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Biomedical subjects

M Schlumpf

Publications and source records attributed to M Schlumpf.

At least 55 records · Page 3Linked to original sources

Maternal stress alters monoamine metabolites in fetal and neonatal rat brain.

Heat-restraint stress given rats during the last week of gestation significantly altered dopaminergic dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA) and noradrenergic 3-methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG) forebrain-hypothalamic monoamine (MA) metabolites in female offspring. On gestational day 21, HVA and MOPEG were significantly higher and lower, and on postnatal day 1 all were higher. There were virtually no differences in brain MA concentrations in males. Thus MA metabolic concentrations differ in fetal-neonatal forebrain-hypothalamus as a function of sex differences and maternal stress.

3,4-Dihydroxyphenylacetic Acid↗

A new device for monitoring early motor development: prenatal nicotine-induced changes.

A new type of activity meter has been designed especially for young rats. It consists of a warmed platform for the animal, a TV camera with monitor and a microprocessor. The TV camera detects the animal as a black figure on a light background. This picture is digitalized and stored in a Z80 microprocessor. Every 200 msec a new image is compared to the foregoing one. The total number of black points that are changing from black to white and vice versa provides a measure for motor activity of the animal. Prenatally nicotine-treated rat pups were tested on the activity meter. The developmental pattern of motor activity was different for male and female pups. Motor activity of nicotine-treated male pups differed significantly from controls at postnatal days 7 and 15 while this drug effect was not seen in females.

Animals↗

The ontogeny of brain neurotensin receptors studied by autoradiography.

Using in vitro receptor autoradiographic techniques we have analysed the pre- and postnatal development of neurotensin receptors in the rat brain. Receptors were labeled with [3H] or [125I]neurotensin in mounted tissue sections from animals of ages gestational day 14 until the postnatal day 21 as well as young adult animals. Very low densities of neurotensin receptors were visualized on gestational days 14 and 15. Between gestational days 16 and 18 a marked increase in the density of neurotensin receptors was seen in the developing neocortex. Densities in other brain areas, particularly the midbrain and brainstem were much lower than cortical densities. The density of neurotensin receptors in the cortex increased through the last part of the gestation and early postnatal life until it peaked at the end of the first postnatal week. After that, neurotensin receptor binding decreased dramatically reaching lower densities seen in the adult animal at the end of the third postnatal week. Development of neurotensin receptors in other brain areas followed very different time patterns. Neurotensin receptors in the midbrain were seen first at gestational day 18 and increased slowly with development to reach adult levels at about the second week of postnatal life. Neurotensin receptors in the hippocampal formation demonstrated postnatal development; they were detected at postnatal day 5 and showed a developmental peak around the second week. These patterns were seen with both 3H- and 125I-labeled neurotensin, thus excluding possible differential quenching artifacts. These clear differential regional ontogenetic patterns for neurotensin receptors are the main findings of these experiments. The very high densities present in the cortex even in fetal stages suggest that neurotensin could play a role in the development of the brain.

Animals↗

Long-term follow-up after percutaneous transluminal coronary angioplasty. The early Zurich experience.

The first 169 patients in whom percutaneous transluminal coronary angioplasty was performed have now been followed for five to eight years. The procedure was technically successful in 133 patients (79 percent). In the follow-up period, nine of the 133 patients died (five of cardiac disease), and actuarial cardiac survival was 96 percent at six years. All patients were symptomatic before angioplasty, but 67 percent of the 133 who had technically successful procedures were asymptomatic at the last follow-up evaluation. Exercise stress testing, positive in 97 percent before angioplasty, was positive at the last follow-up study in only 10 percent of the patients who had technically successful procedures. Stenosis recurred during the first six months in 30 percent of the patients, and six more recurrences were observed among the 41 patients who had follow-up angiograms at two to seven years. A second angioplasty was required in 27 patients, and coronary bypass surgery was subsequently needed in 19. Actuarial event-free survival (freedom from death, myocardial infarction, and coronary bypass surgery) was 79 percent at six years. Follow-up of patients with multivessel disease showed a higher mortality from cardiac causes and a lower rate of long-term success than occurred among patients with single-vessel disease. These long-term results indicate that most episodes of restenosis occurred within six months of angioplasty, but some late recurrences were seen. Patients with single-vessel disease had a better long-term outcome after angioplasty than those with multivessel disease.

Adult↗

Benzodiazepine and muscarinic cholinergic binding sites in striatum and brainstem of the human fetus.

The regional distribution of binding sites for [3H]flunitrazepam and [3H]N-methylscopolamine was studied in human fetal brain of 18 and 23 weeks gestation by in vitro autoradiography. Areas densely labelled by both ligands include the hypoglossal nucleus and the striatum. The latter is characterized by a patchy distribution of both binding sites reminiscent of acetylcholinesterase staining. Similarities with the rat fetus and the occurrence of binding sites in areas of potential significance for fetal behaviour are discussed.

Brain Stem↗

T lymphocytes affect the development of sympathetic innervation of mouse spleen.

We investigated whether the development of sympathetic innervation of the spleen is affected by lymphoid cells. Splenic noradrenaline (NA) levels of athymic nude mice (nu/nu) and normal thymus-bearing littermates (nu/+) were determined at different times during ontogeny. While no differences were detected at birth, higher splenic NA levels were found in 7-, 11-, and 21-day-old athymic mice. Thymus transplantation or thymocyte injection to newborn nude mice resulted in splenic NA levels comparable to those of normal nu/+ mice. Histochemical studies fully confirmed such differences. Taken together with previous studies, these results suggest that T lymphocytes or their products exert an inhibitory influence on sympathetic nerve fibers, thus leading to decreased NA content in the spleen. The data also illustrate the capacity of a nonneuronal cell in a peripheral organ to affect the process of autonomic innervation of this organ.

Aging↗

Beta-adrenergic binding sites in fetal rat central nervous system and pineal gland: their relation to other receptor sites.

Regional development of beta-adrenergic binding sites in the rat fetal central nervous system and pineal gland were studied in relation to the ontogeny of different drug and neurotransmitter binding sites. 3H-dihydroalprenolol labels the olfactory bulb very early in fetal life. A comparatively early development of binding sites is also seen for benzodiazepines during late gestation. 3H-serotonin, 3H-muscimol, 3H-GABA and 3H-(N)-methylscopolamine additionally label the olfactory bulb, revealing quite different patterns. Around gestational day 16, beta-adrenergic sites were found in the neocortex, then in choroid plexus and in the pineal gland. Besides beta-adrenergic, only 3H-flunitrazepam binding sites are detectable in the fetal eye, the latter with a more restricted regional distribution. In the fetal pineal, beta-adrenergic, muscarinic cholinergic and serotonergic binding sites appear at different times in gestation. In the neocortex a variety of binding site patterns develop. Two more general types can be distinguished: appearance along with caudorostral maturation of the brain and appearance within distinct brain regions, possibly related to local differentiation processes. The simultaneous onset of various binding sites in distinct areas of the fetal brain might result in higher sensitivity of individual brain areas to drugs.

Animals↗

[Pharmacological modifications of neuroendocrine ontogenesis. Development of receptors, nicotine and catecholamines].

The prenatal ontogeny of several receptor sites is reviewed. Binding sites for nicotine are found in fetal rat brain from gestational day 14; their regional development is described. Prenatal nicotine exposure interferes with the organization of the gonadal axis of the male rat fetus and is followed by permanent alterations in catecholamine metabolite levels. Cannabis, ethanol, barbiturates and opiates are also capable of disturbing the sexual differentiation of the central nervous system. These observations indicate that interactions with the ontogeny of neuroendocrine systems represent an important pathogenetic mechanism through which drugs can affect brain development. Recent observations on receptor development in the human fetus suggest the existence of a comparable sensitive period.

Animals↗

Permanent alteration of peptide feedback on dopamine neurons after injection of alpha-melanotropin antiserum at a critical period of postnatal development.

Tonic inhibition of alpha-MSH secretion by the tubero-hypophyseal dopamine (DA) neurons of the rat starts at the end of the first postnatal week, after a peak in plasma MSH at days 5 and 6. In order to obtain information on the maturation of central control, we studied the development of alpha-MSH feedback on DA neurons and the possible role of circulating peptide. The characteristic response of these DA neurons to i.p. alpha-MSH, i.e., an acute rise in cellular fluorescence intensity as determined by microfluorimetry, was not yet detected at day 4 but present at day 8. When rats were injected i.v. with antiserum to alpha-MSH on days 5 and 6 and tested as adults, their DA neurons failed to react to i.p. alpha-MSH (2-100 micrograms/kg), but they were still responsive to prolactin (600 micrograms/kg). The DA system was already unresponsive to alpha-MSH at postnatal day 8. Antiserum injection on days 11 and 12, when plasma MSH is low, did not affect the reaction of DA neurons to alpha-MSH on day 14. These developmental processes were analogous in both sexes. Injections of control serum were ineffective. Our observations indicate that the feedback reaction of DA neurons to alpha-MSH develops in conjunction with the onset of inhibitory control of MSH release. The presence of alpha-MSH during a critical period appears to be necessary for the development of the responsiveness of DA neurons to the peptide hormone.

Aging↗

Analysis by HPLC-EC of metabolites of monoamines in fetal and postnatal rat brain.

High performance liquid chromatography with electrochemical detection (HPLC-EC) was adapted for the analysis of metabolites of monoamines (MA) in the developing brain of the rat. 3-Methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG), dihydroxy phenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-3-indoleacetic acid (5-HIAA) were found in significant amounts in forebrain of the foetal rat from gestational day (GD) 17. The development pattern of the four metabolites was essentially similar in male and female animals. Except for transient fluctuations at around birth, concentrations of metabolites increased gradually throughout late gestation and early postnatal life. In late gestation and at birth the absolute amounts were small, while the concentrations were comparable to adult levels.

3,4-Dihydroxyphenylacetic Acid↗

Implantation of PC12 cells into the corpus striatum of rats with lesions of the dopaminergic nigrostriatal neurons.

PC12 cells, which have the capacity to synthesize and release catecholamines, were implanted into the corpus striatum of adult rats with lesions of the dopaminergic nigrostriatal pathway. PC12 cells survived for 1-2 weeks in the host striatum and degenerated thereafter. The presence of these cells was associated with an attenuation of the apomorphine-induced circling behavior in rats with unilateral nigrostriatal lesions. These findings indicate that cells from a cell line are able, at least temporarily, to survive in the rat brain and to compensate functional deficits caused by lesions of specific neuronal systems. Cell lines might therefore be used for intracerebral grafting instead of neurons derived from fetal brains, if their survival can be prolonged and their proliferation in the host brain prevented.

Adrenal Gland Neoplasms↗

[Percutaneous transluminal coronary angioplasty: results after a 5-year follow-up period].

In the first series of 50 patients in whom percutaneous transluminal coronary angioplasty (PTCA) was attempted, the procedure was successful in 32. 23/32 patients were followed up clinically over 62.2 +/- 5.6 (SD) months. Repeated non-invasive laboratory tests were carried out in 15/23 patients. Moreover, 11/15 patients were restudied by arteriography at the end of the follow-up period. Early recurrence of the stenosis occurred in 5/32 patients (16%) and was again successfully treated by a second PTCA in 2. 3 patients underwent surgery as requested. 22/23 (95%) remained symptom-free during the follow-up period. The results of the non-invasive laboratory tests were in close agreement with the clinical findings. Coronary arteriography performed at the end of the follow-up period revealed an excellent lasting effect of PTCA in 8/11 patients. 2 showed a slight progression of the three stenoses treated by PTCA, and in 1 patient late recurrence of the stenosis was suspected since he had been symptom-free up to 2 weeks prior to restudy. Thus, in patients who are suitable for PTCA, this treatment is of long-lasting effect and represents an excellent alternative to coronary artery bypass surgery.

Adult↗

Prenatal nicotine affects fetal testosterone and sexual dimorphism of saccharin preference.

In order to study effects of nicotine on fetal gonadal axis and sexually dimorphic behavior, time-pregnant Sprague Dawley rats were implanted on gestational day (GD) 12 with an osmotic minipump containing either nicotine tartrate, tartaric acid or saline. Others were sham-operated on GD 12 or left untreated. Male fetuses of all control groups displayed the characteristic rise in plasma testosterone at GD 18 (as compared to GD 17 and 19); this was abolished by nicotine. Adult offspring of untreated or tartaric acid-treated dams exhibited a marked sexual dimorphism in their preference for saccharin-containing drinking water at 0.06-0.25%. No such sex difference was seen in offspring of nicotine-treated rats. In controls, the sexes differed with respect to the proportion of rats with high saccharin preference. In the group of males prenatally exposed to nicotine, the proportion of animals with high preference increased to the female level. These data indicate that prenatal exposure to nicotine can interfere with the development of the male gonadal axis and with the organization of sexually dimorphic behavior.

Animals↗

Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia.

The importance of nerve growth factor (NGF) for the development of sensory ganglia was investigated by injecting rat fetuses (16.50 days of gestation) with a single dose of anti-NGF antiserum. Four months later the treated animals showed a very large decrease in substance P- and somatostatin-like immunoreactivities in dorsal root ganglia and skin with a lesser decrease in trigeminal ganglia. Fluoride-resistant acid phosphatase, substance P-, and somatostatin-like immunoreactivities were greatly decreased in the dorsal horn of the spinal cord. No change in neurotensin- and [Met]enkephalin-like immunoreactivities was observed. The anti-NGF antiserum treatment produced a greater than 90% decrease in the number of unmyelinated dorsal root fibers and a 35% decrease in the total number of myelinated fibers. The loss in myelinated fibers was restricted to small-diameter fibers with no change in large-diameter fibers. No change in taste bud morphology was noted, thereby refuting the proposal that anti-NGF antiserum treatment may represent an animal model for familial dysautonomia. The present results indicate that NGF is a necessary requirement for the normal development of a significant population of prenatal rat dorsal root ganglion cells.

Aging↗

Early postnatal development of pituitary intermediate lobe control in the rat by dopamine neurons.

In fetal and postnatal rats, serum melanophore-stimulating hormone (MSH) levels, pituitary 3H-spiperone binding, pituitary catecholamine content, and other parameters were measured to characterize the development of pars intermedia pituitary control by the tubero-hypophyseal dopamine system. Bioassay of serum for MSH revealed low but significant levels 6 days before birth (gestational day 17), rising to a peak 4 days after birth (postnatal day 5). Levels declined after PN 6, reached a low 2 weeks after birth, and then rose gradually throughout the next several weeks until adult values were attained. From excised pituitaries, significant catecholamine fluorescence in the neurointermediate lobe was first demonstrated on the 2nd postnatal day, with the highest density of fibers being attained at 2 weeks after birth. Thereafter, the density of terminals decreased in the pars intermedia until the adult pattern of innervation was observed at day 60. Total dopamine content of the neurointermediate lobe roughly paralleled the morphological observations through the first 2 weeks after birth. Later, content was seen to stabilize, while concentration decreased in line with the reduction in terminal density. Dopamine levels exceeded norepinephrine concentration by a factor of 10. 3H-spiperone binding sites were present in the pituitary before birth. Their density increased rapidly in the neurointermediate lobe during the 2 postnatal weeks, then diminished until adult densities were reached at day 30. Binding in the anterior pituitary slowly rose throughout the first 30 days after birth, although values were only about one-quarter of that found in the neurointermediate lobe. In vitro incubation of neurointermediate lobes with dopamine showed a dose-dependent inhibition of spontaneous MSH secretion as early as 2 days after birth. Blockade of dopaminergic binding sites by i.p. administration of cis-flupenthixol (1 mg/kg) to rat pups had no effect until days 8, 15, and 22 where there was a significant rise in serum MSH levels as compared with controls. These data indicate that the intermediate lobe is responsive to dopamine at around birth, while the inhibitory dopaminergic control develops only during the 1st postnatal week, in conjunction with marked changes in circulating MSH levels.

Animals↗