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Sökning: L773:0143 4179 OR L773:1532 2785 > (2005-2009)

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1.
  • Ali, M Al Haj, et al. (författare)
  • Distribution of neuroendocrine cells in the small and large intestines of the one-humped camel (Camelus dromedarius)
  • 2007
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 41:5, s. 293-299
  • Tidskriftsartikel (refereegranskat)abstract
    • The distribution and relative frequency of neuroendocrine cells in the small and large intestines of one-humped camel were studied using antisera against 5-hydroxytryptamine (5-HT), cholecystokinin (CCK-8), somatostatin (SOM), peptide tyrosine tyrosine (PYY), gastric inhibitory polypeptide (GIP), neuronal nitric oxide synthase (nNOS), gastrin releasing peptide (GRP), substance P (SP), and neurokinin A (NKA). Among these cell types, CCK-8 immunoreactive (IR) cells were uniformly distributed in the mucosa, while others showed varied distribution in the villi or crypts of the small intestine. Immunoreactive cells like 5HT, CCK-8, and SOM showed peak density in the villi and crypts of the small intestine and in the colonic glands of the large intestine, while cells containing SP were discerned predominately in the crypts. 5-HT, CCK-8 and SOM cells were mainly flask-shaped and of the open-variety, while PYY and SP immunoreactive cells were mainly rounded or basket-shaped and of the closed variety. Basically the distribution pattern of the endocrine cells in the duodenum, jejunum and colon of the one-humped camel is similar to that of other mammals. Finally, the distribution of these bioactive agents may give clues as to how these agents aid in the function of the intestinal tract of this desert animal.
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  • Fransson, Rebecca, et al. (författare)
  • Small peptides mimicking substance P (1-7) and encompassing a C-terminal amide functionality
  • 2008
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:1, s. 31-37
  • Tidskriftsartikel (refereegranskat)abstract
    • Some of the biological effects demonstrated after administration of substance P (SP) in vivo can indirectly be attributed to the fragmentation of the undecapeptide to its N-terminal bioactive fragment SP1–7. This heptapeptide (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) is a major bioactive metabolite from SP that frequently exerts similar biological effects as the parent peptide but also, in several cases, completely opposite actions. Specific binding sites for the heptapeptide SP1–7 that are separate from the SP preferred NK receptors have been identified. In this study we demonstrate that (a) the C-terminal part of the SP metabolite SP1–7 is most important for binding as deduced from an Ala scan and that a replacement of Phe7 for Ala is deleterious, (b) truncation of the N-terminal amino acid residues of SP1–7 delivers peptides with retained binding activity, although with somewhat lower binding affinities than SP1–7 and (c) a C-terminal amide group as a replacement for the terminal carboxy group of SP1–7 and for all of the truncated ligands synthesized affords approximately 5–10-fold improvements of the binding affinities.
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4.
  • Grimsholm, Ola, et al. (författare)
  • Observations favouring the occurrence of local production and marked effects of bombesin/gastrin-releasing peptide in the synovial tissue of the human knee joint : comparisons with substance P and the NK-1 receptor.
  • 2008
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:2, s. 133-145
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously shown that levels of the neuropeptides substance P (SP) and bombesin/gastrin-releasing peptide (BN/GRP) in blood and synovial fluid correlate with levels of pro-inflammatory cytokines in patients with rheumatoid arthritis (RA). It is well-established that SP is present in nerve endings in the synovium whilst the source of BN/GRP in human joints is completely unknown. Nor is it known whether GRP-receptors (GRP-R) are present in human synovial tissue. This study aimed to investigate the expression pattern of SP, BN/GRP and their receptors (NK-1R and GRP-R) in synovial tissue. Synovial tissue specimens from patients with RA or osteoarthritis (OA) were processed for immunohistochemistry, in situ hybridisation and ELISA. The results show the presence of BN/GRP, but not SP, in cells in the synovial tissue at both the protein and mRNA level. We did not find immunoreactive BN/GRP in nerve structures. NK-1R and GRP-R were also expressed at both protein and mRNA levels in cells associated with blood vessels and cells in the interstitial tissue. ELISA analyses revealed both SP and BN/GRP to be present in synovial tissue extracts and that synovial levels of SP were higher in RA patients than those with OA. Our results indicate that BN/GRP is produced by non-neuronal cells in the synovial tissue. Furthermore, both BN/GRP and SP may exert their effects on the synovial tissue through the respective receptors. These results suggest that BN/GRP and SP may modulate inflammation and vascular events, and possibly healing processes in the synovium. Finally, nerves should not be considered as the source of BN/GRP in synovial tissue although this peptide is presumably intimately involved functionally in synovial tissue, a previously unrecognised fact.
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5.
  • Gustafsson, Lisa, et al. (författare)
  • The impact of postnatal environment on opioid peptides in young and adult male Wistar rats
  • 2008
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:2, s. 177-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Early environmental influences can change the neuronal development and thereby affect behavior in adult life. The aim in the present study was to thoroughly examine the impact of early environmental factors on endogenous opioids by using a rodent maternal separation (MS) model. The endogenous opioid peptide system is not fully developed at birth, and short- and/or long-term alterations may occur in these neural networks in animals exposed to manipulation of the postnatal environment. Rat pups were subjected to one of five rearing conditions; 15 min (MS15) litter (l) or individual (i), 360 min (MS360) l or i daily MS, or housed under normal animal facility rearing (AFR) conditions during postnatal days 1-21. Measurements of immunoreactive (ir) Met-enkephalin-Arg(6)Phe(7) (MEAP) and dynorphin B (DYNB) peptide levels in the pituitary gland and in a number of brain areas, were performed at three and 10 weeks of age, respectively. MS-induced changes were more pronounced in ir MEAP levels, especially in individually separated rats at three weeks of age and in litter-separated rats at 10 weeks of age. The enkephalin and dynorphin systems have different developmental patterns, dynorphin appearing earlier, which may point at a more sensitive enkephalin system during the early postnatal weeks. The results provide evidence that opioid peptides are sensitive for early environmental factors and show that the separation conditions are critical and also result in changes manifesting at different time points. MS-induced effects were observed in areas related to stress, drug reward and dependence mechanisms. By describing effects on opioid peptides, the study addresses the possible role of a deranged endogenous opioid system in the previously described behavioral consequences of MS.
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6.
  • Hilke, Susanne, et al. (författare)
  • Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17 beta-estradiol
  • 2009
  • Ingår i: NEUROPEPTIDES. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 43:4, s. 327-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen alters excitability and changes synaptic morphology in the rat hippocampal formation. We have compared, by means of radioimmunoassay and in situ hybridization, the effects of short-term treatment with 17 beta-estradiol on neuropeptide Y (NPY) in the brain of ovariectomized mice. A highly significant reduction in concentrations of NPY-like immunoreactivity (LI) was observed in the hippocampal formation, some cortical areas and the caudate nucleus 1 h after administration of 17 beta-estradiol as compared to the control group. In contrast, NPY transcript levels increased in the hippocampal formation (dentate gyrus) and the caudate nucleus, possibly representing a compensatory increase of NPY synthesis following increased estradiol-induced NPY release. These data suggest that 17 beta-estradiol, via membrane-related mechanisms, increases NPY release and synthesis in forebrain areas involved in cognition, mood and motor functions.
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7.
  • Kuteeva, E, et al. (författare)
  • Distribution of galanin in the brain of a galanin-overexpressing transgenic mouse
  • 2005
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 39:3, s. 293-298
  • Tidskriftsartikel (refereegranskat)abstract
    • The distribution of galanin mRNA-expressing cells and galanin-immuno reactive (I R) cell bodies and processes was studied in the brain of mice overexpressing galanin under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in colchicine-treated and non-treated animals. A widespread ectopic expression of galanin (both mRNA and peptide) was found, that is when neither transcript nor peptide could be seen in WT mice, not even after colchicine treatment. However, in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal cells, and Purkinje cells only galanin mRNA could be detected. The highest levels of galanin expression were observed in the Forebrain structures (the mitral cells of the olfactory bulb, throughout the cortex, granular and pyramidal cell layers of the hippocampus), in the mesencephalon (nucleus ruber), in the cerebellum (lateral cerebellar nucleus), in the pons (sensory and motor nuclei of the trigeminal nerve), within the medulla oblongata (facial, prepositus and spinal trigeminal nuclei). High densities of galanin-IR fibers were found in the axonal terminals of the lateral olfactory tract, hippocampal and presumably cerebellar mossy fiber system, in several thalamic and hypothalamic regions and the lower brain stem. (c) 2005 Elsevier Ltd. All rights reserved.
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8.
  • Lundberg, Kristina, 1978-, et al. (författare)
  • Diurnal and seasonal variation of cholecystokinin peptides in humans
  • 2007
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 41:1, s. 59-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Cholecystokinin (CCK) was determined in plasma obtained from 10 female (aged 23.4 ± SD 2.3 years) and nine male (aged 22.0 ± SD 1.4 years) healthy volunteers. Blood samples were drawn three times (8.00 a.m., 12 noon and 8.00 a.m.) on each of two sessions, one in the winter (November-December) and one in the summer (April-July). The participants had fasted (and were nicotine-free) since midnight preceding the sampling. A standardized breakfast was served after the first sampling. CCK was determined by radioimmunoassay. The area under the curve 0-24 h (AUC)CCK Winter was lower than AUCCCK Summer (F1:17 = 4.73, P = 0.0440) in the whole group of volunteers. On comparing the CCK concentrations within each session, there was an overall difference in winter (F2:36 = 14.81, P < 0.0001) as well in summer (F2:36 = 18.39, P < 0.0001). Post hoc comparisons yielded a difference between the 8.00 a.m. and 12 noon concentrations on the first day in winter (t = -3.96, P = 0.0009) as well as in summer (t = -4.64, P = 0.0002). The difference between the summer and winter AUCsCCK correlated with the difference between AUCs for temperatures in summer and winter (r = 0.58, P = 0.0089). The correlation was accounted for by the females (r = 0.73, P = 0.0171). The results are in accord with a diurnal and a seasonal variation of CCK in human plasma. © 2006 Elsevier Ltd. All rights reserved.
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  • Lundström, Linda, et al. (författare)
  • Important pharmacophores for binding to galanin receptor 2
  • 2005
  • Ingår i: Neuropeptides. - 0143-4179 .- 1532-2785. ; 39:3, s. 169-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Galanin(2–11) has been introduced as a receptor subtype selective ligand for the GalR2 subtype of the galanin receptors, and has gained use in pharmacological studies of galaninergic signaling in the past two years. By introducing l-Ala substitutions in the galanin(2–11) sequence, we have examined the amino acid residues which are of importance for binding to the GalR2 receptor. Our study shows that Trp2, Asn5, Gly8 and Tyr9 are of great importance for high affinity binding. When placed in an α-helical conformation, the side chains of these residues are, with the exception of Tyr9, displayed on the same “side” of the peptide. This information is useful in the rational design of non-peptide type GalR2 receptor ligands.
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10.
  • Magnusson, Kristina, et al. (författare)
  • Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography
  • 2009
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 43:2, s. 105-111
  • Tidskriftsartikel (refereegranskat)abstract
    • The kappa opioid receptor ligand [(3)H]CI-977 was used to autoradiographically determine the density of kappa opioid receptors in the male rat brain following chronic treatment with the anabolic androgenic steroid nandrolone decanoate at two different doses. As compared to controls, significantly lower densities of the kappa opioid receptor were encountered after two weeks of high dose nandrolone decanoate (15 mg/kg) in the nucleus accumbens shell (16%), lateral hypothalamic area (36%), ventromedial hypothalamic nucleus (37%), dorsomedial hypothalamic nucleus (49%), central amygdaloid nucleus, capsular part (28%), lateral globus pallidus (35%) and in the stria terminalis (24%). Furthermore, an up-regulation of the receptor level was observed in the caudate putamen (18%) and in the dorsal endopiriform nucleus (23%). These alterations in the kappa opioid receptor expression are possibly attributed to a previously observed pronounced impact of nandrolone decanoate on the dynorphinergic system and could also include involvement of the dopaminergic reward system.
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  • Roman, Erika, et al. (författare)
  • Variations in opioid peptide levels during the estrous cycle in Sprague-Dawley rats
  • 2006
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 40:3, s. 195-206
  • Tidskriftsartikel (refereegranskat)abstract
    • The estrous cycle, with its various hormonal conditions, may provide us with the means of understanding how endocrine states relate to opioid mechanisms. There has been increasing experimental support for interaction between sex steroids and opioid peptides in the central nervous system. Here, we describe fluctuations in endogenous brain immunoreactive (ir) peptide levels during various phases of the estrous cycle in the female Sprague-Dawley rat. Ir levels of dynorphin A, dynorphin B, Leu-enkephalin-Arg(6), Met-enkephalin-Arg(6)Phe(7) and nociceptin/orphanin FQ were measured in the pituitary gland and in 10 areas of the brain during the diestrus, proestrus and estrus phase. In several areas of the brain, basal levels of endogenous opioid peptides showed variation during the course of the estrous cycle. Significant differences were found between the diestrus state and the proestrus and/or estrus conditions, particularly in the nucleus accumbens, caudate putamen and the substantia nigra. The ir levels of the endogenous peptide nociceptin/orphanin FQ became altered in only one of the areas measured, indicating less variance during the estrous cycle. Correlation analyses revealed that significant associations between dynorphin A or dynorphin B and Leu-enkephalin-Arg(6) were found more often during estrus than during the diestrus and proestrus conditions. The ratio between the ir levels of Leu-enkephalin-Arg(6), a cleavage product of the enzymatic conversion of dynorphin peptides into shorter peptides in vivo, and dynorphin peptides was calculated. The significantly lower ratio between Leu-enkephalin-Arg(6) and dynorphin B in diestrus than in proestrus and estrus also indicates cyclic fluctuations in the enzymatic cleavage of dynorphin. These findings are discussed in relation to the possible role of interactions between sex steroids and opioid peptide mechanisms during the normal estrous cycle.
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12.
  • Runesson, Johan, 1980-, et al. (författare)
  • A novel GalR2-specific peptide agonist
  • 2009
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 43:3, s. 187-192
  • Tidskriftsartikel (refereegranskat)abstract
    • The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 [(RG)(2)-N-galanin(2-13)-VL-(P)(3)-(AL)(2)-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target.
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13.
  • Slawecki, Craig J., et al. (författare)
  • Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence : relation to anxiety-like and depressive-like behavior
  • 2005
  • Ingår i: Neuropeptides. - : Elsevier. - 0143-4179 .- 1532-2785. ; 39:4, s. 369-377
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Recently, animal models have been developed that demonstrate that adolescent nicotine exposure produces neurobehavioral changes which persist into adulthood. This study further examined the impact of adolescent nicotine exposure on anxiety-like and depressive-like behavior, as well as on levels of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) in this model.METHODS: Male adolescent rats (35-40 days old) were administered nicotine using Nicoderm CQ patches (Smith-Kline Beecham). Behavior in the elevated plus maze (EPM) and forced swim test (FST) was assessed 2-3 weeks after exposure ended. Brain levels of CRF and NPY were then assessed 5-6 weeks after behavioral tests were completed. In addition, blood and brain levels of nicotine resulting from nicotine treatment were examined.RESULTS: After 5 days of exposure to 5 mg/kg/day nicotine, blood levels of nicotine averaged 66+/-5 ng/ml and brain nicotine levels averaged 52+/-4 ng/g. Rats exposed to nicotine displayed an anxiety-like profile in the EPM (i.e., decreased time spent in the open arms) and an antidepressant-like profile in the FST (i.e., less time spent immobile). Rats exposed to nicotine also had increased hypothalamic and frontal cortical CRF, increased hypothalamic and hippocampal NPY, and a decreased ratio of NPY to CRF in the amygdala.CONCLUSIONS: This study demonstrates that adolescent nicotine exposure produces lasting increases in anxiety-like behavior and may reduce depressive-like behavior. These behavioral changes also occurred in concert with alterations in CRF and NPY systems. Thus, lasting neurobehavioral changes associated with adolescent nicotine exposure may be related to allostatic changes in stress peptide systems.
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  • Theodorsson, Annette, 1958-, et al. (författare)
  • Hypothermia-induced increase in galanin concentrations and ischemic neuroprotection in the rat brain
  • 2008
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:1, s. 79-87
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of hypothermia on galanin concentrations and the relation between ischemic brain lesions, hypothermia and galanin concentrations in a transient and focal rat stroke model were investigated in order to elucidate whether hypothermia-induced alterations in galanin concentrations could constitute a part of the established neuroprotective effect of hypothermia. Female rats were allocated to normothermia (37 °C) or hypothermia (33 °C) treatments during a 60 min microclip middle cerebral artery occlusion. The ischemic lesions were visualized after observation periods of 2 or 7 days and the concentration of galanin measured by radioimmunoassay in extracts of punch biopsies from both the lesioned and the contralateral control hemisphere. Hypothermia-induced an overall increase in the concentrations of immunoreactive galanin (p < 0.001). The elevated galanin levels were predominantly found in the non-ischemic control hemisphere, in the hippocampus, thalamus and the posterior part of parietal cortex. The galanin concentrations were lower in the ischemic hemisphere in both the normo- and hypothermic animals compared to the corresponding contra lateral intact hemisphere (p = 0.049). The factor of time, 2 respectively 7 days, did not show any significant difference regarding the galanin concentrations (p = 0.844). Multivariate analyses of variance revealed significant effect of ischemia on the size of the ischemic brain lesions (p = 0.001) but no overall effect of temperature when data from both 2 and 7 days observation periods were analyzed together. The ischemic lesions were generally larger at 33 degrees after 2 days (p = 0.230). Prolonged observation time of 7 days resulted in a significant reduction of the ischemic brain lesion (p = 0.011) with smaller ischemic lesions in the hypothermic group. Our data support the notion that hypothermia-induced increase in the tissue concentrations of galanin in the brain are the result of changes from optimal homeostatic conditions - the hypothermia-induced stress - rather than the ischemia/re-perfusion lesion induced changes in galanin concentrations. Hypothermia-induced elevation in galanin concentration is therefore not likely to be amongst the major protective mechanisms of hypothermia. © 2007 Elsevier Ltd. All rights reserved.
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  • Grenback, E, et al. (författare)
  • Galanin in human plasma
  • 2005
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179. ; 39:3, s. 337-340
  • Tidskriftsartikel (refereegranskat)
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  • Hilke, Susanne, et al. (författare)
  • Galanin in the hippocampal formation of female rats : effects of 17beta estradiol
  • 2005
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179. ; 39:3, s. 253-257
  • Tidskriftsartikel (refereegranskat)abstract
    • 17β-Estradiol induced an increase in tissue concentrations of galanin in the hippocampal formation of ovariectomized rats. This increase was dose- and time dependent, and occurred already 60 min after steroid administration and was not blocked by Tamoxifen®. There was also an increase in galanin in the pro-estrous phase in regularly cycling rats. The estrogen-induced rapid increase may at least in part be due to decreased release of galanin as demonstrated by in vivo microdialysis studies. Thus, sex steroid hormones may influence signalling molecules in brain areas of importance for cognitive functions.
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  • Persson-Sjögren, Solveig, et al. (författare)
  • Vasoactive intestinal polypeptide and pituitary adenylate cyclase activating polypeptide : effects on insulin release in isolated mouse islets in relation to metabolic status and age.
  • 2006
  • Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179. ; 40:4, s. 283-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity and development of the metabolic syndrome is related to an increased parasympathetic tone and hyperinsulinemia. We have now studied the effects of age and metabolic status on glucose-induced insulin release stimulated by the neuropeptides vasoactive intestinal polypeptide (VIP; 10 nM) and pituitary adenylate cyclase activating polypeptide (PACAP; 10 nM), that are constituents of the parasympathetic nerves in the islets, and the cholinergic agonists acetylcholine (ACh; 10 microM) and carbachol (10 microM), in isolated islets from female obese ob/ob mice and lean mice. Both VIP and PACAP enhanced insulin secretion in islets from 4-week-old hyperglycemic ob/ob mice. VIP did not increase 11.1 mM glucose-induced insulin release in islets from 4-week-old lean normoglycemic mice and neither did PACAP in the absence of bicarbonate. The neuropeptides increased insulin release in islets from 9 to 10-month-old mice but VIP and PACAP had no effect in islets from very old mice. ACh had no effect in islets from 9 to 10-months and older ob/ob mice in the absence of bicarbonate. The combination of VIP and cholinergic agonists had an additive effect in islets from ob/ob mice, and PACAP combined with carbachol potentiated insulin release in islets from 4-week-old lean mice. VIP increased early phase insulin release in perifused islets from young mice. A higher concentration of theophylline was needed to potentiate glucose-induced insulin release in islets from young lean mice than in islets from old lean mice and ob/ob mice. The present results demonstrate age-related dynamics in the effects of neuropeptides affecting cAMP in pancreatic islets. We suggest that VIP and PACAP contribute to the developing metabolic syndrome in ob/ob mice by aggravating hyperinsulinemia.
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  • Thunberg, Johan, et al. (författare)
  • Brain processing of tonic muscle pain induced by infusion of hypertonic saline.
  • 2005
  • Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 9:2, s. 185-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Most of the previous studies on the effects of pain on Regional Cerebral Blood Flow (rCBF) had been done with brief cutaneous or intramuscular painful stimuli. The aim of the present study was to investigate the effect on rCBF of long lasting tonic experimental muscle pain. To this end we performed PET investigations ofrCBF following tonic experimentallow back pain induced by continuous intramuscular infusion ofhypertonic (5%) saline (HS) with computer controIled infusion pump into the right erector spinae on L3 level in 19 healthy volunteers. Changes in rCBF were measured with the use of 150 labelled water during four conditions: Baseline (before start of infusion), Early Pain (4 min after start of infusion), Late Pain (20 min after start of infusion) and Post Pain (> 15 min after stop of infusion) conditions.Results of S PM analysis showed relative rCBF increase in the right insula and bilateral decrease in the temporo-parieto-occipital cortex during initial phase of painful stimulation (Early Pain) followed by activation of the medial prefrontal region and bilateral inhibition ofinsula, anterior cingulat and dorso-lateral prefrontal cortex mainly in ipsilateral hemisphere during Late Pain conditions. The results show that longer lasting tonic experimental muscle pain elicited by i.m infusion ofHS results in decreases rather than increases in rCBF. Possible explanations for differences found in rCBF during tonic hypertonic saline-induced experimental muscle pain as compared with previous findings are discussed.
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  • Antoniou, A. C., et al. (författare)
  • The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions
  • 2008
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 98:8, s. 1457-1466
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes ( polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families ( 301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920 - 1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in userfriendly Web-based program(http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home. html).
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