Biomedical subjects
Publications and source records attributed to W Oelssner.
The measurement of pH is increasingly being used as an additional or prophylactic diagnostic method in gynecology. In this paper a new measuring set-up for this purpose is described. The special rod-shaped probe contains an ISFET pH sensor and a miniaturized reference electrode. Initial experimental results of in vivo applications are discussed.
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Immature and adult female rats were bilaterally implanted in the medial preoptic area (MPOA) or hypothalamic ventromedial-arcuate region (VMAR) with the dopamine (DA) antagonist, pimozide, or the DA agonist, apomorphine, and the sensitivity to the LH-inhibiting effect of a subcutaneous injection of estradiol benzoate (EB), the onset of puberty and ovarian cyclicity were investigated. Diminution of the inhibitory effect of EB on LH secretion was recorded in ovariectomized immature and adult females implanted in the MPOA with pimozide. This response was not obtained in rats implanted in the VMAR. In contrast, medial preoptic, but not intrahypothalamic, implantation of agar pellets containing apomorphine resulted in enhanced sensitivity to estrogen both prepubertally and during the ovarian cycle. The sensitizing effect of apomorphine was completely prevented in prepubertal rats by pretreatment with EB for 6 days. Bilateral implantation of pimozide-agar pellets in the MPOA of 28-day-old intact females induced significant advancement of the onset of puberty, whereas sexual maturation was not affected by daily subcutaneous injections of the DA antagonist from day 28 till the day of vaginal opening. In adult 4-day-cyclic rats fitted with guide cannulae, the forthcoming ovulation was delayed for about 7 days as compared to the controls implanted with agar if apomorphine was placed in the MPOA from the morning of metestrus to the morning of diestrus. Similar implants located in the VMAR were ineffective in this regard. The results suggest that: (1) low DA activity in the MPOA reduces and high activity enhances the sensitivity of the negative estrogen feedback in immature and adult female rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Most of all women submitted to radical operation for a loco-regionally advanced mammary carcinoma show a fateful latent formation of remote metastases necessitating a total body treatment. In a pilot study twenty patients underwent instead of adjuvant chemotherapy an irradiation of both the upper and lower body part administered in two sessions with a dose of 8 Gy to the lung and the median body line, respectively, in order to reduce or to destroy micrometastases. The irradiations were given in one day at intervals of three to four weeks. They were well tolerated. A negative influence on the disease has not yet been observed, however, the manifestation of metastases seems to be delayed. The method is not expensive and involves little inconvenience for the patient, on the other hand it still seems to be capable of improvement.
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Tyrosine hydroxylase (TH) activity was determined by measuring the formation of [3H]DOPA from [3,5-3H]tyrosine in the crude synaptosomal fraction of the nucleus accumbens under conditions preventing dopamine reuptake in 30 mM K+-containing medium. TH seems to be allosterically activated under depolarizing conditions: a 4.4 fold decrease of the Km value for tyrosine of the synaptosomal TH was observed. Synaptosomal TH activity was inhibited concentration dependently by dopamine and apomorphine resulting in IC50 values of 0.4 and 0.25 microM, respectively. The maximal inhibitory effects of dopamine as well as apomorphine were about 50% of the controls. The dopamine-induced inhibition was completely antagonized by neuroleptics. The rank order of antagonistic potencies was haloperidol greater than clozapine greater than sulpiride (with increasing EC50); methiothepine was ineffective. Moreover, synaptosomal TH activity was inhibited by serotonin in a concentration-dependent manner (IC50 = 0.8 microM). This inhibition was completely antagonized by methiothepine while, on the other hand, haloperidol was ineffective. The experimental system demonstrated here appears to be suitable for estimating the presynaptic dopamine and serotonin antagonistic potencies of drugs.
By introduction of fluorine into the position 7 of butaperazine, chlorpromazine, methoxypromazine, perphenazine, prochlorperazine or into the position 3 of promazine derivatives are obtained with higher affinities for the 3H-spiroperidol binding site of the dopamine receptor compared with the corresponding substances free of fluorine.
The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 micrograms), suppressed the LSD effect in the same manner as serotonin antagonists did. Since alpha-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an alpha- adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 micrograms), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.
Locomotor hyperactivity was induced in rats by bilateral injection of picrotoxin (PIC) into the nucleus accumbens (NAC) followed by intraperitoneal (IP) or intra-accumbens (IA) injection of agents affecting dopamine (DA), acetylcholine, serotonin, or GABA receptors. IP injection of haloperidol and diazepam attenuated PIC-induced hypermotility in a dose-dependent manner. Low (sedative) doses of the DA agonists apomorphine (APO) and lisuride, or pretreatment with reserpine abolished PIC-induced hypermotility. Independent of a preceding IA injection of PIC, higher IP doses of APO produced the well-known locomotor effect. LSD, and the atypical neuroleptic, sulpiride, potentiated PIC-induced hypermotility strongly whereas clozapine was ineffective. IA injection of carbachol or haloperidol, in doses which antagonized hypermotility induced by APO IP, did not influence PIC-induced hypermotility. The atypical neuroleptics, clozapine and sulpiride, and the benzodiazepine, diazepam, inhibited PIC-induced hypermotility. The results suggest that there is a complex involvement of GABA, DA and serotonin functions in the effectuation of PIC-induced hypermotility and that PIC-induced hypermotility may be affected by DA-sensitive structures situated outside the NAC.
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In superfusion experiments with a crude synaptosomal fraction from the nucleus accumbens of rats, lysergic acid diethylamide, mescaline and N,N-dimethyltryptamine (representing different chemical classes of psychotomimetics) produced a concentration-related inhibition of K+-evoked [3H]dopamine release whereas spontaneous release remained unchanged. The nonpsychotomimetic ergoline lisuride tested at the same concentration range did not modulate spontaneous or K+-evoked [3H]dopamine release. The inhibitory effects of the psychotomimetics tested were antagonized by equal concentrations of haloperidol or methiothepine. It is postulated that the effects of psychotomimetics on DA release were triggered via simultaneous action at presynaptic dopamine and 5-hydroxytryptamine receptors which are located at dopamine nerve endings in the nucleus accumbens.
The model of LSD-potentiated apomorphine hypermotility (LPAH) in rats in comparison to apomorphine-induced hypermotility (AH) was used to investigate typical and atypical neuroleptics by analyzing complete dose response curves. Haloperidol (0.06 mg/kg) induced a parallel shift to the right of both the AH and LPAH dose response curves indicating dopaminolytic properties without any serotonolytic effect. Chlorpromazine (0.5 mg/kg) caused a mixed inhibitory effect on the LPAH, whereas the AH was not affected, probably due to the variety of actions at different transmission systems. Clozapine (0.125 mg/kg) antagonized the LSD effect indicating serotonolytic properties, whereas an additive influence on the AH might be caused by its cholinolytic properties. Sulpiride (10 mg/kg) potentiated both the AH and the LPAH, probably due to presynaptic dopaminergic mechanisms. Two conclusions can be drawn: (1) The results agree with and support the idea of a serotonergic modulation of the (predominant) mesolimbic dopaminergic system in the induction of locomotor effects. (2) The model of LPAH is useful to clearly differentiate typical from atypical neuroleptics, and to obtain information whether there is a primary involvement of dopaminergic or serotonergic mechanisms.
Influence of serotonin on dopaminergic binding sites investigated on striatum membranes of the rat in vitro Two binding sites could be demonstrated for 3H-apomorphine (3H-APO) as well as for 3H-spiroperidol (3H-SPI) in the used membrane fraction of rat striatum (3H-APO: KD' 0.3 nM, Bmax', 47 fMol/mg protein; KD" 3.5 nM, Bmax" 173 fMol/mg protein. 3H-SPI: KD' 0.08 nM, Bmax', 62 fMol/mg protein; KD" 2 nM, Bmax" 271 fMol/mg protein). After preincubation with serotonin (10 microM, 30 min, 37 degrees C) and washing the membranes twice an increase of the high affinity 3H-APO binding and the low affinity 3H-SPI binding by 64% and 57%, respectively, was shown. This effect of serotonin was counteracted by methiothepin (0.1 microM) in both cases. The results provide evidence for allosteric conformation changes of distinct dopaminergic binding sites which can be triggered by specific serotonin receptors in vitro and may be operative under in vivo conditions.
The content of acetylcholine and choline and the acetylcholine turnover rates were determined in olfactory tubercle, n. accumbens, striatum and hippocampus after the administration of various doses of apomorphine. Whereas apomorphine failed to change the levels of both amines, the acetylcholine turnover rates were markedly influenced in a dose and time dependent manner. A clear-cut decrease of the latter parameter in all four brain structures was observed after administration of higher doses of apomorphine (1 and 2.5 mg/kg). After a low dose of apomorphine (0.25 mg/kg) the acetylcholine turnover in the striatum was depressed, too. However, the acetylcholine turnover was dramatically increased in olfactory tubercle and n. accumbens. An inhibitory dopaminergic modulation of cholinergic neurons has been postulated to exist in these four brain structures. Some functional differences between the nigrostriatal and the mesolimbic dopamine systems have been discussed.
Locomotor hyperactivity in rats was induced by microapplication of apomorphine (1 microgram/microliter) or picrotoxin (0.5 microgram/microliter) bilaterally into the n. accumbens and measured in an open field test. After systemic administration, the dopaminolytic drug haloperidol in doses between 0.06 and 0.25 mg/kg abolished both types of hypermotility. After an intraaccumbens injection of haloperidol (0.4 microgram/microliter, bilaterally) or carbachol (1.0 microgram/microliter, bilaterally), the apomorphine hypermotility was completely suppressed whereas the picrotoxin effect remained unchanged. Scopolamine which is known to induce hypermotility after systemic administration was, as methylatropine (1.0 mu/microliter bilaterally), too, without any locomotor effect after intraaccumbens injection. The locomotor inhibitory effect of haloperidol is discussed to be not restricted to its dopaminolytic action within the n. accumbens.
Neurons of the Wistar-rats' occipital cortex were morphologically investigated after chronical application of amphetamine. The nerve cells impregnated according to the Golgi-Kopsch technique showed in part changes on both the dendrites and in the axonal region. Besides a partial reduction of spines and of peripheral dendritic arborizations round varicosities of different density could be observed on the dendrites and on the axon, either, which were discussed to be due to a neurotoxic effect of amphetamine.
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