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R Landgraf

Publications and source records attributed to R Landgraf.

At least 217 records · Page 12Linked to original sources

Vasopressin and oxytocin in brain areas of rats selectively bred for differences in behavioral performance.

Wistar rats were selectively bred over 10 generations for differences in performance in a footshock-motivated brightness discrimination (BD) test in a Y-maze. High behavioral performance (Wis/HBP) and low behavioral performance (Wis/LBP) rat lines were obtained which differ significantly in all behavioral components tested: frequency of correct responses, number of trials to criterion, response latency (HBP less than LBP), and frequency of freezing behavior (HBP less than LBP), the latter suggesting differences in emotionality. In Wis/LBP rats, furthermore, the normal increase in behavioral performance between the training and the relearning session, which indicates the formation of a memory trace, disappeared during selection. In male breeders sampled during selection of the two lines (Wis/HBP: n = 17; Wis/LBP: n = 21), both arginine vasopressin (AVP) and oxytocin (OXT) contents were measured by radioimmunoassay in the motor cortex, septum/striatum, hippocampus, hypothalamus, medulla oblongata and posterior pituitary. Compared with the Wis/HBP rats, the Wis/LBP rats contained less AVP in the hippocampus (3.1 +/- 0.58 vs 8.3 +/- 1.4 pg/mg wet wt., mean +/- S.E.M., P less than 0.001), but more AVP in the medulla (1.7 +/- 0.20 vs 1.1 +/- 0.18 pg/mg, P less than 0.05). In contrast, no significant differences between the lines were detected with respect to OXT concentrations. In the Wis/LBP rats, moreover, the hippocampal AVP content decreased during selection (r = -0.645, P less than 0.01), while the acquisition response latency increased (r = 0.549, P less than 0.01). As a consequence, a significant, albeit weak, negative correlation (r = -0.483, P less than 0.05) was observed between the individual hippocampal AVP content and the response latency during acquisition. Thus, the results confirm the view that genetically determined differences in the hippocampal content of endogenous AVP may contribute to an individual's level of emotionality and behavioral performance.

Animals↗

Transfer of [3H]leucine across the blood-brain barrier at high blood-side oxytocin concentrations in normal and morphine-dependent rats.

The effects of circulating oxytocin on permeability of the blood-brain barrier (BBB) to L-[3H]leucine were studied in anaesthetized rats using the intracarotid, single pass, bolus injection technique. After bolus intracarotid oxytocin injection (10(-9) M), there were no differences in [3H]leucine uptake, compared with controls, in any of eight brain regions with a 'tight' BBB (olfactory bulb, frontal cortex, visual cortex, corpus striatum, hippocampus, thalamus, hypothalamus and colliculi) or in BBB-free, 'leaky' structures (pineal gland, choroid plexus, neuro-intermediate pituitary, anterior pituitary). [3H]leucine uptake by the 'leaky' structures was 2.4x and 2.6x uptake by 'tight' regions in the oxytocin and control groups respectively. In morphine-dependent rats, naloxone increased oxytocin secretion 28-fold within 5 min, but did not affect [3H]leucine uptake for any BBB-protected brain region or BBB-free 'leaky' structure. Accumulation of [3H]leucine was 8.3x and 7.0x greater in the 'leaky' structures than in the 'tight' regions in the naloxone and control groups respectively; [14C]inulin accumulation by each 'tight' region (measured simultaneously with [3H]leucine to determine the vascular space) was not affected by naloxone. It is concluded that even very high blood plasma concentrations of oxytocin do not affect BBB permeability for leucine. It is unlikely that altered BBB permeability, at least for amino acids, contributes to CNS changes during naloxone-provoked morphine withdrawal.

Animals↗

Microdialysis administration of vasopressin and vasopressin antagonists into the septum during pole-jumping behavior in rats.

Wistar rats (n = 95) were trained in a pole-jumping apparatus (10 trials/session/day) to investigate the involvement of centrally and peripherally released endogenous AVP in their acquisition rate and to examine the feasibility of the microdialysis technique for the administration of peptides during a behavioral test. After session 1, a microdialysis probe was implanted into the septum; during sessions 2 and 3 the probe was perfused with artificial cerebrospinal fluid (aCSF) alone or containing either AVP (delivered amount via the probe: 0.2 ng) or the V1 (d(CH2)5Tyr(Me)AVP, 5.0 ng) or the V2/V1 (d(CH2)5-D-Tyr(Et)VAVP, 5.0 ng) antagonist. Administration of AVP via microdialysis into the septum failed to alter the acquisition rate of pole jumping. Also, ip application of both hypertonic saline and the AVP V1 antagonist (10 micrograms) in another experiment failed to show a significant effect upon behavior. Septal administration of the V1 or the V2/V1 antagonist via microdialysis, however, produced a significantly impaired performance. The results indicate that AVP release within the septum is involved in the acquisition of pole-jumping behavior probably mediated by the V1 receptor subtype. An additional involvement of the V2 receptor subtype, however, cannot be entirely excluded. The microdialysis technique proved to be a potent tool to administer substances concomitantly with behavioral tests.

Animals↗

[Pancreas transplantation].

The results of pancreatic transplantation improved markedly during the last years. Transplantation of the pancreas together with the kidney is the most common treatment of Type I-diabetic patients. At present different surgical techniques are used for the handling of the exocrine secretion of the gland. However, each technique has its own advantages and disadvantages. A successful pancreatic transplantation provides a normal glucose metabolism in the majority of the patients. This leads to an improvement of the peripheral and autonomic neuropathy. Clinical observations suggest a beneficial effect on diabetic retinopathy and peripheral microcirculation. More long-term-results are mandatory to assess the preventive effect of pancreatic transplantation on the development of late diabetic complications. Timing of pancreatic transplantation has a major influence on the course of secondary complications. There is no need for further dietary restrictions or exogenous insulin replacement, so that a better quality of life can be achieved.

Diabetes Mellitus, Type 1↗

Oxytocin and vasopressin release in discrete brain areas after naloxone in morphine-tolerant and -dependent anesthetized rats: push-pull perfusion study.

The effects of naloxone on the release of oxytocin and vasopressin in discrete brain areas were investigated in control and morphine-tolerant/dependent female rats anesthetized with urethane. Two or three consecutive push-pull perfusates were collected for 30-40 min each and the peptide contents measured by radioimmunoassay; naloxone (5 mg/kg, i.v.) was given after the first perfusion. In control rats, naloxone did not increase oxytocin release from any of the regions studied: mediolateral septum, dorsal hippocampus, nucleus of tractus solitarius, or supraoptic nucleus. After naloxone, vasopressin release was approximately doubled in the nucleus of tractus solitarius (p less than 0.05), indicating endogenous opioid inhibition of vasopressin release. Naloxone increased oxytocin concentration in the circulation 3.7-fold (p less than 0.001) but did not affect vasopressin secretion. In rats made morphine tolerant/dependent by intracerebroventricular infusion of morphine for 5 d, oxytocin and vasopressin release in the perfused brain was initially similar to that in control rats, indicating tolerance to any initial morphine effects. In these rats, naloxone increased oxytocin release in the septum threefold relative to control rats (p less than 0.02) but did not alter oxytocin release in hippocampus or nucleus of tractus solitarius. Thus, the oxytocin neurons projecting to septum can develop morphine dependence and may be inhibited acutely by opioids acting via mu-receptors. The results indicate morphine acts selectively on oxytocin neurons projecting to mediolateral septum compared with other central projection areas and compared with centrally projecting vasopressin neurons. In the supraoptic nucleus, naloxone increased oxytocin release 2.3-fold (from 9.2 +/- 3.1 pg/30 min) and increased oxytocin release from axons of these neurons fivefold (from 7.8 +/- 3.2 pg/30 min). Naloxone had no significant effect on vasopressin release from any of the central sites, or on vasopressin secretion into blood, although oxytocin secretion was increased 36-fold (from 17.2 +/- 2.6 pg/ml; p less than 0.001), confirming dependence of magnocellular oxytocin neurons. The central processes of magnocellular supraoptic neurons may be a major source of central oxytocin released during morphine withdrawal.

Anesthesia↗

Vasopressin release within the supraoptic and paraventricular nuclei of the rat brain: osmotic stimulation via microdialysis.

The combination of microdialysis and a highly sensitive radioimmunoassay was used in order to monitor the in vivo release of arginine vasopressin (AVP) within hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei of the rat brain. A dialysis probe was inserted into the SON or PVN area and microdialysis was performed in conscious or urethane-anesthetized animals before, during and after hypertonic artificial cerebrospinal fluid (aCSF, with 1 M NaCl) was delivered via the probe. The recovery of AVP in vitro was 1.60%, that of [3H]OH in vitro 14.2% and in vivo 8.44% (SON) and 9.26% (PVN), respectively. AVP was consistently detected in both SON and PVN dialysates; basal levels averaged 0.87 +/- 0.22 pg/30-min dialysate (SON, n = 51) and 0.80 +/- 0.24 pg/30-min dialysate (PVN, n = 6), respectively. Hypertonic aCSF given over a period of 30 min, 60 min or 90 min, resulted in an increased AVP release within the SON which, however, reached its peak (to 8.86-10.27 pg/sample; P less than 0.001 as compared to basal) only in the poststimulation period, i.e. after replacement of hypertonic with isotonic aCSF. An identical osmotic stimulus given 150-210 min after the first one produced similar, though slightly declined, changes in AVP release. In the PVN, AVP release patterns prior to and in response to the first hypertonic pulse were similar to those in the SON; a possible functional difference between the two nuclei is indicated by the lack of a rebound increase in AVP release following the second stimulation. The physiological significance of intranuclearly released AVP remains to be shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The positive feedback action of vasopressin on its own release from rat septal tissue in vitro is receptor-mediated.

The effect of arginine vasopressin (AVP) on its own septal release was evaluated using an in vitro superfusion procedure. As compared to basal release from septal fragments, pulses of synthetic AVP (15 pg/5 min) resulted in a 25-fold augmented release of endogenous AVP, indicating a positive feedback action. Both the basal and stimulated AVP release were significantly increased by 60 mM potassium and markedly reduced by omission of calcium. Preincubation of the septal fragments with the V2/V1 AVP receptor antagonist d(CH2)5 [D-Tyr (Et)2,Val4]AVP resulted in a dose-dependent inhibition of the positive feedback action of AVP which was nearly completely blocked at doses between 1.25 and 5 ng per 100 microliters incubation medium. As compared to this effect, the V1 antagonist d(CH2)5 Tyr (Me)2 AVP as well as oxytocin were significantly less potent. The results suggest that the positive feedback action of AVP on its own release from septal fragments is potassium-stimulated, calcium-dependent and mainly V2 receptor-mediated. The physiological significance of this phenomenon remains to be shown.

Animals↗

Vasopressin receptors in the brain, liver and kidney of rats following osmotic stimulation.

The binding site concentration (Bmax) and equilibrium dissociation constant (Kd) for [3H]-arginine vasopressin (AVP) binding sites were measured in limbic brain areas (septum, dorsal hippocampus, amygdala) and liver and kidney of control and osmotically stimulated male Wistar rats. Membrane binding was performed in these five areas 30, 60 and 180 min following intraperitoneal injection of hypertonic saline. This paradigm resulted in no significant change in binding characteristics in the septum, dorsal hippocampus, amygdala and liver from control treated rats. In contrast, the kidney Bmax was significantly reduced 60 min following osmotic stimulation, with no effect on affinity. These results also suggest that AVP receptors in the CNS are relatively resistant to regulatory effects of an acute AVP exposure.

Animals↗

Long-term follow-up of diabetic retinopathy for up to 71 months after combined renal and pancreatic transplantation.

This study reports the course of diabetic retinopathy in 25 patients (41 eyes, 9 one-eyed patients) who had undergone successful renal and pancreatic transplantation. The mean duration of follow-up was 38 months (range, 15-71 months). Visual acuity improved in 13 eyes (32%), remained stable in 19 (46%) and deteriorated in 9 (22%); only 2 of the latter 9 eyes (5%) sustained severe visual loss according to the definition of the Diabetic Retinopathy Study Group. The frequency and severity of vitreous hemorrhage improved in 19 eyes (46%), remained unchanged in 18 (44%) and worsened in 4 (10%). In comparison with other modes of treatment such as intensified conventional insulin therapy and artificial insulin-delivery systems, the combined renal and pancreatic transplantation seems to have advantages concerning the course of proliferative diabetic retinopathy.

Adult↗

Long-term results in pancreatic transplantation with special emphasis on the use of prolamine.

Our pancreatic transplantation programme was initiated in 1979. Since then a total of 102 pancreas transplantations have been performed, blocking exocrine secretion using the duct occlusion technique with prolamine. Early non-immunological complications are frequent. The long-term results (9 years) in combined pancreas and kidney transplanted patients are satisfying: the survival rate for pancreas is 38% and 54% for kidney. Patient survival rate in this period is 85%. Beyond the first year post-transplant the exocrine activity disappears whereas the endocrine function remains well preserved.

Diabetes Mellitus, Type 1↗

Outcome of renal grafts after simultaneous kidney/pancreas transplantation.

Nineteen patients with endstage renal failure due to Type 1 (insulin-dependent) diabetes mellitus received simultaneous pancreas/kidney transplants using bladder drainage technique. Another group of 25 Type 1 diabetic patients received pancreas/kidney transplants by the duct occlusion technique. We observed a higher incidence of rejection episodes in the patients of the bladder drainage group than those in the duct occlusion group, 14 of 19 patients (74%) vs 7 of 25 (28%) respectively. Anti CD3 antibodies (OrthocloneR, OKT3) as a part of induction treatment was used more often in the bladder drainage group (58%) than in the control group (20%).

Diabetes Mellitus, Type 1↗