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Biomedical subjects

R Landgraf

Publications and source records attributed to R Landgraf.

At least 199 records · Page 11Linked to original sources
PubMed1994

Rapid effect on suckling of an oxytocin antisense oligonucleotide administered into rat supraoptic nucleus.

Suckling in the lactating rat (days 6-10 of lactation) was used to characterize the effects of intracerebral oxytocin (Oxt) antisense oligonucleotide treatment on the hypothalamo-neurohypophysial system. Vehicle, mixed bases, Oxt antisense, or vasopressin antisense oligonucleotides (2.5 micrograms/0.5 microliter each) were infused directly into the left and right supraoptic nucleus (SON), 4 h before a litter of 10 pups was allowed to suckle for 30 min. In the Oxt antisense group, there was a significant reduction in the number of milk ejection reflexes (to 34.6 +/- 4.88%, P < 0.001), as well as in the weight gain of the litter (to 18.8 +/- 6.98%, P < 0.03) compared with vehicle (100%)-, mixed base-, or vasopressin antisense-treated animals, which did not differ from each other. The time to onset of suckling, however, was unchanged. Compared with presuckling values, plasma Oxt was significantly increased in all four groups 30 min after onset of suckling (vehicle, to 325 +/- 117%; mixed bases, to 258 +/- 48.2%; vasopressin antisense, to 330 +/- 55.7%), but this increase was less pronounced in Oxt antisense-treated rats (to 157 +/- 20.5%; P < 0.05 vs. vasopressin antisense). In contrast to these changes in neuroendocrine functions during suckling, Oxt as well as vasopressin content and Oxt immunoreactivity in posterior pituitaries and the SON, respectively, did not differ among groups. Our data indicate rapid and specific effects of an Oxt antisense oligonucleotide infused into the SON on neuroendocrine, suckling-related parameters that are not due to depleted stores of Oxt in the hypothalamo-neurohypophysial system.

Animals↗
PubMed1994

Stimulation of oxytocin release within the supraoptic nucleus and into blood by CCK-8.

Simultaneous microdialysis in brain and blood was used to monitor the effects of systemic and central cholecystokinin octapeptide (CCK-8) on the release of oxytocin and vasopressin within the hypothalamic supraoptic nucleus (SON) as well as into blood of urethan-anesthetized female rats. Administration of CCK-8 (20 micrograms/kg iv) increased oxytocin contents in 30-min microdialysates sampled simultaneously within the SON (1.8-fold) and blood (2.4-fold, both P < 0.05) compared with prestimulation levels. In another experiment, after bilateral administration of CCK-8 directly into the SON (10 ng/0.5 microliter) via a microdialysis/infusion probe, oxytocin contents in dialysates sampled from the left and right SON were increased 2.3- and 1.7-fold (P < 0.05), respectively. In simultaneously sampled dialysates from the jugular vein, oxytocin content increased 2.3-fold (P < 0.05). In contrast, oxytocin in dialysates sampled outside the hypothalamic nuclei was not altered by systemic or central CCK-8. The direct infusion of CCK-8 into both SON increased the release of vasopressin within the SON 1.7-fold (P < 0.05) but failed to significantly change vasopressin release into blood. The present findings show a coordinated regulation of intranuclear and systemic release of oxytocin in response to systemic and central CCK-8 and provide further evidence for a possible involvement of endogenous oxytocin in the complex regulation of ingestive and reproductive behaviors induced by CCK-8 at the brain level.

Animals↗
PubMed1994

An oxytocin receptor antagonist infused into the supraoptic nucleus attenuates intranuclear and peripheral release of oxytocin during suckling in conscious rats.

We tested the hypothesis that oxytocin (OXT) released within the supraoptic nucleus (SON) during suckling in lactating rats facilitates its own intranuclear release and thereby stimulates its secretion into blood during the milk ejection reflex. In the first study, to examine the positive feedback action of OXT released within the SON, microdialysates of the SON area were sampled before and during suckling. Either vehicle (1.0 microliter) or an OXT receptor antagonist (50 ng/microliters) was infused adjacent to the microdialysis probe into the SON area before suckling began. Compared to the corresponding presuckling values (100%), the OXT content in microdialysates sampled during the suckling period increased after vehicle treatment (to 501 +/- 174%; P < 0.01), whereas infusion of the OXT antagonist significantly (P < 0.05) attenuated the rise in the release of OXT during suckling (130 +/- 22.0%). In the second study, the influence of intranuclear OXT on release of OXT into the blood during suckling was examined. Compared to those in rats infused with vehicle into both SON before suckling started (100%), injection of the OXT antagonist decreased the concentration of OXT in plasma (to 32.1 +/- 5.50%; P < 0.05) and the milk transfer to the pups during the suckling period (to 30.2 +/- 13.3%; P < 0.01). Although the neuroendocrine response to suckling was attenuated in rats receiving the OXT antagonist, maternal behavior, assessed as the time at which six to eight pups began suckling and the time from the onset until the occurrence of the third milk ejection reflex, was unaffected. These findings provide evidence for a receptor-mediated positive feedback action of OXT on its own release within the SON during suckling. The amplification of intranuclear release of OXT is needed for the release of appropriate amounts of OXT into the bloodstream to stimulate milk transfer to the suckling pups.

Animals↗
PubMed1993

High incidence of carpal tunnel syndrome in diabetic patients after combined pancreas and kidney transplantation.

Fifty-eight patients with long-standing type 1 (insulin-dependent) diabetes were studied prospectively after combined pancreas and kidney transplantation for a mean observation period of 47.9 months (range 17-116 months). Thirty-three per cent of these patients (19/58) developed carpal tunnel syndrome after a mean interval of 1.7 years (range 3 months-5 years). This rate is about twice that in type 1 diabetic patients. The manifestation of carpal tunnel syndrome was not significantly associated with worsening of diabetic polyneuropathy or with deterioration of kidney or pancreas function. In all but one patient symptoms improved without surgical intervention. This study suggests that patients after combined pancreas and kidney transplantation have an increased risk of carpal tunnel syndrome for which the etiology and pathophysiology are unknown. In most patients no surgical intervention is necessary.

Adult↗
PubMed1993

Cross-sectional study of peripheral microcirculation in diabetic patients with microangiopathy: influence of pancreatic and kidney transplantation.

Diabetic vascular lesions and peripheral autonomic neuropathy are both closely linked to long-term metabolic control of diabetes. Transcutaneous oxygen tension (PtcO2) measurements were made to elucidate whether autonomic neuropathy disturbs the cutaneous microcirculatory blood flow, and whether long-term glucose normalization ameliorates such impairment. Twenty-eight type 1 (insulin-dependent) diabetic patients in whom clinically significant macroangiopathy had been excluded by angiography were studied, subdivided into group A (n = 14; before simultaneous pancreas/kidney transplantation (SPKT); mean age 35 years, range 22-51 years; mean duration of diabetes 24 years, (range 15-32) years and group B (n = 14; mean 31 months, range 2-101 months, after successful SPKT; mean age 35 years, range 19-56 years; mean duration of diabetes 22 years, range 14-29 years). On addition there was a group (group C) of age- and sex-matched healthy control subjects (n = 14; mean age 35 years, range 23-62 years). PtcO2 measurements included basal recordings at 44 degrees C on the leg and the foot, functional recordings at 44 degrees C after arterial occlusion of the limb for 4 min, measurements during breathing 5 l oxygen per minute and finally while standing up (stand up dP20/dt). All subjects underwent extensive cardiac autonomic testing. In this cross-sectional study the recordings of basal values and of the functional parameters after arterial occlusion and during breathing oxygen did not differ significantly between groups A, B and C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Oxytocin and vasopressin release within the supraoptic and paraventricular nuclei of pregnant, parturient and lactating rats: a microdialysis study.

The release of the nonapeptides oxytocin and vasopressin within the hypothalamic supraoptic and paraventricular nuclei was measured in 30-min microdialysates in conscious female rats in the last three days of pregnancy, during parturition, immediately after parturition and during suckling, all in the same rats, and in virgin controls. Nonapeptide release within the supraoptic and paraventricular nuclei was unchanged during late pregnancy compared to virgin rats, but intranuclear oxytocin and not vasopressin release was elevated during parturition (relative to late pregnancy, supraoptic nucleus: to 254%, paraventricular nucleus: to 300%; P < 0.01) and during suckling also on days 8-10 of lactation (relative to pre-suckling, supraoptic nucleus: to 407%, paraventricular nucleus: to 275%; P < 0.02). Suckling-induced release of oxytocin was significantly reduced using Ca(2+)-free, EDTA-containing (10(-4) M) microdialysis fluid and further stimulated by high K(+)- (56 mM), veratridine-containing (50 microM) microdialysis fluid. The opioid antagonist naloxone whether given by subcutaneous injection (5 mg/kg) or directly into the supraoptic nucleus by microdialysis (5 x 10(-6) M) or microinjection (1.5 microliters, 10(-6) M) did not further enhance oxytocin release within either the supraoptic or paraventricular nuclei during parturition. In contrast to the selective release of oxytocin within the supraoptic and paraventricular nuclei during parturition and suckling, direct osmotic stimulation of the nuclei by microdialysing hypertonic medium (artificial cerebrospinal fluid; 1 M NaCl) increased intranuclear release of both oxytocin and vasopressin which was further enhanced after replacement of hypertonic with isotonic fluid. This rebound phenomenon served to confirm the precise location of the microdialysis probe ante mortem and the ability of the nuclei to adequately respond to the osmotic stimulus at the end of the experiment. The study has shown that oxytocin is released in the supraoptic and paraventricular nuclei during parturition as well as in lactation unrestrained by endogenous opioids during parturition. This intranuclear release of oxytocin may act by local positive feedback stimulation of oxytocin neurons to excite further oxytocin release in the brain and into blood during both parturition and lactation.

Animals↗
PubMed1993

Simultaneous microdialysis in blood and brain: oxytocin and vasopressin release in response to central and peripheral osmotic stimulation and suckling in the rat.

Simultaneous microdialysis in blood and brain has been used to monitor the release of both oxytocin and vasopressin into the systemic circulation (jugular vein/right atrium) and within the hypothalamic supraoptic nucleus of rats. Both home-made probes for blood and brain microdialysis revealed detectable nonapeptide concentrations under basal conditions and differential responses to a variety of stimuli. In urethane-anesthetized male rats, bilateral stimulation of the supraoptic nucleus by microdialyzing hypertonic medium (1 M NaCl) not only significantly increased the intranuclear release of both oxytocin and vasopressin (p < 0.05), but also their release from the neurohypophysis into blood (p < 0.05). In poststimulation microdialysates sampled from blood, the nonapeptides reached basal levels again, whereas intranuclear levels were further elevated. Intraperitoneal injection of hypertonic saline, on the other hand, resulted not only in the well-known increased peripheral release of oxytocin and vasopressin (p < 0.01 each), but also in a delayed increase in intranuclear oxytocin (p < 0.05). In contrast, intranuclear vasopressin release failed to change within the 90-min period following osmotic stimulation. In conscious lactating rats, suckling increased oxytocin contents in microdialysates sampled simultaneously in blood and the supraoptic nucleus (p < 0.05 each) further validating the microdialysis techniques used. The in vivo recovery in blood of approximately 65% determined using both radiolabeled and endogenous oxytocin provides a rough estimate to assess nonapeptide concentrations in plasma from 30-min or even 10-min blood microdialysis data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Diabetic neuropathy 3 years after successful pancreas and kidney transplantation.

Twenty-seven patients with successful transplantation and a control group of 14 patients with early rejection of the pancreas graft but functioning kidney graft were examined in a prospective study for 3 yr. Before transplantation, all patients had long-standing type I diabetes with advanced secondary complications, including end-stage diabetic nephropathy. After transplantation in the patients of both groups, kidney function was almost normal. Mean HbA1 levels were normal in the group with pancreas graft survival. In the control group, HbA1 levels were, on average, 1.5% higher compared with the group with pancreas survival (P = 0.00005). After 3 yr, the patients with functioning pancreas graft showed fewer symptoms (mean difference 1.0 in a symptom score ranging from 0 to 16, P = 0.004) compared with the control group. No statistically significant difference between both groups concerning clinical signs of polyneuropathy could be observed. In the pancreas and kidney transplantation group, peroneal and median nerve conduction velocities increased 7.2 m/s (P < 0.01) and 3.5 m/s (P < 0.05), respectively, whereas no increase was registered in the control group. The change of median and sural sensory nerve conduction velocities, peroneal and median compound muscle action potentials, and sural and median sensory action potentials was insignificant. In conclusion, although the improvement of clinical symptoms and neurophysiological signs of polyneuropathy was modest in the pancreas and kidney transplantation group, our data suggest that successful pancreas transplantation is able not only to halt the progression of diabetic polyneuropathy but also to improve it to some extent even at a far advanced stage.

Action Potentials↗
PubMed1993

[Does combined pancreas-kidney transplantation modify diabetic retinopathy in type-1 diabetic patients?].

The study group consisted of 30 patients with a functioning pancreas graft of at least 12 months. Fifty-seven eyes were examined; 26 eyes from 15 patients with a non-functioning pancreas graft made up the control group. Three patients were in both groups because their graft was rejected after a 12-month period. The mean age in the study group was 37 years, the mean observation time 38 months. The mean duration of diabetes before transplantation was 24 years and all patients were on kidney dialysis. Retinal coagulation for diabetic retinopathy had previously been performed in 80.7% of the patients. The mean age (38 years), observation time (36 months), duration of diabetes before transplantation (24 years), and incidence of retinal coagulation (84.6%) were comparable in the control group. All patients had regular ophthalmological examinations every 6 to 12 months. This included best-corrected visual acuity, applanation tonometry, slit-lamp examination and dilated binocular funduscopy. Seven 30 degrees fundus pictures of the posterior pole were taken: The images were graded by comparing them with the ETDRS (Early Treatment Diabetic Retinopathy Study) Group standard photographs. The original Airlie House grading scale was changed because we did not take stereoscopic pictures. Evaluation and grading were done independently by two examiners. The retinopathy score was graded from 0 (no retinopathy) to 11 (no evaluation possible due to opaque media). Visual acuity remained stable in both the study and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Vasopressin administration via microdialysis into the septum interferes with the acquisition of spatial memory in rats.

The role of vasopressin (AVP) in the septohippocampal system in spatial memory was studied in 27 male hooded rats of the Long-Evans strain. The rats were implanted with a septal microdialysis probe and assigned to 3 groups. Two days later, they were trained on 3 consecutive days (12 daily trials) to locate the hidden underwater platform in the Morris water maze (MWM) while the probes were perfused with either artificial cerebrospinal fluid (aCSF) or aCSF containing vasopressin or the V1 antagonist d(CH2)5Tyr(Me)AVP (AAVP). Another group of rats (n = 8) remained untreated. Groups receiving microdialysis of aCSF or AAVP acquired the MWM task at the same rate as untreated animals. On the other hand, place navigation learning was significantly impaired by microdialysis of AVP during all sessions. The results indicate that endogenous AVP (at least that affecting the V1 receptor subtype) is not indispensable for the acquisition of spatial memories in the MWM, whereas excessive presence of synthetic AVP interferes with spatial learning.

Animals↗
PubMed1992

Does the release of vasopressin within the supraoptic nucleus of the rat brain depend upon changes in osmolality and Ca2+/K+?

Microdialysis in conjunction with a highly sensitive radioimmunoassay was used to monitor the in vivo release of arginine vasopressin (AVP) within the supraoptic nucleus (SON) of the rat brain (n = 70). Thirty-min dialysates were collected in urethane-anesthetized animals before, during and after hypertonic or hypotonic pulses were delivered via the probe. As compared to artificial cerebrospinal fluid (aCSF)-perfused controls, 1M aCSF given over a period of 210 min resulted in an increased intranuclear AVP release which, however, reached its peak only in the post-stimulation period, i.e. after replacement of hypertonic with isotonic aCSF again (rebound phenomenon). Hypertonic (0.5 M, 1 M or 2 M) pulses given 150 min after the first (1 M) pulse resulted in 3 different rebound responses: a marked decrease (to 25.3%, P less than 0.001), no change or slight increase (132%, n.s.). As shown by the response to correction of the hypertonicity to normal as well as by perfusion of hypotonic aCSF (0.01 M), release of AVP within the SON appears more responsive to a reduction than to an elevation in the osmolality of aCSF. Omission of Ca2+ from and addition of EGTA to the aCSF decreased the osmotically stimulated, but not the basal AVP release. If K(+)-hypertonic aCSF was used, however, basal AVP levels increased significantly; in contrast, the rebound increase failed to differ from aCSF-perfused controls. It is concluded from these findings that release of AVP from intact neuronal structures in the SON is responsive to changes in osmolality with an apparent greater sensitivity to decrease in osmolality.

Analysis of Variance↗