Pharmacological characterization of the receptor mediating the adrenergic inhibition of responses to substance P in the cingulate cortex

The excitatory responses of neurones in the anterior cingulate cortex of the rat to iontophoretically applied substance P (SP) are reduced by noradrenaline (NA) applied iontophoretically or released from noradrenergic pathways. In order to determine the receptor involved in this inhibitory effect we have studied the effects of a number of receptor-specific adrenergic agonists and antagonists on responses of cingulate neurones to SP in rats anaesthetized with chloral hydrate. Low iontophoretic currents (0-15 nA) of NA, adrenaline and the beta-agonist, clenbuterol, all strongly reduced responses to SP. Isoprenaline was also effective but less consistently so, although problems were experienced with its iontophoretic release from micropipettes. The alpha 1-agonists, phenylephrine and methoxamine were also able to reduce responses to SP. However, this reduction required higher iontophoretic currents (15-60 nA) and was associated with depressant effects on baseline firing rate. The alpha 2-agonist clonidine was only weakly active at high currents and this too was associated with depression of baseline firing. Similar weak effects were noted with dopamine. The inhibitory effects of NA on SP responses were convincingly blocked or reversed by the beta-antagonist, practolol, but not by the alpha 1-antagonist, prazosin. The reduction of SP responses by phenylephrine was also blocked by practolol but unaffected by prazosin. Finally, reduction of SP excitations by activation of the coeruleocortical pathway was also blocked by practolol applied iontophoretically to the cortical cells. These results are consistent with the hypothesis that the effect of NA on SP responsiveness in the cingulate cortex is mediated by beta-adrenoreceptors.     

Effect of LHRH and its analogues on the progesterone secretion of human granulosa cells in vitro.

Progesterone secretion of cultured human granulosa cells treated with LHRH or its analogues was measured. Granulosa cells were also stimulated with LH, FSH, cAMP or forskolin. No differences could be observed in the progesterone basal secretion of cultures treated with or without LHRH or its analogues and after the various stimulations. It was concluded that the clinical experience that the sensitivity of ovaries for gonadotropins after LHRH desensitization is decreased could not be explained with the peripheral effects of LHRH on the granulosa cells. From the data obtained, the lack of LHRH receptors in the ovaries are suggested in humans.     

Vagal afferents innervating the gastrointestinal tract and CCKA-receptor immunoreactivity.

A large body of evidence derived from electrophysiological recording and pharmacological/behavioral experiments suggests the presence of CCKA-receptors on vagal primary afferent fibers innervating the gastrointestinal tract. With the availability of antibodies specific for the CCKA-receptor, we wanted to demonstrate its presence and distribution on identified vagal afferent fibers and different types of terminals in the mucosa, myenteric plexus, and external muscle layers of the stomach and duodenum. In the duodenal mucosa, neither a C-terminal (Ab-1) nor an N-terminal (Ab-2) specific antibody produced any specific staining; in the myenteric plexus, non-vagal enteric neurons and their processes, but not vagal intraganglionic laminar endings (IGLEs), exhibited CCKAR-immunoreactivity. Similarly, in the gastric myenteric plexus, a population of enteric neurons and their processes, but not identified vagal IGLEs, were labeled by both antibodies. In both external muscle layers of the stomach, CCKAR-immunoreactive axons were in close register with labeled vagal afferent intramuscular arrays, but the two labels were not contained in the same varicosities. Ab-1 immunoreactivity was found in the cell membrane of vagal afferent perikarya in the nodose ganglia and in pancreatic acinar cells. The failure to detect CCKAR-immunoreactivity in peripheral vagal afferent terminals cannot be due to methodological problems because it was present in enteric neurons in the same sections, and because it did not stain structures resembling IGLEs in material without the potentially masking vagal afferent label. We conclude that CCKA-receptors on vagal afferent terminals: 1) are below the immunohistochemical detection threshold, 2) exhibit a conformation or affinity state inaccessible to the two antibodies, or 3) are not transported to the peripheral terminals.     

Effects of EPF treatment in human mononuclear cells.

Early Pregnancy Factor (EPF) is one of the earliest pregnancy associated signals, communicating the ensuing pregnancy to the maternal organism. Data published by others on the mouse suggest that EPF bound to spleen cells causes the release of two H2-restricted "suppressor factors" responsible for the rosette inhibiting activity of EPF in the rosette inhibition test. Using human material, we were able to detect the release of a second entity from mononuclear cells that is able to suppress rosette formation in the human rosette inhibition test. In an attempt to show an intracellular EPF effect in the target cell, cytosolic free calcium concentrations were measured in EPF-treated mononuclear cells from peripheral blood. Our findings did not, however, show any changes of intracellular free Ca(2+)-concentrations under the chosen conditions.     

An Organotypic Spinal Cord - Dorsal Root Ganglion - Skeletal Muscle Coculture of Embryonic Rat. II. Functional Evidence for the Formation of Spinal Reflex Arcs In Vitro

Electrical properties of motoneurons, muscle fibres and dorsal root ganglion (DRG) cells were studied in an organotypic coculture of embryonic rat spinal cord, dorsal root ganglia and skeletal muscle. The motoneurons were identified by their morphology and position in culture. Their size and input conductance were significantly larger than those of spinal interneurons. Intracellular current injection evoked action potentials in all motoneurons, but only evoked stable repetitive firing patterns in some. Excitability was correlated to somatic size and the rate of spontaneous excitatory input. It is suggested that the somatic growth and the increase in excitability is regulated by the excitatory afferents. The motoneurons showed spontaneous excitatory and inhibitory postsynaptic potentials and action potentials which disappeared with the application of various agents known to inhibit excitability or excitatory synaptic transmission. Excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs respectively) were distinguished by their shape, reversal potential and pharmacology. IPSPs could be depolarizing or hyperpolarizing in different cells. A higher percentage of cells with hyperpolarizing IPSPs was found in older cultures and in the presence of skeletal muscle, suggesting a reversal of the polarity of IPSPs with development. The spontaneous muscle contractions observed in the cultures could be due either to innervation, spontaneous oscillations of the membrane potential, or electrical coupling between neighbouring fibres. A small percentage of DRG cells showed spontaneous action potentials, all of which were found in cultures with spontaneous muscle contractions. The electrical stimulation of DRG afferents evoked mono- and polysynaptic EPSPs in motoneurons, endplate potentials and muscle contractions. The stimulation of the ventral horns evoked endplate potentials and muscle contractions via mono- or polysynaptic pathways. Together these results indicate that appropriate and functional contacts were established in the culture between myotubes and DRG cells, between DRG cells and motoneurons, and between motoneurons and muscle fibres.     

Epidemiologie von Krebs während der Schwangerschaft

Zusammenfassung Die Diagnose Krebs in der Schwangerschaft ist ein seltenes Ereignis. Die Inzidenz wird auf 1:1000 geschätzt. Die am häufigsten diagnostizierten Krebsarten in der Schwangerschaft sind in absteigender Reihenfolge: Zervixkarzinom, Mammakarzinom, malignes Melanom, Hodgkin-Lymphom und akute Leukämien. In seltenen Fällen treten Schilddrüsenkarzinome, Non-Hodgkin-Lymphome, chronische Leukämien, maligne Ovarialtumoren, Kolon- und Nierenkarzinome auf. In einer populationsbasierten Studie der Jahre 1970–1979 konnte gezeigt werden, dass bei schwangeren Frauen im Alter von 15–19 Jahren die Inzidenz von Krebsfällen bei 2:100.000 Lebendgeburten lag. Im Alter von 40–44 Jahren war die Inzidenz 230:100.000 Lebendgeburten. Eine transplazentare Metastasierung ist selten. Krebsregister werden zukünftig mehr Informationen über den Zusammenhang von Krebs während der Schwangerschaft ermöglichen.     

Longitudinal Assessment of Food Intake, Fecal Energy Loss, and Energy Expenditure After Roux-en-Y Gastric Bypass Surgery in High-Fat-Fed Obese Rats

Background

The efficacy of Roux-en-Y gastric bypass (RYGB) surgery to produce weight loss has been well-documented, but few studies have measured the key components of energy balance, food intake, and energy expenditure longitudinally.

Methods

Male Sprague-Dawley rats on a high-fat diet underwent either RYGB, sham operation, or pair feeding and were compared to chow-fed lean controls. Body weight and composition, food intake and preference, energy expenditure, fecal output, and gastric emptying were monitored before and up to 4 months after intervention.

Results

Despite the recovery of initially decreased food intake to levels slightly higher than before surgery and comparable to sham-operated rats after about 1 month, RYGB rats maintained a lower level of body weight and fat mass for 4 months that was not different from chow-fed age-matched controls. Energy expenditure corrected for lean body mass at 1 and 4 months after RYGB was not different from presurgical levels and from all other groups. Fecal energy loss was significantly increased at 6 and 16 weeks after RYGB compared to sham operation, and there was a progressive decrease in fat preference after RYGB.

Conclusions

In this rat model of RYGB, sustained weight loss is achieved by a combination of initial hypophagia and sustained increases in fecal energy loss, without change in energy expenditure per lean mass. A shift away from high-fat towards low-fat/high-carbohydrate food preference occurring in parallel suggests long-term adaptive mechanisms related to fat absorption.