Standards for nursing administration. A team approach to implementation.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Gibbs.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In the past 10 years, numerous gut peptides have been tested for their satiating effect on food intake. Cholecystokinin (CCK), bombesin, pancreatic glucagon, and somatostatin have the best supporting evidence for such a specific behavioral effect. The satiety effect of CCK, somatostatin, and glucagon is abolished or markedly reduced by abdominal vagotomy, but the satiety effect of bombesin is not. The effect of vagotomy has been interpreted as the result of the loss of vagal afferent fibers that are necessary for carrying information about visceral effects of these peptides to the brain. This hypothesis is under active investigation. There are three reports that CCK decreases the size of a test meal in lean and obese humans. This suggests that CCK or the other peptides may be useful in treating human obesity and bulimia.
Explore the source record for details and available documents.
Sprague-Dawley male albino rats ate sweet milk at the midpoint of the day or night phase of a 12:12 light/dark cycle 1 min after IP 0.9% NaCl or synthetic bombesin (BBS; 2-32 micrograms/kg) following 24-hr food deprivation. Exogenous BBS inhibited food intake in a dose-related manner during the day; a linear regression line accounted for 85% of the total variance for percentage suppression of food intake by BBS in 30 min. In contrast, inhibition of eating by BBS at night was not dose-related; a linear regression line accounted for only 16% of the variance. Rats were tested under identical conditions following 3-hr food deprivation. Exogenous BBS (4-64 micrograms/kg) inhibited food intake in a dose-related manner at night; a linear regression line accounted for 92% of the total variance. In contrast, inhibition of eating by BBS during the day was not as orderly; a linear regression line accounted for only 44% of the variance. The 8 micrograms/kg dose was twice as potent for inhibition of eating of 25% GIBCO 116EC liquid diet than it was for inhibition of eating sweet milk at the midpoint of the day phase. These results describe diurnal variation in potency of exogenous BBS for inhibition of food intake in the rat. Whether BBS is more or less potent at night than during the day depends upon the particular dose, degree of hunger of the rat, and probably the type of food being eaten.
Litorin (LIT), a bombesin-like nonapeptide, decreased food intake in rats in a dose-related manner after parenteral injection. LIT decreased deprivation-induced water intake only at a dose much higher than required to suppress feeding. LIT administration did not significantly alter the frequency of observed feeding-associated behaviors, nor did it result in subsequent aversion to an associated novel solution. Litorin shares with bombesin structural features and pharmacological actions that include the suppression of food intake in a manner that mimics natural satiation.
Explore the source record for details and available documents.
An analysis of the effect of combinations of chlorambucil and indomethacin, or chlorambucil and prostaglandin E2 (PGE2) on the growth of alkylating agent sensitive and resistant Walker carcinoma in vitro has been made by the isobologram approach. Indomethacin alone acts as a growth inhibitor of the Walker carcinoma. High concentrations of indomethacin (5 microgram/ml) act to inhibit the growth of the resistant line sub-additively with chlorambucil, whereas low concentrations act additively. For the sensitive line indomethacin acts either additively or supra-additively with chlorambucil at all concentrations employed. Both indomethacin and low concentrations of chlorambucil alone inhibit PGE2 secretion into the culture medium of both cell lines and an enhanced inhibition is seen with the combination. PGE2 itself acts as a growth inhibitor of both cell lines, although it causes greater growth inhibition of chlorambucil resistant Walker carcinoma (LD50 1.8 microgram/ml) than of the sensitive line. This correlates with a greater PGE2 secretion capacity by the resistant cell line (40 pg PGE2/ml medium/10(5) cells for the resistant tumour and 17 pg PGE2/ml medium/10(5) cells for the sensitive tumour). Combinations of PGE2 with chlorambucil inhibit growth either additively or sub-additively. It seems unlikely that inhibition of PGE2 secretion is responsible for the interactive effects of chlorambucil and indomethacin, since growth inhibition produced by the combination is not reversed by PGE2 at any of the concentrations employed. Possible mechanisms of the interactive effects are discussed.
Bombesin (BBS, 0.1-4.0 micrograms) administered to the lateral cerebral ventricle (IVT) of rats decreased food intake and feeding behavior. Grooming behavior increased and resting behavior decreased as doses greater than or equal to 0.01 microgram. IVT BBS (4.0 micrograms) caused greater suppression of food-deprivation-induced food intake and feeding behavior than the same dose and volume administered intraperitoneally (IP). After IVT BBS, rats displayed more grooming and less resting than normal, but after IP BBS, rats displayed a normal frequency of grooming and more resting. IVT BBS (greater than or equal to 0.01 microgram) also decreased drinking behavior, and drinking-associated feeding, and suppressed (greater than or equal to 0.1 microgram) water-deprivation-induced water intake. When neither food nor water was present, non-deprived rats displayed increased grooming and decreased resting after IVT BBS (1.0 microgram). The results show that IVT BBS inhibits feeding markedly, but the inhibition of feeding by IVT BBS does not resemble normal satiety or the effect of IP BBS because the central inhibition of feeding is always accompanied by excessive grooming and little resting. Furthermore, since IVT BBS decreases drinking at a dose lower than that required to reduce food intake, and IP BBS does not, the specific satiety effect of IP BBS on feeding cannot be mediated solely by increasing bombesin in the cerebrospinal fluid.
The effect of lateral hypothalamic injections of bombesin on feeding behavior was examined. Rats equipped with stainless steel cannulas directed toward the lateral hypothalamus received bilateral injections of bombesin prior to access to a liquid test diet after a 3 hr food deprivation. Bombesin in doses of 5 ng, 50 ng and 100 ng produced significant reductions in the size of the first meal. Injection of 50 ng of the biologically weak analogue [D-Trp8] bombesin had no effect. Injection of 5 ng or 50 ng of bombesin had no effect on deprivation-induced water intake, and injection of 50 ng of bombesin had no effect on body temperature. The food and water intake data and direct quantitative behavioral measures indicated that lateral hypothalamic injections of bombesin specifically reduced food intake. The structure-activity relationship for this effect was similar to those for other actions of bombesin. A bombesin-like peptide in the lateral hypothalamus or its receptors may play a role in postprandial satiety.
Explore the source record for details and available documents.
The satiety effect of cholecystokinin (CCK) that was first observed in rats has now been extended to chickens, rabbits, pigs, sheep, rhesus monkeys, lean mice, genetically obese mice and rats, neurologically obese rats, lean men and women, and obese men. The effect is specific and can be obtained in animals and humans without reports or signs of sickness. The mechanism of the effect is unknown, but the gastric vagal fibers are necessary for the effect. This has led to the hypothesis that the satiety effect is due to activation of vagal afferent fibers that inhibit the central control system of feeding by CCK acting directly on recently described vagal CCK receptors and/or indirectly through a gastric smooth muscle effect that vagal receptors are sensitive to.
Intraperitoneal injections of tetradecapeptide bombesin (BBS) produced large, dose-related suppressions of liquid and solid food intake in rats, with threshold doses of 1--2 micrograms-kg-1. The feeding-associated behaviors of rats receiving BBS by this route at a test meal were normally sequenced, and several other observations suggested that the effect of BBS was specific and not due to malaise. The structurally related amphibian peptide litorin and the structurally related mammalian gastrin-releasing peptide (GRP) produced similar suppressions of food intake. The satiety effect of BBS administered intraperitoneally did not require the accumulation of food in the gut, the presence of intact adrenals, the abdominal vagus, or the release of cholecystokinin. When BBS and cholecystokinin were administered simultaneous, the suppressive effects on food intake were additive. Lateral cerebroventricular injections of BBS also produced large, dose-related suppressions of food intake, with a threshold dose of 100 ng per rat. The effect by this route, however, was not behaviorally specific: BBS produced equivalent inhibitions of food and water intake at every point on the dose-response curve, and produced a marked increase in grooming which dominated the behavioral display. Thus, (1) peripheral BBS is a putative satiety signal in the rat; (2) the class (endocrine, paracrine, or neural) and mechanism of this satiety action is not established; and (3) the differences in specificity and behavior following intraperitoneal and cerebroventricular routes indicate that peripheral BBS does not act solely via the cerebrospinal fluid to elicity satiety.
Rats injected with bombesin of LiCl showed similar suppression of food-deprivation-induced liquid diet intake, but only rats receiving LiCl avoided water-deprivation-induced consumption of a novel saccharin solution paired with injection. The data demonstrate that bombesin reduces feeding but does not induce conditioned aversion, and suggest that bombesin does not act to suppress food intake by production of gastrointestinal malaise.
Bombesin (2-16 microgram-kg-1, intraperitoneally) inhibited food intake in rats after abdominal vagotomy. Since the same vagotomized rats did not respond to the octapeptide of cholecystokinin (1-8 micrograms-kg-1, intraperitoneally), these data are decisive evidence (1) that bombesin does not produce satiety by releasing endogenous cholecystokinin and (2) that vagal afferents are not necessary for the satiety effect of bombesin.
A sham-feeding preparation utilizing rhesus monkeys was employed to investigate the anatomical site of origin of satiety signals in the gastrointestinal tract. A series of experiments in which food was diverted from the stomach, the small intestine, or both demonstrated that (a) food acting at the pregastric level is not sufficient to produce normal-sized meals, (b) the accumulation of food in the small intestine is necessary to produce normal-sized meals, and (c) a potent preabsorptive or postabsorptive satiety signal originates at the intestinal level. This unidentified satiety signal is sufficient to elicit satiety, can be dissociated from gastric emptying, and does not require the presence of gastric distention to operate.
A xenograft line, HX 53, has been established in immune-suppressed mice from a specimen of a lymph node metastasis in a patient with a histological diagnosis of seminoma but with markedly raised circulating levels of alpha-fetoprotein. Histological, immunocytochemical, and ultrastructural studies of this xenograft line have suggested that a solid variant of yolk sac carcinoma may exist, which morphologically resembles seminoma, or that a continuum of differentiation exists between seminoma and yolk sac carcinoma.
Explore the source record for details and available documents.