Corticotropin-releasing factor (CRF) receptors in intermediate lobe of the pituitary: Biochemical characterization and autoradiographic localization

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Grigoriadis, D.E.; De Souza, E.B.

1989-01-01

CRF receptors were characterized using radioligand binding and chemical affinity cross-linking techniques and localized using autoradiographic techniques in porcine, bovine and rat pituitaries. The binding of 125I-[Tyr0]-ovine CRF (125I-oCRF) to porcine anterior and neurointermediate lobe membranes was saturable and of high affinity with comparable KD values (200-600 pM) and receptor densities (100-200 fmoles/mg protein). The pharmacological rank order of potencies for various analogs and fragments of CRF in inhibiting 125I-oCRF binding in neurointermediate lobe was characteristic of the well-established CRF receptor in anterior pituitary. Furthermore, the binding of 125I-oCRF to both anterior and neurointermediate lobes of the pituitary was guanine nucleotide-sensitive. Affinity cross-linking studies revealed that the molecular weight of the CRF binding protein in rat intermediate lobe was identical to that in rat anterior lobe (Mr = 75,000). While the CRF binding protein in the anterior lobes of porcine and bovine pituitaries had identical molecular weights to CRF receptors in rat pituitary (Mr = 75,000), the molecular weight of the CRF binding protein in porcine and bovine intermediate lobe was slightly higher (Mr = 78,000). Pituitary autoradiograms from the three species showed specific binding sites for 125I-oCRF in anterior and intermediate lobes, with none being apparent in the posterior pituitary. The identification of CRF receptors in the intermediate lobe with comparable characteristics to those previously identified in the anterior pituitary substantiate further the physiological role of CRF in regulating intermediate lobe hormone secretion

Effects of fluoxetine on CRF and CRF1 expression in rats exposed to the learned helplessness paradigm.

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Fernández Macedo, Georgina Valeria; Cladouchos, María Laura; Sifonios, Laura; Cassanelli, Pablo Martín; Wikinski, Silvia

2013-02-01

Stress is a common antecedent reported by people suffering major depression. In these patients, extrahypothalamic brain areas, like the hippocampus and basolateral amygdala (BLA), have been found to be affected. The BLA synthesizes CRF, a mediator of the stress response, and projects to hippocampus. The main hippocampal target for this peptide is the CRF subtype 1 receptor (CRF1). Evidence points to a relationship between dysregulation of CRF/CRF1 extrahypothalamic signaling and depression. Because selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for depression, we investigated the effect of chronic treatment with the SSRI fluoxetine on long-term changes in CRF/CRF1 signaling in animals showing a depressive-like behavior. Male Wistar rats were exposed to the learned helplessness paradigm (LH). After evaluation of behavioral impairment, the animals were treated with fluoxetine (10 mg/kg i.p.) or saline for 21 days. We measured BLA CRF expression with RT-PCR and CRF1 expression in CA3 and the dentate gyrus of the hippocampus with in situ hybridization. We also studied the activation of one of CRF1's major intracellular signaling targets, the extracellular signal-related kinases 1 and 2 (ERK1/2) in CA3. In saline-treated LH animals, CRF expression in the BLA increased, while hippocampal CRF1 expression and ERK1/2 activation decreased. Treatment with fluoxetine reversed the changes in CRF and CRF1 expressions, but not in ERK1/2 activation. In animals exposed to the learned helplessness paradigm, there are long-term changes in CRF and CRF1 expression that are restored with a behaviorally effective antidepressant treatment.

A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats.

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Sanford, Christina A; Soden, Marta E; Baird, Madison A; Miller, Samara M; Schulkin, Jay; Palmiter, Richard D; Clark, Michael; Zweifel, Larry S

2017-01-04

Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing. Copyright © 2017 Elsevier Inc. All rights reserved.

CRF-like diuretic hormone negatively affects both feeding and reproduction in the desert locust, Schistocerca gregaria.

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Pieter Van Wielendaele

Full Text Available Diuretic hormones (DH related to the vertebrate Corticotropin Releasing Factor (CRF have been identified in diverse insect species. In the migratory locust, Locusta migratoria, the CRF-like DH (CRF/DH is localized in the same neurosecretory cells as the Ovary Maturating Parsin (OMP, a neurohormone that stimulates oocyte growth, vitellogenesis and hemolymph ecdysteroid levels in adult female locusts. In this study, we investigated whether CRF-like DH can influence feeding and reproduction in the desert locust, Schistocerca gregaria. We identified two highly similar S. gregaria CRF-like DH precursor cDNAs, each of which also encodes an OMP isoform. Alignment with other insect CRF-like DH precursors shows relatively high conservation of the CRF/DH sequence while the precursor region corresponding to OMP is not well conserved. Quantitative real-time RT-PCR revealed that the precursor transcripts mainly occur in the central nervous system and their highest expression level was observed in the brain. Injection of locust CRF/DH caused a significantly reduced food intake, while RNAi knockdown stimulated food intake. Therefore, our data indicate that CRF-like DH induces satiety. Furthermore, injection of CRF/DH in adult females retarded oocyte growth and caused lower ecdysteroid titers in hemolymph and ovaries, while RNAi knockdown resulted in opposite effects. The observed effects of CRF/DH may be part of a wider repertoire of neurohormonal activities, constituting an integrating control system that affects food intake and excretion, as well as anabolic processes like oocyte growth and ecdysteroidogenesis, following a meal. Our discussion about the functional relationship between CRF/DH and OMP led to the hypothesis that OMP may possibly act as a monitoring peptide that can elicit negative feedback effects.

Involvement of CRF2 signaling in enterocyte differentiation.

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Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Powell, Rebecca; Buisson, Alain; Bonaz, Bruno; Jacquier-Sarlin, Muriel

2017-07-28

To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation. For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CRF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CRF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TRITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mRNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor krüppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by RT-PCR and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric method. CRF2 protein is preferentially expressed in undifferentiated epithelial cells from

Contribution of amygdala CRF neurons to chronic pain.

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Andreoli, Matthew; Marketkar, Tanvi; Dimitrov, Eugene

2017-12-01

We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over

Forebrain CRF1 Modulates Early-Life Stress-Programmed Cognitive Deficits

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Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor; Wolf, Miriam; Liebl, Claudia; Scharf, Sebastian H.; Rice, Courtney J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Stewart, Michael G.; Müller, Marianne B.; Schmidt, Mathias V.

2012-01-01

Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF1), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF1 knock-out (CRF1-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF1 in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF1 signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity. PMID:21940453

Grin1 receptor deletion within CRF neurons enhances fear memory.

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Georgette Gafford

Full Text Available Corticotropin releasing factor (CRF dysregulation is implicated in mood and anxiety disorders such as posttraumatic stress disorder (PTSD. CRF is expressed in areas engaged in fear and anxiety processing including the central amygdala (CeA. Complicating our ability to study the contribution of CRF-containing neurons to fear and anxiety behavior is the wide variety of cell types in which CRF is expressed. To manipulate specific subpopulations of CRF containing neurons, our lab has developed a mouse with a Cre recombinase gene driven by a CRF promoter (CRFp3.0Cre (Martin et al., 2010. In these studies, mice that have the gene that encodes NR1 (Grin1 flanked by loxP sites (floxed were crossed with our previously developed CRFp3.0Cre mouse to selectively disrupt Grin1 within CRF containing neurons (Cre+/fGrin1+. We find that disruption of Grin1 in CRF neurons did not affect baseline levels of anxiety, locomotion, pain sensitivity or exploration of a novel object. However, baseline expression of Grin1 was decreased in Cre+/fGrin1+ mice as measured by RTPCR. Cre+/fGrin1+ mice showed enhanced auditory fear acquisition and retention without showing any significant effect on fear extinction. We measured Gria1, the gene that encodes AMPAR1 and the CREB activator Creb1 in the amygdala of Cre+/fGrin1+ mice after fear conditioning. Both Gria1 and Creb1 were enhanced in the amygdala after training. To determine if the Grin1-expressing CRF neurons within the CeA are responsible for the enhancement of fear memory in adults, we infused a lentivirus with Cre driven by a CRF promoter (LV pCRF-Cre/fGrin1+ into the CeA of floxed Grin1 mice. Cre driven deletion of Grin1 specifically within CRF expressing cells in the CeA also resulted in enhanced fear memory acquisition and retention. Altogether, these findings suggest that selective disruption of Grin1 within CeA CRF neurons strongly enhances fear memory.

The Effect of Citalopram on Midbrain CRF Receptors 1 and 2 in a Primate Model of Stress-Induced Amenorrhea

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Senashova, Olga; Reddy, Arubala P.; Cameron, Judy L.; Bethea, Cynthia L.

2012-01-01

We have demonstrated marked differences in the neurobiology of the serotonin system between stress-sensitive (SS) and stress-resilient (SR) cynomolgus macaques characterized in a model of stress-induced amenorrhea, also called functional hypothalamic amenorrhea (FHA). Dysfunction of the serotonin system in SS monkeys suggested that administration of a selective serotonin reuptake inhibitor (SSRI) might correct FHA. This study examines the effect of escitalopram (CIT) administration to SS and SR monkeys on corticotrophin-releasing factor (CRF) receptor 1 (CRF-R1) and CRF receptor 2 (CRF-R2) gene expression in the serotonin cell body region of the midbrain dorsal raphe. CRF-R1 was not significantly different between groups. There was a significant effect of treatment and a significant interaction between treatment and stress sensitivity on the average CRF-R2-positive pixel area (P < .004 and P < .006, respectively) and on the average number of CRF-R2-positive cells (P < .023 and P < .025, respectively). CIT significantly increased CRF-R2-positive pixel area and cell number in the SS group (pixel area P < .001; cell number P < .01; Bonferoni) but not in the SR group. In summary, CIT administration tended to decrease CRF-R1, but the small animal number precluded significance. CIT administration significantly increased CRF-R2 only in SS animals. These data suggest that the administration of CIT reduces anxiogenic components and increases anxiolytic components of the CRF system in the midbrain serotonin network, which in turn leads to improved ovarian function. Moreover, these data raise the possibility that SSRIs may be effective in the treatment of stress-induced infertility. PMID:22412189

Synthesis and evaluation of radioiodinated NPC 22009, a putative CRF receptor antagonist

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Balasubramanian, V.; Hiner, R.N.; Mavunkel, B.J.; Elliott, R.L.; Abreu, M.E.

1992-01-01

Several studies have suggested that corticotropin-releasing factor (CRF) plays a role in stress-related disorders such as anxiety, depression, anorexia nervosa and stress-induced immune suppression. Hence CRF antagonists have potential therapeutic utility. Recently the authors discovered that pyrazolones such as NPC 22009 and the corresponding disulfide behave as CRF antagonists in vitro with micromolar potency. To probe the nature of this CRF antagonism they developed a convenient synthesis of radioiodinated NPC 22009. Details of the synthesis and preliminary pharmacological studies are presented

Fear extinction learning can be impaired or enhanced by modulation of the CRF system in the basolateral nucleus of the amygdala

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Abiri, Dina; Douglas, Christina E.; Calakos, Katina C.; Barbayannis, Georgia; Roberts, Andrea; Bauer, Elizabeth P.

2014-01-01

The neuropeptide corticotropin-releasing factor (CRF) is released during periods of anxiety and modulates learning and memory formation. One region with particularly dense concentrations of CRF receptors is the basolateral nucleus of the amygdala (BLA), a critical structure for both Pavlovian fear conditioning and fear extinction. While CRF has the potential to modify amygdala-dependent learning, its effect on fear extinction has not yet been assessed. In the present study, we examined the mo...

Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.

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Qi, Xiaoli; Guzhva, Lidia; Yang, Zhihui; Febo, Marcelo; Shan, Zhiying; Wang, Kevin K W; Bruijnzeel, Adriaan W

2016-09-01

Smoking cessation leads to dysphoria and anxiety, which both increase the risk for relapse. This negative affective state is partly mediated by an increase in activity in brain stress systems. Recent studies indicate that prolonged viral vector-mediated overexpression of stress peptides diminishes stress sensitivity. Here we investigated whether the overexpression of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) diminishes nicotine withdrawal symptoms in rats. The effect of nicotine withdrawal on brain reward function was investigated with an intracranial self-stimulation (ICSS) procedure. Anxiety-like behavior was investigated in the elevated plus maze test and a large open field. An adeno-associated virus (AAV) pseudotype 2/5 vector was used to overexpress CRF in the lateral BNST and nicotine dependence was induced using minipumps. Administration of the nicotinic receptor antagonist mecamylamine and cessation of nicotine administration led to a dysphoria-like state, which was prevented by the overexpression of CRF in the BNST. Nicotine withdrawal also increased anxiety-like behavior in the elevated plus maze test and large open field test and slightly decreased locomotor activity in the open field. The overexpression of CRF in the BNST did not prevent the increase in anxiety-like behavior or decrease in locomotor activity. The overexpression of CRF increased CRF1 and CRF2 receptor gene expression and increased the CRF2/CRF1 receptor ratio. In conclusion, the overexpression of CRF in the BNST prevents the dysphoria-like state associated with nicotine withdrawal and increases the CRF2/CRF1 receptor ratio, which may diminish the negative effects of CRF on mood. Published by Elsevier B.V.

Radioimmunoassay for GRF and CRF in humans

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Stalla, G.K.; Losa, M.; Kaliebe, T.; Stalla, J.; Schopohl, J.; Muller, O.A.; Von Werder, K.

1987-01-01

In 1981 the structure of ovine CRF was established. One year later others isolated a 44 amino acid peptide with GH releasing activity from a pancreatic islet cell carcinoma of an acromegalic patient (hp GRF/sup 1-44/). In 1983 the gene of human CRF was cloned and the amino acid sequence of hCRF could be elucidated. It differs in 7 amino acids from oCRF. Many investigators demonstrated the biological activity of these peptides in vitro and in vivo. The aim of the authors study was to establish radioimmunoassays for GRF and hCRF with the synthetic derivates, measure endogenous GFR and CRF and circulating GRF- and CRF-levels after intravenous injection and calculate metabolic clearance rate and half-time of disappearance from serum for both releasing hormones

Inhibition of the CRF1 receptor influences the activity of antidepressant drugs in the forced swim test in rats.

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Wróbel, Andrzej; Serefko, Anna; Szopa, Aleksandra; Rojek, Karol; Poleszak, Ewa; Skalicka-Woźniak, Krystyna; Dudka, Jarosław

2017-08-01

Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of the central corticotropin-releasing factor (CRF) system are factors in the pathogenesis of depression. Though several antagonists of the CRF 1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between CRF 1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of SN003, a CRF 1 receptor blocker, on the activity of imipramine and fluoxetine in the forced swim test (FST) in rats which presented some signs of depression. The experiments were carried out on female Wistar rats subjected to 14-day subcutaneous corticosterone (CORT) administration (20 mg/kg/day). The antidepressant-like effect was determined by the FST and the CRF levels in the hypothalamus, amygdala, and peripheral blood were measured by a high-sensitivity immunoenzymatic test. SN003 (0.5 mg/kg) potentiated the antidepressant-like effect of imipramine (15 mg/kg) and fluoxetine (7.5 mg/kg). Moreover, the co-administration of the tested agents abolished CORT-induced increase in CRF levels in the examined biological material more profoundly than monotherapy. Our present findings give further evidence that the blockage of CRF action may be useful in the treatment of mood disorders. The concurrent use of well-known antidepressants with CRF 1 receptor antagonists could be beneficial in terms of safety, since it requires lower doses of the applied agents.

Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

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Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L., E-mail: laorden@um.es

2014-02-15

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

International Nuclear Information System (INIS)

Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

2014-01-01

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

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Stathopoulos Efstathios N

2010-09-01

Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this

Human CRF2 α and β splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

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Ardati, A.; Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J.; Valdenaire, O.

1999-01-01

Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF 1 and CRF 2 ). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF 2 subtype receptors, CRF 2α and CRF 2β , have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF 2β receptor. We have used radioligand binding with [ 125 I]-tyr 0 -sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [ 125 I]-tyr 0 -sauvagine binding to the hCRF 2β receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF 2α receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF 2α receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [ 125 I]-tyr 0 -sauvagine to both hCRF 2 receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF 2 α-helical CRF (9-41) oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist α-helical CRF (9-41) exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF 2 receptor isoforms. Taken together, these results indicate that the pharmacological profiles of the CRF 2 splice variants are identical. This indicates that the region of the N-terminus that varies

Molecular detection of HIV-1 subtype B, CRF01_AE, CRF33_01B, and newly emerging recombinant lineages in Malaysia.

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Chook, Jack Bee; Ong, Lai Yee; Takebe, Yutaka; Chan, Kok Gan; Choo, Martin; Kamarulzaman, Adeeba; Tee, Kok Keng

2015-03-01

A molecular genotyping assay for human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia is difficult to design because of the high level of genetic diversity. We developed a multiplex real-time polymerase chain reaction (PCR) assay to detect subtype B, CRF01_AE, CRF33_01B, and three newly described circulating recombinant forms, (CRFs) (CRF53_01B, CRF54_01B, and CRF58_01B). A total of 785 reference genomes were used for subtype-specific primers and TaqMan probes design targeting the gag, pol, and env genes. The performance of this assay was compared and evaluated with direct sequencing and phylogenetic analysis. A total of 180 HIV-infected subjects from Kuala Lumpur, Malaysia were screened and 171 samples were successfully genotyped, in agreement with the phylogenetic data. The HIV-1 genotype distribution was as follows: subtype B (16.7%); CRF01_AE (52.8%); CRF33_01B (24.4%); CRF53_01B (1.1%); CRF54_01B (0.6%); and CRF01_AE/B unique recombinant forms (4.4%). The overall accuracy of the genotyping assay was over 95.0%, in which the sensitivities for subtype B, CRF01_AE, and CRF33_01B detection were 100%, 100%, and 97.7%, respectively. The specificity of genotyping was 100%, inter-subtype specificities were > 95% and the limit of detection of 10(3) copies/mL for plasma. The newly developed real-time PCR assay offers a rapid and cost-effective alternative for large-scale molecular epidemiological surveillance for HIV-1. © The American Society of Tropical Medicine and Hygiene.

Spatio-Temporal History of HIV-1 CRF35_AD in Afghanistan and Iran.

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Eybpoosh, Sana; Bahrampour, Abbas; Karamouzian, Mohammad; Azadmanesh, Kayhan; Jahanbakhsh, Fatemeh; Mostafavi, Ehsan; Zolala, Farzaneh; Haghdoost, Ali Akbar

2016-01-01

HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug

The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent.

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Bosch, Oliver J; Nair, Hemanth P; Ahern, Todd H; Neumann, Inga D; Young, Larry J

2009-05-01

Social relationships significantly influence physiology and behavior, including the hypothalamo-pituitary-adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-coping behaviors indicative of depressive-like behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-coping behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.

Repeated restraint stress lowers the threshold for response to third ventricle CRF administration.

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Harris, Ruth B S

2017-03-01

Rats and mice exposed to repeated stress or a single severe stress exhibit a sustained increase in energetic, endocrine, and behavioral response to subsequent novel mild stress. This study tested whether the hyper-responsiveness was due to a lowered threshold of response to corticotropin releasing factor (CRF) or an exaggerated response to a standard dose of CRF. Male Sprague-Dawley rats were subjected to 3h of restraint on each of 3 consecutive days (RRS) or were non-restrained controls. RRS caused a temporary hypophagia but a sustained reduction in body weight. Eight days after the end of restraint, rats received increasing third ventricle doses of CRF (0-3.0μg). The lowest dose of CRF (0.25μg) increased corticosterone release in RRS, but not control rats. Higher doses caused the same stimulation of corticosterone in the two groups of rats. Fifteen days after the end of restraint, rats were food deprived during the light period and received increasing third ventricle doses of CRF at the start of the dark period. The lowest dose of CRF inhibited food intake during the first hour following infusion in RRS, but not control rats. All other doses of CRF inhibited food intake to the same degree in both RRS and control rats. The lowered threshold of response to central CRF is consistent with the chronic hyper-responsiveness to CRF and mild stress in RRS rats during the post-restraint period. Copyright © 2016 Elsevier Inc. All rights reserved.

Four Closely Related HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Identified in East China.

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Li, Fan; Li, Yuxueyun; Feng, Yi; Hu, Jing; Ruan, Yuhua; Xing, Hui; Shao, Yiming

2017-07-01

Five near full-length genomes of novel second-generation HIV-1 recombinant virus (JS150021, JS150029, JS150129, JS150132, and AH150183) were identified from five HIV-positive people in Jiangsu and Anhui province, east China. Phylogenic analyses showed that these five sequences are all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, grouped into four new discovered recombinant forms, which show several very similar but not identical recombinant breakpoints. The four recombinant forms are also identified to be a sort of family or related viruses, seems to be the results of different recombination events. The emergence of a serious new closely related CRF07_BC/CRF01_AE recombinant strain indicates the increasing complexity of sexual transmission of the HIV-1 epidemic in China.

Human CRF{sub 2} {alpha} and {beta} splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay

Energy Technology Data Exchange (ETDEWEB)

Ardati, A. [Rhone-Poulenc Rorer, Cardiovascular Biology, NW4, 500 Arcola Road, Collegeville, PA (United States); Goetschy, V.; Gottowick, J.; Henriot, S.; Deuschle, U.; Kilpatrick, G.J. [Central Nervous System, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland); Valdenaire, O. [Cardiovascular Research, Pharma Division, F. Hoffmann-La Roche AG, CH-4070 Basel (Switzerland)

1999-03-14

Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF{sub 1} and CRF{sub 2}). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF{sub 2} subtype receptors, CRF{sub 2{alpha}} and CRF{sub 2{beta}}, have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF{sub 2{beta}} receptor. We have used radioligand binding with [{sup 125}I]-tyr{sup 0}-sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [{sup 125}I]-tyr{sup 0}-sauvagine binding to the hCRF{sub 2{beta}} receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF{sub 2{alpha}} receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF{sub 2{alpha}} receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [{sup 125}I]-tyr{sup 0}-sauvagine to both hCRF{sub 2} receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF{sub 2}{alpha}-helical CRF{sub (9-41)}oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist {alpha}-helical CRF{sub (9-41)} exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF{sub 2} receptor isoforms. Taken together, these results indicate that the

Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

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Zhiguo Nie

2009-01-01

Full Text Available Corticotropin-releasing factor (CRF is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs in CeA neurons from wild-type (WT and CRF2 knockout (KO mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2 KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63 blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting

Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

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Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

2018-01-04

Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Water-avoidance stress enhances gastric contractions in freely moving conscious rats: role of peripheral CRF receptors.

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Nozu, Tsukasa; Kumei, Shima; Takakusaki, Kaoru; Okumura, Toshikatsu

2014-05-01

Stress alters gastrointestinal motility through central and peripheral corticotropin-releasing factor (CRF) pathways. Accumulating evidence has demonstrated that peripheral CRF is deeply involved in the regulation of gastric motility, and enhances gastric contractions through CRF receptor type 1 (CRF1) and delays gastric emptying (GE) through CRF receptor type 2 (CRF2). Since little is known whether water-avoidance stress (WAS) alters gastric motility, the present study tried to clarify this question and the involvement of peripheral CRF receptor subtypes in the mechanisms. We recorded intraluminal gastric pressure waves using a perfused manometric method. The rats were anesthetized and the manometric catheter was inserted into the stomach 4-6 days before the experiments. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after initiation of WAS in nonfasted conscious rats. Solid GE for 1 h was also measured. WAS significantly increased gastric contractions. Intraperitoneal (ip) administration of astressin (100 μg/kg, 5 min prior to stress), a nonselective CRF antagonist, blocked the response to WAS. On the other hand, pretreatment (5 min prior to stress) with neither astressin2-B (200 μg/kg, ip), a selective CRF2 antagonist, nor urocortin 2 (30 μg/kg, ip), a selective CRF2 agonist, modified the response to WAS. These drugs did not alter the basal MI. WAS did not change GE. WAS may activate peripheral CRF1 but not CRF2 signaling and stimulates gastric contractions without altering GE.

Activity-based anorexia activates CRF immunoreactive neurons in female rats.

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Scharner, Sophie; Friedrich, Tiemo; Goebel-Stengel, Miriam; Kobelt, Peter; Rose, Matthias; Stengel, Andreas

2018-05-01

Activity-based anorexia (ABA) is a well-established animal model mimicking the eating disorder anorexia nervosa (AN). Since the pathophysiology of AN is yet poorly understood and specific drug treatments are lacking so far, animal models might be useful to further understand this disease. ABA consists of time-restricted access to food for 1.5 h/day and the possibility to exercise in a running wheel for 24 h/day. This combination leads to robust body weight loss as observed in AN. Here, we investigated the activation of brain corticotropin-releasing factor (CRF) neurons, a transmitter involved in the response to stress, emotional processes and also food intake. After development of ABA, rat brains were processed for c-Fos and CRF double immunohistochemistry. ABA increased the number of c-Fos/CRF double labeled neurons in the paraventricular nucleus (PVN) and the dorsomedial hypothalamic nucleus (DMH) compared to the ad libitum (AL, ad libitum fed, no running wheel) and activity (AC, ad libitum fed, running wheel, p  0.05) group. Also the number of CRF neurons was increased in the DMH of ABA rats compared to AL and AC (p  0.05). Taken together, brain CRF activated under conditions of ABA might play a role in the development and maintenance of this animal model and possibly also in human AN. Copyright © 2018 Elsevier B.V. All rights reserved.

Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

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Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

2016-09-15

Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic renal failure (CRF in children in Jugoslavia

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Peco-Antić Amira

2003-01-01

Full Text Available The aim of this study was to analyse the demographic variables of chronic non-terminal (CRF and terminal (TRF renal failure patients (pts younger than 19 years treated in Serbia in June 2001. The prevalence of CRF pts was registered as 4,7 per million total population (pmtp or 14,1 per million child population (pmcp while corresponding values for TRF pts were 4,5 pmtp or 13,5 pmcp. The incidence of TRF pts during the period Jan.2000-Jan.2002 was 4,35 pmcp. Boys dominated only among CRF pts (34:14; 60,4% beeing between the ages of 6 and 19 yrs while at the time of diagnosis of HBI, 33,3 % of boys were yanger than 2 yrs.The causes of CRF were: reflux nephropathy 58,3%, congenital kidney disease 16,7%, familial/hereditary 14,6% glomerulonephritis 6,2% and Willms tu 4,1%. Reflux nephropathy was also the most common underlying disease of TRF accounted for 36,9% of total cases while glomerulonephritis was responsible for 23,9 %. Reflux nephropathy was associated with neural tube defect in 53,3% and with congenital lower urinary tract obstruction in 66,7%. The most of CRF (81,25% and TRF pts (95,6% were from Serbia, the others were from Monte Negro and Republic Srpska. The most of CRF (65% and TRF (80% pts were treated in University Children’s Hospital in Belgrade. Of CRF pts 46% had serum sreatinine 100-200 μmol/l, in 11% of pts it was 400-600 μmol/l and 2% of pts were in pre-terminal CRF. One third of CRF pts had proteinuria 150-500 mg/l, and second third had proteinuria greater of 1000 mg/l. Anemia was present in 54% of CRf pts, and arterial hypertension in 56%. Hemodialysis was dominant treatment modality for TRF pts and only 23,9% had functioning transplant. Conclusion: This is the first national study of demographic characteristics of pediatric CRF in Serbia. Since its prevalence is considerably lower than that in Western and North European countries the true prevalence is some what higher. The increasing incidence of pediatric TRF from 2

The Effect of Short Moderate Stress on the Midbrain CRF System in a Macaque Model of Functional Hypothalamic Amenorrhea

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Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

2014-01-01

Objective To study the effect of moderate stress on CRF components in the serotonergic midbrain region in a monkey model of FHA. Design After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days prior to euthanasia. Setting University of Pittsburgh nonhuman primate facility. Animals Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n=5), medium stress resilient (MSR, N=4) or stress sensitive (SS, n=4). Intervention 5 days of diet in a novel room with unfamiliar conspecifics. Main Outcome Measures Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of UCN1 cells; the density of UCN1 axons; the expression of CRF-R1 and CRF-R2 in the dorsal raphe nucleus. Results CRF innervation was higher in HSR than SS animals; UCN1 cell number was higher in HSR than SS animals and UCN1 axon bouton density was not different, all opposite of non-stressed animals. CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than SS animals. The relative expression of CRF-R1 and R2 was similar to non-stressed animals. Conclusions HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. PMID:23849846

Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

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V. S. Kulkarni

2012-04-01

Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

Reversal of CRF- and stress-induced anorexia by an ayurvedic formulation

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V. S. Kulkarni

2011-09-01

Full Text Available Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae and fruits of Piper longum L. and Piper nigrum L. (Piperaceae. The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1 physical stress arising from immobilization for 60 min; (2 intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight; and (3 intraperitoneal administration of fluoxetine (8 mg/kg body weight. Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

Molecular epidemiological study of HIV-1 CRF01_AE transmission in Hong Kong.

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Chen, J H K; Wong, K H; Li, P; Chan, K C; Lee, M P; Lam, H Y; Cheng, V C C; Yuen, K Y; Yam, W C

2009-08-15

The objective of this study was to investigate the transmission history of the HIV-1 CRF01_AE epidemics in Hong Kong between 1994 and 2007. A total of 465 HIV-1 CRF01_AE pol sequences were derived from an in-house or a commercial HIV-1 genotyping system. Phylogenies of CRF01_AE sequences were analyzed by the Bayesian coalescent method. CRF01_AE patient population included 363 males (78.1%) and 102 females (21.9%), whereas 65% (314 of 465) were local Chinese. Major transmission routes were heterosexual contact (63%), followed by intravenous drug use (IDU) (19%) and men having sex with men (MSM) (17%). From phylogenetic analysis, local CRF01_AE strains were from multiple origins with 3 separate transmission clusters identified. Cluster 1 consisted mainly of Chinese male IDUs and heterosexuals. Clusters 2 and 3 included mainly local Chinese MSM and non-Chinese Asian IDUs, respectively. Chinese reference isolates available from China (Fujian, Guangxi, or Liaoning) were clonally related to our transmission clusters, demonstrating the epidemiological linkage of CRF01_AE infections between Hong Kong and China. The 3 individual local transmission clusters were estimated to have initiated since late 1980s and late 1990s, causing subsequent epidemics in the early 2000s. This is the first comprehensive molecular epidemiological study of HIV-1 CRF01_AE in Hong Kong. It revealed that MSM contact is becoming a major route of local CRF01_AE transmission in Hong Kong. Epidemiological linkage of CRF01_AE between Hong Kong and China observed in this study indicates the importance of regular molecular epidemiological surveillance for the HIV-1 epidemic in our region.

Detecting New Words from Chinese Text Using Latent Semi-CRF Models

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Sun, Xiao; Huang, Degen; Ren, Fuji

Chinese new words and their part-of-speech (POS) are particularly problematic in Chinese natural language processing. With the fast development of internet and information technology, it is impossible to get a complete system dictionary for Chinese natural language processing, as new words out of the basic system dictionary are always being created. A latent semi-CRF model, which combines the strengths of LDCRF (Latent-Dynamic Conditional Random Field) and semi-CRF, is proposed to detect the new words together with their POS synchronously regardless of the types of the new words from the Chinese text without being pre-segmented. Unlike the original semi-CRF, the LDCRF is applied to generate the candidate entities for training and testing the latent semi-CRF, which accelerates the training speed and decreases the computation cost. The complexity of the latent semi-CRF could be further adjusted by tuning the number of hidden variables in LDCRF and the number of the candidate entities from the Nbest outputs of the LDCRF. A new-words-generating framework is proposed for model training and testing, under which the definitions and distributions of the new words conform to the ones existing in real text. Specific features called “Global Fragment Information” for new word detection and POS tagging are adopted in the model training and testing. The experimental results show that the proposed method is capable of detecting even low frequency new words together with their POS tags. The proposed model is found to be performing competitively with the state-of-the-art models presented.

The Effect of Peripheral CRF Peptide and Water Avoidance Stress on Colonic and Gastric Transit in Guinea Pigs.

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Hussain, Zahid; Kim, Hae Won; Huh, Cheal Wung; Lee, Young Ju; Park, Hyojin

2017-07-01

Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) diseases; however, there is frequent overlap between FD and IBS patients. Emerging evidence links the activation of corticotropin releasing factor (CRF) receptors with stress-related alterations of gastric and colonic motor function. Therefore, we investigated the effect of peripheral CRF peptide and water avoidance stress (WAS) on upper and lower GI transit in guinea pigs. Dosages 1, 3, and 10 μg/kg of CRF were injected intraperitoneally (IP) in fasted guinea pigs 30 minutes prior to the intragastric administration of charcoal mix to measure upper GI transit. Colonic transits in non-fasted guinea pigs were assessed by fecal pellet output assay after above IP CRF doses. Blockade of CRF receptors by Astressin, and its effect on GI transit was also analyzed. Guinea pigs were subjected to WAS to measure gastrocolonic transit in different sets of experiments. Dose 10 μg/kg of CRF significantly inhibited upper GI transit. In contrast, there was dose dependent acceleration of the colonic transit. Remarkably, pretreatment of astressin significantly reverses the effect of CRF peptide on GI transit. WAS significantly increase colonic transit, but failed to accelerate upper GI transit. Peripheral CRF peptide significantly suppressed upper GI transit and accelerated colon transit, while central CRF involved WAS stimulated only colonic transit. Therefore, peripheral CRF could be utilized to establish the animal model of overlap syndrome. © Copyright: Yonsei University College of Medicine 2017.

Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.

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Gondré-Lewis, Marjorie C; Warnock, Kaitlin T; Wang, Hong; June, Harry L; Bell, Kimberly A; Rabe, Holger; Tiruveedhula, Veera Venkata Naga Phani Babu; Cook, James; Lüddens, Hartmut; Aurelian, Laure; June, Harry L

2016-01-01

Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the

CRF2 signaling is a novel regulator of cellular adhesion and migration in colorectal cancer cells.

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Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Lainé, Michèle; Cristina, Nadine; Vachez, Yvan; Scoazec, Jean-Yves; Bonaz, Bruno; Jacquier-Sarlin, Muriel

2013-01-01

Stress has been proposed to be a tumor promoting factor through the secretion of specific neuromediators, such as Urocortin2 and 3 (Ucn2/3), however its role in colorectal cancer (CRC) remains elusive. We observed that Ucn2/3 and their receptor the Corticotropin Releasing Factor receptor 2 (CRF2) were up-regulated in high grade and poorly differentiated CRC. This suggests a role for CRF2 in the loss of cellular organization and tumor progression. Using HT-29 and SW620 cells, two CRC cell lines differing in their abilities to perform cell-cell contacts, we found that CRF2 signals through Src/ERK pathway to induce the alteration of cell-cell junctions and the shuttle of p120ctn and Kaiso in the nucleus. In HT-29 cells, this signaling pathway also leads to the remodeling of cell adhesion by i) the phosphorylation of Focal Adhesion Kinase and ii) a modification of actin cytoskeleton and focal adhesion complexes. These events stimulate cell migration and invasion. In conclusion, our findings indicate that CRF2 signaling controls cellular organization and may promote metastatic potential of human CRC cells through an epithelial-mesenchymal transition like process. This contributes to the comprehension of the tumor-promoting effects of stress molecules and designates Ucn2/3-CRF2 tandem as a target to prevent CRC progression and aggressiveness.

Molecular epidemiology of HIV type 1 infection in Iran: genomic evidence of CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use.

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Jahanbakhsh, Fatemeh; Ibe, Shiro; Hattori, Junko; Monavari, Seyed Hamid Reza; Matsuda, Masakazu; Maejima, Masami; Iwatani, Yasumasa; Memarnejadian, Arash; Keyvani, Hossein; Azadmanesh, Kayhan; Sugiura, Wataru

2013-01-01

To understand the molecular epidemiology of HIV-1 infection in Iran, we conducted the first study to analyze the genome sequence of Iranian HIV-1 isolates. For this cross-sectional study, we enrolled 10 HIV-1-infected individuals associated with injection drug use from Tehran, Shiraz, and Kermanshah. Near full-length genome sequences obtained from their plasma samples were used for phylogenetic tree and similarity plotting analyses. Among 10 isolates, nine were clearly identified as CRF35_AD and the remaining one as CRF01_AE. Interestingly, five of our Iranian CRF35_AD isolates made two clusters with 10 Afghan CRF35_AD isolates in a phylogenetic tree, indicating epidemiological connections among injection drug users in Iran and Afghanistan. In contrast, our CRF01_AE isolate had no genetic relationship with any other CRF01_AE isolates worldwide, even from Afghanistan. This study provides the first genomic evidence of HIV-1 CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use in Iran.

CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

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2008-07-01

Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

Dominance of HIV-1 subtype CRF01_AE in sexually acquired cases leads to a new epidemic in Yunnan province of China.

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Yong Zhang

2006-11-01

Full Text Available Dating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1 infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized.Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 321 patients representing Yunnan's 16 prefectures from four risk groups, 11 ethnic populations, and ten occupations. We identified three major circulating subtypes: C/CRF07_BC/CRF08_BC (53%, CRF01_AE (40.5%, and B (6.5% by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors, 90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08_BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes.This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development.

Peripheral a-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats

NARCIS (Netherlands)

van den Wijngaard, R. M.; Stanisor, O. I.; van Diest, S. A.; Welting, O.; Wouters, M. M.; de Jonge, W. J.; Boeckxstaens, G. E.

2012-01-01

Background Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of

Evidence for possible biological advantages of the newly emerging HIV-1 circulating recombinant form from Malaysia - CRF33_01B in comparison to its progenitors - CRF01_AE and subtype B.

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Lau, Katherine A; Wang, Bin; Miranda-Saksena, Monica; Boadle, Ross; Kamarulzaman, Adeeba; Ng, Kee-Peng; Saksena, Nitin K

2010-04-01

In Malaysia, co-circulation of CRF01_AE and subtype B has resulted in the emergence of the second generation derivative; CRF33_01B in approximately 20% of its HIV-1 infected individuals. Our objective was to identify possible biological advantages that CRF33_01B possesses over its progenitors. Biological and molecular comparisons of CRF33_01B against its parental subtypes clearly show that CRF33_01B replicated better in activated whole peripheral blood mononuclear cells (PBMCs) and CD4+ T-lymphocytes, but not monocyte-derived macrophages (MDMs). Also, its acquired fitness was greater than CRF01_AE but not subtype B. Moreover, CRF33_01B has higher rate of apoptotic cell death and syncytia induction compared to subtype B. These adaptive and survival abilities could have been acquired by CRF33_01B due to the incorporation of subtype B fragments into the gag-RT region of its full-length genome. Our studies confirm the previously held belief that HIV-1 strains may harbor enhanced biological fitness upon recombination. We therefore estimate a possible gradual replacement of the current predominance of CRF01_AE, as well as wider dissemination of CRF33_01B, together with the identification of other new CRF01_AE/B inter-subtype recombinants in Malaysia.

Expansion of the CRF19_cpx Variant in Spain.

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Patiño Galindo, Juan Angel; Torres-Puente, Manoli; Gimeno, Concepción; Ortega, Enrique; Navarro, David; Galindo, María José; Navarro, Laura; Navarro, Vicente; Juan, Amparo; Belda, Josefina; Bracho, María Alma; González-Candelas, Fernando

2015-08-01

HIV-1 CRF19_cpx, is a recombinant variant found almost exclusively in Cuba and recently associated to a faster AIDS onset. Infection with this variant leads to higher viral loads and levels of RANTES and CXCR4 co-receptor use. The goal of this study was to assess the presence of CRF19_cpx in the Spanish province of Valencia, given its high pathogenicity. 1294 HIV-1 protease-reverse transcriptase (PR/RT) sequences were obtained in Valencia (Spain), between 2005 and 2014. After subtyping, the detected CRF19_cpx sequences were aligned with 201 CRF19_cpx and 66 subtype D sequences retrieved from LANL, and subjected to maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. The presence of resistance mutations in the PR/RT region of these sequences was also analyzed. Among the 9 CRF19_cpx sequences from different patients found (prevalence <0.1%), 7 grouped in two well-supported clades (groups A, n=4, and B, n=3), suggesting the existence of at least two independent introductions which subsequently started to expand in the studied Spanish region. Unprotected sex between men was the only known transmission route. Coalescent analyses suggested that the introductions in Valencia occurred between 2008 and 2010. Resistance mutations in the RT region were found in all sequences from group A (V139D) and in two sequences from group B (E138A). This study reports for the first time the recent expansion of CRF19_cpx outside Cuba. Our results suggest that CRF19_cpx might become an emerging HIV variant in Spain, affecting Spanish native MSM and not only Cuban migrants. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of non-CRF inhibition in contour detection

NARCIS (Netherlands)

Grigorescu, C.; Petkov, N.; Westenberg, M.A.

2003-01-01

We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve the performance of contour detectors. Non-CRF inhibition is exhibited by 80% of the orientation selective neurons in the primary visual cortex of macaque monkeys and has been

Phylodynamic analysis of the dissemination of HIV-1 CRF01_AE in Vietnam.

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Liao, Huanan; Tee, Kok Keng; Hase, Saiki; Uenishi, Rie; Li, Xiao-Jie; Kusagawa, Shigeru; Thang, Pham Hong; Hien, Nguyen Tran; Pybus, Oliver G; Takebe, Yutaka

2009-08-15

To estimate the epidemic history of HIV-1 CRF01_AE in Vietnam and adjacent Guangxi, China, we determined near full-length nucleotide sequences of CRF01_AE from a total of 33 specimens collected in 1997-1998 from different geographic regions and risk populations in Vietnam. Phylogenetic and Bayesian molecular clock analyses were performed to estimate the date of origin of CRF01_AE lineages. Our study reconstructs the timescale of CRF01_AE expansion in Vietnam and neighboring regions and suggests that the series of CRF01_AE epidemics in Vietnam arose by the sequential introduction of founder strains into new locations and risk groups. CRF01_AE appears to have been present among heterosexuals in South-Vietnam for more than a decade prior to its epidemic spread in the early 1990s. In the late 1980s, the virus spread to IDUs in Southern Vietnam and subsequently in the mid-1990s to IDUs further north. Our results indicate the northward dissemination of CRF01_AE during this time.

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

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Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole-rats and solitary Cape mole-rats.

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Coen, Clive W; Kalamatianos, Theodosis; Oosthuizen, Maria K; Poorun, Ravi; Faulkes, Christopher G; Bennett, Nigel C

2015-11-01

Various aspects of social behavior are influenced by the highly conserved corticotrophin-releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF1 and CRF2 , and two of their ligands, CRF and urocortin 3, respectively, in African mole-rat species with diametrically opposed social behavior. Naked mole-rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole-rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF1 binding in naked mole-rats exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole-rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF2 binding, the sites with a greater level in naked mole-rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole-rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF1 binding in the nucleus accumbens of Cape mole-rats reflects their lack of affiliative behavior. © 2015 Wiley Periodicals, Inc.

Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE

OpenAIRE

Poljak, Mario; Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Stuck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie; Alexiev, Ivailo

2016-01-01

Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap...

Laos Organization Name Using Cascaded Model Based on SVM and CRF

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Duan Shaopeng

2017-01-01

Full Text Available According to the characteristics of Laos organization name, this paper proposes a two layer model based on conditional random field (CRF and support vector machine (SVM for Laos organization name recognition. A layer of model uses CRF to recognition simple organization name, and the result is used to support the decision of the second level. Based on the driving method, the second layer uses SVM and CRF to recognition the complicated organization name. Finally, the results of the two levels are combined, And by a subsequent treatment to correct results of low confidence recognition. The results show that this approach based on SVM and CRF is efficient in recognizing organization name through open test for real linguistics, and the recalling rate achieve 80. 83％and the precision rate achieves 82. 75％.

The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

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Valero, E; Gómez-Milanés, I; Almela, P; Ribeiro Do Couto, B; Laorden, M L; Milanés, M V; Núñez, C

2018-06-08

Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse

Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats.

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Watanabe, Mari A; Kucenas, Sarah; Bowman, Tamara A; Ruhlman, Melissa; Knuepfer, Mark M

2010-01-14

Stress or cocaine evokes either a large increase in systemic vascular resistance (SVR) or a smaller increase in SVR accompanied by an increase in cardiac output (designated vascular and mixed responders, respectively) in Sprague-Dawley rats. We hypothesized that the central nucleus of the amygdala (CeA) mediates this variability. Conscious, freely-moving rats, instrumented for measurement of arterial pressure and cardiac output and for drug delivery into the CeA, were given cocaine (5 mg/kg, iv, 4-6 times) and characterized as vascular (n=15) or mixed responders (n=10). Subsequently, we administered cocaine after bilateral microinjections (100 nl) of saline or selective agents in the CeA. Muscimol (80 pmol), a GABA(A) agonist, or losartan (43.4 pmol), an AT(1) receptor antagonist, attenuated the cocaine-induced increase in SVR in vascular responders, selectively, such that vascular responders were no longer different from mixed responders. The corticotropin releasing factor (CRF) antagonist, alpha-helical CRF(9-41) (15.7 pmol), abolished the difference between cardiac output and SVR in mixed and vascular responders. We conclude that greater increases in SVR observed in vascular responders are dependent on AT(1) receptor activation and, to a lesser extent on CRF receptors. Therefore, AT(1) and CRF receptors in the CeA contribute to hemodynamic response variability to intravenous cocaine.

Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan.

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Yue Chen

Full Text Available A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%, together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15% but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a while 12 (38% were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan.

Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan

Science.gov (United States)

Chen, Yue; Hora, Bhavna; DeMarco, Todd; Shah, Sharaf Ali; Ahmed, Manzoor; Sanchez, Ana M.; Su, Chang; Carter, Meredith; Stone, Mars; Hasan, Rumina; Hasan, Zahra; Busch, Michael P.; Denny, Thomas N.; Gao, Feng

2016-01-01

A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%), together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a) within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15%) but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a) while 12 (38%) were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan. PMID:27973597

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

OpenAIRE

Andreas Stengel; Yvette F. Taché; Yvette F. Taché

2017-01-01

Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a br...

HIV-1 CRF_BC recombinants infection in China: molecular epidemic and characterizations.

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Ouyang, Yabo; Shao, Yiming; Ma, Liying

2012-03-01

CRF_BC recombinant strains were first identified in China and are one of the most prevalent and characteristically unique HIV-1 subtypes across China. Here we aim to review the published data about HIV-1 CRF_BC recombinant strains epidemic in China and to characterize the genetics, biology and drug resistance of this virus. This study may help to better understand the current situation of HIV-1 CRF_BC prevalence and facilitate the development of vaccines and more efficient anti-HIV-1 regimens in China.

Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

International Nuclear Information System (INIS)

Perna, A.F.; Smogorzewski, M.; Massry, S.G.

1988-01-01

Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells.

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Pelissier-Rota, M; Chartier, N T; Bonaz, B; Jacquier-Sarlin, M R

2017-07-01

Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction. Non-neuronal acetylcholine (Ach) and muscarinic receptors (mAchR) also contribute to alterations of epithelial cell functions. In this study, we investigated the mechanisms through which stress and Ach modulate epithelial cell adhesive properties. We show that Ach-induced activation of mAchR in HT-29 cells results in cell dissociation together with changes in cell-matrix contacts, which correlates with the acquisition of invasive potential consistent with a matrix metalloproteinase (MMP) mode of invasion. These processes result from mAchR subsequent stimulation of the cascade of src/Erk and FAK activation. Ach-induced secretion of laminin 332 leads to α3β1 integrin activation and RhoA-dependent reorganization of the actin cytoskeleton. We show that Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling. This is reinforced by the fact that Ach-mediated activation of mAchR stimulates both the synthesis and the release of CRF2 ligands in HT-29 cells (effects blocked by atropine). In summary, our data provides evidence for a novel intracellular circuit involving mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier dysfunction and exacerbate mucosal inflammation. Copyright © 2017. Published by Elsevier B.V.

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

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Schwandt, Melanie L; Cortes, Carlos R; Kwako, Laura E; George, David T; Momenan, Reza; Sinha, Rajita; Grigoriadis, Dimitri E; Pich, Emilio Merlo; Leggio, Lorenzo; Heilig, Markus

2016-01-01

Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21–65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced alcohol craving and relapse. PMID:27109623

Sex differences between CRF1 receptor deficient mice following naloxone-precipitated morphine withdrawal in a conditioned place aversion paradigm: implication of HPA axis.

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Juan-Antonio García-Carmona

Full Text Available Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R and the different response of male and female mice in the expression and extinction of the aversive memory.We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10-60 mg/kg. Negative state associated with naloxone (1 mg/kg s.c.-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA paradigm. No sex differences for CPA expression were found in wild-type (n = 29 or CRF1R knockout (KO mice (n = 29. However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH levels observed in wild-type (n = 11 mice after CPA expression, were attenuated in CRF1R KO mice (n = 10. In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and ischaemic conditions.

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De Michele, Manuela; Touzani, Omar; Foster, Alan C; Fieschi, Cesare; Sette, Giuliano; McCulloch, James

2005-09-01

The expression of corticotrophin-releasing factor (CRF) receptors in cerebral arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF). In the present study, the effects of CRF, CRF-like peptides and the CRF broad spectrum antagonist DPhe-CRF on CBF have been investigated under normal physiologic conditions and in the margins of focal ischaemic insult. The experiments were carried out in anaesthetised and ventilated rats. Changes in CBF after subarachnoid microapplication of CRF and related peptides were assessed with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were injected approximately 60 minutes after permanent middle cerebral artery occlusion (MCAo). Microapplication of CRF and related peptides in normal rats into the subarachnoid space produced sustained concentration-dependent increases in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not alter CBF itself. A second microapplication of CRF 30 min after the first failed to produce increases in CBF in normal animals. Microapplication of CRF in the subarachnoid space overlying the ischaemic cortex effected minor increases in CBF whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF peptidergic system increases CBF in the rat. Repeated activation of CRF receptors results in tachyphylaxis of the vasodilator response. CRF vasodilator response is still present after MCAo in the ischaemic penumbra, suggesting that the CRF peptidergic system may modulate CBF in ischaemic stroke.

Robust rooftop extraction from visible band images using higher order CRF

KAUST Repository

Li, Er

2015-08-01

In this paper, we propose a robust framework for building extraction in visible band images. We first get an initial classification of the pixels based on an unsupervised presegmentation. Then, we develop a novel conditional random field (CRF) formulation to achieve accurate rooftops extraction, which incorporates pixel-level information and segment-level information for the identification of rooftops. Comparing with the commonly used CRF model, a higher order potential defined on segment is added in our model, by exploiting region consistency and shape feature at segment level. Our experiments show that the proposed higher order CRF model outperforms the state-of-the-art methods both at pixel and object levels on rooftops with complex structures and sizes in challenging environments. © 1980-2012 IEEE.

Functional Impact of Corticotropin-Releasing Factor Exposure on Tau Phosphorylation and Axon Transport.

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Michelle H Le

Full Text Available Stress exposure or increased levels of corticotropin-releasing factor (CRF induce hippocampal tau phosphorylation (tau-P in rodent models, a process that is dependent on the type-1 CRF receptor (CRFR1. Although these preclinical studies on stress-induced tau-P provide mechanistic insight for epidemiological work that identifies stress as a risk factor for Alzheimer's disease (AD, the actual impact of stress-induced tau-P on neuronal function remains unclear. To determine the functional consequences of stress-induced tau-P, we developed a novel mouse neuronal cell culture system to explore the impact of acute (0.5hr and chronic (2hr CRF treatment on tau-P and integral cell processes such as axon transport. Consistent with in vivo reports, we found that chronic CRF treatment increased tau-P levels and caused globular accumulations of phosphorylated tau in dendritic and axonal processes. Furthermore, while both acute and chronic CRF treatment led to significant reduction in CREB activation and axon transport of brain-derived neurotrophic factor (BDNF, this was not the case with mitochondrial transport. Acute CRF treatment caused increased mitochondrial velocity and distance traveled in neurons, while chronic CRF treatment modestly decreased mitochondrial velocity and greatly increased distance traveled. These results suggest that transport of cellular energetics may take priority over growth factors during stress. Tau-P was required for these changes, as co-treatment of CRF with a GSK kinase inhibitor prevented CRF-induced tau-P and all axon transport changes. Collectively, our results provide mechanistic insight into the consequences of stress peptide-induced tau-P and provide an explanation for how chronic stress via CRF may lead to neuronal vulnerability in AD.

A newly emerging HIV-1 recombinant lineage (CRF58_01B) disseminating among people who inject drugs in Malaysia.

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Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

2014-01-01

The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

A newly emerging HIV-1 recombinant lineage (CRF58_01B disseminating among people who inject drugs in Malaysia.

Directory of Open Access Journals (Sweden)

Wei Zhen Chow

Full Text Available The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K and to date 55 circulating recombinant forms (CRFs. In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B, CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%, CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258. Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

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Stengel, Andreas; Taché, Yvette F

2017-01-01

Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving.

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Epstein, David H; Kennedy, Ashley P; Furnari, Melody; Heilig, Markus; Shaham, Yavin; Phillips, Karran A; Preston, Kenzie L

2016-12-01

In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. To test anticraving properties of the CRF 1 antagonist pexacerfont in humans. We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS). The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r effect  = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect  = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics. The findings may support further investigation of the anticraving properties of CRF 1 antagonists, especially for food.

Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

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Giardino, William J; Mark, Gregory P; Stenzel-Poore, Mary P; Ryabinin, Andrey E

2012-02-01

Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5-10 mg/kg). While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction.

Acute and repeated ECS treatment increases CRF, POMC and PENK gene expression in selected regions of the rat hypothalamus.

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Garcia-Garcia, L; Llewellyn-Jones, V; Fernandez Fernandez, I; Fuentes, J A; Manzanares, J

1998-01-05

The purpose of this study was to investigate the effects of acute and repeated electroconvulsive shock (ECS) on corticotropin releasing factor (CRF), proopiomelanocortin (POMC) and proenkephalin (PENK) gene expression in selected regions of the brain and pituitary of the rat. Acute ECS increased CRF gene expression in the paraventricular nucleus (PVN) by 20%, an effect that was further enhanced to 38% when rats received repeated ECS treatment. Acute and repeated ECS increased POMC gene expression in the arcuate nucleus (ARC) by 49-59% but failed to alter these mRNA levels in the anterior lobe (AL) of the pituitary gland. PENK gene expression was increased by 35% in the nucleus accumbens (NA) and by 180% the ventromedial nucleus (VMN) after acute or repeated ECS treatment but no significant changes were found in the PVN or striatum (ST). Taken together, these results indicate a differential CRF and opioid gene expression regulation after acute or repeated ECS treatment that may be relevant to their therapeutic or side effects in depression.

Internalization of the human CRF receptor 1 is independent of classical phosphorylation sites and of beta-arrestin 1 recruitment

DEFF Research Database (Denmark)

Rasmussen, Trine N; Novak, Ivana; Nielsen, Søren M

2004-01-01

The corticotropin releasing factor receptor 1 (CRFR1) belongs to the superfamily of G-protein coupled receptors. Though CRF is involved in the aetiology of several stress-related disorders, including depression and anxiety, details of CRFR1 regulation such as internalization remain uncharacterized...

Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval.

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Janitzky, K; Peine, A; Kröber, A; Yanagawa, Y; Schwegler, H; Roskoden, T

2014-10-01

The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice. Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure. Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.

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Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

2013-10-01

To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea. After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia. Primate research center. Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4). Five days of diet in a novel room with unfamiliar conspecifics. Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus. The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals. The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Regulation and Roles of Urocortins in the Vascular System

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Kazunori Kageyama

2012-01-01

Full Text Available Urocortins (Ucns are members of the corticotropin-releasing factor (CRF family of peptides. Ucns would have potent effects on the cardiovascular system via the CRF receptor type 2 (CRF2 receptor. Regulation and roles of each Ucn have been determined in the vascular system. Ucns have more potent vasodilatory effects than CRF. Human umbilical vein endothelial cells (HUVECs express Ucns1-3 mRNAs, and the receptor, CRF2a receptor mRNA. Ucns1-3 mRNA levels are differentially regulated in HUVECs. Differential regulation of Ucns may suggest differential roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL-6 gene expression and secretion in rat aortic smooth muscle A7r5 cells. The increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells suggests that smooth muscle cells may be a source of IL-6 secretion under physiological stress conditions. Ucns are important and unique modulators of vascular smooth muscle cells and act directly or indirectly as autocrine and paracrine factors in the vascular system.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

Directory of Open Access Journals (Sweden)

Andreas Stengel

2017-04-01

Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

Short Communication: Reassessing the Origin of the HIV-1 CRF02_AG Lineages Circulating in Brazil.

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Delatorre, Edson; Velasco-De-Castro, Carlos A; Pilotto, José H; Couto-Fernandez, José Carlos; Bello, Gonzalo; Morgado, Mariza G

2015-12-01

HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil. As more CRF02_AG samples have been identified in Brazil, we performed a new phylogeographic analysis using a larger dataset than before. A total of 20 Brazilian (18 from Rio de Janeiro and two from São Paulo) and 1,485 African HIV-1 CRF02_AG pol sequences were analyzed using maximum likelihood (ML). The ML tree showed that the Brazilian sequences were distributed in five different lineages. The Bayesian phylogeographic analysis of the Brazilian and their most closely related African sequences (n = 212) placed the origin of all Brazilian lineages in West Africa, probably Ghana, Senegal, and Nigeria. Two monophyletic clades were identified, comprising only sequences from Rio de Janeiro, and their date of origin was estimated at around 1985 (95% highest posterior density: 1979-1992). These results support the existence of at least five independent introductions of the CRF02_AG lineage from West Africa into Brazil and further indicate that at least two of these lineages have been locally disseminated in the Rio de Janeiro state over the past 30 years.

Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats.

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Blacktop, Jordan M; Vranjkovic, Oliver; Mayer, Matthieu; Van Hoof, Matthew; Baker, David A; Mantsch, John R

2016-03-01

Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1.0 mg/kg/ing; 14 × 6 h/day) and extinction and were tested for reinstatement in response to footshock (0.5 mA, 0.5" duration, average every 40 s; range 10-70 s) or intra-VTA CRF delivery (500 ng/side) following intra-VTA pretreatment with the GABA-A antagonist, bicuculline, the GABA-B antagonist, 2-hydroxysaclofen or vehicle. Intra-VTA bicuculline (1, 10 or 20 ng/side) failed to block footshock- or CRF-induced cocaine seeking at either dose tested. By contrast, 2-hydroxysaclofen (0.2 or 2 μg/side) prevented reinstatement by both footshock and intra-VTA CRF at a concentration that failed to attenuate food-reinforced lever pressing (45 mg sucrose-sweetened pellets; FR4 schedule) in a separate group of rats. These data suggest that GABA-B receptor-dependent CRF actions in the VTA mediate stress-induced cocaine seeking and that GABA-B receptor antagonists may have utility for the management of stress-induced relapse in cocaine addicts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Activation of corticotropin-releasing factor receptors from the basolateral or central amygdala increases the tonic immobility response in guinea pigs: an innate fear behavior.

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Donatti, Alberto Ferreira; Leite-Panissi, Christie Ramos Andrade

2011-11-20

The tonic immobility (TI) behavior is an innate response associated with extreme threat situations such as a predator attack. Several studies have provided evidence suggesting an important role for corticotropin-releasing factor (CRF) in the regulation of the endocrine system, defensive behaviors and behavioral responses to stress. TI has been shown to be positively correlated with the basal plasma levels of corticosterone. CRF receptors and neurons that are immunoreactive to CRF are found in many cerebral regions, especially in the amygdaloid complex. Previous reports have demonstrated the involvement of the basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI response. In this study, we evaluated the CRF system of the BLA and the CeA in the modulation of the TI response in guinea pigs. The activation of CRF receptors in the BLA and in the CeA promoted an increase in the TI response. In contrast, the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the duration of the TI response. Moreover, neither the activation nor inhibition of CRF receptors in the BLA or the CeA altered spontaneous motor activity in the open-field test. These data suggest that the activation of the CRF receptors in the BLA or the CeA probably potentiates fear and anxiety, which may be one of the factors that promote an increase in the TI behavior. Therefore, these data support the role of the CRF system in the control of emotional responses, particularly in the modulation of innate fear. Copyright © 2011 Elsevier B.V. All rights reserved.

Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin

Science.gov (United States)

Martin-Fardon, Rémi; Zorrilla, Eric P.; Ciccocioppo, Roberto; Weiss, Friedbert

2010-01-01

Stress-like symptoms are an integral part of acute and protracted drug withdrawal, and several lines of evidence have shown that dysregulation of brain stress systems, including the extrahypothalamic corticotropin-releasing factor (CRF) system, following long-term drug use is of major importance in maintaining drug and alcohol addiction. Recently, two other neuropeptide systems have attracted interest, the nociceptin/orphanin FQ (N/OFQ) and orexin/hypocretin (Orx/Hcrt) systems. N/OFQ participates in a wide range of physiological responses, and the hypothalamic Orx/Hcrt system helps regulate several physiological processes, including feeding, energy metabolism, and arousal. Moreover, these two systems have been suggested to participate in psychiatric disorders, including anxiety and drug addiction. Dysregulation of these systems by chronic drug exposure has been hypothesized to play a role in the maintenance of addiction and dependence. Recent evidence demonstrated that interactions between CRF-N/OFQ and CRF-Orx/Hcrt systems may be functionally relevant for the control of stress-related addictive behavior. The present review discusses recent findings that support the hypotheses of the participation and dysregulation of these systems in drug addiction and evaluates the current understanding of interactions among these stress-regulatory peptides. PMID:20026088

Corticotropin-releasing factor (CRF) in stress and disease: A review of literature and treatment perspectives with special emphasis on psychiatric disorders

DEFF Research Database (Denmark)

Krohg, K.; Hageman, I.; Jorgensen, M.B.

2008-01-01

The CRF family of neuropeptides and receptors is involved in a variety of stress responses, in the regulation of appetite, metabolic and inflammatory processes as well as intestinal movements. From a primarily psychiatric perspective, the present paper reviews the literature on its anatomy...

Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

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Bryce, Courtney A; Floresco, Stan B

2016-07-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.

Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption.

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Pucci, Mariangela; Micioni Di Bonaventura, Maria Vittoria; Giusepponi, Maria Elena; Romano, Adele; Filaferro, Monica; Maccarrone, Mauro; Ciccocioppo, Roberto; Cifani, Carlo; D'Addario, Claudio

2016-11-01

Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds. © 2015 Society for the Study of Addiction.

PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

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Sullivan, Gregory M.; Parsey, Ramin V.; Kumar, J.S. Dileep; Arango, Victoria; Kassir, Suham A.; Huang, Yung-yu; Simpson, Norman R.; Van Heertum, Ronald L.; Mann, J. John

2007-01-01

Aim: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [ 11 C]R121920 and [ 11 C]DMP696 in the nonhuman primate for application in positron emission tomography (PET) studies of CRF1. Methods: PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET. Results: Both [ 11 C]R121920 and [ 11 C]DMP696 distributed rapidly and uniformly throughout the brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [ 125 I]Tyr 0 -sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (B max ) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded B max of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K D ) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore, B max and K D were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. Conclusion: Neither [ 11 C]R121920 nor [ 11 C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum

The CRF-method for semiconductors' intravalley collision kernels: I – the 2D case

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Claudio Barone

1992-05-01

Full Text Available If the collisions are redefined as a flux a kinetic conservation law can be written in divergence form. This can be handled numerically, in the framework of Finite Particle Approximation, using the CRF-method. In the present paper the relevant quantities needed for computer implementation of the CRF-method are derived in the case of a 2D momentum space for the semiconductors' intravalley collision kernels.

The CRF-method for semiconductors' intravalley collision kernels: II – The 3D case

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Claudio Barone

1993-05-01

Full Text Available If the collisions are redefined as a flux a kinetic conservation law can be written in divergence form. This can be handled numerically, in the framework of Finite Particle Approximation, using the CRF-method. In this paper we use the CRF-method for semiconductors' intravalley collision kernels. We extend the results obtained in a previous paper to the case of a 3D momentum space.

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

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García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

2015-01-01

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

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García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

2015-02-15

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder

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Bremner, J. Douglas; Licinio, Julio; Darnell, Adam; Krystal, John H.; Owens, Michael J.; Southwick, Steven M.; Nemeroff, Charles B.; Charney, Dennis S.

2011-01-01

Objective Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. Method Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N=11) and comparison subjects (N=17). CSF concentrations of CRF and somatostatin were compared between the two groups. Results CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean=29.0 pg/ml, SD=7.8, versus mean=21.9 pg/ml, SD=6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean=19.9 pg/ml, SD=5.4, versus mean=13.7 pg/ml, SD=8.0). However, covarying for age reduced the level of significance. Conclusions Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD. PMID:9137116

Corticotropin-releasing factor receptors in the pituitary gland and central nervous system: methods and overview

International Nuclear Information System (INIS)

De Souza, E.B.; Kuhar, M.J.

1986-01-01

Studies with the radioiodinated oCRF analog, Nle21, 125I-Tyr32-oCRF have identified, characterized, and localized high affinity binding sites for CRF in anterior and intermediate lobes of rat pituitary, in anterior lobe of human pituitary, and in rat, monkey, and human brain. The pharmacology and distribution of Nle21, 125I-Tyr32-oCRF binding in the pituitary gland correlate well with the biological potency and sites of action of CRF and suggest that these CRF binding sites represent specific receptors that mediate the well-established actions of CRF on the anterior pituitary and on the intermediate lobe of the pituitary. The studies in adrenalectomized rats demonstrating that endogenous CRF is capable of modulating its receptor density provide additional evidence that the radioligand labels the functional CRF receptor. The areas of distribution of Nle21, 125I-Tyr32-oCRF binding sites in the rat CNS correlate well with the immunohistochemical distribution of CRF pathways and the pharmacological sites of action of CRF. These data confirm the established role of CRF in regulating secretion of POMC-derived peptides from the pituitary gland. In addition, the data support a physiological role for endogenous CRF in regulating CNS activity and suggest the importance of this neuropeptide in integrating endocrine and visceral functions and behavior, especially in response to stress. Studies to characterize CRF receptors and CRF-containing pathways in the brain provide a means for better understanding the various functions of this neuropeptide in different areas of the CNS. Finally, the ability to map CRF receptors in postmortem human tissue provides a basis for studying the role of CRF in a variety of endocrine, neurological, and psychiatric disorders

Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

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Burke, Andrew R.; Miczek, Klaus A.

2014-01-01

Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

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Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

2015-01-01

The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

Isolation and characterization of a replication-competent molecular clone of an HIV-1 circulating recombinant form (CRF33_01B.

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Kok Keng Tee

Full Text Available A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1, a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5' LTR (long terminal repeat region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone, showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia.

Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

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Mahanand Chatoo

2018-02-01

Full Text Available Irritable bowel syndrome (IBS is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized. Corticotropin-releasing factor (CRF, a major mediator in the stress response, is involved in altered function in GI, including inflammatory processes, colonic transit time, contractile activity, defecation pattern, pain threshold, mucosal secretory function, and barrier functions. This mini review focuses on the recently establish local GI-CRF system, its involvement in modulating the immune response in IBS, and summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF and receptors might be a key molecule involving the immune and movement function via brain–gut axis in IBS.

Expression and hypophysiotropic actions of corticotropin-releasing factor in Xenopus laevis.

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Boorse, Graham C; Denver, Robert J

2004-07-01

Members of the corticotropin-releasing factor (CRF) family of peptides play pivotal roles in the regulation of neuroendocrine, autonomic, and behavioral responses to physical and emotional stress. In amphibian tadpoles, CRF-like peptides stimulate both thyroid and interrenal (adrenal) hormone secretion, and can thereby modulate the rate of metamorphosis. To better understand the regulation of expression and actions of CRF in amphibians we developed a homologous radioimmunoassay (RIA) for Xenopus laevis CRF (xCRF). We validated this RIA and tissue extraction procedure for the measurement of brain CRF content in tadpoles and juveniles. We show that the CRF-binding protein, which is highly expressed in X. laevis brain, is largely removed by acid extraction and does not interfere in the RIA. We analyzed CRF peptide content in five microdissected brain regions in prometamorphic tadpoles and juveniles. CRF was detected throughout the brain, consistent with its role as both a hypophysiotropin and a neurotransmitter/neuromodulator. CRF content was highest in the region of the preoptic area (POa) and increased in all brain regions after metamorphosis. Exposure to 4h of handling/shaking stress resulted in increased CRF peptide content in the POa in juvenile frogs. Injections of xCRF into prometamorphic tadpoles increased whole body corticosterone and thyroxine content, thus supporting findings in other anuran species that this peptide functions as both a corticotropin- and a thyrotropin (TSH)-releasing factor. Furthermore, treatment of cultured tadpole pituitaries with xCRF (100nM for 24h) resulted in increased medium content, but decreased pituitary content of TSHbeta-immunoreactivity. Our results support the view that CRF functions as a stress neuropeptide in X. laevis as in other vertebrates. Furthermore, we provide evidence for a dual hypophysiotropic action of CRF on the thyroid and interrenal axes in X. laevis as has been shown previously in other amphibian species.

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

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Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

2001-09-01

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Corticotropin-releasing Factor in the Rat Dorsal Raphe Nucleus Promotes Different Forms of Behavioral Flexibility Depending on Social Stress History.

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Snyder, Kevin P; Hill-Smith, Tiffany E; Lucki, Irwin; Valentino, Rita J

2015-10-01

The stress-related neuropeptide, corticotropin-releasing factor (CRF) regulates the dorsal raphe nucleus-serotonin (DRN-5-HT) system during stress and this may underlie affective and cognitive dysfunctions that characterize stress-related psychiatric disorders. CRF acts on both CRF1 and CRF2 receptor subtypes in the DRN that exert opposing inhibitory and excitatory effects on DRN-5-HT neuronal activity and 5-HT forebrain release, respectively. The current study first assessed the cognitive effects of intra-DRN microinfusion of CRF or the selective CRF2 agonist, urocortin II in stress-naive rats on performance of an operant strategy set-shifting task that is mediated by the medial prefrontal cortex (mPFC). CRF (30 ng) facilitated strategy set-shifting performance, whereas higher doses of CRF and urocortin II that would interact with CRF2 were without effect, consistent with a CRF1-mediated action. This dose decreased 5-HT extracellular levels in the mPFC, further supporting a role for CRF1. The effects of CRF were then assessed in rats exposed to repeated social stress using the resident-intruder model. Repeated social stress shifted the CRF effect from facilitation of strategy set shifting to facilitation of reversal learning and this was most prominent in a subpopulation of rats that resist defeat. Notably, in this subpopulation of rats 5-HT neuronal responses to CRF have been demonstrated to shift from CRF1-mediated inhibition to CRF2-mediated excitation. Because 5-HT facilitates reversal learning, the present results suggest that stress-induced changes in the cellular effects of CRF in the DRN translate to changes in cognitive effects of CRF. Together, the results underscore the potential for stress history to shift cognitive processing through changes in CRF neurotransmission in the DRN and the association of this effect with coping strategy.

CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

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Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

2015-03-01

Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

Leads Detection Using Mixture Statistical Distribution Based CRF Algorithm from Sentinel-1 Dual Polarization SAR Imagery

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Zhang, Yu; Li, Fei; Zhang, Shengkai; Zhu, Tingting

2017-04-01

Synthetic Aperture Radar (SAR) is significantly important for polar remote sensing since it can provide continuous observations in all days and all weather. SAR can be used for extracting the surface roughness information characterized by the variance of dielectric properties and different polarization channels, which make it possible to observe different ice types and surface structure for deformation analysis. In November, 2016, Chinese National Antarctic Research Expedition (CHINARE) 33rd cruise has set sails in sea ice zone in Antarctic. Accurate leads spatial distribution in sea ice zone for routine planning of ship navigation is essential. In this study, the semantic relationship between leads and sea ice categories has been described by the Conditional Random Fields (CRF) model, and leads characteristics have been modeled by statistical distributions in SAR imagery. In the proposed algorithm, a mixture statistical distribution based CRF is developed by considering the contexture information and the statistical characteristics of sea ice for improving leads detection in Sentinel-1A dual polarization SAR imagery. The unary potential and pairwise potential in CRF model is constructed by integrating the posteriori probability estimated from statistical distributions. For mixture statistical distribution parameter estimation, Method of Logarithmic Cumulants (MoLC) is exploited for single statistical distribution parameters estimation. The iteration based Expectation Maximal (EM) algorithm is investigated to calculate the parameters in mixture statistical distribution based CRF model. In the posteriori probability inference, graph-cut energy minimization method is adopted in the initial leads detection. The post-processing procedures including aspect ratio constrain and spatial smoothing approaches are utilized to improve the visual result. The proposed method is validated on Sentinel-1A SAR C-band Extra Wide Swath (EW) Ground Range Detected (GRD) imagery with a

Distribution of corticotropin-releasing factor receptors in primate brain

International Nuclear Information System (INIS)

Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

1986-01-01

The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [ 125 I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 0 C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

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Paula Madeira Fortes

2017-06-01

Full Text Available Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation, or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF and brain-derived neurotrophic factor (BNDF were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Robust rooftop extraction from visible band images using higher order CRF

KAUST Repository

Li, Er; Femiani, John; Xu, Shibiao; Zhang, Xiaopeng; Wonka, Peter

2015-01-01

In this paper, we propose a robust framework for building extraction in visible band images. We first get an initial classification of the pixels based on an unsupervised presegmentation. Then, we develop a novel conditional random field (CRF

Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

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Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

2007-02-01

Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum

NARCIS (Netherlands)

Gounko, Natalia V.; Gramsbergen, Albert; van der Want, Johannes J. L.

The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRF-R2 alpha is present. In the cerebellum, CRF-R2 alpha has two different isoforms: a full-length form (fl) and truncated (tr). Both forms CRF-R2 have a unique

Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the beta-adrenoceptor-cAMP pathway: dependence on glucocorticoid receptor activation.

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Roozendaal, Benno; Schelling, Gustav; McGaugh, James L

2008-06-25

Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the beta-adrenoceptor-cAMP system in the BLA. In a first experiment, male Sprague Dawley rats received bilateral infusions of the CRF-binding protein ligand inhibitor CRF(6-33) into the BLA either alone or together with the CRF receptor antagonist alpha-helical CRF(9-41) immediately after inhibitory avoidance training. CRF(6-33) induced dose-dependent enhancement of 48 h retention latencies, which was blocked by coadministration of alpha-helical CRF(9-41), suggesting that CRF(6-33) enhances memory consolidation by displacing CRF from its binding protein, thereby increasing "free" endogenous CRF concentrations. In a second experiment, intra-BLA infusions of atenolol (beta-adrenoceptor antagonist) and Rp-cAMPS (cAMP inhibitor), but not prazosin (alpha(1)-adrenoceptor antagonist), blocked CRF(6-33)-induced retention enhancement. In a third experiment, the CRF receptor antagonist alpha-helical CRF(9-41) administered into the BLA immediately after training attenuated the dose-response effects of concurrent intra-BLA infusions of clenbuterol (beta-adrenoceptor agonist). In contrast, alpha-helical CRF(9-41) did not alter retention enhancement induced by posttraining intra-BLA infusions of either cirazoline (alpha(1)-adrenoceptor agonist) or 8-br-cAMP (cAMP analog). These findings suggest that CRF facilitates the memory-modulatory effects of noradrenergic stimulation in the BLA via an interaction with the beta-adrenoceptor-cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site. Moreover, consistent with evidence that glucocorticoids enhance memory consolidation via a similar interaction with the

Molecular Epidemiology of HIV-1 in Jilin Province, Northeastern China: Emergence of a New CRF07_BC Transmission Cluster and Intersubtype Recombinants

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Ning, Chuanyi; Feng, Yi; Xie, Cunxin; He, Xiang; Takebe, Yutaka; Sun, Liuyan; Guo, Qi; Xing, Hui; Kalish, Marcia L.; Shao, Yiming

2014-01-01

Objective To investigate the HIV-1 molecular epidemiology among newly diagnosed HIV-1 infected persons living in the Jilin province of northeastern China. Methods Plasma samples from 189 newly diagnosed HIV-1 infected patients were collected between June 2010 and August 2011 from all nine cities of Jilin province. HIV-1 nucleotide sequences of gag P17–P24 and env C2–C4 gene regions were amplified using a multiplex RT-PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes. Results Based on all sequences generated, the subtype/CFR distribution was as follows: CRF01_AE (58.1%), CRF07_BC (13.2%), subtype B’ (13.2%), recombinant viruses (8.1%), subtype B (3.7%), CRF02_AG (2.9%), subtype C (0.7%). In addition to finding CRF01_AE strains from previously reported transmission clusters 1, 4 and 5, a new transmission cluster was described within the CRF07_BC radiation. Among 11 different recombinants identified, 10 contained portions of gene regions from the CRF01_AE lineage. CRF02_AG was found to form a transmission cluster of 4 in local Jilin residents. Conclusions Our study presents a molecular epidemiologic investigation describing the complex structure of HIV-1 strains co-circulating in Jilin province. The results highlight the critical importance of continuous monitoring of HIV-infections, along with detailed socio-demographic data, in order to design appropriate prevention measures to limit the spread of new HIV infections. PMID:25356726

Urocortin, a CRF-like peptide, restores key indicators of damage in the substantia nigra in a neuroinflammatory model of Parkinson's disease

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Biggs Christopher S

2007-07-01

Full Text Available Abstract We have recently observed that the corticotrophin releasing hormone (CRF related peptide urocortin (UCN reverses key features of nigrostriatal damage in the hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether similar effects are also evident in the lipopolysaccaride (LPS neuroinflammatory paradigm of Parkinson's disease (PD. To do this we have measured restoration of normal motor behaviour, retention of nigral dopamine (DA and also tyrosine hydroxylase (TH activity. Fourteen days following intranigral injections of LPS and UCN, rats showed only modest circling after DA receptor stimulation with apomorphine, in contrast to those given LPS and vehicle where circling was pronounced. In separate experiments, rats received UCN seven days following LPS, and here apomorphine challenge caused near identical circling intensity to those that received LPS and UCN concomitantly. In a similar and consistent manner with the preservation of motor function, UCN 'protected' the nigra from both DA depletion and loss of TH activity, indicating preservation of DA cells. The effects of UCN were antagonised by the non-selective CRF receptor antagonist α-helical CRF and were not replicated by the selective CRF2 ligand UCN III. This suggests that UCN is acting via CRF1 receptors, which have been shown to be anti-inflammatory in the periphery. Our data therefore indicate that UCN is capable of maintaining adequate nigrostriatal function in vivo, via CRF1 receptors following a neuro-inflammatory challenge. This has potential therapeutic implications in PD.

Molecular Diversity of HIV-1 among People Who Inject Drugs in Kuala Lumpur, Malaysia: Massive Expansion of Circulating Recombinant Form (CRF) 33_01B and Emergence of Multiple Unique Recombinant Clusters

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Chow, Wei Zhen; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

2013-01-01

Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B′ of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B′ (11%) and CRF01_AE (5%)] and CRF01_AE/B′ unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B′ recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the

Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

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Chow, Wei Zhen; Ong, Lai Yee; Razak, Siti Humaira; Lee, Yeat Mei; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

2013-01-01

Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating

Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

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Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

2015-01-01

In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

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Hui Ting Cheong

Full Text Available In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs. Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs, especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF 33_01B and emergence of multiple unique recombinant clusters.

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Wei Zhen Chow

Full Text Available Since the discovery of HIV-1 circulating recombinant form (CRF 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11% and CRF01_AE (5%] and CRF01_AE/B' unique recombinants (13% were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the

The effects of corticotrophin-releasing factor and two antagonists on breathing movements in fetal sheep.

Science.gov (United States)

Bennet, L; Johnston, B M; Vale, W W; Gluckman, P D

1990-01-01

1. The respiratory effects of corticotrophin-releasing factor (CRF) and the CRF antagonists alpha-helical CRF 9-41 (alpha hCRF) and [DPhe 12, Nle 21-38] rCRF (12-41) (DPhe CRF) have been studied in unanaesthetized fetal lambs of 125-140 days gestation. 2. CRF when given as a 10 micrograms bolus followed by a 5 micrograms h-1 infusion into a lateral cerebral ventricle caused prolonged continuous fetal breathing movements which were stimulated in both amplitude and frequency but which did not persist during hypoxia. 3. Lower doses of CRF (20 ng bolus followed by 10 ng h-1) increased the amplitude but not the frequency of fetal breathing movements which did not become continuous. 4. At higher doses (20 micrograms bolus followed by 10-15 micrograms h-1) CRF induced cerebral convulsions which were also associated with fetal breathing movements of increased amplitude and frequency. 5. The CRF antagonists alpha hCRF and DPhe CRF both inhibited fetal breathing movements and induced a prolonged apnoea which was resistant to the stimulatory effects of 5-6% hypercapnia. 6. We conclude that CRF stimulates breathing movements in the fetal lamb. The finding that administration of the CRF antagonists alone cause apnoea suggests that CRF may have a tonic role in the regulation of fetal breathing movements. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:2348387

Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health.

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Janssen, Donny; Kozicz, Tamás

2013-01-01

Physiological responses to stress coordinated by the hypothalamo-pituitary-adrenal axis are concerned with maintaining homeostasis in the presence of real or perceived challenges. Regulators of this axis are corticotrophin releasing factor (CRF) and CRF related neuropeptides, including urocortins 1, 2, and 3. They mediate their actions by binding to CRF receptors (CRFR) 1 and 2, which are located in several stress-related brain regions. The prevailing theory has been that the initiation of and the recovery from an elicited stress response is coordinated by two elements, viz. the (mainly) opposing, but well balanced actions of CRFR1 and CRFR2. Such a dualistic view suggests that CRF/CRFR1 controls the initiation of, and urocortins/CRFR2 mediate the recovery from stress to maintain body and mental health. Consequently, failed adaptation to stress can lead to neuropathology, including anxiety and depression. Recent literature, however, challenges such dualistic and complementary actions of CRFR1 and CRFR2, and suggests that stress recruits CRF system components in a brain area and neuron specific manner to promote adaptation as conditions dictate.

Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naïve patients in southern Spain.

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González-Domenech, Carmen M; Viciana, Isabel; Delaye, Luis; Mayorga, María Luisa; Palacios, Rosario; de la Torre, Javier; Jarilla, Francisco; Castaño, Manuel; Del Arco, Alfonso; Clavijo, Encarnación; Santos, Jesús

2018-01-01

CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain. The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data. Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART) responded. We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naïve patients in southern Spain.

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Carmen M González-Domenech

Full Text Available CRF19_cpx is a complex circulating recombination form (CRF of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain.The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain. Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data.Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART responded.We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

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Rivier, Jean E; Rivier, Catherine L

2014-04-01

Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Low-Grade Glioma Segmentation Based on CNN with Fully Connected CRF

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Zeju Li

2017-01-01

Full Text Available This work proposed a novel automatic three-dimensional (3D magnetic resonance imaging (MRI segmentation method which would be widely used in the clinical diagnosis of the most common and aggressive brain tumor, namely, glioma. The method combined a multipathway convolutional neural network (CNN and fully connected conditional random field (CRF. Firstly, 3D information was introduced into the CNN which makes more accurate recognition of glioma with low contrast. Then, fully connected CRF was added as a postprocessing step which purposed more delicate delineation of glioma boundary. The method was applied to T2flair MRI images of 160 low-grade glioma patients. With 59 cases of data training and manual segmentation as the ground truth, the Dice similarity coefficient (DSC of our method was 0.85 for the test set of 101 MRI images. The results of our method were better than those of another state-of-the-art CNN method, which gained the DSC of 0.76 for the same dataset. It proved that our method could produce better results for the segmentation of low-grade gliomas.

Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum

NARCIS (Netherlands)

Swinny, JD; Kalicharan, D; Blaauw, EH; Ijkema-Paassen, J; Shi, F; Gramsbergen, A; van der Want, JJL

Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but

Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

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Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A.; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I.

2015-01-01

Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R–OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–CRF1R–OX1R complex promotes a long-term disruption of the orexin-A–CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. PMID:25926444

Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

Science.gov (United States)

Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

2015-04-29

Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

Study on the chronic inflammatory status in patients with chronic renal failure (CRF)

International Nuclear Information System (INIS)

Deng Lirong; Wang Caili; Wei Hong; Yang Yuhua

2005-01-01

Objective: To study the relationship between the status of chronic inflammation and deterioration of renal function in patients with chronic renal failure (CRF). Methods: Serum CRP, IL-10 (with ELISA), TNF-α, IL-6 (with RIA) and creatinine (with bio-chemistry methods) levels were determined in 126 patients with CRF of various stages as well as in 30 controls. The creatinine clearance rate (CCr) was also calculated. Results: (1)In all these patients, the serum CRP, IL-6, IL-10 and TNF-α contents were significantly higher than those in the controls (P <0.01). (2) CRP, IL-6, IL-10 and TNF-α levels were linearly positively correlated with the creatinine levels (r= 0.716, 0.836, 0.501 and 0.574 respectively), linearly negatively correlated with the creatinine clearance rate (r=-0.755, -0.825, -0.497 and -0.564 respectively). As the renal function deteriorated progressively, the serum levels of CRP, IL-6, IL-10 and TNF-α increased correspondingly. (3) The acute phase protein CRP and inflammatory cytokines IL-6 and TNF-α levels were correlated with those of the anti-inflammatory cytokine IL-10 (r=0.463, 0.546 and 0.402 respectively). Conclusion: The serum acute phase protein CRP, inflammatory cytokines IL-6, TNF-α and anti-inflammatory cytokine IL-10 contents were all gradually increased along with the progression of CRF and these inflammatory mediators were mutually positively correlated with each other. (authors)

Early Life Stress as a Risk Factor for Substance use Disorders: Clinical and Neurobiological Substrates

OpenAIRE

Varghese, Sajoy Purathumuriyil; Montalvo-Ortiz, Janitza L.; Csernansky, John G.; Eiger, Rodney I.; Herrold, Amy A.; Koola, Maju Mathew; Dong, Hongxin

2015-01-01

Background: Early Life Stress (ELS) can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Materials and Methods: Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA) was used for...

Low Cardiorespiratory Fitness in African Americans: A Health Disparity Risk Factor?

Science.gov (United States)

Swift, Damon L.; Staiano, Amanda E.; Johannsen, Neil M.; Lavie, Carl J.; Earnest, Conrad P.; Katzmarzyk, Peter T.; Blair, Steven N.; Newton, Robert L.; Church, Timothy S.

2013-01-01

Low cardiorespiratory fitness (CRF) is a well-established risk factor for all-cause and cardiovascular disease mortality. African Americans have higher rates of cardiovascular disease compared to their Caucasian counterparts. However, the extent to which lower CRF levels contribute to the excess risk in African Americans has not been fully explored. The purpose of this review is to: 1) explore the literature evaluating the relationship between CRF and mortality specifically in African American populations; and 2) critically evaluate the studies which have compared CRF between African American and Caucasians in epidemiological studies and clinical trials. We have further discussed several potential mechanisms that may contribute to the observation of lower CRF levels in African American compared to Caucasian adults including potential racial differences in physical activity levels, muscle fiber type distribution, and hemoglobin levels. If lower CRF is generally present in African Americans compared to Caucasians, and is of a clinically meaningful difference, this may represent an important public health concern. PMID:23982718

[Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

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Yarushkina, N I; Filaretova, L P

2015-01-01

Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

Sex differences in stress responses: a critical role for corticotropin-releasing factor.

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Bangasser, Debra A; Wiersielis, Kimberly R

2018-03-01

Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity.

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Howerton, Alexis R; Roland, Alison V; Fluharty, Jessica M; Marshall, Anikò; Chen, Alon; Daniels, Derek; Beck, Sheryl G; Bale, Tracy L

2014-06-01

Women are twice as likely as men to suffer from stress-related affective disorders. Corticotropin-releasing factor (CRF) is an important link between stress and mood, in part through its signaling in the serotonergic dorsal raphe (DR). Development of CRF receptor-1 (CRFr1) antagonists has been a focus of numerous clinical trials but has not yet been proven efficacious. We hypothesized that sex differences in CRFr1 modulation of DR circuits might be key determinants in predicting therapeutic responses and affective disorder vulnerability. Male and female mice received DR infusions of the CRFr1 antagonist, NBI 35965, or CRF and were evaluated for stress responsivity. Sex differences in indices of neural activation (cFos) and colocalization of CRFr1 throughout the DR were examined. Whole-cell patch-clamp electrophysiology assessed sex differences in serotonin neuron membrane characteristics and responsivity to CRF. Males showed robust behavioral and hypothalamic-pituitary-adrenal axis responses to DR infusion of NBI 35965 and CRF, whereas females were minimally responsive. Sex differences were also found for both CRF-induced DR cFos and CRFr1 co-localization throughout the DR. Electrophysiologically, female serotonergic neurons showed blunted membrane excitability and divergent inhibitory postsynaptic current responses to CRF application. These studies demonstrate convincing sex differences in CRFr1 activity in the DR, where blunted female responses to NBI 35965 and CRF suggest unique stress modulation of the DR. These sex differences might underlie affective disorder vulnerability and differential sensitivity to pharmacologic treatments developed to target the CRF system, thereby contributing to a current lack of CRFr1 antagonist efficacy in clinical trials. © 2013 Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

Emerging Role for Corticotropin Releasing Factor Signaling in the Bed Nucleus of the Stria Terminalis at the Intersection of Stress and Reward

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Yuval eSilberman

2013-05-01

Full Text Available Stress and anxiety play an important role in the development and maintanence of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST, a brain region involved in the production of long-term stress related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF as being critically important in BNST mediated reinstatement behaviors. The BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types and there has only been limited work trying to understand how CRF modulates this complex neuronal system. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of BNST CRF signaling in drug addiction and reinstatment with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward.

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Silberman, Yuval; Winder, Danny G

2013-01-01

Stress and anxiety play an important role in the development and maintenance of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST), a brain region involved in the production of long-term stress-related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF) as being critically important in BNST-mediated reinstatement behaviors. Although numerous studies indicate that the BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types, there has only been limited work to determine how CRF modulates this complex neuronal system at the circuit level. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of CRF signaling in drug addiction and reinstatement with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype.

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Schroeder, Mariana; Jakovcevski, Mira; Polacheck, Tamar; Lebow, Maya; Drori, Yonat; Engel, Mareen; Ben-Dor, Shifra; Chen, Alon

2017-06-06

Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3. Moreover, exposing the offspring to a methyl-balanced diet during adolescence prevents the dysregulation and predisposition from being triggered. We demonstrate that gestational programming, per se, will not lead to BE-like behavior, but pre-existing alterations due to prenatal programming are revealed only when challenged during adolescence. We provide experimental evidence for long-term epigenetic abnormalities stemming from PNS in predisposing female offspring to BE disorder as well as a potential non-invasive prevention strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

Construction and characterization of HIV type 1 CRF07_BC infectious molecular clone from men who have sex with men.

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Jiang, Yan-Ling; Bai, Wen-Wei; Qu, Fan-Wei; Ma, Hua; Jiang, Run-Sheng; Shen, Bao-Sheng

2016-03-01

This study aimed to investigate the biological characterization of HIV type 1 (HIV-1) CRF07_BC infection among men who have sex with men (MSM). From November 2011 to November 2013, a total of 66 blood samples were collected from MSM with acute HIV-1 infection with CRF07_BC subgroup strains. Deletion in the gag p6 region was detected by sequence alignment and comparative analysis. Peripheral blood mononuclear cells (PBMCs) of HNXX1301-1307 samples were separated by density gradient centrifugation. Nested polymerase chain reaction (nPCR) was used to amplify the viral DNA. The near full-length HIV-1 DNA products were ligated to the long terminal repeat (LTR) vector plasmid (07BCLTR) to construct a full-length HIV clone. The molecular clone was transfected into HEK-293T cells, TZM-b1 cells and patients' PBMCs. The pregenome of an infectious molecular clone of HIV-1 (pNL4-3) was amplified, and a subclone with CRF07_BC was developed to construct the full-length chimeric molecular clone pNL4-3/07BCLTR. Detection of p24 antigen and luciferase activity was used to measure the in vitro infectivity of pNL4-3/07BCLTR. Among the 66 MSM patients infected with CRF07_BC strains, deletion mutations of the Gag P6 proteins were found in 7 of 18CRF07_BC strains; deletion mutations of 2-13 amino acids in different regions were discovered in 6 strains; and the remaining 42 strains did not show deletions. Seven strains with amino acids deficiency in the P6 protein accounted for 27% of all strains and 75% of all deletion genotype strains. A total of 186 full-length molecular clones of CRF07_BC were constructed. There were 5, 9, 10 and 11 clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 that resulted in p24-positive supernatant when transfected into HEK-293T cells. Full-length clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 showed slight infection in the transfected TZM-b1 cells, as judged by the fluorescence values of TZM-b1 cells 48h post-transfection. However, we were unable to

Near Full-Length Identification of a Novel HIV-1 CRF01_AE/B/C Recombinant in Northern Myanmar.

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Zhou, Yan-Heng; Chen, Xin; Liang, Yue-Bo; Pang, Wei; Qin, Wei-Hong; Zhang, Chiyu; Zheng, Yong-Tang

2015-08-01

The Myanmar-China border appears to be the "hot spot" region for the occurrence of HIV-1 recombination. The majority of the previous analyses of HIV-1 recombination were based on partial genomic sequences, which obviously cannot reflect the reality of the genetic diversity of HIV-1 in this area well. Here, we present a near full-length characterization of a novel HIV-1 CRF01_AE/B/C recombinant isolated from a long-distance truck driver in Northern Myanmar. It is the first description of a near full-length genomic sequence in Myanmar since 2003, and might be one of the most complicated HIV-1 chimeras ever detected in Myanmar, containing four CRF01_AE, six B segments, and five C segments separated by 14 breakpoints throughout its genome. The discovery and characterization of this new CRF01_AE/B/C recombinant indicate that intersubtype recombination is ongoing in Myanmar, continuously generating new forms of HIV-1. More work based on near full-length sequence analyses is urgently needed to better understand the genetic diversity of HIV-1 in these regions.

Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.

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Wagle, Mahendra; Mathur, Priya; Guo, Su

2011-01-05

The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.

Persistent escalation of alcohol consumption by mice exposed to brief episodes of social defeat stress: suppression by CRF-R1 antagonism.

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Newman, Emily L; Albrechet-Souza, Lucas; Andrew, Peter M; Auld, John G; Burk, Kelly C; Hwa, Lara S; Zhang, Eric Y; DeBold, Joseph F; Miczek, Klaus A

2018-06-01

Episodic bouts of social stress can precede the initiation, escalation, or relapse to disordered alcohol intake. Social stress may engender neuroadaptations in the hypothalamic-pituitary-adrenal (HPA) axis and in extrahypothalamic stress circuitry to promote the escalation of alcohol intake. We aimed to (1) confirm a pattern of escalated drinking in socially defeated mice and to (2) test drugs that target distinct aspects of the HPA axis and extrahypothalamic neural substrates for their effectiveness in reducing murine, stress-escalated drinking. Male C57BL/6J (B6) mice were socially defeated by resident Swiss-derived males for ten consecutive days receiving 30 bites/day. Ten days after the final defeat, cohorts of B6 mice received continuous or intermittent access to 20% EtOH (w/v) and water. After 4 weeks of drinking, mice were injected with weekly, systemic doses of the CRF-R1 antagonist, CP376395; the glucocorticoid receptor antagonist, mifepristone; the 11-beta-hydroxylase inhibitor, metyrapone; or the 5-alpha-reductase inhibitor, finasteride. Prior to drug treatments, defeated mice reliably consumed more EtOH than non-defeated controls, and mice given alcohol intermittently consumed more EtOH than those with continuous access. CP376395 (17-30 mg/kg) reduced continuous, but not intermittent EtOH intake (g/kg) in socially defeated mice. Mifepristone (100 mg/kg), however, increased drinking by defeated mice with intermittent access to alcohol while reducing drinking during continuous access. When administered finasteride (100 mg/kg) or metyrapone (50 mg/kg), all mice reduced their EtOH intake while increasing their water consumption. Mice with a history of episodic social defeat stress were selectively sensitive to the effects of CRF-R1 antagonism, suggesting that CRF-R1 may be a potential target for treating alcohol use disorders in individuals who escalate their drinking after exposure to repeated bouts of psychosocial stress. Future studies will clarify

The effect of corrosion product CrF3 on thermo-physical properties of FLiNaK

International Nuclear Information System (INIS)

Yin Huiqin; Zhang Peng; An Xuehui; Zhao Sufang; Xie Leidong; Wang Wenfeng

2016-01-01

FLiNaK (LiF–NaF–KF: 46.5–11.5–42 mol%) is a promising candidate as the secondary loop coolant in molten salt reactor. The thermo-physical properties of pure FLiNaK and FLiNaK containing up to 6000 ppm (equivalent to mg/kg) corrosion product CrF 3 were measured. The results indicate that the effects of CrF 3 on melting point, enthalpy, specific heat capacity, density and thermal diffusivity of FLiNaK in liquid state are negligible within the allowable error range, meanwhile the change of thermal diffusivity is significant for FLiNaK in solid state. This work provides fundamental knowledge for the thermo-physical properties of coolant in molten salt reactor. (author)

Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

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Peciña, Susana; Schulkin, Jay; Berridge, Kent C

2006-04-13

Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 microg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to

Risk factors for chronic renal failure in Ivory coast: A prospective study of 280 patients

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Ackoundou-N′Guessan K

2011-01-01

Full Text Available Chronic renal failure (CRF represents the major cause of mortality in the nephro-logy unit in Ivory Coast because the means for appropriate management are lacking. The present study was performed to investigate the risk factors for CRF so that strategies for prevention could be elaborated. A case-control study was performed prospectively at the Yopougon Teaching Hos-pital in Abidjan from January 2006 to December 2006. Factors known to cause CRF were investigated in patients and controls. Their prevalence rates were compared with the general population. A total of 280 patients and 113 controls were recruited. The mean age of the patients was 37.88 ± 13.33 years and that of the controls was 41.5 ± 9.72 years. Both genders were equally represented. The main causes of CRF were chronic glomerulonephritis (47.48%, with HIV infec-tion accounting for 15% of them, and essential hypertension (HTA (25%. Essential HTA repre-sented the only factor which, if untreated, inevitably leads to CRF. Thus, our study indicates that HTA is a major public health concern. All efforts should be implemented to reduce the high prevalence of HTA and the deleterious effect of this disorder in Ivory Coast.

Parental LTRs are important in a construct of a stable and efficient replication-competent infectious molecular clone of HIV-1 CRF08_BC.

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Zhang, Qiwei; Zhang, Xiaomin; Wu, Hao; Seto, Donald; Zhang, Hao-Jie; Chen, Zhiwei; Wan, Chengsong; Zheng, Bo-Jian

2012-01-01

Circulating recombinant forms (CRFs) of HIV-1 have been identified in southern China in recent years. CRF08_BC is one of the most predominant subtypes circulating in China. In order to study HIV subtype biology and to provide a tool for biotechnological applications, the first full-length replication-competent infectious molecular clone harboring CRF08_BC is reported. The construction of this clone pBRGX indicates that a moderate-copy number vector is required for its amplification in E. coli. In addition, it is shown that the parental CRF08_BC LTRs are important for generating this efficient replication-competent infectious clone. These observations may aid in the construction of infectious clones from other subtypes. Both the pBRGX-derived virus and its parental isolate contain CCR5 tropism. Their full-length genomes were also sequenced, analyzed, compared and deposited in GenBank (JF719819 and JF719818, respectively). The availability of pBRGX as the first replication-competent molecular clone of CRF08_BC provides a useful tool for a wide range of studies of this newly emergent HIV subtype, including the development of HIV vaccine candidates, antiviral drug screening and drug resistance analysis.

Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing.

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Szu-Wei Huang

Full Text Available The usefulness of ultra-deep pyrosequencing (UDPS for the diagnosis of HIV-1 drug resistance (DR remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF 07_BC among injection drug users (IDUs in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005 and 3 from late epidemic (collected in 2008 were obtained from treatment-naïve patient's peripheral blood mononuclear cells. Viral RNA was extracted directly from patient's plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs (4.4-47.3 fold. Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01-0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.

The Epidemic History of HIV-1 CRF07_BC in Hetian Prefecture and the Role of It on HIV Spreading in China.

Science.gov (United States)

Wu, Jianjun; Guo, Hongxiong; Zhang, Jing; Liu, Xiaoming; Ayoupu, Aideaierli; Shen, Yuelan; Miao, Lifeng; Tang, Jihai; Lei, Yanhua; Su, Bin

2017-04-01

CRF07_BC is one of the most prevalent HIV-1 strains in China, and Xinjiang Uygur Autonomous Region has ever been considered to be a second epidemic center after Yunnan Province in previous studies. Here we use HIV-1 pol gene sequences identified from Hetian Prefecture located in Xinjiang Autonomous Region to reconstruct the epidemic history of HIV CRF07_BC strain circulating in this region. We found that CRF07_BC is the predominant HIV-1 form in Hetian Prefecture, and the estimated tMRCA analysis shows that there is no enough evidence supporting Xinjiang Autonomous Region as a second epidemic center of spreading HIV-1. It may imply that every city may be only a point among the HIV spreading network because of the frequent migration of population in the whole country nowadays.

Global dispersal pattern of HIV type 1 subtype CRF01-AE : A genetic trace of human mobility related to heterosexual sexual activities centralized in southeast Asia

NARCIS (Netherlands)

Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie M J; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Camacho, Ricardo J.; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kostrikis, Leondios G.; Lepej, Snjezana; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Boucher, Charles A B; Kaplan, Lauren; Vandamme, Anne Mieke; Paraskevis, Dimitrios

2015-01-01

Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01-AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01-AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set

Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

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Simon M Agwale

Full Text Available Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G. Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G and consensus tat (CRF02_AG and G antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

Science.gov (United States)

Agwale, Simon M; Forbi, Joseph C; Notka, Frank; Wrin, Terri; Wild, Jens; Wagner, Ralf; Wolf, Hans

2011-01-01

Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA) to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G) and consensus tat (CRF02_AG and G) antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains.

Science.gov (United States)

Guimarães, Monick L; Velarde-Dunois, Ketty G; Segurondo, David; Morgado, Mariza G

2012-01-16

Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005). These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt) and env regions. Alignment and neighbor-joining (NJ) phylogenetic analyses were established from partial env (n = 37) and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay). The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5%) samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%). Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70.0%) or BF1 recombinant (23.8% vs 30.0%) samples from Bolivia.

Peptide YY, neuropeptide Y and corticotrophin-releasing factor modulate gastrointestinal motility and food intake during acute stress.

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Forbes, Sarah C; Cox, Helen M

2014-11-01

Peripheral neuropeptide Y (NPY) provides protection against the endocrine, feeding and gastrointestinal (GI) responses to stress; however, it is not yet established how it interacts with corticotrophin-releasing factor (CRF) to mediate these effects. Peptide YY (PYY) also has significant roles in GI motility and food intake but little is known about its role in stress responses. Upper GI transit, fecal pellet output (FPO) and feeding responses, and the role of CRF1 receptors, during restraint or a novel environment stress, were ascertained in PYY-/-, NPY-/- and wild type (WT) mice, with CRF and the CRF1 antagonist, antalarmin, injected intraperitoneally. Upper GI transit and FPO were significantly increased in PYY-/- mice during restraint stress. Exogenous CRF increased defecation during placement in a novel environment in WT mice through CRF1 , while CRF1 blockade reduced defecation in WT and NPY-/- mice but had no effect in PYY-/- mice. In addition, CRF1 blockade had no effect on upper GI transit in WT mice, or on food intake in PYY-/- or NPY-/- mice, but it significantly increased food intake in WT mice. Endogenous NPY appears to inhibit the colonic motor response induced by CRF1 activation, unlike PYY, while both peptides are required for CRF1 modulation of feeding behavior during stress. Overall, these results provide new insights into the mechanism by which PYY and NPY affect stress responses. © 2014 John Wiley & Sons Ltd.

Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

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Schulkin Jay

2006-04-01

Full Text Available Abstract Background Corticotropin-releasing factor (CRF is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior. Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl or amphetamine (20 μg/0.2 μl. Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng or amphetamine (20 μg selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress

Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists.

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Mochizuki, Michiyo; Kori, Masakuni; Kobayashi, Katsumi; Yano, Takahiko; Sako, Yuu; Tanaka, Maiko; Kanzaki, Naoyuki; Gyorkos, Albert C; Corrette, Christopher P; Cho, Suk Young; Pratt, Scott A; Aso, Kazuyoshi

2016-03-24

Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N(2)-(4-chloro-2-methoxy-6-methylphenyl)-1-methyl-N(7),N(7)-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 μM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 μmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research.

Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia.

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Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie M J; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Camacho, Ricardo J; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kostrikis, Leondios G; Lepej, Snjezana; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean-Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Boucher, Charles A B; Kaplan, Lauren; Vandamme, Anne-Mieke; Paraskevis, Dimitrios

2015-06-01

Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition.

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Gibelin, Aude; Parrot, Antoine; Maitre, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand; Fartoukh, Muriel; de Prost, Nicolas

2016-02-01

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+). Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012. The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival. The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

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Huang Xu

2010-08-01

Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

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Guimarães Monick L

2012-01-01

Full Text Available Abstract Background Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Materials and methods Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005. These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt and env regions. Alignment and neighbor-joining (NJ phylogenetic analyses were established from partial env (n = 37 and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay. The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Results Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5% samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%. Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. Conclusion HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70

SEMANTIC LABELLING OF ULTRA DENSE MLS POINT CLOUDS IN URBAN ROAD CORRIDORS BASED ON FUSING CRF WITH SHAPE PRIORS

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W. Yao

2017-09-01

Full Text Available In this paper, a labelling method for the semantic analysis of ultra-high point density MLS data (up to 4000 points/m2 in urban road corridors is developed based on combining a conditional random field (CRF for the context-based classification of 3D point clouds with shape priors. The CRF uses a Random Forest (RF for generating the unary potentials of nodes and a variant of the contrastsensitive Potts model for the pair-wise potentials of node edges. The foundations of the classification are various geometric features derived by means of co-variance matrices and local accumulation map of spatial coordinates based on local neighbourhoods. Meanwhile, in order to cope with the ultra-high point density, a plane-based region growing method combined with a rule-based classifier is applied to first fix semantic labels for man-made objects. Once such kind of points that usually account for majority of entire data amount are pre-labeled; the CRF classifier can be solved by optimizing the discriminative probability for nodes within a subgraph structure excluded from pre-labeled nodes. The process can be viewed as an evidence fusion step inferring a degree of belief for point labelling from different sources. The MLS data used for this study were acquired by vehicle-borne Z+F phase-based laser scanner measurement, which permits the generation of a point cloud with an ultra-high sampling rate and accuracy. The test sites are parts of Munich City which is assumed to consist of seven object classes including impervious surfaces, tree, building roof/facade, low vegetation, vehicle and pole. The competitive classification performance can be explained by the diverse factors: e.g. the above ground height highlights the vertical dimension of houses, trees even cars, but also attributed to decision-level fusion of graph-based contextual classification approach with shape priors. The use of context-based classification methods mainly contributed to smoothing of

Semantic Labelling of Ultra Dense Mls Point Clouds in Urban Road Corridors Based on Fusing Crf with Shape Priors

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Yao, W.; Polewski, P.; Krzystek, P.

2017-09-01

In this paper, a labelling method for the semantic analysis of ultra-high point density MLS data (up to 4000 points/m2) in urban road corridors is developed based on combining a conditional random field (CRF) for the context-based classification of 3D point clouds with shape priors. The CRF uses a Random Forest (RF) for generating the unary potentials of nodes and a variant of the contrastsensitive Potts model for the pair-wise potentials of node edges. The foundations of the classification are various geometric features derived by means of co-variance matrices and local accumulation map of spatial coordinates based on local neighbourhoods. Meanwhile, in order to cope with the ultra-high point density, a plane-based region growing method combined with a rule-based classifier is applied to first fix semantic labels for man-made objects. Once such kind of points that usually account for majority of entire data amount are pre-labeled; the CRF classifier can be solved by optimizing the discriminative probability for nodes within a subgraph structure excluded from pre-labeled nodes. The process can be viewed as an evidence fusion step inferring a degree of belief for point labelling from different sources. The MLS data used for this study were acquired by vehicle-borne Z+F phase-based laser scanner measurement, which permits the generation of a point cloud with an ultra-high sampling rate and accuracy. The test sites are parts of Munich City which is assumed to consist of seven object classes including impervious surfaces, tree, building roof/facade, low vegetation, vehicle and pole. The competitive classification performance can be explained by the diverse factors: e.g. the above ground height highlights the vertical dimension of houses, trees even cars, but also attributed to decision-level fusion of graph-based contextual classification approach with shape priors. The use of context-based classification methods mainly contributed to smoothing of labelling by removing

Corticotropin-Releasing Factor Receptors Modulate Oxytocin Release in the Dorsolateral Bed Nucleus of the Stria Terminalis (BNST in Male Rats

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Daisy Martinon

2018-03-01

Full Text Available The neuropeptide oxytocin (OT plays an important role in the regulation of social and anxiety-like behavior. Our previous studies have shown that OT neurons send projections from the hypothalamus to the dorsolateral bed nucleus of the stria terminalis (BNSTdl, a forebrain region critically involved in the modulation of anxiety-like behavior. Importantly, these OT terminals in the BNSTdl express presynaptic corticotropin releasing factor (CRF receptor type 2 (CRFR2. This suggests that CRFR2 might be involved in the modulation of OT release. To test this hypothesis, we measured OT content in microdialysates collected from the BNSTdl of freely-moving male Sprague-Dawley rats following the administration of a selective CRFR2 agonist (Urocortin 3 or antagonist (Astressin 2B, As2B. To determine if type 1 CRF receptors (CRFR1 are also involved, we used selective CRFR1 antagonist (NBI35965 as well as CRF, a putative ligand of both CRFR1 and CRFR2. All compounds were delivered directly into the BNSTdl via reverse dialysis. OT content in the microdialysates was measured with highly sensitive and selective radioimmunoassay. Blocking CRFR2 with As2B caused an increase in OT content in BNSTdl microdialysates, whereas CRFR2 activation by Urocortin 3 did not have an effect. The As2B-induced increase in OT release was blocked by application of the CRFR1 antagonist demonstrating that the effect was dependent on CRFR1 transmission. Interestingly, CRF alone caused a delayed increase in OT content in BNSTdl microdialysates, which was dependent on CRF2 but not CRF1 receptors. Our results suggest that members of the CRF peptide family modulate OT release in the BNSTdl via a fine-tuned mechanism that involves both CRFR1 and CRFR2. Further exploration of mechanisms by which endogenous OT system is modulated by CRF peptide family is needed to better understand the role of these neuropeptides in the regulation of anxiety and the stress response.

Novel HIV-1 recombinants spreading across multiple risk groups in the United Kingdom: the identification and phylogeography of Circulating Recombinant Form (CRF 50_A1D.

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Geraldine M Foster

Full Text Available An increase in non-B HIV-1 infections among men who have sex with men (MSM in the United Kingdom (UK has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies.A total of 55,556 pol (reverse transcriptase and protease sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL. Overall 72 patients shared the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug users (IDUs. In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints, which has been classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST. This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a subtype B strain.We report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around 1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B. These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously

Object recognition in images via a factor graph model

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He, Yong; Wang, Long; Wu, Zhaolin; Zhang, Haisu

2018-04-01

Object recognition in images suffered from huge search space and uncertain object profile. Recently, the Bag-of- Words methods are utilized to solve these problems, especially the 2-dimension CRF(Conditional Random Field) model. In this paper we suggest the method based on a general and flexible fact graph model, which can catch the long-range correlation in Bag-of-Words by constructing a network learning framework contrasted from lattice in CRF. Furthermore, we explore a parameter learning algorithm based on the gradient descent and Loopy Sum-Product algorithms for the factor graph model. Experimental results on Graz 02 dataset show that, the recognition performance of our method in precision and recall is better than a state-of-art method and the original CRF model, demonstrating the effectiveness of the proposed method.

Molecular Recognition of Corticotropin releasing Factor by Its G protein-coupled Receptor CRFR1

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Pioszak, Augen A.; Parker, Naomi R.; Suino-Powell, Kelly; Xu, H. Eric (Van Andel)

2009-01-15

The bimolecular interaction between corticotropin-releasing factor (CRF), a neuropeptide, and its type 1 receptor (CRFR1), a class B G-protein-coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form and two in distinct CRF-bound states. The CRFR1 ECD adopts the alpha-beta-betaalpha fold observed for other class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide-binding site of other class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.

GHRELIN ACTIVATES HYPOPHYSIOTROPIC CORTICOTROPIN-RELEASING FACTOR NEURONS INDEPENDENTLY OF THE ARCUATE NUCLEUS

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Cabral, Agustina; Portiansky, Enrique; Sánchez-Jaramillo, Edith; Zigman, Jeffrey M.; Perello, Mario

2016-01-01

Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin’s orexigenic action vs. its role as a stress signal are anatomically dissociated. PMID:26874559

Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain.

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Rotllant, David; Nadal, Roser; Armario, Antonio

2007-05-01

Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

Sex differences in the locus coeruleus-norepinephrine system and its regulation by stress.

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Bangasser, Debra A; Wiersielis, Kimberly R; Khantsis, Sabina

2016-06-15

Women are more likely than men to suffer from post-traumatic stress disorder (PTSD) and major depression. In addition to their sex bias, these disorders share stress as an etiological factor and hyperarousal as a symptom. Thus, sex differences in brain arousal systems and their regulation by stress could help explain increased vulnerability to these disorders in women. Here we review preclinical studies that have identified sex differences in the locus coeruleus (LC)-norepinephrine (NE) arousal system. First, we detail how structural sex differences in the LC can bias females towards increased arousal in response to emotional events. Second, we highlight studies demonstrating that estrogen can increase NE in LC target regions by enhancing the capacity for NE synthesis, while reducing NE degradation, potentially increasing arousal in females. Third, we review data revealing how sex differences in the stress receptor, corticotropin releasing factor 1 (CRF1), can increase LC neuronal sensitivity to CRF in females compared to males. This effect could translate into hyperarousal in women under conditions of CRF hypersecretion that occur in PTSD and depression. The implications of these sex differences for the treatment of stress-related psychiatric disorders are discussed. Moreover, the value of using information regarding biological sex differences to aid in the development of novel pharmacotherapies to better treat men and women with PTSD and depression is also highlighted. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2015 Elsevier B.V. All rights reserved.

Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients

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Kazem Baesi

2014-09-01

Full Text Available Objective: To identify the dominant subtype among the HIV-1 strains circulation in Iran. Methods: In this cross sectional study 100 HIV positive patients participated. HIV-1 RNA was extracted from plasma. RT nested-PCR was performed and the final products were sequenced and phylogenetically analyzed; reference sequences were downloaded from Los Alamos, aligned with Iranian pol sequences in the study and analyzed by neighbor-joining method. Results: The results of the phylogenetic analysis showed that HIV-1 subtype CRF-35AD was the dominant subtype among HIV-1 infected patients in Iran; this analysis also suggested a new circulating recombinant form that had not previously been identified in Iran: CRF-29BF. Conclusions: The impact of HIV diversity on pathogenesis, transmission and clinical management have been discussed in different studies; therefore, analyses of HIV genetic diversity is required to design effective antiretroviral strategies for different HIV subtypes.

Short Communication Phylogenetic Characterization of HIV Type 1 CRF01_AE V3 Envelope Sequences in Pregnant Women in Northern Vietnam

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Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca

2012-01-01

Abstract Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005–2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology. PMID:21936713

Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159.

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Estibaliz Lazaro

Full Text Available BACKGROUND: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding. METHODS: We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores and HLA binding (MHC score. RESULTS: All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9 versus 2 (±0.7 in non-divergent ones (p<0.0001. CONCLUSIONS: Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area.

Predicting survival function and identifying associated factors in patients with renal insufficiency in the metropolitan area of Maringá, Paraná State, Brazil.

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Ramires, Thiago G; Nakamura, Luiz R; Righetto, Ana J; Ortega, Edwin M M; Cordeiro, Gauss M

2018-02-05

Renal insufficiency is a serious medical and public health problem worldwide. Recently, although many surveys have been developed to identify factors related to the lifetime of patients with renal insufficiency, controversial results from several studies suggest that researches should be conducted by region. Thus, in this study we aim to predict and identify factors associated with the lifetime of patients with chronic renal failure (CRF) in the metropolitan area of Maringá, Paraná State, Brazil, based on the generalized additive models for location, scale and shape (GAMLSS) framework. Data used in this study were collected from the Maringá Kidney Institute and comprehends 177 patients (classified with CRF and mostly being treated under the Brazilian Unified National Health System) enrolled in a hemodialysis program from 1978 up to 2010. By using this approach, we concluded that in other regions, gender, kidney transplant indicator, antibodies to hepatitis B and antibodies to hepatitis C are significant factors that affect the expected lifetime.

Predicting survival function and identifying associated factors in patients with renal insufficiency in the metropolitan area of Maringá, Paraná State, Brazil

Directory of Open Access Journals (Sweden)

Thiago G. Ramires

2018-02-01

Full Text Available Renal insufficiency is a serious medical and public health problem worldwide. Recently, although many surveys have been developed to identify factors related to the lifetime of patients with renal insufficiency, controversial results from several studies suggest that researches should be conducted by region. Thus, in this study we aim to predict and identify factors associated with the lifetime of patients with chronic renal failure (CRF in the metropolitan area of Maringá, Paraná State, Brazil, based on the generalized additive models for location, scale and shape (GAMLSS framework. Data used in this study were collected from the Maringá Kidney Institute and comprehends 177 patients (classified with CRF and mostly being treated under the Brazilian Unified National Health System enrolled in a hemodialysis program from 1978 up to 2010. By using this approach, we concluded that in other regions, gender, kidney transplant indicator, antibodies to hepatitis B and antibodies to hepatitis C are significant factors that affect the expected lifetime.

Nucleic acid amplification of HIV-1 integrase sequence subtypes CRF01_AE and B for development of HIV anti-integrase drug resistance genotyping assay

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Adlar, F. R.; Bela, B.

2017-08-01

To anticipate the potential use of anti-integrase drugs in Indonesia for treatment of HIV-1 infection, the development of a drug resistance genotyping assay for anti-integrase is crucial in identifying the genetic drug resistance profile of Indonesian HIV-1 strains. This experiment aimed to amplify a target region in the integrase gene of Indonesian HIV-1 subtypes CRF01_AE and B that contain genetic mutations known to confer resistance to anti-integrase drug. Eleven archived plasma samples from individuals living with HIV-1 were obtained from the Virology and Cancer Pathobiology Research Center for Health Service (VCPRC FKUI-RSCM) laboratory. One of the plasma samples contained HIV-1 subtype B, and the remaining plasma samples contained subtype CRF01_AE. The target regions for all samples were amplified through RT-PCR, with an annealing temperature of 55 °C, using the primer pair AE_POL 4086F and AE_POL 5232R that were designed by VCPRC FKUI-RSCM. The results of this experiment show that 18.2% (2/11) of the samples were successfully amplified using the one-step RT-PCR. While the primer pair was effective in amplifying the target region in the integrase gene sequence for subtype B (100%; 1/1), it had a low efficacy (10%, 1/10) for subtype CRF01_AE. In conclusion, the primer pair can be used to amplify the target region in Indonesian HIV-1 strain subtypes CRF01_AE and B. However, optimization of the PCR condition and an increased number of samples would help to determine an accurate representation of the efficacy of the primer pair.

Favorable cardiovascular risk factor profile is associated with lower healthcare expenditure and resource utilization among adults with diabetes mellitus free of established cardiovascular disease: 2012 Medical Expenditure Panel Survey (MEPS).

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Feldman, David I; Valero-Elizondo, Javier; Salami, Joseph A; Rana, Jamal S; Ogunmoroti, Oluseye; Osondu, Chukwuemeka U; Spatz, Erica S; Virani, Salim S; Blankstein, Ron; Blaha, Michael J; Veledar, Emir; Nasir, Khurram

2017-03-01

Given the prevalence and economic burden of diabetes mellitus (DM), we studied the impact of a favorable cardiovascular risk factor (CRF) profile on healthcare expenditures and resource utilization among individuals without cardiovascular disease (CVD), by DM status. 25,317 participants were categorized into 3 mutually-exclusive strata: "Poor", "Average" and "Optimal" CRF profiles (≥4, 2-3, 0-1 CRF, respectively). Two-part econometric models were utilized to study cost data. Mean age was 45 (48% male), with 54% having optimal, 39% average, and 7% poor CRF profiles. Individuals with DM were more likely to have poor CRF profile vs. those without DM (OR 7.7, 95% CI 6.4, 9.2). Individuals with DM/poor CRF profile had a mean annual expenditure of $9,006, compared to $6,461 among those with DM/optimal CRF profile (p profile is associated with significantly lower healthcare expenditures and utilization in CVD-free individuals across DM status, suggesting that these individuals require aggressive individualized prescriptions targeting lifestyle modifications and therapeutic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Construction and characterisation of a full-length infectious molecular clone from a fast replicating, X4-tropic HIV-1 CRF02.AG primary isolate

International Nuclear Information System (INIS)

Tebit, Denis M.; Zekeng, Leopold; Kaptue, Lazare; Kraeusslich, Hans-Georg; Herchenroeder, Ottmar

2003-01-01

Based on our previous analysis of HIV-1 isolates from Cameroon, we constructed a full-length infectious molecular clone from a primary isolate belonging to the CRF02.AG group of recombinant viruses which dominate the HIV-epidemic in West and Central Africa. The virus derived by transfection of the proviral clone pBD6-15 replicated with similar efficiency compared to its parental isolate and used CXCR4 as coreceptor as well. Furthermore, HIV-1 BD6-15 exhibited similar replication properties and virus yield as the reference B-type HIV-1 strain NL4-3. Sequence analysis revealed open reading frames for all structural and accessory genes apart from vpr. Phylogenetic and bootscanning analyses confirmed that BD6-15 clusters with CRF02.AG recombinant strains from West and Central Africa with similar cross-over points as described for the CRF02.AG prototype strain lbNG. Thus, pBD6-15 represents the first non-subtype B infectious molecular clone of a fast replicating, high producer, X4-tropic primary HIV-1 isolate, which had only been briefly passaged in primary cells

A role for corticotropin-releasing factor signaling in the lateral habenula and its modulation by early-life stress.

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Authement, Michael E; Langlois, Ludovic D; Shepard, Ryan D; Browne, Caroline A; Lucki, Irwin; Kassis, Haifa; Nugent, Fereshteh S

2018-03-06

Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb. Through its receptor CRFR1 and subsequently protein kinase A (PKA), CRF application increased the intrinsic excitability of LHb neurons by affecting changes in small-conductance SK-type and large-conductance BK-type K + channels. CRF also reduced inhibitory γ-aminobutyric acid-containing (GABAergic) synaptic transmission onto LHb neurons through endocannabinoid-mediated retrograde signaling. Maternal deprivation is a severe early-life stress that alters CRF neural circuitry and is likewise associated with abnormal mental health later in life. LHb neurons from pups deprived of maternal care exhibited increased intrinsic excitability, reduced GABAergic transmission, decreased abundance of SK2 channel protein, and increased activity of PKA, without any substantial changes in Crh or Crhr1 expression. Furthermore, maternal deprivation blunted the response of LHb neurons to subsequent, acute CRF exposure. Activating SK channels or inhibiting postsynaptic PKA activity prevented the effects of both CRF and maternal deprivation on LHb intrinsic excitability, thus identifying potential pharmacological targets to reverse central CRF circuit dysregulation in patients with associated disorders. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

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Flandreau, Elizabeth I.; Bourke, Chase H.; Ressler, Kerry J.; Vale, Wylie W.; Nemeroff, Charles B.; Owens, Michael J.

2013-01-01

Summary We have previously demonstrated that viral-mediated overexpression of corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) reproduces many of the behavioral and endocrine consequences of chronic stress. The present experiment sought to determine whether administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram reverses the adverse effects of CeA CRF overexpression. In a 2 × 2 design, adult male rats received bilateral infusions of a control lentivirus or a lentivirus in which a portion of the CRF promoter is used to drive increased expression of CRF peptide. Four weeks later, rats were then implanted with an Alzet minipump to deliver vehicle or 10 mg/kg/day escitalopram for a 4-week period of time. The defensive withdrawal (DW) test of anxiety and the sucrose-preference test (SPT) of anhedonia were performed both before and after pump implantation. Additional post-implant behavioral tests included the elevated plus maze (EPM) and social interaction (SI) test. Following completion of behavioral testing, the dexamethasone/CRF test was performed to assess HPA axis reactivity. Brains were collected and expression of HPA axis-relevant transcripts were measured using in situ hybridization. Amygdalar CRF overexpression increased anxiety-like behavior in the DW test at week eight, which was only partially prevented by escitalopram. In both CRF-overexpressing and control groups, escitalopram decreased hippocampal CRF expression while increasing hypothalamic and hippocampal expression of the glucocorticoid receptor (GR). These gene expression changes were associated with a significant decrease in HPA axis reactivity in rats treated with escitalopram. Interestingly, escitalopram increased the rate of weight gain only in rats overexpressing CRF. Overall these data support our hypothesis that amygdalar CRF is critical in anxiety-like behavior; because the antidepressant was unable to reverse behavioral

Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.

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Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M; Rice, Kenner C; Ubaldi, Massimo; St Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin; Cifani, Carlo

2014-08-20

We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders. Copyright © 2014 the authors 0270-6474/14/3411316-09$15.00/0.

Performance analysis of CRF-based learning for processing WoT application requests expressed in natural language.

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Yoon, Young

2016-01-01

In this paper, we investigate the effectiveness of a CRF-based learning method for identifying necessary Web of Things (WoT) application components that would satisfy the users' requests issued in natural language. For instance, a user request such as "archive all sports breaking news" can be satisfied by composing a WoT application that consists of ESPN breaking news service and Dropbox as a storage service. We built an engine that can identify the necessary application components by recognizing a main act (MA) or named entities (NEs) from a given request. We trained this engine with the descriptions of WoT applications (called recipes) that were collected from IFTTT WoT platform. IFTTT hosts over 300 WoT entities that offer thousands of functions referred to as triggers and actions. There are more than 270,000 publicly-available recipes composed with those functions by real users. Therefore, the set of these recipes is well-qualified for the training of our MA and NE recognition engine. We share our unique experience of generating the training and test set from these recipe descriptions and assess the performance of the CRF-based language method. Based on the performance evaluation, we introduce further research directions.

Behavioral and physiological responses to central administration of corticotropin-releasing factor in the bluebanded goby (Lythrypnus dalli).

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Solomon-Lane, Tessa K; Grober, Matthew S

2012-07-16

Central manipulation of neuromodulators is critical to establishing causal links between brain function and behavioral output. The absence of a rigorous method of evaluating intracerebroventricular (i.c.v.) injection efficacy in small model organisms is one reason why peripheral administration of neuroactive substances is more common. We use the bluebanded goby (Lythrypnus dalli), a small, highly social fish, to 1) validate our method of i.c.v. injection by testing the hypothesis that corticotropin-releasing factor (CRF) elevates ventilation rate (VR) and 2) propose a novel bioassay using basal physiology and behavior during recovery from anesthesia/i.c.v. administration to assess injection efficacy, neuromodulator activity, and procedural confounds. Central CRF administration significantly increased ventilation rate, demonstrating successful delivery of CRF to the brain. There were no significant differences in cortisol among treatments. The injection procedure did, however, decouple the temporal relationship between the initiation of ventilation and time to regain equilibrium present in control fish. Importantly, neither i.c.v. vehicle nor CRF injection affected the initiation of ventilation, disrupted the stereotyped recovery pattern following anesthesia, or initiated an endocrine stress response. Taken together, we suggest that 1) i.c.v. injection can be effectively used to manipulate central levels of CRF in L. dalli and 2) physiological and behavioral recovery from anesthesia may be used to evaluate injection/technique efficacy. We will use these data in future studies as a measure of effective CRF delivery, to allow for appropriate recovery from i.c.v. injection, and to better evaluate independent effects of CRF on social and/or sexual behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

Learning and CRF-Induced Indecision during Escape and Submission in Rainbow Trout during Socially Aggressive Interactions in the Stress-Alternatives Model

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Tangi R. Summers

2017-09-01

Full Text Available Socially stressful environments induce a phenotypic dichotomy of coping measures for populations in response to a dominant aggressor and given a route of egress. This submission- (Stay or escape-oriented (Escape dichotomy represents individual decision-making under the stressful influence of hostile social environments. We utilized the Stress-Alternatives Model (SAM to explore behavioral factors which might predict behavioral phenotype in rainbow trout. The SAM is a compartmentalized tank, with smaller and larger trout separated by an opaque divider until social interaction, and another divider occluding a safety zone, accessible by way of an escape route only large enough for the smaller fish. We hypothesized that distinctive behavioral responses during the first social interaction would indicate a predisposition for one of the behavioral phenotypes in the subsequent interactions. Surprisingly, increased amount or intensity of aggression received had no significant effect on promoting escape in test fish. In fact, during the first day of interaction, fish that turned toward their larger opponent during attack eventually learned to escape. Escaping fish also learn to monitor the patrolling behavior of aggressors, and eventually escape primarily when they are not being observed. Escape per se, was also predicted in trout exhibiting increased movements directed toward the escape route. By contrast, fish that consistently remained in the tank with the aggressor (Stay showed significantly higher frequency of swimming in subordinate positions, at the top or the bottom of the water column, as well as sitting at the bottom. In addition, a corticotropin-releasing factor (CRF-induced behavior, snap-shake, was also displayed in untreated fish during aggressive social interaction, and blocked by a CRF1 receptor antagonist. Especially prevalent among the Stay phenotype, snap-shake indicates indecision regarding escape-related behaviors. Snap-shake was also

Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones.

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Wang, Lixin; Goebel-Stengel, Miriam; Yuan, Pu-Qing; Stengel, Andreas; Taché, Yvette

2017-01-01

Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting

A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

KAUST Repository

Huang, Yangjie; Ajitha, Manjaly John; Huang, Kuo-Wei; Zhang, Zhongxing; Weng, Zhiqiang

2016-01-01

This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

KAUST Repository

Huang, Yangjie

2016-04-13

This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

Radioautographic study of binding and internalization of corticotropin-releasing factor by rat anterior pituitary corticotrophs

International Nuclear Information System (INIS)

Leroux, P.; Pelletier, G.

1984-01-01

In order to identify the anterior pituitary cell type(s) containing corticotropin-releasing factor (CRF) receptors and to study the internalization processes of this peptide by the target cells, radioautography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after intracarotid injection of [ 125 I]iodo-CRF into intact and adrenalectomized female rats. In intact animals, all corticotrophs were labeled, whereas in the adrenalectomized animals about 80% of the hypertrophied corticotrophs (adrenalectomy cells) were. In control animals injected with both iodinated CRF and an excess of unlabeled peptide, no specific reaction could be detected. The time-course study in intact animals showed that 2 min after injection most silver grains were found over or within 160 nm of the plasma membrane. At the 5-min time intervals, grains were observed both over the plasma membrane and within the cytoplasm, associated with lysosomes, and the Golgi apparatus. Fifteen minutes after injection, grains were mostly found over lysosomes and the Golgi apparatus, whereas at the longest time intervals (30 and 60 min) almost no labeling could be detected. The results obtained in this study indicate that in the anterior pituitary CRF receptors are restricted to corticotrophs (as identified by electron microscopy) and that, after binding to the plasma membrane, CRF is rapidly internalized to Golgi elements and lysosomes

Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

Science.gov (United States)

Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

2012-09-01

Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Relationships of physical fitness and obesity with metabolic risk factors in children and adolescents: Chungju city cohort study

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Hyo Jin Kim

2016-03-01

Full Text Available PurposeThe purpose of this study was to investigate the relationships of physical fitness and obesity with metabolic risk factors in children and adolescents.MethodsThis cohort study was conducted in Chungju city, South Korea. Total 843 subjects were enrolled, including 193 elementary school 4th grade male (E4M, 189 elementary school 4th grade female (E4F and 461 male-middle school students (M1M. The subjects were also classified into 2 groups by body mass index; normal weight (NW group and overweight included obesity (OW/OB group. Physical fitness was measured by shuttle run (cardiorespiratory fitness, CRF, sit and reach (flexibility, handgrip strength (muscular strength and stand long jump (agility.ResultsThe prevalence of OW/OB was respectively 33.7% (65 of 193 among E4M, 28.6% (54 of 189 among E4F, and 28.0% (129 of 461 among M1M. Hematocrit, white blood cell, triglyceride, low-density lipoprotein, insulin, homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure were higher, while high-density lipoprotein were lower in the OW/OB group than in the NW group. The OW/OB group presented significantly lower CRF (P<0.01 and lower agility, but higher muscular strength compared with NW group. CRF was negatively correlated with obesity indices and metabolic risk factors. After adjustments for potential confounders, odds ratios for 4th–5th grade CRF of OW/OB compared NW in the E4M, E4F, M1M, were 7.38 (95 % CI, 3.24–16.83, 4.10 (95% CI, 1.83–9.18, 16.06 (95% CI, 8.23–31.00 (P<0.01.ConclusionOur study has shown that CRF has negative correlation with OW/OB in children and adolescents of Chungju city. We suggest that improvement of CRF through regular physical activity would be an important method for reducing the metabolic risks of childhood obesity.

Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health

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Donny eJanssen

2013-03-01

Full Text Available Physiological responses to stress coordinated by the hypothalamo-pituitary-adrenal (HPA- axis are concerned with maintaining homeostasis in the presence of real or perceived challenges. Regulators of this axis are corticotrophin releasing hormone (CRF and CRF related neuropeptides, including urocortins (Ucn 1, 2 and 3. They mediate their actions by binding to CRF receptors (CRFR 1 and 2, which are located in several stress related brain regions. The prevailing theory has been that the initiation of and the recovery from an elicited stress response is coordinated by two elements, viz. the (mainly opposing, but well balanced actions of CRFR1 and CRFR2. Such a dualistic view suggests that CRF/CRFR1 controls the initiation of, and urocortins/CRFR2 mediate the recovery from stress to maintain body and mental health. Consequently, failed adaptation to stress can lead to neuropathology, including anxiety and depression. Recent literature, however, challenges such dualistic and complementary actions of CRFR1 and CRFR2, and suggests that stress recruits CRF system components in a brain area and neuron specific manner to promote adaptation as conditions dictate.

The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

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Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

2012-08-03

N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

Use of physical activity and cardiorespiratory fitness in identifying cardiovascular risk factors in male brazilian adolescents

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Lilian Messias Sampaio Brito

2016-02-01

Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n6p678   The aim of this study was to investigate the impact of physical activity (PA and cardiorespiratory fitness (CRF levels on the prevalence of overweight and high blood pressure levels in adolescents. In this observational, cross-sectional study, 614 boys aged 10-14 years were assessed for height, body mass, body mass index (BMI, waist circumference (WC and blood pressure (BP. CRF was assessed using a run test (Léger Test and subjects were then grouped according to their CRF level. PA level was assessed through a questionnaire (The Three Day Physical Activity Recall and classified into two groups, namely > 300 minutes of PA/week and < 300 minutes of PA/week. Maturational stage was evaluated according to the development of pubic hair (self-assessment as proposed by Tanner. We used statistical descriptive analysis, univariate and multivariate analyses in the total participants and subjects were divided by age. Fifty percent of the sample performed < 300 minutes of PA/week and 67.6% had unsatisfactory CRF levels. There was a higher prevalence of unsatisfactory CRF levels among subjects with altered BMI (overweight, WC (abdominal obesity or BP (high blood pressure for all age groups. PA history, however, did not show any significance. A total of 31% of participants were overweight, 24.8% had abdominal obesity and 15.4% had increased BP. Unsatisfactory CRF levels were found to be a better predictor for the diagnosis of cardiovascular diseases (CV risk factors than PA history, regardless of age group.

Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

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Ding, Xiu-Fang; Zhao, Xiao-Hua; Tao, Yang; Zhong, Wei-Chao; Fan, Qin; Diao, Jian-Xin; Liu, Yuan-Liang; Chen, Yu-Yao; Chen, Jia-Xu; Lv, Zhi-Ping

2014-01-01

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats

International Nuclear Information System (INIS)

Nakade, Yukiomi; Mantyh, C.; Pappas, T.N.; Takahashi, Toku

2007-01-01

Fecal pellet output has been assessed as a colonic motor activity because of its simplicity. However, it remains unclear whether an acceleration of colonic transit correlates well with an increase in fecal pellet output. We examined the causal relationship between colonic transit and fecal pellet output stimulated by the central application of corticotropin-releasing factor (CRF) and restraint stress. Immediately after intracisternal injection of CRF, 51 Cr was injected via a catheter positioned in the proximal colon. Ninety minutes after 51 Cr injection, the total number of excreted feces was counted, and then the rats were killed. The radioactivity of each colonic segment was evaluated, and the geometric center (GC) of the distribution of 51 Cr was calculated. For the restraint stress study, after administration of 51 Cr into the proximal colon, rats were submitted to wrapping restraint stress for 90 min. Then they were killed, and GC was calculated. Both restraint stress and CRF significantly accelerated colonic transit. There was a positive correlation observed between fecal pellet output and GC of colonic transit in response to restraint stress, but not CRF, when the number of excreted feces was more than three. In contrast, there was no significant correlation observed between the two in stress and CRF when the number of excreted feces was less than two. The acceleration of colonic transit in response to restraint stress and central administration of CRF does not always correlate with an increase in fecal pellet output. (author)

The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

DEFF Research Database (Denmark)

Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

2017-01-01

BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain...... fitness (CRF), anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were...

Influence of the shot-peening treatment on the CRF gearing behaviour

International Nuclear Information System (INIS)

Molinie, D.; Lemaire, E.; Randrianarivo, L.; Dorier, C.

1998-01-01

Surface damage are observed in service on CRF case-hardened cases. Such damage is like surface fatigue which appears in the form of frosting and can come to a micro-spalling or even a spalling damage. Survey and studies realised on gears affected by such damage, led EDF and the manufacturer to search for appropriated solutions since 1985 (optimisation of the gear bottom profile, care of the grinding and the thermochemical processing, use of oils with higher viscosity). Simulations on a running wheel device can reproduce the meshing conditions on simplified specimen. The aim is to study the influence of residual stresses following a severe grinding and shot peening treatments. An empiric selection was realised among different shot peening treatments. Endurance tests are realised on case-hardened gears with or without shot-peening treatments. Compared with standard grinded gears, it appears that the shot-peening selected increases up to 40% the gear lifetime till extended spalling. (authors)

Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

Science.gov (United States)

Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

2011-05-01

Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat.

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Linda Sterrenburg

Full Text Available BACKGROUND: Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS after which immediate early gene products, corticotropin-releasing factor (CRF mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN, oval (BSTov and fusiform (BSTfu parts of the bed nucleus of the stria terminalis, and central amygdala (CeA. RESULTS: CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.

Local Optogenetic Induction of Fast (20-40 Hz Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

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Julien eDine

2016-04-01

Full Text Available The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2 expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz field potential oscillations in hippocampal area CA1 in vitro (at 25°C and in vivo (i.e., slightly anaesthetized NEX-Cre-ChR2 mice. As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity.

Science.gov (United States)

Dine, Julien; Genewsky, Andreas; Hladky, Florian; Wotjak, Carsten T; Deussing, Jan M; Zieglgänsberger, Walter; Chen, Alon; Eder, Matthias

2016-01-01

The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells) and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM) in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC) in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1→PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive) P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

Low muscle strength is associated with metabolic risk factors in Colombian children: the ACFIES study.

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Daniel Dylan Cohen

Full Text Available PURPOSE: In youth, poor cardiorespiratory and muscular strength are associated with elevated metabolic risk factors. However, studies examining associations between strength and risk factors have been done exclusively in high income countries, and largely in Caucasian cohorts. The aim of this study was to assess these interactions in schoolchildren in Colombia, a middle income Latin American country. METHODS: We measured body mass index, body composition, handgrip strength (HG, cardiorespiratory fitness (CRF and metabolic risk factors in 669 low-middle socioeconomic status Colombian schoolchildren (mean age 11.52±1.13, 47% female. Associations between HG, CRF and metabolic risk factors were evaluated. RESULTS: HG and CRF were inversely associated with blood pressure, HOMA index and a composite metabolic risk score (p = 0.001, HOMA (β = -0.164; p = 0.005, triglycerides (β = -0.583; p = 0.026 and CRP (β = -0.183; p = 0.037 but not glucose (p = 0.698 or HDL cholesterol (p = 0.132. The odds ratios for having clustered risk in the weakest quartile compared with the strongest quartile were 3.0 (95% confidence interval: 1.81-4.95. CONCLUSIONS: In Colombian schoolchildren both poorer handgrip strength/kg body mass and cardiorespiratory fitness were associated with a worse metabolic risk profile. Associations were stronger and more consistent between handgrip and risk factors than between cardiorespiratory fitness and these risk factors. Our findings indicate the addition of handgrip dynamometry to non-invasive youth health surveillance programs would improve the accuracy of the assessment of cardio-metabolic health.

Characterization of a Cytokinin Response Factor in Arabidopsis thaliana

OpenAIRE

Ketelsen, Bernd

2012-01-01

The papers of this thesis are not available in Munin: 1. Bernd Ketelsen, Rainer Schwacke, Kirsten Krause and Karsten Fischer: 'Transcriptional activation by Cytokinin Response Factor 5 is governed by an acidic Cterminus containing two conserved domains' (manuscript) 2. Bernd Ketelsen, Stian Olsen, Kirsten Krause and Karsten Fischer: 'Cytokinin responsive factor 5 (CRF5) is involved in root development, hormonal crosstalk and sugar metabolism in Arabidopsis thaliana' (manuscript) 3. Bernd K...

Computer Operating System Maintenance.

Science.gov (United States)

1982-06-01

FACILITY The Computer Management Information Facility ( CMIF ) system was developed by Rapp Systems to fulfill the need at the CRF to record and report on...computer center resource usage and utilization. The foundation of the CMIF system is a System 2000 data base (CRFMGMT) which stores and permits access

The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus.

Science.gov (United States)

Miele, Emily M; Headley, Samuel A E

2017-09-12

Aerobic exercise training is a component of diabetes mellitus (DM) care guidelines due to its favorable effects on glycemic control and cardiovascular disease (CVD) risk factors. The purpose of this review is to outline the recent evidence regarding the clinical effects of chronic aerobic exercise on CVD risk factors in persons with DM and to compare the effects of varying intensities and types of exercise. Among individuals with DM, all types of aerobic exercise training can impact positively on some traditional and non-traditional risk factors for CVD. Training programs with a higher volume or intensity induce greater improvements in vascular function, cardiorespiratory fitness (CRF), and lipid profiles. The beneficial outcomes of aerobic training include improvements in glycemic control, endothelial function, oxidative stress, dyslipidemia, myocardial function, adiposity, and CRF. Findings regarding markers of inflammation are discrepant and further research should focus on the role of exercise to impact upon the chronic inflammation associated with DM.

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake

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Lucas Albrechet-Souza

2017-10-01

Full Text Available Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume for 4 weeks, control and stressed mice had CRF type 1 (CRFR1 or type 2 (CRFR2 receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2. Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake.

Science.gov (United States)

Albrechet-Souza, Lucas; Viola, Thiago W; Grassi-Oliveira, Rodrigo; Miczek, Klaus A; de Almeida, Rosa M M

2017-01-01

Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF) neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST) contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume) for 4 weeks, control and stressed mice had CRF type 1 (CRFR1) or type 2 (CRFR2) receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2 . Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates alcohol

Associated factors and prevalence of erectile dysfunction in hemodialysis patients

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Marcio Rodrigues Costa

2014-01-01

Full Text Available Purpose: The proposal of this study was to determine the prevalence and the associated factors of erectile dysfunction (ED among hemodialysis (HD patients. Materials and Methods: This was a cross-sectional study based on data collected from HD male patients. Clinical, demographic and laboratory data of all patients were collected in three HD clinics from December 2010 to June 2011. Patients answered questions of erectile function domain from International Index of Erectile Function. Data were evaluated by descriptive analysis and by univariate (ULRA and multivariate logistic regression analysis (MLRA. Results: Three hundred and five patients participated of the study. The prevalence of ED was 68.19%. ED was associated with diabetes (DM, benign prostatic hyperplasia, glomerulonephritis as cause of chronic renal failure (CRF, smoking habits, lower creatinine levels (ULRA, use of calcium channel blocker (MLRA, aging, lower education level, alcohol consumption, DM (as cause of CRF and coronary insufficiency (ULRA and MLRA. Conclusions: ED was highly prevalent in the HD men. It was independently associated with aging, current use of alcohol, long alcohol use (even for those who do not drink more, lower education level, diabetes as cause of CRF, coronary insufficiency and use of channel blockers calcium.

Common and divergent structural features of a series of corticotropin releasing factor-related peptides.

Science.gov (United States)

Grace, Christy Rani R; Perrin, Marilyn H; Cantle, Jeffrey P; Vale, Wylie W; Rivier, Jean E; Riek, Roland

2007-12-26

Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

Anatomical Organization of Urocortin 3-Synthesizing Neurons and Immunoreactive Terminals in the Central Nervous System of Non-Human Primates [Sapajus spp.

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Daniella S. Battagello

2017-07-01

Full Text Available Urocortin 3 (UCN3 is a neuropeptide member of the corticotropin-releasing factor (CRF peptide family that acts as a selective endogenous ligand for the CRF, subtype 2 (CRF2 receptor. Immunohistochemistry and in situ hybridization data from rodents revealed UCN3-containing neurons in discrete regions of the central nervous system (CNS, such as the medial preoptic nucleus, the rostral perifornical area (PFA, the medial nucleus of the amygdala and the superior paraolivary nucleus. UCN3-immunoreactive (UCN3-ir terminals are distributed throughout regions that mostly overlap with regions of CRF2 messenger RNA (mRNA expression. Currently, no similar mapping exists for non-human primates. To better understand the role of this neuropeptide, we aimed to study the UCN3 distribution in the brains of New World monkeys of the Sapajus genus. To this end, we analyzed the gene and peptide sequences in these animals and performed immunohistochemistry and in situ hybridization to identify UCN3 synthesis sites and to determine the distribution of UCN3-ir terminals. The sequencing of the Sapajus spp. UCN3-coding gene revealed 88% and 65% identity to the human and rat counterparts, respectively. Additionally, using a probe generated from monkey cDNA and an antiserum raised against human UCN3, we found that labeled cells are mainly located in the hypothalamic and limbic regions. UCN3-ir axons and terminals are primarily distributed in the ventromedial hypothalamic nucleus (VMH and the lateral septal nucleus (LS. Our results demonstrate that UCN3-producing neurons in the CNS of monkeys are phylogenetically conserved compared to those of the rodent brain, that the distribution of fibers agrees with the distribution of CRF2 in other primates and that there is anatomical evidence for the participation of UCN3 in neuroendocrine control in primates.

Cardiovascular risk factors in cognitively impaired nursing home patients: A relationship with pain?

NARCIS (Netherlands)

Achterberg, W.P.; Scherder, E.J.A.; Pot, A.M.; Ribbe, M.W.

2007-01-01

Cardiovascular risk factors (CRF) such as hypertension and diabetes mellitus favour the development of both vascular dementia (VaD) and Alzheimer’s disease (AD). The resulting deafferentation may increase the experience of pain in VaD and in AD. The goal of the present study was to examine the

4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization.

Science.gov (United States)

Gully, Danielle; Geslin, Michel; Serva, Laurence; Fontaine, Evelyne; Roger, Pierre; Lair, Christine; Darre, Valerie; Marcy, Claudine; Rouby, Pierre-Eric; Simiand, Jacques; Guitard, Josette; Gout, Georgette; Steinberg, Regis; Rodier, Daniel; Griebel, Guy; Soubrie, Philippe; Pascal, Marc; Pruss, Rebecca; Scatton, Bernard; Maffrand, Jean-Pierre; Le Fur, Gerard

2002-04-01

4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1- (3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A), a new 2-aminothiazole derivative, shows nanomolar affinity for human cloned or native corticotrophin-releasing factor (CRF)(1) receptors (pK(i) values of 8.73 and 9.08, respectively), and a 1000-fold selectivity for CRF(1) versus CRF(2 alpha) receptor and CRF binding protein. SSR125543A antagonizes CRF-induced stimulation of cAMP synthesis in human retinoblastoma Y 79 cells (IC(50) = 3.0 +/- 0.4 nM) and adrenocorticotropin hormone (ACTH) secretion in mouse pituitary tumor AtT-20 cells. SSR125543A is devoid of agonist activity in these models. Its brain penetration was demonstrated in rats by using an ex vivo [(125)I-Tyr(0)] ovine CRF binding assay. SSR125543A displaced radioligand binding to the CRF(1) receptor in the brain with an ID(50) of 6.5 mg/kg p.o. (duration of action >24 h). SSR125543A also inhibited the increase in plasma ACTH levels elicited in rats by i.v. CRF (4 microg/kg) injection (ID(50) = 1, 5, or 5 mg/kg i.v., i.p., and p.o., respectively); this effect lasted for more than 6 h when the drug was given orally at a dose of 30 mg/kg. SSR125543A (10 mg/kg p.o.) reduced by 73% the increase in plasma ACTH levels elicited by a 15-min restraint stress in rats. Moreover, SSR125543A (20 mg/kg i.p.) also antagonized the increase of hippocampal acetylcholine release induced by i.c.v. injection of 1 microg of CRF in rats. Finally, SSR125543A reduced forepaw treading induced by i.c.v. injection of 1 microg of CRF in gerbils (ID(50) = approximately 10 mg/kg p.o.). Altogether, these data indicate that SSR125543A is a potent, selective, and orally active CRF(1) receptor antagonist.

Radiometric calibration of wide-field camera system with an application in astronomy

Science.gov (United States)

Vítek, Stanislav; Nasyrova, Maria; Stehlíková, Veronika

2017-09-01

Camera response function (CRF) is widely used for the description of the relationship between scene radiance and image brightness. Most common application of CRF is High Dynamic Range (HDR) reconstruction of the radiance maps of imaged scenes from a set of frames with different exposures. The main goal of this work is to provide an overview of CRF estimation algorithms and compare their outputs with results obtained under laboratory conditions. These algorithms, typically designed for multimedia content, are unfortunately quite useless with astronomical image data, mostly due to their nature (blur, noise, and long exposures). Therefore, we propose an optimization of selected methods to use in an astronomical imaging application. Results are experimentally verified on the wide-field camera system using Digital Single Lens Reflex (DSLR) camera.

Role of a genetic polymorphism in the corticotropin-releasing factor receptor 1 gene in alcohol drinking and seeking behaviors of Marchigian Sardinian alcohol-preferring (msP rats

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Lydia Ojonemile Ayanwuyi

2013-04-01

Full Text Available Marchigian Sardinian alcohol-preferring (msP rats exhibit innate preference for alcohol, are highly sensitive to stress and stress-induced alcohol seeking. Genetic analysis showed that over-expression of the corticotropin-releasing factor (CRF system of msP rats is correlated with the presence of two single nucleotide polymorphisms (SNPs occurring in the promoter region (position -1836 and -2097 of the CRF1 receptor (CRF1-R gene. Here we examined whether these point mutations were associated to the innate alcohol preference, stress-induced drinking and seeking.We have recently re-derived the msP rats to obtain two distinct lines carrying the wild type (GG and the point mutations (AA, respectively. The phenotypic characteristics of these two lines were compared with those of unselected Wistar rats. Both AA and GG rats showed similar patterns of voluntary alcohol intake and preference. Similarly, the pharmacological stressor yohimbine (0.0, 0.625, 1.25 and 2.5 mg/kg elicited increased operant alcohol self-administration under fixed and progressive ratio reinforcement schedules in all three lines. Following extinction, yohimbine (0.0, 0.625, 1.25 and 2.5 mg/kg significantly reinstated alcohol seeking in the three groups. However, at the highest dose this effect was no longer evident in AA rats. Treatment with the CRF1-R antagonist antalarmin (0, 5, 10 and 20 mg/kg significantly reduced alcohol-reinforced lever pressing in the AA line (10 and 20 mg/kg while a weaker or no effect was observed in the Wistar and the GG group, respectively. Finally, antalarmin significantly reduced yohimbine-induced increase in alcohol drinking in all three groups.In conclusion, these specific SNPs in the CRF1-R gene do not seem to play a primary role in the expression of the msP excessive-drinking phenotype or stress-induced drinking but may be associated with a decreased threshold for stress-induced alcohol seeking and an increased sensitivity to the effects of

Evolutionary history of HIV-1 subtype B and CRF01_AE transmission clusters among men who have sex with men (MSM) in Kuala Lumpur, Malaysia.

Science.gov (United States)

Ng, Kim Tien; Ong, Lai Yee; Lim, Sin How; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

2013-01-01

HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253-3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2-7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion.

Evaluation of atopy through an expert system: description of the database.

Science.gov (United States)

Ray, P; Vervloet, D; Charpin, D; Gautier, V; Proudhon, H; Redier, H; Godard, P

1995-11-01

In order to understand the medical decisions taken during the initial visit of a new asthmatic patient, a group of experts designed an expert system which provides conclusions about severity, precipitating factors and treatment. Rules for atopy and the assessment of allergic factors have been discussed and implemented in the expert system. Conclusions about severity have been yet validated using an appropriate methodology. The aim of this study was to investigate a sample of 471 patients according to conclusions regarding atopy. A total of 471 cases report forms (CRF) was filled in for adult asthmatic outpatients, seen for the first time in our clinic without emergency situations. Data of each CRF were used by the expert system to draw conclusions. The expert system discerns three patterns for atopy, yes, possible or no. The variables known to reflect different features according to the classification of asthma as atopic or not have been studied. The variables used in the rules for atopy, obviously linked to the conclusion, were not compared. For many medical problems no unique objective solution exists and this is why a group of patients with possible atopy was introduced. Patients with atopy had less severe asthma (P = 0.01), a better FEV1 value (P = 0.0007) and showed their first symptoms of asthma earlier (P = 0.00001) than patients without atopy. The characteristics of the group studied here are consistent with the literature. This could be considered as an indirect validation of the expert system. Moreover, patients with possible atopy show intermediate findings for these variables and it is possible to suggest a 'dose-effect' relationship.

Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

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Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

2010-01-01

Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

Assessment of the severity of asthma by an expert system. Description and evaluation.

Science.gov (United States)

Redier, H; Daures, J P; Michel, C; Proudhon, H; Vervloet, D; Charpin, D; Marsac, J; Dusser, D; Brambilla, C; Wallaert, B

1995-02-01

Asthmaexpert, an expert system (ES), was produced at the special request of several clinicians in order to better understand the medical decisions made clinical experts in managing an asthmatic patient. We describe and evaluate this knowledge base, focusing mainly on assessment of the severity of asthma. After compiling data from a patient, Asthmaexpert assesses the severity of the disease and identifies the trigger factors involved, suggests any further investigations that may be required, and offers a treatment strategy. Implemented with Nexpert and Hypercard, it runs on a MacIntosh personal computer. The validation stage involved eight clinical experts who provided 20 case report forms (CRF) with their conclusions about management of asthma. The CRF were then programmed into the ES, which provided its own conclusions about the same subjects. Afterward, all the experts evaluated the conclusions given by ES or by their colleagues in a double-blind manner. One hundred twenty-seven CRF were available. The reliability of the experts' opinions was good, with a substantial consensus between them when assessing severity scores (kappa = 0.27 to 0.54). There was no difference in concordance of opinions on severity scores either between the experts who designed the system and ES or between the other experts and ES (weighted kappa = 0.72 and 0.69, respectively). Experts judged that the severity scores given by ES were as good as those proposed by their colleagues, and that the overall conclusions given by ES were as good as or better than those given by their colleagues. The conclusions drawn by ES were given a good rating.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

Science.gov (United States)

Ip, Stephen; Hussaini, Trana; Daulat, Aliya; Partovi, Nilufar; Erb, Siegfried R; Yoshida, Eric M; Marquez, Vladimir

2017-01-01

Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. To examine the risk factors in the development of CRF in these patients. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

Impact of Constant Rate Factor on Objective Video Quality Assessment

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Juraj Bienik

2017-01-01

Full Text Available This paper deals with the impact of constant rate factor value on the objective video quality assessment using PSNR and SSIM metrics. Compression efficiency of H.264 and H.265 codecs defined by different Constant rate factor (CRF values was tested. The assessment was done for eight types of video sequences depending on content for High Definition (HD, Full HD (FHD and Ultra HD (UHD resolution. Finally, performance of both mentioned codecs with emphasis on compression ratio and efficiency of coding was compared.

Comparison of Corneal Biomechanical Properties between Indian and Chinese Adults.

Science.gov (United States)

Chua, Jacqueline; Nongpiur, Monisha E; Zhao, Wanting; Tham, Yih Chung; Gupta, Preeti; Sabanayagam, Charumathi; Aung, Tin; Wong, Tien Yin; Cheng, Ching-Yu

2017-09-01

To investigate the difference in corneal hysteresis (CH) and corneal resistance factor (CRF) between Indian and Chinese populations. Population-based cross-sectional study. Three hundred eighty-two Singaporean Indian persons and 764 Singaporean Chinese 50 years of age or older were included from the Singapore Indian Eye Study and Singapore Chinese Eye Study, respectively. Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The CH and CRF were measured with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY). Information on genetic ancestry was derived using principal component analysis. Linear regression models were used to investigate the association of CH and CRF with potential risk factors. Corneal hysteresis and CRF. After excluding participants with a history of intraocular surgery, a diagnosis of glaucoma suspect or glaucoma, refractive surgery, or presence of corneal abnormalities, CH and CRF readings were available for 382 Indian persons. For each Indian participant, 2 Chinese participants were selected and matched for age and gender (n = 764). There were no differences in the clinical measurements of CH (10.6±1.6 mmHg; P = 0.670) or CRF (10.3±1.7 mmHg; P = 0.103) between the ethnic groups. However, after adjusting for covariates, Indian persons had, on average, 0.18-mmHg higher CH levels than in Chinese (95% confidence interval [CI], 0.02-0.38; P = 0.031). Consistently, CH level was correlated significantly with genetic ancestry in the Southeast Asian population. Corneal resistance factor level was not associated independently with self-reported ethnicity (95% CI, -0.10 to 0.29; P = 0.335). Chinese have lower CH than Indian persons, and this disparity may reflect biomechanical differences of the cornea. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Nonalcoholic hepatic steatosis: association with metabolic syndrome and cardiovascular risk factors in obese adolescents

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Wener Barbosa Resende

2014-03-01

Full Text Available Objective: To evaluate the association between nonalcoholic hepatic steatosis (NAHS, metabolic syndrome (MS and cardiovascular risk factors (CRF in obese adolescents. Methods: Cross-sectional observational study with a quantitative approach, carried out from June to August 2011. The volunteers were randomly selected and referred to clinical evaluation in the endocrinology and cardiology units at the clinics hospital of the Federal University of Uberlândia, being included 34 adolescents of 14-19 years above the 95th percentile of the growth curve. NAHS was assessed by ultrasonography. The MS and CRF were diagnosed by the International Diabetes Federation criteria. Results: The sample consisted of 14 male and 20 female patients aged 16.8 ± 1.6 and body mass index (BMI of 35.7 ± 3.9. The occurrence of NAHS and MS was 76.5% and 50%, respectively. Males had a higher incidence of NAHS (78.6%, SM (64.3% and association of NAHS with MS (50%. Regarding the CRF, 100% (n=34, 61.8% (n=21 and 52.9% (n=18 of the adolescents had elevated values of waist circumference (WC, low-density lipoprotein cholesterol (LDL-C and systolic blood pressure (SBP, respectively, and 52.9% (n=18 showed low levels of high-density lipoprotein cholesterol (HDL-C. There were correlations between MS and triglycerides; systolic and diastolic blood pressure and HDL-C; and between NAHS and BMI and WC. Conclusion: A high occurrence of NAHS, SM and CRF was observed in obese adolescents. A strong correlation was observed between MS and NAHS, and between FRC and NAHS and SM. doi:10.5020/18061230.2014.p131

Project PANK: Rationale, study protocol and baseline results of a multidisciplinary school based intervention in children with cardiovascular and metabolic risk factors

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Rui Batalau

2017-05-01

Full Text Available Abstract Aims: Cardiovascular disease risk factors occur more frequently in children with obesity. Project PANK is a multidisciplinary school-based intervention lasting 6 months to improve BMI z-score, waist circumference (WC, waist-to-height ratio (WHtR, blood pressure (BP, nutrition, physical activity (PA, sedentary behaviour (SB, cardiorespiratory fitness (CRF, glucose, cholesterol, and triglycerides (TG. Methods/DesignA total of 77 children (7-10 years were recruited from an urban school. The protocol includes PA and SB individual meetings for children/parents; increasing school exercise; PA and SB lessons for children; A goal in the number of steps/day to accomplish in and after school. In nutrition, the protocol includes three individual meetings for children/parents and six lessons for children. ResultsPositive associations were found between the BMI Z-score, WC, and WHtR with TG; the BMI Z-score and WHtR with glucose; the light PA time and HDL-C; the vigorous and moderate-to-vigorous PA with CRF; the caloric intake and lipids with LDL-C, BMI z-score, WC, and WHtR. A negative association was found between CRF and TG. ConclusionBaseline results stress the importance of multidisciplinary school-based interventions. We hypothesized that PANK will improve blood variables, anthropometric measures, and BP, by changing food intake, enhancing PA and CRF, and decreasing SB.

Application of gradient-corrected density functional theory to the structures and thermochemistries of ScF3, TiF4, VF5, and CrF6

International Nuclear Information System (INIS)

Russo, T.V.; Martin, R.L.; Jeffrey Hay, P.

1995-01-01

Density functional theory (DFT) and Hartree--Fock (HF) calculations are reported for the family of transition metal fluorides ScF 3 , TiF 4 , VF 5 , and CrF 6 . Both HF and the local-density approximation (LDA) yield excellent agreement with experimental bond lengths, while the B-LYP gradient-corrected density functional gives bond lengths 0.04-0.05 A too long. An investigation of various combinations of exchange and correlation functionals shows that, for this series, the origin of this behavior lies in the Becke exchange functional. Much improved bond distances are found using the hybrid HF/DFT functional advocated by Becke. This approximation also leads to much improved thermochemistries. The LDA overestimates average bond energies in this series by 30-40 kcal/mol, whereas the B-LYP functional overbinds by only ∼8-12 kcal/mol, and the hybrid HF/DFT method overbinds by only ∼2 kcal/mol. The hybrid method predicts the octahedral isomer of CrF 6 to be more stable than the trigonal prismatic form by 14 kcal/mol. Comparison of theoretical vibrational frequencies with experiment supports the assignment of an octahedral geometry

Evolutionary History of HIV-1 Subtype B and CRF01_AE Transmission Clusters among Men Who Have Sex with Men (MSM) in Kuala Lumpur, Malaysia

Science.gov (United States)

Ng, Kim Tien; Ong, Lai Yee; Lim, Sin How; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

2013-01-01

HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253–3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2–7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion. PMID:23840653

Chronic stress and comfort foods: self-medication and abdominal obesity

NARCIS (Netherlands)

Dallman, Mary F.; Pecoraro, Norman C.; la Fleur, Susanne E.

2005-01-01

Central corticotropin-releasing factor (CRF) networks are recruited by chronic stressors and elevated glucocorticoids (GCs) that initiate recruitment of central CRF activity in the amygdala. Increased central activity of the CRF network stimulates all monoaminergic cell groups, as well as premotor

Sex and Exercise Interact to Alter the Expression of Anabolic Androgenic Steroid-Induced Anxiety-Like Behaviors in the Mouse

Science.gov (United States)

Onakomaiya, Marie M.; Porter, Donna M.; Oberlander, Joseph G.; Henderson, Leslie P.

2014-01-01

Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711

Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats.

Science.gov (United States)

Miwa, Yoshiji; Nagase, Keiko; Oyama, Nobuyuki; Akino, Hironobu; Yokoyama, Osamu

2011-03-01

Corticotropin-releasing factor (CRF) coordinates various responses of the body to stress, and CRF receptors are important targets of treatment for stress-related disorders. To investigate the effect of a nonselective CRF receptor antagonist, astressin, on suppression of masculine sexual behavior by psychological stress in rats. First, we investigated the influence of psychological stress, induced 2 hours per day for three consecutive days, on sexual behavior. Then, rats were divided into 4 groups: a control group, an astressin administration group (A), a psychological stress loading group (PS), and a psychological stress loading and astressin administration group (PS + A). The rats were exposed to sham or psychological stress for three consecutive days. After the last stress loading, the rats were injected with vehicle or astressin, and their sexual behavior was observed. We also measured serum levels of adrenocorticotropic hormone (ACTH). The effects of astressin on sexual behavior and serum levels of ACTH in rats affected by psychological stress were determined. Sexual behavior was reduced after psychological stress loading. The PS rats had significantly longer mount, intromission, and ejaculation latencies and lower ejaculation frequency than did the control, A, and PS + A rats. The intromission latency and ejaculation frequency in the PS + A rats did not achieve the level observed in the controls. There was no significant difference in these parameters between the control and A rats. Serum ACTH levels were significantly lower in PS + A rats than in PS rats. Psychologically suppressed masculine sexual behavior could be partially recovered with astressin administration in rats. These data provide a rationale for the further study of CRF receptor antagonists as novel agents for treating psychological sexual disorders. © 2010 International Society for Sexual Medicine.

Clinical Perspectives of Urocortin and Related Agents for the Treatment of Cardiovascular Disease

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Keiichi Ikeda

2012-01-01

Full Text Available The effects of corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF, on the cardiovascular system have been intensively researched since its discovery. Moreover, the actions of urocortin (Ucn I on the cardiovascular system have also been intensively scrutinized following the cloning and identification of its receptor, CRF receptor type 2 (CRFR2, in peripheral tissues including the heart. Given the cardioprotective actions of CRFR2 ligands, the clinical potential of not only Ucn I but also Ucn II and III, which were later identified as more specific ligands for CRFR2, has received considerable attention from researchers. In addition, recent work has indicated that CRF type 1 receptor may be also involved in cardioprotection against ischemic/reperfusion injury. Here we provide a historical overview of research on Ucn I and related agents, their effects on the cardiovascular system, and the clinical potential of the use of such agents to treat cardiovascular diseases.

Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer.

Science.gov (United States)

James, P; Rivier, C; Lee, S

2008-02-01

Our laboratory has shown that male testosterone levels are not solely controlled by the release of hypothalamic gonadotrophin-releasing hormone and pituitary luteinising hormone, but are also regulated by a multisynaptic pathway connecting the brain and the testis that interferes with the testosterone response to gonadotrophins. This pathway, which is independent of the pituitary gland, is activated by an i.c.v. injection of either the stress-related peptide corticotrophin-releasing factor (CRF) or of beta-adrenoceptor agonists, both of which alter androgen release and decrease levels of the peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein within Leydig cells. Our original studies used the retrograde transganglionic tracer pseudorabies virus (PRV) to map progression of the virus from the testes to upper brain levels. The present study aimed to extend this work by identifying the regions where CRF and catecholamine neurones represented components of the stress-activated, brain-testicular pathway that prevents testosterone increases. To this end, anaesthetised adult male rats received an intra-testicular injection of PRV. Using immunofluorescence, we identified co-labelling of PRV and either CRF or tyrosine hydroxylase (TH), the enzyme responsible for biogenic amine synthesis. Co-labelling of PRV and CRF was found in the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus (PVN) and the central amygdala. Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kölliker-Fuse area, area of A5, locus coeruleus, nucleus of solitary tract, area of C3, area of C2 and the area of C1/A1. These results indicate that most cell groups of the ventral noradrenergic pathway have neurones that are a part of the brain-testicular pathway. This suggests that the stress hormones CRF and catecholamines may act as neurotransmitters that signal the pathway to inhibit increases in plasma testosterone levels.

Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation.

Science.gov (United States)

Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; Fornari, Raquel V; Roozendaal, Benno

2015-05-01

Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.

Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

DEFF Research Database (Denmark)

Jørgensen, Christinna V; Klein, Anders B; El-Sayed, Mona

2013-01-01

Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We...... are particularly interested in the regulation of the 5-hydroxytryptamine receptor 2A (5-HT2A R). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin-releasing factor receptor 1 (CRF-R1). The effect of BDNF on gene...... expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT2A R mRNA was seen...

A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

International Nuclear Information System (INIS)

Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

2008-01-01

The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 μg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 μg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration

Multi-Range Conditional Random Field for Classifying Railway Electrification System Objects Using Mobile Laser Scanning Data

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Jaewook Jung

2016-12-01

Full Text Available Railways have been used as one of the most crucial means of transportation in public mobility and economic development. For safe railway operation, the electrification system in the railway infrastructure, which supplies electric power to trains, is an essential facility for stable train operation. Due to its important role, the electrification system needs to be rigorously and regularly inspected and managed. This paper presents a supervised learning method to classify Mobile Laser Scanning (MLS data into ten target classes representing overhead wires, movable brackets and poles, which are key objects in the electrification system. In general, the layout of the railway electrification system shows strong spatial regularity relations among object classes. The proposed classifier is developed based on Conditional Random Field (CRF, which characterizes not only labeling homogeneity at short range, but also the layout compatibility between different object classes at long range in the probabilistic graphical model. This multi-range CRF model consists of a unary term and three pairwise contextual terms. In order to gain computational efficiency, MLS point clouds are converted into a set of line segments to which the labeling process is applied. Support Vector Machine (SVM is used as a local classifier considering only node features for producing the unary potentials of the CRF model. As the short-range pairwise contextual term, the Potts model is applied to enforce a local smoothness in the short-range graph; while long-range pairwise potentials are designed to enhance the spatial regularities of both horizontal and vertical layouts among railway objects. We formulate two long-range pairwise potentials as the log posterior probability obtained by the naive Bayes classifier. The directional layout compatibilities are characterized in probability look-up tables, which represent the co-occurrence rate of spatial relations in the horizontal and vertical

The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

DEFF Research Database (Denmark)

Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

2017-01-01

.034) and HOMA-IR (Std. β = 0.19, P = 0.004), and negatively associated with CRF (Std. β = -0.15, P = 0.026). In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030) and negatively associated with waist circumference (WC) (Std. β = -0.16, P = 0.012). Conclusion: Serum BDNF was positively...... associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal research is warranted to determine the temporal relationship between BDNF and cardiovascular...

Risk factor assessment and counselling for 12 months reduces metabolic and cardiovascular risk in overweight or obese patients with schizophrenia spectrum disorders: The CRESSOB study.

Science.gov (United States)

Gutiérrez-Rojas, Luis; Pulido, Susana; Azanza, Jose R; Bernardo, Miguel; Rojo, Luis; Mesa, Francisco J; Martínez-Ortega, Jose M

2016-01-01

Metabolic syndrome (MS) and cardiovascular risk factors (CRF) have been associated with patients with schizophrenia. The main objective is to assess the evolution of CRF and prevalence of MS for 12 months in a cohort of overweight patients diagnosed with schizophrenia schizophreniform disorder or schizoaffective disorder in which the recommendations for the assessment and control of metabolic and cardiovascular risk were applied. The Control of Metabolic and Cardiovascular Risk in Patients with Schizophrenia and Overweight (CRESSOB) study is a 12-month, observational, prospective, open-label, multicentre, naturalistic study including 109 community mental health clinics of Spain. The study included a total of 403 patients, of whom we could collect all variables related to CRF and MS in 366 patients. Of these 366 patients, 286 completed the follow-up, (baseline, months 3, 6 and 12) where they underwent a complete physical examination and a blood test (glucose, cholesterol and triglycerides), they were asked about their health-related habits (smoking, diet and exercise) and they were given a series of recommendations to prevent cardiovascular risk and MS. A total of 403 patients were included, 63% men, mean age (mean; (SD)) 40.5 (10.5) years. After 12 months, the study showed statistically significant decrease in weight (prisk of heart disease at 10 years (p=0.0353). Overweight patients with schizophrenia who receive appropriate medical care, including CRF monitoring and control of health-related habits experience improvements with regard to most CRFs.

The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents: The CHAMPS-study DK.

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Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo; Gejl, Anne Kær; Huang, Tao; Peijs, Lone; Bugge, Anna

2017-01-01

Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain-derived neurotrophic factor (BDNF) probably due to diverse methodological approaches when analysing peripheral BDNF levels. Moreover, only a few studies have been performed in youth populations. Consequently, the main objective of this study was to examine the association between serum BDNF and a composite z-score consisting of six cardiovascular risk factors. A secondary aim was to examine the associations between serum BDNF and each of the six risk factors. Four hundred and forty-seven apparently healthy adolescents between 11-17 years of age participated in this cross-sectional study. Cardiorespiratory fitness (CRF), anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were modelled using linear regression analysis. Serum BDNF was positively associated with the composite z-score in the total study sample (standardized beta coefficient (std.β) = 0.10, P = 0.037). In males, serum BDNF was positively associated with the composite z-score (Std. β = 0.14, P = 0.034) and HOMA-IR (Std. β = 0.19, P = 0.004), and negatively associated with CRF (Std. β = -0.15, P = 0.026). In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030) and negatively associated with waist circumference (WC) (Std. β = -0.16, P = 0.012). Serum BDNF was positively associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal research

The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents: The CHAMPS-study DK.

Directory of Open Access Journals (Sweden)

Natascha Holbæk Pedersen

Full Text Available Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain-derived neurotrophic factor (BDNF probably due to diverse methodological approaches when analysing peripheral BDNF levels. Moreover, only a few studies have been performed in youth populations. Consequently, the main objective of this study was to examine the association between serum BDNF and a composite z-score consisting of six cardiovascular risk factors. A secondary aim was to examine the associations between serum BDNF and each of the six risk factors.Four hundred and forty-seven apparently healthy adolescents between 11-17 years of age participated in this cross-sectional study. Cardiorespiratory fitness (CRF, anthropometrics, pubertal status, blood pressure (BP, serum BDNF, high-density lipoprotein cholesterol (HDL-C, triglyceride (TG, blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were modelled using linear regression analysis.Serum BDNF was positively associated with the composite z-score in the total study sample (standardized beta coefficient (std.β = 0.10, P = 0.037. In males, serum BDNF was positively associated with the composite z-score (Std. β = 0.14, P = 0.034 and HOMA-IR (Std. β = 0.19, P = 0.004, and negatively associated with CRF (Std. β = -0.15, P = 0.026. In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030 and negatively associated with waist circumference (WC (Std. β = -0.16, P = 0.012.Serum BDNF was positively associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal

Clinical data miner: an electronic case report form system with integrated data preprocessing and machine-learning libraries supporting clinical diagnostic model research.

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Installé, Arnaud Jf; Van den Bosch, Thierry; De Moor, Bart; Timmerman, Dirk

2014-10-20

Using machine-learning techniques, clinical diagnostic model research extracts diagnostic models from patient data. Traditionally, patient data are often collected using electronic Case Report Form (eCRF) systems, while mathematical software is used for analyzing these data using machine-learning techniques. Due to the lack of integration between eCRF systems and mathematical software, extracting diagnostic models is a complex, error-prone process. Moreover, due to the complexity of this process, it is usually only performed once, after a predetermined number of data points have been collected, without insight into the predictive performance of the resulting models. The objective of the study of Clinical Data Miner (CDM) software framework is to offer an eCRF system with integrated data preprocessing and machine-learning libraries, improving efficiency of the clinical diagnostic model research workflow, and to enable optimization of patient inclusion numbers through study performance monitoring. The CDM software framework was developed using a test-driven development (TDD) approach, to ensure high software quality. Architecturally, CDM's design is split over a number of modules, to ensure future extendability. The TDD approach has enabled us to deliver high software quality. CDM's eCRF Web interface is in active use by the studies of the International Endometrial Tumor Analysis consortium, with over 4000 enrolled patients, and more studies planned. Additionally, a derived user interface has been used in six separate interrater agreement studies. CDM's integrated data preprocessing and machine-learning libraries simplify some otherwise manual and error-prone steps in the clinical diagnostic model research workflow. Furthermore, CDM's libraries provide study coordinators with a method to monitor a study's predictive performance as patient inclusions increase. To our knowledge, CDM is the only eCRF system integrating data preprocessing and machine-learning libraries

Homocystein and carotid atherosclerosis in chronic renal failure.

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Lubomirova, M; Tzoncheva, A; Petrova, J; Kiperova, B

2007-10-01

Since total homocysteine (Hcy) is markedly elevated in patients with chronic renal failure (CRF), it has been presented as potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. The aim of the study was to examine the significance of elevated Hcy and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. Fifty six patients 16-M, 40-F, average age 58+/-14.55, creatinine clearance 39.19+/-10.11 ml/min were examined. In addition, 20 control healthy subjects were examined. The association of Hcy levels and classic risk factors for atherosclerosis with common carotid intima-media thickness (IMT) was examined. B-mode ultrasound measurement of carotid IMT was performed in 56 hypertensive pts with CRF (glomerular filtration rate>20 ml/min and 0.05). Significant predictors for IMT were age (r=0.358, p<0.04), duration of hypertension (r=0.395, p=0.023), diabetes duration (r=0.343, p<0.02), as well as duration of CRF (r=0.324, p<0.006). There was a negative correlation between IMT and glomerular filtration rate assessed by creatinine clearance (r=-0.303, p<0.003). Renal function, described by creatinine clearance was the strongest determinant for Hcy levels (r=-0.332, p<0.008). Increased IMT was estimated in pts with CRF compared to healthy controls (0.74+/-0.10 vs 0.59+/-0.10, p<0.001). We found association between Hcy and carotid IMT ( r=0.344, p<0.015). No consistent association was found between IMT and other specific for CRF cardiovascular risk factors. The study suggests that patients with mild renal failure have increased IMT of the common carotid artery and that elevated plasma Hcy level in CRF is associated with carotid intima- media thickening.

Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

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Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

2012-01-01

Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

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Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

2010-01-01

Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour. PMID:19653930

Central mechanisms underlying variability in the behavioral and neuroendocrine responses to stress in fish

DEFF Research Database (Denmark)

Moltesen, Maria Møller

of the stress response. In mammals, the hippocampus and amygdala in the telencephalon play central roles in the process of discriminating sensory inputs that, potentially, will threaten the homeostasis of an individual. These regions are part of the limbic system, which interacts with the hypothalamic......-pituitary-adrenal axis (HPA axis). This neuroendocrine stress axis includes corticotropin-releasing factor (CRF), which regulates the release of adrenocorticotropic hormone (ACTH) from the pituitary. A peptide is released to the circulation, inducing release of glucocorticoids from the adrenal cortex....... The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) also plays an important role in the neuroendocrine stress response by controlling CRF release in hypothalamus. The transmission of 5-HT and CRF are under feedback control of glucocorticoids and interact with the stress response by affecting processes...

Neurological Disorders in a Murine Model of Chronic Renal Failure

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Jean-Marc Chillon

2014-01-01

Full Text Available Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF. However, data on the impact of CRF on the cerebral circulatory system are scarce—despite the fact that stroke is the third most common cause of cardiovascular death in people with CRF. In the present study, we examined the impact of CRF on behavior (anxiety, recognition and ischemic stroke severity in a well-defined murine model of CRF. We did not observe any significant increases between CRF mice and non-CRF mice in terms of anxiety. In contrast, CRF mice showed lower levels of anxiety in some tests. Recognition was not impaired (vs. controls after 6 weeks of CRF but was impaired after 10 weeks of CRF. Chronic renal failure enhances the severity of ischemic stroke, as evaluated by the infarct volume size in CRF mice after 34 weeks of CRF. Furthermore, neurological test results in non-CRF mice tended to improve in the days following ischemic stroke, whereas the results in CRF mice tended to worsen. In conclusion, we showed that a murine model of CRF is suitable for evaluating uremic toxicity and the associated neurological disorders. Our data confirm the role of uremic toxicity in the genesis of neurological abnormalities (other than anxiety.

Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism.

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Han, Xiao; DeBold, Joseph F; Miczek, Klaus A

2017-09-01

A history of brief intermittent social defeat stress can escalate cocaine self-administration and induce long-term adaptations in the mesolimbic dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has been shown to be closely associated with stress-induced escalation of drug use. How repeated stress modulates CRF release in the ventral tegmental area (VTA) and the roles of CRF receptors during different phases of stress-induced cocaine self-administration remain to be defined. The current study examines the roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self-administration after exposure to social defeat stress in mice. First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior to each social defeat episode prevented later escalated cocaine self-administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days after the last episode of social stress, the escalation of cocaine intake was dose-dependently reversed. Moreover, socially defeated mice showed increased CRF release in the VTA compared to controls. To further explore the role of CRFR1, CP 376,395 (0.5 and 1 μg/0.2 μl) was infused directly into the VTA before the cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient to reverse social defeat stress-escalated cocaine self-administration. These findings suggest that CRF and CRFR1 exert multiple roles in the response to social stress that are relevant to escalated cocaine self-administration.

Impact of Chronic Renal Failure on Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: Subgroup Analysis from Zilver PTX Post-Market Surveillance Study in Japan.

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Ogawa, Yukihisa; Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Saunders, Alan T; Dake, Michael D

2017-11-01

Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported. This study compares the results with the DES in patients with CRF and those without CRF. This retrospective analysis from the Zilver PTX Japan Post-Market Surveillance Study included 321 patients with CRF and 584 patients without CRF. Outcomes included freedom from target lesion revascularization (TLR) and patency. Of the patients included in this subgroup analysis, 2-year data were available for 209 patients in the CRF group and 453 patients in the non-CRF group. The two groups were similar in terms of lesion length and the frequency of in-stent restenosis. Critical limb ischemia, severe calcification, and diabetes were more common in patients with CRF, whereas total occlusion was more common in patients without CRF. Freedom from TLR rates were 81.4 versus 84.9% (p = 0.24), and patency rates were 70.7 versus 70.3% (p = 0.95) in patients with and without CRF at 2 years, respectively. This is the first comparative study of the DES in femoropopliteal artery lesions in patients with and without CRF. These results indicate that the DES placed in femoropopliteal artery lesions of CRF patients is safe and effective with similar patency and TLR rates to patients without CRF. Level 3, Post-Market Surveillance Study.

Consistent realization of Celestial and Terrestrial Reference Frames

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Kwak, Younghee; Bloßfeld, Mathis; Schmid, Ralf; Angermann, Detlef; Gerstl, Michael; Seitz, Manuela

2018-03-01

The Celestial Reference System (CRS) is currently realized only by Very Long Baseline Interferometry (VLBI) because it is the space geodetic technique that enables observations in that frame. In contrast, the Terrestrial Reference System (TRS) is realized by means of the combination of four space geodetic techniques: Global Navigation Satellite System (GNSS), VLBI, Satellite Laser Ranging (SLR), and Doppler Orbitography and Radiopositioning Integrated by Satellite. The Earth orientation parameters (EOP) are the link between the two types of systems, CRS and TRS. The EOP series of the International Earth Rotation and Reference Systems Service were combined of specifically selected series from various analysis centers. Other EOP series were generated by a simultaneous estimation together with the TRF while the CRF was fixed. Those computation approaches entail inherent inconsistencies between TRF, EOP, and CRF, also because the input data sets are different. A combined normal equation (NEQ) system, which consists of all the parameters, i.e., TRF, EOP, and CRF, would overcome such an inconsistency. In this paper, we simultaneously estimate TRF, EOP, and CRF from an inter-technique combined NEQ using the latest GNSS, VLBI, and SLR data (2005-2015). The results show that the selection of local ties is most critical to the TRF. The combination of pole coordinates is beneficial for the CRF, whereas the combination of Δ UT1 results in clear rotations of the estimated CRF. However, the standard deviations of the EOP and the CRF improve by the inter-technique combination which indicates the benefits of a common estimation of all parameters. It became evident that the common determination of TRF, EOP, and CRF systematically influences future ICRF computations at the level of several μas. Moreover, the CRF is influenced by up to 50 μas if the station coordinates and EOP are dominated by the satellite techniques.

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances.

NARCIS (Netherlands)

Wang, S.S.; Kamphuis, W.; Huitinga, I.; Zhou, J.N.; Swaab, D.F.

2008-01-01

Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors

Enhanced metabolic effect of erythropoietin and keto acids in CRF patients on low-protein diet: Czech multicenter study.

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Teplan, Vladimír; Schück, Otto; Knotek, Antonín; Hajný, Jan; Horácková, Miroslava; Kvapil, Milan

2003-03-01

Our study is designed to establish whether supplementation with erythropoietin (EPO) exerts additional beneficial metabolic effects in patients with chronic renal failure (CRF) treated with keto acids (KAs) on a low-protein diet (LPD). A long-term, prospective, randomized study was designed to use three therapeutic protocols: (A) EPO plus KAs plus LPD (group I), (B) EPO plus LPD (group II), and (C) LPD (group III). One hundred eighty-six randomly selected patients (90 men, 96 women; age, 22 to 78 years) with a creatinine clearance of 22 to 36 mL/min were monitored at the beginning and at every 6 months for 3 years. During the study period, glomerular filtration rate measured as inulin clearance decreased slightly (from 26.2 +/- 3.4 to 23.4 +/- 4.1 mL/min in group I), 27.4 +/- 4.8 to 20.2 +/- 4.4 mL/min in group II, and 26.8 +/- 3.6 to 17.4 +/- 4.1 mL/min in group III; P < 0.01). Serum urea levels also declined (P < 0.01), more pronouncedly in group I (P < 0.025). In group I, there was a significant increase in levels of leucine (P < 0.01) and albumin (P < 0.01) and a decrease in proteinuria (P < 0.01). Analysis of the lipid spectrum showed a mild, yet significant, decrease in total cholesterol and low-density lipoprotein cholesterol levels (P < 0.025), more pronounced in group I. In group I, there was a decrease in plasma triglyceride levels (from 362.85 +/- 115.05 mg/dL [4.1 +/- 1.3 mmol/L] to values as low as 203.55 +/- 70.80 mg/dL [2.3 +/- 0.8 mmol/L]; P < 0.01), whereas high-density lipoprotein cholesterol levels increased (from 34.75 +/- 7.72 mg/dL [0.9 +/- 0.2 mmol/L] to 46.33 +/- 7.72 mg/dL [1.2 +/- 0.2 mmol/L]; P < 0.025). Mean arterial blood pressure was stable. EPO supplementation in patients with CRF administered KAs potentiates the beneficial effects on metabolism of proteins, amino acids, and lipids. Long-term coadministration of EPO, KA, and LPD was associated with a delay in progression of renal failure and reduction in proteinuria.

Weight- perception in male career firefighters and its association with cardiovascular risk factors

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Baur Dorothee M

2012-06-01

Full Text Available Abstract Background The prevalence of obesity has reached epidemic proportions worldwide, and is also increasing among public safety professionals like firefighters who are expected to be fit and more active. The present study evaluates the associations among Body Mass Index (BMI, weight perception and cardiovascular risk factors in 768 male career firefighters from two Midwestern states in the United States. Methods A physical examination was performed and fasting blood samples were taken. Cardio-respiratory fitness (CRF was determined from symptom- limited maximal treadmill exercise testing with electrocardiogram (ECG monitoring and estimation of oxygen consumption (metabolic equivalents, METS using the Bruce protocol. A health and lifestyle questionnaire was administered with standardized written instructions for completion. Self-reports of weight perception were extracted from responses to the completed multiple choice questionnaire. Baseline characteristics were described using the mean (standard deviation for continuous variables and frequency for categorical variables. Group comparisons were calculated using analysis of variance (ANOVA. Linear models and logistic regression models were used to adjust for possible confounders. Logistic regression analyses were used to calculate the odds ratios of underestimating one’s weight category. Results A high proportion of overweight and obese male career firefighters underestimate their weight categories (68%. The risk of underestimating one’s weight category increased by 24% with each additional unit of increasing BMI after adjustment for age and CRF. When divided into six groups based on combinations of measured BMI category and weight perception, there were significant differences among the groups for most cardiovascular risk factors. After adjustment for age and BMI, these differences remained statistically significant for CRF, amount of weekly exercise, prevalence of Metabolic Syndrome

RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

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Zh.P. Sharnova

2006-01-01

Full Text Available To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

Cancer-related fatigue in breast cancer patients after surgery: a multicomponent model using partial least squares-path modeling.

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Bortolon, Catherine; Krikorian, Alicia; Carayol, Marion; Brouillet, Denis; Romieu, Gilles; Ninot, Gregory

2014-04-01

The aim of this study is to examine factors contributing to cancer-related fatigue (CRF) in breast cancer patients who have undergone surgery. Sixty women (mean age: 50.0) completed self-rated questionnaires assessing components of CRF, muscular and cognitive functions. Also, physiological and subjective data were gathered. Data were analyzed using partial least squares variance-based structural equation modeling in order to examine factors contributing to CRF after breast surgery. The tested model was robust in terms of its measurement quality (reliability and validity). According to the structural model results, emotional distress (β = 0.59; p accounting for 61% of the explained variance. Also, emotional distress (β = 0.41; p accounted for 41% of the explained variance. However, the relationship between low physical function and CRF was weak and nonsignificant (β = 0.01; p > 0.05). Emotional distress, altered vigilance capacity, and pain are associated with CRF in postsurgical breast cancer. In addition, emotional distress and pain are related to diminished physical function, which, in turn, has no significant impact on CRF. The current model should be examined in subsequent phases of the treatment (chemotherapy and/or radiotherapy) when side effects are more pronounced and may lead to increased intensity of CRF and low physical function. Copyright © 2013 John Wiley & Sons, Ltd.

Water deprivation increases Fos expression in hypothalamic corticotropin-releasing factor neurons induced by right atrial distension in awake rats.

Science.gov (United States)

Benedetti, Mauricio; Rorato, Rodrigo; Castro, Margaret; Machado, Benedito H; Antunes-Rodrigues, Jose; Elias, Lucila L K

2008-11-01

Atrial mechanoreceptors, sensitive to stretch, contribute in regulating heart rate and intravascular volume. The information from those receptors reaches the nucleus tractus solitarius and then the paraventricular nucleus (PVN), known to have a crucial role in the regulation of cardiovascular function. Neurons in the PVN synthesize CRF, AVP, and oxytocin (OT). Stimulation of atrial mechanoreceptors was performed in awake rats implanted with a balloon at the junction of the superior vena cava and right atrium. Plasma ACTH, AVP, and OT concentrations and Fos, CRF, AVP, and OT immunolabeling in the PVN were determined after balloon inflation in hydrated and water-deprived rats. The distension of the balloon increased the plasma ACTH concentrations, which were higher in water-deprived than in hydrated rats (P neurons in the parvocellular PVN, which was higher in the water-deprived than in the hydrated group (P neurons after distension in hydrated and water-deprived groups, compared with respective controls. In conclusion, parvocellular CRF neurons showed an increase of Fos expression induced by stimulation of right atrial mechanoreceptors, suggesting that CRF participates in the cardiovascular reflex adjustments elicited by volume loading. Activation of CRF neurons in the PVN by cardiovascular reflex is affected by osmotic stimulation.

Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?

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Bakshi, Vaishali P; Alsene, Karen M; Roseboom, Patrick H; Connors, Elenora E

2012-02-01

A deficit in prepulse inhibition (PPI) can be one of the clinically observed features of post-traumatic stress disorder (PTSD) that is seen long after the acute traumatic episode has terminated. Thus, reduced PPI may represent an enduring psychophysiological marker of this illness in some patients. PPI is an operational measure of sensorimotor gating and refers to the phenomenon in which a weak stimulus presented immediately before an intense startling stimulus inhibits the magnitude of the subsequent startle response. The effects of stress on PPI have been relatively understudied, and in particular, there is very little information on PPI effects of ethologically relevant psychological stressors. We aimed to develop a paradigm for evaluating stress-induced sensorimotor gating abnormalities by comparing the effects of a purely psychological stressor (predator exposure) to those of a nociceptive physical stressor (footshock) on PPI and baseline startle responses in rats over an extended period of time following stressor presentation. Male Sprague-Dawley rats were exposed (within a protective cage) to ferrets for 5 min or left in their homecage and then tested for PPI immediately, 24 h, 48 h, and 9 days after the exposure. The effects of footshock were evaluated in a separate set of rats. The effects seen with stressor presentation were compared to those elicited by corticotropin-releasing factor (CRF; 0.5 and 3 μg/6 μl, intracerebroventricularly). Finally, the effects of these stressors and CRF administration on plasma corticosterone were measured. PPI was disrupted 24 h after ferret exposure; in contrast, footshock failed to affect PPI at any time. CRF mimicked the predator stress profile, with the lowdose producing a PPI deficit 24 h after infusion. Interestingly, the high dose also produced a PPI deficit 24 h after infusion, but with this dose, the PPI deficit was evident even 9d later. Plasma corticosterone levels were elevated acutely (before PPI deficits

Glycans Flanking the Hypervariable Connecting Peptide between the A and B Strands of the V1/V2 Domain of HIV-1 gp120 Confer Resistance to Antibodies That Neutralize CRF01_AE Viruses

Science.gov (United States)

O’Rourke, Sara M.; Sutthent, Ruengpung; Phung, Pham; Mesa, Kathryn A.; Frigon, Normand L.; To, Briana; Horthongkham, Navin; Limoli, Kay; Wrin, Terri; Berman, Phillip W.

2015-01-01

Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01_AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partially successful RV144 HIV vaccine trial, where the two CRF01_AE immunogens (derived from the A244 and TH023 isolates) both possessed glycosylation sites at N136 and N149. PMID:25793890

Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation

NARCIS (Netherlands)

Atsak, P.; Hauer, D.; Campolongo, P.; Schelling, G.; Fornari, R.V.; Roozendaal, B.

2015-01-01

Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory

The Risk Factors of High Blood Pressure among Young Adults in the Tujia-Nationality Settlement of China

Directory of Open Access Journals (Sweden)

Xiaoli Liu

2017-01-01

Full Text Available Demographics questionnaires, and fitness tests were utilized to identify the risk factors of hypertension among younger adults in the years 2005, 2010, and 2014 in China’s southwest province of Hubei. The results demonstrated that the prevalence of hypertension was higher between 2011 and 2014 among the young people in this area. The main risk factors of developing hypertension were found to be sex (as man, individuals over 40 years old, blue collar employees who worked in rural areas, overweight/obesity, and those with the low CRF.

Enhanced motivation for food reward induced by stress and attenuation by corticotrophin-releasing factor receptor antagonism in rats: implications for overeating and obesity.

Science.gov (United States)

Liu, Xiu

2015-06-01

Overeating beyond individuals' homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. The present study examined whether a pharmacological stressor, yohimbine, enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor (CRF) receptor blockade by a CRF1-selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity.

Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review.

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Al-Mamgani, Abrahim; van Werkhoven, Erik; Navran, Arash; Karakullukcu, Baris; Hamming-Vrieze, Olga; Machiels, Melanie; van der Velden, Lilly-Ann; Vogel, Wouter V; Klop, W Martin

2017-09-01

The head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted. PubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated. Eleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0-5.9%, 95% CI 1.6-3.5%). The incidence of cRF correlated only with T-stage (p=0.008), and involvement of midline (p=0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p=0.344). The incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

Science.gov (United States)

Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

2017-04-01

At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

Risk group characteristics and viral transmission clusters in South-East Asian patients infected with HIV-1 circulating recombinant form (CRF)01_AE and subtype B

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Oyomopito, Rebecca A; Chen, Yen-Ju; Sungkanuparph, Somnuek; Kantor, Rami; Merati, Tuti; Yam, Wing-Cheong; Sirisanthana, Thira; Li, Patrick CK; Kantipong, Pacharee; Phanuphak, Praphan; Lee, Chris KC; Kamarulzaman, Adeeba; Ditangco, Rossana; Huang, Szu-Wei; Sohn, Annette H; Law, Matthew; Chen, Yi Ming A

2016-01-01

HIV-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF)01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multi-centre prospective cohort of HIV-infected patients. Associations between HIV-exposure, patient gender, country of sample origin and HIV-1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of males within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p Malaysia: 47.8%, Philippines: 25.0%; p <0.001). After adjustment, we found increased subtype B infection among men-who-have-sex with-men, relative to heterosexual-reported exposures (OR = 2.4, p <0.001). We further describe four transmission clusters of 8–15 treatment naive, predominantly symptomatic patients (two each for subtype B and CRF01_AE). Risk-group sub-populations differed with respect to the infecting HIV-1 genotype. Homosexual exposure patients had a higher odds of being infected with subtype B. Where HIV-1 genotypes circulate within countries or patient risk-groups, local monitoring of genotype-specific transmissions may play a role in focussing public health prevention strategies. Phylogenetic evaluations provide complementary information for surveillance and monitoring of viruses with high mutation rates such as HIV-1 and Ebola. PMID:26362956

Association between Neighborhood Walkability, Cardiorespiratory Fitness and Body-Mass Index

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Hoehner, Christine M.; Handy, Susan L.; Yan, Yan; Blair, teven N.; Berrigan, David

2011-01-01

Many studies have found cross-sectional associations between characteristics of the neighborhood built environment and physical activity (PA) behavior. However, most are based on self-reported PA, which is known to result in overestimation of PA and differential misclassification by demographic and biological characteristics. Cardiorespiratory fitness (CRF) is an objective marker of PA because it is primarily determined by PA. Furthermore, it is causally related to long-term health outcomes. Therefore, analyses of the association between CRF and built environment could strengthen arguments for the importance of built environment influences on health. We examined the association between neighborhood walkability and CRF and body-mass index (BMI). This cross-sectional analysis included 16,543 adults (5,017 women, 11,526 men) aged 18–90 years with home addresses in Texas who had a comprehensive clinical examination between 1987 and 2005. Outcomes included CRF from total duration on a maximal exercise treadmill test and measured BMI. Three neighborhood walkability factors emerged from principal components analyses of block-group measures derived from the U.S. Census. In multilevel adjusted analyses, the neighborhood walkability factors were significantly associated with CRF and BMI among men and women in the expected direction. An interaction between one of the neighborhood factors and age was also observed. The interaction suggested that living in neighborhoods with older homes and with residents traveling shorter distances to work was more strongly positively associated with CRF among younger adults and more strongly negatively associated with BMI among older adults. In conclusion, neighborhood characteristics hypothesized to support more PA and less driving were associated with higher levels of CRF and lower BMI. Demonstration of an association between built environment characteristics and CRF is a significant advance over past studies based on self-reported PA

CRFR1 is expressed on pancreatic beta cells, promotes beta cell proliferation, and potentiates insulin secretion in a glucose-dependent manner

DEFF Research Database (Denmark)

Huising, Mark O; van der Meulen, Talitha; Vaughan, Joan M

2009-01-01

Corticotropin-releasing factor (CRF), originally characterized as the principal neuroregulator of the hypothalamus-pituitary-adrenal axis, has broad central and peripheral distribution and actions. We demonstrate the presence of CRF receptor type 1 (CRFR1) on primary beta cells and show that acti...

Cardiorespiratory fitness and physical activity in children with cancer

NARCIS (Netherlands)

Braam, Katja I.; van Dijk-Lokkart, Elisabeth M.; Kaspers, Gertjan J. L.; Takken, Tim; Huisman, Jaap; Bierings, Marc B.; Merks, Johannes H. M.; van de Heuvel-Eibrink, Marry M.; van Dulmen-den Broeder, Eline; Veening, Margreet A.

2016-01-01

This study assessed cardiorespiratory fitness (CRF), physical activity (PA), and sedentary behavior (SB), as well as factors associated with these outcomes in children during or shortly after cancer treatment. Cross-sectionally, CRF data, obtained by the cardiopulmonary exercise test, and PA and SB

Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.

Science.gov (United States)

Myers, Jonathan; McAuley, Paul; Lavie, Carl J; Despres, Jean-Pierre; Arena, Ross; Kokkinos, Peter

2015-01-01

The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity. Published by Elsevier Inc.

Physical activity enhances metabolic fitness independently of cardiorespiratory fitness in marathon runners

DEFF Research Database (Denmark)

Laye, M J; Nielsen, M B; Hansen, L S

2015-01-01

High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consisten......High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run...... consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max......). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior...

Favorable Cardiovascular Risk Profile Is Associated With Lower Healthcare Costs and Resource Utilization: The 2012 Medical Expenditure Panel Survey.

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Valero-Elizondo, Javier; Salami, Joseph A; Ogunmoroti, Oluseye; Osondu, Chukwuemeka U; Aneni, Ehimen C; Malik, Rehan; Spatz, Erica S; Rana, Jamal S; Virani, Salim S; Blankstein, Ron; Blaha, Michael J; Veledar, Emir; Nasir, Khurram

2016-03-01

The American Heart Association's 2020 Strategic Goals emphasize the value of optimizing risk factor status to reduce the burden of morbidity and mortality. In this study, we aimed to quantify the overall and marginal impact of favorable cardiovascular risk factor (CRF) profile on healthcare expenditure and resource utilization in the United States among those with and without cardiovascular disease (CVD). The study population was derived from the 2012 Medical Expenditure Panel Survey (MEPS). Direct and indirect costs were calculated for all-cause healthcare resource utilization. Variables of interest included CVD diagnoses (coronary artery disease, stroke, peripheral artery disease, dysrhythmias, or heart failure), ascertained by International Classification of Diseases, Ninth Edition, Clinical Modification codes, and CRF profile (hypertension, diabetes mellitus, hypercholesterolemia, smoking, physical activity, and obesity). Two-part econometric models were used to study expenditure data. The final study sample consisted of 15 651 MEPS participants (58.5±12 years, 54% female). Overall, 5921 (37.8%) had optimal, 7002 (44.7%) had average, and 2728 (17.4%) had poor CRF profile, translating to 54.2, 64.1, and 24.9 million adults in United States, respectively. Significantly lower health expenditures were noted with favorable CRF profile across CVD status. Among study participants with established CVD, overall healthcare expenditures with optimal and average CRF profile were $5946 and $3731 less compared with those with poor CRF profile. The respective differences were $4031 and $2560 in those without CVD. Favorable CRF profile is associated with significantly lower medical expenditure and healthcare utilization among individuals with and without established CVD. © 2016 American Heart Association, Inc.

[Effects of controlled release blend bulk urea on soil nitrogen and soil enzyme activity in wheat and rice fields].

Science.gov (United States)

Zhang, Jing Sheng; Wang, Chang Quan; Li, Bing; Liang, Jing Yue; He, Jie; Xiang, Hao; Yin, Bin; Luo, Jing

2017-06-18

A field experiment was conducted to investigate the effect of controlled-release fertilizer (CRF) combined with urea (UR) on the soil fertility and environment in wheat-rice rotation system. Changes in four forms of nitrogen (total nitrogen, ammonium nitrogen, nitrate nitrogen, and microbial biomass nitrogen) and in activities of three soil enzymes participating in nitrogen transformation (urease, protease, and nitrate reductase) were measured in seven fertilization treatments (no fertilization, routine fertilization, 10%CRF+90%UR, 20%CRF+80%UR, 40%CRF+60%UR, 80%CRF+20%UR, and 100%CRF). The results showed that soil total nitrogen was stable in the whole growth period of wheat and rice. There was no significant difference among the treatments of over 20% CRF in soil total nitrogen content of wheat and rice. The soil inorganic nitrogen content was increased dramatically in treatments of 40% or above CRF during the mid-late growing stages of wheat and rice. With the advance of the growth period, conventional fertilization significantly decreased soil microbial biomass nitrogen, but the treatments of 40% and above CRF increased the soil microbial biomass nitrogen significantly. The soil enzyme activities were increased with over 40% of CRF in the mid-late growing stage of wheat and rice. By increasing the CRF ratio, the soil protease activity and nitrate reductase activity were improved gradually, and peaked in 100% CRF. The treatments of above 20% CRF could decrease the urease activity in tillering stage of rice and delay the peak of ammonium nitrogen, which would benefit nitrogen loss reduction. The treatments of 40% and above CRF were beneficial to improving soil nitrogen supply and enhancing soil urease and protease activities, which could promote the effectiveness of nitrogen during the later growth stages of wheat and rice. The 100% CRF treatment improved the nitrate reductase activity significantly during the later stage of wheat and rice. Compared with the

Normative reference values for the 20 m shuttle‐run test in a population‐based sample of school‐aged youth in Bogota, Colombia: the FUPRECOL study

Science.gov (United States)

Palacios‐López, Adalberto; Humberto Prieto‐Benavides, Daniel; Enrique Correa‐Bautista, Jorge; Izquierdo, Mikel; Alonso‐Martínez, Alicia; Lobelo, Felipe

2016-01-01

Abstract Objectives Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio‐metabolic risk. Methods A total of 7244 children and adolescents attending public schools in Bogota, Colombia (55.7% girls; age range of 9–17.9 years) participated in this study. We expressed CRF performance as the nearest stage (minute) completed and the estimated peak oxygen consumption (V˙O2peak). Smoothed percentile curves were calculated. In addition, we present the prevalence of low CRF after applying a correction factor to account for the impact of Bogota's altitude (2625 m over sea level) on CRF assessment, and we calculated the number of participants who fell below health‐related FITNESSGRAM cut‐points for low CRF. Results Shuttles and V˙O2peak were higher in boys than in girls in all age groups. In boys, there were higher levels of performance with increasing age, with most gains between the ages of 13 and 17. The proportion of subjects with a low CRF, suggestive of future cardio‐metabolic risk (health risk FITNESSGRAM category) was 31.5% (28.2% for boys and 34.1% for girls; X2 P = .001). After applying a 1.11 altitude correction factor, the overall prevalence of low CRF was 11.5% (9.6% for boys and 13.1% for girls; X2 P = .001). Conclusions Our results provide sex‐ and age‐specific normative reference standards for the 20 m shuttle‐run test and estimated V˙O2peak values in a large, population‐based sample of schoolchildren from a large Latin‐American city at high altitude. PMID:27500986

Evaluation of nasal mucociliary activity in patients with chronic renal failure.

Science.gov (United States)

Kucur, Cuneyt; Ozbay, Isa; Gulcan, Erim; Kulekci, Semra; Aksoy, Sinan; Oghan, Fatih

2016-05-01

The ability of respiratory mucosal surfaces to eliminate foreign particles and pathogens and to keep mucosal surfaces moist and fresh depends on mucociliary activity. Chronic renal failure (CRF) is an irreversible medical condition that may result in important extrarenal systemic consequences, such as cardiovascular, metabolic, and respiratory system abnormalities. Although there are studies describing nasal manifestations of CRF, data are lacking concerning the effects of the condition on nasal mucosa. The goal of the current study was to evaluate nasal mucociliary clearance (NMC) time in patients with CRF. This prospective cohort study conducted in a tertiary referral center included 32 non-diabetic end-stage CRF patients and 30 control individuals. The control group consisted of voluntary participants who had been referred to our clinic for symptoms other than rhinological diseases. The mean NMC times in CRF patients and control individuals were 12.51 ± 3.74 min (range 7-22 min) and 8.97 ± 1.83 min (range 6-13 min), respectively. The mean NMC time in patients with CRF was significantly longer than that in control individuals (p < 0.001). Clinicians must keep in mind that NMC time in CRF patients is prolonged and must follow-up these patients more closely for sinonasal and middle ear infections.

Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

Science.gov (United States)

Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

2012-01-01

Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated

Human factors information system

International Nuclear Information System (INIS)

Goodman, P.C.; DiPalo, C.A.

1991-01-01

Nuclear power plant safety is dependent upon human performance related to plant operations. To provide improvements in human performance, data collection and assessment play key roles. This paper reports on the Human factors Information System (HFIS) which is designed to meet the needs of the human factors specialists of the United States Nuclear Regulatory Commission. These specialists identify personnel errors and provide guidance designed to prevent such errors. HFIS is a simple and modular system designed for use on a personal computer. It is designed to contain four separate modules that provide information indicative of program or function effectiveness as well as safety-related human performance based on programmatic and performance data. These modules include the Human Factors Status module; the Regulatory Programs module; the Licensee Event Report module; and the Operator Requalification Performance module. Information form these modules can either be used separately or can be combined due to the integrated nature of the system. HFIS has the capability, therefore, to provide insights into those areas of human factors that can reduce the probability of events caused by personnel error at nuclear power plants and promote the health and safety of the public. This information system concept can be applied to other industries as well as the nuclear industry

Climate mitigation comparison of woody biomass systems with the inclusion of land-use in the reference fossil system

International Nuclear Information System (INIS)

Haus, S.; Gustavsson, L.; Sathre, R.

2014-01-01

While issues of land-use have been considered in many direct analyses of biomass systems, little attention has heretofore been paid to land-use in reference fossil systems. Here we address this limitation by comparing forest biomass systems to reference fossil systems with explicit consideration of land-use in both systems. We estimate and compare the time profiles of greenhouse gas (GHG) emission and cumulative radiative forcing (CRF) of woody biomass systems and reference fossil systems. A life cycle perspective is used that includes all significant elements of both systems, including GHG emissions along the full material and energy chains. We consider the growth dynamics of forests under different management regimes, as well as energy and material substitution effects of harvested biomass. We determine the annual net emissions of CO 2 , N 2 O and CH 4 for each system over a 240-year period, and then calculate time profiles of CRF as a proxy measurement of climate change impact. The results show greatest potential for climate change mitigation when intensive forest management is applied in the woody biomass system. This methodological framework provides a tool to help determine optimal strategies for managing forests so as to minimize climate change impacts. The inclusion of land-use in the reference system improves the accuracy of quantitative projections of climate benefits of biomass-based systems. - Highlights: • We analyze the dynamics of GHG emissions from woody biomass and fossil systems. • With a life cycle perspective, we account for forest land-use in both systems. • Replacing more carbon intensive fossil fuels gives greater climate benefit. • Increasing the intensity of forest management gives greater climate benefit. • Methodological choices in defining temporal system boundaries are important

Best waveform score for diagnosing keratoconus

Directory of Open Access Journals (Sweden)

Allan Luz

2013-12-01

Full Text Available PURPOSE: To test whether corneal hysteresis (CH and corneal resistance factor (CRF can discriminate between keratoconus and normal eyes and to evaluate whether the averages of two consecutive measurements perform differently from the one with the best waveform score (WS for diagnosing keratoconus. METHODS: ORA measurements for one eye per individual were selected randomly from 53 normal patients and from 27 patients with keratoconus. Two groups were considered the average (CH-Avg, CRF-Avg and best waveform score (CH-WS, CRF-WS groups. The Mann-Whitney U-test was used to evaluate whether the variables had similar distributions in the Normal and Keratoconus groups. Receiver operating characteristics (ROC curves were calculated for each parameter to assess the efficacy for diagnosing keratoconus and the same obtained for each variable were compared pairwise using the Hanley-McNeil test. RESULTS: The CH-Avg, CRF-Avg, CH-WS and CRF-WS differed significantly between the normal and keratoconus groups (p<0.001. The areas under the ROC curve (AUROC for CH-Avg, CRF-Avg, CH-WS, and CRF-WS were 0.824, 0.873, 0.891, and 0.931, respectively. CH-WS and CRF-WS had significantly better AUROCs than CH-Avg and CRF-Avg, respectively (p=0.001 and 0.002. CONCLUSION: The analysis of the biomechanical properties of the cornea through the ORA method has proved to be an important aid in the diagnosis of keratoconus, regardless of the method used. The best waveform score (WS measurements were superior to the average of consecutive ORA measurements for diagnosing keratoconus.

Dopamine and Stress System Modulation of Sex Differences in Decision Making.

Science.gov (United States)

Georgiou, Polymnia; Zanos, Panos; Bhat, Shambhu; Tracy, J Kathleen; Merchenthaler, Istvan J; McCarthy, Margaret M; Gould, Todd D

2018-01-01

Maladaptive decision making is associated with several neuropsychiatric disorders, including problem gambling and suicidal behavior. The prevalence of these disorders is higher in men vs women, suggesting gender-dependent regulation of their pathophysiology underpinnings. We assessed sex differences in decision making using the rat version of the Iowa gambling task. Female rats identified the most optimal choice from session 1, whereas male rats from session 5. Male, but not female rats, progressively improved their advantageous option responding and surpassed females. Estrus cycle phase did not affect decision making. To test whether pharmacological manipulations targeting the dopaminergic and stress systems affect decision making in a sex-dependent manner, male and female rats received injections of a dopamine D 2 receptor (D 2 R) antagonist (eticlopride), D 2 R agonist (quinpirole), corticotropin-releasing factor 1 (CRF 1 ) antagonist (antalarmin), and α 2 -adrenergic receptor antagonist (yohimbine; used as a pharmacological stressor). Alterations in mRNA levels of D 2 R and CRF 1 were also assessed. Eticlopride decreased advantageous responding in male, but not female rats, whereas quinpirole decreased advantageous responding specifically in females. Yohimbine dose-dependently decreased advantageous responding in female rats, whereas decreased advantageous responding was only observed at higher doses in males. Antalarmin increased optimal choice responding only in female rats. Higher Drd2 and Crhr1 expression in the amygdala were observed in female vs male rats. Higher amygdalar Crhr1 expression was negatively correlated with advantageous responding specifically in females. This study demonstrates the relevance of dopaminergic- and stress-dependent sex differences to maladaptive decision making.

Association between Cardiorespiratory Fitness and Health-Related Quality of Life among Patients at Risk for Cardiovascular Disease in Uruguay

Science.gov (United States)

Payne, Jonathan P. W.; Rienzi, Edgardo G.; Lavie, Carl J.; Blair, Steven N.; Pate, Russell R.

2015-01-01

To date, few studies have examined the relationship between cardiorespiratory fitness (CRF) and health-related quality of life (HRQoL) in populations at high risk for developing cardiovascular disease (CVD). Purpose To examine the association between objectively measured CRF and physical and mental components of HRQoL in a Uruguayan cohort at risk for developing CVD. Methods Patient data records from 2002–2012 at the Calidad de Vida Center were examined. To assess CRF, participants performed a submaximal exercise test. During the evaluation, participants also completed the SF-36, a HRQoL measure comprised of eight dimensions that are summarized by physical and mental component scores (PCS and MCS, respectively). ANCOVA was used to examine the relationship between HRQoL dimensions and CRF. Logistic regression was then used to compare the odds of having a HRQoL component score above the norm across CRF. All analyses were performed separately for males and females with additional stratified analyses across age and BMI conducted among significant trends. Results A total of 2,302 subjects were included in the analysis. Among females, a significant relationship was observed between CRF and vitality, physical functioning, physical role, bodily pain, and general health dimensions. However, for males the only dimension found to be significantly associated with CRF was physical health. After adjusting for potential confounders, a significant linear trend (p<0.001) for PCS scores above the norm across CRF levels was observed for females only. Conclusion Among females with one or more risk factors for developing CVD, higher levels of CRF were positively associated with the vitality and physical dimensions of HRQoL, as well as the overall PCS. However, among males the only dimension associated with CRF was physical functioning. Future studies should examine this relationship among populations at risk for developing CVD in more detail and over time. PMID:25901358

[Chronic renal failure in sickle cell disease: A retrospective analysis of 100 adults sickle cell patients from black Africa].

Science.gov (United States)

Ackoundou-N'Guessan, Clément; Guei, Cyr Monley; Lagou, Delphine Amélie; Gbekedi, Serges; Tia, Mélanie Weu; Coulibaly, Pessa Albert; Nzoue, Sita; Konan, Serges; Koffi, Gustave; Gnionsahe, Daze Apollinaire

2016-06-01

The prevalence of chronic renal failure (CRF) in sickle cell disease (SCD) patients could vary from one country to another depending on the modalities of management. The aim of the present study was to appreciate the epidemiology of CRF in SCD patients from black Africa in order to search for promoting factors. One hundred SCD adult patients have been considered for the study. The glomerular filtration rate (GFR) has been estimated according to the CKD-EPI formula. Three groups of patients have been identified according to the value of their GFR. The mean age of the patients was 30.84±8.26 years. Male gender has represented 51% of the study population. The mean GFR value was 175.4±86.2 mL/min/1.73 m(2). The prevalence of CRF was 11%. About 3% of them had severe CRF. Subjects with normal GFR were 20%. Subjects with glomerular hyperfiltration (HF) were 69%. By univariate analysis, when subjects with HF were compared with those presenting normal GFR, the following factors have appeared to be significantly associated: female gender (female 60.9% versus male 39.1%; P60 kg; 59.9±9.41 kg; P30 years; OR=0.12 [CI95% 0.03-04]; P60 kg; OR=0.19 [CI95% 0.05-0.72]; P<0.01) were associated with HF. By univariate analysis, when subjects with CRF were compared with those presenting normal GFR, a lower hemoglobin value was significantly associated with CRF (7.92±2.7 g/dL versus 10.43±2.5 g/dL; P<0.009). There was a trend for subjects not being under maintenance therapy to more experience CRF (36.4% versus 70%; P<0.07). By logistic regression analysis, only a low hemoglobin value was associated to CRF (higher hemoglobin level; OR=0.55 [0.20-6.3]; P<0.01). In total, CRF and HF are frequent complications in SCD adult patients from black Africa. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

Science.gov (United States)

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Etravirine and rilpivirine resistance in HIV-1 subtype CRF01_AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens.

Science.gov (United States)

Bunupuradah, Torsak; Ananworanich, Jintanat; Chetchotisakd, Ploenchan; Kantipong, Pacharee; Jirajariyavej, Supunnee; Sirivichayakul, Sunee; Munsakul, Warangkana; Prasithsirikul, Wisit; Sungkanuparph, Somnuek; Bowonwattanuwong, Chureeratana; Klinbuayaem, Virat; Petoumenos, Kathy; Hirschel, Bernard; Bhakeecheep, Sorakij; Ruxrungtham, Kiat

2011-01-01

We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA>1,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS; ≥ 4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS; 2.5-3.5 and ≥ 4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Median (IQR) age was 38 (34-42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8-4.5) years. Median (IQR) CD4(+) T-cell count and HIV RNA were 194 (121-280) cells/mm³ and 4.1 (3.6-4.6) log₁₀ copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥ 4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5-3.5 and ≥4, respectively. Only HIV RNA ≥ 4 log₁₀ copies/ml at failure was associated with both Monogram WS ≥ 4 (OR 2.3, 95% CI 1.3-3.9; P=0.003) and DUET WS ≥ 2.5 (OR 1.9, 95% CI 1.1-3.3; P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.

Ozone Therapy on Rats Submitted to Subtotal Nephrectomy: Role of Antioxidant System

Directory of Open Access Journals (Sweden)

José Luis Calunga

2005-01-01

Full Text Available Chronic renal failure (CRF represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy. Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks. Renal plasmatic flow (RPF, glomerular filtration rate (GFR, the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD and catalase (CAT showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone

Analysis of the risk of disease associated with arsenic exposure in water supply systems for human consumption

International Nuclear Information System (INIS)

Villegas Gonzalez, Nicole

2014-01-01

The risk of disease associated with arsenic exposure is analyzed in water supply systems for human consumption, as well as the control of pollution and effects on health, in the community known as Barrio Hotel of Canas in comparison with the community of San Miguel in Canas, Guanacaste, Costa Rica. A spatial analysis, temporal and classification are realized by an ecological design of the country in the following zones of exposure: without exposure, low (≥3 μg/L and ≤10 μg/L) and medium to high (≥11 μg/L and ≤187 μg/L). The transversal design is tackled through the perceived morbidity. Spatial analysis has found in the districts of Bebedero, Los Chiles, Bagaces and Canas with Standardized Morbidity Index (EMI) by age in the the greatest national range of chronic renal failure (CRF). The protection of skin cancer risk is observed in the communities of Bagaces, Canas, El Amparo and La Cruz. A temporal trend of increase in IME of CRF and skin cancer is identified in Los Chiles. The classification by zone of exposure, the unexposed areas have been protected of kidney cancer, lung and bronchus, bladder and skin. The of low exposure have presented excess risk of CRF and have been protected of skin cancer. The of medium to high are protected of bladder cancer and have maintained the trend of excess in CRF and protection of skin cancer. The transversal design has found in the exposed community the risk to suffer kidneys diseases. Arsenic exposure has increased in men the risk of renal failure and anemia, in women the decrease of vision, and age groups under of 10 years and of 40-69 years of hypopigmentation and keratoses respectively. Multivariate analysis has showed a weak association of arsenic exposure time with the risk of hypertension [es

Parathyroid hormone dependent T cell proliferation in uremic rats

DEFF Research Database (Denmark)

Lewin, E; Ladefoged, Jens; Brandi, L

1993-01-01

Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...... and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After...... parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA...

Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF, and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system

Directory of Open Access Journals (Sweden)

Aloe Luigi

2003-04-01

Full Text Available Abstract Previous studies on the effect of repeated electro-acupuncture (EA treatments in rats with steriod-induced polycystic ovaries (PCO, EA has been shown to modulate nerve growth factor (NGF concentration in the ovaries as well as corticotropin releasing factor (CRF in the median eminence (ME. In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1, a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p p p p

The association between cardiorespiratory fitness and risk of all-cause mortality among women with impaired fasting glucose or undiagnosed diabetes mellitus.

Science.gov (United States)

Lyerly, G William; Sui, Xuemei; Lavie, Carl J; Church, Timothy S; Hand, Gregory A; Blair, Steven N

2009-09-01

To evaluate the independent and joint associations among cardiorespiratory fitness (CRF), body mass index, and risk of mortality from any cause among women with impaired fasting glucose (IFG) or undiagnosed diabetes mellitus (DM). Female patients (N=3044; mean age, 47.4 years) with IFG or undiagnosed DM completed a maximal exercise treadmill test (between January 26, 1971, and March 21, 2001). The women had no history of a cardiovascular disease event or diagnosed DM at baseline. Cardiorespiratory fitness was defined categorically as low (bottom 20%), moderate (middle 40%), or high (upper 40%) according to previously published Aerobics Center Longitudinal Study guidelines. Body mass index was calculated as the weight in kilograms divided by the height in meters squared (kg/m(2)). During a 16-year follow-up period, 171 deaths occurred. There was an inverse association between CRF and all-cause mortality risk. Women with moderate or high CRF were at lower risk of mortality (moderate CRF, 35% lower; high CRF, 36% lower; P(trend)=.03) than those with low CRF. An exercise capacity lower than 7 metabolic equivalents was associated with a 1.5-fold higher risk of death than an exercise capacity of 9 metabolic equivalents or higher (P(trend)=.05). The multivariate adjusted hazard ratios (HRs), including adjustments for CRF, were higher for heavier patients than for patients of normal weight (overweight patients: HR, 0.86; 95% confidence interval, 0.57-1.30; obese patients: HR, 1.19; 95% confidence interval, 0.70-2.03; P(trend)=.84). Combined analyses showed that women who were overweight or obese and unfit (low CRF) were at more than twice the risk of death than women who were of normal weight and fit (moderate or high CRF). Cardiorespiratory fitness, not body mass index, is a significant predictor of all-cause mortality among women with IFG or undiagnosed DM. Assessing CRF levels provides important prognostic information independent of traditional risk factors.

Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women.

Science.gov (United States)

Lee, D-C; Sui, X; Ortega, F B; Kim, Y-S; Church, T S; Winett, R A; Ekelund, U; Katzmarzyk, P T; Blair, S N

2011-05-01

To examine the combined associations and relative contributions of leisure-time physical activity (PA) and cardiorespiratory fitness (CRF) with all-cause mortality. Prospective cohort study. Setting Aerobics centre longitudinal study. 31,818 men and 10 555 women who received a medical examination during 1978-2002. Assessment of risk factors Leisure-time PA assessed by self-reported questionnaire; CRF assessed by maximal treadmill test. Main outcome measures All-cause mortality until 31 December 2003. There were 1492 (469 per 10,000) and 230 (218 per 10,000) deaths in men and women, respectively. PA and CRF were positively correlated in men (r = 0.49) and women (r = 0.47) controlling for age (p men, but the association was eliminated after further adjustment for CRF. No significant association of PA with mortality was observed in women. CRF was inversely associated with mortality in men and women, and the associations remained significant after further adjustment for PA. In the PA and CRF combined analysis, compared with the reference group "not meeting the recommended PA (men and women "not meeting the recommended PA and fit", 0.96 (0.61 to 1.53) and 0.93 (0.33 to 2.58) in men and women "meeting the recommended PA and unfit" and 0.60 (0.51 to 0.70) and 0.56 (0.37 to 0.85) in men and women "meeting the recommended PA and fit", respectively. CRF was more strongly associated with all-cause mortality than PA; therefore, improving CRF should be encouraged in unfit individuals to reduce risk of mortality and considered in the development of future PA guidelines.

Optimization of a multi-gene HIV-1 recombinant subtype CRF02AG DNA vaccine for expression of multiple immunogenic forms

International Nuclear Information System (INIS)

Ellenberger, Dennis; Li Bin; Smith, James; Yi Hong; Folks, Thomas; Robinson, Harriet; Butera, Salvatore

2004-01-01

We developed an AIDS vaccine for Western and West-Central Africa based on a DNA plasmid vector expressing HIV-1 recombinant subtype CRF02 A G gag, pol, and env genes. To optimize the production of noninfectious HIV-like particles (VLPs) and potentially improve the effectiveness of the vaccine, we generated four potential vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and IC90) containing mutations within the HIV protease. While the parental construct IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the production of immature VLPs (the core comprises unprocessed Pr 55Gag ). The remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises processed capsid p24) in addition to immature VLPs and aggregates of Gag proteins. VLPs incorporated significant levels of mature gp120 envelope glycoprotein. Importantly, the mature VLPs were fusion competent and entered coreceptor-specific target cells. The production of multiple antigenic forms, including fusion-competent VLPs, by candidate DNA vaccine constructs may provide immunologic advantages for induction of protective cellular and humoral responses against HIV-1 proteins

Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: The Henry Ford ExercIse Testing Project.

Science.gov (United States)

Hung, Rupert K; Al-Mallah, Mouaz H; Qadi, Mohamud A; Shaya, Gabriel E; Blumenthal, Roger S; Nasir, Khurram; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

2015-08-01

We sought to evaluate the effect of cardiorespiratory fitness (CRF) in predicting mortality, myocardial infarction (MI), and revascularization in patients with hyperlipidemia after stratification by gender and statin therapy. This retrospective cohort study included 33,204 patients with hyperlipidemia (57 ± 12 years old, 56% men, 25% black) who underwent physician-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were stratified by gender, baseline statin therapy, and estimated metabolic equivalents from stress testing. We computed hazard ratios using Cox regression models after adjusting for demographics, cardiac risk factors, comorbidities, pertinent medications, interaction terms, and indication for stress testing. There were 4,851 deaths, 1,962 MIs, and 2,686 revascularizations over a median follow-up of 10.3 years. In men and women not on statin therapy and men and women on statin therapy, each 1-metabolic equivalent increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88), 0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86-0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for revascularization, respectively. No significant interactions were observed between CRF and statin therapy (P > .23). Higher CRF attenuated risk for mortality, MI, and revascularization independent of gender and statin therapy in patients with hyperlipidemia. These results reinforce the prognostic value of CRF and support greater promotion of CRF in this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study

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Sanhueza, Jorge A.; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A.

2016-01-01

Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders. Key points Genetic factors influencing sports performance in the Chilean population are unknown. Differential outcomes from athletes who completed a triathlon competition were associated with five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11). We show that genetic variants within stress- and anxiety-related genes affect athletic performance. PMID:27928199

Calculations of spin Hamiltonian parameters and analysis of trigonal distortions in LiSr(Al,Ga)F6:Cr3+ crystals

International Nuclear Information System (INIS)

Brik, M.G.; Avram, C.N.; Avram, N.M.

2006-01-01

The effective spin-Hamiltonian (SH) parameters (zero-field splitting D and g factors g - parallel and g - perpendicular ) for Cr 3+ ions in LiSr(Al,Ga)F 6 crystals are calculated from the complete high-order perturbation formulae for a d 3 ion. Parameters of trigonal crystal field acting on the Cr 3+ ion are calculated. The magnitude of trigonal distortion of the [CrF 6 ] 3- clusters is related to the experimental measurements of the spin-Hamiltonian parameters in the considered systems. Since in both crystals g parallel perpendicular , [CrF 6 ] 3- clusters undergo an axial compression along the C 3 axis. Experimental values of the hyperfine structure constants A parallel and A perpendicular are used to evaluate the core polarization constant κ for Cr 3+ ion in both crystals

Time-dependent climate benefits of using forest residues to substitute fossil fuels

International Nuclear Information System (INIS)

Sathre, Roger; Gustavsson, Leif

2011-01-01

In this study we analyze and compare the climate impacts from the recovery, transport and combustion of forest residues (harvest slash and stumps), versus the climate impacts that would have occurred if the residues were left in the forest and fossil fuels used instead. We use cumulative radiative forcing (CRF) as an indicator of climate impacts, and we explicitly consider the temporal dynamics of atmospheric carbon dioxide and biomass decomposition. Over a 240-year period, we find that CRF is significantly reduced when forest residues are used instead of fossil fuels. The type of fossil fuel replaced is important, with coal replacement giving the greatest CRF reduction. Replacing oil and fossil gas also gives long-term CRF reduction, although CRF is positive during the first 10-25 years when these fuels are replaced. Biomass productivity is also important, with more productive forests giving greater CRF reduction per hectare. The decay rate for biomass left in the forest is found to be less significant. Fossil energy inputs for biomass recovery and transport have very little impact on CRF. -- Highlights: → Cumulative radiative forcing (CRF) can measure climate impacts of dynamic systems. → Climate impact is reduced when forest slash and stumps are used to replace fossil fuels. → Forest biofuels may cause short-term climate impact, followed by long-term climate benefit. → Forest residues should replace coal to avoid short-term climate impact. → Fossil energy used for biofuel recovery and transport has very little climate impact.

Factors Affecting Successful Implementation of Hospital Information Systems.

Science.gov (United States)

Farzandipur, Mehrdad; Jeddi, Fatemeh Rangraz; Azimi, Esmaeil

2016-02-01

Today, the use of information systems in health environments, like any other fields, is necessary and organizational managers are convinced to use these systems. However, managers' satisfaction is not the only factor in successfully implementing these systems and failed information technology projects (IT) are reported despite the consent of the directors. Therefore, this study aims to determine the factors affecting the successful implementation of a hospital information system. The study was carried out as a descriptive method in 20 clinical hospitals that the hospital information system (HIS) was conducted in them. The clinical and paraclinical users of mentioned hospitals are the study group. 400 people were chosen as samples in scientific method and the data was collected using a questionnaire consisted of three main human, managerial and organizational, and technological factors, by questionnaire and interview. Then the data was scored in Likert scale (score of 1 to 5) and were analyzed using the SPSS software. About 75 percent of the population were female, with average work experience of 10 years and the mean age was 30 years. The human factors affecting the success of hospital information system implementation achieved the mean score of 3.5, both organizational and managerial factors 2.9 and technological factors the mean of 3. Human factors including computer skills, perceiving usefulness and perceiving the ease of a hospital information system use are more effective on the acceptance and successful implementation of hospital information systems; then the technological factors play a greater role. It is recommended that for the successful implementation of hospital information systems, most of these factors to be considered.

Drug-resistant molecular mechanism of CRF01_AE HIV-1 protease due to V82F mutation

Science.gov (United States)

Liu, Xiaoqing; Xiu, Zhilong; Hao, Ce

2009-05-01

Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the major targets of anti-AIDS drug discovery. The circulating recombinant form 01 A/E (CRF01_AE, abbreviated AE) subtype is one of the most common HIV-1 subtypes, which is infecting more humans and is expanding rapidly throughout the world. It is, therefore, necessary to develop inhibitors against subtype AE HIV-1 PR. In this work, we have performed computer simulation of subtype AE HIV-1 PR with the drugs lopinavir (LPV) and nelfinavir (NFV), and examined the mechanism of resistance of the V82F mutation of this protease against LPV both structurally and energetically. The V82F mutation at the active site results in a conformational change of 79's loop region and displacement of LPV from its proper binding site, and these changes lead to rotation of the side-chains of residues D25 and I50'. Consequently, the conformation of the binding cavity is deformed asymmetrically and some interactions between PR and LPV are destroyed. Additionally, by comparing the interactive mechanisms of LPV and NFV with HIV-1 PR we discovered that the presence of a dodecahydroisoquinoline ring at the P1' subsite, a [2-(2,6-dimethylphenoxy)acetyl]amino group at the P2' subsite, and an N2 atom at the P2 subsite could improve the binding affinity of the drug with AE HIV-1 PR. These findings are helpful for promising drug design.

Cardiorespiratory fitness and future risk of pneumonia: a long-term prospective cohort study.

Science.gov (United States)

Kunutsor, Setor K; Laukkanen, Tanjaniina; Laukkanen, Jari A

2017-09-01

We aimed to assess the prospective association of cardiorespiratory fitness (CRF) with the risk of pneumonia. Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed using a respiratory gas exchange analyzer in 2244 middle-aged men in the Kuopio Ischemic Heart Disease cohort. We corrected for within-person variability in CRF levels using data from repeat measurements taken several years apart. During a median follow-up of 25.8 years, 369 men received a hospital diagnosis of pneumonia. The age-adjusted regression dilution ratio of CRF was 0.58 (95% confidence interval: 0.53-0.63). Cardiorespiratory fitness was linearly associated with pneumonia risk. The hazard ratio (95% confidence interval) for pneumonia per 1 standard deviation increase in CRF in analysis adjusted for several risk factors for pneumonia was 0.77 (0.68-0.87). The association remained consistent on additional adjustment for total energy intake, socioeconomic status, physical activity, and C-reactive protein 0.82 (0.72-0.94). The corresponding adjusted hazard ratios (95% confidence intervals) were 0.58 (0.41-0.80) and 0.67 (0.48-0.95) respectively, when comparing the extreme quartiles of CRF levels. Our findings indicate a graded inverse and independent association between CRF and the future risk of pneumonia in a general male population. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

Science.gov (United States)

Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Survivability of systems under multiple factor impact

International Nuclear Information System (INIS)

Korczak, Edward; Levitin, Gregory

2007-01-01

The paper considers vulnerable multi-state series-parallel systems operating under influence of external impacts. Both the external impacts and internal failures affect system survivability, which is determined as the probability of meeting a given demand. The external impacts are characterized by several destructive factors affecting the system or its parts simultaneously. In order to increase the system's survivability a multilevel protection against the destructive factors can be applied to its subsystems. In such systems, the protected subsystems can be destroyed only if all of the levels of their protection are destroyed. The paper presents an algorithm for evaluating the survivability of series-parallel systems with arbitrary configuration of multilevel protection against multiple destructive factor impacts. The algorithm is based on a composition of Boolean and the Universal Generating Function techniques. Illustrative examples are presented

Cancer-related fatigue and physical activity among premenopausal cervical and endometrial cancer survivors in Japan.

Science.gov (United States)

Obama, Kyoko; Maru, Mitsue; Maeda, Rumi; Kubota, Toshiro

2015-09-30

To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had severe fatigue. The participants had higher physical activity levels compared with the findings in previous studies, and reported an average of 40 min/day of moderate to vigorous activity. Moderate to vigorous levels of physical activity were derived from essential social activities rather than leisure time exercise. There were no significant differences in physical activity levels between the lower and higher CRF groups. Our study results suggested that the higher level of physical activity in daily living itself had no relationship with decreasing CRF among premenopausal cervical and endometrial cancer survivors. It would be better to focus on cognitive and psychological factors before introducing physical activity programs and be careful of the characteristics of the participants' physical activity among this population in daily basis.

Is cardiac autonomic function associated with cardiorespiratory fitness and physical activity in children and adolescents? A systematic review of cross-sectional studies.

Science.gov (United States)

Oliveira, Ricardo Santos; Barker, Alan Robert; Wilkinson, Kelly Michelle; Abbott, Rebecca Anne; Williams, Craig Anthony

2017-06-01

Heart rate variability (HRV) is considered to explain improvements in cardiovascular health accrued by physical activity (PA) and cardiorespiratory fitness (CRF) over and above traditional cardiovascular risk factors. To systematically address associations between HRV, PA and CRF in children and adolescents. Medline, EMBASE, SportDISCUS and CINAHL Plus were searched on 5th September 2015 and updated on 4th August 2016. Observational studies comparing HRV in different groups of PA and CRF, and/or studies investigating associations between PA, CRF and HRV. Sports practices and PA intensities were also included. The square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), the spectral density in the high (HF) and low (LF) frequency, and the LF/HF ratio were included. Risk of bias was assessed using the adapted Newcastle-Ottawa Scale (NOS). Heterogeneity exists in the assessment of the exposures and outcomes, and sample characteristics. Risk of bias (NOS) was observed in most of the studies. Studies with low risk of bias showed positive associations between moderate-to-vigorous PA and RMSSD. The evidence for the associations between PA and frequency indices is weak. Similarly, the evidence for the association between CRF and HRV is weak. Despite the heterogeneity in the studies, moderate-to-vigorous PA is positively associated with RMSSD, but less clear are the associations between CRF and HRV, as well as other PA intensities. Further research is needed to clarify the role of PA and CRF on HRV in children and adolescents. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between corneal biomechanical properties and confocal microscopy findings in normal and keratoconic eyes.

Science.gov (United States)

Hurmeric, Volkan; Sahin, Afsun; Ozge, Gokhan; Bayer, Atilla

2010-06-01

To investigate the relationship between corneal biomechanical properties and confocal microscopy (CM) findings in normal and keratoconic eyes. The study consisted of 28 eyes of 28 healthy volunteers and 23 eyes of 15 patients with keratoconus. The diagnosis of keratoconus was made with corneal topography and clinical findings. The corneal hysteresis (CH) and corneal resistance factor (CRF) were measured by the ocular response analyzer. In vivo CM was performed with NIDEK Confoscan 3. CH and CRF were compared with corneal morphological findings (detailed cell counts of endothelial, stromal, and epithelial cells) in vivo. CH was 10.1 +/- 1.3 mm Hg in normal eyes and 7.4 +/- 1.5 mm Hg in keratoconic eyes (P < 0.0001). CRF was 10.1 +/- 1.8 mm Hg in normal eyes and 6.2 +/- 1.4 mm Hg in keratoconic eyes (P < 0.0001). CH and CRF were negatively correlated with full-thickness stromal keratocyte density (P < 0.01; r = -0.52 and P < 0.001; r = -0.67, respectively) in healthy eyes. Keratocyte density of the posterior half of the stroma was found to be significantly related with CRF in healthy eyes (beta = -0.404; P = 0.01). There was no significant relationship among CH, CRF, and CM findings in eyes with keratoconus. There is a significant relationship between CRF and keratocyte density of the posterior half of the stroma in healthy eyes. Our results suggest that corneal elasticity is related to not only stromal matrix but also cellular structure of the cornea.

Relation Between Estimated Cardiorespiratory Fitness and Atrial Fibrillation (from the Reasons for Geographic and Racial Differences in Stroke Study).

Science.gov (United States)

Bose, Abhishek; O'Neal, Wesley T; Bennett, Aleena; Judd, Suzanne E; Qureshi, Waqas T; Sui, Xuemei; Howard, Virginia J; Howard, George; Soliman, Elsayed Z

2017-06-01

Estimated cardiorespiratory fitness (e-CRF) based on readily available clinical and self-reported data is a promising alternative to the costly traditional assessment of CRF using exercise equipment, but its role as a predictor for incident atrial fibrillation (AF) is unclear. This study included 10,126 participants (54.5% women, 35% African-American, mean age 63.2 years) from the Reasons for Geographic and Racial Differences in Stroke study who were free of AF at baseline. Baseline (2003 to 2007) e-CRF was determined using a previously validated nonexercise algorithm. Incident AF cases were identified at a follow-up examination by electrocardiogram and self-reported medical history of previous physician diagnosis. After a median follow-up of 9.4 years, 906 participants (8.9%) developed AF. In a multivariable logistic regression model adjusted for sociodemographics and baseline cardiovascular disease risk factors as well as incident coronary heart disease, heart failure, and stroke, each 1-metabolic equivalent of task increase in e-CRF was associated with a 5% lower risk of AF development (odds ratio [95% CI] 0.95 [0.92 to 0.99]; p = 0.0129). This association was stronger in women (OR [95% CI] 0.85 (0.79, 0.92) than in men (OR (95% CI) 0.88 (0.84, 0.93), interaction p value = 0.05. No significant interactions by age, race, history of cardiovascular disease, or physical limitations were observed. In conclusion, e-CRF using a nonexercise algorithm is a useful predictor of incident AF, which is consistent with previous reports using traditional CRF. This suggests that e-CRF using nonexercise algorithms may serve as a useful alternative to CRF measured by costly and time-consuming exercise testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Physical fitness and performance. Cardiorespiratory fitness in girls-change from middle to high school.

Science.gov (United States)

Pfeiffer, Karin A; Dowda, Marsha; Dishman, Rod K; Sirard, John R; Pate, Russell R

2007-12-01

To determine how factors are related to change in cardiorespiratory fitness (CRF) across time in middle school girls followed through high school. Adolescent girls (N = 274, 59% African American, baseline age = 13.6 +/- 0.6 yr) performed a submaximal fitness test (PWC170) in 8th, 9th, and 12th grades. Height, weight, sports participation, and physical activity were also measured. Moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) were determined by the number of blocks reported on the 3-Day Physical Activity Recall (3DPAR). Individual differences and developmental change in CRF were assessed simultaneously by calculating individual growth curves for each participant, using growth curve modeling. Both weight-relative and absolute CRF increased from 8th to 9th grade and decreased from 9th to 12th grade. On average, girls lost 0.16 kg.m.min.kg.yr in weight-relative PWC170 scores (P interactions between CRF, physical activity, race, BMI, and sports participation.

The effects of CRA 1000, a non-peptide antagonist of corticotropin-releasing factor receptor type 1, on adaptive behaviour in the rat.

Science.gov (United States)

Harro, J; Tõnissaar, M; Eller, M

2001-04-01

Intracerebrally administered CRF has been demonstrated to elicit several behavioural deficits in novel and potentially stressful experimental paradigms, and to promote activity in familiar situations. This study examined the effect of CRA 1000, a novel non-peptide antagonist of CRF(1)receptors, on rat behaviour in tests of anxiolytic and antidepressant activity and novelty-oriented behaviour. CRA 1000 (1.25-10 mg/kg) had no major effect in elevated plus-maze and social interaction tests. However, CRA 1000 (5 mg/kg) significantly reduced immobility in the forced swimming test, suggesting an antidepressant-like effect. In the exploration box test, CRA 1000 (1.25 mg/kg) had an anxiolytic effect on rat exploratory behaviour both in intact rats and after lesioning of the projections of locus coeruleus by DSP-4 (50 mg/kg) treatment. A higher dose of CRA 1000 (5 mg/kg) tended to have anxiolytic-like effects in DSP-4 pretreated rats, but in intact animals this dose prevented the increase in exploration which develops with repeated exposure to initially anxiety-provoking situations. Taken together, these experiments demonstrate that CRF1 receptor blockade by CRA 1000 has antidepressant-like effects, does not have a robust anti-anxiety effect in non-stressed animals, but does have anxiolytic-like effects in more complex tasks, which can be observed also after denervation of the locus coeruleus projections. However, large doses of CRF1 receptor antagonists may reduce motivation of exploratory behaviour in familiar environments. Copyright 2001 Harcourt Publishers Ltd.

Development of Broadly Neutralizing Antibody Mimitopes for Characterization of CRF01_AE HIV-1 Antibody Responses

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Jesse V. Schoen

2017-10-01

Full Text Available Mapping humoral immune responses to HIV-1 over the course of natural infection is important in understanding epitope exposure in relation to elicitation of broadly neutralizing antibodies (bNAbs, which is considered imperative for effective vaccine design. When analyzing HIV-specific immune responses, the antibody binding profiles may be a correlate for functional antibody activity. In this study, we utilized phage display technology to identify novel mimitopes that may represent Env epitope structures bound by bNAbs directed at V1V2 and V3 domains, CD4 binding site (CD4bs and the membrane proximal external region (MPER of Env. Mimitope sequence motifs were determined for each bNAb epitope. Given the ongoing vaccine development efforts in Thailand, these mimitopes that represent CD4bs and MPER epitopes were used to map immune responses of HIV-1 CRF01_AE-infected individuals with known neutralizing responses from two distinct time periods, 1996-98 and 2012-15. The more contemporary cohort showed an increase in binding breadth with binding observed for all MPER and CD4bs mimitopes, while the older cohort showed only 75% recognition of the CD4bs mimitopes and no MPER mimotope binding. Furthermore, mimitope binding profiles correlated significantly with magnitude (p=0.0036 and breadth (p=0.0358 of neutralization of a multi-subtype Tier 1 panel of pseudoviruses. These results highlight the utility of this mimitope mapping approach for detecting human plasma IgG-specificities that target known neutralizing antibody epitopes, and may also provide an indication of the plasticity of antibody binding within HIV-1 Env neutralization determinants.

Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats.

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Nicholas W Gilpin

Full Text Available Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (~postnatal days 28-42 in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF cell in the lateral portion of the central amygdala (CeA, a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity, an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects

Factors influencing the profitability of optimizing control systems

International Nuclear Information System (INIS)

Broussaud, A.; Guyot, O.

1999-01-01

Optimizing control systems supplement conventional Distributed Control Systems and Programmable Logic Controllers. They continuously implement set points, which aim at maximizing the profitability of plant operation. They are becoming an integral part of modern mineral processing plants. This trend is justified by economic considerations, optimizing control being among the most cost-effective methods of improving metallurgical plant performance. The paper successively analyzes three sets of factors, which influence the profitability of optimizing control systems, and provides guidelines for analyzing the potential value of an optimizing control system at a given operation: external factors, such as economic factors and factors related to plant feed; features of the optimizing control system; and subsequent maintenance of the optimizing control system. It is shown that pay back times for optimization control projects are typically measured in days. The OCS software used by the authors for their applications is described briefly. (author)

Cancer-Related Fatigue in Women With Breast Cancer: Outcomes of a 5-Year Prospective Cohort Study.

LENUS (Irish Health Repository)

Goldstein, David

2012-04-16

PURPOSEProlonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear. PATIENTS AND METHODSA prospective cohort study of women receiving adjuvant treatment for early-stage breast cancer was conducted. Women (n = 218) were enrolled after surgery and observed at end treatment and at 1, 3, 6, 9, and 12 months as well as 5 years. Structured interviews and self-report questionnaires were used to record physical and psychologic health as well as disability and health care utilization. Patients with CRF persisting for 6 months were assessed to exclude alternative medical and psychiatric causes of fatigue. Predictors of persistent fatigue, mood disturbance, and health care utilization were sought by logistic regression.ResultsThe case rate for CRF was 24% (n = 51) postsurgery and 31% (n = 69) at end of treatment; it became persistent in 11% (n = 24) at 6 months and 6% (n = 12) at 12 months. At each time point, approximately one third of the patients had comorbid mood disturbance. Persistent CRF was predicted by tumor size but not demographic, psychologic, surgical, or hematologic parameters. CRF was associated with significant disability and health care utilization. CONCLUSIONCRF is common but generally runs a self-limiting course. Much of the previously reported high rates of persistent CRF may be attributable to factors unrelated to the cancer or its treatment.

Environmental Factors, Toxicants and Systemic Lupus Erythematosus

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Anselm Mak

2014-09-01

Full Text Available Systemic lupus erythematosus (SLE is an immune-complex-mediated multi-systemic autoimmune condition of multifactorial etiology, which mainly affects young women. It is currently believed that the onset of SLE and lupus flares are triggered by various environmental factors in genetically susceptible individuals. Various environmental agents and toxicants, such as cigarette smoke, alcohol, occupationally- and non-occupationally-related chemicals, ultraviolet light, infections, sex hormones and certain medications and vaccines, have been implicated to induce SLE onset or flares in a number case series, case-control and population-based cohort studies and very few randomized controlled trials. Here, we will describe some of these recognized environmental lupus triggering and perpetuating factors and explain how these factors potentially bias the immune system towards autoimmunity through their interactions with genetic and epigenetic alterations. Further in-depth exploration of how potentially important environmental factors mechanistically interact with the immune system and the genome, which trigger the onset of SLE and lupus flares, will certainly be one of the plausible steps to prevent the onset and to decelerate the progress of the disease.

Radiographic manifestations of teeth and jaw bones in chronic renal failure patients: A longitudinal study

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Puja Rai

2016-01-01

Full Text Available Introduction: Chronic renal failure (CRF is an important health problem worldwide with a tendency of annual progression. Renal failure could alter the balance of the stomatognathic system, thus conditioning the prevalence of oral diseases at its different stages. Researchers estimate that up to 90% of renal patients show oral manifestations and a wide range of bony anomalies accounting for 92% of the patients. Aims and Objectives: The aim and objective of this study was to evaluate radiographic manifestations in CRF patients and compare the findings between the stages of CRF. Materials and Methods: A longitudinal study on fifty CRF patients was conducted. Patients were divided into three stages depending on the severity of renal failure. Orthopantomograph was taken for all the subjects. Results: The study showed that 88% of the study group had positive radiographic findings. Stage IV renal failure patients had more severe manifestations as compared to Stages II and III. Conclusion: Majority of the patients had positive radiographic findings which can be one of the diagnostic markers in CRF patients.

The changing HIV-1 genetic characteristics and transmitted drug resistance among recently infected population in Yunnan, China.

Science.gov (United States)

Chen, M; Jia, M H; Ma, Y L; Luo, H B; Chen, H C; Yang, C J; Dai, J; Yang, L; Dong, L J; Lu, R; Song, L J; Han, Y; Lu, J Y; Cheung, A K L; Chen, Z W; Lu, L

2018-04-01

Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991-1999 and 1994-1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994-1998 and 2001-2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

Virulence Factors IN Fungi OF Systemic Mycoses

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KUROKAWA Cilmery Suemi

1998-01-01

Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

Involvement of CRFR1 in the Basolateral Amygdala in the Immediate Fear Extinction Deficit.

Science.gov (United States)

Hollis, Fiona; Sevelinges, Yannick; Grosse, Jocelyn; Zanoletti, Olivia; Sandi, Carmen

2016-01-01

Several animal and clinical studies have highlighted the ineffectiveness of fear extinction sessions delivered shortly after trauma exposure. This phenomenon, termed the immediate extinction deficit, refers to situations in which extinction programs applied shortly after fear conditioning may result in the reduction of fear behaviors (in rodents, frequently measured as freezing responses to the conditioned cue) during extinction training, but failure to consolidate this reduction in the long term. The molecular mechanisms driving this immediate extinction resistance remain unclear. Here we present evidence for the involvement of the corticotropin releasing factor (CRF) system in the basolateral amygdala (BLA) in male Wistar rats. Intra-BLA microinfusion of the CRFR 1 antagonist NBI30775 enhances extinction recall, whereas administration of the CRF agonist CRF 6-33 before delayed extinction disrupts recall of extinction. We link the immediate fear extinction deficit with dephosphorylation of GluA1 glutamate receptors at Ser 845 and enhanced activity of the protein phosphatase calcineurin in the BLA. Their reversal after treatment with the CRFR 1 antagonist indicates their dependence on CRFR 1 actions. These findings can have important implications for the improvement of therapeutic approaches to trauma, as well as furthering our understanding of the neurobiological mechanisms underlying fear-related disorders.

Anxiety-like behavior in transgenic mice with brain expression of neuropeptide Y.

Science.gov (United States)

Inui, A; Okita, M; Nakajima, M; Momose, K; Ueno, N; Teranishi, A; Miura, M; Hirosue, Y; Sano, K; Sato, M; Watanabe, M; Sakai, T; Watanabe, T; Ishida, K; Silver, J; Baba, S; Kasuga, M

1998-01-01

Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in behavior and its disorders. To understand the long-term modulation of neuronal functions by NPY, we raised transgenic mice created with a novel central nervous system (CNS) neuron-specific expression vector of human Thy- gene fragment linked to mouse NPY cDNA. In situ hybridization analysis demonstrated transgene-derived NPY expression in neurons (e.g., in the hippocampus, cerebral cortex, and the arcuate nucleus of the hypothalamus) in the transgenic mice. The modest increase of NPY protein in the brain was demonstrated by semiquantitative immunohistochemical analysis and by radioreceptor assay (115% in transgenic mice compared to control littermates). Double-staining experiments indicated colocalization of the transgene-derived NPY message and NPY protein in the same neurons, such as in the arcuate nucleus. The transgenic mice displayed behavioral signs of anxiety and hypertrophy of adrenal zona fasciculata cells, but no change in food intake was observed. The anxiety-like behavior of transgenic mice was reversed, at least in part, by administration of corticotropin-releasing factor (CRF) antagonists, alpha-helical CRF9-41, into the third cerebral ventricle. These results suggest that NPY has a role in anxiety and behavioral responses to stress partly via the CRF neuronal system. This genetic model may provide a unique opportunity to study human anxiety and emotional disorders.

Influence of corneal biomechanical properties on intraocular pressure differences between an air-puff tonometer and the Goldmann applanation tonometer.

Science.gov (United States)

Tranchina, Laura; Lombardo, Marco; Oddone, Francesco; Serrao, Sebastiano; Schiano Lomoriello, Domenico; Ducoli, Pietro

2013-01-01

To estimate the influence of corneal properties on intraocular pressure (IOP) differences between an air-puff tonometer (NT530P; Nidek) and the Goldmann applanation tonometer (Haag-Streit). The influence of central corneal thickness (CCT), keratometry, and Ocular Response Analyzer (Reichert) measurements of corneal viscoelasticity [corneal hysteresis (CH) and corneal resistance factor (CRF)] on IOP differences between tonometers was evaluated. The CRF was calculated to be the best predictor of the differences in IOP readings between tonometers (r2=0.23; Ptonometers. Corneal resistance to applanation induced by either contact or noncontact tonometers was calculated to be the most determinant factor in influencing IOP differences between applanation tonometers.

Comparison of Model Systems (M+n·[CrX63−] and M3CrX6 + 18MX Based on Quantum-Chemical Calculations (X: F, Cl

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Vyacheslav Kremenetsky

2016-01-01

Full Text Available On the basis of quantum-chemical calculations the most stable particle compositions are estimated in such model systems as (M+n·[CrCl6] and M3CrCl6 + 18MCl (M = Na, K, and Cs. In all systems these particles are positively charged. For systems (M+n·[CrCl6], (M+n·[CrF6], M3CrF6 + 18MCl, M3CrF6 + 18MF, and M3CrCl6 + 18MCl (M = Na, K, and Cs a number of energy parameters characterizing the state of the system before and after electron transfer are calculated. The results indicate the possibility of electron transfer from the cathode to the melt system, which is in the initial state. However, this possibility cannot be realized in systems where LUMOs (lowest unoccupied molecular orbitals have purely ligand character. In this case, the preliminary deformation of a cationic shell of electroactive species is required; it transforms the initial system to the transition state. However, in all considered systems the search of the transition state should be carried close to the initial state Pi. This greatly simplifies a problem and transforms it from a purely theoretical sphere to the field of practical tasks that do not require exceptional cost of computer time.

Central neuropeptide Y plays an important role in mediating the adaptation mechanism against chronic stress in male rats.

Science.gov (United States)

Yang, Yu; Babygirija, Reji; Zheng, Jun; Shi, Bei; Sun, Weinan; Zheng, Xiaojiao; Zhang, Fan; Cao, Yu

2018-02-07

Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF), and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days, 1-5, of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, while central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism, and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, over-expressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress. Copyright © 2018 Endocrine Society.

Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations.

Science.gov (United States)

McGregor, D O; Dellow, W J; Lever, M; George, P M; Robson, R A; Chambers, S T

2001-06-01

Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity. Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression. Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy. DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF.

High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

Science.gov (United States)

Kotaki, Tomohiro; Khairunisa, Siti Qamariyah; Sukartiningrum, Septhia Dwi; Arfijanto, M Vitanata; Utsumi, Takako; Normalina, Irine; Handajani, Retno; Widiyanti, Prihartini; Rusli, Musofa; Rahayu, Retno Pudji; Lusida, Maria Inge; Hayashi, Yoshitake; Nasronudin; Kameoka, Masanori

2013-01-01

Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs), we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1) and the prevalence of other blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus C (GBV-C), were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%). In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

Assessing the accuracy of algorithm-derived cardiorespiratory fitness in surgical patients: a prospective cohort study.

Science.gov (United States)

Hammal, Fadi; Quaife, Tanis; Purich, Kieran; Haennel, Robert; Gragasin, Ferrante S; Martin-Feeney, Daniella San; Finegan, Barry A

2017-04-01

To determine if a non-exercise algorithm-derived assessment of cardiorespiratory fitness (CRF A ) accurately predicted estimated values obtained using a six-minute walk test (CRF 6MWD ) and the Duke Activity Status Index (CRF DASI ). Following research ethics board approval, an observational cohort study was conducted in selected, consenting patients undergoing elective surgery. Participants completed questionnaires assessing their self-reported exercise capacity. Their height, weight, waist circumference, and vital signs were measured. A six-minute walk test was performed twice with a 45-min rest interval between tests. The correlation between CRF A and both CRF 6MWD and CRF DASI was determined. Two hundred forty-two participants were included. Mean age was 62 (range 45-88 yr); 150 (62%) were male, 87 (36%) self-reported walking or jogging > 16 km per week, and 49 (20%) were current smokers. The CRF A and CRF 6MWD were highly correlated (Pearson r = 0.878; P 427 m in the six-minute walk test, CRF A , CRF 6MWD , and CRF DASI were equivalent. A non-exercise algorithm can estimate cardiorespiratory fitness in patients presenting for elective surgery. The variables required to compute CRF A can be obtained in a clinic setting without the need to engage in formal exercise testing. Further evaluation of CRF A as a predictor of long-term outcome in patients is warranted.

Factorizations of one-dimensional classical systems

International Nuclear Information System (INIS)

Kuru, Senguel; Negro, Javier

2008-01-01

A class of one-dimensional classical systems is characterized from an algebraic point of view. The Hamiltonians of these systems are factorized in terms of two functions that together with the Hamiltonian itself close a Poisson algebra. These two functions lead directly to two time-dependent integrals of motion from which the phase motions are derived algebraically. The systems so obtained constitute the classical analogues of the well known factorizable one-dimensional quantum mechanical systems

Validation of human factor engineering integrated system

International Nuclear Information System (INIS)

Fang Zhou

2013-01-01

Apart from hundreds of thousands of human-machine interface resources, the control room of a nuclear power plant is a complex system integrated with many factors such as procedures, operators, environment, organization and management. In the design stage, these factors are considered by different organizations separately. However, whether above factors could corporate with each other well in operation and whether they have good human factors engineering (HFE) design to avoid human error, should be answered in validation of the HFE integrated system before delivery of the plant. This paper addresses the research and implementation of the ISV technology based on case study. After introduction of the background, process and methodology of ISV, the results of the test are discussed. At last, lessons learned from this research are summarized. (authors)

Systems competing for mobile factors: decision making based on hard vs. soft locational factors

Directory of Open Access Journals (Sweden)

Clodnițchi Roxana

2017-12-01

Full Text Available The paper explores the links between capital relocation and soft locational factors addressing the quality of the business environment and the quality of life within the European Union. System competition is viewed as a competition between countries for the mobile factors capital and labour. The issue of systems competition is topical and insufficiently explored by contemporary literature. The scarcity of scientific papers describing the links between system competition theories and contemporary corporate geography theories, especially of the ones including the analysis of soft location factors, is a challenging aspect, which motivates the choice of this subject. This paper’s primary aim is to deliver an overview of the basic corporate geography conceptions, stressing the importance of soft location factors in today’s competition between systems for the mobile factors capital and labour. The paper further contains an analysis of the correlations between indicators regarding the institutional design of countries as developed by the World Bank (Ease of Doing Business, the Happiness Scale and the latest available data of FDI Stocks for the EU countries (2016. The relevance of such a study is based on the evidence that the contemporary business education relies on an extensive knowledge of the business environment. In the circumstance of similar infrastructural conditions, the main difference between locations is made by soft location factors. Since developed economies are characterised by a high degree of ubiquity of soft factors, the paper concludes that developing and emerging economies should foster the development of their soft location factors.

Comparison of ocular response analyzer parameters in primary open angle glaucoma and exfoliative glaucoma patients

Directory of Open Access Journals (Sweden)

Emrullah Beyazyildiz

2014-01-01

Full Text Available Aim: We sought to identify differences in the following measures of the ocular response analyser (ORA between primary open angle glaucoma (POAG and exfoliative glaucoma (EXG patients: Corneal hysteresis (CH, corneal resistance factor (CRF, corneal-compensated intraocular pressure (IOPcc and Goldmann-correlated intraocular pressure (IOPg. We also sought to relate these ORA measures with central corneal thickness (CCT. Materials and Methods: This cross-sectional study was conducted on a total of 162 individuals (46 EXG patients, 66 POAG patients and 50 healthy subjects without any ocular and systemic disease. ORA measurements were performed, and a minimum of three readings were obtained from each test subject. Groups were compared according to their ORA parameters. Results: The mean CH levels of the EXG, POAG and healthy subjects were 7.6 ± 2.1, 9.1 ± 1.9 and 9.6 ± 1.7 mmHg, respectively. CH was significantly lower in the EXG patients compared to the other groups (P < 0.001.The mean CRF levels of the EXG, POAG and healthy subjects were 9.0 ± 2.0, 10.1 ± 1.7 and 9.8 ± 1.8mmHg, respectively. CRF levels in the eyes of the EXG patients were significantly lower compared to those of either the POAG patients (P = 0.005 or the healthy subjects (P = 0.03, but there was no significant difference in CRF levels between the POAG patients and the healthy subjects (P = 0.59. There was a significant positive correlation between CH and CCT in the EXG patients and healthy subjects (P < 0.001, but this correlation was not present in the POAG patients (P = 0.70. Conclusions: In this study, CH and CRF were found to be significantly reduced in the eyes of EXG patients compared to both the POAG patients and healthy subjects. Reduced CH in EXG patients might result in decreased support of peripapillary scleral structure and increased damage to the optic nerve during IOP increase.

Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

Science.gov (United States)

Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

2010-02-16

From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

Science.gov (United States)

Wilkens, H; Weingard, B; Lo Mauro, A; Schena, E; Pedotti, A; Sybrecht, G W; Aliverti, A

2010-09-01

Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, pvolume (0.75+/-0.10 and 0.79+/-0.07 litres) (pvolumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

CDC Behavioral Risk Factor Surveillance System (BRFSS)

Data.gov (United States)

U.S. Department of Health & Human Services — The Behavioral Risk Factor Surveillance System (BRFSS) is a state-based system of health surveys that collects information on health risk behaviors, preventive...

Validation of an Experimental Model to Study Less Severe Chronic Renal Failure.

Science.gov (United States)

Fernandes-Charpiot, Ida Mária Maximina; Caldas, Heloisa Cristina; Mendes, Glória Elisa Florido; Gomes de Sá Neto, Luiz; Oliveira, Henrique Lacativa; Baptista, Maria Alice Sperto Ferreira; Abbud-Filho, Mario

2016-10-01

The 5/6 nephrectomy, mimics the stages of human chronic renal failure (CRF), but the procedure causes severe renal functional and morphological damage that could interfere with the evaluation of therapies for slowing the progression of the disease. This study summarizes the results of renal function, histology, and immunohistochemical findings in rats undergoing a 2/3 nephrectomy. The rats were distributed in groups according to the type of nephrectomy: CRF5/6: induced by a 5/6 renal mass reduction and CRF2/3: less severe CRF. The body weight and blood pressure were monitored, and the serum creatinine (SCr), creatinine clearance (CCr), urine osmolality, and 24-h proteinuria (PT24h) were measured. CRF progression was evaluated by the rate of decline of CCr (RCCr). Histology and immunohistochemistry were performed in the remnant kidneys. Statistical analysis was done by unpaired t-test, and a P-value renal histopathological findings revealed fewer chronic lesions in rats with CRF2/3. Similarly, we observed less macrophage accumulation as well as lower proliferative activity and expression of fibronectin and a-smooth muscle-actin in the CRF2/3 model. The CRF2/3 model presented with a pattern of less severe CRF, functionally and morphologically, compared to the classical CRF5/6 model, and the CRF2/3 model may be useful for evaluating therapeutic interventions that target the early stages of CRF.

Learning a constrained conditional random field for enhanced segmentation of fallen trees in ALS point clouds

Science.gov (United States)

Polewski, Przemyslaw; Yao, Wei; Heurich, Marco; Krzystek, Peter; Stilla, Uwe

2018-06-01

In this study, we present a method for improving the quality of automatic single fallen tree stem segmentation in ALS data by applying a specialized constrained conditional random field (CRF). The entire processing pipeline is composed of two steps. First, short stem segments of equal length are detected and a subset of them is selected for further processing, while in the second step the chosen segments are merged to form entire trees. The first step is accomplished using the specialized CRF defined on the space of segment labelings, capable of finding segment candidates which are easier to merge subsequently. To achieve this, the CRF considers not only the features of every candidate individually, but incorporates pairwise spatial interactions between adjacent segments into the model. In particular, pairwise interactions include a collinearity/angular deviation probability which is learned from training data as well as the ratio of spatial overlap, whereas unary potentials encode a learned probabilistic model of the laser point distribution around each segment. Each of these components enters the CRF energy with its own balance factor. To process previously unseen data, we first calculate the subset of segments for merging on a grid of balance factors by minimizing the CRF energy. Then, we perform the merging and rank the balance configurations according to the quality of their resulting merged trees, obtained from a learned tree appearance model. The final result is derived from the top-ranked configuration. We tested our approach on 5 plots from the Bavarian Forest National Park using reference data acquired in a field inventory. Compared to our previous segment selection method without pairwise interactions, an increase in detection correctness and completeness of up to 7 and 9 percentage points, respectively, was observed.

Success Factors of Business Process Management Systems Implementation

NARCIS (Netherlands)

Johan Versendaal; J.P.P. Ravesteijn

2007-01-01

In this research (critical) success factors for Business Process Management Systems implementation are identified and qualitatively validated. Furthermore a list of critical success factors is constructed. Based on the identified factors a BPMS implementation approach is suggested. Future research

High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

Directory of Open Access Journals (Sweden)

Tomohiro Kotaki

Full Text Available Human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs, we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs.The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1 and the prevalence of other blood-borne viruses, hepatitis B virus (HBV, hepatitis C virus (HCV and GB virus C (GBV-C, were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients.The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%. In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

Lithium isotope separation factors of some two-phase equilibrium systems

International Nuclear Information System (INIS)

Palko, A.A.; Drury, J.S.; Begun, G.M.

1976-01-01

Isotope separation factors of seventeen two-phase equilibrium systems for lithium isotope enrichment have been determined. In all cases, lithium amalgam was used as one of the lithium-containing phases and was equilibrated with an aqueous or organic phase containing a lithium compound. In all systems examined, isotopic exchange was found to be extremely rapid, and 6 Li was concentrated in the amalgam phase. The isotopic separation factor for the LiOH(aqueous) vs Li(amalgam) system has been studied as a function of temperature from -2 to 80 degreeC. The values obtained have been compared with the ''electrolysis'' and exchange separation factors given in the literature. The two-phase systems, LiCl(ethylenediamine) vs Li(amalgam) and LiCl(propylenediamine) vs Li(amalgam), have been studied, and the isotopic separation factors have been determined as functions of the temperature. The factors for the two systems have been found to be substantially the same (within limits of the errors involved) over the temperature range studied (0 to 100 degreeC) as those for the aqueous system. The isotopic separation factors for the seventeen systems have been tabulated, and correlations have been drawn that show the salt and solvent effects upon the values obtained

Factorization approach to superintegrable systems: Formalism and applications

Energy Technology Data Exchange (ETDEWEB)

Ballesteros, Á., E-mail: angelb@ubu.es; Herranz, F. J., E-mail: fjherranz@ubu.es [Universidad de Burgos, Departamento de Física (Spain); Kuru, Ş., E-mail: kuru@science.ankara.edu.tr [Ankara University, Department of Physics, Faculty of Science (Turkey); Negro, J., E-mail: jnegro@fta.uva.es [Universidad de Valladolid, Departamento de Física Teórica, Atómica y Óptica (Spain)

2017-03-15

The factorization technique for superintegrable Hamiltonian systems is revisited and applied in order to obtain additional (higher-order) constants of the motion. In particular, the factorization approach to the classical anisotropic oscillator on the Euclidean plane is reviewed, and new classical (super) integrable anisotropic oscillators on the sphere are constructed. The Tremblay–Turbiner–Winternitz system on the Euclidean plane is also studied from this viewpoint.

Factors Associated with Photovoltaic System Costs (Topical Issues Brief)

Energy Technology Data Exchange (ETDEWEB)

Mortensen, J.

2001-06-12

A variety of factors can affect the cost of photovoltaic systems. This report analyses the relationship among such factors by using information entered into a voluntary registry of PV systems and performing regression analyses. The results showed statistically significant relationships between photovoltaic system cost and (a) grid connection, (b) installation year, (c) areas where the utility had entered into volume purchasing agreements.

Integrating high dimensional bi-directional parsing models for gene mention tagging.

Science.gov (United States)

Hsu, Chun-Nan; Chang, Yu-Ming; Kuo, Cheng-Ju; Lin, Yu-Shi; Huang, Han-Shen; Chung, I-Fang

2008-07-01

Tagging gene and gene product mentions in scientific text is an important initial step of literature mining. In this article, we describe in detail our gene mention tagger participated in BioCreative 2 challenge and analyze what contributes to its good performance. Our tagger is based on the conditional random fields model (CRF), the most prevailing method for the gene mention tagging task in BioCreative 2. Our tagger is interesting because it accomplished the highest F-scores among CRF-based methods and second over all. Moreover, we obtained our results by mostly applying open source packages, making it easy to duplicate our results. We first describe in detail how we developed our CRF-based tagger. We designed a very high dimensional feature set that includes most of information that may be relevant. We trained bi-directional CRF models with the same set of features, one applies forward parsing and the other backward, and integrated two models based on the output scores and dictionary filtering. One of the most prominent factors that contributes to the good performance of our tagger is the integration of an additional backward parsing model. However, from the definition of CRF, it appears that a CRF model is symmetric and bi-directional parsing models will produce the same results. We show that due to different feature settings, a CRF model can be asymmetric and the feature setting for our tagger in BioCreative 2 not only produces different results but also gives backward parsing models slight but constant advantage over forward parsing model. To fully explore the potential of integrating bi-directional parsing models, we applied different asymmetric feature settings to generate many bi-directional parsing models and integrate them based on the output scores. Experimental results show that this integrated model can achieve even higher F-score solely based on the training corpus for gene mention tagging. Data sets, programs and an on-line service of our gene

Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the Copenhagen Male Study.

Science.gov (United States)

Jensen, Magnus Thorsten; Holtermann, Andreas; Bay, Hans; Gyntelberg, Finn

2017-09-01

Poor cardiorespiratory fitness (CRF) is associated with death from cancer. If follow-up time is short, this association may be confounded by subclinical disease already present at the time of CRF assessment. This study investigates the association between CRF and death from cancer and any cause with 42 years and 44 years of follow-up, respectively. Middle-aged, employed and cancer-free Danish men from the prospective Copenhagen Male Study , enrolled in 1970-1971, were included. CRF (maximal oxygen consumption (VO 2 max)) was estimated using a bicycle ergometer test and analysed in multivariable Cox models including conventional risk factors, social class and self-reported physical activity. Death from cancer and all-cause mortality was assessed using Danish national registers. Follow-up was 100% complete. In total, 5131 men were included, mean (SD) age 48.8 (5.4) years. During 44 years of follow-up, 4486 subjects died (87.4%), 1527 (29.8%) from cancer. In multivariable models, CRF was highly significantly inversely associated with death from cancer and all-cause mortality ((HR (95% CI)) 0.83 (0.77 to 0.90) and 0.89 (0.85 to 0.93) per 10 mL/kg/min increase in estimated VO 2 max, respectively). A similar association was seen across specific cancer groups, except death from prostate cancer (1.00 (0.82 to 1.2); p=0.97; n=231). The associations between CRF and outcomes remained essentially unchanged after excluding subjects dying within 10 years (n=377) and 20 years (n=1276) of inclusion. CRF is highly significantly inversely associated with death from cancer and all-cause mortality. The associations are robust for exclusion of subjects dying within 20 years of study inclusion, thereby suggesting a minimal influence of reverse causation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Medical and Periodontal Clinical Parameters in Patients at Different Levels of Chronic Renal Failure

Directory of Open Access Journals (Sweden)

Caroline Perozini

2017-01-01

Full Text Available Aim. To assess the clinical periodontal and medical parameters in patients with chronic renal failure (CRF at different levels of renal disease. Background. CRF is a progressive and irreversible loss of renal function associated with a decline in the glomerular filtration rate. Periodontal disease is a destructive inflammatory disease affecting periodontal tissues that shows high prevalence in patients with CRF. Materials and Methods. 102 CRF patients were included and divided into an early stage group (EG, predialysis group (PDG, and hemodialysis group (HDG. The medical parameters were taken from the patients’ records. Results. Periodontal clinical condition differed among the CRF groups. Clinical attachment loss was greater in the HDG and PDG group compared to the EG (p=0.0364; the same was observed in the Plaque Index (p=0.0296; the others periodontal parameters did not show any differences. Ferritin levels were significantly higher in the HDG when compared to the EG and PGD (p<0.0001, and fibrinogen was higher in PDG compared with the others (p<0.0001; the triglycerides also showed higher values in the HDG compared with the other groups (p<0.0001. Conclusion. The patients with renal involvement should have a multidisciplinary approach to an improvement in their oral and systemic health.

Association of plasma manganese levels with chronic renal failure.

Science.gov (United States)

Sánchez-González, Cristina; López-Chaves, Carlos; Gómez-Aracena, Jorge; Galindo, Pilar; Aranda, Pilar; Llopis, Juan

2015-01-01

Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn. Copyright © 2015 Elsevier GmbH. All rights reserved.

Skeletal muscle metaboreflex in patients with chronic renal failure.

Science.gov (United States)

Vieira, Paulo J C; Silva, Leonardo R; Maldamer, Vinicius Z; Cipriano, Gerson; Chiappa, Adriana M G; Schuster, Rodrigo; Boni, Victor H F; Grandi, Tatiani; Wolpat, Andiara; Roseguini, Bruno T; Chiappa, Gaspar R

2017-03-01

The sympathetic nervous system is affected in patients with chronic renal failure (CRF). This study tested the hypothesis that patients with CRF have an altered skeletal muscle metaboreflex. Twenty patients with CRF and 18 healthy subjects of similar age participated in the study. The muscle metaboreflex was determined based on heart rate (HR), mean arterial pressure, calf blood flow and calf vascular resistance (CVR) in response to handgrip exercise. The control of vascular resistance in the calf muscle mediated by the metaboreflex was estimated by subtracting the area under the curve with circulatory occlusion from that without occlusion. Arterial pressure and HR responses during exercise and recovery were similar in two groups of subjects. In the control group, CVR increased during exercise and remained elevated during circulatory occlusion, whereas no significant change was seen in the patients. Thus, the index of the metaboreflex was 7·82 ± 9·57 in the patients versus16·52 ± 14 units in the controls. The findings demonstrate that patients with CRF have a decreased vascular resistance response in the calf during the handgrip exercise, which suggests that CRF condition attenuates this reflex. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Enhanced/Synthetic Vision Systems - Human factors research and implications for future systems

Science.gov (United States)

Foyle, David C.; Ahumada, Albert J.; Larimer, James; Sweet, Barbara T.

1992-01-01

This paper reviews recent human factors research studies conducted in the Aerospace Human Factors Research Division at NASA Ames Research Center related to the development and usage of Enhanced or Synthetic Vision Systems. Research discussed includes studies of field of view (FOV), representational differences of infrared (IR) imagery, head-up display (HUD) symbology, HUD advanced concept designs, sensor fusion, and sensor/database fusion and evaluation. Implications for the design and usage of Enhanced or Synthetic Vision Systems are discussed.

21 CFR 864.7280 - Factor V Leiden DNA mutation detection systems.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Factor V Leiden DNA mutation detection systems....7280 Factor V Leiden DNA mutation detection systems. (a) Identification. Factor V Leiden deoxyribonucleic acid (DNA) mutation detection systems are devices that consist of different reagents and...

Economic growth factors system: theoretical and methodological aspect

OpenAIRE

H.Ya. Hlukha

2014-01-01

The aim of the article. The main objective of the article is to create theoretical grounds to build the system of economic growth factors, to modernize their classification, to define exogenous and endogenous factors, to analyze them within the state economic policy structure. The results of the analysis. The article focuses on economic growth factors theoretical studies: - economic growth factors classification characteristics have been highlighted; - various approaches to determine...

Independent and Combined Association of Muscle Strength and Cardiorespiratory Fitness in Youth With Insulin Resistance and β-Cell Function in Young Adulthood

DEFF Research Database (Denmark)

Grøntved, Anders; Ried-Larsen, Mathias; Ekelund, Ulf

2013-01-01

ergometer test. Insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) and β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) were estimated from fasting serum insulin and glucose that were obtained in youth and at follow-up in young adulthood.......RESULTSFor each 1-SD difference in isometric muscle strength (0.16 N/kg) in youth, fasting insulin, HOMA-IR, and HOMA-B in young adulthood changed with -11.3% (95% CI, -17.0 to -5.2), -12.2% (-18.2 to -5.7), and -8.9% (-14.4 to -3.0), respectively, in young adulthood after adjustment for CRF and personal...... lifestyle and demographic factors. Results for CRF were very similar in magnitude, and the magnitude of associations for both exposures was unchanged with additional adjustment for general or abdominal adiposity in youth. Combined associations of muscle strength and CRF with fasting insulin, HOMA-IR...

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

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Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Implementation of evidence into practice for cancer-related fatigue management of hospitalized adult patients using the PARIHS framework.

Directory of Open Access Journals (Sweden)

Li Tian

Full Text Available This study aimed to explore an evidence-based nursing practice model of CRF management in hospitalized adult patients using the PARIHS evidence-implementation framework as the theoretical structure to provide guidance for similar nursing practices. The implementation of guideline evidence into clinical practice was conducted on the oncology and radiotherapy wards of a university-affiliated hospital. The process of integrating the guideline into the symptom management system of cancer patients was described. The impact of the evidence implementation was evaluated from three aspects: organizational innovations and outcome measures associated with nurses and with patients pre- and post-evidence implementation. During the implementation of evidence into practice on the wards, a nursing process, health education, a quality control sheet and CRF training courses were established. Through this implementation, compliance with evidence related to CRF increased significantly on the two wards, with that of ward B being higher than that of ward A. Regarding nursing outcomes, nursing knowledge, attitude and behavior scores with respect to CRF nursing care increased substantially after its application on the two wards, and the ward B nurses' scoring was higher than that of the ward A nurses. Qualitative analysis concerning the nurses suggested that leadership, patient concern about CRF management, and the need for professional development were the main motivators of the application, whereas the shortage and mobility of nursing human resources and insufficient communication between doctors and nurses were the main barriers. Additionally, most nurses felt more professional and confident about their work. Regarding patient outcomes, patient knowledge, attitude and behavior scores regarding CRF self-management increased significantly. Patients' post-implementation CRF was alleviated compared with the pre-implementation treatment cycle. The PARIHS framework may

UNIPOLAR, BIPOLAR OR MULTIPOLAR INTERNATIONAL SYSTEM? THE DEFENSE INDUSTRY FACTOR

OpenAIRE

ÖZKAN, Gökhan

2008-01-01

International system can be defined as a complex system of systems that is comprised of economic, political, scientific, technological and military systems. It is hard to analyze this complex system. It is even harder to forecast its future. Nonetheless, there are factors such as the defense industry and military power that affect the dynamics of the international system much more than other factors. After the Revolution in Military Affairs, which transformed the military paradigm, significa...

[Study on the molecular-epidemiological characteristics of HIV-1 in Shenzhen, 1992-2008].

Science.gov (United States)

Zhao, Guang-lu; Yu, Wei; Zhang, Juan-juan; Chen, Lin; Feng, Tie-jian; Wang, Feng; Hong, Fu-chang; Wang, Xiao-hui; Li, Qing

2012-01-01

To investigate the epidemiological characteristics of HIV-1 subtype in Shenzhen from 1992 to 2008. 489 HIV-1 positive plasma samples were collected from 1992 to 2008 in Shenzhen. HIV-1 env genes were amplified by nested-PCR from RNA. Phylogenetic analysis was performed on data regarding the nucleotide sequence. A total of 464 sequences were amplified and genotyped. Data from this study revealed that CRF01_AE was a predominant HIV-1 subtype in Shenzhen (64.4%, 299/464), followed by subtypes CRF_BC (17.5%, 81/464), B' (14.7%, 68/464) and B (2.4%, 11/464). Subtype C (0.4%, 2/464), A1 (0.2%, 1/464), CRF02_AG (0.2%, 1/464) and CRF06_cpx (0.2%, 1/464) were also prevalent in Shenzhen. CRF01_AE and CRF_BC were predominant among heterosexuals, homosexuals and injection drug users, while B' was predominant among blood donors. Results from phylogenetic tree analysis showed that some of the HIV-1 clusters had been defined in CRF01_AE strains at different time or groups with different transmission routes. Cross-infections were also seen. CRF01_AE was the predominant HIV-1 subtype in Shenzhen while CRF_BC, B, B', C, A1, CRF02_AG and a small amount of CRF06_cpx or recombinant subtypes were prevalent in this city. Different subtypes showed great variation in the process of epidemics.

Maturity of hospital information systems: Most important influencing factors.

Science.gov (United States)

Vidal Carvalho, João; Rocha, Álvaro; Abreu, António

2017-07-01

Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.

Human factors programs for high-level radioactive waste handling systems

International Nuclear Information System (INIS)

Pond, D.J.

1992-04-01

Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples from other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

Human factors programs for high-level radioactive waste handling systems

International Nuclear Information System (INIS)

Pond, D.J.

1992-01-01

Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples form other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue.

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Katarzyna Kisiel-Sajewicz

Full Text Available PURPOSE: A lack of fatigue-related muscle contractile property changes at time of perceived physical exhaustion and greater central than peripheral fatigue detected by twitch interpolation technique have recently been reported in cancer survivors with fatigue symptoms. Based on these observations, it was hypothesized that compared to healthy people, myoelectrical manifestation of fatigue in the performing muscles would be less significant in these individuals while sustaining a prolonged motor task to self-perceived exhaustion (SPE since their central fatigue was more prominent. The purpose of this study was to test this hypothesis by examining electromyographic (EMG signal changes during fatiguing muscle performance. METHODS: Twelve individuals who had advanced solid cancer and cancer-related fatigue (CRF, and 12 age- and gender-matched healthy controls performed a sustained elbow flexion at 30% maximal voluntary contraction till SPE. Amplitude and mean power frequency (MPF of EMG signals of the biceps brachii, brachioradialis, and triceps brachii muscles were evaluated when the individuals experienced minimal, moderate, and severe fatigue. RESULTS: CRF patients perceived physical "exhaustion" significantly sooner than the controls. The myoelectrical manifestation of muscular fatigue assessed by EMG amplitude and MPF was less significant in CRF than controls. The lower MPF even at minimal fatigue stage in CRF may indicate pathophysiologic condition of the muscle. CONCLUSIONS: CRF patients experience less myoelectrical manifestation of muscle fatigue than healthy individuals near the time of SPE. The data suggest that central nervous system fatigue plays a more important role in limiting endurance-type of motor performance in patients with CRF.

Factors that influence the relative use of multiple memory systems.

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Packard, Mark G; Goodman, Jarid

2013-11-01

Neurobehavioral evidence supports the existence of at least two anatomically distinct "memory systems" in the mammalian brain that mediate dissociable types of learning and memory; a "cognitive" memory system dependent upon the hippocampus and a "stimulus-response/habit" memory system dependent upon the dorsolateral striatum. Several findings indicate that despite their anatomical and functional distinctiveness, hippocampal- and dorsolateral striatal-dependent memory systems may potentially interact and that, depending on the learning situation, this interaction may be cooperative or competitive. One approach to examining the neural mechanisms underlying these interactions is to consider how various factors influence the relative use of multiple memory systems. The present review examines several such factors, including information compatibility, temporal sequence of training, the visual sensory environment, reinforcement parameters, emotional arousal, and memory modulatory systems. Altering these parameters can lead to selective enhancements of either hippocampal-dependent or dorsolateral striatal-dependent memory, and bias animals toward the use of either cognitive or habit memory in dual-solution tasks that may be solved adequately with either memory system. In many learning situations, the influence of such experimental factors on the relative use of memory systems likely reflects a competitive interaction between the systems. Research examining how various factors influence the relative use of multiple memory systems may be a useful method for investigating how these systems interact with one another. Copyright © 2013 Wiley Periodicals, Inc.

A Study of Information Systems Outsourcing Influential Factors.

Science.gov (United States)

Claver, Enrique; Gonzalez, Reyes; Gasco, Jose; Llopis, Juan

2002-01-01

Surveyed information systems managers at Spanish public universities to determine the level of information systems outsourcing. Also determined how factors such as the size of universities and their information systems departments, as well as the degree of involvement of rector's and general manager's teams, influence outsourcing levels. (EV)

How do individuals cope with stress? Behavioural, physiological and neuronal differences between proactive and reactive coping styles in fish

DEFF Research Database (Denmark)

Vindas, Marco A; Gorissen, Marnix; Höglund, Erik

2017-01-01

of the 5-HT1A receptor abundance) in the proposed amygdala homologue (Dm), increased expression of the neuroplasticity marker brain derived neurotropic factor (bdnf) in both Dl and Vv (lateral septum homologue), as well as increased expression of the corticotropin releasing factor 1 (crf1) receptor...

The Correlation Analysis between Corneal Biomechanical Properties and the Surgically Induced Corneal High-Order Aberrations after Small Incision Lenticule Extraction and Femtosecond Laser In Situ Keratomileusis

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Wenjing Wu

2015-01-01

Full Text Available Background. To investigate the correlation between corneal biomechanics and the surgically induced corneal high-order aberrations (HOAs after small incision lenticule extraction (SMILE and femtosecond laser in situ keratomileusis (FS-LASIK. Methods. A total of 150 right myopic eyes that underwent SMILE or FS-LASIK surgery were included in this retrospective study, 75 eyes in each group. The corneal hysteresis (CH and the corneal resistance factor (CRF with the corneal HOAs of the anterior, posterior, and total cornea were assessed preoperatively and three months postoperatively. Multivariate linear regression was applied to determine the correlations. Results. The preoperative CRF was significantly correlated with the induced 3rd–6th-order HOAs and spherical aberration of the anterior surface and the total cornea after SMILE and FS-LASIK surgeries (P<0.05, postoperatively. The CRF was significantly correlated with the induced vertical coma of the anterior and posterior surfaces and the total cornea after SMILE surgery (P<0.05. There was a significant correlation between the CRF and the induced posterior corneal horizontal coma after FS-LASIK surgery (P=0.013. Conclusions. The corneal biomechanics affect the surgically induced corneal HOAs after SMILE and FS-LASIK surgery, which may be meaningful for screening the patients preoperatively and optimizing the visual qualities postoperatively.

Morphology of Design of Aerospace Systems with Inclusion of Human Factors

Science.gov (United States)

1977-08-01

Visual Indicators," Human Factors, 1971, 13(5), pp. 427-433. 22. Mayer, Sylvia R., "Trends in Human Factors Research for Military Information Systems...34The Standardi- zation of Human Factors Data," Human Factors, 1970, 12(1), pp. 55-62. 29. Plath , D.W., "Th’ Readability of Segmented and Con... Sylvia R., "Trends in Human Factors Research for Military Information Systems," Human Factors, 1970, 12(2), pp. 177-186. 35. Meister, David, Dennis 3

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

Science.gov (United States)

Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

2017-09-01

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg -1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the

Predictive value of ADAMTS-13 on concealed chronic renal failure in COPD patients

Science.gov (United States)

Zeng, Mian; Chen, Qingui; Liang, Wenjie; He, Wanmei; Zheng, Haichong; Huang, Chunrong

2017-01-01

Background Impaired renal function is often neglected in COPD patients. Considering that COPD patients usually have an ongoing prothrombotic state and systemic inflammation status, we investigated the association among them and explored the predictive value of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), on concealed chronic renal failure (CRF) in COPD patients. Methods COPD patients were recruited from the First Affiliated Hospital of Sun Yat-Sen University between January 2015 and December 2016. Control was selected from contemporaneous hospitalized patients without COPD and matched by age and gender at a ratio of 1:1. Estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula, and all subjects were categorized as having normal renal function (eGFR ≥60 mL min−1 1.73 m−2) and having concealed CRF (normal serum creatinine while eGFR <60 mL min−1 1.73 m−2). Independent correlates of concealed CRF were investigated by logistic regression analysis, and receiver operating characteristic (ROC) curves were used to determine the predictive value of ADAMTS-13. Results In total, 106 COPD and 106 non-COPD patients were finally recruited, and the incidences of concealed CRF were 19.81% and 7.55%, respectively. ADAMTS-13 (odds ratio [OR] =0.858, 95% CI =0.795–0.926), D-dimer (OR =1.095, 95% CI =1.027–1.169), and C-reactive protein (OR =1.252, 95% CI =1.058–1.480) were significantly associated with concealed CRF. Sensitivity and specificity at an ADAMTS-13 cutoff of 318.72 ng/mL were 100% and 81.2%, respectively. The area under the ROC curve was 0.959. Conclusion Prothrombotic state and systemic inflammation status might contribute to explaining the high incidence of concealed CRF in COPD, and plasma ADAMTS-13 levels may serve as a strong predictor. PMID:29255356

The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors?

Science.gov (United States)

Armario, Antonio

2006-10-01

The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.

Sex differences in stress-related receptors: ″micro″ differences with ″macro″ implications for mood and anxiety disorders

Science.gov (United States)

2013-01-01

Stress-related psychiatric disorders, such as unipolar depression and post-traumatic stress disorder (PTSD), occur more frequently in women than in men. Emerging research suggests that sex differences in receptors for the stress hormones, corticotropin releasing factor (CRF) and glucocorticoids, contribute to this disparity. For example, sex differences in CRF receptor binding in the amygdala of rats may predispose females to greater anxiety following stressful events. Additionally, sex differences in CRF receptor signaling and trafficking in the locus coeruleus arousal center combine to make females more sensitive to low levels of CRF, and less adaptable to high levels. These receptor differences in females could lead to hyperarousal, a dysregulated state associated with symptoms of depression and PTSD. Similar to the sex differences observed in CRF receptors, sex differences in glucocorticoid receptor (GR) function also appear to make females more susceptible to dysregulation after a stressful event. Following hypothalamic pituitary adrenal axis activation, GRs are critical to the negative feedback process that inhibits additional glucocorticoid release. Compared to males, female rats have fewer GRs and impaired GR translocation following chronic adolescent stress, effects linked to slower glucocorticoid negative feedback. Thus, under conditions of chronic stress, attenuated negative feedback in females would result in hypercortisolemia, an endocrine state thought to cause depression. Together, these studies suggest that sex differences in stress-related receptors shift females more easily into a dysregulated state of stress reactivity, linked to the development of mood and anxiety disorders. The implications of these receptor sex differences for the development of novel pharmacotherapies are also discussed. PMID:23336736

Biomaterial-based drug delivery systems for the controlled release of neurotrophic factors

International Nuclear Information System (INIS)

Mohtaram, Nima Khadem; Montgomery, Amy; Willerth, Stephanie M

2013-01-01

This review highlights recent work on the use of biomaterial-based drug delivery systems to control the release of neurotrophic factors as a potential strategy for the treatment of neurological disorders. Examples of neurotrophic factors include the nerve growth factor, the glial cell line-derived neurotrophic factor, the brain-derived neurotrophic factor and neurotrophin-3. In particular, this review focuses on two methods of drug delivery: affinity-based and reservoir-based systems. We review the advantages and challenges associated with both types of drug delivery system and how these systems can be applied to neurological diseases and disorders. While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels and combinations of these systems. Finally, conclusions are drawn about the current state of such drug delivery systems as applied to neural tissue engineering along with some thoughts on the future direction of the field. (topical review)

Rated power factor and excitation system of large turbine generator

International Nuclear Information System (INIS)

Tokumitsu, Iwao; Watanabe, Takashi; Banjou, Minoru.

1979-01-01

As for the rated power factor of turbine generators for thermal power stations, 90% has been adopted since around 1960. On the other hand, power transmission system has entered 500 kV age, and 1,000 kV transmission is expected in the near future. As for the supply of reactive power from thermal and nuclear turbine generators, the necessity of supplying leading reactive power has rather increased. Now, the operating power factor of thermal and nuclear generators becomes 96 to 100% actually. As for the excess stability of turbine generators owing to the strengthening of transmission system and the adoption of super-high voltage, the demand of strict conditions can be dealt with by the adoption of super-fast response excitation system of thyristor shunt winding self exciting type. The adoption of the turbine generators with 90 to 95% power factor and the adoption of the thyristor shunt winding self exciting system were examined and evaluated. The rated power factor of generators, excitation system and economy of adopting these systems are explained. When the power factor of generators is increased from 0.9 to 0.95, about 6% of saving can be obtained in the installation cost. When the thyristor shunt winding self excitation is adopted, it is about 10% more economical than AC excitation. (Kako, I.)

The impact of early life family structure on adult social attachment, alloparental behavior, and the neuropeptide systems regulating affiliative behaviors in the monogamous prairie vole (Microtus ochrogaster

Directory of Open Access Journals (Sweden)

Todd H Ahern

2009-08-01

Full Text Available Early social attachments lie at the heart of emotional and social development in many mammals, including humans. In nature, monogamous prairie voles (Microtus ochrogaster experience considerable natural variation in early social attachment opportunities due to differences in family structure (e.g., single-mothers, solitary breeding pairs, and communal groups. We exploited some of this natural variation in family structure to examine the influence of early social environment on the development of adult social behavior. First, we characterized the parental care received by pups reared biparentally (BP or by a single-mother (SM in the laboratory. Second, we examined whether BP- and SM-reared offspring differed in adult nurturing, bonding, and emotional behaviors. Finally, we investigated the effects of rearing condition on neuropeptide systems that regulate adult social behavior (oxytocin, vasopressin, and corticotropin-releasing factor [CRF]. Observations revealed that SM-reared pups were exposed more frequently (P<0.01, licked and groomed less (P<0.01, and matured more slowly (P<0.01 than BP-reared pups. In adulthood, there were striking socio-behavioral differences: SM-reared females showed low spontaneous, pup-directed alloparental behavior (P<0.01 and both males and females from the SM-reared condition showed delayed partner preference formation. While rearing did not impact neuropeptide receptor densities in the ventral forebrain as we predicted, SM-reared animals, particularly females, had increased OT content (P<0.01 and greater dorsal raphe CRF2 densities (P<0.05 and both measures correlated with licking and grooming experienced during the first 10 days of life. These results suggest that naturalistic variation in social rearing conditions can introduce diversity into adult nurturing and attachment behaviors.

[Molecular epidemiology and transmission of HIV-1 infection in Zhejiang province, 2015].

Science.gov (United States)

Yang, J Z; Chen, W J; Zhang, W J; He, L; Zhang, J F; Pan, X H

2017-11-10

Objective: To understand the distribution of HIV-1 subtype diversity and its transmission characteristics in Zhejiang province. Methods: A total of 302 newly diagnosed HIV-1 positive patients were selected through stratified random sampling in Zhejiang in 2015. HIV-1 pol genes were sequenced successfully with reverse transcription PCR/nested PCR and phylogenetic analysis was conducted for 276 patients. Then a molecular epidemiologic study was performed combined with field epidemiological investigation. Results: Of 276 sequence samples analyzed, 122 CRF07_BC strains (44.2%), 103 CRF01_AE strains (37.3%), 17 CRF08_BC strains (6.1%), 9 B strains (3.2%), 6 CRF55_01B strains (2.2%), 5 C strains (1.8%), 1 CRF59_01B strain (0.4%), 1 CRF67_01B strain (0.4%), 1 A1 strain (0.4%), and 11 URFs strains (4.0%) were identified. Phylogenetic analysis revealed 16 clusters with only 15.1% (34/225) sequences involved among CRF07_BC and CRF01_AE strains. The clustered cases in MSM were higher than that in populations with other transmission routes. And clusters existed between the populations with different transmission routes. Conclusion: The major strains of HIV-1 in Zhejiang are CRF07_BC and CRF01_AE. The HIV subtypes showed more complexity in Zhejiang. It is necessary to strengthen the surveillance for HIV subtypes, carry out classified management and conduct effective prevention and control in the population at high risk.

The cloud-radiative forcing of the U.S. landfalling atmospheric rivers

Science.gov (United States)

Luo, Qianwen

Atmospheric rivers (ARs) are narrow channels in the atmosphere that transport an enormous amount of moisture from the tropics to the higher latitudes. Streaks of highly reflective clouds are observed along with the ARs in satellite imagery. These clouds both influence the moisture transport of ARs, as well as modify the Earth-Atmospheric energy budget through pathways such as cloud-radiative forcing (CRF). This dissertation studies the CRF of the U.S. Landfalling ARs in weather and climate scales. Three crucial questions are addressed. First, how do clouds produced by the ARs modulate the moisture and heat balance of the Earth-Atmospheric system? Even though studies of ARs date back to the 90s, past research has been primarily focused on their hydrological impacts. We addressed this research gap by comparing the dominant types of precipitating clouds and convection of two ARs. Through quantifying their effects on the energy balance in the midlatitudes, we found that when deep convection was the dominant cloud types of an AR, impressive CRF cooling was produced. Second, what are the sufficient climate conditions for the extensive CRF in the continental U.S.? We studied 60 ARs that reached the California coast (the Southwest ARs) and 60 ARs that reached Pacific Northwest during Nov-Mar, 2000-2008. It was found that when these West-Coast ARs were followed by the moisture surge from the Gulf of Mexico (the Gulf-Coast AR), it resulted in apparent statewide CRF. Such condition happened more frequently in the Southwest-AR scenario. Third, how does the subgrid-scale-convection-induced CRF influence the moisture transport of ARs?We ran two WRF ARW simulations for a Southwest-AR that was followed by a Gulf-Coast AR. The only difference between the two simulations was one considered the CRF of subgrid-scale clouds while the other did not. By comparing the two simulations, we found that the subgrid-scale-convection-induced CRF helped prolong the lifespan of clouds in an AR

Identification and characterization of a pituitary corticotropin-releasing factor binding protein by chemical cross-linking

DEFF Research Database (Denmark)

Nishimura, E; Billestrup, Nils; Perrin, M

1987-01-01

appeared to have a molecular weight of approximately 70,000. The cross-linking was specific since an excess (1 microM) of an unrelated peptide (insulin) did not affect the appearance of the Mr 75,000 band. The concentration of CRF required to inhibit cross-linking by 50% was found to be similar...

Classification analysis of organization factors related to system safety

International Nuclear Information System (INIS)

Liu Huizhen; Zhang Li; Zhang Yuling; Guan Shihua

2009-01-01

This paper analyzes the different types of organization factors which influence the system safety. The organization factor can be divided into the interior organization factor and exterior organization factor. The latter includes the factors of political, economical, technical, law, social culture and geographical, and the relationships among different interest groups. The former includes organization culture, communication, decision, training, process, supervision and management and organization structure. This paper focuses on the description of the organization factors. The classification analysis of the organization factors is the early work of quantitative analysis. (authors)

Factors Affecting Quality of Life and Fatigue in Gynaecologic Cancer Patients

Directory of Open Access Journals (Sweden)

Güngör İ

2017-06-01

Full Text Available Background: Cancer-related fatigue (CRF is the most commonly reported and most distressing symptom in cancer patients. Health-related quality of life (QOL is an important outcome in cancer management, the authors sought to better understand its determinants. Aim: This study aims to identify quality of life and fatigue levels and the affecting factors in gynaecologic cancer patients. Method: This descriptive and cross-sectional study was conducted with 154 volunteer women with gynaecologic cancer. The data were collected through the interview form, functional assessment of cancer therapy-general (FACT-G Quality of Life Scale, and Piper Fatigue Scale. Results: The mean score of total quality of life in gynaecologic cancer patients was low, 53.4 ± 15.4. Physical and emotional states were found to be the mostly affected states in the quality of life. According to the Piper Fatigue Scale, the total fatigue score was mild, 3.5 ± 2.4. Total fatigue scores were found to be high in metastatic cancers. Multivariate analyses indicate that the most important factor affecting the quality of life is economic condition, and the most important variables affecting fatigue are the level of activity and use of medicine. Conclusion: This study found that quality of life dimensions in women with gynaecologic cancer was affected by factors such as cancer type, time of diagnosis, and stage and spread of the cancer.

On Signed Incomplete Cholesky Factorization Preconditioners for Saddle-Point Systems

Czech Academy of Sciences Publication Activity Database

Scott, J.; Tůma, Miroslav

2014-01-01

Roč. 36, č. 6 (2014), A2984-A3010 ISSN 1064-8275 R&D Projects: GA ČR GA13-06684S Grant - others:EPSRC(GB) EP/I013067/1 Program:GA Institutional support: RVO:67985807 Keywords : sparse matrices * sparse linear systems * indefinite symmetric systems * saddle-point systems * iterative solvers * preconditioning * incomplete Cholesky factorization Subject RIV: BA - General Mathematics Impact factor: 1.854, year: 2014

Three-year changes in fitness and adiposity are independently associated with cardiovascular risk factors among young danish children

DEFF Research Database (Denmark)

Jago, Russell; Froberg, Karsten; Cooper, Ashley R

2010-01-01

, sum of skinfolds (SSF), and blood pressure were assessed. Fasting blood samples were used to calculate total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C & LDL-C), triglycerides, insulin, glucose, and HOMA-IR. Regression models examined whether CRF change or SSF change were...

Patient safety - the role of human factors and systems engineering.

Science.gov (United States)

Carayon, Pascale; Wood, Kenneth E

2010-01-01

Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety.

Patient Safety: The Role of Human Factors and Systems Engineering

Science.gov (United States)

Carayon, Pascale; Wood, Kenneth E.

2011-01-01

Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety. PMID:20543237

Theory of ground state factorization in quantum cooperative systems.

Science.gov (United States)

Giampaolo, Salvatore M; Adesso, Gerardo; Illuminati, Fabrizio

2008-05-16

We introduce a general analytic approach to the study of factorization points and factorized ground states in quantum cooperative systems. The method allows us to determine rigorously the existence, location, and exact form of separable ground states in a large variety of, generally nonexactly solvable, spin models belonging to different universality classes. The theory applies to translationally invariant systems, irrespective of spatial dimensionality, and for spin-spin interactions of arbitrary range.

Characterization of central and peripheral components of the hypothalamus-pituitary-adrenal axis in the inbred Roman rat strains.

Science.gov (United States)

Carrasco, Javier; Márquez, Cristina; Nadal, Roser; Tobeña, Adolfo; Fernández-Teruel, Albert; Armario, Antonio

2008-05-01

Several studies performed in outbred Roman high- and low-avoidance lines (RHA and RLA, respectively) have demonstrated that the more anxious line (RLA) is characterized by a higher hypothalamic-pituitary-adrenal (HPA) response to certain stressors than the less anxious one (RHA). However, inconsistent results have also been reported. Taking advantage of the generation of an inbred colony of RLA and RHA rats (RHA-I and RLA-I, respectively), we have characterized in the two strains not only resting and stress levels of peripheral HPA hormones but also central components of the HPA axis, including CRF gene expression in extra-hypothalamic areas. Whereas resting levels of ACTH and corticosterone did not differ between the strains, a greater response to a novel environment was found in RLA-I as compared to RHA-I rats. RLA-I rats showed enhanced CRF gene expression in the paraventricular nucleus (PVN) of the hypothalamus, with normal arginin-vasopressin gene expression in both parvocellular and magnocellular regions of the PVN. This enhanced CRF gene expression is not apparently related to altered negative corticosteroid feedback as similar levels of expression of brain glucorticoid and mineralocorticoid receptors were found in the two rat strains. CRF gene expression tended to be higher in the central amygdala and it was significantly higher in the dorsal region of the bed nucleus of stria terminalis (BNST) of RLA-I rats, while no differences appeared in the ventral region of BNST. Considering the involvement of CRF and the BNST in anxiety and stress-related behavioral alterations, the present data suggest that the CRF system may be a critical neurobiological substrate underlying differences between the two rat strains.

[Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province].

Science.gov (United States)

Deng, Yongyue; Zhang, Chunyang; Yan, Yansheng; Yan, Pingping; Wu, Shouli

2014-06-01

In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province. Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology, during 2011-2012. Viral sequences(n = 81) of HIV-1 gag, env, and pol segments were amplified by nested PCR. Subtypes B and four Circulating Recombinant Forms, (CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%) were the two main HIV-1 strains in Fujian province. Compared with previous data, the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly. Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.

Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

Science.gov (United States)

Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

2015-01-01

The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

The Impacts of System and Human Factors on Online Learning Systems Use and Learner Satisfaction

Science.gov (United States)

Alshare, Khaled A.; Freeze, Ronald D.; Lane, Peggy L.; Wen, H. Joseph

2011-01-01

Success in an online learning environment is tied to both human and system factors. This study illuminates the unique contributions of human factors (comfort with online learning, self-management of learning, and perceived Web self-efficacy) to online learning system success, which is measured in terms of usage and satisfaction. The research model…

The Relationship between Serum 25-Hydroxyvitamin D Concentration, Cardiorespiratory Fitness, and Insulin Resistance in Japanese Men

Directory of Open Access Journals (Sweden)

Xiaomin Sun

2014-12-01

Full Text Available Here, we aim to investigate the independent and combined associations of serum 25-hydroxyvitamin D (25(OHD and cardiorespiratory fitness (CRF with glucose metabolism. Fasting blood samples of 107 men aged 40–79 years were analyzed for 25(OHD, glucose, insulin, glycated hemoglobin, and lipid profile. Homeostasis model assessment of insulin resistance index (HOMA-IR was calculated from the fasting concentrations of glucose and insulin. Visceral fat area (VFA was determined by magnetic resonance imaging and CRF by measuring maximal oxygen uptake. Median 25(OHD concentration was 36.3 nmol/L, while the prevalence of 25(OHD deficiency was 74.8%. Participants with high CRF had significantly lower HOMA-IR, glycated hemoglobin, and insulin values than participants with low CRF (p < 0.05. Higher 25(OHD concentration was strongly correlated with lower HOMA-IR and insulin values independent of VFA (p < 0.01 but significantly affected by CRF. In the high CRF group, participants with higher 25(OHD concentration had lower HOMA-IR values than participants with low 25(OHD concentration (p < 0.05. Higher 25(OHD and CRF are crucial for reducing insulin resistance regardless of abdominal fat. In addition, higher 25(OHD concentration may strengthen the effect of CRF on reducing insulin resistance in middle-aged and elderly Japanese men with high CRF.

The effect of non-diabetic chronic renal failure on olfactory function.

Science.gov (United States)

Koseoglu, S; Derin, S; Huddam, B; Sahan, M

2017-05-01

In chronic renal failure (CRF), deterioration of glomerular filtration results in accumulation of metabolites in the body which affect all organs. This study was performed to investigate the olfactory functions, and determine if hemodialysis or peritoneal dialysis improves olfactory function in non-diabetic CRF patients. The olfactory functions were analyzed in CRF patients not on a dialysis program and had a creatinine level≥2mg/dL, in CRF patients on hemodialysis or peritoneal dialysis, and in healthy controls. Diabetic patients were excluded since diabetes alone is a cause of olfactory dysfunction. The study group consisted of a total of 107 individuals including 38CRF patients on a hemodialysis program, 15 CRF patients on peritoneal dialysis, 30 patients with a creatinine level ≥ 2mg/dL without any need for dialysis, and 24 healthy controls with normal renal functions. Olfactory functions were analyzed with "Sniffin' sticks" test, and the groups were compared for the test results. All test parameters were impaired in patients with CRF. The median TDI scores of the patients with CRF and the healthy subjects were 24.75 (13-36) and 32.5 (27.75-37.75), respectively, with a statistically significant difference in between (P<0.001). The olfactory functions for the dialysis patients were better than those for the CRF patients not on a dialysis program (P=0.020). Non-diabetic CRF affects olfactory functions negatively. Dialysis improves olfactory functions in those patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Structure design of human factor data management system for Daya Bay NPP

International Nuclear Information System (INIS)

Zhang Li; Zhang Ning; Guo Jianbing; Huang Weigang; Zhu Minhong; Wang Jin

2000-01-01

Collection, analysis and quantification of human factor data are important compositions of human reliability analysis (HRA) and probabilistic risk assessment (PRA). Various human factor databases have been set up, but there are comparatively little human factor data management systems which can be uses for collection, classification, analysis, calculation and predication of the human factor data. Therefore, the human factor data management system for Daya Bay NPP is developed, with the following three modules and four databases: original data module, computing module, introduced data module, and basic database, other data source of the plant, external database and introduced database. The foundational problems about human factor data and the systemic structure and function are described. The data structure in the database is also discussed, because it is of the most importance in the system

Associations of fractalkine receptor (CX3CR1) and CCR5 gene variants with hypertension, diabetes and atherosclerosis in chronic renal failure patients undergoing hemodialysis.

Science.gov (United States)

Bagci, Binnur; Bagci, Gokhan; Huzmeli, Can; Sezgin, Ilhan; Ozdemir, Ozturk

2016-07-01

We aimed to investigate the associations of fractalkine receptor (CX3CR1) V249I, T280M and CCR5-59029 A/G gene polymorphisms in chronic renal failure (CRF) subjects undergoing hemodialysis and to evaluate possible associations of these polymorphisms with hypertension (HT), diabetes mellitus (DM) and atherosclerosis (AS). A total of 225 CRF subjects undergoing hemodialysis and 201 healthy controls were enrolled in the study. CRF subjects were divided into three major subgroups according to comorbidities including HT (n = 127), DM (n = 65) and AS (n = 33). Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism method. The II genotype and I allele frequencies of CX3CR1 V249I polymorphism were found significantly more frequent in CRF subjects, CRF subjects with DM and CRF subjects with AS compared with controls (p < 0.05 for all comparisons). G allele frequency of CCR5 polymorphism was found significantly more prevalent in CRF subjects with DM than that of controls. Further, GG genotype and G allele frequencies of CCR5 polymorphism were significantly more prevalent in CRF subjects with AS compared with controls (p < 0.05). We also explored these polymorphisms among CRF subjects with and without following comorbidities: HT, DM, AS. We found significant association between CRF subjects with HT and without HT in terms of genotype and allele frequencies of V249I polymorphism (p < 0.05). CX3CR1 T280M polymorphism was not found significantly different in none of the comparisons. These data demonstrate possible associations between CX3CR1 V249I and CCR5-59029 A/G polymorphisms and/or HT, DM and AS in CRF subjects.

Chronic stress-induced effects of corticosterone on brain: direct and indirect

NARCIS (Netherlands)

Dallman, M. F.; Akana, S. F.; Strack, A. M.; Scribner, K. S.; Pecoraro, N.; La Fleur, S. E.; Houshyar, H.; Gomez, F.

2004-01-01

Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their actions in brain and anterior pituitary (canonical feedback). With chronic stress, glucocorticoid feedback inhibition of ACTH secretion changes

Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

DEFF Research Database (Denmark)

Bor, M V; Sørensen, B S; Vinter-Jensen, L

2000-01-01

BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

Development of a web-based glaucoma registry at King Khaled Eye Specialist Hospital, Saudi Arabia: a cost-effective methodology.

Science.gov (United States)

Zaman, Babar; Khandekar, Rajiv; Al Shahwan, Sami; Song, Jonathan; Al Jadaan, Ibrahim; Al Jiasim, Leyla; Owaydha, Ohood; Asghar, Nasira; Hijazi, Amar; Edward, Deepak P

2014-01-01

In this brief communication, we present the steps used to establish a web-based congenital glaucoma registry at our institution. The contents of a case report form (CRF) were developed by a group of glaucoma subspecialists. Information Technology (IT) specialists used Lime Survey softwareTM to create an electronic CRF. A MY Structured Query Language (MySQL) server was used as a database with a virtual machine operating system. Two ophthalmologists and 2 IT specialists worked for 7 hours, and a biostatistician and a data registrar worked for 24 hours each to establish the electronic CRF. Using the CRF which was transferred to the Lime survey tool, and the MYSQL server application, data could be directly stored in spreadsheet programs that included Microsoft Excel, SPSS, and R-Language and queried in real-time. In a pilot test, clinical data from 80 patients with congenital glaucoma were entered into the registry and successful descriptive analysis and data entry validation was performed. A web-based disease registry was established in a short period of time in a cost-efficient manner using available resources and a team-based approach.

Effect of runway training on rat brain tyrosine hydroxylase: differential effect of continuous and partial reinforcement schedules.

Science.gov (United States)

Boarder, M R; Feldon, J; Gray, J A; Fillenz, M

1979-12-01

Previous experiments have implicated ascending noradrenergic systems in the development of the behavioural responses to different patterns of reward. In this report food deprived male Sprague--Dawley rats were trained to run a straight alley for good reward on a continuous reinforcement (CRF) or a partial reinforcement (PRF) schedule. Tyrosine hydroxylase measured in a partially solubilized preparation from hippocampus and hypothalamus at the end of acquisition was not different from controls, indicating that enzyme induction does not occur during either training schedules. However, hippocampal synaptosomal tyrosine hydroxylation rates from the CRF group was significantly higher than from either the PRF group or the handled controls. This indicates that at the end of the acquisition schedule the noradrenergic projection to hippocampus was more active in the CRF group than with the PRF group or the handled control.

Critical Success Factors of Suggestions Systems. | Marx | IFE ...

African Journals Online (AJOL)

A literature study approach is followed to establish which factors contribute to the success and failure of various suggestion systems. It was found ... The value of the paper firstly, shows the importance of creativity and innovation within the organisation's own culture and the framework of a formal suggestion system. Secondly ...

Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

Directory of Open Access Journals (Sweden)

M. J. Laye

2015-01-01

Full Text Available High levels of cardiovascular fitness (CRF and physical activity (PA are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI. Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg (similar-VO2max. The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max. Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy, improved exercise metabolism (lactate threshold, and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

Anti-stress effects of transcutaneous electrical nerve stimulation (TENS) on colonic motility in rats.

Science.gov (United States)

Yoshimoto, Sazu; Babygirija, Reji; Dobner, Anthony; Ludwig, Kirk; Takahashi, Toku

2012-05-01

Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic-pituitary-adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown. We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress. Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment. TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress. It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.

Cardiorespiratory fitness of a Brazilian regional sample distributed in different tables.

Science.gov (United States)

Belli, Karlyse Claudino; Callegaro, Carine C; Calegaro, Carine; Richter, Cleusa Maria; Klafke, Jonatas Zeni; Stein, Ricardo; Viecili, Paulo Ricardo Nazario

2012-09-01

Most classification tables of cardiorespiratory fitness (CRF) used in clinical practice are international and have not been validated for the Brazilian population. That can result in important discrepancies when that classification is extrapolated to our population. To assess the use of major CRF tables available in a Brazilian population sample of the Central High Plan of the state of Rio Grande do Sul (RS). This study assessed the retrospective data of 2,930 individuals, living in 36 cities of the Central High Plan of the state of RS, and considered the following: presence of risk factors for cardiovascular disease and estimated maximum oxygen consumption (VO2peak) values obtained through exercise test with Bruce protocol. To classify CRF, the individuals were distributed according to sex, inserted in their respective age groups in the Cooper, American Heart Association (AHA) and Universidade Federal de São Paulo (Unifesp) tables, and classified according to their VO2peak. Women had lower VO2peak values as compared with those of men (23.5 ± 8.5 vs. 31.7 ± 10.8 mL.kg-1.min-1, p Unifesp x AHA). Our findings indicate important discrepancy in the CRF classification levels of the tables assessed. Future studies could assess whether international tables could be used for the Brazilian population and populations of different regions of Brazil.

An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure

Science.gov (United States)

Zhang, Zhi-Hao; Vaziri, Nosratola D.; Wei, Feng; Cheng, Xian-Long; Bai, Xu; Zhao, Ying-Yong

2016-01-01

Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine-induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro-fibrotic proteins including TGF-β1, α-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF. PMID:26903149

The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster

DEFF Research Database (Denmark)

Cannell, Elizabeth; Dornan, Anthony J.; Halberg, Kenneth Agerlin

2016-01-01

Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin...

Underlying Factors for Practicality of the Production Control Systems

DEFF Research Database (Denmark)

Arica, Emrah; Strandhagen, Jan Ola; Hvolby, Hans-Henrik

2012-01-01

and communication technology, coordination and feedback, human factors and decision making, and measurement are the identified factors to be taken into account. Industrial interviews with three case companies, that are participating to the research program called The Norwegian Manufacturing Future (SFI NORMAN......This paper gives indications to important factors that must be considered for effectiveness of the production control systems under uncertainty. Five key factors have been identified by the literature study. Production schedule generation and execution approach under uncertainty, information...

Surveying the critical success factors of BPM-systems implementation.

NARCIS (Netherlands)

Ravesteyn, P.; Batenburg, R.

2010-01-01

Purpose – The purpose of this paper is to explore if there is a common ground for the definition of business process management (BPM) and BPM-systems, as well as the critical success factors (CSFs) for BPM-system implementation. A BPM-system implementation framework is validated that classifies the

Failure and factors of safety in piping system design

International Nuclear Information System (INIS)

Antaki, G.A.

1993-01-01

An important body of test and performance data on the behavior of piping systems has led to an ongoing reassessment of the code stress allowables and their safety margin. The codes stress allowables, and their factors of safety, are developed from limits on the incipient yield (for ductile materials), or incipient rupture (for brittle materials), of a test specimen loaded in simple tension. In this paper, we examine the failure theories introduced in the B31 and ASME III codes for piping and their inherent approximations compared to textbook failure theories. We summarize the evolution of factors of safety in ASME and B31 and point out that, for piping systems, it is appropriate to reconsider the concept and definition of factors of safety

Prognostic factors and scoring system for survival in colonic perforation.

Science.gov (United States)

Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

2005-01-01

No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis.

Science.gov (United States)

Sahore, Vishal; Sonker, Mukul; Nielsen, Anna V; Knob, Radim; Kumar, Suresh; Woolley, Adam T

2018-01-01

We have developed multichannel integrated microfluidic devices for automated preconcentration, labeling, purification, and separation of preterm birth (PTB) biomarkers. We fabricated multilayer poly(dimethylsiloxane)-cyclic olefin copolymer (PDMS-COC) devices that perform solid-phase extraction (SPE) and microchip electrophoresis (μCE) for automated PTB biomarker analysis. The PDMS control layer had a peristaltic pump and pneumatic valves for flow control, while the PDMS fluidic layer had five input reservoirs connected to microchannels and a μCE system. The COC layers had a reversed-phase octyl methacrylate porous polymer monolith for SPE and fluorescent labeling of PTB biomarkers. We determined μCE conditions for two PTB biomarkers, ferritin (Fer) and corticotropin-releasing factor (CRF). We used these integrated microfluidic devices to preconcentrate and purify off-chip-labeled Fer and CRF in an automated fashion. Finally, we performed a fully automated on-chip analysis of unlabeled PTB biomarkers, involving SPE, labeling, and μCE separation with 1 h total analysis time. These integrated systems have strong potential to be combined with upstream immunoaffinity extraction, offering a compact sample-to-answer biomarker analysis platform. Graphical abstract Pressure-actuated integrated microfluidic devices have been developed for automated solid-phase extraction, fluorescent labeling, and microchip electrophoresis of preterm birth biomarkers.

Hepatic vagotomy alters limbic and hypothalamic neuropeptide responses to insulin-dependent diabetes and voluntary lard ingestion

NARCIS (Netherlands)

la Fleur, Susanne E.; Manalo, Sotara L.; Roy, Monica; Houshyar, Hani; Dallman, Mary F.

2005-01-01

Hypothalamic anorexigenic [corticotropin-releasing factor (CRF) and proopiomelanocortin] peptides decrease and the orexigen, neuropeptide Y, increases with diabetic hyperphagia. However, when diabetic rats are allowed to eat lard (saturated fat) as well as chow, both caloric intake and hypothalamic

Sedentary Patterns, Physical Activity, and Cardiorespiratory Fitness in Association to Glycemic Control in Type 2 Diabetes Patients

Directory of Open Access Journals (Sweden)

Luís B. Sardinha

2017-04-01

Full Text Available Background: Sedentary behavior has been considered an independent risk factor for type-2 diabetes (T2D, with a negative impact on several physiological outcomes, whereas breaks in sedentary time (BST have been proposed as a viable solution to mitigate some of these effects. However, little is known about the independent associations of sedentary pursuits, physical activity, and cardiorespiratory fitness (CRF variables with glycemic control. We investigated the independent associations of total sedentary time, BST, moderate-to-vigorous physical activity (MVPA, and CRF with glycemic outcomes in patients with T2D.Methods: Total sedentary time, BST, and MVPA were assessed in 66 participants (29 women with T2D, using accelerometry. Glucose and insulin were measured during a mixed meal tolerance test, with the respective calculations of HOMA-IR and Matsuda index. Glycated hemoglobin (HbA1c was also analyzed. CRF was measured in a maximal treadmill test with breath-by-breath gases analysis. Multiple regressions were used for data analysis.Results: Regardless of CRF, total sedentary time was positively associated with HbA1c (β = 0.25, p = 0.044. Adjusting for MVPA, total sedentary time was related to fasting glucose (β = 0.32, p = 0.037. No associations between total sedentary time and the remaining glycemic outcomes, after adjusting for MVPA. BST had favorable associations with HOMA-IR (β = −0.28, p = 0.047 and fasting glucose (β = −0.25, p = 0.046, when adjusted for MVPA, and with HOMA-IR (β = −0.25, p = 0.036, Matsuda index (β = 0.26, p = 0.036, and fasting glucose (β = −0.22, p = 0.038, following adjustment for CRF. When adjusting for total sedentary time, only CRF yielded favorable associations with HOMA-IR (β = −0.29, p = 0.039, fasting glucose (β = −0.32, p = 0.012, and glucose at 120-min (β = −0.26, p = 0.035, and no associations were found for MVPA with none of the metabolic outcomes.Conclusion: The results from this

A Human Factors Approach to Bridging Systems and Introducing New Technologies

Science.gov (United States)

Kanki, Barbara G.

2011-01-01

The application of human factors in aviation has grown to cover a wide range of disciplines and methods capable of assessing human-systems integration at many levels. For example, at the individual level, pilot workload may be studied while at the team level, coordinated workload distribution may be the focal point. At the organizational level, the way in which individuals and teams are supported by training and standards, policies and procedures may introduce additional, relevant topics. A consideration of human factors at each level contributes to our understanding of successes and failures in pilot performance, but this system focused on the flight deck alone -- is only one part of the airspace system. In the FAA's NextGen plan to overhaul the National Airspace System (NAS), new capabilities will enhance flightdeck systems (pilots), flight operations centers (dispatchers) and air traffic control systems (controllers and air traffic managers). At a minimum, the current roles and responsibilities of these three systems are likely to change. Since increased automation will be central to many of the enhancements, the role of automation is also likely to change. Using NextGen examples, a human factors approach for bridging complex airspace systems will be the main focus of this presentation. It is still crucial to consider the human factors within each system, but the successful implementation of new technologies in the NAS requires an understanding of the collaborations that occur when these systems intersect. This human factors approach to studying collaborative systems begins with detailed task descriptions within each system to establish a baseline of the current operations. The collaborative content and context are delineated through the review of regulatory and advisory materials, letters of agreement, policies, procedures and documented practices. Field observations and interviews also help to fill out the picture. Key collaborative functions across systems

[Analysis on HIV-1 subtypes and transmission clusters in newly reported HIV/AIDS cases in Yiwu, Zhejiang Province, 2016].

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Zhang, J F; Yao, J M; Fan, Q; Chen, W J; Pan, X H; Ding, X B; Yang, J Z; Fu, T

2017-12-10

Objective: To understand the characteristics of distribution on HIV-1 subtypes and the transmission clusters in Yiwu in Zhejiang province. Methods: A cross-sectional study of molecular epidemiology was carried out on newly reported HIV/AIDS cases in Yiwu. RNA was extracted from 168 plasma samples, followed by RT-PCR and nest-PCR for pol gene amplification, sequencing, phylogenetic tree construction used for analyzing the subtypes and transmission clusters. Mutations on drug resistance was analyzed by CPR 6.0 online tool. Results: Subjects were mainly males (86.3%, 145/168), with average age as (39.1±13.4) years old and most of them were migrants (66.7%, 112/168). The major routes of transmission included homosexual (51.2%, 86/168) and heterosexual (48.8%, 82/168) contacts. The rate of success for sequence acquisition was 89.9% (151/168). The dominant subtypes showed as CRF01_AE (74, 49.0%) and CRF07_BC (64, 42.4%), followed by CRF08_BC (5, 3.3%), CRF55_01B (3, 2.0%), each case of subtype B, CRF45_cpx, CRF59_01B, CRF85_BC and URF (B/C). CRF45_cpx and CRF85_BC were discovered the first time in Zhejiang province. Twenty-six transmission clusters involving 65 cases were found, with the total clustered rate as 43.0% (65/151), in which the CRF01_AE clustered rate appeared as 54.1% (40/74), higher than that of CRF07_BC (21/64, 32.8%). The average size of cluster was 2.5 cases/cluster, with average size of cluster in CRF01_AE patients infected through heterosexual transmission as the largest (3.5 cases/cluster). The prevalence of transmitted drug resistance was 4.6% (7/151). Seven cases with surveillance drug resistant mutations (SDRM) were found, including 5 cases of M46L (3.3%), and one case of F77L or Y181C. Conclusion: HIV genetic diversity and a variety of transmission clusters had been noticed in this study area (Yiwu). Programs on monitoring the subtypes and transmission clusters should be continued and strengthened.

The affective dimension of pain as a risk factor for drug and alcohol addiction.

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LeBlanc, Dana M; McGinn, M Adrienne; Itoga, Christy A; Edwards, Scott

2015-12-01

Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction. Copyright © 2015 Elsevier Inc. All rights reserved.

The efficacy of the PACER versus the modified PACER test for assessing aerobic fitness in overweight children

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Overweight status is negatively related to health in children. Achieving adequate cardiorespiratory fitness (CRF) may reduce the health problems associated with pediatric overweight. It is important to accurately measure CRF. There is limited research concerning the validity of existing CRF field te...

Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study.

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Sanhueza, Jorge A; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A

2016-12-01

Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety ( 5HTT , CRH2R , ACE , NK1R , 5HT1AR and CRF-BP ) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms ( 5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.