Effects of epidermal growth factor on lung maturation in fetal lambs

The ability of epidermal growth factor (EGF) to induce lung maturation was evaluated in fetal and neonatal lambs. EGF was infused (3-5 days) into one member of 10 fetal twin pairs, one member of 2 term twin pairs, and 2 singleton term lambs. All EGF-treated lambs had evidence of epithelial hyperplasia of the conducting airways typical of the EGF effect. With the exception of the most immature pair, the lungs of treated versus control lambs were judged more mature by morphologic criteria by use of light and electron microscopy. None of the 6 premature lambs treated with EGF and allowed to breath showed evidence of hyaline membrane disease, while 3 untreated control lambs developed typical hyaline membranes when delivered by cesarean section after maternal hypotension. All untreated control animals showed more severe clinical symptoms of respiratory distress than did the EGF-treated animals.     

Effects of partial hepatectomy on plasma fibronectin concentrations in the rat.

Rats were subjected to 60% partial hepatectomy. In the immediate postoperative period, there was a small decline in plasma fibronectin concentrations, which was normalized already 12 h post-operatively. Metabolic labelling of fibronectin with 35S-methionine showed that the rate of incorporation of label was unchanged after partial hepatectomy. However, when the abdominal viscera were excluded from the circulation, no incorporation of label was found. These results show that the rate of fibronectin biosynthesis has the rapid regulation characteristics of an acute phase reactant. Peripheral tissues do not contribute significantly to the plasma fibronectin concentration. Intra- or retro-peritoneal viscera, most likely the liver, are responsible for the synthesis of rat plasma fibronectin.     

Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings.

In a study of whether oscillations in plasma glucose and insulin occur in human beings, plasma samples were taken at one-minute intervals from 10 normal subjects for periods lasting between one and two hours. In five subjects the basal plasma insulin concentrations cycled regularly, with a mean period of 13 minutes and mean amplitude of 1.6 mU per liter (11.5 pmol per liter). A concurrent plasma glucose cycle was demonstrated, with a mean amplitude (after averaging to minimize random error) of 0.05 mmol per liter (1 mg per decliter). The average plasma glucose cycle was two minutes in advance of the plasma insulin. In the subjects with less regular plasma insulin cycles, a similar plasma glucose rise was demonstrated two minutes before the insulin rise. These phase relations are compatible with the presence of a negative-feedback loop between the liver and pancreatic beta cells that regulates both basal plasma insulin and glucose concentrations, although the cyclic beta-cell secretion could be independent of plasma glucose.     

Effects of V.M.H. lesions on plasma insulin in the goose

The effects of bilateral electrolytic lesions of the ventromedial hypothalamus (V.M.H.) were examined in male geese. In addition to the known effects (hyperphagia, obesity and liver steatosis), V.M.H. lesions slightly increased plasma insulin level in the fasting and the fed state and largely enhanced insulin levels observed during an oral glucose and amino acid load. Therefore, V.M.H. lesions potentiate insulin release which may in turn participate in the development of hyperphagia and fattening in the goose as in mammals.     

Effects of alpha- and beta-adrenergic stimulation on free magnesium concentrations in platelets from healthy and obese individuals.

We performed this study to investigate whether alpha- and beta-adrenergic agonists are able to regulate intracellular free magnesium concentrations [Mg2+]i in platelets from healthy and obese individuals. Twenty-six informed-consent men (14 healthy and 12 obese) were enrolled in the study. We measured fasting plasma glucose, insulin, epinephrine and norepinephrine. Platelet [Mg2+]i at the baseline and after stimulation with clonidine or isoproterenol was measured by fluorescent probe mag-fura-2. In platelets from healthy subjects, alpha-adrenergic stimulation by clonidine led to a dose-dependent decrease in [Mg2+]i (basal: 245 +/- 39 microM; clonidine 5 pg/mL: 109 +/- 27 microM, p < 0.05; clonidine 10 pg/mL: 77 +/- 26 microM, p < 0.01), while no significant change in platelet [Mg 2+]i was detected in obese men. Furthermore, the co-incubation with clonidine (10 pg/mL) and yohimbine (50-100 pg/mL) completely abated the effect of clonidine on [Mg2+]i in platelets from healthy individuals. Analysis of the time course for platelet magnesium showed that the intracellular magnesium loss induced by clonidine (10 pg/mL) was time-dependent. Conversely, the beta-adrenergic agonist isoproterenol was able to produce a significant rise in [Mg2+]i in platelets from healthy individuals (basal: 234 +/- 40 microM; isoproterenol 2.5 pg/mL: 594 +/- 44 microM, p < 0.05: isoproterenol 5 pg/mL: 681 +/- 56 microM, p < 0.01), while no such finding was detectable in platelets from obese patients. When platelets from healthy subjects were co-stimulated with isoproterenol (5 pg/mL) and propranolol (10-20 pg/mL), the ionophoric effect of the beta-adrenergic agonist was completely reverted. The time course of isoproterenol (5 pg/mL) effect on platelet [Mg2+]i showed that the ionophoric effect of isoproterenol was time-dependent. In conclusion, (1) the stimulation of alpha-adrenergic receptor by clonidine is able to induce a significant dose- and time-dependent fall in platelet [Mg2+]i; (2) the stimulation of beta-adrenoceptors by isoproterenol lead to a signifcant time- and dose-dependent rise in platelet [Mg2+]; (3) the ionic effect of alpha- and beta-adrenergic stimulation is not detectable in obese subjects, in whom is probably present a reduced sensitivity to the ionic effect of adrenergic agonists.     

Inability of fetal skin to induce allograft tolerance in fetal lambs.

Fetal lambs of 53-55 days gestation invariably failed to accept skin allografts from fetal donors of similar age but retained allografts from adult donors. Autografts of skin were accepted by 53-55-day fetuses. When the survival of allografts transplanted from fetal donors of a range of gestational ages was examined, skin from fetuses of up to 85 days was rejected but that from a 95-day donor was retained. Histological examination of fetal skin allografts revealed that these were subject to lymphocytic invasion, evident as the entry of lymphatic vessels and extravasation of lymphocytes within the first week after placement. These manifestations of an allograft reaction became more prominent during the following 2 weeks, with graft rejection being evident by the end of a month. Allografts of adult skin were subject to occasional focal lymphocytic infiltration but otherwise healed in uneventfully.     

Absence of fetal placental waterfall phenomenon in chronically prepared fetal lambs.

An electromagnetic flow sensor was placed on the distal fetal aorta (umbilical flow fraction 78.1 +/- 1.6 SEM, %), an inflatable occluder was tied around the umbilical cord, and catheters were placed in distal branches of an umbilical artery and vein, a uterine vein, and in the amniotic cavity. An inflatalbe occluder was tied around the vagina of some of the ewes. Control values 3 days after surgery were (mean +/- SE): fetal femoral artery pH, 7.37 +/- 0.01; umbilical blood flow, 186 +/- 14 ml-min-1 .kg fetus-1; fetal arterial blood pressure, 39 +/- 3 mmHg; and umbilical venous pressure, 7.4 +/- 1.0 mmHg (above intrauterine pressure). Fetal weight at autopsy was 3.1 +/- 0.3 kg, n = 11. Small increases in umbilical vein pressure caused immediate decreases in placental blood flow without decreases in fetal arterial blood pressure. The relation between venous pressure and umbilical blood flow at constant arterial pressure was that of an inert system, i.e., no evidence of a surrounding pressure (Starling resistor effect or waterfall phenomenon) could be found with increases in venous pressures of 2-40 mmHg. The results were not affected by increases in uterine vein pressure between 2 and 30 mmHg, nor by anesthesia and supine position of the ewe, nor by ganglionic blockade of the fetal ANS. It was concluded that surrounding pressures in the fetal placental circulation could not be demonstrated.     

The effects of ACTH on lung maturation in fetal lambs.

The ability of adrenocorticotrophic hormone (ACTH) to induce lung maturation was evaluated in fetal lambs. One member of 14 twin pairs between 114 and 138 days of gestation was infused intravenously with 0.5 mg ACTH over 5 days. The lungs of treated versus control lambs were judged more mature by morphologic criteria by the use of light and electron microscopy and by biochemical criteria by the use of lamellar-body-rich cell fractions. None of 5 premature lambs treated with ACTH and allowed to breathe showed evidence of hyaline membrane disease, while 3 untreated control lambs showed typical hyaline membranes.     

Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

AIMS--To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS--Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS--Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS--The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.     

Sleep,wakefulness and the monosynaptic reflex in fetal and newborn lambs

1. Electrocorticogram (ECoG), electromyogram (EMG) of the lateral rectus and antigravity muscles (neck and masseter) and breathing activity (FB) were monitored in chronically prepared fetal sheep of 125–140 days gestation and in newborn lambs up to 11 days postnatal age.
2. Awake state (AW), non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) were defined using standard criteria for ECoG, eye movements and postural muscle tone.
3. The percentage of time the fetuses spent in each state was: NREM sleep 53%, REM sleep 41.4%, and AW 5.6%.
4. Spontaneous intrauterine breathing activity occurred only during REM sleep, but 35% of REM sleep was not associated with FB.
5. Gasps (isolated deep inspirations) appeared occasionally throughout the recording and were not related to any specific sleep state or wakefulness.
6. In the fetus, the monosynaptic reflex (MSR) induced by direct electrical stimulation of the fibular nerve was enhanced by about 75% during REM sleep compared to NREM and AW. In the newborn lamb the adult pattern of suppression of MSR during REM sleep was not seen until several days after birth.

     

Effects of external potassium concentrations on the cell sodium and potassium contents of isolated rat kidney tubules

The effects of 20 mol/l amiloride, 10 mol/l furosemide and 1 mmol/l ouabain on cell Na and K concentrations were investigated by flame microphotometry in isolated rat medullary collecting tubules and medullary thick ascending limbs (MCT and MAL) as a function of the external potassium concentration [K_e]. The results are expressed as Na and K concentrations per liter cell volume ([Na_c] and [K_c], mmol/l) and relative sodium content, [Na_c]/([Na_c]+[K_c]). From the experimental curves, [K_e]_1/2 is defined as the [K_e] value corresponding to half maximal exchange of K against Na in cells. When [K_e] was 5 mmol/l, the relative Na content was less than 15% in control and amiloride-treated MCT as well as in control and furosemide-treated MAL, and about 24% in ouabain-treated MCT and MAL. In MCT, relative cell Na content increased up to 90% or more when [K_e] was reduced from 2.5 to 0.25 mmol/l. [Ke]_1/2 was 0.55, 0.45 and 1.25 mmol/l for control, amiloride-treated and ouabain-treated MCT respectively. In MAL, similar increases in relative Na content were observed when [K_e] was reduced from 0.5 to 0.05 mmol/l. [K_e]_1/2 was 0.25, 0.10 and 1.75 mmol/l for control, furosemide-treated and ouabain-treated MAL respectively. When [K_e] was reduced from 5 to 1 mmol/l, [Na_c] dropped from 16.4 to 8.4 mmol/l (P<0.01) in control MAL. When [K_e] was 5 mmol/l, [Na_c] was lower in furosemide-treated MAL (7.8 mmol/l) than control MAL (P<0.01). At 1 mmol/l [K_e], [Na_c] was similar in both groups.These results are discussed in terms of the balance between the active and passive components of Na and K fluxes across apical and basolateral cell membranes. They indicate that a K-dependent passive Na entry process exists in the membranes of MAL cells but not of MCT cells. This process was proportionally more inhibited than the active Na pump when [K_e] was reduced from 5 to 1 mmol/l. In addition, it was found sensitive to furosemide. It presumably corresponds to the luminal 1 Na-1 K-2 Cl contransport mechanism known to exist in the thick ascending limb.     

The influence of blood sample treatment on plasma potassium concentrations in avian blood

Plasma potassium concentrations were determined in racing pigeons (Columba livia domestica), chickens (Gallus domesticas) and man (Homo sapiens) after different storage times of uncentrifuged blood samples at room temperature. In the pigeon plasma potassium concentrations declined rapidly. After 10 min the reduction was 9.5% and declined by 65% after 120 min. No further reduction was noted up to 24 hours. In chickens decreases were also noted but were smaller overall with a 29% decrease being noted after 2 hours. No significant changes of plasma potassium concentrations in human blood were found during the first 2 hours of storage. The need to describe the treatment of blood after sampling is indicated. It is concluded that for most blood chemical measurements plasma is preferred to serum and blood samples should be centrifuged within minutes of sampling.     

Effects of oral administration of maltitol on plasma glucose,plasma sorbitol,and serum insulin levels in man

Summary The present study was aimed to investigate the metabolic effects of acute and chronic oral administration of maltitol (4-O-i-d-glucopyranosyl-d-glucitol), a hypocaloric sweetener obtained from maltose by catalytic hydrogenation. Fifty grams of maltitol induced a increase lower glycemic and insulinemic than the same dose of glucose or sucrose. No variations of plasma glucose and serum insulin levels were observed after 180 min. A slight increase of plasma maltitol was observed 45 min after maltitol. The chronic administration of maltitol (10 g 3× daily for 5 days) induced no variations of glycemia or insulinemia when compared with the same dose of sucrose. Plasma sorbitol levels were slightly higher after maltitol than after sucrose. Low amounts of maltitol were detected in the urine and feces.Abbreviations AUC Areas Under the Curves - BG Blood Glucose - IRI Immuno Reactive Insulin - SEM Standard Error of Mean - TID Ter In Die     

Effects of partial hepatectomy on plasma fibronectin concentrations in the rat

Rats were subjected to 60% partial hepatectomy. In the immediate postoperative period, there was a small decline in plasma fibronectin concentrations, which was normalized already 12 h post-operatively. Metabolic labelling of fibronectin with 35S-methionine showed that the rate of incorporation of label was unchanged after partial hepatectomy. However, when the abdominal viscera were excluded from the circulation, no incorporation of label was found. These results show that the rate of fibronectin biosynthesis has the rapid regulation characteristics of an acute phase reactant. Peripheral tissues do not contribute significantly to the plasma fibronectin concentration. Intra- or retro-peritoneal viscera, most likely the liver, are responsible for the synthesis of rat plasma fibronectin.     

Kinetics of plasma potassium concentrations during exhausting exercise in trained and untrained men

The purpose of this study was to examine the time course of changes in plasma potassium concentration during high intensity exercise and recovery in trained and untrained men. The subjects performed two exercise protocols, an incremental test and a sprint, on a cycle ergometer. A polyethylene catheter was inserted into the antecubital vein to obtain blood samples for the analysis of plasma electrolyte concentrations and acid-base parameters, during and after exercise. During both tests, venous plasma sodium, potassium and chloride concentrations increased in all the subjects, although the largest relative increase was detected in potassium concentration - 35% and 31% over rest in the progressive test and 61% and 37.7% in the sprint test, for cyclists and controls, respectively. After exercise plasma potassium concentration decreased exponentially to below resting values. There was a linear correlation between the amount of potassium accumulated in plasma during exercise and the amount eliminated from plasma when the exercise ceased. We found that, although plasma potassium accumulation occurred in both forms of exercise in the trained and nontrained subjects, the time constant of potassium decrease following exercise was shorter in the trained subjects. Thus, the trained subjects exhibited a better capacity to recover to resting concentrations of plasma potassium. We propose that the extracellular potassium accumulation acts as a negative feedback signal for sarcolemma excitability depending on the muscle metabolic rate.