RESUMEN
BACKGROUND: Adipose tissue has emerged as an important endocrine regulator by secreting hormones referred to as adipokines. Recent studies showed that adipose tissue considerably responds to hypoxia. Although the impact of white adipose tissue on regulative processes is established, the importance of brown adipose tissue in adults has emerged just recently. METHODS: Brown (BA) and white adipocytes (WA) were cultured either in the presence of chemical hypoxia-mimetics or under hypoxic atmosphere of 1% oxygen. Expression of hypoxia-inducible factor 1α (HIF- 1α) was assessed by western blot. The expression levels of several known HIF-1α-regulated proteins [vascular endothelial growth factor (VEGF), leptin, adiponectin, and angiotensinogen (AGT)] were quantified. RESULTS: Both chemical hypoxia-mimetics and physical hypoxia led to increased nuclear HIF-1α expression and to decreased cytoplasmatic adiponectin in both cell types. In contrast, VEGF and AGT expression did not change upon hypoxic stimulation. Leptin was exclusively detectable in WA, while uncoupling-protein 1 (UCP-1) was expressed in BA only. CONCLUSIONS: WA and BA are sensitive to hypoxia, in which HIF-1α expression is induced. Protein expression of adiponectin is hypoxia-dependent, whereas AGT, VEGF, leptin, and UCP-1 expression do not change secondary to hypoxia.
Asunto(s)
Adipocitos Blancos/metabolismo , Adipoquinas/metabolismo , Tejido Adiposo Pardo/metabolismo , Hipoxia/metabolismo , Adipocitos Blancos/citología , Tejido Adiposo Pardo/citología , Animales , Antimutagênicos/toxicidad , Células Cultivadas , Cobalto/toxicidad , Deferoxamina/toxicidad , Hipoxia/inducido químicamente , Immunoblotting , Leptina/metabolismo , Ratones , Sideróforos/toxicidadRESUMEN
BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is activated by cAMP-dependent phosphorylation. CFTR channel activity is also stimulated by cGMP-dependent protein kinase and protein kinase C. RESULTS: Here, we show that CFTR channel activation by cGMP may also occur directly. In oocytes from one-third of Xenopus donors, the activation of CFTR by cGMP averaged 87% of the level achieved by cAMP. The currents activated by either cyclic nucleotide displayed similar current-voltage relationships, kinetics, pharmacology and halide selectivity. Sequential stimulation by cAMP and cGMP was not additive, suggesting that both cyclic nucleotides activate the same channel; cGMP was one order of magnitude more potent than cAMP, and its action was insensitive to protein kinase inhibitors. Analysis of the amino-acid sequence of CFTR revealed a domain in the amino-terminal portion of the third cytoplasmic loop that resembles a class of cyclic-nucleotide-binding domains related to that of the catabolite-gene activator protein, CAP. Two CFTR residues in this domain--Val397 and Lys420--were identified which, when changed to alanine, altered the response to cGMP independently of the response to cAMP. CONCLUSIONS: We conclude that direct cyclic nucleotide binding may play a role in channel gating of CFTR. The cGMP-binding domain may provide a useful target for pharmacologic intervention in cystic fibrosis.
Asunto(s)
AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Secuencia de Aminoácidos , Animales , Aniones , Sitios de Unión , Proteína Receptora de AMP Cíclico/química , Regulador de Conductancia de Transmembrana de Fibrosis Quística/química , Regulador de Conductancia de Transmembrana de Fibrosis Quística/efectos de los fármacos , Citosol , Humanos , Isoquinolinas/farmacología , Datos de Secuencia Molecular , Oocitos , Proteínas Recombinantes , Homología de Secuencia de Aminoácido , Relación Estructura-Actividad , Xenopus laevisRESUMEN
Protein- and fat-rich test meals elicit a strong stimulatory effect on postprandial somatostatin (SLI) and pancreatic polypeptide (PP) release, whereas carbohydrate-rich meals rather attenuate the response of both hormones. Since there is evidence that intestinal hormones might contribute to the postprandial SLI and PP response, it was the aim of the present study to determine in dogs the effect of low-dose cholecystokinin octapeptide (CCK-8) on basal hormone levels and also during a background infusion of amino acids or glucose. In a group of six conscious dogs, sulfated CCK-8 was infused intravenously (i.v.) via a hindleg vein at stepwise increasing infusion rates of 10, 30, and 50 pmol X kg-1 X h. The infusion of CCK was applied during a background infusion of saline (2 ml/min), glucose (0.2 g/min), or an amino acid mixture (8.5%, 2 ml/min). CCK-8 had no effect on plasma insulin and glucagon levels under all experimental conditions. Plasma SLI levels were significantly stimulated by all doses of CCK. This stimulatory effect was similar during background infusions of either saline, glucose, or amino acids, respectively. Pancreatic polypeptide (PP) levels rose 200-300 pg/ml during CCK plus saline. This was slightly attenuated by glucose. During CCK plus amino acids, the PP response was augmented to 600-800 pg/ml. Since secretin is also released after the ingestion of a meal and intraduodenal acidification is a potent stimulus not only of secretin but also of gastric and pancreatic SLI release, the effect of secretin was examined additionally.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Aminoácidos/farmacología , Glucosa/farmacología , Polipéptido Pancreático/metabolismo , Secretina/farmacología , Sincalida/farmacología , Somatostatina/metabolismo , Animales , Glucemia/análisis , Perros , Glucagón/sangre , Insulina/sangre , Polipéptido Pancreático/sangre , Somatostatina/sangreRESUMEN
In the present study, the effects of orally administered beta-casomorphins (beta-CM) and met-enkephalin on postprandial plasma somatostatin-like immunoreactivity (SLI) were assessed in conscious dogs. The intragastric instillation of a liver extract-sucrose test meal containing 12 mg beta-CM or 10 mg met-enkephalin, respectively, augmented the postprandial rise of peripheral vein plasma SLI levels significantly. This effect was inhibited by the additional administration of the specific opiate-receptor antagonist, naloxone. When liver extract-sucrose was dissolved in fresh bovine milk the increase of plasma SLI levels was significantly greater than liver extract-sucrose dissolved in water. This milk-induced augmentation of SLI levels was also reduced by naloxone. Since these opiate-active compounds have an influence upon insulin release when given iv, the effect of beta-CM-7, beta-CM-5, beta-CM-4 beta-CM-4-amide, and met-enkephalin on SLI levels was assessed during their iv infusion at a rate of 1 nmol/kg . h during an iv background infusion of a glucose-amino acid mixture. The infusion of beta-CM-5 elicited a stimulation of peripheral vein SLI levels, whereas the infusion of met-enkephalin resulted in a significant decrease of SLI levels. beta-CM-7, beta-CM-4, and beta-CM-4-amide had no effect on plasma SLI levels at the dose employed. The present data demonstrate that in dogs the ingestion of opiate-active peptide stimulates postprandial SLI release, indicating that nutrient-contained opiate-active material (exorphins) might participate in the regulation of postprandial gastrointestinal endocrine function.
Asunto(s)
Caseínas/farmacología , Endorfinas/farmacología , Somatostatina/metabolismo , Aminoácidos/metabolismo , Animales , Perros , Ingestión de Alimentos , Encefalina Metionina/farmacología , Cinética , Naloxona/farmacologíaRESUMEN
In this study, an examination was made of the sites in the brain of the rat at which the injection of cholecystokinin octapeptide (CCK-8) would alter food intake. Rats fasted for 24 hr received intracerebral injections of CCK-8 (1 nmol) or an equal volume of saline (0.5 microliters), into various sites in the brain through permanently implanted stainless steel cannulae. After prior acclimatisation to individual plexiglass compartments, latency to feed, as well as consumption of food and water during 0-20, 20-40 and 40-60 min after the injection, were recorded. The available food was the standard rat pellets, to which the animal otherwise had constant daily access. With this paradigm, active sites at which CCK-8 suppressed feeding were defined as sites at which consumption of food for 0-20 min was reduced by 25% or more, or the latency to feed was increased by 3 min or more after the injection of CCK-8, as compared to the effect of the injection of saline, made at the same site. Such active sites were most densely distributed in the rostral diencephalon, e.g. hypothalamus, the medial pontine area and lateral medulla, in the vicinity of the nucleus tractus solitarii (NTS). By grouping data for injections according to histologically identified sites, statistical analysis of groups of injections confirmed that these three major areas of the brain were active with regard to the suppression of feeding by CCK-8. These data suggest that CCK may not only initiate satiety messages, as a circulating hormone at peripheral sites, but also participate in the conduction of such information to the target in the brain by serving as a neurotransmitter in the lateral medulla (e.g. NTS), medial pontine area (e.g. relay station between the NTS and hypothalamus) and the lateral hypothalamus, where local release of CCK-8 after stomach loading has been observed.
Asunto(s)
Química Encefálica/efectos de los fármacos , Encéfalo/anatomía & histología , Conducta Alimentaria/efectos de los fármacos , Sincalida/farmacología , Animales , Mapeo Encefálico , Conducta de Ingestión de Líquido/efectos de los fármacos , Privación de Alimentos , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Endogámicas , Sincalida/administración & dosificaciónRESUMEN
The neuropeptide cholecystokinin (CCK), which is localized within the hypothalamus in integrative centers of feeding regulation, can suppress feeding behavior when exogenously applied into the lateral hypothalamus. Moreover, the endogenous peptide can be released from the same brain locus by stimuli that physiologically are associated with satiety (i.e., gastric meal loads). This endogenously released CCK contributes to the inhibition of feeding behavior during meal intake. These data strongly suggest that hypothalamic CCK may play a physiological role in the termination of feeding behavior. The presence of additional sites sensitive to CCK in extrahypothalamic regions (e.g., medial pons and lateral medulla) argue that the CCK receptor systems may functionally (1) have several links in a linear chain or (2) exist as several parallel systems. The relevance of these extrahypothalamic loci for feeding regulation will require further studies which need to be directed towards the physiological role of the endogenously released CCK in these particular areas, by use of selective CCK antagonists.
Asunto(s)
Encéfalo/fisiología , Colecistoquinina/farmacología , Colecistoquinina/fisiología , Conducta Alimentaria/efectos de los fármacos , Saciedad/fisiología , Animales , Encéfalo/efectos de los fármacos , Ingestión de Alimentos/fisiología , Humanos , Hipotálamo/fisiología , Saciedad/efectos de los fármacos , Nervio Vago/fisiologíaRESUMEN
Somatostatin release in dogs is modulated by exogenous and endogenous opioids. Since postprandial somatostatin secretion is in part due to the stimulatory effect of postprandially activated gastrointestinal hormones as well as endogenous opioids, it was of interest to determine the interaction between motilin, a known stimulus of somatostatin release, and endogenous opioids with regard to activation of D-cell function. In a group of eight conscious dogs the infusion of synthetic porcine motilin at doses of 0.05, 0.25 and 0.5 micrograms/kg X hr elicited a significant increase of peripheral vein plasma somatostatin-like immunoreactivity (SLI), confirming previously reported data. The additional infusion of the opiate receptor antagonist naloxone attenuated this SLI response, suggesting that endogenous opioids participate in motilin-induced SLI release. Since previous studies have shown that the interaction between endogenous opioids and postprandial somatostatin secretion is modified by elevated plasma glucose levels, the experiments were repeated during an IV glucose (0.2 g/min) background infusion increasing circulating glucose levels by 20-30 mg/dl. During IV glucose, the SLI response to motilin was almost abolished. In this group the addition of naloxone restored the SLI response, indicating that the inhibitory effect of elevated glucose on D-cell function is, at least in part, mediated by endogenous opioids. These data suggest that motilin has to be considered as one regulatory factor which participates in the previously observed interaction between glucose and endogenous opioids during postprandial SLI release.
Asunto(s)
Motilina/farmacología , Naloxona/farmacología , Somatostatina/metabolismo , Animales , Glucemia/análisis , Perros , Glucosa/farmacología , Motilina/antagonistas & inhibidores , RadioinmunoensayoRESUMEN
Cholecystokinin octapeptide (CCK-8), administered intracerebroventricularly (i.c.v.), will suppress feeding. The aim of the present study was to determine the pharmacological characteristics of this satiety inducing effect in rats. For this purpose, we employed a feeding bioassay model in 24 h fasted rats and examined the effects of CCK-8 and a variety of structurally related analogs on latency to feed after i.c.v. injection and on the amount of food and water consumed as measured after the initiation of feeding in sequential 20-min epochs for 1 h. CCK-8, given in doses of 0.1, 1 and 10 nmol, produced a dose-dependent increase in feeding latency and a reduction of food intake during the first 20 min after initiation of feeding. Food intake during the next 40 min and water consumption were not altered. Plasma levels of CCK-like immunoreactivity after an i.c.v. injection of a dose of CCK-8 which blocked feeding (10 nmol) rose insignificantly from 117 to 125 pg/ml. In contrast, at the minimally effective dose of CCK-8 after i.v. administration (10 nmol), which also produced an inhibition of feeding, the plasma level was 1430 pg/ml. This difference indicates that plasma levels of CCK after i.c.v. CCK-8 are not adequate to produce the observed feeding suppression and suggests that the effects of i.c.v. CCK-8 are not mediated by a peripheral redistribution. Systematic dose response studies revealed the following rank order of potencies: CCK-8 greater than or equal to G-17 II much greater than CCK-8 NS = G-17 I greater than or equal to CCK-4 = CCK 26-29 = 0. Only gastrin-17 II (sulfated) produced an effect comparably significant to CCK-8. I.c.v. proglumide at 2500 nmol failed to modify the effects of CCK-8 at 10 nmol after i.c.v. injection. These data demonstrate that the structural requirements for feeding suppressive activity in rat brain are the carboxyterminus with a sulfated tyrosine residue, located 6 to 7 residues from the carboxyterminus, as present in CCK-8 and gastrin-17 II.
Asunto(s)
Ventrículos Cerebrales/fisiología , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Sincalida/farmacología , Animales , Ventrículos Cerebrales/efectos de los fármacos , Colecistoquinina/análogos & derivados , Colecistoquinina/sangre , Colecistoquinina/farmacología , Privación de Alimentos , Inyecciones Intraventriculares , Masculino , Proglumida/farmacología , Ratas , Ratas Endogámicas , Sincalida/administración & dosificaciónRESUMEN
In the rat the exact role of vagal fibers and the interaction between the extrinsic and intrinsic neural system in distention-induced gastrin release are still a matter of debate. Accordingly, the aim of the present study was to examine the contribution of afferent and efferent vagal fibers as well as intrinsic neurons on gastrin response to gastric distention. In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent increase of plasma gastrin levels by 12+/-6 pg/ml (5 ml saline, n = 8, P =0.05), 26+/-7 pg/ml (10 ml saline, n = 10, P < 0.05) and 37+/-7 pg/ml (15 ml saline, n = 8, P < 0.01 ), respectively. To examine the role of the extrinsic vagal innervation, gastrin response to distention was studied in anesthetized rats after bilateral truncal vagotomy (n = 9) or selective afferent vagotomy following pretreatment with capsaicin (n = 6). Stimulation of gastrin release by 10 ml distention in sham-operated control rats was reversed to an inhibition after truncal vagotomy (26+/-7 vs. -11+/-4 pg/ml; P<0.05) and capsaicin-treatment (37+/-18 vs. -34+/-11 pg/ml; P<0.05). A contribution of cholinergic mechanisms to this vagovagal-mediated stimulation of distention-induced gastrin release was excluded, since atropine (100 microg/kg/h; n = 8) further augmented distention-stimulated gastrin release. Since bombesin/gastrin-releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin secretion, we have examined gastrin response to distention in the presence of the specific bombesin-receptor antagonist D-Phe6-BN(6-13)OMe (400 microg/kg/h: n = 10). This bombesin-antagonist completely reduced distention-stimulated gastrin release in vivo. In contrast, distention of the isolated, extrinsically denervated stomach significantly decreased gastrin release by 13+/-5 pg/min (5 ml saline, n = 8, P < 0.05), 28+/-8 pg/min (10 ml saline, n = 11, P < 0.05) and 35+/-10 pg/min (15 ml saline, n = 8, P < 0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release was attenuated to 50 percent by atropine (10(-7) M: n = 10) or tetrodotoxin (TTX) (10(-6) M; n = 10), respectively. These data demonstrate, that in anesthetized rats distention-stimulated gastrin secretion depends on the activation of a vagovagal reflex and intrinsic bombesin/GRP-neurons. In contrast distention of the isolated rat stomach inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms.
Asunto(s)
Bombesina/metabolismo , Gastrinas/metabolismo , Neuronas/metabolismo , Péptidos/metabolismo , Nervio Vago/fisiología , Animales , Atropina/farmacología , Bombesina/análogos & derivados , Bombesina/farmacología , Capsaicina/farmacología , Ingestión de Alimentos , Péptido Liberador de Gastrina , Masculino , Parasimpatolíticos/farmacología , Fragmentos de Péptidos/farmacología , Ratas , Ratas Wistar , Receptores de Bombesina/antagonistas & inhibidores , Estómago/inervación , Tetrodotoxina/farmacología , VagotomíaRESUMEN
The release of cholecystokinin-like immunoreactivity (CCK-LI) from feline hypothalamus was studied in relation to a meal by use of the push-pull perfusion technique. While levels of CCK-LI in the perfusate of overnight-fasted anesthetized cats were below assay sensitivity (less than 7 pg/30 min), intragastric administration of a carbohydrate-amino acid meal elicited a 3-fold increase in CCK-LI, identified by high-performance liquid chromatography as the C-terminal octapeptide of CCK (CCK-8). Examination of an extrahypothalamic site showed no comparable release in CCK-LI. Intravenous infusions of CCK-8 at doses imitating physiological blood levels up to 400 times higher than those seen after physiological stimulation demonstrated the existence of a CCK blood-brain barrier in the lateral hypothalamus. These observations provide support that CCK may play a physiological role in termination of feeding behavior.
Asunto(s)
Colecistoquinina/metabolismo , Nutrición Enteral , Hipotálamo/metabolismo , Neuronas/fisiología , Saciedad , Respuesta de Saciedad , Animales , Gatos , Colecistoquinina/análisis , Cromatografía Líquida de Alta Presión , Femenino , Hipotálamo/efectos de los fármacos , Cinética , Masculino , Perfusión , Saciedad/efectos de los fármacos , Respuesta de Saciedad/efectos de los fármacos , Sincalida/farmacología , Factores de TiempoRESUMEN
Central administration of neuropeptide Y (NPY) induces food intake in freely feeding animals and this effect is mediated by hypothalamic sites. Little is known, however, about the effect of NPY on food intake and site of action in food-deprived animals. To examine this further, 24-h fasted rats received injections of saline or NPY into the lateral cerebral ventricle (10 micrograms/10 microliters; n = 8) or into the lateral (LH) or ventromedial hypothalamus (VMH) (1 microgram/0.5 microliters; n = 44). In addition, intracerebroventricular (i.c.v.) injections of NPY were carried out with or without i.c.v. naloxone (25 micrograms), a specific opioid receptor antagonist. During the first 40 min food intake was not different with or without NPY. After 60 and 120 min, food intake was 5.9 +/- 0.4 g and 8.3 +/- 0.6 g with i.c.v. saline which was significantly augmented by i.c.v. NPY to 8.7 +/- 0.9 g and 14.4 +/- 1.5 g, respectively (P less than 0.05). This increase in food consumption was due to a prolongation of feeding time. The opioid receptor antagonist naloxone significantly augmented latency to feed, both in the absence and presence of NPY (8.0 vs 1.7 min or 14.7 vs 2.8 min, respectively) and abolished the NPY-induced increase in food intake. Following intrahypothalamic injection of NPY, an increase in food intake (greater than 20%) was observed in 50% of the histologically identified LH and VMH sites, but only in 15% of the injection sites outside the LH/VMH.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Ventrículos Cerebrales/fisiología , Ayuno/fisiología , Conducta Alimentaria/efectos de los fármacos , Naloxona/farmacología , Neuropéptido Y/farmacología , Animales , Ventrículos Cerebrales/efectos de los fármacos , Diencéfalo/efectos de los fármacos , Diencéfalo/fisiología , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Inyecciones Intraventriculares , Masculino , Naloxona/administración & dosificación , Neuropéptido Y/administración & dosificación , Ratas , Ratas Endogámicas , Valores de Referencia , Factores de TiempoRESUMEN
Peptides related to the amphibian octapeptide xenopsin are present in various locations in mammalians, such as the gastrointestinal mucosa or brain tissue. In the gastrointestinal tract, xenopsin-related peptides induce partially neurogenic contractions of the colon in humans. In brain, however, their function is not known. Structural similarities of xenopsin-related peptides with neurotensin, a known modulator of ingestive behavior, suggest a possible role in feeding regulation. Therefore, we examined the effect of xenin, a recently identified xenopsin-related pentacosa peptide, on feeding behavior of fasted rats. Male Wistar rats (n=12) were intracerebroventricularly (i.c.v.) injected with either saline (10 microl) or xenin at 0.5, 1.5, 5 or 15 microg dissolved in an identical volume of 10 microl, respectively. In further experiments, xenin 15 microg/0.5 microl or 0.5 microl saline were injected into the lateral hypothalamus (LH). After injections, food intake (g), percentage of time spent with feeding (%) and prandial water intake (ml) were subsequently recorded for 2 h. After i.c.v. injection of 15 microg of xenin 1-h food intake was significantly reduced by 42% and 2-h food intake was diminished by 25%, respectively, compared to saline injection (p<0.01). This reduction of food intake was paralleled by a significant decrease of time spent with feeding by 41% (after 1 h) or 23% (after 2 h). The xenin-induced suppression of feeding behavior was dose-dependent. Thus, the minimal effective dose of xenin was 1.5 microg, while the dose of 0.5 microg was ineffective. Prandial water intake was significantly reduced only by the highest dose of xenin. Following injection of 15 microg of xenin into the lateral hypothalamus food intake was not different from control experiments. These data demonstrate a potent feeding suppressive action of xenin following intracerebroventricularly injection but not injection into the lateral hypothalamus suggesting a possible role of xenin in the central control of feeding termination and satiety.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Hormonas Gastrointestinales/farmacología , Péptidos/farmacología , Proteínas de Xenopus , Secuencia de Aminoácidos , Animales , Ayuno , Hormonas Gastrointestinales/química , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Inyecciones Intraventriculares , Masculino , Microinyecciones , Datos de Secuencia Molecular , Neurotensina/química , Oligopéptidos/química , Péptidos/química , Ratas , Ratas Wistar , Saciedad/efectos de los fármacos , Cloruro de Sodio/farmacologíaRESUMEN
Cholecystokinin octapeptide (CCK-8) is known to suppress feeding in sheep, pigs, golden hamsters and rats following acute intracerebroventricular (i.c.v.) injection. In this study, we report the effects of chronically administered i.c.v. CCK-8 on long-term food intake in rats. After baseline food intake was established over a period of 3 days, rats were implanted with Alzet osmotic minipumps, which delivered 1.0 microliter/h. Three groups of animals were prepared which received saline (vehicle) or CCK-8 at 12.25 micrograms/day (low dose) or CCK-8 at 122.5 micrograms/day (high dose). Surgical preparation of the animals with the intraventricular cannula and the osmotic minipump resulted in an initial reduction in food consumption in all groups. In the saline group daily food consumption returned to presurgery values by day 4. Similar results were observed with the low dose of CCK-8. In contrast, in animals receiving the high concentrations of CCK-8, the initial fall in feeding was more prominent and though it rose during the 7-day infusion interval, it remained statistically below control during this period. After termination of the infusion, daily food consumption rose to normal levels during the next 3 days. For comparison, the cumulative difference between daily food consumption over the period of 8 days during infusion and pre-infusion control was 39.9 +/- 10.0 g/24 h in the saline group. In CCK-8-infused animals, food consumption after pump implantation was reduced by an integrated value of 35.5 +/- 5.0 g/24 h at low dose and 117.4 +/- 20.2 g/24 h at high dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Encéfalo/fisiología , Conducta Alimentaria/efectos de los fármacos , Sincalida/farmacología , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Ritmo Circadiano/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Conducta de Ingestión de Líquido/efectos de los fármacos , Bombas de Infusión , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Endogámicas , Sincalida/administración & dosificaciónRESUMEN
By use of the push-pull perfusion technique, release of neuronal cholecystokinin-like immunoreactivity (CCK-LI) from hypothalamus of owl monkeys was investigated in relation to an intragastric meal. In overnight fasted, halothane-anesthetized owl monkeys, levels of CCK-LI in the hypothalamic push-pull perfusate were below assay sensitivity (less than 4 pg/30 min). After intragastric administration of a carbohydrate/amino acid meal, however, a 10-fold increase in CCK-LI release (51 +/- 7 pg/30 min) was observed in 5 out of 15 perfusion sites during the first postprandial 30 min. During the subsequent two 30-min intervals, release of CCK-LI was still increased with 32 +/- 5 pg/30 min and 15 +/- 6 pg/30 min, respectively. Thereafter, CCK-LI release was below assay sensitivity again. Addition of 40 mM potassium chloride (KCl) to the perfusion solution, which causes neuronal depolarization, resulted in a second increase in CCK-LI release of 56 +/- 7 pg/30 min which was comparable to the meal-induced release. All sites that exhibited an increase in CCK-LI were located in the anterolateral aspect of the hypothalamus. In experiments without meal-induced release, KCl did not have any effect on CCK-LI in perfusate, suggesting that these particular sites did not contain CCK-releasing terminals. High performance liquid chromatography (HPLC) identified the C-terminal octapeptide of CCK (CCK-8) as the predominant molecular form of CCK within the owl monkey hypothalamus. No gastrin-17 was present.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Colecistoquinina/metabolismo , Ingestión de Alimentos , Hipotálamo/metabolismo , Animales , Aotus trivirgatus , Hipotálamo/fisiología , Radioinmunoensayo , Factores de TiempoRESUMEN
Areas of signal loss in brain overlying air-containing structures at the skull base are commonly observed on axial fast MR images. The nature of this effect, which can mimic the appearance of cerebral hemorrhage, is investigated in a phantom study and in a normal volunteer. The magnitude of the signal loss is found to be inversely related to the distance of the scanning plane from the air-containing structure and directly related to the echo time.
Asunto(s)
Neoplasias Encefálicas/patología , Hemorragia Cerebral/patología , Malformaciones Arteriovenosas Intracraneales/patología , Imagen por Resonancia Magnética/métodos , Encéfalo/patología , Humanos , Modelos AnatómicosRESUMEN
Dural venous sinus thrombosis is an important complication of L-asparaginase chemotherapy. The diagnosis and followup of this condition, using spin echo and fast imaging techniques, is described in three patients. Magnetic Resonance (MR) imaging is a rapid, noninvasive technique for diagnosis and follow-up of this condition. Fast imaging techniques can improve the assessment of these patients.
Asunto(s)
Asparaginasa/efectos adversos , Duramadre , Imagen por Resonancia Magnética , Trombosis de los Senos Intracraneales/diagnóstico , Adulto , Asparaginasa/uso terapéutico , Niño , Estudios de Seguimiento , Humanos , Leucemia Prolinfocítica de Células T/tratamiento farmacológico , Masculino , Trombosis de los Senos Intracraneales/inducido químicamente , Factores de TiempoRESUMEN
Osteogenesis imperfecta is a disease of bone formation subdivided into two types, congenita and tarda. It is associated with bony fragility, blue sclerae and abnormality of tooth dentin. Rarely the tarda form is associated with basilar invagination or infolding of the foramen magnum and upper cervical segments into the posterior fossa. This results in hydrocephalus and a spectrum of neurologic dysfunction known as the foramen magnum compression syndrome. Many radiologic methods have been used to evaluate basilar invagination including plain film and CT. We describe a patient with osteogenesis imperfecta tarda examined with CT, with a unique finding of diffuse cerebral atrophy associated with basilar invagination.
Asunto(s)
Encefalopatías/patología , Osteogénesis Imperfecta/complicaciones , Platibasia/complicaciones , Adulto , Atrofia , Femenino , HumanosRESUMEN
Responses of atopic dogs to intradermal challenge with 60 allergens were determined and compared for 4 regions of the United States Twenty-seven allergens incited significantly higher responses in atopic dogs residing in northern Florida, when compared with dogs in Illinois; responses to 28 allergens were more significant in dogs residing in southern Florida vs Illinois. Only 1 allergen caused more responses in atopic dogs in northern Florida, compared with dogs in southern Florida. Females had a higher tendency to develop clinical signs of atopy. Dogs of the West Highland White Terrier, Cairn Terrier, English Setter, Irish Setter, Dalmatian, Lhasa Apso, Golden Retriever, and Labrador Retriever breeds were found to be predisposed to develop clinical signs of atopy. Dogs of the Poodle, Pug, German Shepherd Dog, Cocker Spaniel, Bulldog, Schnauzer, Doberman Pinscher breeds, of mixed breeding, and of terrier breeds other than the 2 aforementioned were not found to have a higher prevalence, when compared with the general hospital population. Of the atopic dogs evaluated in Florida, 79% had a significant response to flea antigen, compared with only 9% of atopic dogs evaluated in Illinois.
Asunto(s)
Alérgenos , Dermatitis Atópica/veterinaria , Enfermedades de los Perros/inmunología , Animales , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/etiología , Enfermedades de los Perros/diagnóstico , Perros , Pruebas Cutáneas/veterinaria , Estados UnidosRESUMEN
Two cats were diagnosed with generalized demodicosis. Serotest results were negative for FeLV and positive for feline immunodeficiency virus. In one cat, demodicosis resolved in response to topical application of lime-sulfur solution, but the other cat was euthanatized.
Asunto(s)
Enfermedades de los Gatos , Síndromes de Inmunodeficiencia/veterinaria , Infestaciones por Ácaros/veterinaria , Infecciones por Retroviridae/veterinaria , Animales , Enfermedades de los Gatos/inmunología , Gatos , Femenino , Tolerancia Inmunológica , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/inmunología , Masculino , Infestaciones por Ácaros/etiología , Ácaros , Infecciones por Retroviridae/complicaciones , Infecciones por Retroviridae/inmunologíaRESUMEN
A cat with cutaneous lymphosarcoma and leukemia, similar to Sézary syndrome in human beings, had initial clinical signs that included pruritus and exfoliative dermatosis, associated with weight loss and lymphadenopathy. Dermatopathologic findings and ultrastructural morphologic features of the circulating cells and cellular infiltrate were consistent with Sézary cells. Cutaneous lymphosarcoma and leukemia should be considered in cats with chronic pruritic exfoliative dermatoses.