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Biomedical subjects

J M van Ree

Publications and source records attributed to J M van Ree.

At least 145 records · Page 8Linked to original sources

Involvement of the pituitary-adrenal axis in socio-behavioral disturbances after short-term isolation.

Short-term social isolation increased socio-explorative behavior of pairs of adult male Wistar rats. Hypophysectomy or adrenomedullectomy did not prevent this increase in social behavior. No differences between 7-day isolated (I) and non-isolated (socially housed, S) animals were observed in basal plasma corticosterone levels and these levels increased to the same level in I- and S-rats during individual exposure to the observation cage. The increase in corticosterone levels found immediately after the social interaction test was higher in I- than in S-rats. When I- and S-rats were tested together, a negative correlation was present between plasma-corticosterone levels and frequencies of social interactions. Blood pressure and heart rate were not affected by the isolation procedure. ACTH1-24 (5 micrograms/100 g) did not affect the frequencies of social interactions, neither in I- nor in S-rats. Although a role for corticosterone in "basal" social behavior could not be excluded, it seems that pituitary-adrenal hormones are not important for the development and expression of socio-behavioral disturbances due to short-term isolation.

Animals↗

Effects of desglycinamide-arginine-vasopressin (DG-AVP) on memory processes in diabetes insipidus patients and non-diabetic subjects.

The effects of desglycinamide9-arginine8-vasopressin (DG-AVP) on memory processes have been studied in patients with central diabetes insipidus (DI) and in non-diabetic control patients. Acute im injection of DG-AVP improved some aspects of short-term memory. Subchronic intranasal administration of DG-AVP facilitated short-term memory more consistently and in addition improved long-term memory. DG-AVP increased the attention, but only in the non-diabetic subjects. The effects of DG-AVP on memory processes persisted after discontinuation of treatment. DG-AVP did not affect the parameters for water and electrolyte metabolism, blood pressure and pulse rate neither in DI nor in the control patients. Thus, the memory effects of DG-AVP are probably mediated by a direct action on the central nervous system.

Adolescent↗

Des-Gly9-[Arg8]-vasopressin may facilitate methadone detoxification of heroin addicts.

Mild to moderate heroin addicts started on ambulatory detoxification with methadone were sublingually treated with placebo or desglycinamide9-arginine8-vasopressin (DGAVP, 1 mg/day) for 5 days using a double-blind design. Treatment with DGAVP (6 patients) led to a longer time course of clinic attendance and resulted in a higher percentage of successful detoxifications as compared to placebo treatment (6 patients). The analyses of urine samples revealed that DGAVP treatment decreased the use of heroin and cocaine below that with placebo treatment. The medical attendant judged DGAVP treatment superior to placebo treatment. It is concluded that treatment with DGAVP during the initial phase of methadone detoxification of heroin addicts may facilitate detoxification. This beneficial effect of DGAVP is consistent with animal data showing that this peptide may attenuate the reinforcing qualities of heroin.

Adult↗

Neuropeptides, mental performance and aging.

The presence of peptidergic neuronal networks in the brain and the modulating action of neuropeptides on brain functions as evidenced by their behavioral influence in particular support the concept that the brain like the peripheral endocrine glands is an endocrine target organ which is as sensitive to treatment with neuropeptides as the peripheral glands are to pituitary hormones. Animal and human data are reviewed showing that neuropeptides related to ACTH/MSH affect motivational and attentional processes and that those related to vasopressin are involved in memory processes. Since these functions decline during aging it is postulated that a decreased bioavailability of neuropeptides in brain of elderly people is associated with specific disturbances in mental performance. Thus, the decreased mental ability of the aged may be restored by treatment with neuropeptides particularly those with little, if any, peripheral, endocrine activity, like the ACTH neuropeptide Org 2766 and the vasopressin neuropeptide DGAVP.

Adrenocorticotropic Hormone↗

beta-Endorphin proteolysis by guinea-pig ileum myenteric plexus membranes: increased gamma-endorphin turnover after chronic exposure to morphine.

The influence of chronic morphine exposure in vitro on the biotransformation of beta-endorphin (beta E) was investigated using the myenteric plexus-longitudinal muscle of guinea-pig ileum. A membrane preparation was incubated with beta E and the degradation of beta E as well as the accumulation of several beta E fragments in the incubation medium were followed with time. The levels of peptides were determined by specific radioimmunoassays after separation by high-pressure liquid chromatography. It was found that exposure to morphine did not affect the disappearance of beta E, but altered the time course of accumulation of beta E fragments. In fact, the accumulation of gamma-endorphin, alpha-endorphin and des-tyrosine1-alpha-endorphin was enhanced, while that of des-tyrosine1-gamma-endorphin was not change. Additionally, the disappearance of gamma-endorphin appeared to be stimulated by morphine exposure. These data provide evidence that the fragmentation of beta E is changed by chronic morphine exposure in such a way that the turnover of gamma-endorphin is increased.

Animals↗

Antipsychotic properties of Des-enkephalin-gamma-endorphin in treatment of schizophrenic patients.

Animal experiments have shown that the gamma-endorphin fragment des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine-gamma-endorphin. We postulated that DE gamma E may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DE gamma E, 23 patients with different types of relapsing schizophrenia were treated with DE gamma E dissolved in saline or placebo. Neuroleptic medication was continued during the experimental period. In the first single-blind trial, two patients were treated with 1 mg of DE gamma E and two with 10 mg of DE gamma E intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DE gamma E IM daily for ten days and six received placebo. Of the 17 patients treated with DE gamma E, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DE gamma E appeared to be negatively correlated with the dosage of neuroleptic medication and the duration of the last psychotic episode. These results support the hypothesis that disturbances in gamma-endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.

Adult↗

Opposite interactions between alpha- and beta-endorphin fragments with dopamine mediated responses on the rat rectum in vitro.

Dopamine causes a dose-dependent contraction of the rat rectum in vitro followed by a relaxation. This contraction can be inhibited by apomorphine and phenylephrine. This inhibition can be attenuated by the beta-endorphin (beta E) fragments 2-17 (des-Tyr1-gamma-endorphin, DT gamma E) and 6-17 (des-enkephalin-gamma-endorphin, DE gamma E). beta E 6-17 seems to be the shortest sequence with full activity in this respect since a shorter fragment (beta E 10-17) was less effective. The atypical neuroleptics oxypertine, sulpiride, and clozapine, the classic neuroleptic haloperidol and metoclopramide have a similar action to DE gamma E. The peptides and atypical neuroleptics do not affect the dopamine response per se while the classic neuroleptics haloperidol and metoclopramide enhance the dopamine response. The effects of the alpha-type endorphins are opposite to those of the gamma-type endorphins, since des-Tyr1-alpha-endorphin (DT alpha E, beta E 2-16) and des-enkephalin-alpha-endorphin (DE alpha E, beta E 6-16) enhance the phenylephrine-induced decreased responsiveness to dopamine. Structure-activity studies revealed that the active moiety of the alpha-endorphin fragments probably resides in the 6-9 region. In addition the alpha-type endorphins directly inhibit the dopamine response. It is concluded that the rat rectum may be used to analyse neuroleptic-like action. In this model alpha- and gamma-endorphin fragments may directly or indirectly influence the interaction of dopamine with the rectum. Because of the strong similarities between the effects of gamma-type endorphins and that of neuroleptics the results support the purported neuroleptic-like action of gamma-type endorphins. The influence of alpha-type endorphins and gamma-type endorphins on the apomorphine or phenylephrine induced decreased responsiveness to dopamine, although opposite, seems to be mediated by an influence on different dopamine sensitive systems.

Acetylcholine↗

Interaction of calcium with 3H-morphine binding to synaptosomes of the guinea-pig ileum.

Specific binding sites for 3H-morphine were assayed in subcellular fractions of a crude mitochondrial P2 pellet from the guinea-pig ileum longitudinal muscle-myenteric plexus, prepared by discontinuous sucrose-gradient fractionation. The highest specific binding (ca. 100 fmol/mg protein) was obtained in the fraction containing synaptosomes, as examined by electron microscopy. A synaptosomal fraction prepared from guinea-pig brain had comparable specific binding (ca 130 fmol/mg) to that of the ileal synaptosomal fraction. Addition of calcium (10 mM) to the binding assay medium resulted in a marked decrease in particular of the specific 3H-morphine binding. Detailed analysis of the specific 3H-morphine binding. Detailed analysis of the specific 3H-morphine binding in the synaptosomal fraction of the ileum revealed that 1) a saturable component of specific opiate binding was present between 0.34 and 21.74 nM of 3H-morphine; 2) in the presence of 3 and 10 nM of calcium similar decreases of specific 3H-morphine binding were obtained, indicating that this binding was maximally inhibited already by 3 mM of calcium; 3) both in the absence and presence of calcium the KD of specific 3H-morphine binding was about 38 nM, indicating a non-competitive nature of the calcium inhibition; 4) addition of magnesium exhibited a similar effect as that of calcium, although magnesium appeared to be less potent than calcium in this respect. The data are discussed in the context of previously observed calcium effects on opioid actions in the electrically stimulated guinea-pig ileum bioassay and may contribute to the evidence that the interaction of calcium and opioids on the stimulus-release coupling mechanism at the neuromuscular junction of the guinea-pig ileum is occurring beyond opioid receptor activation as well.

Animals↗

Short-term isolation increases social interactions of male rats: a parametric analysis.

Frequencies of social interactions were higher in pairs of short-term individually housed male Wistar rats as compared to group-housed animals. This was most pronounced when an individually housed rat and a group-housed conspecific were tested together in the morning under red light conditions. Then, in particular the behavioral elements exploration partner, anogenital investigation, crawl over/mount and social grooming were enhanced. The increases in social interactions was dependent on the duration of the period of individual housing and appeared to be maximal after 4 to 7 days of individual housing. The effect extinguished after repeated testing. The observed behavioral changes were hardly affected by habituation to the test cage and were also present in young animals. The increase in social interactions is apparently not due to a general increase in locomotor or exploratory behavior, since no differences in ambulation between individually- and group-housed animals were observed when they were tested together in the social interaction test, and locomotor activities hardly differed in an open field test procedure.

Age Factors↗

Hla, and the response to treatment with gamma-type endorphins in schizophrenia.

In order to investigate whether genetic factors are involved in the response of schizophrenic patients to treatment with gamma-type endorphins, we typed 32 Dutch schizophrenic patients for the HLA-A, -B, -C and -DR antigens. The total patient group showed an increase of HLA-Bw4 and HLA-Cw1. A subgroup of 20 paranoid patients showed an increase of HLA-Cw1 and a significant heterogeneity for the HLA-C locus. In 16 patients who responded moderately or markedly to treatment with gamma-type endorphins, an increase of HLA-B15/Cw3 and a decrease of HLA-B17 were found as compared to 16 patients with no or a slight response. Moreover, HLA-B15 was particularly increased in those patients who responded markedly and remained free of psychotic symptoms for a period of at least 6 months after treatment with gamma-type endorphins (RR = 24.6, Puncorr. = 0.0015). Our results suggest that genetic factors coded for within the HLA region are associated with paranoid schizophrenia, and that HLA-B15/Cw3 is associated with a marked and prolonged response to treatment with gamma-type endorphins.

Endorphins↗

The treatment of schizophrenic psychoses with gamma-type endorphins.

The pharmacological actions of gamma-type endorphins show similarities to those of the neuroleptics. Two fragments of gamma-endorphin (beta-LPH 61-77) were therefore tested in patients with schizophrenic and schizo-affective psychoses who had shown an insufficient response to neuroleptics. The fragments were DT gamma E (beta-LPH 62-77) and DE gamma E (beta-LPH 66-77). Some of the patients studied responded favorably to this treatment. A number of criteria of differentiation between responders and nonresponders are discussed. The influence of DT gamma E on the central DA metabolism differs from that of the neuroleptics. It is therefore conceivable that gamma-type endorphins represent a different principle of action. The therapeutic efficacy of these compounds lends support to the hypothesis that disorders of central endorphin metabolism may play a role in the pathogenesis of psychoses of the schizophrenic type.

Brain↗