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In this study, the experimental model of Wigglesworth was used to limit the maternal blood supply to the rat fetus and induce intrauterine growth retardation. The associated changes in plasma somatomedin activity, insulin, glucose, and cartilage metabolic activity are reported. The mean body weight ( ± SEM) of 108 fetuses in ligated uterine horns was significantly lower than that of 146 control fetuses (ligated, 2820 ± 50 mg; control, 3180 ± 50 mg; p< 0.001), as was mean nose-tail tip length (ligated, 55.6 ± 0.4 mm; control, 59.4 ± 0.3 mm; p< 0.001) and mean liver weight (ligated, 222 ± 5 mg; control, 274 ± 5 mg; p< 0.001). The uptake of [35S]sulfate by fetal costal cartilage in basal culture medium was significantly lower in growth-retarded fetuses than in controls. Plasma somatomedin activity measured by fetal rat cartilage bioas-say was significantly lower in growth-retarded than in control fetuses (p< 0.001). The growth-retarded fetuses were relatively hypoinsulinemic and hypoglycemic compared to control animals. These studies suggest that nutrient supply may become a limiting factor in the release of insulin and the circulating levels of somatomedin activity in the rat fetus, and hence in its growth.

ABSTRACT. In this study, the experimental model of Wigglesworth was used to limit the maternal blood supply to the rat fetus and induce intrauterine growth retardation. The associated changes in plasma somatomedin activity, insulin, glucose, and cartilage metabolic activity are reported. The mean body weight ( ± SEM) of 108 fetuses in ligated uterine horns was significantly lower than that of 146 control fetuses (ligated, 2820 ± 50 mg; control, 3180 ± 50 mg; p < 0.001), as was mean nose-tail tip length (ligated, 55.6 ± 0.4 mm; control, 59.4 ± 0.3 mm; p < 0.001) and mean liver weight (ligated, 222 ± 5 mg; control, 274 ± 5 mg; p < 0.001). The uptake of [35S]sulfate by fetal costal cartilage in basal culture medium was significantly lower in growth-retarded fetuses than in controls. Plasma somatomedin activity measured by fetal rat cartilage bioas-say was significantly lower in growth-retarded than in control fetuses (p < 0.001). The growth-retarded fetuses were relatively hypoinsulinemic and hypoglycemic compared to control animals. These studies suggest that nutrient supply may become a limiting factor in the release of insulin and the circulating levels of somatomedin activity in the rat fetus, and hence in its growth.

1. The effect of bilateral renal denervation on sodium excretion was studied in conscious rats on normal, low and high sodium diet, and in rats recovering from anaesthesia, as well as in anaesthetized rats fed a normal sodium diet. 2. Sodium excretion of bilaterally denervated conscious rats on normal sodium intake and during either 2 weeks of sodium depletion or 6 days of sodium loading was not different from that of controls, despite changes in sodium supply of more than two orders of magnitude. Cortical noradrenaline concentration of control kidneys was 138 +/‐ 12 ng/g, but was only 7 +/‐ 3 ng/g (P less than 0 . 001) 6 weeks after denervation. 3. In rats recovering from anaesthesia urine flow, sodium excretion and glomerular filtration rate (G.F.R.) were not affected by denervation. 4. In anaesthetized non‐diuretic rats on normal sodium diet chronic bilateral renal denervation increased urine flow and sodium excretion four and five times, respectively, with no changes in G.F.R. 5. Mean arterial blood pressure in bilaterally denervated anaesthetized rats and in those recovering from anaesthesia was decreased by 2 . 7 kPa, P less than 0 . 001 and 1 . 2 kPa, P less than 0 . 05, respectively. 6. The participation of renal nerves in the regulation of sodium excretion in conscious rats seems improbable. The denervation natriuresis in anaesthetized rats can be related to higher pre‐denervation renal sympathetic nervous activity due to narcosis and surgical stress.

The effects of morphine and fentanyl on plasma prolactin levels in rats have been measured. It was found that a prolonged immobilization stressful procedure for 5 h inhibited the response to morphine and fentanyl to increase prolactin secretion, but did not influence the increase in plasma prolactin caused by haloperidol. The injection of a large dose of cortisol (25 mg/kg, s.c.) also evoked an inhibition of morphine-induced prolactin release. The inhibition was maximal 24 h after the administration of the glucocorticoid. These results indicate that stress may induce prolonged alteration in endogenous opioid-mediated neuro-modulation via a prolonged release of glucocorticoids.J. Endocr.(1984) 101, 169–172

Plasma somatomedin activity, cartilage metabolism and the levels of insulin and growth hormone were studied during relative neonatal malnutrition in the rat, produced by the small and large litter method. In growth-retarded rats reduced somatomedin activity and raised growth hormone concentration were found. Neither basal cartilage activity nor cartilage responsiveness to somatomedin was altered in the growth-retarded animals.

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

The paper reports on the human interface problems between the knowledge engineer, an expert group and the general users. Experiences are derived from a several years' teamwork in computer-aided diagnosis and rehabilitation of newborn babies, neural lesions, although other different expert system design projects have been considered too. Details of the methods for getting acquainted with system analysis, system design, man-machine interface design, other realization aspects included economic and technical trade-offs are given. The lifetime of the system from the conception of ideas to marketing and support is overviewed. The paper can be treated as a short psychology of expert systems.

Extract: It seemed desirable and interesting to study the total energy expended during a period of several hours under conditions most commonly encountered under different infant care practices.The investigations were carried out on a total of 23 premature infants with a birth weight ranging from 1100 to 2120 g and aged from 2 to 31 days. Oxygen consumption was measured by an open circuit method using the Kipp diaferometer. Using three thermal conditions, measurements were started when four hours had elapsed after the last feed. Physical activity was observed and recorded continuously by an arbitrary method. The basal metabolic rate and the metabolic response to cold subtracted from the total metabolism measured under different experimental conditions gave the combined number of calories produced by specific dynamic action and physical activity. The information obtained from a previous study on specific dynamic action made it possible to approximate the calorigenic effect of food in the four series of examinations reported.Details of the studies carried out on premature infants while receiving human milk and kept in incubators with temperature maintained between 33–36° are shown in table I. In addition to the basal metabolic rate, total heat production observed throughout the observational period, calculated total daily heat production, and the percentage distribution of times spent in sleep and in physical activity with various intensity are also listed. The average total heat production observed exceeds the minimal metabolic rate by 9.8 kcal/kg/24 h per subject. If allowance is made for the specific dynamic action expected from the average daily intake of human milk (1.1 g protein/ml) 3.0 kcal/kg/24 h can be attributed to muscular activity. The magnitude of this component of the total energy expenditure is consistent with the markedly reduced physical activity exhibited by premature infants maintained in a thermally neutral environment.The results obtained on premature infants receiving an artificial formula containing 3.43% protein are listed in table II and shown diagrammatically in figure 1. The total daily caloric output averages 55.0 kcal/kg/24 h, a value roughly 39% above the basal rate, in contrast to the average increase of 25% observed in breast milk-fed infants. This difference in the combined quota of specific dynamic action and physical activity (8.8 and 15.3 kcal/kg/24 h, respectively) is due partly to the higher protein and caloric intake, and partly to the lesser proportion of time spent in deep sleep.Table III summarizes the results of studies of the energy exchange of five swaddled premature infants kept at a room temperature of 20–22°. It can be seen that the total daily heat production averages 58.3 kcal/kg/24 h, which is not appreciably greater than that observed in Adapta-fed infants maintained at neutral temperature. The extra calories above the basal amount to 18.6 kcal/kg/24 h, representing a 47 % rise above the minimal rate. This amount of heat includes not only the specific dynamic action and the activity quota, but also thermoregulatory heat production. The metabolic response to cold amounts roughly to 10 kcal/kg/24 h. The remaining extra calories above those required for basal heat production are partitioned between specific dynamic action and physical activity; this distribution is consistent with the proportion of times spent sleeping and with activity of various intensity. It is also consistent with the observation that the calorigenic effect of food manifests itself as an additional amount of heat in a heat-losing environment.Table IV presents the observations made on six premature infants kept unclothed at 28–29°. The total daily energy expenditure, almost 100% above that of basal heat production, averaged 80 kcal/kg: 41.3 for basal metabolism; 15.3 for chemical heat regulation without gross, visible muscular activity; 7.3 for specific dynamic action; and 16.1 for activity. The relative proportion of these components is shown in figure 3. The magnitude of the activity quota is readily explained by the percentage of time spent awake while displaying periodically increasing struggling and restless crying.Speculation: The results obtained have much bearing on the feeding of premature infants. It appears important to reevaluate the caloric needs for maintenance at neutral temperatures, since it has become increasingly accepted that the majority of small premature infants should be cared for under neutral thermal conditions. The observations suggest, in addition to the caloric need for maintenance, that the total caloric requirements are considerably lower than the widely employed figures used to approximate the caloric need of premature infants. Hence, the desirability of extending such studies to include the total caloric requirement is quite obvious. It would be most interesting to complete our knowledge concerning the adequacy and physiological basis of the caloric feeding of premature infants cared for under different thermal conditions.