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Biomedical subjects

R Landgraf

Publications and source records attributed to R Landgraf.

At least 289 records · Page 16Linked to original sources

Plasma vasopressin levels in healthy young men in response to stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate.

The plasma arginine vasopressin (AVP) concentration, the plasma osmolality as well as the systemic arterial blood pressure, the heart rate, and the minute ventilation were determined in four healthy, normotensive, normoxic young men undergoing moderate osmotic diuresis. Each subject was measured in two experiments, both lasting from 7:30 a.m. to 6:00 p.m.. In one of them they obtained 50 mg almitrine bismesylate (Vectarion) at 12:00 o'clock, whereas the other test served as control experiment. There were only negligible changes of the parameters measured in the control experiments and also only weak responses of the cardiorespiratory values in the almitrine treated group. Compared with the data obtained 30 min before administration of the drug, measurements carried out 90 min after the ingestion showed a decrease of plasma AVP in all four subjects through plasma osmolality was increased in three of the four cases. A comparison of the mean values of all data obtained in the morning, i.e. before the oral administration of the drug, with those determined in the afternoon revealed that three out of four subjects had responded to almitrine with a fall of plasma AVP regardless of an increase of plasma osmolality in all these three cases. One person did not react to almitrine ingestion, neither with plasma AVP nor with plasma osmolality. In the control experiments the corresponding reaction pattern was uncharacteristic. The data do not support the assumption that arterial chemoreceptor stimulation increases plasma AVP. They rather indicate that excitation of these pO2-sensors in normoxic humans suppresses plasma AVP by mechanisms so far unknown.

Adult↗

Vasopressin binds to microvessels from rat hippocampus.

Recent evidence suggests that vasopressin may influence the permeability of the endothelium of brain capillaries. We measured the binding of [125I]arginine-8-vasopressin ([125I]AVP) to microvessels isolated from different regions of the rat brain. The study revealed saturable and specific binding of [125I]AVP to microvessels isolated from hippocampus. Scatchard analysis confirmed a single class of high affinity sites with an equilibrium dissociation constant, Kd, of 3.2 nM and an apparent maximal binding capacity of 205 fmol/mg protein. No binding was observed to microvessels from neocortex and striatum.

Animals↗

Vasopressin and oxytocin in brain areas of rats with high or low behavioral performance.

Animals were selected from a population of 55 rats which differed significantly in their ability to perform a behavioral task, a foot-shock motivated brightness discrimination (BD). Using highly specific and sensitive radioimmunoassays, the contents of arginine vasopressin (AVP) and oxytocin (OXT) were measured in 5 brain areas and the plasma of these animals. AVP levels in the septum/striatum and posterior pituitary of rats with high performance significantly exceeded those of the low performance group. Compared to the low performance rats, the OXT content of the high performance rats was higher in the septum/striatum, but was lower in the hippocampus. No significant differences between the groups were found in the hypothalamus, motor cortex and the plasma. The results suggest that both AVP and OXT are signals in central pathways involved in information processing. In particular, high endogenous AVP and OXT levels in neurons of the septum/striatum and low OXT levels within hippocampal neurons might be prerequisites for high performance in the conditioned BD reaction.

Animals↗

Treatment of Graves' ophthalmopathy with cyclosporin A.

To evaluate the effect of Cyclosporin A in the management of Graves' ophthalmopathy, we treated 13 patients with severe euthyroid endocrine eye disease with the immunosuppressive drug. Follow up consisted of clinical investigation, laboratory evaluation with detailed thyroid function tests and complete ophthalmological assessments including A and B scan ultrasound and computerized tomography (CT) of the orbits. Cyclosporin A given over 4-7 months resulted in improvement of clinical signs and symptoms of the disease due to a positive effect of the drug on soft tissue changes. The more objective methods did not demonstrate any unequivocal change in proptosis, visual acuity, intraocular pressure and thickness of extraocular muscles. Cyclosporin A was not able to stop acute progression of ophthalmopathy in one patient and did not obviate surgical decompression of the orbits in two more patients. There was no measurable effect of treatment on the underlying immunological process with regard to thyroid disease.

Adult↗

Hormone-active intradural spinal metastasis of a prolactinoma--a case report.

A 44-year-old woman developed acute severe visual field defects and was operated on a macroprolactinoma. Since complete resection of the tumor was not possible, radiotherapy was performed and in addition to hormone replacement therapy, bromocriptine (up to 60 mg daily) was started without however complete normalization of PRL levels. Four years later PRL levels increased to 10(5) microU/ml despite continuation of dopamin agonist (mesulergin) treatment. As shown by ophthalmological examination and computer tomography there were no signs of regrowth of the pituitary tumor. At that time the patient complained of severe lumbar pain and myelography revealed a tumor mass in the spinal cord (L1-L2). Since the spinal tumor was not removable, laminectomy was performed. Histology and immunohistochemistry demonstrated a metastasis of the prolactinoma. Radiotherapy and bromocriptine in extreme doses (140 mg daily) together with an antiestrogen were not able to improve the neurological deficits (paraparesis) and to lower the PRL levels. This case of a metastasis of a prolactinoma after operation, radiotherapy, and dopamin agonist treatment stresses the importance of close surveillance of patients with prolactinomas without PRL normalization during dopamin agonist therapy and shows for the first time the possibility of ectopic PRL production due to an intradural spinal metastasis.

Adenoma↗

Blood-brain barrier and peptides.

The brain is both the source and the recipient of peptide signals. The question is: Do endogenous, blood-borne peptide molecules influence brain function? Brain regions with the tight capillaries of the blood-brain barrier (BBB) extract low but measurable amounts of labeled peptide molecules from an intracarotid bolus injection. In the rat, the extraction fractions of beta-casomorphin-5, DesGlyNH2-arginine-vasopressin, arginine-vasopressin, lysine-vasopressin, oxytocin, gonadoliberin, substance P, and beta-endorphin, studied in this laboratory, range from 0.5% (substance P) to 2.4% (arginine-vasopressin). Extraction varies little among the 15 examined brain regions. As shown for arginine-vasopressin, the extracted peptides may be bound in part to specific binding sites located on the luminal membrane of the tight endothelial cells. Transport of peptide molecules across the BBB cannot be ruled out, but it is unlikely that endogenous peptides pass the BBB in physiologically significant amounts. In contrast, in brain regions with leaky capillaries, e.g., selected circumventricular organs including the pineal gland, neurohypophysis, and choroid plexus, the peptide fraction extracted approaches that of water. Within the circumventricular organs, the peptide molecules actually reach the cellular elements of the tissue. However, no studies definitively show that peptides reach neurons in the deeper layers of the brain. On the other hand, blood-borne peptides influence the BBB permeability by altering the transport of essential substances. The effect may be mediated by specific peptide binding sites located at the luminal membrane of the endothelium. It is possible that the effect of peptides on the BBB is necessary for proper brain function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Plasma oxytocin concentrations in man after different routes of administration of synthetic oxytocin.

Plasma oxytocin was determined by RIA in three male subjects under basal conditions and following administration of synthetic oxytocin. As compared to basal levels (below 10 pg/ml), plasma oxytocin was found to be elevated markedly (36 to 85 pg/ml) in response to application by nasal spray (total dose: 65 to 100 micrograms). Intramuscular injection (25 micrograms) resulted in very high oxytocin levels (360 to 480 pg/ml), whereas buccal administration (70 micrograms) was proved to be ineffective (levels below 10 pg/ml plasma). In each case, plasma vasopressin remained unchanged.

Administration, Intranasal↗

On the blood-brain barrier to peptides: accumulation of labelled vasopressin, DesGlyNH2-vasopressin and oxytocin by brain regions.

After intracarotid injection of 125I-arginine vasopressin (AVP), 125I- or 3H-lysine vasopressin (LVP), 3H-DesGlyNH2-arginine vasopressin (DGAVP), and 125I- or 3H-oxytocin (OXT), the accumulation of radioactivity was determined in 13 to 18 brain regions and anterior pituitary in rats. Calculated extraction by tight capillary regions amounts to about 1-2% independently of the peptide doses injected (4 X 10(-4) to 5 X 10(-9) mol-1). This indicates a low but measurable extraction of labelled peptides which furthermore is nonsaturable. Among brain regions with tight capillaries, the extraction does not vary obviously. Blood-brain barrier (BBB)-free regions extract up to 30 fold more peptide than BBB-protected regions and the extraction varies considerably between individual regions. Within BBB-free regions, the peptides passed the leaky capillary endothelium, but there is no evidence for a penetration to deeper layers of the brain. It is concluded that endogenous blood-borne peptides cannot pass brain barriers in physiologically significant amounts. This does not exclude a possibility that passive transport of minute but effective amounts might occur if high pharmacological amounts of peptides are injected peripherally. But, as shown, none of the peptides studied possesses properties that favour its passage across the BBB.

Animals↗

[Cystine aminopeptidase and oxytocin in the plasma of pregnant patients with premature labor].

L-cystine aminopeptidase (CAP) activity in plasma was determined by spectrophotometry in 243 normal pregnant women in week 20-40 and 68 pregnant women with premature pains in week 28-37 of pregnancy. For significantly diminished CAP activity, pains and the subsequent premature birth correlated with infantile dystrophy, while in case of normal CAP activity the number of premature births was significantly less and newborns had eutrophic birth weights. In addition, radioimmunological measurements of oxytocin concentration in plasma were performed in ten pregnant women each of these groups. In women with premature pains, the oxytocin concentration was significantly higher than in normals. The present findings suggest that fetal oxytocin release might be the trigger signal for pains, thus causing premature birth. This signal might be chronically induced by a stress situation which manifests itself in hypotrophy of the newborns.

Aminopeptidases↗

Counterregulatory hormone release after human and porcine insulin in healthy subjects and patients with pituitary disorders.

Human and porcine insulin were administered intravenously to a group of healthy volunteers in two different doses (0.075 IU/kg body weight and 0.12 IU/kg body weight) and to two groups of randomly selected patients with pituitary disorders in a dose adapted to their individual glucose tolerance (0.12-0.17 IU/kg body weight for porcine and 0.15-0.18 IU/kg body weight for human insulin). The blood glucose and potassium lowering effect, the feedback regulation of endogenous insulin release, and the liberation of the counterregulatory hormones glucagon, cortisol, adrenocorticotropic hormone (ACTH), prolactin (hPRL), human growth hormone (hGH), and catecholamines were measured before and after injection of human or porcine insulin. The maximal effect, the area under the concentration-time curve, the percentage effect, and the increase above baseline for the two doses of insulin and the two types of insulin were compared. There were no significant differences in the calculated parameters between the two insulin types at the same doses except with prolactin. At 0.075 IU/kg human insulin induced significantly less prolactin release than porcine insulin. Comparing the two doses of the same insulin serum insulin levels, blood glucose, glucagon, norepinephrine, and prolactin were lower at the low dose of each insulin. In addition ACTH and epinephrine were also lower after human insulin at 0.075 IU/kg. The subjective signs of hypoglycemia were less pronounced after human insulin. It is concluded that the biological effects of human insulin are comparable to porcine insulin although prolactin release is significantly reduced after human insulin. If this difference is an indication of different receptor sensitivities for human and porcine insulin in the central nervous system and if the diminished signs of hypoglycemia are a consequence of this, then further studies are required.

Adult↗

Levels of vasopressin and oxytocin in neurohypophysis and plasma of the postnatally developing rat and the influence of hypothyroidism on rat fetuses.

Arginine vasopressin (AVP) and oxytocin (OXT) were measured simultaneously by radioimmunoassay in neurohypophyses of rats immediately before birth (fetal day 22) onward to day 50 of life. The neurohypophysial content of AVP exceeded that of OXT by factor 17 at fetal day 22, by 20 immediately post natum, and by 2 at day 21 of life, respectively. As compared to day 0, the content at day 21 is considerably higher (AVP 24 fold, OXT 270 fold). The poor correlation between neurohypophysial AVP and OXT content suggests the possibility of a different onto-genetic development of both neuropeptide systems. Both AVP and OXT were detected in pooled rat plasma at various postnatal stages. Hypo- and hyperthyroidism induced experimentally during gestation did not result in a significant change in neuropeptide content of fetal neural lobes.

Age Factors↗