Les psychodysleptiques: II. Quelques problèmes relatifs à leur usage

In the first part of this paper, a classification was proposed which divided dysleptic drugs into two categories. Further evidence in support of this classification is drawn from the variability of the clinical picture in schizophrenics elicited by mescaline or allied substances, whereas dysleptics with potent anticholinergic properties always induce the same symptomatology. If the therapeutic usefulness of LSD-25 for instance still may be argued, dysleptics belonging to the second group seem to have no therapeutic usefulness. The dysleptics of the first group include in their chemical formula an aromatic or an indole nucleus; the second group is characterized by a phenylglycolate group. The classification proposed here may be compared with Henri Ey''s ideas: in this Jacksonian perspective, dysleptics like LSD would impair the superior strata of the psycho-organic structure whereas Ditran (in the second group) would act at a lower level.     

Radioimmunoassays of 3,4,5-trimethoxyphenethylamine (mescaline) and 2,5-dimethoxy-4-methylphenyl-isopropylamine(DOM)

Mescaline (3,4,5-trimethoxyphenethylamine) and N-succinylmescaline were coupled to human serum albumin with carbodiimide. DOM (2,5-dimethoxy-4-methylphenylisopropylamine) was linked to human serum albumin by reaction with glutaraldehyde. These conjugates were used for immunization of rabbits. Derivatives of mescaline [N-(3′,4′,5′-trimethoxyphenethyl)-4-hydroxyphenylacetamide] and of DOM [N-(2′,5′-dimethoxy-4′-methylphenylisopropyl)-4-hydroxyphenylacetamide], which could be iodinated to high specific activity, were synthesized. The antibodies bound specifically to these iodinated compounds. In competition experiments with a mescaline antiserum, 6 pmoles of mescaline inhibited 50%; with a DOM antiserum, 50% inhibition was observed with 118 pmoles of DOM. Thus, 100 pg of mescaline and 2 ng of DOM can be detected. The specificity of both antibodies is such that structurally related molecules, such as p-methoxy-phenethylamine or 3-methoxytyramine, are several orders of magnitude less effective as inhibitors than the parent molecules. With the use of antimescaline, it was determined that mescaline administered intravenously to rabbits disappeared rapidly from the circulation. The acid was identified as the major metabolite in the serum and urine of these animals.     

Heart Rate Orcadian Rhythm as a Biological Marker of Desynchronization in Major Depression: A Methodological and Preliminary Report

Heart rate (HR) was continuously monitored during successive 24-hr periods in 19 healthy subjects and 26 major depressed patients (DSM III-R). Recordings were performed after a 2-week wash-out period and the morningness or eveningness typology of each subject was determined. The chronobiological parameters and rhythm percentage (RP) were calculated by the single cosinor method from the smoothed HR curves of each subject. In normal subjects, HR follows a circadian rhythm (RP > 65%) with the lowest values at night. Morning type subjects have an earlier peak time (13:30) than evening type subjects (17:30). Major depressive patients were split into two groups; in the first one HR circadian rhythm was still present (RP > 63%) with a decrease in amplitude (24%) while in the second group, no circadian rhythm of HR could be detected (RP < 25%, decrease in amplitude > 70%). In the group of patients with a persisting HK circadian rhythm, no veritable phase advance was observed. Our results suggest that circadian HR rhythm, which can be easily studied with non-invasive methods, might represent a chronobiological marker of some depressions. Given the lag that exists between the rhythms of morning type and evening type subjects, our study also stresses the importance of taking into account this behavioural trait in chronobiological studies.     

Heart rate circadian rhythm as a biological marker of desynchronization in major depression: a methodological and preliminary report

Heart rate (HR) was continuously monitored during successive 24-hr periods in 19 healthy subjects and 26 major depressed patients (DSM III-R). Recordings were performed after a 2-week wash-out period and the morningness or eveningness typology of each subject was determined. The chronobiological parameters and rhythm percentage (RP) were calculated by the single cosinor method from the smoothed HR curves of each subject. In normal subjects, HR follows a circadian rhythm (RP greater than 65%) with the lowest values at night. Morning type subjects have an earlier peak time (13:30) than evening type subjects (17:30). Major depressive patients were split into two groups; in the first one HR circadian rhythm was still present (RP greater than 63%) with a decrease in amplitude (24%) while in the second group, no circadian rhythm of HR could be detected (RP less than 25%, decrease in amplitude greater than 70%). In the group of patients with a persisting HR circadian rhythm, no veritable phase advance was observed. Our results suggest that circadian HR rhythm, which can be easily studied with non-invasive methods, might represent a chronobiological marker of some depressions. Given the lag that exists between the rhythms of morning type and evening type subjects, our study also stresses the importance of taking into account this behavioural trait in chronobiological studies.     

Modifications du rythme de fructification de Coprinus congregatus par le dépôt de carpophores mûrs exogènes à la surface des cultures

Changes in Fruiting Rhythm of Coprinus congregatus by Addition of Exogenous Mature Sporophores on the Surface of Cultures. Researches were performed over the regulating effect of mature sporophores on the fruiting rhythm of Coprinus congregatus Bull. ex Fr. Placing exogenous mature fruit-bodies on the vegetative mycelium before the accomplishment of the first flush gives an abundant and perfectly synchronized fructification for this flush. But the fruiting rhythm is then disturbed: compared to control cultures, less sporophores are produced in the following flushes, and, in most cases, the cultures are finally characterized by fewer flushes than the controls. The nature of the substance(s) hypothetically produced by mature sporophores, which may regulate the production of other fruit-bodies, and, correlatively, the fruiting rhythm, is as yet unknown.     

Effect of circadian rhythm type on serum lipid levels in shift workers: A 5-year cohort study

We investigated how differences in circadian rhythm type affect the health of workers engaged in shift work. Employees, who were newly hired in a steel company between 2007 and 2011, received the Morningness–Eveningness Questionnaire (MEQ) survey. The target participants were 153 male shift workers who were not being treated with any antihyperlipidemic drugs and underwent periodic physical examinations including blood tests at least twice. According to the score of the MEQ at the time of joining the company, we classified the subjects into five types. Longitudinal changes in serum lipid level were estimated among the circadian rhythm types adjusted for age, BMI, and other covariates using a linear mixed model. The regression coefficient of total cholesterol level in the “definitely and moderately morning” group was ?17.83 (95% confidence interval (CI): ?33.42 to ?2.23), and in the “intermediate ‘group’ was ?16.84 [95% CI: ?30.40 to ?3.28], compared to the moderate evening type.” The total cholesterol level was higher in the moderately evening type than in any of the other groups. Between the Morningness–Eveningness (ME) type and Low-density lipoprotein (LDL) cholesterol levels, compared with the “moderately evening type” group, the regression coefficient in the “intermediate type” group was ?16.08 (95% CI: ?28.79 to ?3.37), and in the “definitely and moderately morning type” group was ?17.50 [95% CI: ?32.11 to ?2.88]. The “moderately evening type” group had a higher LDL cholesterol level than any of the other groups. Evening-type circadian rhythm type shift workers are more prone to elevated serum lipid levels.     

Effects of mescaline and its derivative N-[3,4,5-trimethoxyphenylethyl]-aziridine on the spatial orientation of rats in a T-maze

The central effect of mescaline and of its derivative N-[3,4,5- trimethoxyphenylethyl]-aziridine (FAZ) after their stereotaxic administration into the lateral ventricle of the brain was studied in behavioural experiments on rats. The effect of the two substances was tested by a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. The results show that both substances worsened the behaviour in question. The negative effect of mescaline (lengthening of the time of passage through the maze) was manifested both immediately and several weeks after a single dose. FAZ likewise worsened the test reaction, but its effect was less pronounced than that of mescaline.     

Effect of 2,4,5-trichlorophenol on hyphal membrane potentials in rhythmic mutants of Neurospora crassa

The uncoupler 2,4,5-trichlorophenol (TCP) was used to test for differences in maintaining the hyphal membrane potentials in the wild type and rhythmic mutants of Neurospora crassa. Trichlorophenol (0.1 mmol·1^–1) resulted in a depolarization of 93 mV (wild type) and 144 mV in the mutant clock. A total recovery was achieved in both strains after washing out the uncoupler. The circadian conidiation mutant band was more sensitive than the two other strains and showed two different reaction patterns: one with delayed reaction, total breakdown and without recovery; the other one with nearly immediate reaction, slow but not entirely total decline and partial recovery. These differences are discussed in their relation to the circadian rhythm of conidiation.Abbreviations PD potential difference - TCP trichlorophenol     

Effect of mescaline on an innate behaviour of mice

The action of mescaline on mice innate behaviour was studied. In the first experiment the drug modified the innate behaviour of mice. The dose-effect curve was obtained by the second. The results pointed out that, in the range of doses examined, there was one for which the disruptive action of mescaline reach the maximum so that mice behaviour became completely casual.     

Regional localization of [14C]mescaline in rabbit brain after intraventricular administration

Albino rabbits of either sex were anesthetized, and a cannula was implanted permanently into the lateral ventricle. About 1 week later, the distribution of [¹⁴C]mescaline and its deaminated metabolite, [¹⁴C]trimethoxyphenylacetic acid ([¹⁴C]TMPA) in 12 brain regions was examined at 15, 60, and 180 min after the intraventricular injection of [¹⁴C]mescaline (0.5 mol in 0.05 ml saline).¹⁴C-radioactivity was rapidly distributed in all regions, reaching peak levels within 15 min. The spinal cord, superior colliculus, pons, hypothalamus, caudate, medulla oblongata, and inferior colliculus contained 23–57 nmol/g of mescaline; the thalamus, tegmentum, and cerebellum, 12–15 nmol/g; and the cerebrum and hippocampus, less than 10 nmol/g; the levels of [¹⁴C]TMPA ranged from 0.5 to 5 nmol/g. The levels of [¹⁴C]mescaline and of [¹⁴]TMPA in all brain areas were considerably decreased 180 min after its injection. Pretreatment with chlorpromazine (15 mg/kg, i.p., 30 min) lowered [¹⁴C]mescaline concentrations in the hippocampus, caudate, thalamus, and cerebrum and elevated them in the spinal cord, medulla oblongata, pons, and tegmentum; [¹⁴C]TMPA levels as the percentage of total radioactivity were not affected. Pretreatment with iproniazid (150 mg/kg, i.p., 18 h), on the other hand, uniformly reduced the TMPA levels in all brain areas, with the resultant increases in mescaline levels. The CPZ-effect in lowering the mescaline concentrations in the areas belonging to the limbic system may have significance in explaining its antihallucinogenic effect in humans and its ability to block the altered behavior induced by the latter drug in laboratory animals.     

Study of circadian activity in the crayfish <Emphasis Type="Italic">Pontastacus Leptodactylus</Emphasis> during their multimonth maintenance in the river water flow

By the method of non-invasive on-line recording and processing of photoplethysmograms of testaceous invertebrates, the circadian rhythm of cardioactivity was studied in crayfish Pontastacus leptodactylus by recording for several month of the heart rate (HR) and stress-index (characteristics of variational pulsometry). The crayfish were kept in the natural running water in regime of the natural illumination alternation (the first group) or at constant artificial illumination of low intensity (the second group). The circadian rhythm was more frequent and more pronounced in crayfish of the first group. The criteria were established to determine the appearance and stabilization of the nocturnal, active rhythm phase: an increase of HR by more than 30% as compared with the daytime rest period and duration of such increase for at least 2.5 h. The stress-index has been shown to be a reliable parameter of the beginning of the nocturnal phase of cardioactivity, while preservation of the typical circadian rhythm can be considered as a bioindicator in the biomonitoring systems of the quality of surface waters.     

Chronopharmacology of pancuronium in rats anesthetized by CT 1341 (Alfatésine)]

A circadian variation in the curarizing ability of pancuronium bromide (Pavulon) has been documented in an homogenous group of 100 Wistar AF-SPF adult male rats anaesthetized by the steroid anaesthetic althesin (Alfatésine, CT 1341). Animals were maintained at 24 +/- 2 degrees C and synchronized with natural light 06.00 to 18.00 and darkness (october 1977). We observed significant circadian rhythms for both of these agents: first the induction of anaesthesia by althesin was markedly pronounced at 15.30 and varied with season. Secondly the maximum effect of pancuronium was recorded at 08.00. When rats were anaesthetized by sodium pentobarbital under similar experimental conditions but during a different season (january to may) we observed a similar circadian rhythm for pancuronium. These data indicate that: a) the type of anaesthesia used in the protocol may not be of importance in demonstration of a curarizing rhythm in the rat but, b) the possibility of a seasonal component being present and effecting this rhythm needs to be investigated.     

Mescaline-induced changes of brain-cortex ribosomes. Role of spermidine in counteracting the destabilizing effect of mescaline on brain-cortex ribosomes

1. The effect of spermidine on the mescaline-induced changes of brain-cortex ribosomes was studied by adding spermidine during the treatment of goat brain-cortex slices with mescaline. 2. Mescaline treatment of brain-cortex slices removed a portion of the endogenous spermidine from ribosomes and this removal was significantly prevented when spermidine was present during mescaline treatment. 3. Spermidine present during mescaline treatment of brain-cortex slices counteracted, to some extent, the destabilizing effect of mescaline on ribosomes with respect to heat denaturation. 4. Mescaline treatment of brain-cortex slices made ribosomes more susceptible to breakdown, releasing protein and RNA, and resulting in loss of ribosomal enzymic activities. However, spermidine present during mescaline treatment counteracted moderately the mescaline-induced ribosomal susceptibility to breakdown and ribosomal loss of enzymic activities. 5. Ribosomes of mescaline-treated cortex slices were rapidly degraded by ribonuclease and trypsin. However, if spermidine was present during mescaline treatment of brain-cortex slices the rates of degradation diminished.     

Effects of nutritional cues on the duration of the winter anovulatory phase and on associated hormone levels in adult female Welsh pony horses (Equus caballus)

Background

Mares have an annual reproductive rhythm, with a phase of inactivity in midwinter. The aim of this study was to determine the impact of food restriction on physiological and metabolic hallmarks of this rhythm.

Methods

Over three successive years, 3 groups of 10 mares were kept under natural photoperiod. A 'well-fed' group was fed to maintain the mares in good body condition; a 'restricted' group received a diet calculated to keep the mares thin and a 'variable' group was fed during some periods like the 'restricted' group and during some other periods like the 'well-fed' group, with the aim of mimicking the natural seasonal variation of pasture availability, but a few months in advance of this natural rhythm.

Results

Winter ovarian inactivity always occurred and was long in the restricted group. In contrast, in the 'well-fed' group, 40% of mares showed this inactivity, which was shorter than in the other groups. Re-feeding the 'variable' group in autumn and winter did not advance the first ovulation in spring, compared with the 'restricted' group. Measurements of glucose and insulin concentrations in mares from the 'restricted' group during two 24 h periods of blood sampling, revealed no post-prandial peaks. For GH (Growth hormone), IGF-1 and leptin levels, large differences were found between the 'well-fed' group and the other groups. The glucose, insulin, GH and leptin levels but not melatonin level are highly correlated with the duration of ovulatory activity.

Conclusions

The annual rhythm driven by melatonin secretion is only responsible for the timing of the breeding season. The occurrence and length of winter ovarian inactivity is defined by metabolic hormones.     

Influence of certain stimulation parameters on the character of the cortical self-sustained after-discharge

The ECoG pattern of self-sustained after-discharges (SSADs) evoked by rhythmic electrical stimulation of the cerebral cortex is far from uniform. In acute experiments on male rats the authors studied the significance of the frequency, intensity and length of stimulation for the character of the resultant SSAD. In the first group (11 rats), a stimulation frequency of 8 Hz was used; the stimulation series, which lasted 10 and 20 s, always led to the formation of a SSAD composed of spike-and-wave rhythm right from the outset. Shortening the time of stimulation markedly reduced its effectiveness. In the second group (10 animals), stimulation with 50 Hz frequency often evoked a complex SSAD starting with desynchronization, which was followed by fast spike activity of increasing amplitude and only later by spike-and-wave rhythm or by polyspike-and-wave rhythm. Towards the end, serrated waves--i.e. graphoelements typical of SSADs evoked by electrical stimulation of limbic structures--often appeared in the SSAD. A higher stimulation intensity increased the incidence of this complex SSAD. In this group a minimum duration of stimulation was also essential (series of less than 2 s were not reliably effective). When this second type of SSAD ended, depression of ECoG activity was followed in 27% of the cases by a spontaneous recurrent seizure (RS). The ECoG character of these RS can be very variable. The two types of seizures evoked by slow and fast stimulation differ from each other not only in respect of their ECoG pattern (where the difference is probably due to more pronounced propagation to subcortical structures after faster stimulation), but also as regards the presumed mechanism of their onset.     

Phylogenèse des Phoronida

Phylogenese of Phoronida. Lophophorata and the Archimerata concept The main phylogenetic characteristics of Phoronida and other Lophophorates are discussed: 1. Archimeric segmentation of the body; 2. Egg cleavage of radial (or biradial) type, coeloblastula and gastrulation by invagination (emboly); 3. Mesoderm formation by a derived enteroccelous method (primitive stage of enteroc? ly); 4. Bringing of the anus anteriorly to lie rocoelous method (primitive stage of enterocoely); 4. Bringing of the anus anteriorly to lie sence of a true lophophore; 6. Larva not of trochophoral type, but actinotroch related to Tornaria-Dipleurula; 7. Nervous system basi-epithelial with primitive neurulation in Phoronopsis, without any orthogons; 8. Adult nervous ganglion neo-formed, not issuing from the apicale plate; in Phoronida this ganglion is located in the prosome and not in the mesosome; 9. Lack of cephalization. All these characteristics are closely related to that of the primitive phyla of the Chordata assemblage. The only exception is the presence of protonephridia with solenocytes in actinotroch, but such organs are also described in Cephalochordata. The Lophophorata (Phoronida, Brachiopoda, Bryozoa) are undoubtedly a primitive group on the Chordata trend and the Phoronida appear to be the most phylogenetically evolved phylum of this group with predominating position. The validity of placing the Lophophorata within the Echinoderm-Hemichordata assemblage is demonstrated. The term Archic?lomata appears not suitable and its substitution by Archimerata, assemblage at the base of the Chordata, is here proposed. The Archimerata concept brings together the Lophophorata, Echinodermata and Hemidiordata and is considered as a phylogenetic stage and a natural systematic unit.     

Behavioral disinhibition by mescaline.

Rats were exposed to a CER procedure in which sucrose drinking was suppressed by a tone previously paired with shock. Suppression of drinking during the tone was reduced by mescaline (50 mg/kg) independently of whether training took place under mescaline or placebo. Additional data on the effect of mescaline on sucrose drinking indicated that the result could not be attributed to an increased drive to drink sucrose. It was proposed that mescaline releases behavior from inhibitory control. A number of studies from the literature were cited which supported this hypothesis.     

O139型霍乱菌苗人群副反应观察报告

在广西田阳县中学生中,分６组共６９７人进行了Ｏ１３９型霍乱菌苗与Ｏ１群霍乱菌苗的双盲、有对照的人体反应现场观察。结果表明,不加铝佐剂的Ｏ１３９型霍乱菌苗及Ｏ１群霍乱菌苗,不论是低剂量组（两剂全程接种４５亿菌体）抑或常剂量组（全程接种９０亿）接种人群均可产生１０～２５％的体温呈轻度升高的弱反应,并且同种菌苗的两剂量组的反应率无显著差异;第一剂接种的反应率（１９～２５％）较第二剂接种的（１０～１５％）高,Ｐ＜０．０５;接种局部反应轻微,只有个别受试者出现直径小于１５ｍｍ的硬结;加佐剂的Ｏ１群吸附霍乱菌苗的反应较其它组强。结果证实,甲醛灭活的Ｏ１３９型霍乱菌苗和Ｏ１群霍乱菌苗是安全的,接种人体对之具有良好的耐受性     

Non-enzymic incorporation of amines into proteolipid protein

—Proteolipid protein binds biogenic amines irreversibly. The bound amines can be recovered as the original compounds and as complexes with polypeptide after proteolysis or acid hydrolysis. The properties of the protein-bound tryptamine are consistent with the concept that the amine is covalently linked by its primary amine group. Mescaline, 3,4-dihydroxyphenylethylamine, 5-hydroxytryptamine (5-HT) and histamine also bind irreversibly to proteolipid protein. 5-Hydroxytryptamine and mescaline bind similarly to other proteins (casein, ovalbumin, serum albumin and a serum protein mixture), but proteolipid binds the amines to a greater extent.