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Biomedical subjects

T Barth

Publications and source records attributed to T Barth.

At least 55 records · Page 3Linked to original sources

Tissue plasminogen activator enhancing activity of vasopressin analogues in monkeys: structure-activity study.

Marmocets were used in a structure activity study of the ability of vasopressin analogues to activate plasminogen activator (tPA). In evaluation of dDAVP analogues with L-alanine migrating from position 2 to 9 we found [L-Ala4]dDAVP and [L-Ala5]dDAVP to be potent activators of tPA. Double substitutions in dDAVP showed that combinations of a modification in position 4 valine with a change at position 2 (2-O-methyltyrosine) generated tPA releasing activity. On the other hand enlargement of the substituent at position 2 (2-O-ethyltyrosine) completely eliminated the activity of [L-Val4]dDAVP. The tPA activity is dependent on the position of a positively charged group at the amino acid in position 8 of the peptide chain. A shift of the guanido group further away from the backbone (D-arginine to D-homoarginine) resulted in a loss of tPA activating properties.

Animals↗

[Eye-pressure tonometry in prevention of glaucoma].

Oculo-pression tonometry (OPT) was introduced in 1984 as a clinical method of examining ocular hydrodynamics. The method involves measuring intraocular pressure (IOP) by applanation tonometry performed before, during and after application of a pressure load that disturbs the dynamic balance between aqueous production and aqueous outflow. From the IOP before (P0) and immediately after (Pr0) the 8-min pressure load period, the outflow facility C(u) can be calculated: [formula: see text] The examinations performed so far have shown that (1) reduced outflow facility can be detected by OPT with a high degree of reliability, and (2) reduced outflow facility is always preceded by the development of glaucoma damage to the optic nerve head. A prospective study has shown that in the group of patients with reduced outflow facility but without glaucoma damage, 73% developed glaucoma damage with typical changes of the papilla and visual field within 3-7 years after the first examination.

Equipment Design↗

[Disordered peripapillary microcirculation in glaucoma patients].

To study the haemodynamics of the peripapillary choroid, perfusion pressure videoangiography (PVA) was performed in six healthy subjects and in seven patients with primary open-angle glaucoma (poag). In healthy subjects the peripapillary part of the choroid starts filling at distinctly lower ocular perfusion pressures than other parts of the choroid. The mean difference in perfusion pressure between peripapillary and perimacular filling was 13.6 mmHg in the six healthy subjects. A different filling pattern of the choroid was found in the seven glaucoma patients. The mean difference in perfusion pressure between the beginning of peripapillary and the beginning of perimacular perfusion of the choroid was found to be as small as 1.9 mmHg. That the filling of the peripapillary choroid observed by PVA in healthy subjects is found to start at lower perfusion pressures than in the other parts is explained by autoregulative dilatation of the peripapillary choroidal arterioles resulting from artificially raised intraocular pressure during the PVA examination. In the poag patients the peripapillary choroidal arterioles were dilated either insufficiently or not at all. The following conclusions are drawn: (1) The peripapillary choroid of healthy persons shows effective autoregulation securing the blood supply to the prelaminar part of the optic nerve. (2) In poag the peripapillary choroid has lost the capability of effective autoregulation.

Adult↗

Pr VECPs related to ciliary perfusion pressure in primary open angle glaucoma. A study using contact lenses to compensate for refraction changes during artificially raised IOP.

Pr VECP studies in glaucoma patients with the IOP raised artificially by the suction cup method have recently been performed by several authors, who arrived at different results. The reason for those differences may be the changes employed. The refraction changes depend on the shape of the suction cup and the height of the artificial IOP raise. By using contact lenses and a suitably shaped suction cup refraction changes could be compensated for. Studies of the pr VECP with suction cup IOP elevation and simultaneous compensation for refraction changes by applying contact lenses were made on 17 patients with primary open angle glaucoma and 21 healthy volunteers. In healthy subjects pr VECP amplitudes were found unaltered or even slightly increased until 120 mmHg of negative pressure were reached in the cup. Beyond that range they dropped. Latencies remained unaltered over that range of negative pressures. Plotting the pr VECP amplitudes and latencies against ciliary perfusion pressure we obtained unaltered potentials over a range of ca. 20 mmHg, which we interpreted as autoregulative capacity. In the 17 glaucoma patients various degrees of impaired autoregulation were found corresponding to the progression of glaucoma damage.

Adult↗

Inhibition of human serum oxytocinase (cystine aminopeptidase, E. C. 3.4.11.3) by GnRH peptides.

The hydrolysis of H-Cys(Bzl)-NH-Meq by human serum oxytocinase (E.C. 3.4.11.3) was inhibited non-competitively by various pyroglutamyl peptides. The most effective were the chicken GnRH II (Ki = 6 x 10(-6) mol l-1) and salmon GnRH (Ki = 12 x 10(-6) mol l-1), while the inhibitory potency of human GnRH was substantially lower (Ki = 60.0 x 10(-6) mol l-1). Variations in inhibitory potency of individual peptides reflected mostly the differences in N-terminal and C-terminal parts of the molecules.

Amino Acid Sequence↗

On the blood-brain barrier to peptides: effects of immobilization stress on regional blood supply and accumulation of labelled peptides in the rat brain.

Tritiated arginine-vasopressin (AVP), desglycinamide-vasopressin (DGAVP), chicken gonadotropin releasing hormone (GnRH) or carbetocin were injected intracarotidally into rats exposed to a restraint stress for 60 min. The peptide accumulations were determined in 9-13 brain regions and anterior pituitary. In separate experiments the cerebral blood flow was measured. The blood supply to the brain was decreased in stressed animals as indicated by: 1. significant decrease (17-50%) of cerebral blood flow; 2. diminished accumulation of tritiated AVP in the regions lacking a blood-brain barrier (BBB). Consequently, the values of peptide accumulation were corrected for the changed blood supply. Compared with control animals, restraint stress induced a higher accumulation of AVP (+41%), DGAVP (+60%), carbetocin (+81%) and GnRH (+104%).

Animals↗

Selective attenuation of cocaine-induced stereotyped behaviour by oxytocin: putative role of basal forebrain target sites.

The effects of oxytocin (OXT), arginine- and lysine-vasopressin (AVP and LVP) and an OXT-receptor antagonist on cocaine-induced sniffing behaviour were investigated in rats. OXT, but not AVP or LVP injected subcutaneously (s.c.) attenuated cocaine-induced sniffing. The effect of OXT (s.c.) was inhibited by an OXT-receptor antagonist administered intracerebroventricularly (i.c.v.). I.c.v. administration of different doses of OXT in nanogram quantities caused a dose-dependent attenuation of cocaine-induced sniffing. Local cerebral microinjection of OXT into the accumbens nucleus and olfactory tubercle but not into the olfactory nucleus, central amygdaloid nucleus or caudate nucleus, inhibited the cocaine-induced sniffing behaviour. These results demonstrate that OXT selectively attenuates the cocaine-induced stereotyped behaviour through basal forebrain target sites.

Animals↗

Structure-activity relationships of vasopressin analogues on release of factor VIII in dogs.

In order to study structure-activity relationships as to Factor VIII release conscious dogs were injected with analogues of vasopressin. The peptides used were chemically modified either in the hexapeptide ring structure of the vasopressin molecule or in the C-terminal tripeptide or in both. The results showed that an intact C-terminal appears to be of importance for retaining Factor VIII releasing activity of the analogues, whereas at least some modifications of the ring structure are tolerated without loss of activity. Decreased activity was also observed when the disulphide bridge was substituted with a monocarba bond.

Animals↗

The release of factor VIII and tissue plasminogen activator can not be blocked by specific antagonists to vasopressin.

Vasopressin and in particular 1-deamino-8-D-arginine vasopressin (DDAVP) can release factor VIII (FVIII) and tissue plasminogen activator (tPA) to the blood. In the present study DDAVP was injected in conscious dogs which had been preloaded with specific antagonists either against vasopressin's vasopressor response (V1-receptors) or its antidiuretic response (V2-receptors). The presence in the blood of either of the antagonists had no effect on the increase of FVIII or tPA following stimulation with DDAVP. It is therefore concluded that the effect of DDAVP on coagulation and fibrinolysis is elicited via a new class of receptors different from the known V1- and V2-receptors.

Animals↗

[Psychiatric diagnoses in self-help groups of the "Only Anxiety" society in Bergen].

45 members of self-help groups for persons with anxiety disorders were interviewed using Structured Clinical Interview of DSM-III-R. 21 interviews were video-recorded and rated by an independent rater. Panic disorder was the most common diagnosis, together with present or past serious depression. We discuss the relation between anxiety disorders and affective disorders. Interrater agreement was high for panic disorder, but not for the diagnoses generalized anxiety disorder and simple phobia. Questions are raised about the clinical validity of generalized anxiety disorder.

Adult↗

Tritiation of [8-L-arginine, 9-desglycineamide] vasopressin.

Tritiated vasopressin analogue, [8-L-arginine, 9-desglycineamide]-vasopressin was prepared from its diiodo-derivative by means of catalytic reductive dehalogenation. The reaction products were purified by reversed-phase HPLC resulting in a labelled peptide with high specific radioactivity (629 TBq/mmol).

Arginine Vasopressin↗

[Synthesis and pharmacological properties of des-9-glycine analogs of [Orn8]vasopressin].

Three new analogues of vasopressin, viz. des-Gly9-[Phe2, Orn8]vasopressin, diglycyl-des-Gly9-[Phe2, Orn8]vasopressin, and diglycyl-des-Gly9-[Val4, Orn8]vasopressin, were synthesized to investigate the structure-function relationship. Hormonal (vasopressor, antidiuretic, uterotonic, galactogogic) activities of the new compounds were determined, their effect on elaboration and retention of the active avoidance behaviour in rats was studied.

Animals↗

Substantia nigra pars reticulata modulates spontaneous and goal-directed behaviour of rat.

Spontaneous and active avoidance behaviour was compared pre- and postoperatively on 11 six month old male hooded rats of the Long-Evans strain. Seven of them with small bilateral symmetric lesions only in the ventromedial part of substantia nigra pars reticulata (SNR) were characterized by a strong decrease of exploratory parameters except rearings, without differences of ambulatory activity in the open field (OF) test. The SNR group showed a significant retention loss, increased reaction times and run durations in three variants of preoperatively consolidated Y-maze performance and weakened brightness discrimination. They were unable to relearn the tasks and to reduce errors to the preoperative level which was zero. Postoperative acquisition of a new active avoidance stereotype in the jump test box was impossible. They ignored the hanging rod in this box and did not find the escape possibility. Prevailing flexor tonus of trunk and forelegs after SNR lesions was no sufficient reason for these changes, because inborn and automated programs were far less concerned than learnt or operative programs and the accuracy of goal-directed behaviour.

Animals↗

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↗