Fos expression in feeding-related brain areas following intracerebroventricular administration of orphanin FQ in rats.

While the influence of orphanin FQ (OFQ) on the regulation of food intake has been substantiated, little is known about feeding-related brain regions that mediate OFQ-induced feeding. To further investigate this, we injected OFQ intracerebroventricularly and evaluated c-Fos immunoreactivity in brain areas thought to be involved in the regulation of food intake. Altered c-Fos expression as a consequence of OFQ injection was observed in the nucleus of the solitary tract, paraventricular nucleus of the hypothalamus, supraoptic nucleus, central nucleus of amygdala, lateral septal nucleus and lateral habenular nucleus.

Discriminative stimulus effects of morphine: central versus peripheral training.

While it is well known that rats can discriminate a peripheral injection of morphine from a saline injection, to our knowledge no one has trained rats to discriminate a direct brain-site injection of morphine from saline. In the present series of studies, one group of rats was trained to discriminate morphine (0.3 microgram) from saline injected into the perifornical area of the hypothalamus (PFA), a process that took rats about 37 sessions to learn.

Role of lipid type on morphine-stimulated diet selection in rats.

Administration of morphine is said to increase fat consumption among rats allowed to self-select nutrients. However, fats represent a diverse group of molecules, differing in metabolic and sensory properties. Despite this, lipid has yet to be manipulated as a variable in drug-stimulated nutrient selection studies.

Inflammatory and contractile agents sensitize specific adenylyl cyclase isoforms in human airway smooth muscle.

Beta-agonists, through activation of the beta(2)-adrenergic receptor (beta(2)AR)-G(s)-adenylyl cyclase (AC) pathway, promote bronchodilation via functional antagonism of airway smooth muscle (ASM) spasmogens associated with the asthmatic state. Although previous studies have demonstrated that beta(2)AR signaling in ASM is subject to homologous (beta-agonist-induced) beta(2)AR desensitization, the potential for inflammatory and contractile agents to impact beta(2)AR signaling in ASM through heterologous mechanisms has not been defined. Here we report that chronic exposure of human ASM (HASM) to carbachol, serotonin, the thromboxane analogue U46619, or histamine induced little change or a small increase in isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) formation, but significantly increased cAMP formation elicited by stimulation with forskolin.

The regulation of MMPs and TIMPs in cartilage turnover.

The treatment of cartilage with mediators initiates the breakdown of proteoglycan followed by collagen. This is accompanied by the modulation of different proteinases and inhibitors that include members of the MMP family and TIMPs. We have evidence that a chondrocyte membrane-associated metalloproteinase cleaves aggrecan.

Differential effects of neuropeptide Y and the mu-agonist DAMGO on 'palatability' vs. 'energy'.

Differential effects of neuropeptide Y (NPY) and mu-opioid DAMGO on 'palatability' vs. 'energy'. A variety of studies suggest that NPY is an important manager of energy metabolism.

Binding of GM-CSF to adherent neutrophils activates phospholipase D.

When the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor was incubated with neutrophils adherent to plastic tissue culture plates or plates coated with extracellular matrix proteins, a rapid (3 min) but transient formation of phosphatidic acid was observed. This stimulation was dependent on the dose of GM-CSF, with an EC50 of 140 pM, and was further enhanced (up to 350%) with the PA phosphatase inhibitor propranolol in a dose-dependent manner. Conversely, GM-CSF was unable to trigger any PA formation in neutrophils maintained in suspension, even in the presence of soluble fibronectin.

Obesity and aging.

This review focuses on studies that pertain to obesity and aging. The prevalence of obesity in the elderly is discussed, with an emphasis on body-fat distribution as it relates to morbidity and mortality rates. Treatment options, such as physical activity, growth hormones, and drug therapy, are briefly mentioned.

STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats.

Effects of streptozotocin (STZ)-induced diabetes and insulin on opioid peptide gene expression were examined in rats. In experiment 1, three groups were administered STZ (75 mg/kg ip single injection). Two groups were killed at either 2 or 4 wk.

Thyroid function and energy intake during weight gain following treatment of hyperthyroidism.

Objective: Individuals with hyperthyroidism lose weight despite increased appetite and food intake, and weight is regained after treatment of hyperthyroidism. We asked whether this weight regain is purely a function of lowered metabolic rate coincident with lowered thyroid hormone concentrations or if the weight gain is related to food-energy overconsumption.

Methods: Ten unselected patients with hyperthyroidism treated with 131I were studied.

The effect of naltrexone on taste detection and recognition threshold.

Eighteen healthy female volunteers were administered 50 mg naltrexone in a double-blind, placebo control study. Relative taste detection and recognition thresholds for sweet, salty, sour and bitter taste and liking for and perception of sucrose solutions were determined at baseline and 1 hour after administration of naltrexone. Naltrexone did not alter relative taste detection and recognition thresholds for any of the four tastes or perception of sweetness.

The effect of naloxone on food-motivated behavior in the obese Zucker rat.

We assessed differences in food reinforced behavior between obese and lean Zucker rats with a progressive ratio schedule 3 (PR3) in which a subject emitted three additional lever-presses each time a reinforcer was delivered. The number of responses required for a reinforcer eventually exceeded its value, termed the "break point", a sensitive measure of food motivated behavior. Break points were higher in obese rats than lean controls for grain pellets (27.

Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition.

Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) on proliferation of cultured HASM cells. At concentrations selective for the type 3 phosphodiesterase isoform, siguazodan inhibited both [3H]thymidine incorporation (IC50 2 microM) and the increase in cell number (10 microM; 64% reduction) induced by platelet-derived growth factor-BB (20 ng/ml).

Feeding response to central orexins.

Orexin A and orexin B were microinjected into the perifornical hypothalamus (PFH), lateral hypothalamus (LH), hypothalamic paraventricular nucleus (PVN), and ventral tegmental area (VTA) of male Sprague-Dawley rats. Orexin B (15 nmol) was also injected into the lateral cerebral ventricle (i.c.

Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands.

It has been reported that intraventricular administration of the melanocortin 4 receptor (MC4-R) agonist MT II and antagonist SHU9119 alter food intake. We found that MT II and SHU9119 have extremely potent effects on feeding when injected in the paraventricular nucleus (PVN), a site where MC4-R gene expression is very high. Our finding provides direct evidence that MC4-R signaling is important in mediating food intake and that melanocortin neurons in the PVN exert a tonic inhibition of feeding behavior.

Neuroleptic malignant syndrome associated with olanzapine.

Objective: To report a case of neuroleptic malignant syndrome (NMS) associated with the use of olanzapine.

Case Summary: A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic.

An aggrecan-degrading activity associated with chondrocyte membranes.

The breakdown of aggrecan in cartilage is, in part, mediated by an enzyme named aggrecanase that cleaves within the interglobular domain of the molecule between a glutamic residue and an alanine residue. Although the enzyme cleavage site has been identified, the identity, characteristics and localization of this enzyme remain unclear. We have demonstrated that membranes isolated from stimulated chondrocytes are able to generate aggrecan fragments that are labelled by an antibody that recognizes the new N-terminus formed by aggrecanase activity.

Association between the amygdala and nucleus of the solitary tract in mu-opioid induced feeding in the rat.

The central nucleus of the amygdala (CNA) and the nucleus of the solitary tract (NTS) are important in the regulation of ingestive behavior. We evaluated whether opioid-opioid signaling between the CNA and rostral NTS (rNTS) affect feeding behavior. To test this, rats were doubly cannulated with one cannula placed in the rNTS and one cannula in the CNA, allowing for co-administration of an opioid agonist into one site and an opioid antagonist into the other.

Effects of palatability-induced hyperphagia and food restriction on mRNA levels of neuropeptide-Y in the arcuate nucleus.

This study examined the effect of feeding either a bland cornstarch-based diet (BCD) or a highly palatable, high fat diet containing sucrose (HPD) on hypothalamic arcuate nucleus (ARC) gene expression for neuropeptide-Y (NPY). Male Sprague-Dawley rats received either BCD ad libitum, HPD ad libitum, HPD pair-fed to the caloric intake of the BCD, or the HPD at 60% of ad libitum HPD intake for 7 days. Animals receiving the HPD ad libitum consumed more calories and gained more weight than animals receiving the BCD (P<0.

Neural site of leptin influence on neuropeptide Y signaling pathways altering feeding and uncoupling protein.

Inhibition of a signal that produces positive energy balance involving neuropeptide Y (NPY) projection from arcuate nucleus (Arc; site of NPY synthesis) to paraventricular nucleus (PVN; site of NPY release) is one potential mechanism of leptin action. NPY in the PVN increases feeding and decreases uncoupling protein (UCP) activity in brown fat, whereas leptin decreases NPY biosynthesis in the Arc, which presumably decreases PVN NPY. It is hypothesized that decreased NPY activity is necessary for the satiety and thermogenic effects of leptin.

Divergence of the feeding and thermogenic pathways influenced by NPY in the hypothalamic PVN of the rat.

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) increases feeding and decreases brown adipose tissue (BAT) uncoupling protein (UCP) and lipoprotein lipase (LPL) mRNA. Previously we reported that the feeding and BAT effects induced by NPY in the PVN are blocked by 50 microg naltrexone (NTX) in the rostral nucleus of the solitary tract (rNTS). We sought to determine whether the effect of rNTS NTX on PVN NPY-induced alterations in energy metabolism occurred at lower doses of NTX.

Regulation of proliferation of human colonic subepithelial myofibroblasts by mediators important in intestinal inflammation.

An increase in myofibroblast number may be necessary for wound healing but may also lead to postinflammatory scarring. We have, therefore, studied the role of mediators important in inflammatory bowel disease in regulating proliferation of human colonic myofibroblasts. Using primary cultures of these cells, we have shown increases in [3H]thymidine incorporation in response to platelet-derived growth factor (EC50 = 14 ng/ml), basic fibroblast growth factor (EC50 = 2.

Effect of peripheral 2-DG on opioid and neuropeptide Y gene expression.

It is well known that 2-Deoxy-d-glucose (2-DG) blocks intracellular utilization of glucose and increases food intake. The aim of the present study was to determine whether administration of 2-DG alters gene expression of the orexigenic peptides, neuropeptide Y (NPY) and endogenous opioids, in the arcuate nucleus of the hypothalamus (ARC). Male Sprague-Dawley rats were injected peripherally (i.

Obesity: progress through genetic manipulation.

Transgenic mice have been produced that either lack or overproduce neuroregulatory substances implicated in the control of food intake and body weight. Are such mice useful models for understanding the underlying etiology of obesity in humans?