Biomedical subjects

J Kruisbrink

Publications and source records attributed to J Kruisbrink.

12 recordsLinked to original sources

PubMed1989

Testosterone treatment restores reduced vasopressin-binding sites in the kidney of the ageing rat.

Young, middle-aged and aged rats received s.c. testosterone implants for 50-52 days in order to investigate whether supplementation of testosterone in aged rats could normalize the reported reduction of kidney arginine vasopressin (AVP)-binding sites and increase the plasma concentration of AVP. Receptor number, which was measured by means of a membrane-binding assay with [3H]AVP as ligand, was below the detection level in the untreated aged rat. Following testosterone treatment, no effects were seen in the youngest groups, but in the aged group AVP receptors became clearly detectable, albeit with a lower affinity. A remarkable observation was the increase in affinity for renal AVP binding in the middle-aged compared with the young rat. Plasma levels of AVP in control aged rats tended to be higher. Such a tendency was completely absent in the testosterone-treated aged rats. Possible mechanisms underlying the restoration of reduced AVP-binding sites in the kidney of the aged rat by testosterone treatment are discussed.

Aging↗

PubMed1988

Decrease of rapid-eye-movement sleep in the light by intraventricular application of a VIP-antagonist in the rat.

Vasoactive intestinal polypeptide (VIP) has been shown to increase the amount of time spent in rapid-eye-movement (REM) sleep both in cats and in rats. In the present study we examined the effect of a newly available competitive VIP-antagonist ([4Cl-D-Phe6-Leu17]-VIP) on sleep-wake patterns in male rats during both the light and the dark phase of 24 h. Continuous intracerebroventricular application of this VIP-antagonist reduced by 44% the amount of time spent in REM sleep during the light period. It is concluded that VIP may play a role in the generation and maintenance of REM sleep.

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

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

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↗

PubMed1984

Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use.

Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero.

Animals↗

PubMed1984

Successful ventricular application of the miniaturized controlled-delivery Accurel technique for sustained enhancement of cerebrospinal fluid peptide levels in the rat.

A recently developed small controlled-delivery peptide device has now been further miniaturized (3.5 mm3 rod) and its action has been tested in vitro and in vivo using vasopressin (VP) as experimental substance. In vitro immersion showed a constant and lasting release of VP for weeks, as had been described for larger devices. By introducing the mini-device into the lateral ventricle of rat brain and by sampling CSF via a permanent cannula in the cisterna magna, a steadily enhanced level of VP could be attained for CSF. These increased levels persisted for one week, but most likely continue for longer periods.

Animals↗

PubMed1984

Effects of continuous administration of oxytocin by an accurel device on parturition in the rat and on development and diuresis in the offspring.

A controlled-delivery module based on microporous Accurel polypropylene tubing, implanted subcutaneously in the rat, was used to release oxytocin for at least 40 days both in vitro and in vivo. Using a dosage rate of approximately 650 ng oxytocin per day and implanting the device in rats on day 17 of pregnancy, the known physiological action of oxytocin in advancing labour was confirmed. The increased concentrations of oxytocin in the mothers gave rise to adverse effects; the course of labour was protracted during expulsions of the first pups and the birth weight was reduced. Postnatally, body development of the pups was also affected, although there was partial recovery when the pups started to feed independently. Both pre- and postnatal exposure of pups to an oxytocin-treated mother reduced their body water turnover measured at 1 month of age. The effects on the course of parturition and during lactation might be explained by a blockade of uterine and mammary gland oxytocin receptors respectively, thereby inhibiting a proper response to pulsatile endogenous oxytocin secretion. The changes in water metabolism, which are opposite to those described for the heterologous hormone vasopressin, are less easy to explain since maternal oxytocin is not supposed to pass the placenta. The results may indicate that clinical use of oxytocin for induction of labour and lactation may have hitherto unrecognized side-effects.

Animals↗

PubMed1983

Long-term and constant release of vasopressin from Accurel tubing: implantation in the Brattleboro rat.

A long-lasting and constant release of vasopressin in serum solution (in vitro) for periods up to 50 days can be obtained by the use of small-diameter microporous Accurel polypropylene tubing, filled with vasopressin and covered with collodion. The potency of the preparation is shown in vivo after subcutaneous implantation in the adult vasopressin-deficient Brattleboro rat, for which normal levels of urine production and osmolality were achieved at least for 1 month. The possible use of this method for other peptides and its application in small or immature laboratory animals and in fetuses is emphasized.

Animals↗

PubMedDate not supplied

Vasopressin fails to restore postnatally the stunted brain development in the Brattleboro rat, but affects water metabolism permanently.

An attempt was made to prevent the growth impairment of body and brain of the Brattleboro rat congenitally deficient in vasopressin (VP), by postnatal treatment with VP between the ages of 5 and 28 days. Neither repeated daily subcutaneous injections of either Pitressin tannate or VP in oil, continuous peripheral application of VP in various dosage rates using the long-acting Accurel/collodion implantable delivery module, nor daily intracerebroventricular injections of VP in saline, improved postnatal body or brain growth. Brain parts known to be particularly impaired in the Brattleboro neonate, viz. cerebellum and medulla oblongata, also remained unaffected by the VP treatment with regard to both size and cell content as measured on day 33 of age. A possible trophic action of VP would therefore have to take place before neonatal day 5. At dosage rates of VP higher than 1 microgram/d and given peripherally on day 5 or shortly thereafter, a permanent enhancement of diuresis of approximately 30% was noticed in these Brattleboro rats, which were already suffering from a severe diabetes insipidus. Since VP is not circulating at that stage, other systems than the hypothalamo-neurohypophyseal/kidney axis might be affected. Normal antidiuresis obtained following a sub-maximal dosage of Pitressin tannate, indeed showed that the VP receptors of the kidney were still intact. This observation should serve as a warning against application of VP or its analogues during development in clinical practice.

Animals↗