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Biomedical subjects

E Vogel

Publications and source records attributed to E Vogel.

At least 19 recordsLinked to original sources

Prolactin similar to ectopic pituitary isograft restores responsiveness in Snell dwarf mice.

The effects of ovine prolactin (PRL) (2 x 5 IU a day) and an ectopic pituitary isograft on the responsiveness were examined using locomotor and exploratory activities as measures in PRL-growth-hormone-thyrotropin-deficient Snell dwarf mice (dw/dw). After 5 weeks of treatment, both PRL and the graft restored the two behavioural measures to normal levels. Results clearly demonstrate the involvement of PRL in global behavioural responsiveness and suggest a possible role for PRL in the changes induced by the graft.

Animals

[An epidural spinal abscess with caudal symptoms as a complication of Crohn's disease].

Progressive symptoms of caudal compression (flaccid paraparesis, sensory disorders), accompanied by severe pain and fever, developed over a few days in a 26-year-old man with Crohn's disease for 11 years. Spinal computed tomography, performed under the diagnosis of herniated disc, revealed intraspinal soft tissue, as well as gas in the spinal canal (L2-S3) and the paravertebral muscles. This led to the diagnosis of acute epidural abscess and a laminectomy was performed (at L4-S2). Intraspinally there was thickened, bluish fatty tissue; thick pus exuded between dura and the sacral roots. Suction-irrigation of the spinal canal was undertaken via an epidural drain. Postoperative contrast infusion into the colon demonstrated a fistula directed towards the sacrum. The postoperative course was complicated by severe respiratory impairment of which the patient died.--Epidural abscess is a rare complication of Crohn's disease. Because of its poor prognosis early diagnosis with magnetic resonance imaging or computed tomography should be undertaken in every patient with Crohn's disease who has back pain, fever or, particularly, symptoms of spinal compression.

Abscess

Comparison of the behavioural effects of an adenosine A1/A2-receptor antagonist, CGS 15943A, and an A1-selective antagonist, DPCPX.

CGS 15943A is the first reported nonxanthine adenosine antagonist and it shows high affinity towards A1 and A2 receptors. The present data show that CGS 15943A increased in a dose-dependent manner locomotor activity of mice confronted with a free exploratory test without markedly modifying rears or, at low or medium doses, novelty seeking responses. In the light/dark choice procedure, which is especially appropriate for revealing anxiolytic and anxiogenic drug-effects, CGS 15943A decreased the time spent by mice in the lit box and increased the number of transitions. By contrast, the highly selective adenosine A1 receptor, DPCPX, did not significantly modify the behavior of mice except at high doses, which decreased it in the free exploratory test. It is suggested that the present findings confirm the hypothesis that the behavioral effects of adenosine antagonists are linked to their actions at adenosine A2 receptors.

Adenosine

Behavioral effects of rolipram and structurally related compounds in mice: behavioral sedation of cAMP phosphodiesterase inhibitors.

The behavioral effects of specific cAMP phosphodiesterase inhibitors (PDE-I) such as rolipram and structurally related compounds were investigated in mice. Selected PDE-I induced a potent dose-dependent decrease in locomotion and in rearing of mice confronted with a free exploratory procedure, these effects being considered as a behavioral sedation. However, in the light/dark choice test especially conceived to reveal disinhibitory and/or anxiolytic action, they did not show obvious effects. These results suggest that the increase of cAMP probably does not account for our previously observed anxiolytic properties of BW A78U, an adenine derivative PDE-I (20).

3',5'-Cyclic-AMP Phosphodiesterases

m-Chlorophenylpiperazine enhances neophobic and anxious behaviour in mice.

1-(3-Chlorophenyl)piperazine (mCPP) reduced novelty-seeking behaviour as well as the number of rears in mice confronted with a free exploratory test. Moreover, mCPP was found to decrease the time spent by mice in the lit box and the number of transitions in a two-box light/dark choice situation validated for the detection of anxiolytic or anxiogenic drugs. These results suggest that mCPP enhances emotional responses towards novel and aversive places. Since mCPP has been reported as a 5-HT1C receptor agonist, it can be hypothesized that increased activity of serotonin may play a role in regulating certain forms of emotional behaviour in animals.

Analysis of Variance

Serenics fluprazine (DU 27716) and eltoprazine (DU 28853) enhance neophobic and emotional behaviour in mice.

Two tests designed to elicit responses to novelty and to aversive stimuli were used to study the effects of the serenics fluprazine and eltoprazine on the behaviour of male Swiss mice: a free exploratory test (fluprazine; 2.5, 5 and 10 mg/kg; eltoprazine: 2.5, 5, 10 and 15 mg/kg) and a two-box choice procedure (fluprazine: 1.25, 2.5, 5 and 7.5 mg/kg; eltoprazine: 2.5, 5, 7.5 and 10 mg/kg). Both drugs increased the neophobic reaction, as well as the avoidance of a brightly illuminated box. These effects closely resemble those of psychostimulant drugs such as methamphetamine and caffeine. It is hypothesized that the behavioural changes induced by these drugs may be due to a nonspecific increase of the emotional reactivity of animals.

Animals

Anxiolytic and sedative properties of BW A78U, a novel anticonvulsant adenine derivative.

The anticonvulsant BW A78U, tested in a free mouse exploratory situation, reduced in a dose-dependent fashion the locomotion and the number of rearings, this sedative effect being significant up to a dose of 15 mg/kg (IP, 20 min before testing). In an unconditioned conflict test, the light/dark box choice situation, specific for anxiolytics, low doses of BW A78U increased the time spent by mice in the lit box as well as the number of transitions between the two boxes. Finally, we demonstrated that this drug was able to protect mice against pentylenetetrazole-induced convulsions. Our data show that BW A78U possesses some of the characteristic properties of the minor tranquilizers. However, since this compound binds to the benzodiazepine receptor with a very low affinity (IC50 = 13.6 microM), it can be assumed that this drug does not exert its behavioral effects through these receptors. It may interfere with other targets involving adenosine, another potent physiological regulator of neuronal excitability.

Animals

Anxiogenic effects of a benzodiazepine receptor partial inverse agonist, RO 19-4603, in a light/dark choice situation.

In a light/dark choice procedure, the imidazothienodiazepinone RO 19-4603, given alone, induced a dose-dependent decrease in the time spent by mice in the lit box as well in the number of transitions between the two boxes. These data confirm the anxiogenic intrinsic properties of inverse agonists of the benzodiazepine receptor. Since RO 19-4603 also reversed the anxiolytic effects of ethanol and exhibited proconvulsant properties, it is suggested that the antagonistic action of this drug against ethanol could be due to an additive rather than an interactive process.

Animals

The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. I. Recessive lethal mutations and translocations in Drosophila.

The relationship in Drosophila males between chemical reaction pattern of mono-functional alkylating agents (AA), described in terms of primary alkylation pattern with DNA and proteins as well as the Swain--Scott s factor, and their biological effectiveness were investigated. The agents chosen for comparative analysis were the nitrosamides ENU and MNU, the methanesulfonic esters iPMS, EMS and MMS, the dialkylsulfate DMS, and the nitrosamines DEN and DMN. Parameters of their biological activity were mortality (LC50) of treated adult males, induction in post-meiotic stages of X-chromosomal recessive lethal mutations and 2--3 translocations after either adult feeding or injection. Induced frequencies of recessive lethals, determined for each AA with a range of concentrations, served as biological dosimeter for interaction with target DNA in the germ line. The results are interpreted as indicating for these AA a causal connection between the pattern of primary alkylation of DNA and the quality of genetic damage observed. 1. The agent with the lowest s value, ENU, and its pendant DEN, failed to produce translocations at mutation frequencies that reached 44% for ENU. The highest chromosome-breaking activity was attributed to AA with high s, MMS and DMS. For MMS, the proportions of translocations (T) to mutations (M) approximately reached a 1 : 1 ratio in stored spermatozoa, at a recessive-lethal frequency of 14%. Ability to break chromosomes, as indicated by the T : M ratios, decreased in the sequence MMS greater than or equal to DMS, MNU greater than DMN greater than EMS greater than iPMS greater than ENU = DEN. 2. Nearly the reversed sequence in relative mutagenci effectivenss was obtained when the (directly acting) AA were arranged on the basis of their CM4/LC50 ratios (CM4, the exposure condition producing 4% recessive lethals after injection): ENU greater than EMS greater than iPMS, MNU greater than MMS = DMS. 3. Among the AA, EMS had a somewhat unique position, in that it was slightly less effective in the translocation test, and also less cytotoxic but more mutagenic in the recessive-lethal test than one would expect from its s value. This is taken as an indication of the influence on biological effectiveness of factors other than the s value, e.g. methylation versus ethylation and the lipid/water partition ratio. An example of the latter was also provided by DMS which, although having the same s as MMS, with its 5-fold higher lipid/water partition ratio, was more toxic than MMS. 4. For those AA that were clearly active in the translocation tests--MMS, DMS, MNU, DMN and EMS--delayed formation of exchanges was observed. Only in 17 out of 555 translocation tests with positive response translocations were already found in progeny from unstored spermatozoa. Consequently, it was concluded that performance of storage experiments in Drosophila is an absolute necessity for the detection of this type of rearrangement by AA. 5...

Alkylating Agents

The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. II. Total and partial sex-chromosome loss in Drosophila.

In Drosophila the connection between primary alkylation pattern and genetic activity of 8 mono-functional alkylating agents (AA)--ENU, DEN, iPMS, MNU, DMN, EMS, MMS and DMS--was investigated in spermatozoa and spermatids of treated R 1 (2), y B/BS Y y+ males. The induction of ring-X loss, Y-chromosome loss, and Y-rearrangements served as parameters of their effectiveness to produce chromosomal aberrations. (1) The ability to cause chromosomal losses decreased in the sequence MMS = DMS greater than MNU = DMN greater than EMS greater than iPMS greater than ENU = DEN. This ranking is consistent with the sequence in effectiveness in producing translocations. (2) The low frequencies of Y-chromosome rearrangements made any meaningful comparison between the AA impossible. The diagnostic value of such tests is poor, because even at toxic concentrations large numbers of offspring must be scored to obtain statistically significant effects. (3) With MNU, DMN, EMS, MMS and DMS, a time-dependent increase in the frequencies of ring-X losses ("storage effect") was found. (4) A stage-by-stage comparison revealed a differential response of spermatozoa and spermatids to these AA. Mature spermatozoa tended to be more resistant to the induction of breaks by MNU, DMN, EMS and MMS. (5) A general observation with all the AA was a reduced rate in survival of X-bearing sperm after treatment with mutagen. There was, however, no apparent quantitative relationship between the shift in the sex ratios observed and the yield of chromosomal aberrations. It is concluded that differences between these AA in their selectivity to numerous nucleophiles of DNA, as expressed by their s values, account for most of the diversity in their genetic effectiveness. The significance for genetic activity of other parameters than the s value appeared from the lower activity of EMS relative to MNU, indicating that methylation was more effective than ethylation in breaking chromosomes.

Alkylating Agents

[Epidemiology of duodenal ulcer (author's transl)].

The epidemiology of peptic ulcer was investigated in 1105 endoscopy patients in a Zurich city hospital and in a random nongastroenterological hospital population. A raised susceptibility for duodenal ulcer was found in young, mainly unskilled, foreign labourers. There was no raised susceptibility in female foreign workers who also suffered less often from gastric ulcer than Swiss women. A tendency to ulceration in certain other diseases previously incriminated and in alcohol and nicotine consumers was not observed. A connection between susceptibility to ulceration and migration is assumed.

Adult

Absence of mutagenicity of praziquantel, a new, effective, anti-schistosomal drug, in bacteria, yeasts, insects and mammalian cells.

Praziquantel (Embay 8440, Droncit) a new, effective anti-schistosomal drug, was tested in various short-term assays that have shown a predictive value for the detection of potential carcinogens. Indicator organisms S. typhimurium strains, S. pombe, S. cerevisiae, cultured V79 Chinese hamster cells or human heteroploid cells and Drosophila melanogaster were treated with Praziquantel. The induction of reverse and forward mutations, mitotic gene conversions, X-linked recessive lethals, sister-chromatid exchanges and unscheduled DNA-repair synthesis was scored; rodent-liver microsome-, cell- and host-mediated assays were also performed. Hycanthone, another schistosomicide was included as a positive control. The absence of a genetic activity of Praziquantel uniformly observed in such a battery of tests (i) confirms the assumption that the anti-schistosomal effectiveness of this drug is not related to the mutagenic activity and (ii) should encourage the implementation of extended clinical and field trials.

Animals