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Biomedical subjects

T Barth

Publications and source records attributed to T Barth.

At least 73 records · Page 4Linked to original sources

Plasma concentrations of factor VIII after administration of DDAVP to conscious dogs.

The effect of the vasopressin analogue DDAVP on Factor VIII in plasma has been extensively studied in humans. To examine the effect of new and potentially better analogues a suitable animal model has to be established. In the present study trained Beagle dogs were injected with DDAVP and the time course of the Factor VIII response was monitored by a modification of the chromogenic substrate assay for Factor VIII. In most of the dogs DDAVP caused a biphasic increase of plasma concentrations of Factor VIII with an initial smaller increment within 10 min after the injection followed by a larger secondary rise after approximately 45 min. The average increase in Factor VIII was smaller than found in humans after comparable doses of DDAVP, and a few dogs responded very poorly. Despite these qualitative and quantitative differences it is concluded that trained dogs may serve as a useful model for testing the ability of other analogues than DDAVP to increase Factor VIII.

Animals↗

Improved behavioral performance of rats after pre- and postnatal administration of vasopressin.

In two separate and independent experimental series it was studied, whether 8-arginine-vasopressin (AVP) or 8-lysine-vasopressin (LVP) administered daily in microgram amounts to pregnant rats, and/or to their offspring postnatally for 30 days, induce alterations that can be registered by a behavioral test. The realization of the test used, a foot-shock motivated brightness discrimination (BD) reaction, includes learning and memory processes. There is one general result of the two experimental series, which include 263 rats divided up in different combinations of pretreatment. Vasopressin (VP), AVP or LVP, pre- and postnatally administered, induces a significantly improved BD performance of approximately 40%, compared to the control groups. The improvement is detectable in different ages of the offspring, in females as well as in males. A smaller though also significant improvement was observed when AVP or LVP was injected only postnatally. The critical period in which the peptides are able to induce the alterations measured probably includes prenatal and postnatal periods in the lives of the rats. What molecular interactions actually underly the improved behavioral performance remain to be clarified.

Animals↗

Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists.

The hormonally and behaviorally active nonapeptide oxytocin (OXT), its behaviorally active N-terminal octapeptide desglycinamide9-OXT and Z-prolyl-D-leucine, a synthetic analog of the C-terminal prolyl7-leucine8 sequence, inhibited the development both of a moderate and of a strong tolerance to morphine. N-alpha-Acetyl-(2-0-methyltyrosine)-OXT and (penicillamine1-2-0-methyltyrosine)- lysine8-vasopressin, both OXT receptor antagonists, facilitated the development of a moderate morphine tolerance. The i.c.v. injection of either antagonist prevented the effects of i.c.v. and s.c. OXT treatment on the development of tolerance. The effect of desglycinamide9-OXT, but not that of Z-prolyl-D-leucine was also prevented by N-alpha-acetyl-(2-0-methyltyrosine)-OXT. It is concluded that OXT and desglycinamide9-OXT, but not Z-prolyl-D-leucine, attenuate morphine tolerance by affecting putative oxytocinergic binding sites in the mouse brain. The fact that i.c.v. injection of the receptor antagonist also blocked the effect of s.c. OXT treatment argues in favor of the possibility that a minor proportion of s.c. OXT (or behaviorally active fragments thereof) may reach central nervous system target sites.

Analgesia↗

Effect of threonine in position 4 in oxytocin and vasotocin analogs on the time course of uterotonic response.

The substitution of glutamine by threonine in position 4 of oxytocin, deamino-oxytocin, deamino-1-carba-oxytocin, and deamino-6-carba-oxytocin was found to increase the elimination rate of all analogs examined from the uterine receptor compartment in rat. However, this substitution was without any effect on the time course of uterotonic response in the case of vasotocin and deamino-vasotocin. These results suggest that the topological relationships of the 4 and 8 positions may show an important effect on elimination rate of oxytocin and vasotocin analogs from the rat uterine compartment.

Animals↗

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↗

On the nature of the vasoreactivity depressing factor (VDF) in inflammation and anaphylaxis in the rat and mouse.

In anaphylactic paw edema the reactivity of blood vessels to norepinephrine in the isolated perfused hind legs of rats and mice is reduced. A vasoreactivity depressing factor was postulated and searched for. PAF-acether, histamine and lipoxygenase products were found as being possibly responsible for depression of the vascular reactivity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Nacartocin--analogue of oxytocin with enhanced natriuretic properties: natriuretic and hemodynamic characteristics.

Nacartocin, [2-p-ethylphenylalanine]deamino-6-carba-oxytocin, is almost three times more potent than oxytocin as a natriuretic agent. The natriuretic effect is mainly due to the inhibitory action of the peptide on tubular sodium resorption. Nacartocin decreased the blood pressure of anesthetized rats by the decrease of the total peripheral resistance which was greater than that observed after oxytocin administration. In conscious rats, Nacartocin caused a slight but prolonged increase of blood pressure.

Animals↗

Comparison of antidiuretic and natriuretic effects of [8-lysine]vasopressin and [8-D-arginine]deaminovasopressin in conscious rats.

The relation between the duration of antidiuresis and sodium excretion and the route of administration of [8-lysine-vasopressin or [8-D-arginine]-deaminovasopressin to conscious rats was investigated. Both compounds were administered either intravenously through a chronically inserted catheter in the right jugular vein, or subcutaneously. The rats were then placed into individual metabolic cages and urine was collected quantitatively. Subcutaneous administration of both compounds resulted in a more prolonged antidiuretic response, lower sodium excretion and higher total urine osmolality. In order to achieve a comparable half-time antidiuresis, it was necessary to apply about 1000 times higher does of [8-lysine]vasopressin than those of [8D-arginine]deaminovasopressin. The relation between the duration of both antidiuresis and sodium excretion and the way of administration was, however, more pronounced in the case of [8-lysine]vasopressin. The excretion of potassium was increased after both compounds, the highest value being found after subcutaneous administration of [8-lysine]vasopressin.

Animals↗

Effect of some oxytocin analogues on natriuresis in rats.

Non-anaesthetized rats were used for studying the relationship between the amount of sodium excreted and structural modifications of oxytocin molecule. Any change performed in position 4 (i.e. the glutamine residue) resulted in a decrease of natriuretic activity as compared to that of oxytocin. The analogues with modifications in the amino-terminal part of the molecule (e.g. substitution of the amino group in position 1 by hydrogen, or of the disulfide bond by a thioether group) resulted in a higher natriuretic effect than oxytocin.

Animals↗