bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptide Y Counteracts the Anorectic and Weight Reducing Effects of Ciliary Neurotropic Factor
Authors: Pu S. , Dhillon H. , Moldawer L. L. , Kalra P. S. , Kalra S. P.
Published: March 2003

Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin‐6 superfamily, has been shown to induce hypophagia and weight loss. Neuropeptide Y (NPY) and orexin are potent orexigenic signals in the hypothalamus. Anorexia, normally seen in response to infection, injury and inflammation, may result from diminished hypothalamic orexigenic signalling caused by persistently elevated cytokines, including CNTF. To test this hypothesis, we first examined the effects of chronic intracerebroventricular (i.c.v.) infusion of CNTF for 6–7 days on food intake and body weight as well as hypothalamic NPY and orexin gene expression in male rats. Subsequently, the effectiveness of NPY replacement to counteract the effects of CNTF by coinfusion of NPY and CNTF was evaluated. Chronic i.c.v. infusion of CNTF (2.5 µg/day) reduced body weight (14.3% vs control) at the end of 7 days. Food intake remained suppressed for 5 days postinfusion and subsequently gradually returned to the control range by day 7. Serum leptin concentrations in these rats were in the same range seen in control rats. Chronic i.c.v. infusion of higher doses of CNTF (5.0 µg/day) produced sustained anorexia and body weight loss (29% vs controls) through the entire duration of the experiment. This severe anorexia was accompanied by markedly suppressed serum leptin concentrations. Furthermore, CNTF infusion alone significantly reduced hypothalamic NPY gene expression (P < 0.05) without affecting orexin gene expression. As expected, in fusion of NPY alone (18 µg/day) augmented food intake (191.6% over the initial control, P < 0.05) and produced a 25.1% weight gain in conjunction with a 10‐fold increase in serum leptin concentrations at the end of the 7‐day period. Interestingly, coinfusion of this regimen of NPY with the highly effective anorectic and body reducing effects of CNTF (5.0 µg/day) not only prevented the CNTF‐induced anorexia and weight loss, but also normalized serum leptin concentrations and hypothalamic NPY gene expression. These results demonstrate that chronic central infusion to produce a persistent elevation of the cytokine at pathophysiological levels (a situation that may normally manifest during infection, injury and inflammation) produced severe anorexia and weight loss in conjunction with reduction in both serum leptin concentrations and hypothalamic NPY gene expression. Reinstatement of hypothalamic NPY signalling by coinfusion of NPY counteracted these CNTF‐induced responses.
Selective Blockade of the Mineralocorticoid Receptor Impairs Hypothalamic‐Pituitary‐Adrenal Axis Expression of Habituation
Authors: Cole M. A. , Kalman B. A. , Pace T. W. W. , Topczewski F. , Lowrey M. J. , Spencer R. L.
Published: March 2003

The present study investigated the role of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the expression of habituation of the hypothalamic‐pituitary‐adrenal (HPA) axis response to stress. Male rats were restrained for 1 h per day for six consecutive days. On day 6, 1 h prior to restraint stress, both restraint‐naive and repeatedly restrained rats were injected s.c. with either vehicle (propylene glycol) or one of three corticosteroid receptor antagonist treatments: selective MR antagonist (RU28318 or spironolactone), selective GR antagonist (RU40555), or both MR and GR antagonists combined (RU28318 + RU40555). Blood samples were collected for corticosterone measurement at the beginning of stress, during stress, and 1 h after stress termination. Repeated restraint stress produced significant habituation of corticosterone responses. Acute treatment with the combined MR and GR antagonists prevented the expression of habituation. When tested alone, the MR antagonist also blocked the expression of corticosterone‐response habituation, whereas the GR antagonist had no effect. Neither the MR, nor the GR antagonists alone, significantly altered the corticosterone response to restraint in rats exposed to restraint for the first time. The final experiment examined the corticosterone response to a corticotropin releasing hormone (CRH, 3 µg/kg i.p.) challenge. Neither previous exposure to restraint or acute pretreatment with the combined MR and GR antagonists (RU28318 + RU40555) altered the corticosterone response to CRH challenge. This result indicates that the expression of habituation and its blockade by corticosteroid receptor antagonists is not a result of altered pituitary‐adrenal response to CRH. Overall, this study suggests that MR plays an important role in constraining the HPA axis response to restraint stress in restraint‐habituated rats. The dependence of the HPA axis on MR‐mediated corticosteroid negative feedback during acute stress may be an important mechanism that helps maximize the expression of stress habituation and thereby minimize exposure of target tissues to corticosteroids in the context of repeated stress.
Analysis of Adrenocortical Secretory Responses During Acute and Prolonged Immune Stimulation in Inflammation‐Susceptible and‐Resistant Rat Strains
Authors: Andersson I. M. , Lorentzen J. C. , Ericsson‐Dahlstrand A.
Published: March 2003

Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine–immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation‐susceptible Dark Agouti (DA) rats and resistant, MHC‐identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast β‐glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of β‐glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan‐injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1–30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, β‐glucan‐challenged DA rats responded with an aggravated arthritic process, indicating an anti‐inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with β‐glucan. Moreover, substitution with subcutaneous corticosterone‐secreting pellets, yielding moderate stress‐levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan‐challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone‐independent mechanisms. In conclusion, the hypothalamic‐pituitary‐adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal corticosterone levels observed strains during a prolonged arthritic process. No correlation between ability to secrete corticosterone and susceptibility to inflammation could be demonstrated. Basal levels of endogenous corticosterone appeared to restrain inflammation in β‐glucan‐challenged DA rats whereas resistance to inflammation in PVG.1AV1 rats may be mediated via corticosterone‐independent mechanisms.
Priming with Interleukin‐1β Suppresses Experimental Allergic Encephalomyelitis in the Lewis Rat
Authors: Huitinga I. , Schmidt E. D. , Van Der Cammen M. J. F. , Binnekade R. , Tilders F. J. H.
Published: March 2003

Lewis rats exhibit multiple defects in their hypothalamus‐pituitary‐adrenal (HPA) system that are considered to play a causal role in the susceptibility of this strain to autoimmune diseases, i.e. experimental allergic encephalomyelitis (EAE). In the present study, we aimed to modulate the HPA response of the Lewis rat and establish its consequences for the susceptibility to EAE. Because in Wistar rats, single administration of interleukin (IL)‐β (priming) is known to induce long‐lasting (weeks) sensitization of HPA responses to stressors and immune stimuli, Lewis rats were given a single dose of hIL‐1β or vehicle 1 week prior to induction of EAE by immunization with myelin basic protein (MBP). Subsequently, neurological deficits were monitored once daily. The results show that IL‐1 priming markedly suppresses the neurological symptoms of EAE, without affecting the onset or duration of the disease. Measurement of vasopressin and corticotropin releasing hormone (CRH) in the external zone of the median eminence revealed that, as compared to Wistar rats, Lewis rats exhibit low vasopressin but identical CRH, and that IL‐1 priming increases (0.001) vasopressin without affecting CRH stores, which is consistent with a shift to vasopressin‐dominated control of adrenocorticotropic hormone (ACTH) secretion as described in Wistar rats under conditions of HPA hyper(re)activity. However, IL‐1 priming did not affect a.m. corticosterone levels following immunization with MBP or during the clinical phase of EAE. IL‐1 priming of Lewis rats attenuated the ACTH responses to an IL‐1 challenge 11 days later, which may relate to an increase in resting corticosterone levels. Thus, the mechanisms underlying IL‐1 induced suppression of EAE are not related to enhanced HPA responses. In addition, we did not find IL‐1 priming‐induced alterations in MBP‐specific immunoglobulin (Ig)M, IgG1, IgGa and IgGb plasma titres, or gross alterations in T cell activation as reflected in spontaneous or concanavalin‐induced T cell proliferation. We therefore speculate that IL‐1‐induced elevation of resting corticosterone levels may influence the development of EAE.
Localization of the Melatonin‐Related Receptor in the Rodent Brain and Peripheral Tissues
Authors: Drew J. E. , Barrett P. , Mercer J. G. , Moar K. M. , Canet E. , Delagrange P. , Morgan P. J.
Published: March 2003

Previous studies have provided a limited examination of the expression of the orphan melatonin‐related receptor in the pituitary and hypothalamus of human and sheep and retinal tissue in the sheep. The present study reports evidence of conservation of expression in regions of the hypothalamus (dorsal medial hypothalamus, lateral hypothalamus, arcuate nucleus), the epithelial layer lining the third ventricle and the paraventricular thalamic nucleus of the mouse, rat and hamster. An extensive and detailed analysis of melatonin‐related receptor mRNA expression in the mouse central nervous system and peripheral tissues is presented. Mapping the distribution throughout the entire mouse brain has revealed new sites of expression in a number of brain nuclei, including preoptic areas, parabrachial nuclei and widespread distribution in the olfactory bulb. Reverse transcriptase‐polymerase chain reaction was performed with RNA isolated from peripheral tissues revealing expression of the melatonin‐related receptor mRNA in the mouse kidney, adrenal gland, intestine, stomach, heart, lung, skin, testis and ovary. These results suggest a conserved function in neuroendocrine regulation and a potential role in coordinating physiological responses in the central nervous system and peripheral tissues.
Corticosterone Exerts Site‐Specific and State‐Dependent Effects in Prefrontal Cortex and Amygdala on Regulation of Adrenocorticotropic Hormone, Insulin and Fat Depots
Authors: Akana S. F. , Chu A. , Soriano L. , Dallman M. F.
Published: March 2003

Chronic stress stimulates corticosterone secretion and recruits brain pathways that regulate energy balance (caloric acquisition and deposition) and facilitate hypothalamic‐pituitary‐adrenal responsiveness to new stressors. We implanted corticosterone or cholesterol bilaterally either near the central nucleus of the amygdala (CeA) or in the prefrontal cortex to determine whether high concentrations of the steroid act at either site, with or without chronic stress. Rats were adrenalectomized and treated systemically with low doses of corticosterone. Half were maintained at room temperature and the other half were exposed to 5 °C cold for 5 days before all rats were restrained. There was limited diffusion of corticosterone from brain implants. Corticosterone in prefrontal cortex, but not CeA, decreased plasma insulin and adrenocorticotropic hormone (ACTH) responses to acute restraint in both control and chronically cold stressed rats. Corticosterone implants near CeA decreased the weight of fat depots only in cold; corticosterone implants in prefrontal cortex were ineffective. We conclude that (i) corticosterone inhibits insulin and ACTH secretion by an action in prefrontal cortex but not CeA; (ii) high concentrations of corticosterone secreted during chronic stress alter metabolism through (autonomic) outputs of the CeA and prefrontal cortex in site‐ and variable‐specific fashion; and (iii) the amygdala is a component of a stress‐recruited, state‐dependent pathway.
Nitric Oxide Directly Activates GABAA Receptor Function Through a cGMP/Protein Kinase‐Independent Pathway in Frog Pituitary Melanotrophs
Authors: Castel H. , Vaudry H.
Published: March 2003

The direct effects of nitric oxide (NO) donors and sulfhydryl‐modifying agents on the GABAA receptor function were examined by perforated patch, whole‐cell and single channel recordings in cultured frog melanotrophs. In amphotericin B‐perforated cells incubated with the soluble guanylyl cyclase inhibitors LY 83583 and ODQ (10−4 M each), the NO donor sodium nitroprusside (SNP) (10−3 M) reversibly increased the current evoked by GABA (5 × 10−6 M). In the whole‐cell configuration, internal application of the oxidizing agent H2O2 (0.05%) potentiated the GABA‐evoked current while the reducing agent 2‐mercaptoethanol (5 × 10−3 M) slightly decreased the current amplitude. In inside‐out patches, GABA (2 × 10−7 M) triggered single channel bursts of openings. Incubation with the NO donors SNP or DEA/NO (10−4 M each) enhanced the open probability of the GABAA receptor channel but did not modify the chloride reversal potential and did not affect the conductance states. The oxidizing agents H2O2 (0.05%) or DTNB (10−4 M) mimicked the stimulatory effect of the NO donors on the open probability while the reducing compounds 2‐mercaptoethanol (5 × 10−3 M) or DTT (10−4 M) markedly attenuated the channel activity. Potentiation of the GABA‐induced single channel activity by SNP or H2O2 was blocked by 2‐mercaptoethanol. Similarly, the potentiating effect produced by DEA/NO or DTNB on the open probability was reversed by DTT. In outside‐out patches, incubation with SNP also significantly enhanced the open probability of single channels activated by GABA (10−6 M). These data indicate that, in frog pituitary melanotrophs, NO potentiates the GABA‐evoked current independently of the cGMP/protein kinase pathway. The effect of NO can be accounted for by S‐nitrosylation/oxidation of thiol groups either directly on the GABAA receptor subunits or on a regulatory protein tightly associated with the GABAA receptor.
Food Restriction Affects the Gonadotropin Releasing Hormone Neuronal System of Male Prairie Voles (Microtus ochrogaster)
Authors: Kriegsfeld L. J. , Ranalli N. J. , Trasy A. G. , Nelson R. J.
Published: March 2003

Individuals of species inhabiting temperate and boreal latitudes optimize the timing of energetically costly processes by curtailing nonessential energetically demanding processes when environmental conditions are not favourable. One proximate environmental variable used to fine‐tune moment‐to‐moment changes in reproductive physiology and behaviour is food intake. The neuroendocrine mechanisms by which food restriction leads to the cessation of reproduction in seasonally breeding rodent species remain largely unspecified. The present study sought to determine the effects of extended food restriction on the gonadotropin releasing hormone (GnRH) neuronal system. Male prairie voles (Microtus ochrogaster) were either fed ad libitum or were exposed to either 1, 2 or 3 weeks of moderate (70% of daily mean) food restriction. In accordance with previous studies of food restriction, gross reproductive organ masses and body mass were unaffected by food deprivation. Although 1 week of food restriction did not result in alterations in the GnRH neuronal system, food restriction for 2 weeks was associated with increased GnRH‐immunoreactive (GnRH‐ir) neurone soma size. Three weeks of food restriction resulted in a pronounced increase in GnRH‐ir neurone numbers, as well as an increase in fibre intensity in the main fibre pathway to the median eminence. Taken together, these findings suggest that extended food restriction leads to modifications in the GnRH neuronal system, providing a means for temporary cessation of reproduction without gross alterations in reproductive physiology. This transient change in the hypothalmo‐pituitary‐gonadal axis, without pronounced changes in reproductive organ morphology, likely provides a mechanism for the rapid reinitiation of breeding in nature when local conditions provide adequate food availability.
Increased Corticosterone Pulse Frequency During Adjuvant‐Induced Arthritis and its Relationship to Alterations in Stress Responsiveness
Authors: Windle R. J. , Wood S. A. , Kershaw Y. M. , Lightman S. L. , Ingram C. D. , Harbuz M. S.
Published: March 2003

Frequent blood sampling from males rats was used to study hypothalamic‐pituitary‐adrenal (HPA) axis activation during arthritis and its association with diminished responses to acute psychological stress. In control rats, corticosterone release occurred in a series of 13 ± 1 pulses per 24 h. Induction of arthritis by Mycobacterium‐adjuvant injection initially increased the rate of hormone release within each pulse and, by day 14 postinjection, when hind‐paw inflammation was established, caused a marked increase in pulse frequency to 22 ± 1 per 24 h leading directly to elevated circulating corticosterone levels. In both control and adjuvant‐treated rats, there was a marked response to a 10‐min noise stress when the stimulus coincided with a rising or interpulse phase of the endogenous corticosterone rhythm. However, when the noise stress coincided with a falling phase of this rhythm, the response was greatly diminished. Since corticosterone pulse frequency was markedly increased and hence interpulse interval decreased by day 14, there was an increased probability of the noise stress occurring during the nonstress responsive falling phase of the corticosterone secretory cycle. As a result, the group mean response to noise stress was significantly smaller in the arthritic than the controls (70.2 ± 9.2 versus 107.8 ± 13.0 ng/ml, respectively). In contrast to the differential response to noise stress, all rats showed similar responses to the acute immunological challenge with i.v. lipopolysaccharide. Thus, altered basal pulse frequency is a major factor influencing HPA activation during acute psychological stress.
Involvement of Postsynaptic EP4 and Presynaptic EP3 Receptors in Actions of Prostaglandin E2 in Rat Supraoptic Neurones
Authors: Shibuya I. , Setiadji S. V. , Ibrahim N. , Harayama N. , Maruyama T. , Ueta Y. , Yamashita H.
Published: March 2003

We have reported that supraoptic nucleus (SON) neurones are excited by prostaglandin E2 (PGE2) presumably via dual postsynaptic PG receptors, FP receptors and unidentified EP receptors, and that presynaptic EP receptors may also be involved in the excitation. In the present study, to clarify the receptor mechanism of the PGE2‐mediated actions on SON neurones, we studied the pre‐ and postsynaptic effects of four newly developed EP agonists that are selective for each of the four EP receptors, EP1−4, on rat SON neurones using extracellular recording and whole‐cell patch‐clamp techniques. The EP4 agonist ONO‐AE1‐329 mimicked the excitatory effects of PGE2, whereas the EP1 agonist ONO‐DI‐004, the EP2 agonist ONO‐AE1‐257 and the EP3 agonist ONO‐AE‐248 had little or no effect. The effects of ONO‐AE1‐329 were unaffected by the EP1/FP/TP antagonist, ONO‐NT‐012, which potently suppressed the excitation caused by the FP agonist fluprostenol and PGE2. ONO‐AE1‐329 caused marked excitation when responses to fluprostenol were desensitized by repeated applications of fluprostenol. Patch‐clamp analysis in SON neurones showed that ONO‐AE1‐329 induced inward currents at a holding potential of −70 mV and the reversal potential of the currents was −35.1 ± 2.3 mV. On the other hand, the frequency of spontaneous inhibitory postsynaptic currents recorded from SON slice preparations was suppressed by ONO‐AE‐248, but unaffected by the other three EP agonists. These results suggest that SON neurones possess postsynaptic EP4 receptors and that γ‐aminobutyric acid neurones innervating SON neurones possess presynaptic EP3 receptors in their terminals. Activation of the two EP receptors may be involved in the excitatory regulation of SON neurones by PGE2.
Ghrelin Stimulates Insulin Secretion from the Pancreas of Normal and Diabetic Rats
Authors: Adeghate E. , Ponery A. S.
Published: March 2003

Ghrelin is a novel 28‐amino acid gut–brain peptide, which was first isolated in the rat stomach. This study examined the effect of ghrelin on insulin secretion from the isolated pancreas of normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin. Four weeks after the induction of diabetes, pancreatic tissue fragments of normal and diabetic rats were treated with different concentrations (10−12, 10−9 and 10−6 M) of ghrelin. Ghrelin evoked large and significant increases in insulin secretion from the pancreas of both normal and diabetic rats. In the pancreas of normal rats, diltiazem (calcium channel antagonist) or a combination of atropine (muscarinic cholinergic receptor antagonist), propranolol (β‐adrenergic receptor antagonist) and yohimbine (α2‐adrenergic receptor antagonist) significantly reduced the stimulatory effect of ghrelin on insulin secretion. Diltiazem and yohimbine failed to inhibit ghrelin‐evoked insulin release in diabetic rat pancreas. Ghrelin‐immunoreactivity cells was observed in 2.6% and 3.8% of the total cell population in the islet of Langerhans of normal and diabetic rats, respectively.
Regulation of Sex Differences in Progesterone Receptor Expression in the Medial Preoptic Nucleus of Postnatal Rats
Authors: Quadros P. S. , Goldstein A. Y. N. , De Vries G. J. , Wagner C. K.
Published: March 2003

The medial preoptic nucleus (MPN) of the rat, an excellent model for understanding the mechanisms involved in sexual differentiation, is highly sensitive to gonadal hormones during both pre‐ and post‐natal life. Progesterone receptor (PR) expression is sexually dimorphic in the prenatal MPN. Males have significantly higher levels of PR‐immunoreactivity (PRir) than females from approximately embryonic day 19 through at least the day of birth, suggesting that PR may play a role in sexual differentiation. Because the MPN is still sensitive to steroid hormones postnatally, the present study investigated PR expression in the MPN of males and females after birth using immunocytochemistry. Results indicate that a sex difference in PR expression persists until at least postnatal day (P) 28. However, females begin to express PR around P10. Because oestradiol regulates PR expression in the adult brain, this study also examined the influence of gonadal hormones on PR expression in the neonatal male and female MPN. Castration on the day of birth significantly reduced levels of PRir in the MPN by 24 h following surgery. Ovariectomy on P4, before the onset of ovarian steroidogenesis, prevented the induction of PR expression in the female MPN, observed in controls by P13. In both sexes, the presence of PRir in the MPN is dependent on gonadal hormone exposure. These findings suggest that differences in steroid secretion by the neonatal male and female gonads are responsible for producing sex differences in the level of PR expression in the postnatal MPN.
Sauvagine Regulates Ca2+ Oscillations and Electrical Membrane Activity of Melanotrope Cells of Xenopus laevis
Authors: Cornelisse L. N. , Deumens R. , Coenen J. J. A. , Roubos E. W. , Gielen C. C. A. M. , Ypey D. L. , Jenks B. G. , Scheenen W. J. J. M.
Published: March 2003

Ca2+ oscillations regulate secretion of the hormone alpha‐melanphore‐stimulating hormone (α‐MSH) by the neuroendocrine pituitary melanotrope cells of the amphibian Xenopus laevis. These Ca2+ oscillations are built up by discrete increments in the intracellular Ca2+ concentration, the Ca2+ steps, which are generated by electrical membrane bursting firing activity. It has been demonstrated that the patterns of Ca2+ oscillations and kinetics of the Ca2+ steps can be modulated by changing the degree of intracellular Ca2+ buffering. We hypothesized that neurotransmitters known to regulate α‐MSH secretion also modulate the pattern of Ca2+ oscillations and related electrical membrane activity. In this study, we tested this hypothesis for the secretagogue sauvagine. Using high temporal‐resolution Ca2+ imaging, we show that sauvagine modulated the pattern of Ca2+ signalling by increasing the frequency of Ca2+ oscillations and inducing a broadening of the oscillations through its effect on various Ca2+ step parameters. Second, we demonstrate that sauvagine caused a small but significant decrease in K+ currents measured in the whole‐cell voltage‐clamp, whereas Ca2+ currents remained unchanged. Third, in the cell‐attached patch‐clamp mode, a stimulatory effect of sauvagine on action current firing was observed. Moreover, sauvagine changed the shape of individual action currents. These results support the hypothesis that the secretagogue sauvagine stimulates the frequency of Ca2+ oscillations in Xenopus melanotropes by altering Ca2+ step parameters, an action that likely is evoked by an inhibition of K+ currents.
Centrally Administered Galanin‐Like Peptide Modifies Food Intake in the Rat: A Comparison with Galanin
Authors: Lawrence C. B. , Baudoin F. M.‐H. , Luckman S. M.
Published: March 2003

Galanin‐like peptide (GALP) is a recently identified neuropeptide that shares sequence homology with the orexigenic neuropeptide, galanin. In contrast to galanin, GALP is reported to bind preferentially to the galanin receptor 2 subtype (GalR2) compared to GalR1. The aim of this study was to determine the effect of GALP on feeding, body weight and core body temperature after central administration in rats compared to the effects of galanin. Intracerebroventricular (i.c.v.) injection of GALP (1 µg−10 µg) significantly stimulated feeding at 1 h in both satiated and fasted Sprague‐Dawley rats. However, 24 h after GALP injection, body weight gain was significantly reduced and food intake was also usually decreased. In addition, i.c.v. GALP caused a dose‐related increase in core body temperature, which lasted until 6–8 h after injection, and was reduced by peripheral administration of the cyclooxygenase inhibitor, flurbiprofen (1 mg/kg). Similar to GALP, i.c.v. injection of galanin (5 µg) significantly increased feeding at 1 h in satiated rats. However, there was no difference in food intake and body weight at 24 h, and galanin only caused a transient rise in body temperature. Thus, similar to galanin, GALP has an acute orexigenic effect on feeding. However, GALP also has an anorectic action, which is apparent at a later time. Therefore, GALP has complex opposing actions on energy homeostasis.
Oestrogens, Via Transforming Growth Factor α, Modulate Basic Fibroblast Growth Factor Synthesis in Hypothalamic Astrocytes: In Vitro observations
Authors: Galbiati M. , Martini L. , Melcangi R. C.
Published: March 2003

The data presented here show that, in cultures of type 1 astrocytes obtained from the hypothalamus of neonatal female rat, 17β‐oestradiol is able to increase both the mRNA and the protein levels of basic fibroblast growth factor (bFGF). In particular, after 24 h of exposure to 17β‐oestradiol (10−9 and 10−10 m), an increase of messenger levels of bFGF appears in hypothalamic type 1 astrocytes. Similarly, an induction of bFGF protein is also evident at this time of exposure. The effect on the mRNA and protein levels of bFGF is blocked by the presence in the medium of an antibody raised against the transforming growth factor α (TGFα) receptor. This observation indicates that, TGFα, whose synthesis is modulated by oestrogens in hypothalamic astrocytes and which is able to increase, both the mRNA and the protein levels of bFGF in our experimental model, may act as the mediator of the oestrogenic induction of bFGF. Hypothalamic astrocytes, together with hypothalamic neurones synthesizing and secreting luteinizing hormone‐releasing hormone (LHRH), form the LHRH network in conjunction with other neuronal systems. Gonadal steroids in general, and oestrogens in particular, play an important role in the control of the activity of this network. In addition, bFGF and TGFα, two growth factors released from astrocytes, are able to influence the activity of LHRH neurones. The present observations suggest that oestrogens may also act on LHRH neurones in an indirect fashion (i.e. by modulating the expression of bFGF and TGFα in glial cells).
Interleukin‐1β Depolarizes Paraventricular Nucleus Parvocellular Neurones
Authors: Ferri C. C. , Ferguson A. V.
Published: March 2003

Interleukin‐1β (IL‐1β) is involved in hypothalamic regulation of corticotropin releasing hormone (CRH) secretion and consequent downstream modulation of the neuroimmune response. In this study, whole‐cell patch clamp recordings of rat parvocellular neurones in a slice preparation of the paraventricular nucleus (PVN) of the hypothalamus were performed to examine the cellular effects of IL‐1β. In response to 1 nm IL‐1β, 65% of parvocellular neurones tested exhibited a clear depolarization, which was abolished in the presence of tetrodotoxin (TTX). This depolarization was partially dependent on nitric oxide formation, as demonstrated by attenuation of the response in the presence of N‐ω‐nitro‐l‐arginine methylester, a nitric oxide synthase inhibitor. The effects of IL‐1β on responsive parvocellular neurones were associated with a decrease in the frequency of inhibitory post synaptic potentials (IPSPs). Bicuculline administration blocked the effects of IL‐1β, suggesting that this cytokine modulates GABA‐ergic output, resulting in a decrease in inhibitory input (IPSPs) and consequent depolarization. These data support the conclusion that IL‐1β influences the excitability of parvocellular neurones in the PVN, as a secondary consequence of nitric oxide generation and modulation of GABAergic inhibitory input to these cells. They elucidate cellular correlates underlying the well‐established neuroimmune roles of IL‐1β in the paraventricular nucleus of the hypothalamus.
Validation of a recording protocol for assessing temporomandibular sounds and a method for assessing jaw position
Authors: Prinz
Published: March 2003

SUMMARY Sounds are often produced by the temporomandibular joint (TMJ) during movement in both symptomatic and asymptomatic subjects. However, subjective methods of describing these sounds have been shown to have poor inter‐ and intra‐observer reliability. In this study, a low cost system in which TMJ sounds were detected using the loudspeakers of lightweight in‐ear headphones as microphones is evaluated. The sounds were recorded on tape and then analysed using a computer. Sounds were elicited by asking subjects to bring their teeth together with sufficient force to produce a tooth contact sound, then open their mouths as far as possible and then close again. Placing the microphones in the ears attenuated ambient sounds by 58%, thus providing a degree of immunity from ambient noise. Sampling was performed on the left microphone only at 3·4 kHz and from the left and right microphones together at 1·7 kHz for 60 TMJ sounds and 60 tooth contact sounds. Spectral analysis of sounds recorded at the two sample rates revealed no significant differences. Therefore, a sample rate of 1·7 kHz is adequate to resolve the frequency components present in the TMJ sounds. Although simply recording TMJ sounds does not give a direct measurement of the position of the mandible, using this protocol allows the length of the open close cycle to be determined. If the envelope of movement is assumed to approximate a sinusoid, then the direction of mandibular movement can be assumed to reverse at the half way point in the cycle. The accuracy of this assumption was calculated by comparing the mid‐point of the cycle to the point of maximum gape in 129 cycles from nine subjects. The mean difference expressed as percentage of cycle length was 1·3 ± 0·9%.
Posterior bite collapse – revisited
Authors: Shifman  , LauFer B‐Z. , Chweidan
Published: March 2003

SUMMARY Although there are different definitions of posterior bite collapse, only the classical definition of Amsterdam provides a definite diagnosis and treatment plan. This situation entails a subtle loss of the occlusal vertical dimension with resultant flaring of the maxillary incisors. Other causes for flaring, such as derangements of form and functions of lips and tongue, bruxism, habits, as well as the presence of advanced periodontal disease or malocclusions, should be ruled out before the diagnosis of posterior bite collapse can be made. The complexity of differential diagnosis is illustrated with three case reports.
Component release from light‐activated glass ionomer and compomer cements
Authors: Hamid A. , Okamoto A. , Iwaku M. , Hume W. R.
Published: March 2003

The purpose of this study was to identify and quantify any component released from seven commercially available light‐cured or resin‐modified glass ionomer and compomer cements. Twenty‐one separate cylindrical stainless steel moulds 6 mm in diameter and 1·0 mm deep were filled with one of seven glass ionomer or compomer cements, light activated and then immediately immersed in separate containers of distilled water. Water samples were retrieved over a time period of up to 30 days and retained for analysis. An occlusal cavity 6 mm in diameter was prepared in extracted human third molar teeth with a remaining dentin thickness of 1·6–2·0 mm. A polypropylene chamber was attached to the cemento‐enamel junction of each tooth to contain 1 mL of distilled water. Ten teeth were each filled with one of three cements and light activated. Water samples (eluates) were retrieved over a period of time. All samples were analysed by high performance liquid chromatography. Only one component, hydroxyethyl methacrylate (HEMA), was detected in the eluates from both tooth and mould samples. Analysis of diffusion of the HEMA through dentin showed a relatively sustained movement into the pulp space during the first day, with exponential decline thereafter. Our data show that HEMA was released from all of the light activated glass ionomer cements studied and from the compomer, both directly into water and through dentin. This release may be relevant both to the risk of adverse pulpal responses in patients and to the risk of allergy in patients and dental personnel.
Monitoring the state of the occlusion – gnathosonics can be reliable
Authors: Tyson
Published: March 2003

Monitoring the state of the occlusion should include records that can be compared. Gnathosonics has not become generally accepted as an everyday method of assessing the quality of the occlusion. It is suggested that this may be due to inconsistencies in the results obtained by various workers in the field. It is further suggested that such inconsistencies could be due to the manner of data gathering in the areas of equipment, transfer of data from the patient and interpretation of the records. A reliable method of data gathering using accelerometers is suggested and, taking account of the complexities of sound transmission through the skull, concludes that the overall envelope of the sounds produced by the occlusion of the teeth is more informative that the actual frequencies generated. Ways in which gnathosonics could be placed on a scientific footing and areas where further investigation might be useful are suggested. Gnathosonics, properly controlled, can provide a simple, quick and reliable method of making permanent records of occlusal sounds for comparison and assessment of stability or change in the state of the occlusion.
Bacterial leakage into and from prefabricated screw‐retained implant‐borne crowns in vitro
Authors: Guindy  , Besimo CH. E.
Published: March 2003

A mean gap of less than 4 μm following laboratory procedures and continuous loading was demonstrated in prefabricated crowns of the Ha‐Ti® implant system in earlier studies. The clinical relevance of such high precision in maintaining inflammation free marginal mucosa is yet to be determined. In this present investigation, the complete assembly of Ha‐Ti® implants including prefabricated screw‐retained crowns was tested for bacterial leakage under controlled conditions in vitro. The gaps were shown not to be a barrier for Staphylococcus aureus which were used as test bacteria. Bacterial leakage through these gaps from the environment to the interior of the assembly and vice versa was observed within 24–120 h. The main path of bacterial penetration was possibly found to be through the transversal screw hole and not through the marginal gap of the prefabricated crowns.
The simulation and calculation of the fatigue of the lower complete denture in function by means of the finite element analysis
Authors: Panduric° J. , Husnjak M. , Guljas K. , Kraljevic° K. , Zivko‐babic° J.
Published: March 2003

SUMMARY This paper presents a finite element analysis, by which the stress distribution during function of a lower jaw acrylic‐resin complete denture can be shown. The geometry of a prosthesis has been approximated by measuring, its elementary dimensions, as well as the dimensions of the characteristic cross‐sections, on an already completed denture. Based upon these dimensions a mesh, (a three‐dimensional network diagram) of finite elements was made. The results obtained are presented both graphically and numerically. The equivalent fatigue stresses, according to von Mises’ energetic theory of firmness, expressed in MPa (or in N/mm2), are also shown. The results obtained enable us to gain an insight into lower complete denture fatigue, and could also be used when optimizing the shape of a denture. Furthermore, they could indicate possible causes of the fatigue fractures of a denture, particularly in the area between the left and the right canines.
Physical mechanisms involved in the genesis of temporomandibular joint sounds
Authors: Prinz J. F.
Published: March 2003

Several different mechanisms are potentially capable of generating sounds in the temporomandibular joint (TMJ). These include impact, sliding and stick‐slip friction, fluid dynamic effects and the release of elastic strain energy. It is the aim of this paper to provide a framework with which to separate sounds resulting from the different underlying causes. Each mechanism is described and its relevance to TMJ sounds and clinical significance discussed. Since it is not possible to observe these mechanisms in vivo the arguments are based mainly on analogies which are used to make predictions of the characteristic acoustic signatures of the sounds produced by these different mechanisms. In particular the changes in the characteristics of the sounds as parameters such as mandibular speed and loading are stressed. It is suggested that single short duration sounds (clicks) are due to impact, multiple short duration sounds (creaks) to stick‐slip friction and defects of form and long duration sounds (crepitus) to simple sliding friction. Several other mechanisms which have no obvious clinical significance but which are capable of producing similar sounds are also described and methods of distinguishing them from the sounds that do have clinical implications are discussed.
Displacement of a mobile tooth during impression procedure: effect of impression tray design
Authors: Nishi Y. , Hamano T. , Kawahata N. , Nagaoka E.
Published: March 2003

When fabricating prostheses in a partially edentulous arch with some mobile teeth, it is important to minimize tooth displacement during the impression procedure. The present study examined the effect of custom tray designs on the displacement of a mobile central incisor in a mandibular simulation model with six anterior teeth. Twelve custom trays were designed according to the different spaces and perforated holes in the region of the remaining teeth. As a result, the degree of displacement of the mobile tooth could be reduced according to the size of spaces and the location of perforated holes in the custom tray.

Introduction
Fracture resistance of endodontically treated roots after restoration
Authors: Fraga R. C. , Chaves B. T. , Mello G. S. B. , Jr J. F. Siqueira
Published: March 2003

This study evaluated the shear strength resistance of endodontically treated roots that were restored by two different techniques. Twenty‐seven recently extracted single‐rooted teeth with similar anatomic characteristics were sectioned to obtain the same length for all specimens. Group I (GI) consisted of 14 roots restored with cast post‐core (nickel–chromium alloy) and cemented using zinc phosphate cement; group II (GII) consisted of 13 roots restored with steel prefabricated posts (FKG®) cemented with zinc phosphate cement and rotated with caution for anchorage. The crown portion of this group was made using a hybrid composite resin (Prisma APH®). Results showed that on all specimens of GI the fracture occurred in the cervical root structure while in GII the composite resin fractured in all specimens. Statistical analysis showed a significantly higher resistance to fracture for GI than GII. The specimens were sectioned longitudinally for stereoscopic microscope analysis (63×) and did not show fracture lines in the dentin anchorage post area for any of the specimens.
Acoustic myography, electromyography and bite force in the masseter muscle
Authors: Tortopidis D. , Lyons M. F. , Baxendale R. H.
Published: March 2003

Acoustic myography (AMG) offers some advantages over electromyography (EMG) in certain circumstances, but the use of AMG on the jaw‐closing muscles has not been fully tested. The purpose of this study was to examine the relationship between AMG, EMG and force in the masseter muscles of nine healthy male subjects. The AMG was recorded using a piezoelectric crystal microphone and the EMG was recorded simultaneously with surface electrodes. Force was recorded between the anterior teeth with a strain‐gauge transducer. Analysis showed that Pearson’s correlation coefficient was 0·913 for force/AMG and 0·973 for force/EMG in all subjects, indicating a linear relationship between force, AMG and EMG at the four different force levels tested (25–75% of maximum). It is apparent that AMG may be used as an accurate monitor of masseter muscle force production, although some care is required in the technique.
Techniques for the production of dental eroded lesions in vitro
Authors: Amaechi B. T. , Higham S. M. , Edgar W. M.
Published: March 2003

This project firstly demonstrated an in vitro technique for the production of eroded lesions which simulates the in vivo conditions, and secondly evaluated the influence of salivary parameters on the degree of erosion in vitro. Teeth were sectioned sagitally into three equal portions. The portions were randomly assigned to one of three experimental groups (A, B and C). Lesions were produced by cycling the teeth between orange juice and either artificial saliva (A) or water (B) for a total period of 12 h, or by a single 12 h immersion in orange juice (C). Sections were prepared from each specimen and mineral loss was quantified using transverse microradiography. Mineral loss was significantly lower in group A compared with B and C. Greatest mineral loss was observed in B though not significant when compared with C. The present technique mimics the in vivo conditions with the saliva reducing the degree of erosion and possibly remineralizing the lesions.
Influence of surface treatment on adherence energy of alloys used in bonded prosthetics
Authors: Moulin P. , Degrange M. , Picard B.
Published: March 2003

Usually, shear or tensile tests are used to assess bond strengths between resin and metal. In this study, a cleavage test, the Double Cantilever Beam test, was performed to measure the adherence energy in air and in water between a 4‐META resin, and five alloys (palladium, palladium–silver, gold, cobalt–chromium and nickel–chromium alloys) whose surfaces have been treated by sandblasting only or by two methods of silica coating (Silicoater MD, Rocatec) or by painting with a primer (V‐Primer). Results showed that, after storage in water, it is difficult to divide the studied alloys into a dental base alloys group and a noble alloys group. Therefore, the silica coating has significantly limited the propagation of fissures in water. Higher values of adherence energy were recorded with the Rocatec system except with the palladium alloy which must be treated with the Silicoater MD system. The treatment with V‐Primer was sensitive to hydrolytic attack.
A laboratory assessment of enamel hypoplasia of teeth with varying severities of dental fluorosis
Authors: Sapov K. , Gedalia I. , Grobler S. , Lewinstein I. , Roman I. , Shapira L. , Hirschfeld Z. , Teotia S.
Published: March 2003

The effect of lifelong exposure to drinking‐water containing fluoride on tooth enamel microhardness was investigated. Dental fluorosis of teeth from adult subjects, who lived continuously since birth in areas characterized by the hot climate of India, supplied by drinking‐water containing between 0·5 and 8·7 parts/10 F, was estimated by the Dean score. Tooth enamel sections were examined from the enamel surface towards the dentino–enamel junction (DEJ) for microhardness. Separated enamel crowns were pulverized and analysed for fluoride. Regarding the distribution of the fluoride concentrations in the drinking‐water, we selected a partition below and above 0·8 parts/10 F as a criterion for comparison between the results. Tooth enamel of humans from Israel living in a drinking‐water area containing about 0·5 parts/10 F was also examined. Positive associations were evident between fluoride in drinking‐water, fluoride concentrations in the bulk enamel and fluorosis selection. A significantly high inverse relationship was evident between the fluoride concentration of the drinking‐water and the subsurface enamel microhardness. In similar fluoride‐concentration drinking‐water areas of India and Israel the microhardness of the subsurface enamel was less for the Indian teeth. The microhardness of the enamel near the DEJ for the three different water fluoride‐concentration areas was not significantly different.