Biomedical subjects

G J Boer

Publications and source records attributed to G J Boer.

At least 91 records · Page 5Linked to original sources

PubMed1988

Prenatal development of the Brattleboro rat is influenced by genotype and lysine vasopressin treatment of the mother.

Homozygous (Hom) Brattleboro rats suffer from severe diabetes insipidus (DI) as a consequence of the lack of arginine-vasopressin (AVP) in the brain. Compared with heterozygous (Het) AVP-synthesizing Brattleboro rats, Hom rats show disturbed body and brain development. In this study breeding experiments with Het and Hom rats were performed to determine whether prenatal conditions might contribute to the developmental disturbances in Hom pups. For this purpose Het and Hom females were mated with Hom and Het males, respectively. In addition lysine-vasopressin (LVP) was administered to half of the pregnant females, since this has previously been shown to stimulate birth weight of Hom pups. On day 1 postnatally the body and brain weight of Hom pups of nontreated Hom mothers was significantly smaller than that of the Het litter mates, whereas no difference was found between the weight of Het or Hom pups of nontreated or LVP-treated Het mothers. These results indicate an important role of the genotype of the mother in prenatal development of Hom pups. LVP administration failed to diminish the growth deficits, but increased protein and DNA content of the cerebellum of both Het and Hom pups. Notwithstanding the improved prenatal growth of Hom pups from Het mothers, postnatally retarded development was still observed: at 1 month of age there was a significant difference between the body, brain and cerebellar weight of Het and Hom pups from Het mothers. It was therefore concluded that the prenatal situation of the Hom mother, i.e. AVP-deficiency, significantly contributes to the developmental disturbance of the Hom pup, but also that growth impairment is linked to the presence of the mutation in the Hom pups themselves.

Analysis of Variance↗

PubMed1988

Elevated serum oxytocin of the vasopressin-deficient Brattleboro rat is present throughout life and is not sensitive to treatment with vasopressin.

The postnatal developmental course of the enhanced OT serum level of the vasopressin-deficient (homozygous) Brattleboro rat was investigated radioimmunochemically together with the response to treatment with Pitressin tannate. Compared with heterozygous Brattleboro (control) pups, in which serum OT appeared to have an adult value from birth onwards (about 10 pmol/l), homozygous rats had approximately 2-fold enhanced OT serum level throughout early development. Between day 55 and adulthood the levels of OT rose further to 40-50 pmol/l. A 3-day treatment with Pitressin tannate both in the period before or after the age (day 16) at which the polyuria of the homozygous Brattleboro mutant can be revealed, failed to reduce the serum OT. It was therefore concluded that the high OT serum levels in the vasopressin-deficient Brattleboro rat are not induced by osmotic imbalance, but probably originates from functional teratological aspects of the mutation.

Animals↗

PubMed1988

Osmoregulation in rats with long-term enhanced cerebrospinal fluid levels of vasopressin or vasoactive intestinal polypeptide.

The cerebrospinal fluid level of arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) was enhanced chronically by implantation of a device for controlled drug delivery in the lateral ventricle of the rat. Urine production, water consumption, urine osmolality as well as urinary AVP excretion were then measured for a period of 26 days. During this period the rats were studied under normal hydration and under conditions of osmotic stress induced by water deprivation (2 days) and the drinking of 2% (w/v) NaCl (6 days), in order to see whether the capacity of central systems to react adequately to osmotic stimuli was affected by high central peptide levels. Immediately after the central AVP treatment was started, a temporary increase was found in urinary AVP levels which was not accompanied by a change in any of the other parameters but which decreased again to control levels within 10 days. After this burst of AVP excretion, AVP-treated rats showed a tendency during periods of normal hydration for a lower urine osmolality, combined with a higher water intake and urine production without changes in urinary AVP excretion. Since there was no clear-cut correlation between urinary AVP excretion and body water turnover, this could still indicate a slowly acquired and slight inhibition of pituitary AVP release by long-term centrally administered AVP. However, the capacity of these rats to respond to osmotic stimuli was not different from the controls. In the VIP-treated rats a slight but significant reduction in urine production was found in all three periods of normal hydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of enhanced cerebrospinal fluid levels of vasopressin, vasopressin antagonist or vasoactive intestinal polypeptide on circadian sleep-wake rhythm in the rat.

Several endogenous peptides have been implicated in the regulation of sleep and wakefulness. The present study was carried out in order to determine whether the light-dark rhythm of vasopressin (VP) in the cerebrospinal fluid (CSF) had functional significance in relaying information from the circadian pacemaker, i.e. the suprachiasmatic nuclei (which synthesize VP as well as vasoactive intestinal polypeptide (VIP], to the centra regulating sleep. After constant delivery of VP in the CSF via an Accurel/collodion implant in the lateral ventricle, the VP CSF level was raised from 20-35 pg/ml to ca. 265 pg/ml whereby a VP rhythm in the CSF could no longer be detected. Under these conditions VP was found to increase the arousal state of the rat in the dark period, which resulted in a higher amplitude of the circadian sleep-wake rhythm. Application of the VP antagonist d(CH2)5[Tyr(Me)2]VP partly had opposite effects. A similar approach with central application of VIP resulted in an increase in rapid eye movement and quiet sleep but did not affect the amplitude of the circadian rhythm. It was concluded that although peptide levels in the CSF may show clear temporal variations with the light-dark cycle, this rhythmicity is not causally related to the circadian aspect of sleep-wakefulness. However, both VP and VIP contribute to the regulation of the amount of time spent in sleep and wakefulness and the level of VP in the CSF is correlated with the amplitude of the rhythm.

Animals↗

PubMed1987

A polymeric controlled drug delivery device for peptides based on a surface desorption/diffusion mechanism.

Further investigations of the mechanisms underlying continuous peptide delivery from a newly developed Accurel polypropylene/collodion device are described. This module was prepared by lumen-loading an aqueous peptide solution into a piece of microporous Accurel polypropylene tubing which was subsequently end-sealed and encapsulated by a collodion membrane. By using vasopressin (VP) as a 'model' peptide, various aspects of the known semi-reversible protein/polymer surface interaction are shown to be present for VP and polypropylene i.e. prominent adsorption on the large surface area, which follows a bimodal adsorption isotherm, but with very limited desorption, and which can be enhanced by exchange with other proteins. Based on these findings as well as the observed steady state levels of VP on 24 h immersions in a small fixed volume, the previously proposed mechanism of pseudo-zero-order release could be evaluated further: the adsorbed peptide molecules function as a stock of near-constant activity, since desorption is rather limited, and as long as rapid exchange of bound peptide by external proteins can be prevented by a sufficiently thick (greater than 60 micron) collodion membrane, a slow long-term diffusion process will take place. Under 'infinite sink' conditions, the devices gave linear cumulative release curves for weeks. The present module is a novelty among the known membrane-controlled drug-delivery reservoir systems, since it has been loaded by an unsaturated drug solution and because the encapsulating membrane is not the sole release-rate-controlling factor.

Adsorption↗

PubMed1986

Effects of vasopressin on female sexual behavior in male rats.

Intracerebroventricular (i.c.v.) injection of an Arg-vasopressin (AVP) antagonist did not stimulate female sexual behavior in adult castrated male rats treated with ovarian hormone but stimulated this behavior in male rats which were castrated on the day of birth. It is suggested that neonatal androgen stimulation in the male rat offsets the influence of AVP on female sexual behavior in the adult.

Animals↗

PubMed1986

Vasopressin gene expression is attenuated in the fetal Brattleboro rat.

Due to a genetic defect the homozygous Brattleboro rat is unable to synthesize vasopressin gene products but still transcribes a mutant vasopressin mRNA from the gene. To study the influence of vasopressin gene products on the development of vasopressin gene expression, vasopressin mRNA levels of the supraoptic and paraventricular nucleus were measured at fetal day 20, postnatal day 1, 15 and 30 in the Wistar rat and in the heterozygous and homozygous Brattleboro rat by Northern blot analysis and in situ hybridization. In the homozygous Brattleboro rat of fetal day 20 and postnatal day 1, no or minute amounts of vasopressin mRNA were detectable but vasopressin mRNA was readily detectable at postnatal day 15 and 30. The Wistar rat and heterozygous Brattleboro rat had abundant vasopressin mRNA at fetal day 20 with increasing amounts towards postnatal day 30. The results indicate that vasopressin gene expression in the development of the homozygous Brattleboro rat is attenuated, possibly due to the absence of vasopressin gene products.

Animals↗

PubMed1986

Immunocytochemically stained binding sites for oxytocin and alpha-melanocyte-stimulating hormone in rat brain following ventricular administration.

Binding sites for oxytocin (OXT) and alpha-melanocyte-stimulating hormone (alpha-MSH) in brain of homozygous Brattleboro rats were immunocytochemically visualized after ventricular administration of the peptides by Accurel implants. Two patterns were found: 'ring type' staining in perineuronal structures was observed in CA1 and CA3 areas of ventral hippocampus and in subiculum for OXT implanted brains and a very weak staining in striatum for alpha-MSH-implanted brains; cytoplasmic staining of intracellular binding sites was observed in the bed nucleus of the stria terminalis (BST) in brains with OXT implants and in the anterodorsal thalamic nucleus (AD) and postcingulate cortex in brains with alpha-MSH implants. These localizations are different from those described for vasopressin binding sites in the same rat strain.

Animals↗

PubMed1986

Postnatal development of vasopressin mRNA content in supraoptic and paraventricular nucleus of the Wistar rat.

Levels of mRNA coding the vasopressin precursor (VP mRNA) were determined in the supraoptic and paraventricular nucleus during the first month of postnatal development of the Wistar rat by solution hybridization assay and Northern blot analysis. The supraoptic and paraventricular nuclei showed a marked increase in VP mRNA to adult levels during that period. These results indicate an upregulation of vasopressin gene expression in supraoptic and paraventricular nuclei after birth, a period in which vasopressin starts to become involved in kidney function.

Animals↗

PubMed1986

The relevance of various tests for the study of specificity in immunocytochemical staining: a review.

Factors determining the specificity of immunocytochemical (ICC) tissue stainings as well as the various tests to study these factors are discussed. Since every specificity test only deals with particular aspects of the ICC procedure, a practical sequence of known test methods is proposed, which enables the determination of the specificity of the ICC tissue staining and, after possibly needed antiserum purification steps, may result in a monospecific staining. It is made clear that such a sequence has always to include a tissue-spectrum affinity test, in which the spectrum of tissue antigens is controlled for antibody binding. A variety of such tests, consisting of separation of tissue compounds, fixation, and ICC detection, are discussed as well as their pros and cons with respect to their predictability for the actual serum specificity in the tissue section.

Actins↗

PubMed1986

Recovery from peripheral nerve transection is accelerated by local application of alpha-MSH by means of microporous Accurel polypropylene tubes.

The peptide hormone alpha-melanocyte stimulating hormone (alpha-MSH), accelerates the return of sensitivity to the rat hindpaw after nerve transection. A marked reduction in the recovery time is observed when alpha-MSH is applied locally to the repair site by means of the microporous Accurel polypropylene tube delivery system. The tubes alone have a significant but smaller beneficial effect. These results have implications for the mode of action of neurotrophic melanocortins and suggest a potential means of improving the outcome of surgical nerve repair in the clinic.

Animals↗

PubMed1986

Immunocytochemically-stained vasopressin binding sites in rat brain. Ventricular application of vasopressin/Accurel in the Brattleboro rat.

An immunocytochemical procedure was developed to localize binding sites for vasopressin (VP) in the brain of Brattleboro (di/di) rats after 2 weeks of continuous ventricular administration of the peptide. Accurel-polypropylene tubing loaded with 0.15, 1.5 or 15 micrograms vasopressin was implanted into the lateral ventricle. Subsequently, bound VP was detected immunocytochemically in 2 distinct patterns: in perineuronal structures and dots between cells, in the lateral septum (dorsorostral part), striatum, cingulate cortex, granular cells of the dentate gyrus of the hippocampus, pyramidal cells of CA1 and CA3 hippocampal areas and around cerebellar Purkinje cells. The high dose (15 micrograms) loaded implants revealed the most intense staining; in the cytoplasm of neuronal cell bodies in the lateral and medial septum, striatum, cingulate cortex, bed nucleus of the stria terminalis, organum vasculosum of the laminae terminalis and locus coeruleus. The most intense staining in cell bodies was observed in brains which had low-loaded implants (0.15-1.5 microgram). A variety of controls, proved that no aspecific uptake was involved in the present procedure. The distribution of VP binding sites was only partly coincident with known sites of VP fiber innervation, and largely agrees with data obtained by autoradiographic techniques for [3H]VP binding. The present immunocytochemical technique gave a higher resolution than the currently used autoradiographic techniques. The differences in pattern and intensity of staining due to increasing the dosage rate of the in vivo vasopressin treatment, might mean that the current procedure retains preferentially either low or high affinity populations of binding sites depending on the implanted dose.

Animals↗

PubMed1986

Manipulation of vasopressin level in the cerebrospinal fluid of the rat by means of an easily interchangeable controlled-delivery Accurel mini-device.

The procedure described for the continuous release of vasopressin (VP) in the rat lateral ventricle via implantation of a VP-loaded Accurel/collodion mini-device has now been further developed, allowing the introduction, removal and exchange of the Accurel device through a polyethylene guide cannula. In this way, manipulation of the VP level in the cerebrospinal fluid can easily be accomplished. VP levels were measured by radioimmunoassay in liquor withdrawn from the cisterna magna.

Animals↗

PubMed1986

Vasopressin and oxytocin in the developing rat brain as shown by isoelectric focusing of radioimmunoassayable peptides.

Vasopressin and oxytocin content were measured by radioimmunoassay in tissue extracts from rat pituitary, hypothalamus and the extrahypothalamic brain from gestational day 14 until postnatal day 14. Assayable compounds were subsequently characterized by isoelectric focusing in gels. Fetal day 14 extracts contained only low amounts of both hormones (around 1-2 pg per fetus). Vasopressin content rapidly increased to levels of 41 ng in pituitary, 20 ng in hypothalamus, 0.3 ng in extrahypothalamic brain on postnatal day 14. Oxytocin content showed only measurable amounts around day 20 prenatally, reaching levels of, respectively, 10, 0.5 and 0.2 ng on postnatal day 14. The presence of radioimmunoassayable vasopressin in the extrahypothalamic brain on fetal day 14 (around 2 pg) confirms the early ontogeny of vasopressinergic innervation of the brain. Whenever measurable, immunoreactivity had an isoelectric point similar to that of synthetic vasopressin or oxytocin. The possibility that the detected amounts of vasopressin were due to vasotocin, which had been claimed to be present in fetal brain, was excluded by comparison of the regression coefficients of serial dilutions of the extracts in the radioimmunoassay with those of synthetic vasotocin or vasopressin.

Animals↗

PubMed1986

The use of [3H]vasopressin for in-vivo studies of controlled delivery from an Accurel/collodion device in the Brattleboro rat.

Accurel polypropylene/collodion controlled drug-delivery devices containing 22 micrograms [3H]vasopressin (VP) were implanted s.c. in VP-deficient Brattleboro rats. This caused a decrease in their urine production for at least 50 days, at which time the Accurel device was removed. Release of VP was followed by measurements of tritium radioactivity and by radioimmunoassay of VP in the urine. These parameters showed a constant pattern during the whole period. After re-implantation of the Accurel devices in another group of Brattleboro rats, release of VP continued to give the same level of urine production as during the last period of the first implantation. It is concluded that release of VP in-vivo is not influenced by encapsulation of the Accurel polymer by connective tissue, or that adaptation of the kidney adds to the maintenance of the urine production at this low level. In-vivo release rate is calculated to be about 1% of the original load each day. The in-vitro release in a flow cell system appeared to produce the same release rate which indicates that these data have a predictive value for the in-vivo situation.

Animals↗

PubMed1985

Body and brain growth following continuous perinatal administration of arginine- and lysine-vasopressin to the homozygous Brattleboro rat.

Using a recently developed controlled-drug-delivery implantation technique, arginine-vasopressin (AVP) or lysine-vasopressin (LVP) was administered to homozygous (HOM) Brattleboro rats throughout pregnancy in order to study the influence of compensation for the deficiency of AVP on body and brain development in their HOM offspring. This mutant is retarded in both body and brain growth from the neonatal period onwards. In one subgroup the LVP-treatment was continued postnatally by means of subcutaneous implantation in the pups. AVP treatment had no growth-stimulating effect either on pup body weight at day one or on postnatal body growth, nor did it affect noticeably the day of eye opening, or a number of brain parameters measured at one month of age. LVP treatment, in contrast, resulted in higher body weights at birth, which could be maintained postnatally if the pups were reared with a Wistar foster-mother. At one month of age body as well as brain weights were still larger in the treated pups. Although cerebellar weight was larger than in untreated Brattleboro pups in this group, cerebellar DNA content or gross morphology, known to be impaired in HOM rats, were not changed. LVP treatment of the pups, as well as maternal AVP-treatment beginning on day 15 of pregnancy, had inhibiting rather than growth-stimulating effects, high-lighting the different effects created by these two peptides at different stages of development.

Animals↗

PubMed1985

Vasopressin and brain development: studies using the Brattleboro rat.

Anomalies in hormonal and neurotransmitter status during early stages of brain development, can lead to lifespan alterations in the functioning of central systems. The neuropeptide vasopressin is nowadays recognized as a putative neurotransmitter, after years of study on its neurosecretory hormonal aspect in water metabolism. Since vasopressin is moreover present early in the brain, and has various mitogenic, metabolic and physiological actions, one might expect vasopressin to be of importance for normal brain development as well. Indeed, the absence of brain vasopressin in the Brattleboro mutant rat coincides with impaired brain development, and some physiological and behavioral defects of these rats are not adjusted by treatment with vasopressin. Regionally the cerebellum seems to be the most affected brain area, both morphologically and biochemically. Only when vasopressin supplementation was done prenatally, this disturbed growth could be restored, which suggests an early role for vasopressin in neurogenesis. Enhanced levels of vasopressin during the perinatal period on the other hand, have been shown to affect permanently the 'setting' of peripheral vasopressin functions in cardiovascular and renal regulatory systems. It is not excluded as yet that after such treatments central organization of vasopressin systems is not impaired as well.

Aging↗

PubMed1985

Neuropeptide effects on brain development to be expected from behavioral teratology.

A wealth of literature has become available about lasting functional consequences of perinatal psychotropic drug exposure, having affected brain development in a subtle rather than gross structural way (behavioral teratology or functional neuroteratology). The underlying mechanism is thought to result from changing levels of neurotransmitters during neurogenesis induced by these neuroactive drugs, which as a consequence appears to lead to impaired cell acquisition and receptor setting i.e., to irreversible changes in particular neuronal circuitries. Neuropeptides are true candidates for a neurotransmission function as well, and are also present early in brain development. As for the classical neurotransmitters, a role for neuropeptides in the growth and functional organization of the nervous system, might therefore be expected. Anomalies in neuropeptide levels also would lead to functional neuroteratology. Although not overwhelming, several studies support this view, and the current state is summarized in this paper: a trophic role for some neuropeptides as well as neuroteratological effects upon perinatal manipulation for others were revealed. However, more detailed studies are necessary, certainly also because of the crying need for exposing possible adverse effects at a time when clinical applications of neuropeptides and their analogues are becoming a mode.

Animals↗