and their relationship to retinal topography. Three unresolved issues in the conduction velocity groupings among the axons of cat retinal ganglion cells have been investigated. These are (i) the degree of separation of the velocity ranges of the axons of X-and W-type ganglion cells; (ii) the question whether the velocities of X-and Y-cell axons (i.e. of t1 and t2 axons have faster velocities than contralaterally projecting axons. Evidence is presented that the velocity ranges of W- and X-cell axons are almost completely separate; that the velocities of X- and Y-cell axons are not graded with retinal eccentricity (except in the immediate vicinity of the area centralis) and that ipsilaterally projecting axons are not faster conducting that contralaterally projecting axons. These results provide a context for summarising present understanding of conduction velocity groupings among the axons of cat retinal ganglion cells.


Functional characterization of primary vestibular afferents in the frog. 1. In order to more accurately identify the nature of the vestibular input to central neurons, the response properties of single semicircular canal and otolith units in the frog VIIth nerve were studied in curarized preparations. 2. An equation describing the response plane was calculated for each canal on the basis of null point measurements. These results show that the ipsilateral canal planes are orthogonal within 2-5 degrees, and the pairs of right-left synergists are essentially coplanar. A head position of 10-20 degrees maxilla nose up produces optimal horizontal canal and minimal vertical canal activation with horizontal rotation. 3. The frequency response of the horizontal canal was examined in the range 0.025-0.5 Hz. Comparatively shorter phase-lags and a 10 fold greater acceleration gain in this frequency range distinguish the frog from the mammalian species studied. 4. Otolithic responses were tonic, phasic-tonic, and phasic in nature. The preponderance of the latter two groups is stressed (94%). Tonic responses were proportional to the gravitational vector change. Phasic responses were proportional to velocity during transitions in head position and phase-led displacement (30-80%) with sinusoidal acceleration in roll and pitch. 5. Efferent vestibular neurons respond to rotation in the horizontal (usually Type III) as well as vertical planes. Responses in the vertical planes result from canal and/or otolithic input to these neurons indicating that the vestibular efferent system receives extensive multi-labyrinthine convergence.


The in vivo inactivation of GABA and other inhibitory amino acids in the cat nervous system. In cats anaesthetised with pentobarbitone, the effect of inhibitors of the in vitro cellular uptake of GABA were tested on the responses of single central neurones to GABA and other depressant amino acids. (4)- AND (-)-nepecotic acid, (4)-2,4-diaminobutyric acid (DABA) and 2,2-dimethyl-beta-alanine, enhanced the action of GABA on spinal, cerebellar and cerebral cortical neurones. In the spinal cord DABA, and to a less estent (-)-nipecotic acid, enhanced the action of beta-alanine, whereas the actions of glycine and taurine were unaffected by DABA and reduced by (-)-nipecotic acid. In the cerebellum and cerebral cortex, these two substances enhanced the action of GABA, usually to a greater extent than that of beta-alanine and taurine, although this specificity was not marked. The GABA-mediated basket cell inhibition of Purkinje cells in the cerebellum was unaffected by DABA and (-)-nipecotic acid, and neither substance appears suitable for determining the role of uptake processes in the inactivation of synapitcally released GABA. Quantitatively these in vivo results agree more closely with recent vitro uptake studies in cat tissue than the previously published data on rat cerebral cortex and dorsal root ganglia, and the observations provide further evidence for the importance of cellular uptake in maintaining low extraneuronal concentrations of inhibitory amino acid transmitters.


Calcium uptake in preterminal central synapses: importance of mitochondria. Energy dependent 45Ca2+ uptake in the synaptosomal preparation from guinea pig cortex has been investigated. 45Ca2+ uptake was stimulated by ATP, the absolute value of uptake being dependent on the extent of synaptosomal disruption caused by osmotic shock. A quantitative comparison of microsomal and mitochondrial ATP-dependent 45Ca2+ uptake showed that only mitochondria had a large enough capacity to account for the Ca uptake levels observed in the synaptosomal preparation. ATP-stimulated 45Ca2+ uptake in mitochondria, 'intact' and 'shocked' synaptosomes was inhibited by atractyloside, DNP, oligomycin and ruthenium red but unaffected by antimycin A and rotenone. This was interpreted as evidence that mitochondria were responsible for ATP-dependent synaptosomal Ca2+ uptake, the increase in uptake seen on osmotic lysis being due to the deocclusion of intraterminal mitochondria. Synaptosomal and mitochondrial 45Ca2+ uptake was also stimulated by the mitochondrial respiratory substrate glutamate; this uptake was sensitive to antimycin A, DNP, rotenone and ruthenium red but insensitive to atractyloside or oligomycin thus indicating it was of mitochondrial origin. No change in glutamate-dependent 45Ca2+ uptake was seen on osmotic lysis of the synaptosomes as the expected increase due to the release of occluded mitochondria was counterbalanced by the damaging effect of hypo-osmotic shock on the glutamate-stimulated 45Ca2+ uptake process.


Hepatic and cerebral coenzyme A contents after intravenous injection of coenzyme A in rats. Hepatic CoA concentrations and contents were significantly higher in rats having received i.v. CoA injections that in control rats. Maximum hepatic CoA concentrations were found 0.5-1 h after injection. In rat brain, no increase in CoA concentration was detected after i.v. injection of CoA.


[Isoenzymes of alkaline phosphatase - reference values in young people and effects of protein diet (author's transl)]. In 260 normal students, 20-25 years old, the variation in the activities of serum alkaline phosphatase and its isoenzymes with sex, ABO blood groups, and protein intake were studied. The values are on the whole higher in males than in females. The activity of the intestinal isoenzyme was higher in subjects taking protein-rich diet than in those taking protein poor diet.


Cholesterol esterification activities in the intestines and pancreas of the albino rat. Cholesterol esterification activities in intestines and pancreas are much greater with unsaturated fatty acids than with the saturated ones; the maximum activity is with arachidonic acid in intestines and with oleic acid in pancreas. The pancreatic cholesterol esterification activity is higher than the intestinal one.


Lipolytic response of "diabetic" mice (db/db) to isoproterenol and propranolol in vivo. The genetically diabetic and obese db/db mice responded lipolytically to isoproterenol and propranolol similarly to normal mice in vivo. However, considering the large amount of triglyceride in a db/db mouse, we conclude that the in vivo response of db/db adipose tissue is deficient in magnitude.


The effects of various agents in vitro on homocarnosine-carnosine synthetase from rat brain. The present paper reports the first evidence that homocarnosine-carnosine synthetase from rat brain requires free sulfhydryl groups for activity. The activity of the synthetase can be stabilized by dithioerythritol and inhibited strongly by Cu2+, Cd2+, Hg2+, Zn2+, and to a lesser extent by Ca2+, Ni2+, Li, chlorpromazine, alpha-methyl DOPA and norepinephrine at the concentrations tested.


Effects of pre- and simultaneous treatment with urea on the induction of chromatid aberrations in Vicia faba. Pre- and simultaneous treatments of Vicia faba root tip meristems with urea and ethyl alcohol, mitomycin C, maleic hydrazide, 3H-thymidine and X-rays, respectively, were found to result in mutagen-specific changes of the spectrum and yield of induced chromatid aberrations.


Nuclear projections in tumour cells and large chromosome markers. The application of banding techniques on cytological smears from pleural effusion in a case of histiocytic sarcoma has provided direct evidence for correspondence between nuclear projections in tumour cells and extra large chromosome markers observed in the neoplastic karyotype obtained by direct preparations.


Genetic variation in constant environments. Allozymic variation in proteins encoded by 32 gene loci was analyzed electrophoretically in 64 specimens from 6 localities representing 2 species of the spadefoot toads Pelobates syriacus and P. cultripes from Israel and Portugal, respectively. Out of the 32 loci examined, Esterase-1 was the only locus that proved strongly polymorphic in all 6 localities and in the 2 species. The pattern of genetic variation in Pelobates is best explained by the environmental variability model. Selection for homozygosity as an adaptive strategy seems to operate in the relatively constant and narrow subterranean niche.


The behavior of alloxan in the Hill reaction. Hill activity induced by alloxan is characterized by non-stoichiometric oxygen evolution and cyclic electron flow due to autoxidation of dialuric acid and alloxantin, the reduction products of alloxan.


Poly(A) associated RNA from mitochondria and microsomes of rat brain. Rat brain mitochondria contain a significant proportion of poly(A) associated RNA which is higher than that found in microsomes from the same source. When steady state poly(A) RNA of brain mitochondria was analyzed by microelectrophoresis, it displayed a characteristic separation pattern with a large amount of "free" poly(A).


Spontaneous thermoregulatory oscillations in cutaneous efferent sympathetic activity. Patterns of changes in cutaneous efferent sympathetic activity which have previously been shown to occur during experimental manipulation of the temperature of various thermosensitive body sites, have now been shown to accompany spontaneous thermoregulatory activity. That is, under thermoneural conditions, concurrent spontaneous oscillations in skin blood flow and efferent sympathetic activity were observed.


The time course of plasma enzyme changes accompanying skeletal muscle stimulation. 30 min electrical stimulation of hind limb skeletal muscle in nembutal anaesthetised dogs was accompanied by increases in arterial haematocrit, plasma GOT and plasma LDH, which were almost completed within the first 10 min of stimulation. This fast response indicated that a rapid change in either the entry and/or clearance of enzyme from the plasma must have occurred.


On the role of the decreased renal vascular resistance in the mechanism of volume natriuresis. Acute hypophysectomy (AH) prevented the increase of the cardiac output, renal cortical blood flow (e.g. the decrease of the renal vascular resistance) and renal sodium excretion during the ECFV expansion. The non-occurrence of natriuresis in AH rats is suggested as being partly in causal relation to the inability to decrease the renal vascular resistance and thus to increase the peritubular hydrostatic pressure.


A presynaptic effect of whole venom of Dendroaspis jamesoni on the hemidiaphragm of rat. Dendroaspis jamesoni venom in a dose of 12.5 mug/ml restricts the uptake of Ca+ leading to inhibition of release of Ach from the motor nerve terminals of the hemidiaphragms of rats.


The influence of salt intake on glomerular count in compensatory kidney hypertrophy in rats of different ages. Drinking saline instead of water elevated the glomerular count in hypertrophied kidneys of rats uninephrectomized as adults. No changes occurred in glomerular concentration in kidney tissue indicating a more marked increase of other kidney structures. This procedure was ineffective in immature animals.


Exocrine pancreatic enzymes in cycloheximide treated rats. Cycloheximide, even in a dose of 0.25 mg/kg administered s.c. to rats stimulated by pancreozymin and secretin, inhibited lipase activity in pancreatic juice. Lipase activity in serum of control animals was inhibited by cycloheximide. The secretion of trypsin and chymotrypsin was also decreased.


[3H]-Noncocaine and [3H]-pseudococaine: effect of N-demethylation and C2-epimerization of cocaine on its pharmacokinetics in the rat. After i.v. injections of cocaine, norcocaine, pseudococaine to the rat, the T 1/2 in brain were 0.4, 0.6, 0.2 h respectively and in plasma 0.4, 0.5, 0.2 h respectively. Benzoylnorecgonine and norecgonine were the metabolites of norcocaine in brain. Pseudonorcocaine, pseudobenzoylnorecgonine, pseudobenzoylecgonine and pseudoecgonine were the metabolites of pseudococaine in rat brain. Benzolynorecgonine and pseudobenzoylecgonine had potent stimulant activity intracisternally in the rats.


On the mechanism of pyrogenic action of ricin. The incubation of rabbit white blood cells with ricin, the toxic protein of castor oil seeds, leads to the production of endogenous pyrogens. This induction can be inhibited by the antibiotics actinomycin D or cycloheximide. The results are discussed in terms of disturbed corticosteroid- and Mg2+-levels.


Monamines in brain and urine of rats with hereditary hypothalamic diabetes insipidus. Monoamine levels in brain and urine of homozygous and heterozygous diabetes insipidus (DI) rats (Brattleboro strain) were assessed. Homozygous DI rats had a higher whole brain content of serotonin than their heterozygous littermates. However, when corrected for differences in brain weight, homozygous DI also appeared to have higher brain concentrations of noradrenaline, tyrosine and GABA. The total 24 h excretion of all amines and their precursors was greater in the homozygous than in the heterozygous rats.


Inhibition of high affinity uptake of GABA by branched fatty acids. Several branched fatty acids including an antiepileptic agent nDPA were tested as potential inhibitors of high affinity uptake of GABA by brain slices and synaptosomes. Only three compounds (2-butyl-3-propylhexanoic acid, 5-propyloctanoic acid, 2-propylpenten-2-oic acid) were found to be relatively weak inhibitors of the uptake system. There was no correlation between anticonvulsant properties of the branched fatty acids and their potencies as inhibitors of high affinity uptake of GABA.


The electrophysiological effects of ionophore X-537A on cardiac purkinje fibres. Using classical microelectrode techniques in canine cardiac Purkinje fibres, calcium ionophore X-537A was shown to shorten the action potential, hyperpolarizing the membrane and lowering the plateau, suggesting that intracellular calcium controls membrane permeability to potassium in this preparation.


Ultrastructural study of binucleation in cells of the rat adrenal glomerular zone after a prolonged low-sodium diet. Binucleate cells have been found in the glomerular zone of the adrenal cortex in rats subjected to low-sodium diets. By considering the various possibilities for their production, both the findings of nuclei in process of constriction and nuclei identical in form, confronted and smaller in size than those of neighbour cells, are in agreement with an amitotic nuclear division as the possible mechanism for the formation of these cells.


Epidermal growth factor enhancement of skin tumor induction in mice. Subcutaneous injection of epidermal growth factor 1. significantly shortened the latency period for the appearance of methylcholanthrene induced skin tumors and 2. increased the average number of papillomas elicited per mouse in both the Swiss Webster and C3HeB/FeJ strains.


Calcium and magnesium deficiency-induced atrophy of muscle and calcium accumulation in the spinal cord. After severe dietary calcium-magnesium deficiency in rats, succinic dehydrogenase and acetylcholinesterase enzyme activity of gastrocnemius muscle showed a neurogenic atrophy. This alteration was associated with a high concentration of calcium in the spinal cord.


Sister chromatid differential staining pattern in prematurely condensed chromosomes. Application of sister chromatid differential (SCD) procedure on G1, S and G2 prematurely condensed chromosomes (PCC) of cells in the second and third cycle of DNA replication in medium containing BrdU reveals differential staining patterns characteristic of their respective stages in the cell cycle. These findings also suggest a structural similarity between PCC and metaphase chromosomes.


Chemical modification of genetic damage from continuous irradiation in mice. It has been demonstrated that Adeturon (S-2-aminoethyl-iso-thiuronium adenosine triphosphate) showed a marked protective effect against translocations induction in mice germ cells after chronic gamma-or neutron-irradiation.


Unstable L-forms of micrococci in human foetal blood. In human foetal blood the presence of Micrococcaceae in the unstable L-form, probably taking origin from the placental transmission of minimal reproductive units, has been recognized by means of microscopic and cultural methods.


High levels of free fatty acids and their esters in lymphoid cells resistant to cortisone or cyclophosphamide. The lymphoid cells from thymus, spleen or mesenteric lymph node of mice treated with hydrocortisone or cyclophosphamide contained the significantly high levels of free fatty acids, triglycerides and cholesterol esters as compared to the corresponding cells from untreated animals.


Distribution of the A blood-group activity in porcine serum. The A blood-group activity of pig serum is bound to a lipid, in some cases also to a nonlipid fraction. The major lipidic A activity (roughly 50%) is carried with the HDL class, while the VLDL and LDL classes contain roughly 25% each.


The effect of renal hydrodynamics on immune complex deposition. The role of renal hydrodynamics on renal deposition of immune complexes was evaluated in acute serum sickness. Using i.v. radiolabelled antigen in rabbits under a variety of hydrodynamic alterations, these studies suggested that although intrarenal hydrodynamics influence renal deposition of immune complexes factors other than intrarenal hydrostatic pressure may be important.


Subcellular steroid distribution in the rat adrenal cortex. The subcellular distribution of main steroids (pregnenolone, progesterone, corticosterone) and of cholesterol -- this last after correction according to exchanges occuring during differential centrifugation -- is presented in the rat adrenal cortex. The distribution patterns are not necessarily the same as established according to the localization of hydroxylating enzymes.


Effects of thyroxine and exercise on the glandular and plasma levels of corticosterone in the male rat. The results presented here demonstrates that the thyroid gland is essential for normal corticosterone production. They further show that exercise stimulates this production whether the thyroid gland is present or not. The release or metabolism of corticosterone seems dependent upon an intact thyroid gland since plasma levels of corticosterone are decreased during exercise if the thyroid is absent. The administration of thyroxine is not sufficient to renew these levels.


Testosterone in human saliva.

Testosterone in human saliva. Testosterone has been detected in whole human saliva. Levels averaged (+/- SE) 295 +/- 36 and 195 +/- 25 pg/ml in adult males and females, respectively, and usually were undetectable in children. In adult males, the excretion of testosterone in saliva appeared to follow a circadian rhythm.


Monoamine oxidase localization in the ependyma and infundibular recess in the catfish Clarias batrachus and its probable significance. The presence of monoamine oxidase (MAO) in the cerebrospinal fluid (CSF) and MAO positive tracts bridging the CSF and the subependyma strongly suggest the involvement of CSF in the neuroendocrine control of hypophysial function.


New karyological data of Rhinoderma: the chromosomes of Rhinoderma rufum. The chromosomes of the Chilean frog Rhinoderma rufum are described for the first time. This chromosome set is compared with the karyotype of R. darwinii. The importance of the karyological data applied to the phylogeny and systematics of this genus are discussed. A tentative hypothesis of karyological evolution of Rhinoderma is given.


Thermodynamic aspects of development for Tenebrio molitor L. Predictions of the thermodynamics of irreversible processes are tested for the development and aging of an insect. Specific heat production and specific respiration rate decrease towards a steady state with deviations for the time of hatching of the imago.


Growth and development of the American bollworm Heliothis armigera Hubn. under laboratory mass rearing conditions. A kidney bean meal diet was the most satisfactory laboratory diet for the larvae of the American bollworm Heliothis armigera Hubn. Optimum rates of survival (63.5%) occurred and the larval growth was better than that of larvae reared on castor oil plant leaves. The pupal weight and the fecundity of the resulting adults were also much better than those on the control host plant.


Electric organ discharges of the weakly electric fish Gymnarchus niloticus (Mormyriformes) in its natural habitat. Electric organ discharges (EODs) of Gymnarchus niloticus in its natural habitat (Chari River, Chad Basin) and accompanying ecological data (pH, conductivity, temperature, turbidity, O2 dissolved) were recorded. The EOD frequencies ranged from 204 to 313 Hz (day) and 196-326 Hz (night). In social swimming the range of interfish EOD frequency differences was from 4 to 82 Hz. The EOD frequency seems to decrease with the age of the fish.


Primary nucleolus and amphinucleoli in the oocytes of Patella coerulea L. (Moll. Gast.). Electron microscope observations show in the primary nucleolus some granulations with dimensions less 70 A than those of the amphinucleoli (90 A). Even though the primary nucleolus has a high RNA content, this has not a very active turnover except at the periphery, probably in relation to the emission of 'daughter-nucleoli'. The amphinucleoli, even though they do not have RNA which is cytochemically discloseable, possess, however, RNA at a very high rate of turnover.


Relation of efferent impulse activity in splenic nerve to reflexly induced reactions of resistance and capacitance vessels to spleen. Constrictory responses of splenic resistance vessels arising under pressor reflexes were abolished by hexonium (2 mg/kg) as well as the high amplitude (above 15 muV) impulses in sympathetic splenic nerves. Constrictory and dilatory responses of splenic capacitance vessels were preserved after administration of the same dose of hexonium and correlated as to the directivity with the changes of the low amplitude (15 muV and lower) impulsation in the splenic nerve.


'Binding' of glutamate and asparatate to synaptosomal fractions of six regions of the feline brain. The order of potency of 'binding' of both glutamate and aspartate to synaptosomal fractions of brain regions was: cerebellar cortex greater than caudate nucleus greater than or equal to cerebral cortex greater than medulla approximately pons greater than corona radiata. Glutamate was bound to a greater extent than aspartate to particles of all regions studied, except for cerebral cortex.


Deficiency in renomedullary prostaglandin synthesis related to the evolution of essential hypertension. Continued PG synthesis in the early stages of essential hypertension might reflect an activation of the renal antihypertensive function in respect to neurogenic and/or hormonal pression stimuli, subsequently a deficiency of renal PG synthesis related to irreversible changes with the kidney would lead to the prepoderance of a pressure mechanism, resulting to a further increase of blood pressure.


The Fusus coli of the rabbit as a pacemaker area. Section of the rabbit's proximal colon orad to the fusus coli resulted in a marked reduction in both slow-wave frequency and differentiation of the two kinds of faeces produced. This indicates the existence of a pacemaker area and a mechanical role for the reversed oral-aboral gradient of the proximal colon.


High altitude influence on the level and turn-over time of cardiac norepinephrine in rats. In rats exposed to an altitude of 2,900 meters the level of endogenous cardiac norepinephrine decreases after the 5th day of exposure. The turner-over time of the amine proceeds in 3 steps which are probably related to periods of stress and adaptation: initial increase, important decrease from the 5th day and return to a normal value from the 12th day.


A new quinoline-carbamate aphicide.

A new quinoline-carbamate aphicide. We found that it was nearly impossible to apply the quinoline-carbamate aphicide per os by means of synthetic diets, owing to its high feeding-deterrent-effect. After application via the roots of the host plant, this systemic compound is deposited on the leaf surface. The results suggest that the toxic effect is not the result of the oral uptake of phloem sap, but of the tarsal contact with the toxicant. Sensitivity of aphids to this compound and LD50-values were determined after topical applications.


3-hydroxy-3-methylglutaric acid and experimental atherosclerosis in rats. In rats 3-hydroxy-3-methylglutaric acid effectively counteracts the lipemic and atherosclerotic response of massive doses of vitamin D2. It regressed the formation of atheromatous arterial lesions. Furthermore the significant decrease in serum beta-lipoprotein levels on HMG treatment could be due to decrease in VLDL triglyceride and cholesterol levels.


Effect of acetylcholine on melanophores of Rana tigrina. Acetylcholine produced melanin aggregation and blanching of skin colour in Rana tigrina, the common Indian frog. The effects were more prolonged in frogs pretreated with an anticholinesterase agent. Acetylcholine effects were not antagonized by either m-cholinolytic (atropine) or n-cholinolytic (pentolinium) agents, but were markedly inhibited by procaine. The results have been discussed in the light of the well-known membrane-stabilizing effect of procaine.


Action of stannous and stannic chlorides on bacteria. Stannous or stannic chlorides reduced the growth rate of K. aerogenes, Ps. reptilovora and an unidentified bacterium in a minimal liquid medium and on agar plates. The greatest effect was observed with K. aerogenes and was accompanied by a decreased viability, but 100% survival occurred with other strains. The metal was loosely bound to the cells and there was no direct correlation between the amount adsorbed and the biological response.


Nerves and muscles regulating feather follicle movements in the chicken. It was found that most feather follicles posses more than a single muscle system but only single nerve endings were observed in a feather follicle. It seems that muscles exist which antagonize each other. Anastomoses of nerves originating from different sources and flowing of mixed nerves into the feather follicle could explain the antagonistic action of the muscles on the feather follicle.


DNA-mediated transformation in the platyfish-swordtail melanoma system. A genetic marker, the tumor gene Tu, which causes the formation of abnormal melanophores, the T-melanophores, in the skin of Xiphophorine fish has been transferred by donor DNA from a Tu genotype to recipient embryos lacking Tu. Abnormal melanophores which are identical to the T-melanophores of the donor genotype occurred only in recipients treated with Tu-DNA and not in those treated with Tu-free control DNA.


Reappearance in vivo of neuraminidase-sensitive sialic acid in L 5222 rat leukemia cells. Cell electrophoretic data and quantitative sialic acid determination show that, 16 to 20 h after i.p. implantation of neuraminidase-treated L 5222 rat leukemia cells, the original sialic acid content at the cell periphery is reconstituted.


Extravesicular noradrenaline in developing peripheral adrenergic nerves. Using a fluorescence technique numerous developing noradrenergic nerve terminals were observed in the muscle coat of the rat ductus deferens between 2 and 6 days postpartum. In the electron microscope similar developing nerve terminals possessed an extensive system of tubular endoplasmic reticulum but did not contain the small dense cored vesicles characteristic of mature noradrenergic nerve terminals. Thus the tubular reticulum is proposed as an alternative storage site for noradrenaline in developing adrenergic nerves.


Plating efficiency of mouse embryo cells as a function of gestational age. Mouse embryo cells can be plated directly from single-cell suspensions of fresh embryos. For randomly bred Swiss mice, there is an increase in plating efficiency as a function of gestational age. Colony-forming units appear at about day 10 and there is an exponential increase in colony-forming ability up to day 16, after which there is no further increase.


Kinetics of DNA repair synthesis in guinea-pig pancreatic slices following in vitro exposure to N-methyl-N-nitrosourethane. In vitro exposure of guinea-pig pancreatic slices to NMUT resulted in an increase in hydroxyurea-insensitive 3H-TdR incorporation into DNA; this represents DNA repair synthesis following NMUT-induced DNA damage. The kinetics of this hydroxyurea-insensitive 3H-TdR incorporation suggest that the NMUT-induced DNA damage is largely repaired within 2 hours.


Peripheral sympathetic innervation of the deep pineal gland of the golden hamster. Both the superficial and deep pineal components of the intact hamster contain a rich network of green to yellow-green fluorescent nerve fibres. After either superior cervical ganglionectomy or after transection of the nervi conarii the majority of the fluorescing fibres disappeared from both the superficial and deep pineal masses. Although the deep pineal remained intact after surgical removal of the superficial pineal, it was devoid of any green or yellow-green fluorescent fibres.


[Development of the rudimentary prostates of Ellobius lutescens (Microtinae) in organ culture; effects of androgens (author's transl)]. The structure of the rudimentary prostates of Ellobius lutescens is maintained intact after 6 days of organotypic culture in the absence of male hormones. Comparison with controls even shows a noticeable increase in the size of the epithelial cells. Adding male hormones to the culture medium does not modify the morphology of adult prostates, while it induces a sharp stimulation of immature prostates. In accordance with our previous results, these experiments show that the prostates of Ellobius lutescens lose their sensivity to androgens after puberty.


Large scale cultivation of a free-living nematode (Caenorhabditis elegans). A method is presented for the large scale cultivation of the free-living nematode Caenorhabditis elegans, using continuous aeration and agitation in glass ware (stirrer flasks) developed for the continuous culture of suspended cells. With this technique, populations up to 10(9) nematodes may be obtained in a 10 1 culture in less than 6 weeks with an inoculum of some 50 worms. Costs can be reduced by using an inexpensive yeast extract, available from the food industry.


Continuous labelling method for autoradiographic analysis of cell cycle parameters in steady state cell systems. Under certain conditions, continuous availability of 3H-thymidine in steady-state cell systems results in a linear increase of the fraction of labelled cells, the equation of which can be used to determine cell cycle parameters of the system investigated.


Phaeomelanic pigments from a human melanoma. The pigments in melanomas from 2 patients were studied with regard to solubility and chemical composition. Melanoma pigment from a patient with red-blonde hair was alkali-soluble and contained 9 or 10% sulfur and was thus of phaeomelanic type. Melanoma pigment from a patient with red-brown hair was insoluble in 0.2 N NaOH. Its sulfur content was 6%. This pigment was eumelanic with regard to solubility characteristics but the sulfur content was higher than previously observed for eumelanin.


Resistance of purified cholera toxin to enzymatic treatment with pancreatic elastase and papain. Treatment of Cholera toxin with pancreatic elastase and papain in vitro showed a high resistance of the toxin molecule to these enzymes, under non-denaturing conditions or in the presence of 2 M urea. These experiments support the hypothesis of a particularly stable molecular structure of the toxin, as an explanation of its activity in the intestinal lumen where the pancreatic proteases are active.


Genotype dependence of monoamine oxidase in inbred strains of mice. MAO activity was found to be influenced by the genotype or strain of mouse up to 20 days of age. The strain differences observed may derive from different rates of brain development. A number of neurological mutations comprizing three pathological classes had no effect on MAO.


Serum enzyme activities in the African elephant (loxodonta africana). The serum activities of aspartate aminotransferase, alanine aminotransferase, alpha-hydroxybutyrate dehydrogenase and creatine phosphokinase have been measured in the African elephant. In general, the values were broadly comparable with those of man except that alanine aminotransferase was much lower and creatine phosphokinase higher. No variation due to age, sex, season or location was observed.


Labile protein-methyl ester: comparison between chemically and enzymatically synthesized. The rate of hydrolysis of protein-methyl ester, the enzymatic product of S-adenosylmethionine: protein-carboxyl methyltransferase (EC.2.1.1.24) acting on oxidized ribonuclease, was measured at pH 7.1 and 8.6 at 37 degrees C. The half-life of the hydrolysis of the ester is 25 min at pH 7.1, and 4 min at 8.6. The rate of hydrolysis of the enzymatically formed esters at pH 7.0, in 0.1 M phosphate buffer, was about 25 times faster than that of esters formed chemically by reaction with methanol in HCl. The lability of the enzymatically synthesized protein-methyl ester suggests that the esterification is specific to sites such that ionization of neighboring amino acid side chains enhances the rate of the hydrolysis.


Early development of gap junctions between the mouse embryonic myocardial cells. A freeze-etching study. Using the freeze-etch technique, nexuses have been shown to exist at a very early stage in developing mouse hearts (10 dpc). At this time they are rare, but become more progressively frequent and extensive at 12 and 14 dpc. Special arrangements of particles progressively observed on the fracture faces PF (linear arrays, small associated groups of linear arrays, then hexagonal arrays with 'arms' formed by linear clusters) suggest that in ontogenesis the gap junctions may be built up by successive aggregation of the linear arrays of particles.


Synthesis of new alpha-hydrazinoarylacetic acids and derivatives. The synthesis of some alpha-hydrazinoarylacetic acids (I) by reaction of alpha-bromoarylacetic acids with hydrazine, alkylhydrazines and carbobenzyloxyhydrazines is described. Reduction of the hydrazones of 2- and 3-thienylglyoxylic acids provided a general and effective route to the thienylic series. In view of the use of compounds (I) for the preparation of new penicillins, the experimental conditions for their conversion into cyclohexylamides (XI) via the corresponding carbobenzyloxyderivatives (III) were also investigated.


Circular dichroism studies of some aralkylamines. Circular dichroism curves are reported for a number of aralkylamines having a general formula R--CH(NH2)--R' (in which R and R' are alkyl-, aryl- or aralkyl-groups) and for 1-aminobenzocyclobutene, 1-aminoindane, 1-amino-1,2,3,4-tetrahydronaphthalene and 2-amino-1,2,3,4-tetrahydronaphthalene. The Cotton effects due to aromatic chromophore 1Lb and 1La absorption bands are discussed and simple correlations between absolute configuration and the signs of Cotton effects are deduced.


Synthesis and pharmacological activity of some 3-amino-11H-indolo[3,2-c] [1,8]naphthyridines. The preparation of some 3-amino-11H-indolo [3,2-c]-[1,8] naphthyridines using the Fischer indole synthesis on the appropriate phenylhydrazones is described. Some compounds (IV b, c, d) were effective in inhibiting  the reactions of delayed hypersensitivity, but the testing has been discontinued because of toxicity observed.


Structure-activity relationships for homoserine derivatives as inhibitors of the enzymatic synthesis of S-adenosyl-L-methionine. The adenosyltransferase inhibitory activities of a series of homoserine derivatives were studied using Hansch equations and CNDO/2 calculations. Structure-activity relationships are established involving electronic and lipophilic parameters.


[Research on substances with antiviral activity. V. Structural analogs of arginine]. Some arginine analogues were synthesized and tested for antiviral activity. Two compounds showed weak activity in vitro against vaccinia virus.


["De novo substituent constants" in the study of quantitative structure-activity relationship]. The basic features of the Free-Wilson method for assigning additivity constants to structural features of related compounds is described. The method is presented in considerable operational detail with special emphasis on its development. An original example is discussed. Showing that the substituent  constants can be related to more fundamental physico-chemical substituent parameters such as the hydrophobic constants pi.


A simple method for the perfusion of isolated liver cells. The perfusion technique described in this paper offers a new and simple method for studying liver cell metabolism in a more dynamic way. It has potential use in hormonal response studies, pulsechase experiments and many other types of investigations. Finally, the perfusion technique may be applicable to other isolated cell preparations as well. The method combines some advantages of the flow-through technique with the great advantages of using isolated liver cells, apparently without disturbing the viability of the cells.


The victim is guilty.

The victim is guilty. Our society in many situations tends to blame the victim. Questions are raised whether this occurs more commonly with women and what its effects are. An examination of the treatment of women as patients may help answer these questions. In 1971 twice as many men as women were on chronic hemodialysis, raising the possibility of different allotment of medical resources and different admission criterion for this very expensive therapy. This example only indicates that women may be treated differently. The following commentary indicates women may be blamed for their illness. A prestigious medical journal has published articles claiming the clinical syndrome, Iceland disease, is really epidemic hysteria. One of the three main reasons given for such a claim is that it occurs primarily in women. Aside from the fact that many physiologic diseases do have skewed sex ratios, one wonders why it is considered inappropriate for a physiologic disease to have a male/femal ratio different from 1.0 yet not so for a psychological disease. Once women are put into this category, in essence blamed for their illness, there will be no more search for pathology that might be corrected. they may undergo detrimental therapy, in this case removal of their uteri-a hysterectomy, probably in the true sense of the word.


Adventures of a woman in science.

Adventures of a woman in science. This paper is divided into two parts. The first part describes the difficulties encountered in entering the scientific profession and staying there if one is a woman; the difficulties in combating the degrading sterotypes about women that are commonly held (women are believed to be submissive, unintelligent, uncreative, etc.); and the discrimination that accompanies beliefs in these sterotypes. The second part of the paper examines the evidence for the truth or falsity of the proposition that these stereotypes reflect woman's "innate" nature, and shows that there is no evidence to suggest that the proposition is true. On the other hand, there is evidence from social psychology that, for the most part, people act the way people around them expect them to act, and they believe that they are what others expect them to be. So if the scientific profession holds the outragious and erroneous belief that women can't be scientists, it is likely that few women will become scientists. This must change: the integrity of the progession is at stake.


Women and discrimination in academe.

Women and discrimination in academe. Affirmative action on the campus has led to some changes, but women and minorities have made little headway, especially in terms of being hired. At some institutions, after a year or two of affirmative action, the number and percentage of women has decreased while the number and percentage of men increased. The greatest progress has been in the areas of new legislation, general awareness, and correction of salary inequities. Various laws and court decisions relative to discrimination are discussed, as well as the relationship between women's and minority issues--Sandler, B. Women and discrimination in academe.


Genetic influence on nutritional aspects of metabolic regulation I. Examples of two genetic models of growth and development are described. Mice selected for growth rate from 3 to 6 weeks of age show an increase in mature body size and an increase in tissue cellularity. Manipulation of dietary intake at various ages resulted in different responses in the control and growth strain mice. Futher trials are needed to determine metabolic or endocrine adaptations that are responsible for enhanced growth in these mice. The second model discussed was the genetically obese Zucker rat. When compared to its lean littermates, the obese rat is hyperphagic and metabolically efficient in storing calories as fat, and has impaired development of muscle tissue. The shift in the growth of muscle tissue to the growth of adipose tissue cannot be prevented by dietary manipulation or exercise. Increases in liver lipogenic rate can be prevented by feeding a high fat diet. It appears from the nutritional studies presented hear that many of the metabolic lesions associated with the development of spontaneous obesity in this animal model are secondary to the primary causal event.


Inadequate cervical mucus--a cause of "idiopathic" infertility. The purpose of this study was to investigate and treat a group of patients referred for "idiopathic" infertility in whom no apparent cause for infertility, apart from inadequate cervical mucus, was found. Hormone investigations revealed that these patients could be divided into two groups: those with low sex steroid profiles despite apparent ovulation, and a second group with normal sex steroid profiles. All patients were treated with ovulation-inducing agents in an attempt to produce "controlled" ovarian hyperstimulation and an improved cervical mucus. Four of six patients conceived. The rationale behind the use of ovulation-inducing agents in this situation is discussed.


Studies on low-dose oral contraceptives: cervical mucus and plasma hormone changes in relation to circulating D-norgestrel and 17alpha ethynyl-estradiol concentrations. A study was undertaken to determine the effects of a low-dose oral contraceptive comprising 150 mug of D-norgestrel and 30 mug of 17alpha-ethynyl estradiol (Microgynon) on the plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17BETA-ESTRADIOL, AND PROGESTERONE AND ON THE PHYSICAl properties of cervical mucus. Samples of blood and cervical mucus were obtained from three women during a treated cycle and the immediately-following "withdrawal" cycle. Specific radioimmunoassay methods were used to determine LH, FSH, 17beta-estradiol, and progesterone levels in treated and withdrawal cycles, and D-norgestrel and 17alpha-ethynyl estradiol in samples obtained during treated cycles. The concentration of synthetic steroids was also measured in blood samples obtained before and 1 hour after ingestion of the contraceptive to determine the maximal daily variation. The results indicated that the contraceptive action of this combined low-dose oral contraceptive is mediated through suppression of ovulation and by rendering the cervical mucus impenetrable to sperm. Plasma FSH levels appeared to be one of the most sensitive indices of suppression. Determination of D-norgestrel and 17alpha-ethynyl estradiol showed that 3 to 4 days were required to reach maximal plasma levels and that daily fluctuations were considerable. Withdrawal of the pill resulted in an immediate return to ovulatory cycles in all three subjects studied.


Carbohydrate and lipid metabolic studies before and after one year of treatment with ethynodiol diacetate in "normal" women. A 3-hour oral glucose tolerance test was conducted in "normal" women before and after 12 months of contraceptive treatment with daily 0.25-mg ethynodiol diacetate tablets. There was no significant change in the subjects' weight between the two tests. All but the 3-hour individual group glucose values were significantly elevated at the 1-year test, and 16.7% of the tolerance curves became "borderline abnormal". The group plasma insulin values for the 0.5-, 1-, and 2-hour samples during the 1-year test were also significantly elevated. There was a significant decrease in the group fasting triglyceride levels but no change in the fasting cholesterol levels. These data suggest that some of the 19-norprogestogens may adversely affect carbohydrate metabolism.


Histology of the endometrium in long-term use of a sequential oral contraceptive. Non-atypical adenomatous hyperplasia was found in 13.5% of 111 biopsies obtained from long-term, predominantly black, users of Oracon. An association between length of time of use (95 cycles for those with adenomatous hyperplasia versus 73 for those without) and the development of adenomatous hyperplasia was noted, but there was no association with hypertension or obesity. Cystic glandular dilatation was seen in 63% but was not thought to represent hyperplasia. No more advanced lesions were seen.


17beta-ol androgens and free index in hirsute and hirsute obese women. We have found the mean levels of combined serum testosterone and dihydrotestosterone (T+DHT) and the free index (FI) to be significantly higher and the mean dihydrotestosterone precipitation index (DHT-PI) to be significantly lower in hirsute women than in normal women. Although the mean T+DHT values of the different groups of hirsute patients were comparable, the FI value of the oligomenorrheic and/or obese patient was higher than that of the nonobese, normally menstruating group. In addition, the mean DHT-PI level of obese patients was significantly lower than that of nonobese patients. The lowest androgen binding was found in obese patients with oligomenorrhea. In our experience, hirsutism is associated with T+DHT values of 150 ng/dl or lower. Measurement of androgen binding and androgen levels in unchromatographed serum extracts provides valuable information in the treatment of hirsute women.


Levels of luteinizing hormone in semen of fertile and infertile men and possible significance of luteinizing hormone in sperm metabolism. Luteinizing hormone (LH) levels were measured in the seminal plasma of 68 fertile and infertile men. LH levels in the seminal plasma were severalfold higher than those normally found in serum and were significantly higher in oligospermic and normospermic samples than in azoospermic samples. However, no significant difference was observed in LH levels of oligospermic and normospermic men. The effects of LH on fructose utilization, glucose oxidation, and adenyl cyclase activity of spermatozoa were also examined. The results indicate a possible role of seminal plasma LH in sperm motility and metabolism.


Vasectomy and vasovasostomy. I. Timing of histologic changes in immature and mature dog testis after vasectomy. The effects of vasectomy on the development and maintenance of spermatogenesis was studied using immature and mature dog testes. Bilateral vasectomy in immature dogs delayed the development of advanced spermatocytes, spermatids, and spermatozoa for about 3 months postsurgery. Spermatogenesis appeared to be recovered to control levels by 4 months postvasectomy. Spermatogenesis in mature dogs was also altered after bilateral vasectomy. Decreased numbers of advanced spermatocytes as well as maturation arrest was observed by 3 weeks postvasectomy. Seminiferous tubule cell layers quickly decreased to one to three layers as the lumina became occluded with sloughed cells by 3 to 6 weeks postvasectomy. Recovery in terms of the numbers of spermatocytes, spermatids, and spermatozoa was evident by 13 weeks postvasectomy, although occasional dog testes did not recover and appeared to be more sensitive to vasectomy-induced damage. It thus appears that vasectomy temporarily inhibits both the development and maintenance of spermatogenesis in immature as well as mature dog testes. Spermatogenesis does recover but may be maintained at somewhat lower levels after vasectomy. Changes are rapid in onset and take several weeks to be reversed. Some dog testes appear to be more sensitive to the damage and it may be irreversible in these testes.


Vasectomy and vasovasostomy. II. A comparison of two methods of vasovasostomy: silastic versus chromic stents. Twelve adult, bilaterally vasectomized dogs were used to compare two different procedures for reuniting the severed vas deferens. Approximately 5 months postvasectomy six dogs had vasovasostomies utilizing Silastic stents and the vasa deferentia of six additional dogs were rejoined with intravasal chromic stents. Ejaculates were subsequently obtained at 2-week intervals and evaluated for sperm count, motility, viability, and seminal ion concentrations. All of the dogs in which Silastic had been utilized as the stent had sperm reappear in the ejaculate, whereas only 40% of the dogs in which chromic catgut had been utilized had reappearance of spermatozoa. The over-all quality of the ejaculate was also better in the animals in which Silastic had been utilized. Testicular and epididymal histology was normal in most dogs of both groups, but three of the dogs with chromic stents in which the anastomosis had not been a success had abnormal histology, with reduced numbers of spermatocytes, spermatids, and spermatozoa. The data suggest that Silastic stents are better than chromic stents for vas reanastomosis. They also suggest that some dog testes react negatively to vasectomy and do not recover by 1 year postvasectomy when vas patency is not reversed.


The molecular weight of aspermatogenic antigen as determined by equilibrium ultracentrifugation. The extraction of antigen from testis and sperm is described. This antigen, when administered in microgram amounts in a single injection, induces aspermatogenesis in 100% of guinea pigs so treated. The deletion of the seminiferous cell line is specific (no cross-reactions) and provides a tool for investigating inhibition of cell replication as well as reproductive control. The antigen is a polypeptide-polysaccharide complex and has been determined to have a molecular weight of 10,520, using the equilibrium ultracentrifugation method.


[Changes in the pulmonary ventilation of cats with a combination of increased respiratory resistance and hypercapnia before and after vagotomy]. In cat+s, increased resistance against breathing at the background of hyperventilation with a hypercapnic mixture reduces the 1-min ventilation. However, the bioelectric activity of the diaphragmatic nerve becomes augmented, thus indicating an increase in the respiratory center inspiratory activity. Vagotomy was followed by a decreased ventilatory response to CO2. Suppression of ventilation and augmentation of the diaphragmatic nerve activity during additional resistance against breathing in vagotomized animals were preserved on account of a considerably greater activity of the respiratory center. The data obtained suggest that, in conditions of combination of increased resistance against breathing with hypercapnia, the lungs afferent system fulfills an optimization of activity of the ventilatory apparatus.


An enzymologic study of corpora lutea in early pregnant rats treated with abortifacient agents. Luteal metabolism was investigated in corpora lutea of early pregnant rats treated with four abortifacient agents. In corpora lutea of rats treated with prostaglandin F2alpha or of rats 1 day postpartum, glucose-6-phosphate dehydrogenase (G6PDH) activity increased 140 to 170% and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) was activated to significantly high levels, whereas malic enzyme activity decreased to 29% of control values. In aminoglutethimide-treated rats, the activities of G6PDH and malic enzyme decreased, while 20alpha-HSD activity was maintained at a very low level. With the increased dose, complete abortion was observed. In corpora lutea of these aborted rats, 20alpha-HSD was activated moderately and G6PDH values were slightly higher than control values, whereas malic enzyme activity fell to lower levels. All rats treated with clomiphene citrate aborted within 63 hours after the last injection. The activities of G6PDH, malic enzyme, and ATP citrate lyase in these corpora lutea decreased to 66, 68, and 72% of control levels, respectively; 20alpha-HSD activity was maintained at a very low level, and activities of 3beta-hydroxysteroid dehydrogenase, 6-phosphogluconate dehydrogenase, and pyruvate kinase were not appreciably altered. These findings indicated that, at the beginning of luteolysis and fetal resorption, the activities of steroidogenic enzymes decreased and 20alpha-HSD was not yet activated. Therefore, we could gauge the early changes of luteolysis by measuring the activities of G6PDH, MALIC ENZYME, AND ATP citrate lyase as well as 20alpha-HSD.


[Reaction of the human ventilatory apparatus to supplementary respiratory resistance upon inhalation of normo- and hypercapnic mixtures]. In 5 healthy young subjects, the intrathoracic pressure, pneumotachogram, and CO2 tension in exhaled air were recorded--under conditions of breathing with additional resistance (15 cm water/1/sec). While breathing with air, starting from the 1st respiratory cycle after switching on of the additional resistance, a respiratory regimen had been formed (decreased ventilation and increased respiratory activity) which did not alter during next 10 min. When breathing with hypercapnic mixture (4% CO2 in air), the respiratory regimen changed in two stages: a stepwise increase of respiratory activity and reducing of ventilation, and further gradual increase of these parameters. Increase in the respiratory activity was invariably followed by an increase in the CO2 alveolar tension. Role of chemo- and mechanoreceptors in formation of the ventilatory apparatus response to additional resistance against breathing, is discussed.


[Response of the human ventilatory apparatus to additional respiratory resistance upon inhalation of normo- and hypercapnic mixtures]. In 78 healthy subjects, at 760 m (Frunze) and 3600 m (the Pamirs) above sea level, apneic points and ventilatory responses to increasing hypercapnia were assessed (rebreathing method). At 3600 m (4 to 11-month adaptation), regulation of breathing was achieved at lesser threshold CO2 values than in lowlanders, with no quantitative difference in ventilatory responses. On days 5 to 7 of deadaptation (at 760 m) following 45 days of adaptation at 3870 m, there was a decrease in ventilatory responses to a 1 mm Hg increment in PACO2, while apneic point values approached base-line values (prior to ascent to the high altitude).


[Ventilatory responses in man to hypoxia and hypercapnia under conditions of decreased respiratory resistance]. In young healthy male adults, a decrease in the mechanical load of the ventilatory apparatus was followed by readjustment in the respiratory cycle. During hyperventilation due to an enhanced hypercapnic stimulus, a reduction of resistance against breathing tells on the value of ventilatory response, the latter being greater than when breathing with mixtures of ordinary density. The data obtained confirm the significance of value of the mechanical load of respiratory apparatus for formation of ventilatory response to hypoxia and hypercapnia.


[Reorganization of the function of several intrinsic laryngeal muscles as a result of exclusion of one of them during respiration]. Electromyographic data on the effect of unilateral extirpation of the cricoarytenoid posterior muscle on other intrinsic muscles activity and on the vocal fold mobility were obtained in a series of chronic experiments in dogs,--before the extirpation, immediately after it, and in 1.5, 3, 6, and more months. The respiration was recorded simultaneously with the EMG of the intrinsic laryngeal muscles and with laryngoscopy and photography of the larynx. The data obtained showed a decrease in the electric activity of the lateral and vocal muscles on the side of the extirpated cricoarytenoid posterior muscle within 1.5-3 months after the operation, and traces of this activity sometimes not only in expiration as well. In about 6 months or more after the extirpation, the electric activity of the lateral and vocal muscles on the side of the extirpation occurred not in expiration, as before the operation, but in inspiration only. The vocal fold on this side of the larynx was in the paramedian position and immobile at the state of respiration during the whole period after the extirpation. The reconstruction of activity of the larynx sphincter muscles after extirpation of dilatatory muscles may be a result of the central reconstruction of coordination of some motoneurons connected with different muscles of the larynx and may have a compensatory character. This reconstruction occurring after the cricoarytenoid posterior muscle extirpation provides most favourable conditions for the respiratory function of the larynx.


[Dynamics of the process of gas transport into the body using a mathematical model]. Dynamics of mass-transport of oxygen, carbon dioxide, and inert gases in lungs, blood, and tissues, as well as gas transport through alveolar capillary and erythrocyte membranes at rest and during exercise under normal and increased ambient pressures, were studied on a mathematical model. The model consists of 34 differential and 58 algebraic equations and makes it possible to estimate the dynamics of changes of over 90 parameters. The effect of various factors: duration of the respiratory cycle, tidal volume, airways resistance, the surface of diffusion, the resistance of alveolar-capillary wall, erythrocyte membrane, ventilation-perfusion relations, pulmonary blood shunts, blood supply to the tissues, Haldane and Verigo-Bohr effect, buffer capacity of the blood, and others) on the mass-transport of gases were quantitatively estimated.


[Changes in the oxygen tension of rat cerebral cortex subsequent to hyperoxia and the protective effect of urea]. When breathing with air, pO2 in anesthetized rats was 24.1+/-1.8 mm Hg, while after urea administration it was 19.4+/-1.7 mm Hg. A sharp increase in pO2 was revealed in hyperoxia(911+/-48 mm Hg at 6 atm during first 5 min, and 924+/-38 mm Hg--by the 7th min). The high pO2 was only reduced in 10-15 min after decompression. At a combined action of urea and hyperoxia, pO2 was significantly lower (714+/-52 mm Hg); pO2 in successive cortical layers (0-2400 mcm with a 200-mcm step) was progressively decreasing (from 40.7+/-4.9 mm Hg to 16.0+/-1.0 mm Hg in control, and from 928+/-35 mm Hg to 274+/-64 mm Hg in hyperoxia).


[External respiration and oxygenation of arterial blood in animals in an atmosphere with an increased concentration of oxygen]. In 8 unanesthetized rabbits, the breathing rate, oxygenation of blood, and some other parameters were recorded during 1-hr stay in hyperoxic gas milieau with 40, 60, and 80% oxygen in nitrogen. In 40% mixture, the parameters changed insignificantly. In 60% oxygen, the 1-min respiratory volume first decreased then normalized while oxygenation of blood increased; in 80% mixture, both these parameters decreased due probably, to reduced ventilation, vasoconstrictive effect of oxygen, and shunting of blood in the lungs.


[Functional capabilities of the papillary muscles of the left heart in rats during adaptation to high altitude conditions]. The amplitude of papillary muscles shortening at gradual increase of the rate of stimulation from 12 to 60, 120 180/min in conditions of permanent high altitude hypoxia on 3rd, 15th, 30th, and 45th day of adaptation noticeably increased at 180/min stimulation starting from the 15th day of mountain exposure and remaining till the 30th and 45th day. The performance of the muscles had been considerably decreased as compared with the control tests, on the 3rd day of adaptation.


[Regional redistribution of blood during air cooling of unanesthetized rats]. 3-hr exposure to air at +5 degrees C of unrestrained rats evoked a relative reduction of blood volume in vessels of the skin, skeletal muscles, abdominal and pelvic organs (except liver). Increase of the blood volume occurred in the brain, thoracic organs, and in the liver. No significant decrease of the rectal temperature was noticed at that, in spite of cooling of the skin of different parts of the body and tail. Cooling of restrained rats at +5 degrees C during 1 and 3 hrs decreased the rectal temperature. The main direction of the blood redistribution involved its removal from the liver to the deep muscle tissues. At the beginning of the cooling and immediately after self--warming the relative increase of the blood volume was more obvious in the skeletal muscles of the anterior body parts.


[Reactions of respiratory center neurons to local cooling of the ventral surface of the medulla oblongata]. In anesthetized cats, in conditions of vagal and sinus deafferentation, the effect of bilateral cooling of portions of the medulla oblongata ventral surface on electric activity of the respiratory volley neurons, was studied. The main types of the responses were as follows: cessation or reduction of firing, transformation of the volley discharges into continuous those or continuous with respiratory modulation. These responses were followed by cessation or sharp depression of respiration. Data on  localization of fields whose cooling entails maximal inhibitory responses of the respiratory neurons, are presented.


[Effect of transection of the forebrain, diencephalon and midbrain on respiration in cats]. In vagotomized cats, after removal of the brain portion 5 mm rostral to the visual nerves crossing, the eupnoea type of respiration was preserved. Transection in the area of the visual nerves crossing was followed by a stable acceleration of respiration. Starting from the level of the posterior border of the visual nerves crossing and more caudal, successive transections of the brain entailed sharp decrease in the breathing rate, increase of the respiratory volume, and complicated changes of the lungs ventilation.


[Regulation of respiration under conditions of inhibition of carbonic anhydrase activity by diamox]. The functional state of the respiratory center and the mechanism of increase in pulmonary ventilation before and after inhibition of activity of carbonic anhydrase by diamox were studied in anesthetized cats. During the inhibition, activity of bulbar inspiratory neurons functionally connected with motoneurons of the diaphragm was markedly reduced and that of the neurons connected with motoneurons of intercostal muscles was sharply increased. A steady thoracic respiration occurred. The aferents from the carotid sinus nerve and vagus nerve did not affect the steady thoracic respiration. Increased efferent influence upon the intercostal muscles led to forced thoracic respiration which ensured a high pulmonary ventilation during the whole period of action of the diamox.


[Analysis of the imperative stimulus restricting voluntary breath holding]. In 5 healthy young men, the maximal voluntary breath holding--was studied under conditions of different initial values of PACO2--after oxygen inhalation at ordinary minute volume of respiration or at hyperventilation, or after breathing with oxygen mixtures with 2, 4, 6, 8 or 10% CO2. PACO2 was recorded at the moment of resuming of the intercostal muscles electric activity and at the point of breaking up the apnoea. A mathematical model was constructed. The hypothesis of participation of two independent factors (chemo- and mechanoreceptive) in genesis of the imperative stimulus for breathing was checked. The data obtained suggest that, in fact, the only factor restricting the duration of voluntary breath holding--is the summed up in time chemoreceptive stimulation. The involuntary contractions of respiratory muscles observed during apnoea are, apparently, a connecting link in formation of the imperative stimulus which breaks up the cessation of breathing.


Length of residence, social ties, and economic opportunities,. This study examines length of residence for movers--that subsection of the population which accounts for the high mobility rates in the United States. The propensity for repeated migration is studied in relation to economic opportunities and previous familial and personal contacts. The results indicate no influence of economic opportunities on duration of residence. This finding is consistent with recent research that indicates economic conditions are not a general stimulus for out-migration, although they are for inmigration. On the other hand, length of residence is found to be longer where previous familial and personal contacts existed. Overall, the results provide additional evidence of the importance of social, as opposed to strictly economic variables in the migration process.


The relation of psychological, social, and economic variables to fertility-related decisions. To test a recent model of social behavior, a questionnaire was designed and administered to 270 married women in a midwestern city. A stratified random sample was obtained, comprising a 2 X 3 factorial design (Catholic vs. Protestant and high vs. middle vs. low socioeconomic status). It was hypothesized that an individual's intention to engage in a fertility-related behavior would be highly correlated with (a) her beliefs about the consequences of performing that behavior weighted by the value of those consequences, and/or (b) her beliefs about what relevant others think she should do and her motivation to comply with those others. The data strongly supported this hypothesis for each of three different behaviors. Analysis of variance revealed a significant religious differential for intentions to have a two-child family (Catholics were less likely to intend to have a two-child family than Protestants). This differential was further examined in terms of the proposed model of behavior.


Female work experience, employment status, and birth expectations: sequential decision-making in the Philippines. The influence of women's birth parity and accumulated market skills on their current labor force participation and birth expectations is examined within a sequential choice framework. Analysis of household data from the 1973 Philippines National Demographic Survey suggests these patterns: (a) women who have accumulated larger families work less in the current period and anticipate fewer additional births; (b) women with more past work experience tend to work more hours in the current period; and (c) work experience appears to have only a weak negative effect on birth expectations among older women.


Compensating changes in fertility and mortality. This paper illustrates a method of studying changes in vital rate schedules which have no effect on the intrinsic rate of population growth. These changes are described as compensating changes in fertility and mortality. The analysis proceeds from the discrete perspective of Leslie matrices, wherein the central idea is to establish the set of all compensating changes by identifying that class of Leslie matrices which possess the same positive eigenvalue, lambda1. A root-squaring technique is adapted for the purpose of estimating lambda1. Finally, a variety of compensating fertility and mortality changes is illustrated using data from Japan.


Report on a multiple regression method for making population estimates. A new method of making population estimates is introduced and contrasted to the standard ratio-correlation method. The new method, called the "difference-correlation method," produced population estimates for the counties of Michigan which had a smaller mean percentage error than estimates produced by the ratio-correlation method. The differences of proportions which are used in the difference-correlation method will always have means of zero, while the ratios used in the ratio-correlation method have means which vary. Higher intercorrelations among the variables and increased temporal stability of the intercorrelations are two advantages of using differences rather than ratios.


Report on matching procedures of a dual record system in the southern Philippines. There are generally three stages to the development of rules for matching vital events data from two sources covering the same population: (a) establishing a set of "true" matches and nonmatches; (b) determining the best tolerance limits for each single characteristic which might be used in matching; and (c) experimenting to determine the set or sets of characteristics and the weights to be used in classifying a pair of records as matched or nonmatched. Specific examples, based on early matching experiments with data from the dual record system of the Mindanao Center for Population Studies (MCPS), are presented. Successive application of different sets of characteristics (differential valence rule) to the remaining unmatched events produced an acceptable rule for matching in this study.


Provisional evaluation of the 1970 census count of American Indians. Estimates of the American Indian population under 20 years of age on April 1, 1970, based on birth and death statistics for a 20-year period, show a possible net undercount of 6.9 percent for this age group in the 1970 census. However, for some particular ages the estimates indicate net overcounts in the census. Likewise, the net increase of the entire American Indian population as measured by the difference between the 1960 and 1970 censuses is 67,000 greater than the natural increase for the decade. Detailed analysis of cohort data with respect to the possible causes of the differences between the estimates and the census figures indicate that a portion of the estimated net overcounts can be attributed to classification, as well as coverage, problems. The estimated net overcounts offer support for the hypothesis that many individuals who were registered as white at birth and who were counted as white in the 1960 census shifted their racial self-identification from white to American Indian during the 1960's.


Sweat studies in hyperhidrosis palmaris and plantaris. A survey of 60 patients before and after cervical sympathectomy. 60 patients suffering from excessive sweating in the hands underwent cervical sympathectomy. At follow-up 1-7 years after operation the hands were dry in 55. No differences in electrolyte concentrations were found in the sweat from palms, arms, or body prior to and after the surgical intervention. Similarly no differences were found in electrolyte concentrations between healthy subjects and hyperhidrotics. Palmar sweat was hypertonic in comparison to arm or body sweat. The Na and K sweat concentrations were: palmar 50 +/- 20 and 16 +/- 7 mEq/1; arm 30 +/- 11 and 8 +/- 2 mEq/1; and body 21 +/- 20 and 4 +/- 3 mEq/1, respectively. Na/K ratio was: palmar 3.2; arms 3.6 and body 5.8. Total sweat loss prior to the operation was 5.7 +/- 4.2 g/kg BW/h; afterwards it was 5.9 +/- 4 g/kg BW/h. These equal sweat rates were associated with compensatory sweating in areas of the body not affected prior to the operation.


[Pattern of epithelium formation in human and guinea-pig skin (author's transl)]. Comparative histometry of human and guinea-pig epidermis revealed that in the latter development of the (subcorneal) superficial epithelium is significantly less, and that of the (mostly follicular) deep epithelium is markedly more pronounced than in man.


[Basophils in the infiltrate of guinea pig experimental contact dermatitis. Dinitrochlorobenzene and citraconic anhydride (author's transl)]. We observed, in addition to the lymphocytes of the classical descriptions, large numbers of basophils in the infiltrate of the specific sensitization reaction with dinitrochlorobenzene and citraconic acid, a few eosinophils in the reaction with dinitrochlorobenzene and rather more eosinophils in the reaction with citraconic acid.


The mechanism of photochemotherapy.

The mechanism of photochemotherapy. As a contribution to the mechanisms of photochemotherapy, human skin homogenates were irradiated in the presence or absence of methoxsalen. The changes induced in LDH-, G-6-PDH-, GAPDH-, and GOT-activities were registered. Methoxsalen (50 mug/ml) failed to produce any significant effect. On pure G-6-PDH, methoxsalen exhibited a photoprotective action.


[In vitro and in vivo experiments on the immunosuppressive properties of cytostatic substances (author's transl)]. Various cystostatic substances are tested with the lymphocyte transformation test and compared with the effect on the experimental contact eczema of the guinea pig. Only methotrexate influences the eczematous reaction. The in vitro and in vivo effects are not identical.


[Photosensitization of the skin and fluorescence spectra (author's transl)]. We have carried out spectrofluorometric determinations of numerous substances such as drugs, chemicals and plants in order to find out whether there is a correlation between fluorescence data and photosensitization of the skin. A hypothesis on the mechanism of photosensitization is discussed and the data on the fluorescent properties of some 50 products is given.


Therapy of resistant psoriasis with topical corticosteroids and dimethylsulfoxide. The sequential application of full-strength dimethylsulfoxide (DMSO) and potent topical corticosteroid preparations was very effective in resistant plaque-type psoriasis. Complete clearing may be achieved in 3-4 weeks. Lower strengths of DMSO were less beneficial. Irritation from the solvent was effectively controlled by corticosteroids and was limited to transient burning or stinging. Resistance to topical corticosteroids may be overcome by the concomitant use of DMSO.


Particle size of dexamethasone incorporated in ointment and its behaviour during penetration in the stratum corneum of living skin. The particle size of dexamethasone was microscopically determined in polarized light in two emulsion ointments: a standard water-in-old formula (aqueous wool alcohol ointment), and a standard oil-in-water formula (aqueous hydrophilic ointment), both containing 0.023% dexamethasone. The distribution of dexamethasone was on average smaller and finer in the water-in-oil emulsion than in the oil-in-water emulsion. In a further series of experiments we studied by means of the adhesive tape-stripping method the proportions of the particle size and counted the total number of particles in various layers of the stratum corneum in vivo. The difference between the two emulsion types once again proved to be significant, but only as far as the epidermal barrier. A new, uniform particle size spectrum was formed at this level, having a maximum value of 24 mum, which, irrespective of the type of ointment, allows a release of the desamethasone in the live epidermis and dermis. The original particle size distribution is thus qualitatively insignificant in so far as the therapeutic effect of dexamethasone below the barrier zone is concerned. Since the particle size has a strongly distorted frequency distribution, with amarked shift to the left, only about 0.5% of the particles in the w/o emulsion and only about 2% in the o/w emulsion are in fact larger than 56mum, the maximum value measured lying just below the surface of the horny layer. Any loss during further penetration is probably negligible.


In vivo percutaneous penetration of corticoids in man and unresolved problems in their efficacy. This paper review the percutaneous penetration of corticosteroids in vivo in man utilizing urinary excretion of 14C-hydrocortisone as the experimental method. In general corticosteroids are only minimally absorbed from most areas of glabrous skin. Increasing the amount that penetrates-by use of occlusion-and increasing concentration provides the most practical method currently available for increasing efficacy in treatment-resistant dermatoses. Some practical research problems relevant to topical corticoid efficacy are discussed.


Objective measurement of topically applied corticosteroids. The vasoconstriction caused by four topical corticosteroid preparations was compared according to subjective ranking and according to measurement by a tristimulus colourimeter (Momcolor). The measured results agreed well with visual evaluation. The colourimeter was proved to be measuring the degree of vasoconstriction. Among the preparations examined, the vasoconstriction effected by hydrocortisone 17-butyrate cream (Locoid) and by betamethasone dipropionate ointment (Diprosone) was stronger than that exerted by triamcinolone acetonide (Ftorocort) and fluocinolone acetonide (Flucinar). With the aid of colourimetric measurement of the vasoconstriction, differences could be demonstrated between clinically effective topical corticosteroid preparations. An open question remains, what the predictive significance is of the objectively measured vasoconstriction test, for clinical practice.


Topical and systemic effects of hydrocortisone 17-butyrate. In a series of hydrocortisone 17-esters, hydrocortisone 17-butyrate (HC-17B) has almost optimal lipophilicity resulting in a topical effect comparable to that of the fluorinated corticosteroids as measured in the McKenzie test on the human skin. In rats its systemic effects are weak, being in the order of those of hydrocortisone. In man systemic effects have been demonstrated, but no exact comparative. In man systemic effects have been demonstrated, but no exact comparative data are available. Important FACTORS controlling the intensity of systemic effects are: rate of liberation into plasma from the depot in the horny LAYER, RATE of metabolic degradation, and rate of plasma clearance. In rats the main factor seems to be rapid clearance from plasma (t 1/2 = 0.5h) by selective concentration in the liver and, to a lesser extent, in the kidneys. Rapid hydrolysis by esterases in plasma and liver plays an additional role. In man hydrolysis by esterases appears to be rather slow; the rate of clearance from plasma is still unknown, whereas the absorption from the intact skin into the blood seems to be very slow (t 1/2 = 25 h).


Systemic effects and percutaneous absorption of topically applied 0.1% hydrocortisone 17-butyrate. The systemic effects of topically applied 0.1% hydrocortisone 17-butyrate during treatment with and without occlusion were measured in terms of the functions of the pituitary-adrenal axis. Corticosteroid levels in the blood were determined by the modified method of MURPHY, a competitive protein-binding radioassay. Circulating eosinophils were counted and the urinary 17-OHCS and 17-KS excretion were also determined. Percutaneous absorption following the topical application of 14C hydrocortisone 17-butyrate 1 (HC 17-B, Locoid) was measured by means of autoradiography. The application of the corticosteroid to the normal skin without occlusion did not induce systemic effects, whilst the application of the drug under occlusive dressing showed that systemic effects may possibly be induced. The number of circulating eosinophils, corticosteroid levels in the blood and urinary 17-OHCS excretion all decreased. However, these values returned to normal about 2 days after the withdrawal of the application, so we consider the systemic effect induced by the topical corticosteroid to be of a temporary nature. The percutaneous absorption of the corticosteroid was proved by an autoradiographic technique using 14C-labelled HC 17-B. At various intervals after the application, radioactive substances were observed as silver grains in the horny layer of the epidermis and skin appendages, and the density of the silver grains gradually increased with the course of time. It may be surmised that locally applied HC 17-B will be retained in the horny layer of the epidermis at a very early stage after the application and then absorbed in the blood via the epidermis and skin appendages. The reservoir of the corticosteroid in the skin was demonstrated 24 h after the withdrawal of the application.


Effect of hydrocortisone 17-butyrate on the percutaneous absorption of antibiotics. Abrption of antibiotics from combined preparations containing oxytetracycline, chlortetracycline, doxycycline or gentamicin and hydrocortisone 17-butyrate into the skin of rats was examined. The penetration of antibiotics from the ointment into the skin was inhibited by 0.2% hydrocortisone 17-butyrate to a significant degree. It is suggested that this effect of hydrocortisone 17-butyrate is the consequence of its vasoconstrictor action.


Penetration of corticosteroids through the skin in relation to the vehicle. Results of in vitro studies on the penetration of a corticosteroid hydrocortisone 17-butyrate (HCN) in relation to the vehicle are reported. When HCB is dissolved completely in the vehicle, penetration is enhanced, and only under this condition an increase in HCB concentration (in the range 0.05-0.2%) leads to an increase in the penetration. Evaluation of the efficiency of various vehicles (an oil/water cream, Plastibase or gels) in which HCB was dissolved in propylene glycol or ethanol, showed that Plastibase with propylene glycol was the most effective for both 0.1 and 0.2% HCB. The results of experiments in which HCB was applied in ethanolic solutions suggests that at least initially HCB and ethanol together penetrate through the epidermis.


Bioavailability of topical steroids.

Bioavailability of topical steroids. This paper review our modification of the vasoconstrictor (blanching) assay for topical corticosteroids using human volunteers, which we have improved and extended so that it may be used as a useful screening test for clinical efficacy besides being employed to determine the bioavailability of steroids from topical bases. Work is reported on the blanching activities of (1) 14 novel steroids in ethanol, (2)hydrocortisone 17-butyrate in eight topical vehicles, (3) betamethasone 17-benzoate in foam, ointment, cream and gel bases, and (4) 61 commercial formulations used in Great Britain. Pharmacokinetic/pharmacodynamic relationships are discussed as aids to optimizing topical steroid treatment.


Effects of local corticosteroids in skin infections. Glucocorticoids exert valuable therapeutic activities in skin infections, although their use is limited by the occurrence of undesiderable effects: glucocorticoids depress the local defense mechanisms and in low concentrations, stimulate microbiol metabolism. For these reasons, combined preparations containing an antimicrobiol substance besides the glucocorticoid are recommended. However, interactions between the steroids and the antimicrobiols must be ruled out beforehand, i.e. the unimpaired activity of both steroid and antimicrobial must be assured. Examples of such investigations are reported for the most widely used compounds for topical therapy. The simultaneous use of a glucocorticoid and an antimicrobial is not recommended in only a few instances.


Effect of bases and accelerants on the anti-inflammatory activity of topical corticosteroids. The use of measurement of skin thickness in guinea pigs has been compared with other techniques for assessment of topical applications. This method has provided us with an accurate evaluation of the corticosteroid dose-response curve and the effect of bases. The method has shown that non-steroid prostaglandin synthesis inhibitors can also be demonstrated to possess topical anti-inflammatory activity. As expected, indomethacin acts synergistically when formulated with hydrocortisone. Contrary to our expectation, both salicylic acid and acetylsalicylic acid show antagonism with hydrocortisone. This finding may be of clinical significance. We have also found that a combination of salicylic acid and indomethacin produces striking inflammatory changes in guinea pig skin which points to interaction of these two drugs in the guinea pig. The relevance of this phenomenon to both the mode of action of the two drugs and their use in clinical practice remains to be elucidated, but preliminary tests suggest that similar changes take place in human skin.


Vasoconstriction in response to corticosteroids observed in human lips. Following epimucous application of corticosteroids on the lips, narrowing and shortening of the terminal network of vessels occurs within 5-7 min. The decrease in infrared radiation needs a few more minutes. Contrary to the application of epinephrine-like substances, the change of the vessels occurs first in the superficial layers and only later on in the deeper layers. In addition to the effect on the muscles of the vessels, a narrowing of the capillaries can also be influenced by the effect of corticosteroids on the endothelial cells. Changes of the ground substance of the capillary vessel bed are also a possibility.


Thyroid thermogenesis: minimal contribution of energy requirement for protein synthesis. Cycloheximide (5.0 mug/ml) had no significant effect on respiration of liver slices prepared from euthyroid rats (i.e., QO2 of 15.5 +/- 0.8 vs. 14.9 +/- 0.8 mul/mg protein) despite an 83.8 +/- 2.1% inhibition of protein synthesis as judged by [3H]leucine incorporation into the trichloroacetic acid precipitable fraction. Injection of triiodothyronine increased the QO2 of rat liver slices to 22.6 +/- 1.1 mul/h/mg protein. The QO2 of hyperthyroid slices remained high in the presence of cycloheximide although protein synthesis was inhibited by 84.4 +/- 2.0%. These results imply that the energy requirement for protein synthesis contributes little to QO2 of euthyroid liver and does not account for a significant fraction of the increase in hepatic QO2 obtained in the transition from the euthyroid to the hyperthyroid state.