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J Schipper

Publications and source records attributed to J Schipper.

At least 109 records · Page 6Linked to original sources
PubMed1991

Inverse relation between iodine intake and thyroid blood flow: color Doppler flow imaging in euthyroid humans.

High intake of iodine inhibits iodide trapping, iodide organification, and hormone release from the human thyroid. We investigated whether iodine intake also affects thyroid blood flow, as was suggested by a recent study in euthyroid rats. With a Color Doppler device we made 14 consecutive Duplex-Doppler registrations of both superior thyroid arteries in 10 euthyroid volunteers during baseline iodine intake (1 week), iodine restriction (2 weeks), return to baseline (1 week), and iodine excess (1 week; 80 mumol sodium iodide/day). Vessel diameters and mean flow velocity were measured on videotape recordings by a "blinded" observer. Baseline iodide excretion was 0.88 +/- 0.38 (+/- SD) mumol/day. Mean flow velocity was 13.9 +/- 4.1 cm/s, and vessel diameter was 1.07 +/- 0.22 mm. Blood flow was 7.7 +/- 3.8 mL/min.superior thyroid artery. During the low iodine diet, excretion dropped to 0.49 +/- 0.16 mumol/day, and blood flow increased to 11.0 +/- 5.0 mL/min (P less than 0.001), remaining elevated (10.3 +/- 4.4 mL/min) during the second baseline diet. During high iodide intake, blood flow averaged 5.8 +/- 3.4 mL/min (P less than 0.001), and the expected decrease in thyroid hormone levels and increase in TSH were seen. We conclude that thyroid blood flow responds inversely, and independently from TSH, to changes in iodine intake in euthyroid humans.

Adult↗
PubMed1990

The anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor subtypes in rat brain: sensitivity to guanine nucleotides.

Eltoprazine (DU 28853) inhibits offensive aggressive behaviour in several animal species. We characterized the binding of radiolabelled eltoprazine in rat brain by autoradiography. [3H]Eltoprazine displayed saturable and high-affinity binding to several brain areas, including the basal ganglia, hippocampal formation and cerebral cortex (Kd values ranging from 4.2 to 9.5 nM). The maximal binding capacities (Bmax) for [3H]eltoprazine were similar to those for [3H]5-HT and were highest in the substantia nigra and subiculum. Competition with eltoprazine for [3H]ligand binding to the various 5-HT1 receptor subtypes revealed preferential binding to 5-HT1A (IC50 values ranging from 42 to 50 nM) and 5-HT1B (IC50 values ranging from 25 to 38 nM) recognition sites. The drug had moderate affinity for 5-HT1C sites (IC50 = 282 nM). Addition of GTP or its stable analogue Gpp(NH)p to the radioligand assay caused a marked reduction (50-90%) in both [3H]eltoprazine and [3H]5-HT binding. These effects were substantially less in the choroid plexus. The binding of the antagonist (-)[125I]Iodocyanopindolol ([125I]ICYP) to 5-HT1B recognition sites, as quantified in the subiculum and substantia nigra, was either unaltered or slightly enhanced by the addition of 10(-3) M GTP. Furthermore, GTP did not affect the competition for [125I]ICYP binding by the 5-HT1-antagonist methiothepin, whereas it did significantly reduce the displacement by eltoprazine, resulting in an almost twofold increase in IC50 values. The data indicate that the anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor sites and that this interaction is modulated by guanine nucleotides.

Aggression↗
PubMed1990

Eltoprazine, a drug which reduces aggressive behaviour, binds selectively to 5-HT1 receptor sites in the rat brain: an autoradiographic study.

Eltoprazine, a phenylpiperazine derivative, selectively reduces offensive aggression in animal models. The present study was designed to localize and characterize the binding sites of [3H]eltoprazine in the rat brain and to compare the distribution of these sites with the distribution of [3H]5-HT binding sites. The binding of [3H]eltoprazine to whole tissue sections was saturable and revealed an apparent dissociation constant (Kd) of 11 nM. Autoradiographic studies demonstrated a widespread distribution of [3H]eltoprazine binding sites throughout the brain. Specific [3H]eltoprazine binding was completely displaced by 5-HT; conversely, unlabelled eltoprazine reduced [3H]5-HT binding to the levels of non-specific binding. The overall distribution of [3H]eltoprazine binding sites showed a strong resemblance to the location of 5-HT1 binding sites labelled with [3H]5-HT. Yet, regions enriched in 5-HT1A and 5-HT1C sites (e.g. dentate gyrus and choroid plexus, respectively) revealed relatively more [3H]5-HT binding as compared to [3H]eltoprazine binding, whereas [3H]eltoprazine binding was more pronounced in 5-HT1B receptor dense areas such as the dorsal subiculum, substantia nigra, ventral pallidum and globus pallidus. Displacement of [3H]eltoprazine with various selective serotonergic drugs demonstrated binding of [3H]eltoprazine to 5-HT1 receptor subtypes. The pharmacological and anatomical data indicate that eltoprazine binds to 5-HT1A, 5-HT1B and to a lesser extent to 5-HT1C binding sites in the rat brain. These results emphasize the important role of serotonin in the regulation of offensive aggression and suggest that eltoprazine may serve as a new tool to study the involvement of central 5-HT1 receptors in the expression of this behaviour.

Aggression↗
PubMed1990

Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants.

In 15 preterm infants with symptomatic patent ductus arteriosus, blood flow velocity changes in the superior mesenteric artery were investigated with Doppler ultrasound just before and during the first 12 hours after a single dose of indomethacin. Indomethacin administration led to an instantaneous decrease in all infants of temporal mean flow velocity in the superior mesenteric artery, which was maximal 10 minutes after administration of indomethacin, followed by a more sustained recovery, slightly greater than baseline values, 12 hours after indomethacin treatment. Simultaneously determined temporal mean flow velocity of the anterior cerebral artery, used as an indicator of changes in cerebral blood flow, had a similar pattern as in the mean flow velocity in the superior mesenteric artery (r = 0.49; p less than 0.001). Our data suggest that indomethacin lowered blood supply to the bowel, similar to its action on cerebral blood flow.

Blood Flow Velocity↗
PubMed1990

Superior mesenteric artery blood flow velocity and estimated volume flow: duplex Doppler US study of preterm and term neonates.

To obtain information about intestinal hemodynamics of healthy neonates, the authors assessed velocity and volume of blood flow with duplex Doppler sonography in the superior mesenteric artery (SMA) in 91 stable preterm and term neonates. Blood flow velocity in the SMA and estimated volume blood flow increased linearly with gestational age and increasing body weight. The mean estimated volume blood flow (+/- standard deviation) was 43 mL/kg/min +/- 13 and did not depend on differences in body weight. The authors also assessed blood flow velocity in the SMA and volume blood flow in 18 infants with conditions that may affect blood supply to the bowel. Twelve infants who were small for gestational age appeared to have an abnormally low resistance of the vascular bed of the SMA during the 1st days of life, as compared with stable appropriate-for-gestational-age infants matched for gestational age. Three of six term neonates with cardiovascular abnormalities had left ventricular outflow obstruction and an abnormal blood flow velocity waveform of the SMA, suggesting a decrease in blood supply to the bowel. The results of this study may help in evaluations of intestinal perfusion in infants with abnormal conditions.

Blood Flow Velocity↗
PubMed1990

Neurochemical profile of eltoprazine.

In this paper we present the neurochemical profile of eltoprazine, a drug that specifically inhibits offensive aggression. Eltoprazine interacts selectively with serotonin (5-HT) receptor subtypes (Ki-values for 5-HT1A, 5-HT1B and 5-HT1C receptors are 40, 52 and 81 nM respectively). Affinity for other neurotransmitter receptors is much lower (Ki-values greater than 400 nM) than for 5-HT1 receptors. The selective interaction with 5-HT1 receptor subtypes is confirmed by in vitro autoradiographic studies using radiolabelled eltoprazine. The overall distribution of [3H]eltoprazine bears a strong resemblance to the localization of 5-HT1 binding sites labelled by [3H]5-HT, although some differences are observed. Eltoprazine (1 microM) inhibits the forskolin stimulated c-AMP production in hippocampus slices of the rat, indicating an agonistic action on the 5-HT1A receptor. The K+ stimulated release of 5-HT from rat cortex slices is inhibited by eltoprazine (pD2 = 7.8). The maximal response, however, was clearly less than that of the full agonist 5-HT, indicating partial agonistic activity on the 5-HT1B receptor (alpha = 0.5). Eltoprazine has a weak antagonistic action (IC50 = 7 microM) on the 5-HT1C receptor as revealed by inhibition of the 5-HT-induced accumulation of inositol phosphates in the choroid plexus of the pig. In vivo, eltoprazine reduces 5-HIAA levels in the striatum, without affecting the 5-HT levels. Eltoprazine also reduces the 5-HT synthesis rate as shown by 5-HTP accumulation after decarboxylase inhibition. These data indicate that eltoprazine acts as a 5-HT agonist in vivo in a dose range that affects aggressive behaviour (0.3-3 mg/kg p.o.). Taken together from a variety of neurochemical studies there is strong evidence both in vitro and in vivo that the pharmacological actions of eltoprazine can be attributed to an interaction with the 5-HT system, most probably via a (partial) agonistic action on 5-HT1A and 5-HT1B receptors.

Animals↗
PubMed1990

Abdominal ultrasonography: improved image quality with the combined use of a diet and laxatives.

Intestinal contents (gas and food particles) are well known to cause problems in abdominal ultrasonography by inducing confusing and inconclusive images. We prospectively studied the effect on the combination of a 2-day low-calorie, low gas-forming diet with laxatives on abdominal sonographic image quality. For a total group of 100 consecutive outpatients, 50 patients (diet-laxative or DL group) were randomly assigned to follow the preparation of a diet and laxatives, and 50 patients (control or C group) served as a control group without any special preparation. The sonographic imaging quality of abdominal organs and retroperitoneal structures was assessed without knowledge of which group the patients were assigned to. The DL group patients showed a significant improvement in visibility of the extra-hepatic common bile duct (p = 0.009), head and body of the pancreas (p = 0.015 and 0.004, respectively), para-aortic region (p = 0.001), and the iliac vessels (p = 0.0005). The combined use of a low-calorie, low gas-forming diet and laxatives improves the abdominal sonographic image quality of the above-mentioned structures to such an extent that the sonographer will be able to make more pertinent statements about the presence or absence of pathology.

Abdomen↗
PubMed1990

Eltoprazine suppresses hyperpolarizing responses to serotonin in rat hippocampus.

In this study we report the effects of eltoprazine, a phenylpiperazine derivative with high affinity for 5-hydroxytryptamine1 (5HT1) binding sites, on membrane properties of hippocampal neurons. Intracellular recordings were made from cornus ammoni-1 pyramidal neurons in rat hippocampal slices. Responses to eltoprazine were compared with 5HT-induced responses. Superfusion with 5HT induced a dose-dependent hyperpolarization of the membrane accompanied by a resistance decrease. Eltoprazine evoked membrane changes that were similar to but much weaker than those induced by 5HT. Both the 5HT- and eltoprazine-evoked membrane hyperpolarizations were largely suppressed in the presence of spiperone. The eltoprazine-induced effects persisted in the presence of tetrodotoxin and tetraethylammonium and also when haloperidol and phentolamine were added to the medium, indicating that the small agonistic effects of eltoprazine are not due to an indirect activation of dopamine or alpha adrenergic receptors. Superfusion with eltoprazine furthermore resulted in a marked reduction of the response to concomitantly applied 5HT. Dose-response curves for 5HT were shifted to the right in the presence of eltoprazine, while the maximal response was diminished. Hyperpolarizations induced by baclofen, which presumably activates the same K+ conductance as 5HT, were not significantly reduced by eltoprazine. Our data, added to the previously demonstrated high affinity of eltoprazine for 5HT1 sites, suggest that in the hippocampal cornus ammoni-1 area eltoprazine acts as a partial 5HT1 agonist with a relatively low intrinsic activity but a considerable potency to suppress hyperpolarizing responses to 5HT.

Aggression↗
PubMed1989

31P NMR study of the impact of dietary manipulation on tumor metabolism and response to methotrexate.

The effects of nutritional manipulation and subsequent chemotherapeutic treatment upon growth and metabolism of a transplanted rat rhabdomyosarcoma were investigated by in vivo 31P NMR spectroscopy. Nutritional manipulation was accomplished by administration of a protein deprived diet containing no protein and 75.5% glucose. After 5 days the protein deprived rats (PD rats) were nutritionally replenished with a normal protein diet containing 27% protein and 47.3% glucose. Twenty-four hours after nutritional replenishment the PD rats and continuously well-fed controls (NP rats) received methotrexate (MTX, 30 mg/kg, i.p.). 31P NMR spectroscopy of the tumors 24 h after MTX administration showed a decreased ratio of nucleoside triphosphates to inorganic phosphate (referred to as 'ATP/Pi ratio') in PD rats in contrast to an unchanged ATP/Pi ratio in the NP controls. At the time of MTX administration the PD rats had a significantly lower tumor pH than the NP group (6.75 +/- 0.03 [SEM] vs 6.95 +/- 0.04; p less than 0.02). Tumor response in the PD group was significantly (p less than 0.01) enhanced compared to the NP group. These findings indicate that a period of dietary protein deprivation combined with a high glucose load and followed by nutritional replenishment impairs tumor metabolism. The altered metabolic status is expressed by acidification of the tumor and distinct changes in ATP/Pi ratio and appears to relate to an enhanced susceptibility to MTX chemotherapy.

Animals↗
PubMed1989

cGMP immunocytochemistry in aorta, kidney, retina and brain tissues of the rat after perfusion with nitroprusside.

The distribution of cyclic guanosine 3',5' monophosphate (cGMP) producing cells in various organs of the rat were studied immunocytochemically using antibodies raised against formaldehyde-fixed cGMP. Sodium nitroprusside (SNP), a direct activator of guanylate cyclase and vasodilator, was used to enhance cGMP levels. In order to reach all organs optimally, whole body perfusion was performed using a modified Krebs-Ringer buffer at 37 degrees C, aerated with 5% CO2/95% O2, also containing isobutyl methyl xanthine (IBMX); a phosphodiesterase inhibitor. After 15-min pre-perfusion, SNP was added to the perfusate, followed by fast fixation with ice-cold 4% paraformaldehyde-phosphate buffer. After vehicle perfusion, only the retina showed cGMP immunoreactivity in the photoreceptor and ganglion layer, while other organs lacked cGMP immunoreactivity. After 15-min perfusion with SNP (10 microM), enhanced cGMP immunostaining was seen in smooth muscles of the aorta, amacrine-like cells in the retina, glomeruli of the kidney cortex, blood vessels in the dura mater, as well as cells in the pineal and in the median eminence. The results indicate that the distribution and the reactivity of cGMP producing cells, situated outside the blood brain barrier, can be studied by immunocytochemistry after pharmacological manipulations of the intact tissue with a nitrovasodilator using whole body perfusion.

Animals↗
PubMed1989

Formaldehyde fixation of cGMP in distinct cellular pools and their recognition by different cGMP-antisera. An immunocytochemical study into the problem of serum specificity.

Three different antisera raised against the same formaldehyde fixed cGMP conjugate were tested for their specificity in two non-biological and two biological model systems. The first non-biological model system was based on nucleotides fixed to gelatin by formaldehyde and the other non-biological model was nitrocellulose paper as a carrier for nucleotides coupled to proteins by formaldehyde. All antisera proved specific for cGMP in both models. As biological models we used the in vitro incubated hippocampus slice and the in vitro incubated aortic ring. In hippocampus slices all three antisera showed cGMP-producing cells after atrial natriuretic factor stimulation. However, there were significant differences in the visualization of cGMP-immunoreactivity between the three antisera when sodium nitroprusside or potassium were used to stimulate cGMP production. Nevertheless, these differential staining patterns all showed cGMP-immunoreactivity using the conventional immunocytochemical control tests. In the aorta ring all three antisera showed the same strong increase in cGMP-immunoreactivity after in vitro stimulation with sodium nitroprusside. These results were corroborated by biochemical assay of cGMP. We conclude that these three antisera all demonstrate cGMP-immunoreactivity in the biological models used. The different staining patterns that occur are caused by differences in the microchemical milieu of the formaldehyde-fixed cGMP. The use of different antibodies to cGMP may give information about this microchemical milieu which may eventually contribute to a better understanding of different intracellular cGMP pools.

Animals↗
PubMed1989

Relationship between electrocortical activity and beta-adrenergic receptor function in the rat after chronic desimipramine treatment.

The aim of this study was to investigate the effects of chronic administration of desimipramine (DMI) after 2, 7 or 20 mg/kg per day, administered by osmotic minipumps, on electrocortical activity and beta-adrenergic receptors in rat brain. Rats receiving DMI chronically show a dose- and time-dependent increase of electrocortical activity above 15 Hz as well as a dose- and time-dependent decrease below 15 Hz. Already after 3 days of treatment a clear effect on the electrocorticogram (ECoG) was seen. The maximal change in the ECoG was reached at the end of the study, after 24 days of treatment. After acute treatment (20 and 45 minutes after 2, 4 or 10 mg/kg i.p.) with DMI, a decrease of electrocortical activity is seen above 15 Hz. Thus the effect of acute DMI treatment on the ECoG is different from that of chronic treatment. In the same group of rats the effect of chronic DMI treatment on the beta-adrenergic receptor number was determined 24 hours after the last ECoG recording. The number of beta-adrenergic receptors was dose dependently reduced in the DMI-treated rats as determined by [3H]-dihydroalprenolol binding. There was no change in affinity (KD) of the ligand for the beta-receptor. This finding was corroborated by a decrease in the functional activity of the beta-adrenergic receptors, as determined by isoprenaline stimulated efflux of cyclic-AMP in cortex slices. These data indicate that chronic treatment with DMI, resulting in a down-regulation of the cortical beta-adrenergic system, is paralleled by pronounced effects on the ECoG of rats. The different ECoG profiles after chronic DMI treatment compared with acute treatment suggest that adaptive changes in the electrical brain activity continually develop during the chronic treatment with this antidepressant drug.

Animals↗
PubMed1989

Effects of microwave-induced hyperthermia on the anterior segment of healthy rabbit eyes.

Hyperthermia was induced in nine healthy rabbit eyes by means of a microwave 2450 MHz stripline applicator. The anterior segment of each eye was heated to a fixed temperature of between 42 degrees C and 46 degrees C for 30 min. The temperature distribution in the eye was calculated using a thermal model and the actual boundary temperatures and microwave intensity were measured. The effects of treatment were evaluated by daily macroscopic examination, fluorescein angiography and fluorophotometry, as well as by histology. Histological examination of changes induced by this hyperthermic delivery system revealed a sharp transition at 44 degrees-45 degrees C from no permanent damage to the anterior chamber at lower temperatures to serious damage such as local necrosis, pigment disruption and local cataract at high temperatures. A sharp transition in the same temperature range was observed in vivo in the fluorescein leakage of the iris vessels by comparative fluorescein angiography and by anterior segment fluorophotometry.

Animals↗
PubMed1989

The effect of pH-adjusted 2-chloroprocaine on the onset of epidural analgesia in pregnant patients in the lying and sitting position during the first stage of labor.

The purpose of this prospective, randomized, double-blind study was to compare the epidural onset time of 2% 2-chloroprocaine with pH-adjusted 2-chloroprocaine administered in either the sitting or supine position in pregnant patients during the first stage of labor. Patients in Groups I and III received the control solution in the sitting and supine position, respectively. Patients in Groups II and IV received the buffered solution in the sitting and supine position, respectively. The pH and pCO2 of the control and buffered solutions differed significantly. The pH and pCO2 of the control and buffered solutions were 4.38 +/- 0.01, 18.4 +/- 2.2 mm Hg and 7.70 +/- 0.04, 114.9 +/- 3.0 mmHg, respectively. A statistically significant reduction in the time of onset of analgesia in the pH-adjusted groups was noted. Groups I and II had onset times of 4 +/- 1.2 and 4.3 +/- 1.0, whereas Groups II and IV had onset times of 2.6 +/- 0.9 and 2.7 +/- 0.6 min., respectively. There were no intergroup differences in the cephalad spread of analgesia or duration of analgesia. Position had no effect on the onset of analgesia at the S2-3 dermatomes nor on the bilateral cephalad spread of the epidural study solutions. Our results indicate that a pregnant patient may be dosed in the lateral supine position without adversely affecting the caudad or cephalad spread of plain or pH-adjusted 2% 2-chloroprocaine, which is clinically important because the incidence of aortocaval compression is increased in the supine position when compared with the lateral supine position.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The effect of pH and PCO2 on epidural analgesia with 2% 2-chloroprocaine.

Increasing the pH of local anesthetics with sodium bicarbonate has been reported to hasten their onset of action. The purpose of this study was to compare the onset and duration of epidural analgesia with the use of sodium bicarbonate and tromethamine to increase the pH of 2% chloroprocaine (2CP). Five groups of patients were studied: Group I received 2CP; Group II received 2CP buffered to a pH of 7.1 with tromethamine; Group III received 2CP buffered to a pH of 7.1 with sodium bicarbonate; Group IV received 2CP buffered to a pH of 7.7 with tromethamine; and Group V received 2CP buffered to a pH of 7.7 with sodium bicarbonate. The final pH and PCO2 of each solution were measured. Time to onset of analgesia was significantly delayed with either of the tromethamine buffered groups (II [5.6 +/- 1.0 minutes] and IV [5.4 +/- 0.4 minutes]) when compared with data from the unbuffered control (I [4.4 +/- 0.1 minutes]) and the sodium bicarbonate buffered (III [4.5 +/- 0.8 minutes] groups and Group V [2.7 +/- 0.9 minutes]). Only when sodium bicarbonate buffer adjusted to pH 7.7 (Group IV) was onset significantly more rapid than the unbuffered 2CP (I) and tromethamine buffered 2CP (II and IV). Multiple regression analysis revealed that onset times were significantly related to both pH and PCO2. The coefficient of determination for this model was 0.5156.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Atrial natriuretic factor-responding and cyclic guanosine monophosphate (cGMP)-producing cells in the rat hippocampus: a combined micropharmacological and immunocytochemical approach.

Atrial natriuretic factor (ANF)-responding, cyclic guanosine monophosphate (cGMP)-producing cells were visualized in the hippocampus of the rat applying cGMP immunocytochemistry to hippocampal tissue slices incubated in vitro. These cells were found scattered throughout the hippocampus with their highest density in the hilus fascia dentata. Staining with an antibody against glial fibrillary acidic protein showed a completely different pattern, suggesting a non-glial nature of the ANF-responding cells. cGMP accumulation assayed biochemically was observed already at 10 microM ANF and was sensitive to inhibition by Methylene blue. The immunocytochemical data were fully supported by the biochemical measurements of cGMP under these conditions. Our results show for the first time a response to ANF of individual, cGMP-producing cells in the CNS of the rat.

Animals↗