Cardiovascular and endocrine responses to feeding in the young calf.

A number of cardiovascular and endocrine responses which occur during and after feeding in the unweaned calf are described. 2. There was a substantial increase in both heart rate and mean aortic blood pressure during feeding in these animals. This occurred within the first few seconds and persisted throughout the period of ingestion. 3. The concentrations of glucose, insulin and gastrin in arterial plasma rose abruptly during, or immediately after, feeding and elevated values persisted for at least 2 hr. A transient increase in glucagon concentration was also observed. In contrast, feeding appeared to produce no immediate rise in enteroglucagon concentration. 4. The adrenal output of glucocorticoids rose transiently in response to feeding but that of catecholamines was unaffected. 5. Cardiovascular responses to feeding were also examined in other species. In unweaned kids the changes were essentially similar to those observed in the calf but were less pronounced. In lambs a persistent hypertension occurred which was associated with a brief initial tachycardia. In adult dogs ingestion of solid food also caused tachycardia but although the aortic blood pressure rose for a short period at the beginning of feeding, hypotension developed thereafter. 6. The possibility that both the cardiovascular and endocrine responses, which occur during or immediately after feeding, are mediated by the autonomic nervous system is discussed.     

Prophylactic treatment of very premature infants with human surfactant

We undertook a randomized, controlled trial to determine whether human surfactant administered endotracheally at birth to very premature infants (gestational age, 24 to 29 weeks) would prevent the respiratory distress syndrome or reduce its severity. Thirty-one treated infants (birth weight, 938 +/- 286 g) were compared in a blinded fashion with 29 control infants (birth weight, 964 +/- 174 g). The lecithin/sphingomyelin ratio was less than 2 in all infants, and phosphatidylglycerol was not present in amniotic fluid or tracheal fluids at birth, indicating a deficiency of surfactant in the lungs. The principal dependent variables were neonatal death, the incidence of bronchopulmonary dysplasia, and the infant's requirement for respiratory support (and its complications). The surfactant-treated group had significantly fewer deaths than the control group (16 percent vs. 52 percent, P less than 0.001), fewer cases of bronchopulmonary dysplasia (16 percent vs. 31 percent), and significantly fewer cases of pulmonary interstitial emphysema (P less than 0.001) and pneumothorax (P less than 0.02). Prophylactic treatment with human surfactant also substantially reduced the period of neonatal intensive care. We conclude that treatment with human surfactant offers promise for improving the survival of very premature infants with a surfactant deficiency and for reducing the pulmonary sequelae of the respiratory distress syndrome.     

c-Fos protein expression in the rat subfornical organ following osmotic stimulation.

To examine the role of the subfornical organ (SFO) in the osmotic activation of hypothalamic neurons, the responses of the SFO to osmotic stimulation were evaluated by using c-Fos protein immunohistochemistry. Numerous c-Fos-immunoreactive nuclei were found in the SFO of rats injected i.p. with hypertonic saline solution as early as 30 min after stimulation, and the effect lasted up to 3 h. Only a few c-Fos-positive cells were detected in the SFO of rats injected with isotonic saline. However, electrolytic lesions of the SFO did not prevent the osmotic activation of the hypothalamic paraventricular and supraoptic nuclei. These data suggest that the SFO and the hypothalamic magnocellular nuclei are simultaneously but separately activated by osmotic stress.     

The hormonal responses to repetitive brief maximal exercise in humans

Summary The responses of nine men and nine women to brief repetitive maximal exercise have been studied. The exercise involved a 6-s sprint on a non-motorised treadmill repeated 10 times with 30 s recovery between each sprint. The total work done during the ten sprints was 37,693±3,956 J by the men and 26,555±4,589 J by the women (M > F,P<0.01). This difference in performance was not associated with higher blood lactate concentrations in the men (13.96± 1.70 mmol·^–1) than the women (13.09±3.04 mmol·l^–1). An 18-fold increase in plasma adrenaline (AD) occurred with the peak concentration observed after five sprints. The peak AD concentration in the men was larger than that seen in the women (9.2 +- 7.3 and 3.7 ± 2.4 nmol · l^–1 respectively,P<0.05). The maximum noradrenaline (NA) concentration occurred after ten sprints in the men (31.6±10.9 nmol·l^–1) and after five sprints in the women (27.4 ± 20.8 nmol · l^–1). Plasma cardiodilatin (CDN) and atrial natriuretic peptide (ANP) concentrations were elevated in response to the exercise. The peak ANP concentration occurred immediately postexercise and the response of the women (10.8 ± 4.5 pmol · l^–1 was greater than that of the men (5.1 ± 2.6 pmol · l^–1,P<0.05). The peak CDN concentrations were 163 ± 61 pmol · l^–1 for the women and 135 ± 61 pmol · l^–1 for the men. No increases in calcitonin gene related peptide (CGRP) were detected in response to the exercise. These results indicate differences between men and women in performance and hormonal responses. There was no evidence for a role of CGRP in the control of the cardiovascular system after brief intermittent maximal exercise.     

Senescent changes in a neurobiological model system: Cerebellar Purkinje cell electrophysiology and correlative anatomy

A within-subjects design was used to assess age changes in cerebellar Purkinje neurons. Four groups of naive male Sprague-Dawley rats, aged 3, 10, 20, and 28 months, underwent single cell recording for electrophysiological assessment of Purkinje cell firing patterns, followed by perfusion for glyoxylic acid induced catecholamine fluorescence. Cerebellar sections were photographed first by fluorescence microscope for catecholamines, and 2–3 weeks later for quantification of lipofuscin autofluorescence. Finally, these same tissues were treated with cresyl violet and photographed a third time to permit quantitative estimates of age changes in the number of Nissl staining Purkinje neurons. Electrophysiological studies revealed significant effects of age on a number of Purkinje cell firing parameters: in particular, increasing numbers of aberrant, very slow-firing cells were encountered in older animals. These cells showed normal climbing fiber mediated burst activity, but spontaneous simple spike firing rates 3–5 times less than normal. Rats exhibiting the highest numbers of such abnormal cells also exhibited the poorest Nissl staining. Conversely, good Nissl staining of Purkinje neurons in an old rat was a reliable predictor of relatively normal Purkinje cell firing. Lipofuscin was found to accumulate measurably in Purkinje neurons by 20 months of age, and to increase significantly thereafter. Deposition of the substance occurred almost exclusively at the apical pole of the soma. Our data suggest, however, that accumulation of lipofuscin in Purkinje neurons, as well as its reported accumulation in the inferior olive, is not a primary cause of electrophysiological dysfunction. There was no apparent age change in glyoxylic acid induced catecholamine fluorescence nor, in separate pharmacological studies, could any senescent alteration in cerebellar catecholamine levels be found.     

The role of the autonomic innervation in the control of glucagon release during hypoglycaemia in the calf

1. The extent to which the autonomic innervation to the pancreas is implicated in the control of glucagon release during hypoglycaemia has been investigated in calves 3-6 weeks after birth.2. A pronounced rise in plasma glucagon concentration occurred in normal conscious calves in response to hypoglycaemia following administration of insulin (0.1 u./kg). Prior treatment with atropine caused no significant change in the hypoglycaemic response to insulin in these animals but the rise in plasma glucagon concentration was delayed.3. Section of both splanchnic nerves produced no significant change in the tolerance of conscious calves to this small dose of insulin and the changes in plasma glucagon concentration in these animals were within the normal range.4. In contrast, the same dose of insulin produced severe hypoglycaemia, accompanied by convulsions, in atropinized calves with cut splanchnic nerves. In spite of the intensity of the hypoglycaemic stimulus the rise in plasma glucagon concentration was both delayed and diminished in these animals.5. Administration of atropine alone (0.2 mg/kg) to normal fasting calves produced a significant fall in the mean plasma concentrations of both glucose and glucagon (P < 0.01) within 30 min, without affecting that of insulin.6. A significant increase in plasma glucagon concentration also occurred in response to stimulation of the peripheral ends of the thoracic vagi in adrenalectomized calves with cut splanchnic nerves under barbiturate anaesthesia. A rise in mean plasma glucose concentration was also observed in these experiments and found to be significantly correlated with the glucagon response.7. It is concluded that changes in either sympathetic or parasympathetic efferent activity may modify plasma glucagon concentration in the conscious calf, but that only the latter mechanism is likely to be implicated in the response to changes in plasma glucose concentration within the physiological range.     

Quantitative analysis of peptide levels and neurogenic extravasation following regeneration of afferents to appropriate and inappropriate targets

We have studied quantitatively the levels of substance P and calcitonin gene-related peptide in nerves innervating skin and muscle of rats, and examined the effects of cross-anastomosing these nerves so that they regenerate to an inappropriate target. We have also compared the ability of nerves to induce neurogenic extravasation with their peptide content. Peptide was measured by radioimmunoassay in the proximal section of ligated peripheral nerves, and neurogenic oedema was measured by determination of Evans Blue extravasation induced by either systemic capsaicin treatment or topical mustard oil application. The levels of these peptides are higher in cutaneous nerves than muscle nerves. This cannot be explained by differences in the number of fibres in the nerves studied. The levels of peptides fall when cutaneous afferents reinnervate muscle, and rise when muscle afferents reinnervate skin. We suggest that these changes occur because of some tissue-specific trophic influence arising from the tissue innervated. The ability to produce extravasation in skin is highly correlated with the substance P and calcitonin gene-related peptide levels of its innervation, even when this occurs in inappropriate nerves which do not normally produce extravasation.     

What — if any — is the role of adrenergic mechanisms in histamine release from mast cells?

The effects of catecholamines on histamine release from rat peritoneal mast cells, was studied in an in vitro system. It was found that norepinephrine (10^–5–10^–3 M) exerts a significant, dose related, repressive effect on compound 48/80-induced histamine release. This effect is greatly potentiated by -antagonists and is noticeable throughout the concentration range 10^–11–10^–3 M norepinephrine. Phentolamine diminishes the repressive effect that norepinephrine shows at 10^–5 M.Norepinephrine (10^–5 M) totally inhibits the progressive histamine release induced by both compound 48/80 and strontium (10 M) in non-Ca²⁺-depleted cells. The release that is dependent on extracellular calcium is inhibited by norepinephrine.The repressive effect of norepinephrine at 10^–3 is counteracted by 5.6 mM d-glucose, 2-deoxyglucose abolishes this effect. The repression of histamine release by 10^–5 M norepinephrine is not influenced byd-glucose.These results suggest that the effects on histamine release, observed within a low concentration range of norepinephrine (<10^–3 M), may be due to -adrenoreceptor mechanisms and an interference in transmembrane calcium transport. Our data further suggest that norepinephrine at 10^–3 M may inhibit oxidative phosphorylation.Isoproterenol and epinephrine (10^–9–10^–5 M) show little effect on 48/80-induced histamine release in a normal medium. However, when calcium is excluded from the medium, histamine release is potentiated. These results seem to indicate that isoproterenol and epinephrine act by displacing intracellular calcium, making it available for the exocytosis process.     

Unilateral atrophoderma of Pasini and Pierini

Atrophoderma of Pasini and Pierini usually appears as isolated, round to oval depressed areas of otherwise normal-appearing skin. The clinical appearance has been likened to "footprints in the snow" or depressions with "cliff drop" borders. The condition is of unknown cause and most commonly occurs on the back, but it is occasionally seen elsewhere on the body. A literature search revealed only one previous report of unilateral atrophoderma of Pasini and Pierini.