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Sample records for sp nk-1 receptor

  1. The substance P/NK-1 receptor system: NK-1 receptor antagonists ...

    Indian Academy of Sciences (India)

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, ...

  2. The substance P/NK-1 receptor system: NK-1 receptor antagonists ...

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the ... NK-1 receptor may be a promising target in the treatment of cancer; NK-1 receptor antagonists could act as specific ...... mycin, ifosfamide, cisplatin) in MG-63 human osteosarcoma cells, but not in ...

  3. NK-1 receptor antagonists as anti-cancer drugs

    Indian Academy of Sciences (India)

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, ...

  4. Biological and Pharmacological Aspects of the NK1-Receptor

    Directory of Open Access Journals (Sweden)

    Susana Garcia-Recio

    2015-01-01

    Full Text Available The neurokinin 1 receptor (NK-1R is the main receptor for the tachykinin family of peptides. Substance P (SP is the major mammalian ligand and the one with the highest affinity. SP is associated with multiple processes: hematopoiesis, wound healing, microvasculature permeability, neurogenic inflammation, leukocyte trafficking, and cell survival. It is also considered a mitogen, and it has been associated with tumorigenesis and metastasis. Tachykinins and their receptors are widely expressed in various human systems such as the nervous, cardiovascular, genitourinary, and immune system. Particularly, NK-1R is found in the nervous system and in peripheral tissues and are involved in cellular responses such as pain transmission, endocrine and paracrine secretion, vasodilation, and modulation of cell proliferation. It also acts as a neuromodulator contributing to brain homeostasis and to sensory neuronal transmission associated with depression, stress, anxiety, and emesis. NK-1R and SP are present in brain regions involved in the vomiting reflex (the nucleus tractus solitarius and the area postrema. This anatomical localization has led to the successful clinical development of antagonists against NK-1R in the treatment of chemotherapy-induced nausea and vomiting (CINV. The first of these antagonists, aprepitant (oral administration and fosaprepitant (intravenous administration, are prescribed for high and moderate emesis.

  5. Biological and Pharmacological Aspects of the NK1-Receptor

    Science.gov (United States)

    Garcia-Recio, Susana; Gascón, Pedro

    2015-01-01

    The neurokinin 1 receptor (NK-1R) is the main receptor for the tachykinin family of peptides. Substance P (SP) is the major mammalian ligand and the one with the highest affinity. SP is associated with multiple processes: hematopoiesis, wound healing, microvasculature permeability, neurogenic inflammation, leukocyte trafficking, and cell survival. It is also considered a mitogen, and it has been associated with tumorigenesis and metastasis. Tachykinins and their receptors are widely expressed in various human systems such as the nervous, cardiovascular, genitourinary, and immune system. Particularly, NK-1R is found in the nervous system and in peripheral tissues and are involved in cellular responses such as pain transmission, endocrine and paracrine secretion, vasodilation, and modulation of cell proliferation. It also acts as a neuromodulator contributing to brain homeostasis and to sensory neuronal transmission associated with depression, stress, anxiety, and emesis. NK-1R and SP are present in brain regions involved in the vomiting reflex (the nucleus tractus solitarius and the area postrema). This anatomical localization has led to the successful clinical development of antagonists against NK-1R in the treatment of chemotherapy-induced nausea and vomiting (CINV). The first of these antagonists, aprepitant (oral administration) and fosaprepitant (intravenous administration), are prescribed for high and moderate emesis. PMID:26421291

  6. The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

    Science.gov (United States)

    Barbier, Estelle; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Juergens, Nathan; Park, Paula E; Misra, Kaushik K; Cheng, Kejun; Rice, Kenner C; Schank, Jesse; Schulteis, Gery; Koob, George F; Heilig, Markus

    2013-01-01

    Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1 h: ShA) or long (12 h: LgA) access to intravenous heroin self-administration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxiety-like behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward- and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects. PMID:23303056

  7. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: A New Therapeutic Approach

    International Nuclear Information System (INIS)

    Muñoz, Miguel; Coveñas, Rafael

    2015-01-01

    Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert an antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC

  8. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: A New Therapeutic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Miguel, E-mail: mmunoz@cica.es [Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, 41013 Sevilla (Spain); Coveñas, Rafael [Laboratory of Neuroanatomy of the Peptidergic System (Lab. 14), Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, 37008 Salamanca (Spain)

    2015-07-06

    Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert an antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC.

  9. Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells.

    Science.gov (United States)

    Thomas, Ajit G; Stathis, Marigo; Rojas, Camilo; Slusher, Barbara S

    2014-08-01

    Current therapy for chemotherapy-induced nausea and vomiting includes the use of both 5-HT3 and NK1 receptor antagonists. Acute emesis has largely been alleviated with the use of 5-HT3 receptor antagonists, while an improvement in preventing delayed emesis has been achieved with NK1 receptor antagonists. Delayed emesis, however, remains a problem with a significant portion of cancer patients receiving highly emetogenic chemotherapy. Like other drugs in its class, palonosetron, a 5-HT3 receptor antagonist, has shown efficacy against acute emesis. However, palonosetron has also shown consistent improvement in the suppression of delayed emesis. Since both 5-HT3 and NK1 receptor antagonists are often simultaneously administered to patients, the question remains if palonosetron's effect on delayed emesis would remain distinct when co-administered with an NK1 receptor antagonist. Recent mechanistic studies using NG108-15 cells have shown that palonosetron and netupitant, an NK1 receptor antagonist currently in phase 3 clinical trials, exhibited synergistic effects when inhibiting the substance P response. The present studies showed that both netupitant and palonosetron-induced NK1 receptor internalization in NG108-15 cells and that when used together receptor internalization was additive. Palonosetron-induced NK1 receptor internalization was dependent on the presence of the 5-HT3 receptor. Results provide a possible explanation for palonosetron's enhancement of the inhibition of the SP response and suggest that the effect of palonosetron and NK1 receptor antagonists on prevention of delayed emesis could be additive.

  10. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: a New Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Miguel Muñoz

    2015-07-01

    Full Text Available Pancreatic cancer (PC is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1 receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase, the peptide substance P (SP—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert An antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis, and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC.

  11. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs

    OpenAIRE

    Palea, Stefano; Guilloteau, V?ronique; Rekik, Mo?z; Lovati, Emanuela; Guerard, Marc; Guardia, Maria-Alba; Lluel, Philippe; Pietra, Claudio; Yoshiyama, Mitsuharu

    2016-01-01

    Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant) on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe). Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060) were studie...

  12. Functional characterization of tachykinin NK1 receptors in the mouse uterus

    Science.gov (United States)

    Patak, Eva; Pennefather, Jocelyn N; Fleming, Anna; Story, Margot E

    2002-01-01

    Contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of oestrogen-treated mice. In the presence of thiorphan, (3 μM), captopril (10 μM) and bestatin (10 μM), substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) produced concentration-related contractions of uterine preparations. The order of potency was SP ⩾NKA>NKB. Neither atropine (0.1 μM) nor l-NOLA (100 μM), nor indomethacin (10 μM) alone or in combination with either ranitidine (10 μM) or mepyramine (10 μM), affected responses to SP. These findings indicate that SP actions are not mediated or modulated through the release of acetylcholine, nitric oxide, prostanoids or histamine. In the presence of peptidase inhibitors, the tachykinin NK1 receptor-selective agonist [Sar9Met(O2)11]SP, produced a concentration-dependent contractile effect. The tachykinin NK2 and NK3 receptor-selective agonists [Lys5MeLeu9Nle10]NKA(4-10) and [MePhe7]NKB were relatively inactive. The potencies of SP analogues in which Glu replaced Gln5 and/or Gln6 were similar to that of SP. The tachykinin NK1 receptor-selective antagonist, SR140333 (10 nM), alone or combined with the tachykinin NK2 receptor-selective antagonist, SR48968 (10 nM), shifted log concentration curves to SP, NKA and NKB to the right. SR140333 (10 nM) reduced the effect of [Sar9Met(O2)11]SP. SR48968 did not affect responses to SP or [Sar9Met(O2)11]SP, but reduced the effect of higher concentrations of NKA and shifted the log concentration-response curve to NKB to the right. The tachykinin NK3 receptor-selective antagonist, SR 142801 (0.3 μM), had little effect on responses to SP and NKB. We conclude that the tachykinin NK1 receptor mediates contractile effects of SP, NKA and NKB and [Sar9Met(O2)11]SP in myometrium from the oestrogen-primed mouse. The tachykinin NK2 receptor may also participate in the responses to NKA and NKB. PMID:12466234

  13. NK1 receptor blockade is ineffective in improving outcome following a balloon compression model of spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Anna Victoria Leonard

    Full Text Available The neuropeptide substance P (SP is a well-known mediator of neurogenic inflammation following a variety of CNS disorders. Indeed, inhibition of SP through antagonism of its receptor, the tachykinin NK1 receptor, has been shown to be beneficial following both traumatic brain injury and stroke. Such studies demonstrated that administration of an NK1 receptor antagonist reduced blood-brain-barrier permeability, edema development and improved functional outcome. Furthermore, our recent studies have demonstrated a potential role for SP in mediating neurogenic inflammation following traumatic spinal cord injury (SCI. Accordingly, the present study investigates whether inhibition of SP may similarly play a neuroprotective role following traumatic SCI. A closed balloon compression injury was induced at T10 in New Zealand White rabbits. At 30 minutes post-injury an NK1 receptor antagonist was administered intravenously. Animals were thereafter assessed for blood spinal cord barrier (BSCB permeability, spinal water content (edema, intrathecal pressure (ITP, and histological and functional outcome from 5 hours to 2 weeks post-SCI. Administration of an NK1 receptor antagonist was not effective in reducing BSCB permeability, edema, ITP, or functional deficits following SCI. We conclude that SP mediated neurogenic inflammation does not seem to play a major role in BSCB disruption, edema development and consequential tissue damage seen in acute traumatic SCI. Rather it is likely that the severe primary insult and subsequent hemorrhage may be the key contributing factors to ongoing SCI injury.

  14. Kinetic binding and activation profiles of endogenous tachykinins targeting the NK1 receptor.

    Science.gov (United States)

    Nederpelt, I; Bleeker, D; Tuijt, B; IJzerman, A P; Heitman, L H

    2016-10-15

    Ligand-receptor binding kinetics (i.e. association and dissociation rates) are emerging as important parameters for drug efficacy in vivo. Awareness of the kinetic behavior of endogenous ligands is pivotal, as drugs often have to compete with those. The binding kinetics of neurokinin 1 (NK1) receptor antagonists have been widely investigated while binding kinetics of endogenous tachykinins have hardly been reported, if at all. Therefore, the aim of this research was to investigate the binding kinetics of endogenous tachykinins and derivatives thereof and their role in the activation of the NK1 receptor. We determined the binding kinetics of seven tachykinins targeting the NK1 receptor. Dissociation rate constants (k off ) ranged from 0.026±0.0029min -1 (Sar 9 ,Met(O 2 ) 11 -SP) to 0.21±0.015min -1 (septide). Association rate constants (k on ) were more diverse: substance P (SP) associated the fastest with a k on value of 0.24±0.046nM -1 min -1 while neurokinin A (NKA) had the slowest association rate constant of 0.001±0.0002nM -1 min -1 . Kinetic binding parameters were highly correlated with potency and maximal response values determined in label-free impedance-based experiments on U-251 MG cells. Our research demonstrates large variations in binding kinetics of tachykinins which correlate to receptor activation. These findings provide new insights into the ligand-receptor interactions of tachykinins and underline the importance of measuring binding kinetics of both drug candidates and competing endogenous ligands. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Tachykinin NK1 and NK2 receptors mediate inhibitory vs excitatory motor responses in human isolated corpus cavernosum and spongiosum

    Science.gov (United States)

    Patacchini, Riccardo; Barbagli, Guido; Palminteri, Enzo; Lazzeri, Massimo; Turini, Damiano; Maggi, Carlo Alberto

    2002-01-01

    Motor effects produced by tachykinins were studied in human isolated corpus spongiosum and cavernosum. In quiescent preparations neurokinin A caused potent contractions (pD2=8.3 – 7.9 respectively) prevented by the NK2 receptor-selective antagonist nepadutant, whereas [Sar9]SP sulfone and senktide (NK1 and NK3 receptor-selective agonists) produced no effect or spare contractions. In KCl-precontracted corpus spongiosum septide (pD2=7.1) and [Sar9]SP sulfone (pD2=7.7) produced tetrodotoxin-resistant relaxations, abolished by the tachykinin NK1 receptor-selective antagonist SR 140333. [Sar9]SP sulfone (1 μM) produced similar relaxations in precontracted corpus cavernosum. Electrical field stimulation (EFS) elicited tetrodotoxin-sensitive relaxations, which were additive to those produced by [Sar9]SP sulfone. Nω-nitro-L-arginine (L-NOARG) totally prevented both [Sar9]SP sulfone- and EFS-induced relaxations. These results show that tachykinin NK1 and NK2 receptors mediate opposite motor effects in human penile tissues, suggesting a possible modulatory role of tachykinins on smooth muscle tone in these organs. PMID:11906947

  16. Peristalsis regulation by tachykinin NK1 receptors in the rabbit isolated distal colon.

    Science.gov (United States)

    Onori, Luciano; Aggio, Annalisa; Taddei, Gennaro; Loreto, Maria F; Ciccocioppo, Rachele; Vicini, Riccardo; Tonini, Marcello

    2003-08-01

    In the gastrointestinal tract, tachykinin NK1 receptors are widely distributed in a number of neuronal and nonneuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as noncholinergic excitatory transmitters, the influence of NK1 receptors in the regulation of peristalsis is not known. The selective NK1-receptor antagonists SR-140333 (0.3 and 1 nM) and MEN-10930 (0.3-10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR-140333 was prevented by N(omega)-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, indicating that NK1 receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK1-receptor agonist septide (3-10 nM) significantly inhibited colonic propulsion. In the presence of L-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK1 receptors.

  17. Novel method for the study of receptor Ca2+ signalling exemplified by the NK1 receptor

    DEFF Research Database (Denmark)

    Heding, A; Elling, C E; Schwartz, T W

    2002-01-01

    We have used a novel technology (NovoStar from BMG Labtechnologies) for the study of the Ca2+ signalling of the human tackykinin NK1 (hNK-I receptor). The NovoStar is a microplate reader based on fluorescence and luminescence. The instrument implements a robotic pipettor arm and two microplate...... carriers, typically one for samples and one for cells. The robotic pipettor arm can transfer sample (agonist or antagonist) from the sample plate or other liquid containers to the cell plate, facilitating the study of Ca2+ signalling to such a degree that the instrument can be used for Medium Throughput...

  18. Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens.

    Science.gov (United States)

    Jordan, Karin; Gralla, Richard; Rizzi, Giada; Kashef, Kimia

    2016-11-01

    Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting. One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated. Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %). Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin.

  19. Development and labeling of EP-00652218 analogues, NK1 receptors antagonist, for PET and SPECT imaging

    International Nuclear Information System (INIS)

    Bagot-Gueret, C.

    2001-12-01

    The aim of this work was the synthesis and radiosynthesis of compounds labelled either with a positron emitter (fluorine-18, t 1/2 = 109 minutes) or with a gamma emitter (iodine-123, t 1/2 = 16.2 hours), for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) studies. EP-00652218 is a novel potent antagonist, with a sub-nano-molar affinity towards the NK 1 receptors. In order to develop ligands that could be used either in PET or SPECT, we undertook the synthesis of poly-halogenated analogues of EP-00652218. Compound 17 was synthesized through two different synthetic pathways. A series of original compounds has been obtained from compound 17 by halogen exchanges on the naphthyridone or the benzene ring. These molecules were tested to determine their in vitro affinity towards NK 1 receptors. Compound 21 was labelled with fluorine-18 in 135 minutes and with a 20% radiochemical yield. Compound 26 was radioiodinated following reaction with Na 125 I (t 1/2 = 60.14 days) in a 18% radiochemical yield. Despite expectation, these analogues of EP-00652218 exhibited an insufficient affinity for NK 1 receptors (IC 50 = 10 -7 M) and thus unlikely usable for in vivo studies with PET and SPECT. (author)

  20. Molecular mechanisms of 5-HT(3) and NK(1) receptor antagonists in prevention of emesis.

    Science.gov (United States)

    Rojas, Camilo; Raje, Mithun; Tsukamoto, Takashi; Slusher, Barbara S

    2014-01-05

    Nausea and vomiting are major side effects of chemotherapy and one key reason for non-compliance with cancer treatment. The introduction of 5-HT3 receptor antagonists in the 1990s was a major advance in the prevention of acute emesis, and highlighted the critical role of serotonin in the emetic response. The next major advance in the treatment of chemotherapy induced nausea and vomiting (CINV) occurred in 2003 with the introduction of aprepitant, a tachykinin 1 (NK1) receptor antagonist. Aprepitant not only reduced acute emesis but also helped in the reduction of delayed emesis. Also in 2003, palonosetron, a second generation 5-HT3 receptor antagonist became available. Unlike the first generation 5-HT3 receptor antagonists, palonosetron demonstrated efficacy in preventing both acute and delayed emesis. This review focuses on the mechanism of action of 5-HT3 and NK1 receptor antagonists in acute and delayed CINV prevention. We discuss first, the medicinal chemistry that led to the discovery of these antagonists to underline their common structural features. Second, we discuss their performance in the clinic and what it tells us about the emetic response. Finally, we present recent mechanistic studies that help provide a rationale for efficacy differences between palonosetron and other 5-HT3 receptor antagonists in the clinic. In vitro and in vivo experiments have shown that palonosetron can inhibit substance P-mediated responses, presumably through its unique interactions with the 5-HT3 receptor. The crossroads of acute and delayed emesis seem to include interactions among the 5-HT3 and NK1 receptor signaling pathways and inhibitions of these interactions could lead to improved treatment of CINV. © 2013 Elsevier B.V. All rights reserved.

  1. Involvement of tachykinins and NK1 receptor in the joint inflammation with collagen type II-specific monoclonal antibody-induced arthritis in mice.

    Science.gov (United States)

    Makino, Akira; Sakai, Atsushi; Ito, Hiromoto; Suzuki, Hidenori

    2012-01-01

    Rheumatoid arthritis (RA) is a chronic multisystem disease characterized by persistent joint inflammation associated with severe pain. Because RA is an immune-mediated joint disease and because type II collagen is considered an autoantigen, rodent models of arthritis using collagen type II-specific monoclonal antibodies are valuable for studying the pathogenesis of autoimmune arthritis and for evaluating therapeutic strategies. The tachykinin family peptides, substance P (SP) and hemokinin-1 (HK-1), are expressed in the nervous systems and in many peripheral organs and immunocompetent cells and activate tachykinin NK1 receptors with similar affinities. NK1 receptors are involved in the inflammation and hyperalgesia associated with a variety of inflammatory diseases. In the present study, we examined the involvement of SP and HK-1 in the joint inflammation and hyperalgesia in a collagen antibody-induced arthritis (CAIA) model in mice. The messenger RNA expression levels of the TAC1 gene encoding SP and of the TAC4 gene encoding HK-1 were decreased in the dorsal root ganglia and spinal cord at the peak of the inflammatory symptoms in CAIA. Systemic injection of an NK1 receptor antagonist, WIN 51708, significantly inhibited the joint swelling, but not the mechanical allodynia, on day 7 in CAIA mice. The messenger RNA expression levels of TAC1 and TAC4 in the dorsal root ganglia and dorsal spinal cord were unaffected by treatment with WIN 51708. These findings suggest that tachykinins and NK1 receptors play a key role in joint inflammation, rather than in nociceptive sensitization, in CAIA.

  2. Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists.

    Science.gov (United States)

    Bošnjak, Snežana M; Gralla, Richard J; Schwartzberg, Lee

    2017-05-01

    Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK 1 RAs when combined with 5-HT 3 RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK 1 RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK 1 RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.

  3. Role of the tachykinin NK1 receptor in a murine model of cigarette smoke-induced pulmonary inflammation

    Directory of Open Access Journals (Sweden)

    Brusselle Guy G

    2009-05-01

    Full Text Available Abstract Background The tachykinins, substance P and neurokinin A, present in sensory nerves and inflammatory cells such as macrophages and dendritic cells, are considered as pro-inflammatory agents. Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD and increased tachykinin levels are recovered from the airways of COPD patients. The aim of our study was to clarify the involvement of the tachykinin NK1 receptor, the preferential receptor for substance P, in cigarette smoke (CS-induced pulmonary inflammation and emphysema in a mouse model of COPD. Methods Tachykinin NK1 receptor knockout (NK1-R-/- mice and their wild type controls (all in a mixed 129/sv-C57BL/6 background were subjected to sub acute (4 weeks or chronic (24 weeks exposure to air or CS. 24 hours after the last exposure, pulmonary inflammation and development of emphysema were evaluated. Results Sub acute and chronic exposure to CS resulted in a substantial accumulation of inflammatory cells in the airways of both WT and NK1-R-/- mice. However, the CS-induced increase in macrophages and dendritic cells was significantly impaired in NK1-R-/- mice, compared to WT controls, and correlated with an attenuated release of MIP-3α/CCL20 and TGF-β1. Chronic exposure to CS resulted in development of pulmonary emphysema in WT mice. NK1-R-/- mice showed already enlarged airspaces upon air-exposure. Upon CS-exposure, the NK1-R-/- mice did not develop additional destruction of the lung parenchyma. Moreover, an impaired production of MMP-12 by alveolar macrophages upon CS-exposure was observed in these KO mice. In a pharmacological validation experiment using the NK1 receptor antagonist RP 67580, we confirmed the protective effect of absence of the NK1 receptor on CS-induced pulmonary inflammation. Conclusion These data suggest that the tachykinin NK1 receptor is involved in the accumulation of macrophages and

  4. Role of the tachykinin NK1 receptor in a murine model of cigarette smoke-induced pulmonary inflammation.

    Science.gov (United States)

    De Swert, Katelijne O; Bracke, Ken R; Demoor, Tine; Brusselle, Guy G; Joos, Guy F

    2009-05-15

    The tachykinins, substance P and neurokinin A, present in sensory nerves and inflammatory cells such as macrophages and dendritic cells, are considered as pro-inflammatory agents. Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and increased tachykinin levels are recovered from the airways of COPD patients. The aim of our study was to clarify the involvement of the tachykinin NK1 receptor, the preferential receptor for substance P, in cigarette smoke (CS)-induced pulmonary inflammation and emphysema in a mouse model of COPD. Tachykinin NK1 receptor knockout (NK1-R-/-) mice and their wild type controls (all in a mixed 129/sv-C57BL/6 background) were subjected to sub acute (4 weeks) or chronic (24 weeks) exposure to air or CS. 24 hours after the last exposure, pulmonary inflammation and development of emphysema were evaluated. Sub acute and chronic exposure to CS resulted in a substantial accumulation of inflammatory cells in the airways of both WT and NK1-R-/- mice. However, the CS-induced increase in macrophages and dendritic cells was significantly impaired in NK1-R-/- mice, compared to WT controls, and correlated with an attenuated release of MIP-3alpha/CCL20 and TGF-beta1. Chronic exposure to CS resulted in development of pulmonary emphysema in WT mice. NK1-R-/- mice showed already enlarged airspaces upon air-exposure. Upon CS-exposure, the NK1-R-/- mice did not develop additional destruction of the lung parenchyma. Moreover, an impaired production of MMP-12 by alveolar macrophages upon CS-exposure was observed in these KO mice. In a pharmacological validation experiment using the NK1 receptor antagonist RP 67580, we confirmed the protective effect of absence of the NK1 receptor on CS-induced pulmonary inflammation. These data suggest that the tachykinin NK1 receptor is involved in the accumulation of macrophages and dendritic cells in the airways upon CS-exposure and in the

  5. NK1 receptor fused to beta-arrestin displays a single-component, high-affinity molecular phenotype.

    Science.gov (United States)

    Martini, Lene; Hastrup, Hanne; Holst, Birgitte; Fraile-Ramos, Alberto; Marsh, Mark; Schwartz, Thue W

    2002-07-01

    Arrestins are cytosolic proteins that, upon stimulation of seven transmembrane (7TM) receptors, terminate signaling by binding to the receptor, displacing the G protein and targeting the receptor to clathrin-coated pits. Fusion of beta-arrestin1 to the C-terminal end of the neurokinin NK1 receptor resulted in a chimeric protein that was expressed to some extent on the cell surface but also accumulated in transferrin-labeled recycling endosomes independently of agonist stimulation. As expected, the fusion protein was almost totally silenced with respect to agonist-induced signaling through the normal Gq/G11 and Gs pathways. The NK1-beta-arrestin1 fusion construct bound nonpeptide antagonists with increased affinity but surprisingly also bound two types of agonists, substance P and neurokinin A, with high, normal affinity. In the wild-type NK1 receptor, neurokinin A (NKA) competes for binding against substance P and especially against antagonists with up to 1000-fold lower apparent affinity than determined in functional assays and in homologous binding assays. When the NK1 receptor was closely fused to G proteins, this phenomenon was eliminated among agonists, but the agonists still competed with low affinity against antagonists. In contrast, in the NK1-beta-arrestin1 fusion protein, all ligands bound with similar affinity independent of the choice of radioligand and with Hill coefficients near unity. We conclude that the NK1 receptor in complex with arrestin is in a high-affinity, stable, agonist-binding form probably best suited to structural analysis and that the receptor can display binding properties that are nearly theoretically ideal when it is forced to complex with only a single intracellular protein partner.

  6. Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma

    NARCIS (Netherlands)

    Boot, Johan D.; de Haas, Sanne; Tarasevych, Svetlana; Roy, Christine; Wang, Lin; Amin, Dilip; Cohen, Judith; Sterk, Peter J.; Miller, Barry; Paccaly, Anne; Burggraaf, Jacobus; Cohen, Adam F.; Diamant, Zuzana

    2007-01-01

    RATIONALE: The tachykinins substance P and neurokinin A (NKA) are implicated in the pathophysiology of asthma. Objective: We tested the safety, tolerability, and pharmacologic and biological efficacy of a tachykinin NK(1)/NK(2) receptor antagonist, AVE5883, in patients with asthma in two

  7. Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression

    NARCIS (Netherlands)

    Czeh, B; Pudovkina, O; van der Hart, MGC; Simon, M; Heilbronner, U; Michaelis, T; Watanabe, T; Frahm, J; Fuchs, E

    Rationale: Substance P antagonists have been proposed as candidates for a new class of antidepressant compounds. Objectives: We examined the effects of SLV-323, a novel neurokinin 1 receptor (NK1R) antagonist, in the chronic psychosocial stress paradigm of adult male tree shrews. Methods: Animals

  8. A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Fuglsang, S.; Madsen, Jan Lysgård

    2008-01-01

    BACKGROUND: Little is known about the role of tachykinins on human gastrointestinal motility and no data exist on the possible effect of an NK1 receptor antagonist. AIM: To examine the effect of an antiemetic dose of the selective NK1 receptor antagonist aprepitant on gastrointestinal propulsion...

  9. Two active molecular phenotypes of the tachykinin NK1 receptor revealed by G-protein fusions and mutagenesis

    DEFF Research Database (Denmark)

    Holst, B; Hastrup, H; Raffetseder, U

    2001-01-01

    either Galpha(s) or Galpha(q) and the NK1 receptor with a truncated tail, which secured non-promiscuous G-protein interaction, demonstrated monocomponent agonist binding closely corresponding to either of the two affinity states found in the wild-type receptor. High affinity binding of both substance P...... and neurokinin A was observed in the tail-truncated Galpha(s) fusion construct, whereas the lower affinity component was displayed by the tail-truncated Galpha(q) fusion. The elusive difference between the affinity determined in heterologous versus homologous binding assays for substance P and especially...... in the tail-truncated Galpha(q) fusion construct. Thus, the heterogenous pharmacological phenotype displayed by the NK1 receptor is a reflection of the occurrence of two active conformations or molecular phenotypes representing complexes with the Galpha(s) and Galpha(q) species, respectively. We propose...

  10. Two active molecular phenotypes of the tachykinin NK1 receptor revealed by G-protein fusions and mutagenesis.

    Science.gov (United States)

    Holst, B; Hastrup, H; Raffetseder, U; Martini, L; Schwartz, T W

    2001-06-08

    The NK1 neurokinin receptor presents two non-ideal binding phenomena, two-component binding curves for all agonists and significant differences between agonist affinity determined by homologous versus heterologous competition binding. Whole cell binding with fusion proteins constructed between either Galpha(s) or Galpha(q) and the NK1 receptor with a truncated tail, which secured non-promiscuous G-protein interaction, demonstrated monocomponent agonist binding closely corresponding to either of the two affinity states found in the wild-type receptor. High affinity binding of both substance P and neurokinin A was observed in the tail-truncated Galpha(s) fusion construct, whereas the lower affinity component was displayed by the tail-truncated Galpha(q) fusion. The elusive difference between the affinity determined in heterologous versus homologous binding assays for substance P and especially for neurokinin A was eliminated in the G-protein fusions. An NK1 receptor mutant with a single substitution at the extracellular end of TM-III-(F111S), which totally uncoupled the receptor from Galpha(s) signaling, showed binding properties that were monocomponent and otherwise very similar to those observed in the tail-truncated Galpha(q) fusion construct. Thus, the heterogenous pharmacological phenotype displayed by the NK1 receptor is a reflection of the occurrence of two active conformations or molecular phenotypes representing complexes with the Galpha(s) and Galpha(q) species, respectively. We propose that these molecular forms do not interchange readily, conceivably because of the occurrence of microdomains or "signal-transductosomes" within the cell membrane.

  11. Casopitant: a novel NK1-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Christina Ruhlmann

    2009-05-01

    Full Text Available Christina Ruhlmann, Jørn HerrstedtOdense University Hospital, Department of Oncology, Odense, DenmarkAbstract: Chemotherapy-induced nausea and vomiting (CINV are among the most feared and distressing symptoms experienced by patients with cancer. The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT3- and neurokinin (NK1 receptors in the emetic reflex arch. This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors. These drugs have had a huge impact in the protection from chemotherapy-induced vomiting, whereas the effect on nausea seems to be limited. The first NK1 receptor antagonist, aprepitant, became clinically available in 2003, and casopitant, the second in this class of antiemetics, has now completed phase III trials. This review delineates the properties and clinical use of casopitant in the prevention of CINV.Keywords: casopitant, GW679769, NK1 receptor antagonist, chemotherapy, emesis

  12. NETUPITANT, A POTENT AND HIGHLY SELECTIVE NK1 RECEPTOR ANTAGONIST, ALLEVIATES ACETIC ACID-INDUCED BLADDER OVERACTIVITY IN ANESTHETIZED GUINEA-PIGS

    Directory of Open Access Journals (Sweden)

    Stefano Palea

    2016-08-01

    Full Text Available Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe. Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060 were studied in anesthetized guinea-pigs using two experimental models, the isovolumetric bladder contractions and a model of bladder overactivity induced by intravesical administration of acetic acid (AA. Methods and Results. Detrusor muscle strips were mounted in 5 mL organ baths and isometric contractions to cumulative concentrations of SP-OME were recorded before and after incubation with increasing concentrations of netupitant. In anesthetized female guinea-pigs, reflex bladder activity was examined under isovolumetric conditions with the bladder distended with saline or during cystometry using intravesical infusion of acetic acid (AA. After a 30 min stabilization period, netupitant (0.1-3 mg/kg, i.v. or L-733,060 (3-10 mg/kg, i.v. were administered. In the detrusor muscle, netupitant produced a concentration-dependent inhibition (mean pKB = 9.24 of the responses to SP-OMe. Under isovolumetric conditions, netupitant or L-733,060 reduced bladder contraction frequency in a dose-dependent manner, but neither drug changed bladder contraction amplitude. In the AA model, netupitant dose-dependently increased intercontraction interval (ICI but had no effect on the amplitude of micturition (AM. L-733,060 dose-dependently increased ICI also but this effect was paralleled by a significant reduction of AM. Conclusion. Netupitant decreases the frequency of reflex bladder contractions without altering their amplitude, suggesting that this drug targets the afferent limb of the

  13. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs.

    Science.gov (United States)

    Palea, Stefano; Guilloteau, Véronique; Rekik, Moéz; Lovati, Emanuela; Guerard, Marc; Guardia, Maria-Alba; Lluel, Philippe; Pietra, Claudio; Yoshiyama, Mitsuharu

    2016-01-01

    Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant) on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe). Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060) were studied in anesthetized guinea-pigs using two experimental models, the isovolumetric bladder contractions and a model of bladder overactivity induced by intravesical administration of acetic acid (AA). Methods and Results. Detrusor muscle strips were mounted in 5 mL organ baths and isometric contractions to cumulative concentrations of SP-OME were recorded before and after incubation with increasing concentrations of netupitant. In anesthetized female guinea-pigs, reflex bladder activity was examined under isovolumetric conditions with the bladder distended with saline or during cystometry using intravesical infusion of AA. After a 30 min stabilization period, netupitant (0.1-3 mg/kg, i.v.) or L-733,060 (3-10 mg/kg, i.v.) were administered. In the detrusor muscle, netupitant produced a concentration-dependent inhibition (mean pKB = 9.24) of the responses to SP-OMe. Under isovolumetric conditions, netupitant or L-733,060 reduced bladder contraction frequency in a dose-dependent manner, but neither drug changed bladder contraction amplitude. In the AA model, netupitant dose-dependently increased intercontraction interval (ICI) but had no effect on the amplitude of micturition (AM). L-733,060 dose-dependently increased ICI also but this effect was paralleled by a significant reduction of AM. Conclusion. Netupitant decreases the frequency of reflex bladder contractions without altering their amplitude, suggesting that this drug targets the afferent limb of the micturition reflex circuit

  14. Septide and neurokinin A are high-affinity ligands on the NK-1 receptor: evidence from homologous versus heterologous binding analysis.

    Science.gov (United States)

    Hastrup, H; Schwartz, T W

    1996-12-16

    The three main tachykinins, substance P, neurokinin A (NKA), and neurokinin B, are believed to be selective ligands for respectively the NK-1, NK-2 and NK-3 receptors. However, NKA also has actions which cannot be mediated through its normal NK-2 receptor and the synthetic peptide [pGlu6,Pro9]-Substance P9-11--called septide--is known to have tachykinin-like actions despite its apparent lack of binding to any known tachykinin receptor. In the cloned NK-1 receptor expressed in COS-7 cells NKA and septide as expected were poor competitors for radiolabeled substance P. However, by using radiolabeled NKA and septide directly, it was found that both peptides in homologous binding assays as well as in competition against each other in fact bound to the NK-1 receptor with high affinity: Kd values of 0.51 +/- 0.15 nM (NKA) and 0.55 +/- 0.03 nM (septide). It is concluded that NKA and septide are high-affinity ligands for the NK-1 receptor but that they are poor competitors for substance P, which in contrast competes very well for binding with both NKA and septide.

  15. Investigating racial disparities in use of NK1 receptor antagonists to prevent chemotherapy-induced nausea and vomiting among women with breast cancer.

    Science.gov (United States)

    Check, Devon K; Reeder-Hayes, Katherine E; Basch, Ethan M; Zullig, Leah L; Weinberger, Morris; Dusetzina, Stacie B

    2016-04-01

    Chemotherapy-induced nausea and vomiting (CINV) is a major concern for cancer patients and, if uncontrolled, can seriously compromise quality of life (QOL) and other treatment outcomes. Because of the expense of antiemetic medications used to prevent CINV (particularly oral medications filled through Medicare Part D), disparities in their use may exist. We used 2006-2012 SEER-Medicare data to evaluate the use of neurokinin-1 receptor antagonists (NK1s), a potent class of antiemetics, among black and white women initiating highly emetogenic chemotherapy for the treatment of early-stage breast cancer. We used modified Poisson regression to assess the relationship between race and (1) any NK1 use, (2) oral NK1 (aprepitant) use, and (3) intravenous NK1 (fosaprepitant) use. We report adjusted risk ratios (aRR) and 95 % confidence intervals (CI). The study included 1130 women. We observed racial disparities in use of any NK1 (aRR: 0.68, 95 % CI 0.51-0.91) and in use of oral aprepitant specifically (aRR: 0.54, 95 % CI 0.35-0.83). We did not observe disparities in intravenous fosaprepitant use. After controlling for variables related to socioeconomic status, disparities in NK1 and aprepitant use were reduced but not eliminated. We found racial disparities in women's use of oral NK1s for the prevention of CINV. These disparities may be partly explained by racial differences in socioeconomic status, which may translate into differential ability to afford the medication.

  16. Role of tachykinin NK1 and NK2 receptors in allergen-induced early and late asthmatic reactions, airway hyperresponsiveness, and airway inflammation in conscious, unrestrained guinea pigs

    NARCIS (Netherlands)

    Schuiling, M; Zuidhof, A.B; Zaagsma, Hans; Meurs, Herman

    Using a guinea pig model of allergic asthma, we investigated the effects of the inhaled, highly selective nonpeptide tachykinin NK1 and NK2 receptor antagonists SR 140333 and SR 48968, respectively, on allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR)

  17. Involvement of tachykinin NK1 receptor in the development of allergen-induced airway hyperreactivity and airway inflammation in conscious, unrestrained guinea pigs

    NARCIS (Netherlands)

    Schuiling, M; Zuidhof, A.B; Zaagsma, Hans; Meurs, Herman

    It has been suggested that tachykinin NK1 receptor-mediated neurogenic inflammation, characterized by microvascular leakage, mucus secretion, and infiltration and activation of inflammatory cells in the airways, may be involved in allergic asthma. Therefore, in a guinea pig model of allergic asthma,

  18. Partial agonism through a zinc-Ion switch constructed between transmembrane domains III and VII in the tachykinin NK(1) receptor

    DEFF Research Database (Denmark)

    Holst, B; Elling, C E; Schwartz, T W

    2000-01-01

    -ion site located between AspIII:08-or a His residue introduced at this position in transmembrane domain (TM)-III-and a Cys residue substituted for AsnVII:06 in TM-VII. Here, this interhelical, bidentate metal-ion site is without loss of Zn(2+) affinity transferred to the tachykinin NK(1) receptor...

  19. Neurokinin-1 (NK-1 receptor and brain-derived neurotrophic factor (BDNF gene expression is differentially modulated in the rat spinal dorsal horn and hippocampus during inflammatory pain

    Directory of Open Access Journals (Sweden)

    McCarson Kenneth E

    2007-10-01

    Full Text Available Abstract Persistent pain produces complex alterations in sensory pathways of the central nervous system (CNS through activation of various nociceptive mechanisms. However, the effects of pain on higher brain centers, particularly the influence of the stressful component of pain on the limbic system, are poorly understood. Neurokinin-1 (NK-1 receptors and brain-derived neurotrophic factor (BDNF, known neuromediators of hyperalgesia and spinal central sensitization, have also been implicated in the plasticity and neurodegeneration occurring in the hippocampal formation during exposures to various stressors. Results of this study showed that injections of complete Freund's adjuvant (CFA into the hind paw increased NK-1 receptor and BDNF mRNA levels in the ipsilateral dorsal horn, supporting an important role for these nociceptive mediators in the amplification of ascending pain signaling. An opposite effect was observed in the hippocampus, where CFA down-regulated NK-1 receptor and BDNF gene expression, phenomena previously observed in immobilization models of stress and depression. Western blot analyses demonstrated that in the spinal cord, CFA also increased levels of phosphorylated cAMP response element-binding protein (CREB, while in the hippocampus the activation of this transcription factor was significantly reduced, further suggesting that tissue specific transcription of either NK-1 or BDNF genes may be partially regulated by common intracellular transduction mechanisms mediated through activation of CREB. These findings suggest that persistent nociception induces differential regional regulation of NK-1 receptor and BDNF gene expression and CREB activation in the CNS, potentially reflecting varied roles of these neuromodulators in the spinal cord during persistent sensory activation vs. modulation of the higher brain structures such as the hippocampus.

  20. Mechanisms and latest clinical studies of new NK1 receptor antagonists for chemotherapy-induced nausea and vomiting: Rolapitant and NEPA (netupitant/palonosetron).

    Science.gov (United States)

    Rojas, Camilo; Slusher, Barbara S

    2015-12-01

    Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapy-induced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. PET evaluation of the uptake of N-[11C]methyl CP-643,051, an NK1 receptor antagonist, in the living porcine brain

    International Nuclear Information System (INIS)

    Bender, D.; Olsen, A.K.; Marthi, M.K.; Smith, D.F.; Cumming, P.

    2004-01-01

    Antagonists of neurokinin receptors such as CP-643,051 are presently under investigation as potential antidepressants, but little is known about the brain uptake and distribution of these agents. We developed a method for the efficient N-[ 11 C]methylation of CP-122,721, yielding the NK 1 antagonist N-[ 11 C]methyl CP-643,051. The brain uptake and distribution of N-[ 11 C]methyl CP-643,051 were studied by positron emission tomography (PET) in the anaesthetized pig, first in a baseline condition, and again after displacement of specific binding with the NK 1 receptor antagonist L-732,138 (0.6 mg/kg, i.v.). In order to validate this displacement procedure, we tested the effects of L-732,138 on cerebral blood flow (CBF) in one pig. We found that N-[ 11 C]methyl CP-643,051 had a distribution volume close to 3 ml g -1 , and a binding potential (pB) of 0.3 in the pig striatum; this binding was displaceable by the L-732,138 pre-treatment, which evoked a small (10-20%) global increase in CBF. We conclude that of N-[ 11 C]methyl CP-643,051 may serve as a lead structure for the development of PET NK-1 ligands of higher specific binding in vivo

  2. Design, synthesis and biological studies of a library of NK1-Receptor Ligands Based on a 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyran core: Switch from antagonist to agonist effect by chemical modification.

    Science.gov (United States)

    Recio, Rocío; Vengut-Climent, Empar; Mouillac, Bernard; Orcel, Hélène; López-Lázaro, Miguel; Calderón-Montaño, José Manuel; Álvarez, Eleuterio; Khiar, Noureddine; Fernández, Inmaculada

    2017-09-29

    A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for agonists), compared to the substance P (SP) effect, in IPone assay. A set of these amino compounds was found to inhibit the action of SP, and therefore can be considered as a new family of SP-antagonists. Interestingly, the acylation of the 2-amino position causes a switch from antagonist to agonist activity. The 5-phenylsulfonyl-2-amino derivative 17 showed the highest antagonist activity, while the 5-p-tolylsulfenyl-2-trifluoroacetamide derivative 20R showed the highest agonist effect. As expected, in the case of the 5-sulfinylderivatives, there was an enantiomeric discrimination in favor of one of the two enantiomers, specifically those with (S S ,R C ) configuration. The anticancer activity studies assessed by using human A-549 lung cancer cells and MRC-5 non-malignant lung fibroblasts, revealed a statistically significant selective cytotoxic effect of some of these 2-amino-4H-pyran derivatives toward the lung cancer cells. These studies demonstrated that the newly synthesized 4H-pyran derivatives can be used as a starting point for the synthesis of novel SP-antagonists with higher anticancer activity in the future. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Tachykinins are involved in local reflex modulation of vagally mediated striated muscle contractions in the rat esophagus via tachykinin NK1 receptors.

    Science.gov (United States)

    Shiina, T; Shimizu, Y; Boudaka, A; Wörl, J; Takewaki, T

    2006-05-12

    The objective of the present study was to investigate the hypothesis of the presence of a local neural reflex modulating the vagally mediated contractions of striated muscle in the rat esophagus and to determine the possible involvement of tachykinins in such a local neural reflex. Electrical stimulation of the vagus nerve evoked twitch contractile responses that were abolished by d-tubocurarine (5 microM). Capsaicin (1-100 microM) inhibited the vagally mediated twitch contractions o f the normal rat esophageal preparations concentration-dependently but not those of the neonatally capsaicin-treated ones. NG-nitro-L-arginine methyl ester (100 microM), a nitric oxide synthase inhibitor, blocked the inhibitory effect of capsaicin and exogenous application of a nitric oxide donor (1 mM) inhibited the vagally mediated twitch contractions. Capsaicin suppressed acetylcholine release from the normal rat esophageal segments evoked by vagus nerve stimulation but not that from the neonatally capsaicin-treated ones. A selective tachykinin NK1 receptor antagonist (0.1 or 1 microM) attenuated the inhibitory effect of capsaicin. However, antagonists of tachykinin NK2, tachykinin NK3 and calcitonin gene-related peptide receptors (1 microM) did not have any effect. A tachykinin NK1 receptor agonist (1 or 5 microM) inhibited the vagally mediated twitch contractions, which was prevented by NG-nitro-L-arginine methyl ester (100 microM). These data suggest that the rat esophagus might have a local neural reflex inhibiting the vagally mediated striated muscle motility, which consists of capsaicin-sensitive sensory neurons and myenteric nitrergic neurons, and that tachykinins might be involved in the neural reflex through tachykinin NK1 receptors.

  4. Effect of a Bicyclic Pyrimidine Derivative (KRP-103), a Novel Selective Tachykinin NK1 Receptor Antagonist, on Bladder Function in Guinea Pigs.

    Science.gov (United States)

    Tanioka, Asao; Deguchi, Takashi

    2017-05-01

    We evaluated the pharmacological characteristics of KRP-103, chemically named as ((2-(4-acetylpiperazin-1-yl)-6-[3,5-bis(trifluorometheyl)-phenylmethyl]-4- (2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one), and its effects on lower urinary tract function in guinea pigs. In radioligand binding assay, KRP-103 showed higher selectivity for human NK1 receptor (hNK1R) than for human NK2 receptor (hNK2R) and human NK3 receptor (hNK3R) (Ki for hNK1R, hNK2R and hNK3R=0.126 nM, > 10 000 nM and > 10 000 nM). In distention-induced rhythmic bladder contractions (RBCs) in urethane-anesthetized guinea pigs, intravenous administration of KRP-103 dose-dependently increased the shutdown time of RBCs and slightly decreased the amplitude of RBCs (only about 20%). In acutely spinalized guinea pig cystometory, intraduodenal administration of KRP-103 dose-dependently increased the effective bladder capacity with a minimum effective dose of 1 mg/kg. Furthermore, to clarify the site of action of KRP-103, we evaluated the inhibitory effects of KRP-103 on bladder contractions induced by electrical stimulation (ES) of the central or peripheral cut end of the pelvic nerve (PN). KRP-103 inhibited the bladder contractions induced by ES of the central cut end of PN but not those induced by ES of the peripheral cut end of PN. These results indicate that KRP-103 enhances bladder storage function by inhibiting sensory transmission from the bladder at the level of spinal cord without affecting bladder efferent function, suggesting that KRP-103 may be a suitable therapeutic drug for treatment of overactive bladder. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Distinct tachykinin NK(1) receptor function in primate nucleus tractus solitarius neurons is dysregulated after second-hand tobacco smoke exposure.

    Science.gov (United States)

    Sekizawa, Shin-Ichi; Joad, Jesse P; Pinkerton, Kent E; Bonham, Ann C

    2011-06-01

    Second-hand tobacco smoke (SHS) exposure in children increases the risk of asthma and sudden infant death syndrome. Epidemiological and experimental data have suggested SHS can alter neuroplasticity in the CNS, associated with substance P. We hypothesized that exposure to SHS in young primates changed the effect of substance P on the plasticity of neurons in the nucleus tractus solitarius (NTS), where airway sensory information is first processed in the CNS. Thirteen-month-old rhesus monkeys were exposed to filtered air (FA, n= 5) or SHS (n= 5) for >6 months from 50 days of their fetal age. Whole-cell patch-clamp recordings were performed on NTS neurons in brainstem slices from these animals to record the intrinsic cell excitability in the absence or presence of the NK(1) receptor antagonist, SR140333 (3 µM). Neurons were electrophysiologically classified based on their spiking onset from a hyperpolarized membrane potential into two phenotypes: rapid-onset spiking (RS) and delayed-onset spiking (DS) types. In RS neurons, SR140333 reduced the spiking response, similarly in both FA- and SHS-exposed animals. In DS neurons, SR140333 almost abolished the spiking response in FA-exposed animals, but had no effect in SHS-exposed animals. The contribution of NK(1) receptors to cell excitability depended on firing phenotype of primate NTS neurons and was disrupted by SHS exposure, specifically in DS neurons. Our findings reveal a novel NK(1) receptor function in the primate brainstem and support the hypothesis that chronic exposure to SHS in children causes tachykinin-related neuroplastic changes in the CNS. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  6. Distinct tachykinin NK1 receptor function in primate nucleus tractus solitarius neurons is dysregulated after second-hand tobacco smoke exposure

    Science.gov (United States)

    Sekizawa, Shin-ichi; Joad, Jesse P; Pinkerton, Kent E; Bonham, Ann C

    2011-01-01

    BACKGROUND AND PURPOSE Second-hand tobacco smoke (SHS) exposure in children increases the risk of asthma and sudden infant death syndrome. Epidemiological and experimental data have suggested SHS can alter neuroplasticity in the CNS, associated with substance P. We hypothesized that exposure to SHS in young primates changed the effect of substance P on the plasticity of neurons in the nucleus tractus solitarius (NTS), where airway sensory information is first processed in the CNS. EXPERIMENTAL APPROACH Thirteen-month-old rhesus monkeys were exposed to filtered air (FA, n = 5) or SHS (n = 5) for >6 months from 50 days of their fetal age. Whole-cell patch-clamp recordings were performed on NTS neurons in brainstem slices from these animals to record the intrinsic cell excitability in the absence or presence of the NK1 receptor antagonist, SR140333 (3 µM). KEY RESULTS Neurons were electrophysiologically classified based on their spiking onset from a hyperpolarized membrane potential into two phenotypes: rapid-onset spiking (RS) and delayed-onset spiking (DS) types. In RS neurons, SR140333 reduced the spiking response, similarly in both FA- and SHS-exposed animals. In DS neurons, SR140333 almost abolished the spiking response in FA-exposed animals, but had no effect in SHS-exposed animals. CONCLUSIONS AND IMPLICATIONS The contribution of NK1 receptors to cell excitability depended on firing phenotype of primate NTS neurons and was disrupted by SHS exposure, specifically in DS neurons. Our findings reveal a novel NK1 receptor function in the primate brainstem and support the hypothesis that chronic exposure to SHS in children causes tachykinin-related neuroplastic changes in the CNS. PMID:21323902

  7. Partial agonism through a zinc-Ion switch constructed between transmembrane domains III and VII in the tachykinin NK(1) receptor

    DEFF Research Database (Denmark)

    Holst, B; Elling, C E; Schwartz, T W

    2000-01-01

    -ion site located between AspIII:08-or a His residue introduced at this position in transmembrane domain (TM)-III-and a Cys residue substituted for AsnVII:06 in TM-VII. Here, this interhelical, bidentate metal-ion site is without loss of Zn(2+) affinity transferred to the tachykinin NK(1) receptor...... metal-ion binding residues located at positions III:08 and VII:06. It is suggested that only partial agonism is obtained through this simple well defined metal-ion coordination due to lack of proper interactions with residues also in TM-VI....

  8. Efficient synthesis of novel NK1 receptor antagonists: selective 1,4-addition of grignard reagents to 6-chloronicotinic acid derivatives.

    Science.gov (United States)

    Hoffmann-Emery, Fabienne; Hilpert, Hans; Scalone, Michelangelo; Waldmeier, Pius

    2006-03-03

    A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C4 of the pyridine ring was achieved by a one-pot selective 1,4-Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the carboxylic function can be converted to a methyl amino group by a Hofmann rearrangement followed by reduction. Furthermore, a new high-yielding synthesis of 2-(3,5-bistrifluoromethylphenyl)-2-methyl propionic acid based on the carbonylation of the tertiary alcohol obtained by Grignard addition of 3,5-bis(trifluoromethyl)bromobenzene to acetone was established.

  9. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging.

    Science.gov (United States)

    Syvänen, Stina; Eriksson, Jonas; Genchel, Tove; Lindhe, Orjan; Antoni, Gunnar; Långström, Bengt

    2007-07-30

    The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/mumol and 270 GBq/mumol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S)-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)-2-phenylpiperidin-3-amine (I) and (2S,3S)-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)piperidin-3-amine (II) was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II) had no specific binding in striatum. Ligand (I) had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I) displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. The propyl-analogue (II) cannot be used for detecting changes in NK1-ligand levels, while further studies should be performed with the ethyl-analogue (I).

  10. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

    Directory of Open Access Journals (Sweden)

    Genchel Tove

    2007-07-01

    Full Text Available Abstract Background The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. Methods [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine (I and (2S,3S-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine (II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. Results All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II had no specific binding in striatum. Ligand (I had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. Conclusion The propyl-analogue (II cannot be used for detecting changes in NK1-ligand levels, while further studies should be

  11. Evidence of NK1 and NK2 Tachykinin Receptors and their Involvement in Histamine Release in a Murine Mast Cell Line

    Science.gov (United States)

    1992-01-01

    and NK2 tachykinin receptors and their involvement in histamine release in a murine mast cell line 61102A 3M161 102BSI AA 6. AUTHOR(S) Krumins, SA...NK2 Tachykinin Receptors and their Involvement in Histamine Release in a Murine Mast Cell Line S. A. KRUMINS and C. A. BROOMFIELD Biochemical...the biological effects of SPt, NKA and[ NKII t),ue rmeecd 28 Nla t991 are mediated through their respective tachykinin I),lie cccPIC(I3 Ociotc 1991

  12. Biased Gs Versus Gq Proteins and β-Arrestin Signaling in the NK1 Receptor Determined by Interactions in the Water Hydrogen Bond Network

    DEFF Research Database (Denmark)

    Valentin-Hansen, Louise; Frimurer, Thomas M; Mokrosinski, Jacek

    2015-01-01

    X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans-membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing different active and inactive helical constella......X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans-membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing different active and inactive helical...... constellations during the seven-trans-membrane receptor activation. The neurokinin-1 receptor signals efficiently through Gq, Gs, and β-arrestin when stimulated by substance P, but it lacks any sign of constitutive activity. In the water hydrogen bond network the neurokinin-1 has a unique Glu residue instead....... It is concluded that the interface between position II:10 (2.50), III:15 (3.39), and VII:16 (7.49) in the center of the water hydrogen bond network constitutes a focal point for fine-tuning seven trans-membrane receptor conformations activating different signal transduction pathways....

  13. Differential and additive suppressive effects of 5-HT3 (palonosetron)- and NK1 (netupitant)-receptor antagonists on cisplatin-induced vomiting and ERK1/2, PKA and PKC activation.

    Science.gov (United States)

    Darmani, Nissar A; Zhong, Weixia; Chebolu, Seetha; Mercadante, Frank

    2015-04-01

    To better understand the anti-emetic profile of the 5-HT3 (palonosetron)- and the tachykinin NK1 (netupitant) -receptor antagonists, either alone or in combination, we evaluated the effects of palonosetron and/or netupitant pretreatment on cisplatin-evoked vomiting and changes in the phosphorylation of brainstem kinases such as the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), protein kinase C alpha/beta (PKCα/β), and protein kinase A (PKA) in the least shrew. Our results demonstrate that cisplatin (10mg/kg, i.p.) causes emesis in the least shrew over 40h with respective peak early- and delayed-phases occurring at 1 - 2 and 32 - 34h post-injection. During the early phase (0 - 16h post cisplatin), palonosetron (0.1mg/kg, s.c.) significantly protected shrews from vomiting with a near complete suppression of vomit frequency. Palonosetron also significantly protected shrews from vomiting during the delayed phase (27 - 40h post cisplatin), but the reduction in mean vomit frequency failed to achieve significance. On the other hand, netupitant (5mg/kg, i.p.) totally abolished vomiting during the delayed phase, and tended to suppress the mean vomit frequency during the acute phase. The combined treatment protected shrews almost completely from vomiting during both phases. Brainstem pERK1/2 levels were significantly elevated at all time-points except at 40h post-cisplatin administration. PKA phosphorylation tended to be elevated throughout the delayed phase, but a significant increase only occurred at 33h. Brainstem pPKCα/β levels were enhanced during acute-phase with a significant elevation at 2h. Palonosetron, netupitant or their combination had no effect on elevated pERK1/2 levels during acute phase, but the combination reversed ERK1/2 phosphorylation at 33h post-cisplatin treatment. In addition, only the combined regimen prevented the cisplatin-induced PKCα/β phosphorylation observed at the acute phase. On the other hand, palonosetron and

  14. Localization of tachykinin binding sites (NK1, NK2, NK3 ligands) in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Saffroy, M.; Beaujouan, J.C.; Torrens, Y.; Besseyre, J.; Bergstroem, L.G.; Glowinski, J.

    1988-03-01

    A comparative autoradiographic analysis of the distribution of tachykinin binding sites was made on brain serial sections using several ligands. (1) /sup 3/H-SP, /sup 125/I-BHSP and /sup 3/H-physalaemin labeled identical binding sites (NK1 type). (2) /sup 3/H-NKB, /sup 125/I-BHE and /sup 3/H-eledoisin also labeled identical sites (NK3 type). (3) /sup 125/I-BHNKA preferentially labeled NK3 binding sites, the distribution of /sup 125/I-BHNKA binding sites being identical to that of /sup 3/H-NKB or /sup 125/I-BHE binding sites. (4) The distributions of /sup 3/H-SP and /sup 3/H-NKB binding sites were markedly different. (5) A very low density of labeling was found with /sup 3/H-NKA or /sup 125/I-NKA, and these binding sites were distributed only in areas rich in either /sup 3/H-SP or /sup 3/H-NKB binding sites. (6) Particular efforts were made to look for the presence of tachykinin binding sites in the substantia nigra, since this structure is particularly rich in SP and NKA and contains functional tachykinin receptors of the NK1 and NK2 types as suggested by physiological studies. Confirming previous reports, low or very low labeling was observed in the substantia nigra with /sup 3/H-SP or /sup 125/I-BHSP and /sup 3/H-NKB or /sup 125/I-BHE. Similar results were found with /sup 3/H-NKA, /sup 125/I-NKA or /sup 125/I-BHNKA. In conclusion, our data do not provide evidence yet for the existence of NK2 binding sites in the rat brain.

  15. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Directory of Open Access Journals (Sweden)

    Elizabeth Harford-Wright

    Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

  16. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Science.gov (United States)

    Harford-Wright, Elizabeth; Lewis, Kate M; Ghabriel, Mounir N; Vink, Robert

    2014-01-01

    The neuropeptide substance P (SP) has been implicated in the disruption of the blood-brain barrier (BBB) and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg), dexamethasone (8 mg/kg) or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05). Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants further

  17. Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.

    Directory of Open Access Journals (Sweden)

    Clas Linnman

    Full Text Available Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1 receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis were selected out of a larger (n = 120 randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis. These ten subjects were examined by positron emission tomography (PET with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA, was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

  18. The antiproliferative action of [D-Arg(1), D-Phe(5), D-Trp(7,9), LEU(11)] substance P analogue antagonist against small-cell- and non-small-cell lung cancer cells could be due to the pharmacological profile of its tachykinin receptor antagonist.

    Science.gov (United States)

    Munoz, M; Recio, S; Rosso, M; Redondo, M; Covenas, R

    2015-06-01

    It is known that in human lung cancer samples, both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cells express the neurokinin-1 (NK-1) receptor; that after binding to the NK-1 receptor the peptide substance P (SP) elicits tumour cell proliferation and an antiapoptotic effect. By contrast, it has been demonstrated that non-peptide NK-1 receptor antagonists, after binding to the NK-1 receptor and hence by blocking the SP action in SCLC/NSCLC, exert an antiproliferative action (inhibit lung cancer cell proliferation and induce the death of tumour cells by apoptosis). It is also known that SP peptide NK-1 receptor antagonists also called SP analogue antagonists (broad-spectrum GPCR antagonists, broad-spectrum neuropeptide antagonists or synthetic analogues of SP), also exert antiproliferative actions against SCLC/NSCLC. However, the underlying mechanisms involved in this antiproliferative action remain unknown. By using competition assays with SP, here we demonstrate that the antiproliferative action exerted by the [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)] SP analogue on human H-69 SCLC and COR-L23 NSCLC cell lines, occurs at least through the NK-1 receptor.

  19. Modulation of cutaneous SP receptors in atopic dermatitis after UVA irradiation.

    Science.gov (United States)

    Staniek, V; Liebich, C; Vocks, E; Odia, S G; Doutremepuich, J D; Ring, J; Claudy, A; Schmitt, D; Misery, L

    1998-03-01

    Atopic dermatitis is a pruritic inflammatory skin disorder, involving immunological and non-immunological factors. Substance P seems to be involved in the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are increased in the lesional skin of patients with atopic dermatitis and a reduced weal and flare reaction to intradermal injection of substance P has been observed. We investigated the distribution of substance P receptors in the involved skin of patients before and after single or repetitive UVA irradiations. Our results indicate that substance P receptors of the NK-1 subtype are expressed on blood vessels and on epidermal keratinocytes of involved skin of patients with atopic dermatitis. UVA irradiations did not modify the epidermal distribution of substance P receptors but decreased their expression intensity on blood vessels. UVA irradiations seem to decrease skin inflammation through the modulation of NK-1 receptor expression on endothelial cells.

  20. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

    International Nuclear Information System (INIS)

    Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong; Lee, Lu-Yuan; Xu, Fadi

    2016-01-01

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA 1 receptor, ADA 1 R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA 1 R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and protein changes in

  1. Mapping Substance P Binding Sites on the Neurokinin-1 Receptor Using Genetic Incorporation of a Photoreactive Amino Acid

    DEFF Research Database (Denmark)

    Valentin-Hansen, Louise; Park, Minyoung; Huber, Thomas

    2014-01-01

    the photoreactive unnatural amino acid p-benzoyl-l-phenylalanine (BzF) at 11 selected individual positions in the Nt tail (residues 11-21) and 23 positions in the ECLII (residues 170(C-10)-193(C+13)) of NK1. The 34 NK1 variants were expressed in mammalian HEK293 cells and retained the ability to interact...... with a fluorescently labeled SP analog. Notably, 10 of the receptor variants with BzF in the Nt tail and 4 of those with BzF in ECLII cross-linked efficiently to SP, indicating that these 14 sites are juxtaposed to SP in the ligand-bound receptor. These results show that two distinct regions of the NK1 receptor...

  2. Activation of neurokinin-1 receptors increases the excitability of guinea pig dorsal root ganglion cells.

    Science.gov (United States)

    Zhang, Xiulin; Pietra, Claudio; Lovati, Emanuela; de Groat, William C

    2012-10-01

    The suppression of overactive bladder symptoms in patients and overactive bladder reflexes in animal models by neurokinin (NK)-1 receptor antagonists raises the possibility that these drugs target sensory neurons. This mechanism was evaluated by examining the interactions between a specific NK-1 agonist, [Sar(9),Met(O(2))(11)]-substance P (Sar-Met-SP), and a potent NK-1 antagonist, netupitant (NTP), on small size (20-30 μm) dissociated L6 and S1 dorsal root ganglion (DRG) neurons from female guinea pigs. Current-clamp recording revealed that Sar-Met-SP (1 μM) elicited membrane depolarization (average 8.05 ± 1.38 mV) in 27% (18 of 65) of DRG neurons. In 74% of the remaining neurons (35 of 47) Sar-Met-SP decreased the rheobase for action potential (AP) generation and increased the response to a suprathreshold stimulus (3 times rheobase) without changing the membrane potential. Sar-Met-SP also induced changes in the action potential (AP) wave form, including 1) an increase in overshoot (average 5 mV, n = 35 neurons), 2) a prolongation of AP duration (from 4.64 to 5.29 ms, n = 34), and 3) a reduction in the maximal rate of AP repolarization. NTP (200 nM) reversed the Sar-Met-SP-induced changes. Ca(2+) imaging showed that application of Sar-Met-SP (1 μM) decreased the tachyphylaxis induced by repeated application of capsaicin (0.5 μM), an effect blocked by pretreatment with NTP (200 nM). These results raise the possibility that activation of NK-1 receptors in primary sensory neurons plays a role in the generation of overactive bladder and that block of NK-1 receptors in these neurons may contribute to efficacy of NK-1 antagonists in the treatment of overactive bladder symptoms.

  3. In vitro and in vivo pharmacological characterization of the novel NK₁ receptor selective antagonist Netupitant.

    Science.gov (United States)

    Rizzi, Anna; Campi, Barbara; Camarda, Valeria; Molinari, Stefano; Cantoreggi, Sergio; Regoli, Domenico; Pietra, Claudio; Calo', Girolamo

    2012-09-01

    The novel NK(1) receptor ligand Netupitant has been characterized in vitro and in vivo. In calcium mobilization studies CHO cells expressing the human NK receptors responded to a panel of agonists with the expected order of potency. In CHO NK(1) cells Netupitant concentration-dependently antagonized the stimulatory effects of substance P (SP) showing insurmountable antagonism (pK(B) 8.87). In cells expressing NK(2) or NK(3) receptors Netupitant was inactive. In the guinea pig ileum Netupitant concentration-dependently depressed the maximal response to SP (pK(B) 7.85) and, in functional washout experiments, displayed persistent (up to 5h) antagonist effects. In mice the intrathecal injection of SP elicited the typical scratching, biting and licking response that was dose-dependently inhibited by Netupitant given intraperitoneally in the 1-10mg/kg dose range. In gerbils, foot tapping behavior evoked by the intracerebroventricular injection of a NK(1) agonist was dose-dependently counteracted by Netupitant given intraperitoneally (ID(50) 1.5mg/kg) or orally (ID(50) 0.5mg/kg). In time course experiments in gerbils Netupitant displayed long lasting effects. In all the assays Aprepitant elicited similar effects as Netupitant. These results suggest that Netupitant behaves as a brain penetrant, orally active, potent and selective NK(1) antagonist. Thus this molecule can be useful for investigating the NK(1) receptor role in the control of central and peripheral functions. Netupitant has clinical potential in conditions such as chemotherapy induced nausea and vomiting, in which the blockade of NK(1) receptors has been demonstrated valuable for patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Expression of Tachykinins and Tachykinin Receptors and Interaction with Kisspeptin in Human Granulosa and Cumulus Cells.

    Science.gov (United States)

    García-Ortega, Jordán; Pinto, Francisco M; Prados, Nicolás; Bello, Aixa R; Almeida, Teresa A; Fernández-Sánchez, Manuel; Candenas, Luz

    2016-06-01

    The neurokinin B/NK3 receptor (NK3R) and kisspeptin/kisspeptin receptor (KISS1R), two systems which are essential for reproduction, are coexpressed in human mural granulosa (MGC) and cumulus cells (CCs). However, little is known about the presence of other members of the tachykinin family in the human ovary. In the present study, we analyzed the expression of substance P (SP), hemokinin-1 (HK-1), NK1 receptor (NK1R), and NK2 receptor (NK2R) in MGCs and CCs collected from preovulatory follicles of oocyte donors at the time of oocyte retrieval. RT-PCR, quantitative RT-PCR, immunocytochemistry, and Western blotting were used to investigate the patterns of expression of tachykinin and tachykinin receptor mRNAs and proteins and the possible interaction between the tachykinin family and kisspeptin. Intracellular free Ca(2+) levels ([Ca(2+)]i) in MGCs after exposure to SP or kisspeptin in the presence of SP were also measured. We found that SP, HK-1, the truncated NK1R isoform NK1R-Tr, and NK2R were all expressed in MGCs and CCs. NK1R-Tr mRNA and NK2R mRNA and protein levels were higher in MGCs than in CCs from the same patients. Treatment of cells with kisspeptin modulated the expression of HK-1, NK3R, and KISS1R mRNAs, whereas treatment with SP regulated kisspeptin mRNA levels and reduced the [Ca(2+)]i response produced by kisspeptin. These data demonstrate that the whole tachykinin system is expressed and acts in coordination with kisspeptin to regulate granulosa cell function in the human ovary. © 2016 by the Society for the Study of Reproduction, Inc.

  5. Tachykinins and tachykinin receptors in bone.

    Science.gov (United States)

    Goto, Tetsuya; Tanaka, Teruo

    2002-07-15

    Tachykinins are neuropeptides that are widely distributed in the body and function as neurotransmitters and neuromodulators. Five tachykinin subtypes: substance P (SP), neurokinin A, neurokinin B, neuropeptide K, and neuropeptide gamma; and three receptor subtypes: neurokinin-1, -2, and -3 receptors, have been identified. SP was the first peptide of the tachykinin family to be identified. It is considered to be an important neuropeptide, and to function in the nervous system and intestine. However, recent advances in the analysis of SP receptors, particularly neurokinin-1 receptors (NK(1)-Rs) that have high affinity for SP, have demonstrated that NK(1)-Rs are distributed not only in neurons and immune cells, but also in other peripheral cells, including bone cells. This article reviews the current understanding of the distribution of SP and other tachykinins in bone, and the function of tachykinins, through neurokinin receptors. The distribution of tachykinin-immunoreactive axons and neurokinin receptors suggests that tachykinins may directly modulate bone metabolism through neurokinin receptors. Copyright 2002 Wiley-Liss, Inc.

  6. Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity

    Science.gov (United States)

    Janelsins, Brian M.; Mathers, Alicia R.; Tkacheva, Olga A.; Erdos, Geza; Shufesky, William J.; Morelli, Adrian E.

    2009-01-01

    Dendritic cells (DCs) are the preferred targets for immunotherapy protocols focused on stimulation of cellular immune responses. However, regardless of initial promising results, ex vivo generated DCs do not always promote immune-stimulatory responses. The outcome of DC-dependent immunity is regulated by proinflammatory cytokines and neuropeptides. Proinflammatory neuropeptides of the tachykinin family, including substance P (SP) and hemokinin-1 (HK-1), bind the neurokinin 1 receptor (NK1R) and promote stimulatory immune responses. Nevertheless, the ability of pro-inflammatory tachykinins to affect the immune functions of DCs remains elusive. In the present work, we demonstrate that mouse bone marrow–derived DCs (BMDCs) generated in the presence of granulocyte macrophage–colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), express functional NK1R. Signaling via NK1R with SP, HK-1, or the synthetic agonist [Sar9Met(O2)11]-SP rescues DCs from apoptosis induced by deprivation of GM-CSF and IL-4. Mechanistic analysis demonstrates that NK1R agonistic binding promotes DC survival via PI3K-Akt signaling cascade. In adoptive transfer experiments, NK1R-signaled BMDCs loaded with Ag exhibit increased longevity in draining lymph nodes, resulting in enhanced and prolonged effector cellular immunity. Our results contribute to the understanding of the interactions between the immune and nervous systems that control DC function and present a novel approach for ex vivo–generation of potent immune-stimulatory DCs. PMID:18987361

  7. DX5+NKT cells display phenotypical and functional differences between spleen and liver as well as NK1.1-Balb/c and NK1.1+ C57Bl/6 mice.

    Science.gov (United States)

    Werner, Jens M; Busl, Elisabeth; Farkas, Stefan A; Schlitt, Hans J; Geissler, Edward K; Hornung, Matthias

    2011-04-29

    Natural killer T cells represent a linkage between innate and adaptive immunity. They are a heterogeneous population of specialized T lymphocytes composed of different subsets. DX5+NKT cells are characterized by expression of the NK cell marker DX5 in the context of CD3. However, little is known about the phenotype and functional capacity of this unique cell population. Therefore, we investigated the expression of several T cell and NK cell markers, as well as functional parameters in spleen and liver subsets of DX5+NKT cells in NK1.1- Balb/c mice and compared our findings to NK1.1+ C57Bl/6 mice. In the spleen 34% of DX5+NKT cells expressed CD62L and they up-regulated the functional receptors CD154 as well as CD178 upon activation. In contrast, only a few liver DX5+NKT cells expressed CD62L, and they did not up-regulate CD154 upon activation. A further difference between spleen and liver subsets was observed in cytokine production. Spleen DX5+NKT cells produced more Th1 cytokines including IL-2, IFN-γ and TNF-α, while liver DX5+NKT cells secreted more Th2 cytokines (e.g. IL-4) and even the Th17 cytokine, IL-17a. Furthermore, we found inter-strain differences. In NK1.1+ C57Bl/6 mice DX5+NKT cells represented a distinct T cell population expressing less CD4 and more CD8. Accordingly, these cells showed a CD178 and Th2-type functional capacity upon activation. These results show that DX5+NKT cells are a heterogeneous population, depending on the dedicated organ and mouse strain, that has diverse functional capacity.

  8. In vitro and in vivo pharmacological characterization of Pronetupitant, a prodrug of the neurokinin 1 receptor antagonist Netupitant.

    Science.gov (United States)

    Ruzza, Chiara; Rizzi, Anna; Malfacini, Davide; Molinari, Stefano; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio; Calo', Girolamo

    2015-07-01

    The aim of the present study was to investigate the pharmacological activity of Pronetupitant, a novel compound designed to act as prodrug of the NK1 antagonist Netupitant. In receptor binding experiments Pronetupitant displayed high selectivity for the NK1 receptor. In a calcium mobilization assay performed on CHONK1 cells Pronetupitant (100 nM, 15 min preincubation) behaved as an NK1 antagonist more potent than Netupitant (pK(B) 8.72 and 7.54, respectively). In the guinea pig ileum bioassay Pronetupitant antagonized the contractile effect of SP showing a similar potency as Netupitant (pK(B)≈9). Similar results were obtained with 5 min preincubation time while at 2 min only Pronetupitant produced significant effects. In vivo in mice the intrathecal injection of 0.1 nmol SP elicited the typical scratching, biting and licking (SBL) nociceptive response. This effect of SP was dose dependently (0.1-10 mg/kg) antagonized by Pronetupitant given intravenously 2 h before the peptide. Superimposable results were obtained using Netupitant. Pharmacokinetic studies performed in rats demonstrate that Pronetupitant, after i.v. administration, is quickly (few minutes) and completely converted to Netupitant. Collectively the present results indicated that Pronetupitant acts in vitro as selective NK1 antagonist more potent than Netupitant. However based on the short half-life measured for Pronetupitant in rats, the in vivo action of Pronetupitant can be entirely interpreted as due to its conversion to Netupitant. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation

    Science.gov (United States)

    Sosulina, L.; Strippel, C.; Romo-Parra, H.; Walter, A. L.; Kanyshkova, T.; Sartori, S. B.; Lange, M. D.; Singewald, N.

    2015-01-01

    Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at −101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K+ conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar9,Met(O2)11]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observed between the major types of CEl neurons (late firing, regular spiking, low-threshold bursting). In addition, SP increased the frequency and amplitude of GABAergic synaptic events in CEl neurons depending on upstream spike activity. These data indicate a NK1R-mediated increase in excitability and GABAergic activity in CEl neurons, which seems to mostly involve the PKCδ-negative subpopulation. This influence can be assumed to increase reciprocal interactions between CElon and CEloff pathways, thereby boosting the medial CE (CEm) output pathway and contributing to the anxiogenic-like action of SP in the amygdala. PMID:26334021

  10. Requirement for Innate Immunity and CD90+ NK1.1− Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy

    Science.gov (United States)

    Moskalenko, Marina; Pan, Michael; Fu, Yichun; de Moll, Ellen H.; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Jayaraman, Padmini; Bernardo, Sebastian; Sikora, Andrew G.; Wolchok, Jedd; Bhardwaj, Nina; Merad, Miriam; Saenger, Yvonne

    2015-01-01

    We sought to define cellular immune mechanisms of synergy between tumor-antigen–targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1−/− mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, mice deficient in both classical natural killer (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain IL2γc−/−) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1+ cells does not impair antitumor effect. Depletion of CD90+NK1.1− lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the tumor. Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90+NK1.1− ILCs in chemo-immunotherapy. PMID:25600438

  11. Ablating spinal NK1-bearing neurons eliminates the development of pain and reduces spinal neuronal hyperexcitability and inflammation from mechanical joint injury in the rat.

    Science.gov (United States)

    Weisshaar, Christine L; Winkelstein, Beth A

    2014-04-01

    The facet joint is a common source of pain, especially from mechanical injury. Although chronic pain is associated with altered spinal glial and neuronal responses, the contribution of specific spinal cells to joint pain is not understood. This study used the neurotoxin [Sar(9),Met(O2)(11)]-substance P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 receptor (NK1R) in a rat model of painful facet joint injury to determine the role of those spinal neurons in pain from facet injury. Following spinal administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was imposed and behavioral sensitivity was assessed. Spinal extracellular recordings were made on day 7 to classify neurons and quantify evoked firing. Spinal glial activation and interleukin 1αα (IL1α) expression also were evaluated. SSP-SAP prevented the development of mechanical hyperalgesia that is induced by joint injury and reduced NK1R expression and mechanically evoked neuronal firing in the dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons that is seen after injury. Spinal astrocytic activation and interleukin 1α (IL1α) expression were reduced to sham levels with SSP-SAP treatment. These results suggest that spinal NK1R-bearing cells are critical in initiating spinal nociception and inflammation associated with a painful mechanical joint injury. Results demonstrate that cells expressing NK1R in the spinal cord are critical for the development of joint pain, spinal neuroplasticity, and inflammation after trauma to the joint. These findings have utility for understanding mechanisms of joint pain and developing potential targets to treat pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  12. Photoaffinity labeling the substance P receptor using a derivative of substance P containing para-benzoylphenylalanine

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, N.D.; White, C.F.; Leeman, S.E. (Univ. of Massachusetts Medical Center, Worcester (USA)); Cerpa, R.; Kaiser, E.T. (The Rockfeller Univ., New York (USA))

    1991-01-01

    A novel photoreactive substance P (SP) analogue has been synthesized by solid-phase peptide synthesis methodology to incorporate the amino acid p-benzoyl-L-phenylalanine (L-Phe(pBz)) in place of the Phe{sup 8} residue of SP. (Phe{sup 8}(OpBz))SP was equipotent with SP in competing for SP binding sites on rat submaxillary gland membranes and had potent sialagogic activity in vivo. In the absence of light, the {sup 125}I-labeled Bolton-Hunter conjugate of (Phe{sup 8}(pBz))SP bound in a saturable and reversible manner to an apparently homogeneous class of binding sites with an affinity K{sub D} = 0.4 nM. The binding of {sup 125}I-(Phe{sup 8}(pBz))SP was inhibited competitively by various tachykinin peptides and analogues with the appropriate specificity for SP/NK-1 receptors. Upon photolysis, up to 70{percent} of the specifically bound {sup 125}I-(Phe{sup 8}(pBz))SP underwent covalent linkage to two polypeptides of M{sub r} = 53 000 and 46 000, identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Quantitative analysis of the inhibitory effects of SP and related peptides on {sup 125}I-(Phe{sup 8}(pBz))SP photoincorporation indicated that the binding sites of the two photolabeled polypeptides have the same peptide specificity, namely, that typical of NK-1-type SP receptors. Further information on the relationship between the two labeled SP binding sites was provided by enzymatic digestion studies. The highly specific and remarkably efficient photolabeling achieved with {sup 125}I-(Phe{sup 8}(pBz))SP suggests that this photoaffinity probe will be of considerable value for the characterization of the molecular structure of the SP receptor.

  13. Fine tuning a well-oiled machine: Influence of NK1.1 and NKG2D on NKT cell development and function.

    Science.gov (United States)

    Joshi, Sunil K; Lang, Mark L

    2013-10-01

    Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but nonetheless expressed by NKT cells. These include several activating and inhibitory receptors that may fine-tune NKT development and survival, as well as activation via antigen receptors. Herein, we review the possible roles of the NK1.1 and NKG2D receptors in regulating development and function of NKT cells in health and disease. We suggest that pharmacological alteration of NKT activity should consider the potential complexities commensurate with NK1.1 and NKG2D expression. Published by Elsevier B.V.

  14. Phosphorylation of the transcription factor Sp4 is reduced by NMDA receptor signaling.

    Science.gov (United States)

    Saia, Gregory; Lalonde, Jasmin; Sun, Xinxin; Ramos, Belén; Gill, Grace

    2014-05-01

    The regulation of transcription factor function in response to neuronal activity is important for development and function of the nervous system. The transcription factor Sp4 regulates the developmental patterning of dendrites, contributes to complex processes including learning and memory, and has been linked to psychiatric disorders such as schizophrenia and bipolar disorder. Despite its many roles in the nervous system, the molecular mechanisms regulating Sp4 activity are poorly understood. Here, we report a site of phosphorylation on Sp4 at serine 770 that is decreased in response to membrane depolarization. Inhibition of the voltage-dependent NMDA receptor increased Sp4 phosphorylation. Conversely, stimulation with NMDA reduced the levels of Sp4 phosphorylation, and this was dependent on the protein phosphatase 1/2A. A phosphomimetic substitution at S770 impaired the Sp4-dependent maturation of cerebellar granule neuron primary dendrites, whereas a non-phosphorylatable Sp4 mutant behaved like wild type. These data reveal that transcription factor Sp4 is regulated by NMDA receptor-dependent activation of a protein phosphatase 1/2A signaling pathway. Our findings also suggest that the regulated control of Sp4 activity is an important mechanism governing the developmental patterning of dendrites. © 2014 International Society for Neurochemistry.

  15. Characterization of G-protein coupled receptor kinase interaction with the neurokinin-1 receptor using bioluminescence resonance energy transfer

    DEFF Research Database (Denmark)

    Jorgensen, Rasmus; Holliday, Nicholas D; Hansen, Jakob L

    2007-01-01

    activation, the full-length NK-1 receptor, but not a functional C-terminal tail-truncated receptor, is preassociated with GRK5 in a relatively low-affinity state. We demonstrate that GRK5 can compete for agonist induced GRK2 interaction with the NK-1 receptor, whereas GRK2 does not compete for receptor...

  16. Role of tachykinin 1 and 4 gene-derived neuropeptides and the neurokinin 1 receptor in adjuvant-induced chronic arthritis of the mouse.

    Science.gov (United States)

    Borbély, Eva; Hajna, Zsófia; Sándor, Katalin; Kereskai, László; Tóth, István; Pintér, Erika; Nagy, Péter; Szolcsányi, János; Quinn, John; Zimmer, Andreas; Stewart, James; Paige, Christopher; Berger, Alexandra; Helyes, Zsuzsanna

    2013-01-01

    Substance P, encoded by the Tac1 gene, is involved in neurogenic inflammation and hyperalgesia via neurokinin 1 (NK1) receptor activation. Its non-neuronal counterpart, hemokinin-1, which is derived from the Tac4 gene, is also a potent NK1 agonist. Although hemokinin-1 has been described as a tachykinin of distinct origin and function compared to SP, its role in inflammatory and pain processes has not yet been elucidated in such detail. In this study, we analysed the involvement of tachykinins derived from the Tac1 and Tac4 genes, as well as the NK1 receptor in chronic arthritis of the mouse. Complete Freund's Adjuvant was injected intraplantarly and into the tail of Tac1(-/-), Tac4(-/-), Tacr1(-/-) (NK1 receptor deficient) and Tac1(-/-/)Tac4(-/-) mice. Paw volume was measured by plethysmometry and mechanosensitivity using dynamic plantar aesthesiometry over a time period of 21 days. Semiquantitative histopathological scoring and ELISA measurement of IL-1β concentrations of the tibiotarsal joints were performed. Mechanical hyperalgesia was significantly reduced from day 11 in Tac4(-/-) and Tacr1(-/-) animals, while paw swelling was not altered in any strain. Inflammatory histopathological alterations (synovial swelling, leukocyte infiltration, cartilage destruction, bone damage) and IL-1β concentration in the joint homogenates were significantly smaller in Tac4(-/-) and Tac1(-/-/)Tac4(-/-) mice. Hemokinin-1, but not substance P increases inflammation and hyperalgesia in the late phase of adjuvant-induced arthritis. While NK1 receptors mediate its antihyperalgesic actions, the involvement of another receptor in histopathological changes and IL-1β production is suggested.

  17. Role of tachykinin 1 and 4 gene-derived neuropeptides and the neurokinin 1 receptor in adjuvant-induced chronic arthritis of the mouse.

    Directory of Open Access Journals (Sweden)

    Eva Borbély

    Full Text Available Substance P, encoded by the Tac1 gene, is involved in neurogenic inflammation and hyperalgesia via neurokinin 1 (NK1 receptor activation. Its non-neuronal counterpart, hemokinin-1, which is derived from the Tac4 gene, is also a potent NK1 agonist. Although hemokinin-1 has been described as a tachykinin of distinct origin and function compared to SP, its role in inflammatory and pain processes has not yet been elucidated in such detail. In this study, we analysed the involvement of tachykinins derived from the Tac1 and Tac4 genes, as well as the NK1 receptor in chronic arthritis of the mouse.Complete Freund's Adjuvant was injected intraplantarly and into the tail of Tac1(-/-, Tac4(-/-, Tacr1(-/- (NK1 receptor deficient and Tac1(-/-/Tac4(-/- mice. Paw volume was measured by plethysmometry and mechanosensitivity using dynamic plantar aesthesiometry over a time period of 21 days. Semiquantitative histopathological scoring and ELISA measurement of IL-1β concentrations of the tibiotarsal joints were performed.Mechanical hyperalgesia was significantly reduced from day 11 in Tac4(-/- and Tacr1(-/- animals, while paw swelling was not altered in any strain. Inflammatory histopathological alterations (synovial swelling, leukocyte infiltration, cartilage destruction, bone damage and IL-1β concentration in the joint homogenates were significantly smaller in Tac4(-/- and Tac1(-/-/Tac4(-/- mice.Hemokinin-1, but not substance P increases inflammation and hyperalgesia in the late phase of adjuvant-induced arthritis. While NK1 receptors mediate its antihyperalgesic actions, the involvement of another receptor in histopathological changes and IL-1β production is suggested.

  18. Tachykinin receptors mediating airway marcomolecular secretion

    Energy Technology Data Exchange (ETDEWEB)

    Gentry, S.E. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1991-01-01

    Three tachykinin receptor types, termed NK1, NK2, and NK3, can be distinguished by the relative potency of various peptides in eliciting tissue responses. Airway macromolecular secretion is stimulated by the tachykinin substance P (SP). The purposes of this study were to determine the tachykinin receptor subtype responsible for this stimulation, and to examine the possible involvement of other neurotransmitters in mediating this effect. Ferret tracheal explants maintained in organ culture were labeled with {sup 3}H-glucosamine, a precursor of high molecular weight glycoconjugates (HMWG) which are released by airway secretory cells. Secretion of labeled HMWG then was determined in the absence and presence of the tachykinins SP, neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY), and eledoisin (ELE). To evaluate the possible contribution of other mediators, tachykinin stimulation was examined in the presence of several receptor blockers.

  19. Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus.

    Science.gov (United States)

    Patak, Eva; Pinto, Francisco M; Story, Margot E; Pintado, C Oscar; Fleming, Anna; Page, Nigel M; Pennefather, Jocelyn N; Candenas, M Luz

    2005-05-01

    The aim of this study was to analyze the function and expression of tachykinins, tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the tachykinin NK1 receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of late pregnant mice. Endpoint and real-time quantitative RT-PCR were used to analyze the expression of the genes that encode the tachykinins SP/NKA, NKB, and hemokinin-1 (HK-1) (Tac1, Tac2, and Tac4); and the genes that encode tachykinin NK1 (Tacr1), NK2 (Tacr2), and NK3 (Tacr3) receptors in uteri from pregnant and nonpregnant mice. The data show that the mRNAs of tachykinins (particularly NKB and HK-1), tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy. The tachykinin NK1 receptor is the predominant tachykinin receptor in the nonpregnant and early pregnant mouse and may mediate tachykinin-induced uterine contractions in the nonpregnant mouse. The tachykinin NK2 receptor is predominant in the late pregnant mouse and is the main receptor mediating uterotonic responses to tachykinins at late pregnancy. The tachykinin NK3 receptor is expressed in considerable amounts only in uteri from nonpregnant diestrous animals, and its physiological significance remains to be clarified.

  20. Tachykinins and tachykinin receptors: structure and activity relationships.

    Science.gov (United States)

    Almeida, T A; Rojo, J; Nieto, P M; Pinto, F M; Hernandez, M; Martín, J D; Candenas, M L

    2004-08-01

    In addition to the classical neurotransmitters, acetylcholine and noradrenaline, a wide number of peptides with neurotransmitter activity have been identified in the past few years. Among them, the tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) appear to act as mediators of nonadrenergic, noncholinergic (NANC) excitatory neurotransmission. Tachykinins interact with specific membrane proteins, belonging to the family of G protein-coupling cell membrane receptors. Until now, three tachykinin receptors termed NK1 (NK1R), NK2 (NK2R) and NK3 (NK3R) have been cloned in different species. A large amount of reports suggests that these peptides are involved in nociception and neuroimmunomodulation, and in the development of different diseases such as bronchial asthma, inflammatory bowel syndrome and psychiatric disorders. Tachykinin receptor antagonists are therefore promising, therapeutically relevant agents. However, and in spite of extensive research, the obtention of selective antagonists of tachykinin receptors have revealed very difficult. An understanding of how ligands interact with their receptors is essential to permit a rational design of compounds acting selectively at the tachykinin receptor level. The major aim of the present article is to review the structure-activity data that exist for tachykinins and their receptors, with the purpose of getting insight into basic structural requirements that determine ligand/receptor interaction. Copyright 2004 Bentham Science Publishers Ltd.

  1. Postsynaptic dorsal column neurons express NK1 receptors following colon inflammation

    Czech Academy of Sciences Publication Activity Database

    Paleček, Jiří; Palečková, V.; Willis, W. D.

    2003-01-01

    Roč. 116, č. 2 (2003), s. 565-572 ISSN 0306-4522 Grant - others:NIH(US) NS09743; NIH(US) NS11255 Institutional research plan: CEZ:AV0Z5011922 Keywords : visceral pain * substance P * postsynaptic dorsal column Subject RIV: FH - Neurology Impact factor: 3.601, year: 2003

  2. Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency.

    Directory of Open Access Journals (Sweden)

    Alexandra Berger

    Full Text Available Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1(-/- showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1 (-/-, Tac4 (-/- and Tac1 (-/-/Tac4 (-/- mice repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.

  3. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

    Science.gov (United States)

    Saban, Ricardo; Simpson, Cindy; Vadigepalli, Rajanikanth; Memet, Sylvie; Dozmorov, Igor; Saban, Marcia R

    2007-01-01

    Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs). Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2). In the absence of NK1R, the matrix Nkx2

  4. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2007-05-01

    Full Text Available Abstract Background Tachykinins (TK, such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs. Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2. In the absence of

  5. Respiratory actions of tachykinins in the nucleus of the solitary tract: characterization of receptors using selective agonists and antagonists

    Science.gov (United States)

    Mazzone, Stuart B; Geraghty, Dominic P

    2000-01-01

    The respiratory response to microinjection of tachykinins and analogues into the commissural nucleus of the solitary tract (cNTS) of urethane-anaesthetized rats was investigated in the presence and absence of selective tachykinin NK1, NK2 and NK3 antagonists (RP 67580, SR 48968 and SR 142801, respectively). All tachykinins, except for the selective NK2 agonist, [Nle10]-NKA(4-10), increased tidal volume (VT). The rank potency order of naturally-occurring tachykinins was neurokinin A (NKA)⩾substance P (SP)>>NKB, whereas the rank order for selective analogues was senktide⩾septide>> [Sar9,Met(O2)11]-SP>>[Nle10]-NKA(4-10). Septide (NK1-selective) and senktide (NK3-selective) were 22 fold more potent (pD2∼12) at stimulating VT than SP (pD2∼10.5). Tachykinin agonists produced varying degrees of respiratory slowing, independent of changes in VT. At doses producing maximum stimulation of VT, agonists induced either a mild (tachykinin receptors (NK1, NK2 and NK3) are present in the cNTS and are involved in the central control of respiration. PMID:10725260

  6. Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ.

    Science.gov (United States)

    Słoniecka, Marta; Le Roux, Sandrine; Boman, Peter; Byström, Berit; Zhou, Qingjun; Danielson, Patrik

    2015-01-01

    Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the α1 and β2 adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides

  7. SR140333 counteracts NK-1 mediated cell proliferation in human breast cancer cell line T47D

    Directory of Open Access Journals (Sweden)

    Wei Hong-Jun

    2010-05-01

    Full Text Available Abstract Background It has been demonstrated that certain NK-1 antagonists could reduce proliferation of several cancer cell lines, however, it is unknown whether SR140333 exerts proliferation inhibition in breast cancer cell line. Methods Immunohistochemical staining was carried out to investigate the immunolocation of NK-1 in breast cancer tissues and T47D cell line, thereafter, various concentrations of [Sar9, Met(O211]substance P and SR140333 were applied alone or combined. MTT assay was applied to detect cytoactivation and coulter counter was to detect growth curve. The Hoechst33258 staining was performed to detect apoptosis. Results We found that breast cancer and T47D cells bear positive expression of NK-1. SR140333 inhibited cell growth in a dose dependent manner. Furthermore, SR140333 could counteract [Sar9, Met(O211]substance P induced proliferation. Hoechst33258 staining revealed the presence of apoptosis after SR140333 treatment. Conclusions Our study demonstrated SR140333 exert proliferation inhibition in breast cancer cell line T47D and indicates NK-1 play a central role in the substance P related cell proliferation in breast cancer.

  8. SR140333 counteracts NK-1 mediated cell proliferation in human breast cancer cell line T47D.

    Science.gov (United States)

    Huang, Wei-Qing; Wang, Ji-Gang; Chen, Lei; Wei, Hong-Jun; Chen, Hua

    2010-05-24

    It has been demonstrated that certain NK-1 antagonists could reduce proliferation of several cancer cell lines, however, it is unknown whether SR140333 exerts proliferation inhibition in breast cancer cell line. Immunohistochemical staining was carried out to investigate the immunolocation of NK-1 in breast cancer tissues and T47D cell line, thereafter, various concentrations of [Sar9, Met(O2)11]substance P and SR140333 were applied alone or combined. MTT assay was applied to detect cytoactivation and coulter counter was to detect growth curve. The Hoechst33258 staining was performed to detect apoptosis. We found that breast cancer and T47D cells bear positive expression of NK-1. SR140333 inhibited cell growth in a dose dependent manner. Furthermore, SR140333 could counteract [Sar9, Met(O2)11]substance P induced proliferation. Hoechst33258 staining revealed the presence of apoptosis after SR140333 treatment. Our study demonstrated SR140333 exert proliferation inhibition in breast cancer cell line T47D and indicates NK-1 play a central role in the substance P related cell proliferation in breast cancer.

  9. Inhibition of enterovirus 71 replication by an α-hydroxy-nitrile derivative NK-1.9k.

    Science.gov (United States)

    Wang, Yaxin; Cao, Lin; Zhai, Yangyang; Ma, Jiaming; Nie, Quandeng; Li, Ting; Yin, Zheng; Sun, Yuna; Shang, Luqing

    2017-05-01

    Enterovirus 71 (EV71) is one of the major etiological agents of human hand-foot-and-mouth disease (HFMD) worldwide. EV71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. However, there is still no approved drugs to treat such infections. Based on our previous report of a peptide-aldehyde anti-EV71 protease, we present here a highly specific α-hydroxy-nitrile derivative NK-1.9k, which inhibited the proliferation of multiple EV71 strains and coxsackievirus A16 (CVA16) in various cells with EC 50 of 37.0 nM with low cytotoxicity (CC 50  > 200 μM). The hydroxy-nitrile covalent warhead conferred NK-1.9k high potency and selectivity to interact with the cysteine residue of the active site of the viral protease. We also documented the resistance to NK-1.9k with a N69S mutation in EV71 3C pro . The combination of NK-1.9k and EV71 polymerase or entry inhibitors produced strong synergistic antiviral effects. Collectively, our findings suggest our compounds can potentially be developed as drugs for the treatment of HFMD. Copyright © 2017. Published by Elsevier B.V.

  10. Tachykinins and tachykinin receptors in the gut, with special reference to NK2 receptors in human.

    Science.gov (United States)

    Lecci, Alessandro; Capriati, Angela; Altamura, Maria; Maggi, Carlo Alberto

    2006-06-30

    Tachykinins (TKs), substance P (SP), neurokinin A (NKA) and B (NKB) are important peptide modulators of intestinal motility in animal species studied so far, including humans. Modulation of motility by TKs can occur at various levels, since these peptides are expressed in cholinergic excitatory motor neurons projecting to both circular and longitudinal muscle, interneurons, and intramural and extramural sensory neurons. The effects of SP, NKA and NKB are preferentially mediated through the stimulation of NK1, NK2 and NK3 receptors, respectively; however, the selectivity of natural TKs for their preferred receptors is relative. In addition, SP and NKA are expressed in similar quantities in the human intestine and adequate stimuli can release similar amount of these TKs from enteric nerves. Furthermore, a single anatomical substrate can express more than one TK receptor type, so that the blockade of a single receptor type may not reveal functional effects in integrated models of motility. In isolated human small intestine and colon circular muscle strips, both NK1 and NK2 receptors mediate contractile effects. Indeed, in the human small intestine, smooth muscle electrical and motor events induced by electrical field stimulation (EFS) can involve either or both NK1 and NK2 receptors or these latter receptors predominantly, depending on the experimental conditions. In contrast, in the human colonic smooth muscle, only the NK2 receptor-mediated component of the response to EFS is prominent and some evidence would suggest that this component is the main excitatory motor mechanism at this level. Furthermore, a NK2 receptor-mediated secretory component in the human colonic mucosa has been recently demonstrated. Thus, it could be speculated that the blockade of both NK1 and NK2 receptors will be necessary to antagonise motor effects induced by exogenous administration or endogenous release of TKs in the small intestine, whereas the blockade of the NK2 receptors would be

  11. Neurokinin B- and specific tachykinin NK3 receptor agonists-induced airway hyperresponsiveness in the guinea-pig

    Science.gov (United States)

    Daoui, Samira; Naline, Emmanuel; Lagente, Vincent; Emonds-Alt, Xavier; Advenier, Charles

    2000-01-01

    The aim of this study was to determine whether neurokinin B (NKB) or specific agonists of tachykinin NK3 receptors, [MePhe7]NKB and senktide, were able to induce airway hyperresponsiveness in guinea-pigs. The effects of these compounds were compared to those of substance P (SP), neurokinin A (NKA) and the preferential tachykinin NK1 ([Sar9, Met(02)11]SP) or NK2 ([βAla8]NKA (4-10)) receptor agonists.In guinea-pigs pretreated with phosphoramidon (10−4 M aerosol for 10 min) and salbutamol (8.7×10−3 M for 10 min), all tachykinins administrated by aerosol (3×10−7 to 10−4 M) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor effect of acetylcholine (i.v.). The rank order of potency was: [βAla8]NKA (4-10)>NKA=NKB=senktide=[MePhe7]NKB=[Sar9,Met(02)11]SP>SP.Airway hyperresponsiveness induced by [MePhe7]NKB was prevented by the tachykinin NK3 (SR 142801) and NK2 (SR 48968) receptor antagonists.Bronchoconstriction induced by tachykinins administered by aerosol was also determined. SP, NKA, NKB and the tachykinin NK1 and NK2 receptor agonist induced bronchoconstriction. The rank order of potency was: NKA=[βAla8]NKA (4-10)>NKB=SP=[Sar9,Met(02)11]SP. Under similar conditions, and for concentrations which induce airway hyperresponsiveness, senktide and [MePhe7]NKB failed to induce bronchoconstriction.It is concluded that tachykinin NK3-receptor stimulation can induce airway hyperresponsiveness and that this effect is not related to the ability of tachykinins to induce bronchoconstriction. PMID:10780997

  12. sp

    African Journals Online (AJOL)

    Vihar

    adopted as the first line drug. SP has few untoward effects if used carefully in therapeutic doses. Nausea, vomiting, generalized body weakness; diarrhea, skin rashes and hematological reactions are some of the associated side effects. The drug can cause severe skin reactions such as Steven Johnson's syndrome. This.

  13. Transcription factor Sp1 is involved in expressional regulation of coxsackie and adenovirus receptor in cancer cells.

    Science.gov (United States)

    Chung, Sun-Ku; Kim, Joo-Young; Lim, Joong-Yeon; Park, Young Mi; Hwang, Ha-Young; Nam, Jae-Hwan; Park, Sang Ick

    2011-01-01

    Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (-503/-498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression.

  14. Molecular recognition of tachykinin receptor selective agonists: insights from structural studies.

    Science.gov (United States)

    Ganjiwale, Anjali; Cowsik, Sudha M

    2013-12-01

    This Review deals essentially with the elucidation of structural features of Tachykinin family of neuropeptides, which are known to interact through three distinct GPCR subtypes, namely NK1 (Neurokinin 1), NK2 (Neurokinin 2) and NK3 (Neurokinin 3) receptors. In mammals, Tachykinins have been shown to elicit a wide array of activities such as powerful vasodilatation, hypertensive action and stimulation of extravascular smooth muscle and are known to be involved in a variety of clinical conditions including chronic pain, Parkinson's disease, Alzheimer's disease, depression, rheumatoid arthritis, irritable bowel syndrome and asthma. This broad spectrum of action of Tachykinins is attributed to the lack of selectivity of tachykinins to their receptors. All tachykinins interact with all the three-receptor subtypes with SP preferring NK1, NKA preferring NK2 and NKB preferring NK3. This lack of specificity can be accounted for by the conformational flexibility of these short, linear peptides. Hence, identification of structural features of the agonists important for receptor binding and biological activity is of great significance in unraveling the molecular mechanisms involved in tachykinin receptor activation and also in rational design of novel therapeutic agents. Understanding structure of the ligand-receptor complex and analysis of topography of the binding pocket of the tachykinin receptor is also crucial in rational design of drugs.

  15. Identification of a Novel Substance P–Neurokinin-1 Receptor MicroRNA-221-5p Inflammatory Network in Human Colonic Epithelial CellsSummary

    Directory of Open Access Journals (Sweden)

    Kai Fang

    2015-09-01

    Full Text Available Background & Aims: Substance P (SP, a neuropeptide member of the tachykinin family, plays a critical role in colitis. MicroRNAs (miRNAs are small noncoding RNAs that negatively regulate gene expression. We examined whether SP modulates expression of microRNAs in human colonic epithelial cells. Methods: We performed microRNA profiling analysis of SP-stimulated human colonic epithelial NCM460 cells overexpressing neurokinin-1 receptor (NCM460-NK-1R. Targets of SP-regulated microRNAs were validated by real-time polymerase chain reaction (RT-PCR. Functions of miRNAs were tested in NCM460-NK-1R cells and the trinitrobenzene sulfonic acid (TNBS and dextran sulfate sodium (DSS models of colitis. Results: SP stimulated differential expression of 29 microRNAs, including miR-221-5p, the highest up-regulated miR (by 12.6-fold upon SP stimulation. Bioinformatic and luciferase reporter analyses identified interleukin-6 receptor (IL-6R mRNA as a direct target of miR-221-5p in NCM460 cells. Accordingly, SP exposure of NCM460-NK-1R cells increased IL-6R mRNA expression, and overexpression of miR-221-5p reduced IL-6R expression. Nuclear factor κB and c-Jun N-terminal kinase inhibition decreased SP-induced miR-221-5p expression. MiR-221-5p expression was increased in both TNBS- and DSS-induced colitis and in colonic biopsy samples from ulcerative colitis but not Crohn’s disease patients compared with controls. In mice, intracolonic administration of a miR-221-5p chemical inhibitor exacerbated TNBS- and DSS-induced colitis and increased colonic tumor necrosis factor-α, C-X-C motif chemokine 10 (Cxcl10, and collagen, type II, α 1 (Col2α1 mRNA expression. In situ hybridization in TNBS- and DSS-exposed colons revealed increased miR-221-5p expression primarily in colonocytes. Conclusions: Our results reveal a novel NK-1R-miR-221-5p-IL-6R network that protects from colitis. The use of miR-221-5p mimics may be a promising approach for colitis

  16. The role of NK1.1+ cells in the protection against MHC class I+ HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Bubeník, Jan; Bieblová, Jana; Jandlová, Táňa

    2004-01-01

    Roč. 50, č. 6 (2004), s. 200-202 ISSN 0015-5500 R&D Projects: GA AV ČR IAA5052203; GA AV ČR KSK5011112; GA MZd NC7148; GA MZd NR7807 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * MHC class I expression * NK1.1+ cells Subject RIV: EC - Immunology Impact factor: 0.507, year: 2004

  17. Tachykinin regulation of cholinergic transmission in the limbic/prefrontal territory of the rat dorsal striatum: implication of new neurokinine 1-sensitive receptor binding site and interaction with enkephalin/mu opioid receptor transmission.

    Science.gov (United States)

    Pérez, Sylvie; Tierney, Adrienne; Deniau, Jean-Michel; Kemel, Marie-Louise

    2007-12-01

    The tachykinin neurokinin 1 receptors (NK(1)Rs) regulation of acetylcholine release and its interaction with the enkephalin/mu opioid receptors (MORs) transmission was investigated in the limbic/prefrontal (PF) territory of the dorsal striatum. Using double immunohistochemistry, we first showed that in this territory, cholinergic interneurons contain tachykinin NK(1)Rs and co-express MORs in the last part of the light period (afternoon). In slices of the striatal limbic/PF territory, following suppression of the dopaminergic inhibitory control of acetylcholine release, application of the tachykinin NK(1)R antagonist, SSR240600, markedly reduced the NMDA-induced acetylcholine release in the morning but not in the afternoon when the enkephalin/MOR regulation is operational. In the afternoon, the NK(1)R antagonist response required the suppression of the enkephalin/MOR inhibitory control of acetylcholine release by betafunaltrexamine. The pharmacological profile of the tachykinin NK(1)R regulation tested by application of the receptor agonists [[Pro(9)]substance P, neurokinin A, neuropeptide K, and substance P(6-11)] and antagonists (SSR240600, GR205171, GR82334, and RP67580) indicated that the subtype of tachykinin NK(1)R implicated are the new NK(1)-sensitive receptor binding site. Therefore, in the limbic/PF territory of the dorsal striatum, endogenous tachykinin facilitates acetylcholine release via a tachykinin NK(1)R subtype. In the afternoon, the tachykinin/NK(1)R and the enkephalin/MOR transmissions interact to control cholinergic transmission.

  18. Tachykinins and tachykinin receptors in human uterus.

    Science.gov (United States)

    Patak, Eva; Candenas, M Luz; Pennefather, Jocelyn N; Ziccone, Sebastian; Lilley, Alison; Martín, Julio D; Flores, Carlos; Mantecón, Antonio G; Story, Margot E; Pinto, Francisco M

    2003-06-01

    (1) Studies were undertaken to determine the nature of the receptors mediating contractile effects of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell-surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women. (2) The neurokinin B (NKB) precursor PPT-B was expressed in higher levels in the myometrium from nonpregnant than from pregnant women. Faint expression of PPT-A mRNA was detectable in the myometrium from nonpregnant but not pregnant women. PPT-C, the gene encoding the novel tachykinin peptide hemokinin-1 (HK-1), was present in trace amounts in the uteri from both pregnant and nonpregnant women. (3) Tachykinin NK(2) receptors were more strongly expressed in tissues from nonpregnant than from pregnant women. NK(1) receptor mRNA was present in low levels in tissues from both pregnant and nonpregnant women. A low abundance transcript corresponding to the NK(3) receptor was present only in tissues from nonpregnant women. (4) The mRNA expression of the tachykinin-degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant women. (5) Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of myometrium from nonpregnant women. The order of potency was NKA>SP>/=NKB. The potency of NKA was unchanged in the absence of peptidase inhibitors. (6) The tachykinin NK(2) receptor-selective agonist [Lys(5)MeLeu(9)Nle(10)]NKA(4-l0) was approximately equipotent with NKA, but the tachykinin NK(1) and NK(3) receptor-selective agonists [Sar(9)Met(O(2))(11)]SP and [MePhe(7)]NKB were ineffective in the myometrium from nonpregnant women. (7) The uterotonic effects of [Lys(5)MeLeu(9)Nle(10)]NKA(4-10) were antagonized by the tachykinin NK(2) receptor-selective antagonist SR48968. Neither atropine, nor phentolamine nor tetrodotoxin affected responses to [Lys(5

  19. Estrogen regulates transcription of the ovine oxytocin receptor gene through GC-rich SP1 promoter elements.

    Science.gov (United States)

    Fleming, Joann G W; Spencer, Thomas E; Safe, Stephen H; Bazer, Fuller W

    2006-02-01

    Establishment of pregnancy in ruminants results from paracrine signaling by interferon tau (IFNT) from the conceptus to uterine endometrial luminal epithelia (LE) that prevents release of luteolytic prostaglandin F(2alpha) pulses. In cyclic and pregnant ewes, progesterone down-regulates progesterone receptor (PGR) gene expression in LE. In cyclic ewes, loss of PGR allows for increases in estrogen receptor alpha (ESR1) and then oxytocin receptor (OXTR) gene expression followed by oxytocin-induced prostaglandin F(2alpha) pulses. In pregnant ewes, IFNT inhibits transcription of the ESR1 gene, which presumably inhibits OXTR gene transcription. Alternatively, IFNT may directly inhibit OXTR gene transcription. The 5' promoter/enhancer region of the ovine OXTR gene was cloned and found to contain predicted binding sites for activator protein 1, SP1, and PGR, but not for ESR1. Deletion analysis showed that the basal promoter activity was dependent on the region from -144 to -4 bp that contained only SP1 sites. IFNT did not affect activity of the OXTR promoter. In cells transfected with ESR1, E2, and ICI 182,780 increased promoter activity due to GC-rich SP1 binding sites at positions -104 and -64. Mutation analyses showed that the proximal SP1 sites mediated ESR1 action as well as basal activity of the promoter. In response to progesterone, progesterone receptor B also increased OXTR promoter activity. SP1 protein was constitutively expressed and abundant in the LE of the ovine uterus. These results support the hypothesis that the antiluteolytic effects of IFNT are mediated by direct inhibition or silencing of ESR1 gene transcription, thereby precluding ESR1/SP1 from stimulating OXTR gene transcription.

  20. to view fulltext PDF

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress ...

  1. Role of neurokinin 1 receptors in dextran sulfate-induced colitis: studies with gene-deleted mice and the selective receptor antagonist netupitant.

    Science.gov (United States)

    Szitter, István; Pintér, Erika; Perkecz, Anikó; Kemény, Agnes; Kun, József; Kereskai, László; Pietra, Claudio; Quinn, John P; Zimmer, Andreas; Berger, Alexandra; Paige, Christopher J; Helyes, Zsuzsanna

    2014-05-01

    The function of the neurokinin 1 (NK1) receptor was investigated in the DSS-induced mouse colitis model using NK1 receptor-deficient mice and the selective antagonist netupitant. Colitis was induced by oral administration of 20 mg/ml DSS solution for 7 days in C57BL/6 and Tacr1 KO animals (n = 5-7). During the induction, one-half of the C57BL/6 and Tacr1 KO group received one daily dose of 6 mg/kg netupitant, administered intraperitoneally, the other half of the group received saline, respectively. Disease activity index (DAI), on the basis of stool consistency, blood and weight loss, was determined over 7 days. Histological evaluation, myeloperoxidase (MPO) measurement, cytokine concentrations and receptor expression analysis were performed on the colon samples. NK1 receptors are up-regulated in the colon in response to DSS treatment. DSS increased DAI, histopathological scores, BLC, sICAM-1, IFN-γ, IL-16 and JE in wildtype mice, which were significantly reduced in NK1 receptor-deficient ones. NK1 receptor antagonism with netupitant significantly diminished DAI, inflammatory histopathological alterations, BLC, IFN-γ, IL-13 and IL-16 in wildtype mice, but not in the NK1-deficient ones. MPO was similarly elevated and netupitant significantly decreased its activity in both groups. NK1 receptor antagonism could be beneficial for colitis via inhibiting different inflammatory mechanisms.

  2. Tachykinin-induced contraction of the guinea-pig isolated oesophageal mucosa is mediated by NK2 receptors

    Science.gov (United States)

    Kerr, Karen P; Thai, Binh; Coupar, Ian M

    2000-01-01

    The tachykinin receptor present in the guinea-pig oesophageal mucosa that mediates contractile responses of the muscularis mucosae has been characterized, using functional in vitro experiments. The NK1 receptor-selective agonist, [Sar9(O2)Met11]SP and the NK3 receptor-selective agonists, [MePhe7]-NKB and senktide, produced no response at submicromolar concentrations. The NK2 receptor-selective agonists, [Nle10]-NKA(4–10), and GR 64,349 produced concentration-dependent contractile effects with pD2 values of 8.20±0.16 and 8.30±0.15, respectively. The concentration-response curve to the non-selective agonist, NKA (pD2=8.13±0.04) was shifted significantly rightwards only by the NK2 receptor-selective antagonist, GR 159,897 and was unaffected by the NK1 receptor-selective antagonist, SR 140,333 and the NK3 receptor-selective antagonist, SB 222,200. The NK2 receptor-selective antagonist, GR 159,897, exhibited an apparent competitive antagonism against the NK2 receptor-selective agonist, GR 64,349 (apparent pKB value=9.29±0.16) and against the non-selective agonist, NKA (apparent pKB value=8.71±0.19). The NK2 receptor-selective antagonist, SR 48,968 exhibited a non-competitive antagonism against the NK2 receptor-selective agonist, [Nle10]-NKA(4–10). The pKB value was 10.84±0.19. It is concluded that the guinea-pig isolated oesophageal mucosa is a useful preparation for studying the effects of NK2 receptor-selective agonists and antagonists as the contractile responses to various tachykinins are mediated solely by NK2 receptors. PMID:11090121

  3. Cell-Autonomous Regulation of Mu-Opioid Receptor Recycling by Substance P

    Directory of Open Access Journals (Sweden)

    Shanna L. Bowman

    2015-03-01

    Full Text Available How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP, a neuropeptide associated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R receptor, increases the post-endocytic recycling of the mu-opioid receptor (MOR in trigeminal ganglion (TG neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase in recycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Our results define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeostatic interaction between the pain and analgesic systems.

  4. Cell-Autonomous Regulation of Mu-Opioid Receptor Recycling by Substance P

    Science.gov (United States)

    Bowman, Shanna L.; Soohoo, Amanda L.; Shiwarski, Daniel J.; Schulz, Stefan; Pradhan, Amynah A.; Puthenveedu, Manojkumar A.

    2015-01-01

    SUMMARY How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP), a neuropep-tide associated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R) receptor, increases the post-endocytic recycling of the muopioid receptor (MOR) in trigeminal ganglion (TG) neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC) activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase in recycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Our results define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeo-static interaction between the pain and analgesic systems. PMID:25801029

  5. Transcription of human resistin gene involves an interaction of Sp1 with peroxisome proliferator-activating receptor gamma (PPARgamma.

    Directory of Open Access Journals (Sweden)

    Anil K Singh

    2010-03-01

    Full Text Available Resistin is a cysteine rich protein, mainly expressed and secreted by circulating human mononuclear cells. While several factors responsible for transcription of mouse resistin gene have been identified, not much is known about the factors responsible for the differential expression of human resistin.We show that the minimal promoter of human resistin lies within approximately 80 bp sequence upstream of the transcriptional start site (-240 whereas binding sites for cRel, CCAAT enhancer binding protein alpha (C/EBP-alpha, activating transcription factor 2 (ATF-2 and activator protein 1 (AP-1 transcription factors, important for induced expression, are present within sequences up to -619. Specificity Protein 1(Sp1 binding site (-276 to -295 is also present and an interaction of Sp1 with peroxisome proliferator activating receptor gamma (PPARgamma is necessary for constitutive expression in U937 cells. Indeed co-immunoprecipitation assay demonstrated a direct physical interaction of Sp1 with PPARgamma in whole cell extracts of U937 cells. Phorbol myristate acetate (PMA upregulated the expression of resistin mRNA in U937 cells by increasing the recruitment of Sp1, ATF-2 and PPARgamma on the resistin gene promoter. Furthermore, PMA stimulation of U937 cells resulted in the disruption of Sp1 and PPARgamma interaction. Chromatin immunoprecipitation (ChIP assay confirmed the recruitment of transcription factors phospho ATF-2, Sp1, Sp3, PPARgamma, chromatin modifier histone deacetylase 1 (HDAC1 and the acetylated form of histone H3 but not cRel, C/EBP-alpha and phospho c-Jun during resistin gene transcription.Our findings suggest a complex interplay of Sp1 and PPARgamma along with other transcription factors that drives the expression of resistin in human monocytic U937 cells.

  6. MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Maywan Hariono

    2016-05-01

    Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

  7. Kaempferol stimulates gene expression of low-density lipoprotein receptor through activation of Sp1 in cultured hepatocytes

    Science.gov (United States)

    Ochiai, Ayasa; Miyata, Shingo; Iwase, Masamori; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    A high level of plasma low-density lipoprotein (LDL) cholesterol is considered a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) is essential for clearing plasma LDL cholesterol, activation of LDLR is a promising therapeutic target for patients with atherosclerotic disease. Here we demonstrated how the flavonoid kaempferol stimulated the gene expression and activity of LDLR in HepG2 cells. The kaempferol-mediated stimulation of LDLR gene expression was completely inhibited by knockdown of Sp1 gene expression. Treatment of HepG2 cells with kaempferol stimulated the recruitment of Sp1 to the promoter region of the LDLR gene, as well as the phosphorylation of Sp1 on Thr-453 and Thr-739. Moreover, these kaempferol-mediated processes were inhibited in the presence of U0126, an ERK pathway inhibitor. These results suggest that kaempferol may increase the activity of Sp1 through stimulation of Sp1 phosphorylation by ERK1/2 and subsequent induction of LDLR expression and activity. PMID:27109240

  8. Ligand structure-dependent activation of estrogen receptor alpha/Sp by estrogens and xenoestrogens.

    Science.gov (United States)

    Wu, Fei; Khan, Shaheen; Wu, Qian; Barhoumi, Rola; Burghardt, Robert; Safe, Stephen

    2008-05-01

    This study investigated the effects of E2, diethylstilbestrol (DES), antiestrogens, the phytoestrogen resveratrol, and the xenoestrogens octylphenol (OP), nonylphenol (NP), endosulfan, kepone, 2,3,4,5-tetrachlorobiphenyl-4-ol (HO-PCB-Cl(4)), bisphenol-A (BPA), and 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on induction of luciferase activity in breast cancer cells transfected with a construct (pSp1(3)) containing three tandem GC-rich Sp binding sites linked to luciferase and wild-type or variant ERalpha. The results showed that induction of luciferase activity was highly structure-dependent in both MCF-7 and MDA-MB-231 cells. Moreover, RNA interference assays using small inhibitory RNAs for Sp1, Sp3 and Sp4 also demonstrated structure-dependent differences in activation of ERalpha/Sp1, ERalpha/Sp3 and ERalpha/Sp4. These results demonstrate for the first time that various structural classes of ER ligands differentially activate wild-type and variant ERalpha/Sp-dependent transactivation, selectively use different Sp proteins, and exhibit selective ER modulator (SERM)-like activity.

  9. LIGAND STRUCTURE-DEPENDENT ACTIVATION OF ESTROGEN RECEPTOR α/Sp BY ESTROGENS AND XENOESTROGENS

    Science.gov (United States)

    Wu, Fei; Khan, Shaheen; Wu, Qian; Barhoumi, Rola; Burghardt, Robert; Safe, Stephen

    2008-01-01

    This study investigated the effects of E2, diethylstilbestrol (DES), antiestrogens, the phytoestrogen resveratrol, and the xenoestrogens octylphenol (OP), nonylphenol (NP), endosulfan, kepone, 2,3,4,5-tetrachlorobiphenyl-4-ol (HO-PCB-Cl4), bisphenol-A(BPA), and 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on induction of luciferase activity in breast cancer cells transfected with a construct (pSp13) containing three tandem GC-rich Sp binding sites linked to luciferase and wild-type or variant ERα. The results showed that induction of luciferase activity was highly structure-dependent in both MCF-7 and MDA-MB-231 cells. Moreover, RNA interference assays using small inhibitory RNAs for Sp1, Sp3 and Sp4 also demonstrated structure-dependent differences in activation of ERα/Sp1, ERα/Sp3 and ERα/Sp4. These results demonstrate for the first time that various structural classes of ER ligands differentially activate wild-type and variant ERα/Sp-dependent transactivation, selectively use different Sp proteins, and exhibit selective ER modulator (SERM)-like activity. PMID:18400491

  10. Role of tachykinin and neurokinin receptors in the regulation of ovine omasal contractions.

    Science.gov (United States)

    Onaga, Takenori; Oh-ishi, Taro; Shimoda, Tomohiko; Nishimoto, Seira; Hayashi, Hideaki

    2012-01-10

    The present study investigated a role of tachykinins (TK) and neurokinin (NK) receptors (NK-R) in the non-cholinergic regulation of omasal contractions in sheep. Semiquantitative reverse transcription (RT)-PCR revealed that both preprotachykinin (PPT)-A and PPT-B mRNA were distributed in the omasal muscle layers and that NK-R type-1 (NK-1R) and type-2 (NK-2R) mRNA were largely expressed in the same tissues. Cumulative application of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) at 0.03-10μM induced tonic contractions of omasal muscle strips, and the contractile amplitude increased in order of NKBNK-1R antagonist, L-732,138, at 1-100μM did not significantly inhibit SP- and NKA-induced contractions in both muscle layers, NK-2R antagonist GR159897 at 30-100μM significantly inhibited NKA-induced contraction of longitudinal muscles and showed tendency to inhibit that in circular muscles. Electric field stimulation (EFS)-induced contractions of omasal muscle strips, which were atropine-resistant, were significantly inhibited by GR159897 at 30 and 100μM in both muscle strips, and L-732,138 at 30 and 100μM in longitudinal muscles, though the inhibition in the latter was very weak. The results of the present study suggest that, though all mRNA coding TKs and NK-R subtypes were expressed in omasal muscle layer, NK-2R in both muscle layers and, to much lesser extent, NK-1R in longitudinal muscles are involved in the regulation of omasal contraction, and that NKA is presumably a primary non-cholinergic excitatory neurotransmitter released from motor neurons in the ovine omasum. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Neuronal kappa B-binding factors consist of Sp1-related proteins. Functional implications for autoregulation of N-methyl-D-aspartate receptor-1 expression.

    Science.gov (United States)

    Mao, Xianrong; Moerman, Andrea M; Barger, Steven W

    2002-11-22

    Neurons contain a protein factor capable of binding DNA elements normally bound by the transcription factor NF-kappaB. However, several lines of evidence suggest that this neuronal kappaB-binding factor (NKBF) is not bona fide NF-kappaB. We have identified NKBF from cultures of neocortical neurons as a complex containing proteins related to Sp1. This complex was bound by antibodies to Sp1, Sp3, and Sp4 and was competed from binding to an NF-kappaB element by an oligonucleotide containing an Sp1-binding site. This Sp1 oligonucleotide detected an abundant factor in neuronal nuclei that migrated in electrophoretic mobility shift assays at a position consistent with NKBF. Expression of transfected Sp1 stimulated transcription in a manner dependent upon a kappaB cis-element. Similar to our previous reports for NKBF (Mao, X., Moerman, A. M., Lucas, M. M., and Barger, S. W. (1999) J. Neurochem. 73, 1851-1858 and Moerman, A. M., Mao, X., Lucas, M. M., and Barger, S. W. (1999) Mol. Brain Res. 67, 303-315), the activity of the Sp1-related factor was reduced by activation of ionotropic glutamate receptors, consistent with proteolytic degradation of all three Sp1-related factors. Expression of the N-methyl-d-aspartate receptor-1 (NR1) subunit of glutamate receptors correlated with the activity of the Sp1-related factor, specifically through an Sp1 element in the NR1 promoter. These data provide the first evidence that Sp1 or related family members are responsible for kappaB-binding activity and are involved in a negative feedback for NR1 in central nervous system neurons.

  12. Tachykinin receptors as therapeutic targets in stress-related disorders.

    Science.gov (United States)

    Ebner, Karl; Sartori, Simone B; Singewald, Nicolas

    2009-01-01

    The first report demonstrating the therapeutic efficacy of an orally applied neurokinin-1 (NK1) receptor antagonist in depression was published 10 years ago. Although there were difficulties to reproduce this particular finding, a huge amount of data has been published since this time, supporting the potential therapeutic value of various tachykinin ligands as promising novel tools for the management of stress-related disorders including anxiety disorders, schizophrenia and depression. The present review summarizes evidence derived from anatomical, neurochemical, pharmacological and behavioral studies demonstrating the localization of tachykinin neuropeptides including substance P (SP), neurokinin A, neurokinin B and their receptors (NK1, NK2, NK3) in brain areas known to be implicated in stress-mechanisms, mood/anxiety regulation and emotion-processing; their role as neurotransmitters and/or neuromodulators within these structures and their interactions with other neurotransmitter systems including dopamine, noradrenaline and serotonin (5-hydroxytryptamine, 5-HT). Finally, there is clear functional evidence from animal and human studies that interference with tachykinin transmission can modulate emotional behavior. Based on these findings and on evidence of upregulated tachykinin transmission in individuals suffering from stress-related disorders, several diverse tachykinin receptor antagonists, as well as compounds with combined antagonist profile have been developed and are currently under clinical investigation revealing evidence for anxiolytic, antidepressant and antipsychotic efficacy, seemingly characterized by a low side effect profile. However, substantial work remains to be done to clarify the precise mechanism of action of these compounds, as well as the potential of combining them with established and experimental therapies in order to boost efficacy.

  13. NK1.1+ cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Šímová, Jana; Bieblová, Jana; Bubeník, Jan; Reiniš, Milan

    2011-01-01

    Roč. 25, č. 1 (2011), s. 281-288 ISSN 1021-335X R&D Projects: GA AV ČR IAA500520807 Grant - others:EU-FP6-NOE(XE) Project 018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : MHC class I-deficient tumours * CD8+, CD4+, NK1.1+cell subpopulations * interferon gamma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.835, year: 2011

  14. Structure of the Enterovirus 71 3C Protease in Complex with NK-1.8k and Indications for the Development of Antienterovirus Protease Inhibitor.

    Science.gov (United States)

    Wang, Yaxin; Cao, Lin; Zhai, Yangyang; Yin, Zheng; Sun, Yuna; Shang, Luqing

    2017-07-01

    Hand-foot-and-mouth disease (HFMD), caused by enterovirus, is a threat to public health worldwide. To date, enterovirus 71 (EV71) has been one of the major causative agents of HFMD in the Pacific-Asia region, and outbreaks with EV71 cause millions of infections. However, no drug is currently available for clinical therapeutics. In our previous works, we developed a set of protease inhibitors (PIs) targeting the EV71 3C protease (3C pro ). Among these are NK-1.8k and NK-1.9k, which have various active groups and high potencies and selectivities. In the study described here, we determined the structures of the PI NK-1.8k in complex with wild-type (WT) and drug-resistant EV71 3C pro Comparison of these structures with the structure of unliganded EV71 3C pro and its complex with AG7088 indicated that the mutation of N69 to a serine residue destabilized the S2 pocket. Thus, the mutation influenced the cleavage activity of EV71 3C pro and the inhibitory activity of NK-1.8k in an in vitro protease assay and highlighted that site 69 is an additional key site for PI design. More information for the optimization of the P1' to P4 groups of PIs was also obtained from these structures. Together with the results of our previous works, these in-depth results elucidate the inhibitory mechanism of PIs and shed light to develop PIs for the clinical treatment of infections caused by EV71 and other enteroviruses. Copyright © 2017 American Society for Microbiology.

  15. The NK1R-/- mouse phenotype suggests that small body size, with a sex- and diet-dependent excess in body mass and fat, are physical biomarkers for a human endophenotype with vulnerability to attention deficit hyperactivity disorder.

    Science.gov (United States)

    Pillidge, Katharine; Heal, David J; Stanford, S Clare

    2016-09-01

    The abnormal behaviour of NK1R-/- mice (locomotor hyperactivity, inattentiveness and impulsivity in the 5-Choice Serial Reaction-Time Test) is arguably analogous to that of patients with attention deficit hyperactivity disorder (ADHD). Evidence suggests that small body size and increased body weight are risk factors for ADHD. Here, we compared the body size, body mass and body composition of male and female NK1R-/- mice and their wildtypes that had been fed either standard laboratory chow or a high-fat (45%: 'Western') diet. Male NK1R-/- mice from both cohorts were approximately 7% shorter than wildtypes. A similar trend was evident in females. Male NK1R-/- mice fed the normal diet weighed less than wildtypes but the 'body mass index' ('mBMI': weight (mg)/length (cm)(2)) of female NK1R-/- mice was higher than wildtypes. When given the high-fat diet, the mBMI of both male and female NK1R-/- mice was higher than wildtypes. There were no consistent genotype or sex differences in protein, ash or water content of mice from the two cohorts. However, the fat content of male NK1R-/- mice on the Western diet was considerably (35%) higher than wildtypes and resembled that of females from both genotypes. We conclude that a lack of functional NK1R is associated with small body size but increases vulnerability to an increase in mBMI and fat content, especially in males. This phenotype could also be evident in ADHD patients with polymorphism(s) of the TACR1 gene (the human equivalent of Nk1r). © The Author(s) 2016.

  16. Biaryls as potent, tunable dual neurokinin 1 receptor antagonists and serotonin transporter inhibitors.

    Science.gov (United States)

    Degnan, Andrew P; Tora, George O; Han, Ying; Rajamani, Ramkumar; Bertekap, Robert; Krause, Rudolph; Davis, Carl D; Hu, Joanna; Morgan, Daniel; Taylor, Sarah J; Krause, Kelly; Li, Yu-Wen; Mattson, Gail; Cunningham, Melissa A; Taber, Matthew T; Lodge, Nicholas J; Bronson, Joanne J; Gillman, Kevin W; Macor, John E

    2015-08-01

    Depression is a serious illness that affects millions of patients. Current treatments are associated with a number of undesirable side effects. Neurokinin 1 receptor (NK1R) antagonists have recently been shown to potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs) in a number of animal models. Herein we describe the optimization of a biaryl chemotype to provide a series of potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors. Through the choice of appropriate substituents, the SERT/NK1R ratio could be tuned to afford a range of target selectivity profiles. This effort culminated in the identification of an analog that demonstrated oral bioavailability, favorable brain uptake, and efficacy in the gerbil foot tap model. Ex vivo occupancy studies with compound 58 demonstrated the ability to maintain NK1 receptor saturation (>88% occupancy) while titrating the desired level of SERT occupancy (11-84%) via dose selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. S-layer proteins from Lactobacillus sp. inhibit bacterial infection by blockage of DC-SIGN cell receptor.

    Science.gov (United States)

    Prado Acosta, Mariano; Ruzal, Sandra M; Cordo, Sandra M

    2016-11-01

    Many species of Lactobacillus sp. possess Surface(s) layer proteins in their envelope. Among other important characteristics S-layer from Lactobacillus acidophilus binds to the cellular receptor DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; CD209), which is involved in adhesion and infection of several families of bacteria. In this report we investigate the activity of new S-layer proteins from the Lactobacillus family (Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus helveticus and Lactobacillus kefiri) over the infection of representative microorganisms important to human health. After the treatment of DC-SIGN expressing cells with these proteins, we were able to diminish bacterial infection by up to 79% in both gram negative and mycobacterial models. We discovered that pre-treatment of the bacteria with S-layers from Lactobacillus acidophilus and Lactobacillus brevis reduced bacteria viability but also prevent infection by the pathogenic bacteria. We also proved the importance of the glycosylation of the S-layer from Lactobacillus kefiri in the binding to the receptor and thus inhibition of infection. This novel characteristic of the S-layers proteins may contribute to the already reported pathogen exclusion activity for these Lactobacillus probiotic strains; and might be also considered as a novel enzymatic antimicrobial agents to inhibit bacterial infection and entry to host cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis

    Directory of Open Access Journals (Sweden)

    Prema Robinson

    2015-01-01

    Full Text Available Viral-myocarditis is an important cause of heart failure for which no specific treatment is available. We previously showed the neuropeptide substance P (SP is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (EMCV. The current studies determined if pharmacological inhibition of SP-signaling via its high affinity receptor, NK1R and downstream G-protein, Ras homolog gene family, member-A (RhoA, will be beneficial in viral-myocarditis. Aprepitant (1.2 mg/kg, a SP-receptor antagonist, or fasudil (10 mg/kg, a RhoA inhibitor, or saline control was administered daily to mice orally for 3 days, prior to, or 5 days following, intraperitoneal infection with and without 50 PFU of EMCV, following which disease assessment studies, including echocardiogram and cardiac Doppler were performed in day 14 after infection. Pretreatment and posttreatment with aprepitant significantly reduced mortality, heart and cardiomyocyte size, and cardiac viral RNA levels (P<0.05 all, ANOVA. Only aprepitant pretreatment improved heart functions; it significantly decreased end systolic diameter, improved fractional shortening, and increased peak aortic flow velocity (P<0.05 all, ANOVA. Pre- or posttreatment with fasudil did not significantly impact disease manifestations. These findings indicate that SP contributes to cardiac-remodeling and dysfunction following ECMV infection via its high affinity receptor, but not through the Rho-A pathway. These studies suggest that SP-receptor antagonism may be a novel therapeutic-option for patients with viral-myocarditis.

  19. The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding for sucrose and ethanol.

    Directory of Open Access Journals (Sweden)

    Pia Steensland

    2010-09-01

    Full Text Available The current obesity epidemic is thought to be partly driven by over-consumption of sugar-sweetened diets and soft drinks. Loss-of-control over eating and addiction to drugs of abuse share overlapping brain mechanisms including changes in motivational drive, such that stimuli that are often no longer 'liked' are still intensely 'wanted' [7], . The neurokinin 1 (NK1 receptor system has been implicated in both learned appetitive behaviors and addiction to alcohol and opioids; however, its role in natural reward seeking remains unknown.We sought to determine whether the NK1-receptor system plays a role in the reinforcing properties of sucrose using a novel selective and clinically safe NK1-receptor antagonist, ezlopitant (CJ-11,974, in three animal models of sucrose consumption and seeking. Furthermore, we compared the effect of ezlopitant on ethanol consumption and seeking in rodents. The NK1-receptor antagonist, ezlopitant decreased appetitive responding for sucrose more potently than for ethanol using an operant self-administration protocol without affecting general locomotor activity. To further evaluate the selectivity of the NK1-receptor antagonist in decreasing consumption of sweetened solutions, we compared the effects of ezlopitant on water, saccharin-, and sodium chloride (NaCl solution consumption. Ezlopitant decreased intake of saccharin but had no effect on water or salty solution consumption.The present study indicates that the NK1-receptor may be a part of a common pathway regulating the self-administration, motivational and reinforcing aspects of sweetened solutions, regardless of caloric value, and those of substances of abuse. Additionally, these results indicate that the NK1-receptor system may serve as a therapeutic target for obesity induced by over-consumption of natural reinforcers.

  20. Influence of Artemisia annua L. on toll-like receptor expression in brain of mice infected with Acanthamoeba sp.

    Science.gov (United States)

    Wojtkowiak-Giera, Agnieszka; Derda, Monika; Kosik-Bogacka, Danuta; Kolasa-Wołosiuk, Agnieszka; Solarczyk, Piotr; Cholewiński, Marcin; Wandurska-Nowak, Elżbieta; Jagodziński, Paweł P; Hadaś, Edward

    2018-02-01

    The treatment of acanthamoebiasis is a still a problem. Our previous studies showed that the application of extracts from Artemisia annua L. significantly prolonged the survival of mice infected by Acanthamoeba. This plant has medicinal properties in the treatment of human parasitic diseases. The aim of this study was to evaluate the effects of A. annua on expression of Toll-like receptors (TLRs) 2 and 4 in brain of mice with Acanthamoeba infection. Mice were infected with Acanthamoeba sp. strain Ac309 (KY203908) by intranasal inoculation without and after application of A. annua extract. The administration of extract from A. annua significantly reduced the level of expression of TLR2 and modified the level of expression of TLR4. A. annua extract is a natural substance that is well tolerated in animals and may be considered as a combination therapy in treatment of acanthamoebiasis. Our study suggested that A. annua extract may be used as an alternative therapeutic tool. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

    NARCIS (Netherlands)

    R. de Wit (Ronald)

    2003-01-01

    textabstractThe advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients

  2. Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1 promoter and its regulation by Sp1

    Directory of Open Access Journals (Sweden)

    Botella Luisa M

    2010-06-01

    Full Text Available Abstract Background Activin receptor-like kinase 1 (ALK1 is a Transforming Growth Factor-β (TGF-β receptor type I, mainly expressed in endothelial cells that plays a pivotal role in vascular remodelling and angiogenesis. Mutations in the ALK1 gene (ACVRL1 give rise to Hereditary Haemorrhagic Telangiectasia, a dominant autosomal vascular dysplasia caused by a haploinsufficiency mechanism. In spite of its patho-physiological relevance, little is known about the transcriptional regulation of ACVRL1. Here, we have studied the different origins of ACVRL1 transcription, we have analyzed in silico its 5'-proximal promoter sequence and we have characterized the role of Sp1 in the transcriptional regulation of ACVRL1. Results We have performed a 5'Rapid Amplification of cDNA Ends (5'RACE of ACVRL1 transcripts, finding two new transcriptional origins, upstream of the one previously described, that give rise to a new exon undiscovered to date. The 5'-proximal promoter region of ACVRL1 (-1,035/+210 was analyzed in silico, finding that it lacks TATA/CAAT boxes, but contains a remarkably high number of GC-rich Sp1 consensus sites. In cells lacking Sp1, ACVRL1 promoter reporters did not present any significant transcriptional activity, whereas increasing concentrations of Sp1 triggered a dose-dependent stimulation of its transcription. Moreover, silencing Sp1 in HEK293T cells resulted in a marked decrease of ACVRL1 transcriptional activity. Chromatin immunoprecipitation assays demonstrated multiple Sp1 binding sites along the proximal promoter region of ACVRL1 in endothelial cells. Furthermore, demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1. Conclusions Our results describe two new transcriptional start sites in ACVRL1 gene, and indicate that Sp1 is a key regulator of ACVRL1 transcription, providing new insights into

  3. The 10 sea urchin receptor for egg jelly proteins (SpREJ are members of the polycystic kidney disease-1 (PKD1 family

    Directory of Open Access Journals (Sweden)

    Miyata Shinji

    2007-07-01

    Full Text Available Abstract Background Mutations in the human polycystic kidney disease-1 (hPKD1 gene result in ~85% of cases of autosomal dominant polycystic kidney disease, the most frequent human monogenic disease. PKD1 proteins are large multidomain proteins involved in a variety of signal transduction mechanisms. Obtaining more information about members of the PKD1 family will help to clarify their functions. Humans have five hPKD1 proteins, whereas sea urchins have 10. The PKD1 proteins of the sea urchin, Strongylocentrotus purpuratus, are referred to as the Receptor for Egg Jelly, or SpREJ proteins. The SpREJ proteins form a subfamily within the PKD1 family. They frequently contain C-type lectin domains, PKD repeats, a REJ domain, a GPS domain, a PLAT/LH2 domain, 1–11 transmembrane segments and a C-terminal coiled-coil domain. Results The 10 full-length SpREJ cDNA sequences were determined. The secondary structures of their deduced proteins were predicted and compared to the five human hPKD1 proteins. The genomic structures of the 10 SpREJs show low similarity to each other. All 10 SpREJs are transcribed in either embryos or adult tissues. SpREJs show distinct patterns of expression during embryogenesis. Adult tissues show tissue-specific patterns of SpREJ expression. Conclusion Possession of a REJ domain of about 600 residues defines this family. Except for SpREJ1 and 3, that are thought to be associated with the sperm acrosome reaction, the functions of the other SpREJ proteins remain unknown. The sea urchin genome is one-fourth the size of the human genome, but sea urchins have 10 SpREJ proteins, whereas humans have five. Determination of the tissue specific function of each of these proteins will be of interest to those studying echinoderm development. Sea urchins are basal deuterostomes, the line of evolution leading to the vertebrates. The study of individual PKD1 proteins will increase our knowledge of the importance of this gene family.

  4. Mushroom acidic glycosphingolipid induction of cytokine secretion from murine T cells and proliferation of NK1.1 α/β TCR-double positive cells in vitro

    International Nuclear Information System (INIS)

    Nozaki, Hirofumi; Itonori, Saki; Sugita, Mutsumi; Nakamura, Kimihide; Ohba, Kiyoshi; Suzuki, Akemi; Kushi, Yasunori

    2008-01-01

    Interferon (IFN)-γ and interleukin (IL)-4 regulate many types of immune responses. Here we report that acidic glycosphingolipids (AGLs) of Hypsizigus marmoreus and Pleurotus eryngii induced secretion of IFN- γ and IL-4 from T cells in a CD11c-positive cell-dependent manner similar to that of α-galactosylceramide (α-GalCer) and isoglobotriaosylceramide (iGb3), although activated T cells by AGLs showed less secretion of cytokine than those activated by α-GalCer. In addition, stimulation of these mushroom AGLs induced proliferation of NK1.1 α/β TCR-double positive cells in splenocytes. Administration of a mixture of α-GalCer and AGLs affected the stimulation of α-GalCer and generally induced a subtle Th1 bias for splenocytes but induced an extreme Th2 bias for thymocytes. These results suggested that edible mushroom AGLs contribute to immunomodulation

  5. Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Lucibello, M; Holst, B

    1998-01-01

    In the wild-type tachykinin NK3A receptor histidyl residues are present at two positions in TM-V, V:01 and V:05, at which Zn2+ functions as an antagonist in NK1 and kappa-opioid receptors with engineered metal-ion sites. Surprisingly, in the NK3A receptor Zn2+ instead increased the binding...

  6. Simultaneous detection of decidual Th1/Th2 and NK1/NK2 immunophenotyping in unknown recurrent miscarriage using 8-color flow cytometry with FSC/Vt extended strategy.

    Science.gov (United States)

    Dong, Peng; Wen, Xi; Liu, Jia; Yan, Cui-Yan; Yuan, Jing; Luo, Lan-Rong; Hu, Qiao-Fei; Li, Jian

    2017-06-30

    Th1/Th2 imbalance is considered as a mechanism for recurrent miscarriage. The NK1/NK2 paradigm is hypothesised to play an important role in pregnancy. However, few results showed simultaneous changes of these subsets in vivo in decidual tissues. The present study aimed to detect the decidual mononuclear cells (dMo), and the Th1/Th2, and NK1/NK2 paradigm simultaneously using multiparametric flow cytometry (MFC) in unexplained recurrent miscarriages (URM). Mononuclear cells were isolated from the decidual tissues of URM cases and early pregnant women. The mononuclear cell percent was demonstrated by detecting the expression of CD3, CD4, CD8, CD56, and CD16 extracellular markers, interferon (IFN)-γ, and interleukin (IL)-4 intracellular markers in live cells using 8-color flow cytometry with forward scatter (FSC)/side scatter (SSC) and FSC/viability (Vt) initial gating strategies, and the ratios of Th1/Th2 and decidual NK1 (dNK1)/decidual NK2 (dNK2) cells were compared between the subject groups. Two initial gating strategies of the FSC/SSC or FSC/Vt, with central or extended gating scales, were adapted, and there was no main effect or interaction for the cell proportions, except for the type 1 and type 2 subsets in the FSC/Vt extended gating strategy. There was no significant difference of the proportions of the decidual T, dNK, NKT-like, Th, and Tc cells between the two groups. However, the Th1/Th2 and dNK1/dNK2 ratios in the URM patients were higher compared with the normal group when using the FSC/Vt extended gating strategy. The present study provides means to detect Th1/Th2 and dNK1/dNK2 simultaneously in URM patients for large sample investigations in the future. © 2017 The Author(s).

  7. β-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition.

    Science.gov (United States)

    Zhang, Yi-Xin; Li, Xiao-Fang; Yuan, Guo-Qiang; Hu, Hui; Song, Xiao-Yun; Li, Jing-Yi; Miao, Xiao-Kang; Zhou, Tian-Xiong; Yang, Wen-Le; Zhang, Xiao-Wei; Mou, Ling-Yun; Wang, Rui

    2017-05-26

    Glioblastoma is the most common malignant brain tumor and has a poor prognosis. Tachykinin receptor neurokinin-1 (NK1R) is a promising target in glioblastoma therapy because of its overexpression in human glioblastoma. NK1R agonists promote glioblastoma cell growth, whereas NK1R antagonists efficiently inhibit cell growth both in vitro and in vivo However, the molecular mechanisms involved in these effects are incompletely understood. β-Arrestins (ARRBs) serve as scaffold proteins and adapters to mediate intracellular signal transduction. Here we show that the ARRB1-mediated signaling pathway is essential for NK1-mediated glioblastoma cell proliferation. ARRB1 knockdown significantly inhibited NK1-mediated glioblastoma cell proliferation and induced G 2 /M phase cell cycle arrest. ARRB1 knockdown cells showed remarkable down-regulation of CDC25C/CDK1/cyclin B1 activity. We also demonstrated that ARRB1 mediated prolonged phosphorylation of ERK1/2 and Akt in glioblastoma cells induced by NK1R activation. ERK1/2 and Akt phosphorylation are involved in regulating CDC25C/CDK1/cyclin B1 activity. The lack of long-term ERK1/2 and Akt activation in ARRB1 knockdown cells was at least partly responsible for the delayed cell cycle progression and proliferation. Moreover, we found that ARRB1-mediated ERK1/2 and Akt phosphorylation regulated the transcriptional activity of both NF-κB and AP-1, which were involved in cyclin B1 expression. ARRB1 deficiency increased the sensitivity of glioblastoma cells to the treatment of NK1R antagonists. Taken together, our results suggest that ARRB1 plays an essential role in NK1R-mediated cell proliferation and G 2 /M transition in glioblastoma cells. Interference with ARRB1-mediated signaling via NK1R may have potential significance for therapeutic strategies targeting glioblastoma. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene 'knockout' mice: sex differences and implications for the treatment of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Porter, Ashley J; Pillidge, Katharine; Grabowska, Ewelina M; Stanford, S Clare

    2015-04-01

    Mice lacking functional neurokinin-1 receptors (NK1R-/-) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R-/- and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R-/- mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R-/- and wildtype mice. Both antagonists increased the locomotor activity of NK1R-/- mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R-/- and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R-/- mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  9. The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene ‘knockout’ mice: Sex differences and implications for the treatment of attention deficit hyperactivity disorder

    Science.gov (United States)

    Porter, Ashley J.; Pillidge, Katharine; Grabowska, Ewelina M.; Stanford, S. Clare

    2015-01-01

    Mice lacking functional neurokinin-1 receptors (NK1R−/−) display behavioural abnormalities resembling attention deficit hyperactivity disorder (ADHD): locomotor hyperactivity, impulsivity and inattentiveness. The preferred ligand for NK1R, substance P, is metabolised by angiotensin converting enzyme (ACE), which forms part of the brain renin angiotensin system (BRAS). In view of evidence that the BRAS modulates locomotor activity and cognitive performance, we tested the effects of drugs that target the BRAS on these behaviours in NK1R−/− and wildtype mice. We first tested the effects of the ACE inhibitor, captopril, on locomotor activity. Because there are well-established sex differences in both ADHD and ACE activity, we compared the effects of captopril in both male and female mice. Locomotor hyperactivity was evident in male NK1R−/− mice, only, and this was abolished by treatment with captopril. By contrast, male wildtypes and females of both genotypes were unaffected by ACE inhibition. We then investigated the effects of angiotensin AT1 (losartan) and AT2 (PD 123319) receptor antagonists on the locomotor activity of male NK1R−/− and wildtype mice. Both antagonists increased the locomotor activity of NK1R−/− mice, but neither affected the wildtypes. Finally, we tested the effects of captopril on the performance of male NK1R−/− and wildtype mice in the 5-choice serial reaction-time task (5-CSRTT) and found that ACE inhibition prevented the impulsivity of NK1R−/− mice. These results indicate that certain behaviours, disrupted in ADHD, are influenced by an interaction between the BRAS and NK1R, and suggest that ACE inhibitors could provide a novel treatment for this disorder. PMID:25703442

  10. The Role of Hydrophobicity and Surface Receptors at Hyphae of Lyophyllum sp. Strain Karsten in the Interaction with Burkholderia terrae BS001 – Implications for Interactions in Soil

    Science.gov (United States)

    Vila, Taissa; Nazir, Rashid; Rozental, Sonia; dos Santos, Giulia M. P.; Calixto, Renata O. R.; Barreto-Bergter, Eliana; Wick, Lukas Y.; van Elsas, Jan Dirk

    2016-01-01

    The soil bacterium Burkholderia terrae strain BS001 can interact with varying soil fungi, using mechanisms that range from the utilization of carbon/energy sources such as glycerol to the ability to reach novel territories in soil via co-migration with growing fungal mycelia. Here, we investigate the intrinsic properties of the B. terrae BS001 interaction with the basidiomycetous soil fungus Lyophyllum sp. strain Karsten. In some experiments, the ascomycetous Trichoderma asperellum 302 was also used. The hyphae of Lyophyllum sp. strain Karsten were largely hydrophilic on water-containing media versus hydrophobic when aerial, as evidenced by contact angle analyses (CA). Co-migration of B. terrae strain BS001 cells with the hyphae of the two fungi occurred preferentially along the - presumably hydrophilic - soil-dwelling hyphae, whereas aerial hyphae did not allow efficient migration, due to reduced thickness of their surrounding mucous films. Moreover, the cell numbers over the length of the hyphae in soil showed an uneven distribution, i.e., the CFU numbers increased from minima at the inoculation point to maximal numbers in the middle of the extended hyphae, then decreasing toward the terminal side. Microscopic analyses of the strain BS001 associations with the Lyophyllum sp. strain Karsten hyphae in the microcosms confirmed the presence of B. terrae BS001 cells on the mucous matter that was present at the hyphal surfaces of the fungi used. Cell agglomerates were found to accumulate at defined sites on the hyphal surfaces, which were coined ‘fungal-interactive’ hot spots. Evidence was further obtained for the contention that receptors for a physical bacterium-fungus interaction occur at the Lyophyllum sp. strain Karsten hyphal surface, in which the specific glycosphingolipid ceramide monohexoside (CMH) plays an important role. Thus, bacterial adherence may be mediated by heterogeneously distributed fungal-specific receptors, implying the CMH moieties. This

  11. Neurokinin-1 receptor antagonism in a rat model of subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Ansar, Saema; Svendgaard, Niels-Aage; Edvinsson, Lars

    2007-01-01

    OBJECT: Cerebral vasospasm following subarachnoid hemorrhage (SAH) leads to reduced cerebral blood flow (CBF) and to cerebral ischemia, in some cases even producing infarction and long-term disability. The goal of the present study was to investigate the hypothesis that inhibition of neurokinin-1...... receptors (NK1Rs) by administration of L-822429 blunts the decrease in CBF as well as cerebrovascular receptor upregulation in an animal model of SAH. METHODS: Subarachnoid hemorrhage was induced in rats by injection of 250 microl of blood into the prechiasmatic cistern. The NK1R inhibitor L-822429...

  12. Immunohistochemical localization of 3β-Hydroxysteroid dehydrogenase and progesterone receptors in the ovary and placenta during gestation of the placentotrophic lizard Mabuya sp (Squamata: Scincidae).

    Science.gov (United States)

    Duarte-Méndez, Melissa; Quintero-Silva, Jennifer; Ramírez-Pinilla, Martha Patricia

    2018-02-27

    In squamates, progesterone (P) plays a key role in the inhibition of uterine mobility during egg retention in oviparous species, and during gestation in viviparous species. The corpus luteum (CL) is the main organ responsible for the production of P; however, in some species, the CL degenerates early and the P needed for gestation maintenance should be produced in other tissues. Mabuya sp (Scincidae) is a viviparous lizard with a prolonged gestation, it produces microlecithal eggs and, consequently, has an obligate placentotrophy related with a highly complex placenta. Its CL degenerates at early stages of gestation and therefore, other sources of P should exist. The aim of this study was to determine and localize by immunohistochemistry the production of P by detection of the enzyme 3β-Hydroxysteroid dehydrogenase (3β-HSD) and P receptors (PR) during gestation in the ovary and placenta of Mabuya sp. Positive and negative control sections were used. The ovary of this species localizes 3β-HSD and PR in the same tissues. The CL of the ovaries of females at early stages of gestation were positive for both molecules, whereas they did not localize from mid gestation to the end of pregnancy. Previtellogenic and vitellogenic follicles labelled for both molecules in the follicular epithelium and thecae. The placenta of Mabuya sp. demonstrated the potential for P production from mid gestation to the end of gestation in the uterine and chorionic tissues. PR were located in the uterine tissues throughout gestation, with a decrease towards its completion. Western blot analysis confirmed the presence of 3β-HSD mainly in the ovary of early pregnant females and in the placental tissues at mid gestation stages. Therefore, the chorioallantoic placenta of Mabuya sp. has an endocrine function producing the P needed for gestation and replacing the CL from mid gestation to the end of pregnancy. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Clinical pharmacology of neurokinin-1 receptor antagonists for the treatment of nausea and vomiting associated with chemotherapy.

    Science.gov (United States)

    Rapoport, Bernardo; Smit, Teresa

    2017-06-01

    Five NK-1 RA formulations are commercially available to treat the delayed phase of chemotherapy-induced nausea and vomiting (CINV) occurring between days 2-5 post chemotherapy (aprepitant oral capsule and suspension, fosaprepitant intravenous infusion, netupitant/palonosetron capsules and rolapitant tablet) but no direct comparative studies have been conducted to determine their relative clinical utility. Areas covered: Information on pharmacology and safety of the NK-1 RAs derived from PubMed showed that all bind the NK-1 receptor with high affinity and selectivity. There is substantial variation in the disposition and time course in the body of NK-1 RAs because of the differential effects of hepatic metabolism. Unlike netupitant and rolapitant, aprepitant is metabolized extensively by cytochrome P450 (CYP) 3A4. Aprepitant and netupitant also both inhibit CYP3A4. Consequently, aprepitant not only has a much shorter elimination half-life than netupitant and rolapitant but also a more prolific drug interaction profile. All of the NK-1 RAs are efficacious and safe, and are suitable for use in a range of different patient populations, including those with mild or moderate hepatic or renal impairment. Expert opinion: While discovery of NK-1 RAs represents a major breakthrough in CINV control, further work is needed to improve control of chemotherapy-induced nausea.

  14. Expression of tachykinins and their receptors in plaque psoriasis with pruritus.

    Science.gov (United States)

    Amatya, B; El-Nour, H; Holst, M; Theodorsson, E; Nordlind, K

    2011-05-01

    BACKGROUND Various mediators of pruritus have been suggested that might be responsible for the mechanism of pruritus in psoriasis. To study the expression levels of members of the tachykinin family, substance P and neurokinin (NK) A and their receptors, NK-1 and NK-2, in psoriasis and to correlate their expression with the intensity of pruritus. A possible correlation with chronic stress and depression was also evaluated. Biopsies were obtained from 28 patients with chronic plaque psoriasis; the majority had pruritus. The samples were taken from lesional and nonlesional areas on the back and also from 10 healthy controls, for immunohistochemistry staining, and from lesional skin for radioimmunoassay. Prior to biopsy, the clinical severity of the psoriasis of each patient was assessed by the Psoriasis Area and Severity Index (PASI) and the intensity of pruritus was measured by using a visual analogue scale (VAS). Levels of depression and stress were measured using Beck's Depression Inventory (BDI) and the salivary cortisol test, respectively. Substance P-, NKA- and NK-2 receptor-immunoreactive nerves, and non-neuronal inflammatory cells positive for substance P and NKA and their respective receptors, NK-1 and NK-2, were numerous in psoriasis compared with healthy controls. The numbers of substance P-positive nerves and NK-2 receptor-positive cells in lesional skin were significantly correlated to pruritus intensity. The cortisol ratio was inversely correlated with the number of NK-1 receptor-immunoreactive inflammatory cells in lesional and nonlesional psoriasis skin. There was also a positive correlation between the BDI score and the number of substance P-positive cells in nonlesional skin and with NK-1 receptor-positive cells in lesional and nonlesional skin. Tachykinins may play a role in psoriasis per se, in addition to pruritus in this disease. Targeting the combined NK-1 and NK-2 receptors might be a possible treatment. © 2011 The Authors. BJD © 2011 British

  15. Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons

    OpenAIRE

    Gray, Paul A.; Janczewski, Wiktor A.; Mellen, Nicholas; McCrimmon, Donald R.; Feldman, Jack L.

    2001-01-01

    The normal breathing rhythm in mammals is hypothesized to be generated by neurokinin-1 receptor (NK1R)-expressing neurons in the preBötzinger complex (preBötC), a medullary region proposed to contain the kernel of the circuits generating respiration. If this hypothesis is correct, then complete destruction of preBötC NK1R neurons should severely perturb and perhaps even fatally arrest breathing. Here we show that specific and near complete bilateral (but not unilateral) destruction of preBötC...

  16. Immunocytochemical localization of the neurokinin 1 receptor in rat dental pulp.

    Science.gov (United States)

    Kido, Mizuho A; Ibuki, Teiichi; Danjo, Atsushi; Kondo, Teruyoshi; Zhang, Jing-Qi; Yamaza, Takayoshi; Yamashita, Yoshio; Higuchi, Yoshinori; Tanaka, Teruo

    2005-12-01

    The dentin-pulp complex is a peripheral end-organ supplied by dense sensory nerve fibers. Substance P, a representative neuropeptide widely distributed in the dental pulp, has been reported to play roles in pain transmission and the amplification of inflammation. We analyzed here the expression of the neurokinin 1 (NK1) receptor, preferentially activated by substance P, using immunocytochemistry in rat dental pulp at both the light and electron microscopic levels. Conspicuous NK1 receptor immunoreactivity was found in the odontoblasts; immunolabelings were present at their plasma membrane and endosomal structures, especially in their cytoplasmic processes. Immunoreactions for NK1 receptor were also detectable in a part of the nerve terminals associated with the cytoplasmic processes of the odontoblasts. Furthermore, the endothelial cells of capillaries and post-capillary venules and the fibroblasts were labeled with the NK1 receptor in the subodontoblast layer. These findings suggest that pulpal cells and nerve fibers are targets for substance P that mediate multiple functions, including a vasoactive function and the regulation of vascular permeability as well as the modulation of pain transmission.

  17. Construction of covalently coupled, concatameric dimers of 7TM receptors

    DEFF Research Database (Denmark)

    Terpager, Marie; Scholl, D Jason; Kubale, Valentina

    2009-01-01

    -Ala repeats flanked by flexible spacers and positively charged residues to ensure correct inside-out orientation plus an extracellular HA-tag to construct covalently coupled dimers of 7TM receptors. Such 15 TM concatameric homo- and heterodimers of the beta(2)-adrenergic and the NK(1) receptors, which...... for either of the protomers, which was not observed upon simple coexpression of the two receptors. It is concluded that covalently joined 7TM receptor dimers with surprisingly normal receptor properties can be constructed with use of an artificial transmembrane connector, which perhaps can be used to fuse...

  18. Altered expression of the tachykinins substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors in uterine leiomyomata.

    Science.gov (United States)

    González-Santana, Ayoze; Marrero-Hernández, Sara; Dorta, Idaira; Hernández, Mariano; Pinto, Francisco María; Báez, Delia; Bello, Aixa R; Candenas, Luz; Almeida, Teresa A

    2016-11-01

    To study the expression levels of tachykinins and tachykinin receptors in uterine leiomyomas and matched myometrium. Laboratory study. University research laboratories and academic hospital. Women undergoing hysterectomy for symptomatic leiomyomas. Quantitative polymerase chain reaction, immunohistochemistry and Western blot. Expression and tissue immunostaining of substance P, neurokinin A, hemokinin-1, neurokinin 1 receptor full-length (NK1R-Fl) and truncated (NK1R-Tr) isoforms, and neurokinin 2 receptor (NK2R) in paired samples of leiomyoma and adjacent normal myometrium. TAC1 messenger RNA (mRNA) was significantly up-regulated in leiomyomas, whereas intense immunoreaction for the three peptides was particularly abundant in connective tissue cells. Differential regulation of TACR1 mRNA was observed, and at the protein level there was a significant increased expression of NK1R short isoform (NK1R-Tr). TACR2 mRNA was significantly up-regulated in leiomyomas, although levels of NK2R protein were similar in normal and tumor cells. These and our previous data demonstrate that the whole tachykinin system is differentially regulated in leiomyomas. The increased expression of NK1R-Tr might stimulate leiomyoma growth in a similar way to that observed in other steroid-dependent tumors. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. TMPRSS2-ERG fusion protein regulates insulin-like growth factor-1 receptor (IGF1R) gene expression in prostate cancer: involvement of transcription factor Sp1.

    Science.gov (United States)

    Meisel Sharon, Shilhav; Pozniak, Yair; Geiger, Tamar; Werner, Haim

    2016-08-09

    Prostate cancer is a major health issue in the Western world. The most common gene rearrangement in prostate cancer is the TMPRSS2-ERG fusion, which results in aberrant expression of the transcription factor ERG. The insulin-like growth factor-1 receptor (IGF1R) plays a key role in cell growth and tumorigenesis, and is overexpressed in most malignancies, including prostate cancer. In this study we show that TMPRSS2-ERG mediates its tumorigenic effects through regulation of IGF1R gene expression. Silencing of T-ERG in VCaP cells resulted in downregulation of both IGF1R and Sp1, a critical IGF1R regulator. Co-immunoprecipitation assays revealed a physical interaction between transcription factors ERG and Sp1, with potential relevance in IGF1R gene regulation. In addition, transactivation of the IGF1R gene by ERG was mediated at the level of transcription, as indicated by results of promoter assays. To identify new co-activators of the TMPRSS2-ERG fusion protein we performed mass spectrometry-based proteomic analyses. Among other interactors, we identified AP-2 complex subunit mu (AP2M1) and caveolin-1 (CAV1) in association with ERG in cell nuclei. These proteins play a mechanistic role in IGF1R internalization. Our analyses are consistent with a potential novel function of TMPRSS2-ERG as a major regulator of IGF1R gene expression. Results may impinge upon ongoing efforts to target the IGF1R in the clinics.

  20. Expression profile of toll-like receptor 2 mRNA in selected tissues of shark (Chiloscyllium sp.).

    Science.gov (United States)

    Anandhakumar, C; Lavanya, V; Pradheepa, G; Tirumurugaan, K G; Raj, G Dhinakar; Raja, A; Pazhanivel, N; Balachandran, C

    2012-11-01

    Sharks are a species of delight for immunologists from the evolutionary perspective since it is considered as the first species to have evolved the adaptive immune responses in addition to the innate immune system. One of the components of the highly conserved innate immune system is the toll-like receptors (TLR) which has a conserved overall protein structure throughout deuterostome evolution. There is no report that demonstrates the expression of these receptors in sharks. In this study we successfully amplified a 270 bp amplicon using a degenerate primer design strategy that corresponded to the Toll/IL-1 receptor (TIR) domain of TLR2 (GenBank ID: JF792813). BLAST analysis revealed a maximum nucleotide identity of 87% and 76% with the TLR2 of higher mammals and teleost fishes respectively. Domain prediction revealed a TIR structure between 1 and 87 amino acids that had a maximum identity of 58% and 76% with TLR2 - TIR protein of teleost fishes and higher mammals respectively. Phylogenetic analysis revealed a closer clustering of the shark TIR sequence with those from human, cattle, goat, sheep and chicken than with other fish species. Basal expression levels of the TLR2-TIR mRNA were found to be significantly higher in kidneys followed by fins, spleen and intestinal spiral valve (ISV). In tissues such as spleen and kidney the expression of the TLR2-TIR mRNA could be localized to lymphoid and macrophages like cells and tubular epithelial cells respectively. In-vivo exposure of sharks to peptidoglycan (TLR 2 ligand) resulted in 9 folds higher expression of TLR2-TIR mRNA in gills followed by 5 folds in the fins. However, when inoculated with a TLR ligand pool, the expression levels significantly increased to 12 fold in skin followed by epigonal, kidneys and ISV. These findings not only support the presence of the TLRs in sharks but also their induction upon exposure to specific ligands. Further studies are needed to identify their numbers, their ligand specificity

  1. Tachykinin receptors mediating responses to sensory nerve stimulation and exogenous tachykinins and analogues in the rabbit isolated iris sphincter.

    Science.gov (United States)

    Hall, J. M.; Mitchell, D.; Morton, I. K.

    1993-01-01

    1. We have used selective tachykinin receptor agonists and antagonists to investigate the nature of the receptors mediating responses to endogenous and exogenous tachykinins in the rabbit iris sphincter preparation in vitro. 2. The NK1-selective agonist, substance P methyl ester, induced contraction with a pD2 of 9.16 indicating the presence of NK1 receptors. In confirmation, the NK1-selective antagonist, GR82334, competitively antagonized responses to substance P methyl ester with high affinity (pKB 7.46). 3. NK3 receptors also mediate contraction since NK3-selective agonists exhibited high potency, e.g. the pD2 of [Me-Phe7]-neurokinin B was 9.67, and their responses were not inhibited by GR82334 (10 microM). 4. NK2 receptor activation does not seem to contribute to contraction since the NK2-selective agonist [beta-Ala8]-neurokinin A(4-10) had relatively low potency (pD2 6.43), and the NK2-selective antagonists MEN10207 (1 microM) and L-659,877 (10 microM) were inactive or had low affinity, respectively. 5. GR82334 (1 microM) significantly inhibited responses to electrical field-stimulation of non-adrenergic non-cholinergic sensory nerves (3, 10 and 30 Hz), and caused a rightward shift of the log concentration-response curve to bradykinin (lateral shift ca. 1000 fold). Higher concentrations of GR82334 (10 microM) significantly attenuated responses to capsaicin (1-60 microM) whilst completely abolishing responses to field-stimulation (3, 10 and 30 Hz) and bradykinin (1 nM- 3 microM). 6. In conclusion, NK1 and NK3 receptor activation results in contraction of the rabbit iris sphincter. The contractile response following sensory nerve stimulation by bradykinin, capsaicin and electrical field stimulation results from NK1 receptor activation. PMID:8401912

  2. Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists.

    Science.gov (United States)

    Hoffmann, Torsten; Bös, Michael; Stadler, Heinz; Schnider, Patrick; Hunkeler, Walter; Godel, Thierry; Galley, Guido; Ballard, Theresa M; Higgins, Guy A; Poli, Sonia M; Sleight, Andrew J

    2006-03-01

    The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1)) receptor antagonists is described. The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration.

  3. The NK-2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma

    NARCIS (Netherlands)

    Kraan, J; Vink-Klooster, H; Postma, DS

    Background When stimulated, excitatory nonadrenergic noncholinergic (e-NANC) nerves locally release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic inflammation and airway obstruction via activation of specific NK-1 and NK-2 receptors. The recently developed nonpeptide NK-2

  4. Role of tachykinin receptors in the modulation of colonic peristaltic activity in mice.

    Science.gov (United States)

    Deiteren, Annemie; De Winter, Benedicte Y; Nullens, Sara; Pelckmans, Paul A; De Man, Joris G

    2011-09-30

    Tachykinins are important mediators of neuroneuronal and neuromuscular transmission in the gastrointestinal tract, however their contribution to colonic peristalsis in mice remains unclear. Therefore, our aim was to characterise the functional role of tachykinins in mediating peristalsis by evaluating the effect of selective tachykinin NK(1), NK(2) and NK(3) receptor agonists and antagonists on in vitro colonic peristaltic activity in mice. Using a modified Trendelenburg set-up, gradual distension of proximal and distal colonic segments evoked rhythmic, aborally migrating contractions. Peristaltic activity was assessed by quantifying the amplitude and interval of the corresponding pressure waves. Stimulation of NK(1) receptors showed regional differences as both the pressure amplitude and interval were enhanced in the distal colon without affecting peristalsis proximally. Blockade of NK(1) receptors reduced the peristaltic pressure amplitude in the proximal and distal colon while the interval was not significantly altered. NK(2) receptor stimulation resulted in a modest enhancement of the amplitude in proximal and distal segments and a slightly prolonged interval distally. Blockade of NK(2) receptors reduced the peristaltic pressure amplitude and interval in the distal colon. NK(3) receptor stimulation significantly augmented the amplitude in both segments and prolonged the interval distally. However, NK(3) receptor blockade had no effect on peristaltic activity. In conclusion, tachykinins contribute to colonic peristalsis in mice by acting mainly on NK(1) and NK(2) receptors and their effects show a proximal-to-distal gradient. NK(3) receptors might play a role in conditions of excess tachykinin release but appear not to be involved under the conditions of the present study. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Qualidade de um sistema latossolo-argissolo como receptor de efluentes no município de Lins(SP Quality of a latosol-argisol system in the county of Lins/SP, Brazil

    Directory of Open Access Journals (Sweden)

    Liliane Ibrahim

    2008-12-01

    Full Text Available Este trabalho objetivou caracterizar um sistema de solos, evidenciando a propriedades que possam esclarecer sua dinâmica e contribuir para a definição de critérios que condicionem a aptidão destes solos como receptores de efluentes. Trata-se de uma área experimental de estudos, contígua à Estação de Tratamento de Esgoto do município de Lins (SP, onde o efluente é gerado a partir do tratamento de esgoto por sistema de lagoas de estabilização. Os solos, situados ao longo de uma vertente com ligeira inclinação, foram caracterizados por meio de análises, morfológica, granulométrica, química, mineralógica e micromorfológica, realizadas em amostras coletadas em cinco trincheiras em toposseqüência. Os solos são desenvolvidos a partir dos sedimentos arenosos da Formação Adamantina (Grupo Bauru e constituem um sistema Latossolo - Argissolo onde a transição Bw - Bt ocorre lateralmente do topo para a base da vertente. Foram identificadas três fases pedogenéticas nesta associação de solos. A primeira, argiluviação e adensamento de partículas, responsável pela formação dos horizontes texturais, foi superposta pelos processos de latossolização e hidromorfismo, atuantes na dinâmica atual destes solos. Análises micromorfológicas mostraram tratar-se de solos com intensa porosidade, caracterizada pelo empilhamento dos grãos do esqueleto quartzoso amplamente predominante e pelo arranjo entre os microagregados granulares. A permeabilidade é ainda favorecida pela intensa ação da mesofauna. Os solos são distróficos e compostos por caulinita e óxidos de Fe na fração argilosa. Por constituírem um sistema frágil, a disposição de quaisquer tipos de resíduos nestes solos requer o monitoramento constante de suas propriedades, tanto para a manutenção, quanto para a recuperação da qualidade desta cobertura pedológica.The purpose of this study was the characterization of a soil system, focused on proprieties that

  6. Tachykinins and tachykinin-receptors in the rat pineal gland.

    Science.gov (United States)

    Mukda, S; Chetsawang, B; Govitrapong, P; Schmidt, P T; Hay-Schmidt, A; Møller, M

    2005-05-01

    High-pressure liquid chromatography of extracts of rat pineal glands, followed by radio immunological analysis with antibodies against tachykinins, demonstrated the presence of substance P, neurokinin A and neurokinin B in the superficial rat pineal gland. Immunohistochemistry on perfusion-fixed rat brain sections showed substance P and neurokinin A to be present in nerve fibers located both in the perivascular spaces as well as intraparenchymally between the pinealocytes. After extracting total RNA, followed by reverse transcription and polymerase chain reaction amplification with primers specific for NK1-, NK2- and NK3-receptors, agarose gel analysis of the reaction products showed the presence of mRNA encoding all three neurokinin receptors. Immunohistochemical analysis showed NK1 receptor to be located in the interstitial cells of the gland. This location was confirmed by use of in situ hybridization using radioactively labeled antisense oligonucleotide probes. Double immunohistochemical stainings showed that the NK1-immunoreactive cells were not a part of the macrophages or antigen-presenting cells of the gland. Our study suggests that tachykinins, after release from intrapineal nerve fibers, are involved in an up to now unknown function, different from that of melatonin synthesis.

  7. Airway inflammation and tachykinins: prospects for the development of tachykinin receptor antagonists.

    Science.gov (United States)

    Joos, G F; De Swert, K O; Pauwels, R A

    2001-10-19

    The tachykinins substance P and neurokinin A are contained within sensory airway nerves. Immune cells form an additional source of tachykinins in inflamed airways. Elevated levels of tachykinins have been recovered from the airways of patients with asthma and chronic obstructive pulmonary disease. Airway inflammation leads to an upregulation of tachykinin NK(1) and NK(2) receptors. Preclinical studies have indicated a role for the tachykinin NK(1), NK(2) and NK(3) receptors in bronchoconstriction, airway hyperresponsiveness and airway inflammation caused by allergic and nonallergic stimuli. Compounds that are able to block two or three tachykinin receptors hold promise for the treatment of airways diseases such as asthma and/or chronic obstructive pulmonary disease.

  8. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  9. Broad-spectrum antiemetic potential of the L-type calcium channel antagonist nifedipine and evidence for its additive antiemetic interaction with the 5-HT(3) receptor antagonist palonosetron in the least shrew (Cryptotis parva).

    Science.gov (United States)

    Darmani, Nissar A; Zhong, Weixia; Chebolu, Seetha; Vaezi, Mariam; Alkam, Tursun

    2014-01-05

    Cisplatin-like chemotherapeutics cause vomiting via release of multiple neurotransmitters (dopamine, serotonin (5-HT), or substance P (SP)) from the gastrointestinal enterochromaffin cells and/or the brainstem via a calcium dependent process. Diverse channels in the plasma membrane allow extracellular Ca(2+) entry into cells for the transmitter release process. Agonists of 5-HT3 receptors increase calcium influx through both 5-HT3 receptors and L-type Ca(2+) channels. We envisaged that L-type calcium agonists such as FPL 64176 should cause vomiting and corresponding antagonists such as nifedipine would behave as broad-spectrum antiemetics. Administration of FPL 64176 did cause vomiting in the least shrew in a dose-dependent fashion. Nifedipine and the 5-HT3 receptor antagonist palonosetron, potently suppressed FPL 64176-induced vomiting, while a combination of ineffective doses of these antagonists was more efficacious. Subsequently, we investigated the broad-spectrum antiemetic potential of nifedipine against diverse emetogens including agonists of serotonergic 5-HT3- (e.g. 5-HT or 2-Me-5-HT), SP tachykinin NK1- (GR73632), dopamine D2- (apomorphine or quinpirole), and cholinergic M1- (McN-A-343) receptors, as well as the non-specific emetogen, cisplatin. Nifedipine by itself suppressed vomiting in a potent and dose-dependent manner caused by the above emetogens except cisplatin. Moreover, low doses of nifedipine potentiated the antiemetic efficacy of non-effective or semi-effective doses of palonosetron against vomiting caused by either 2-Me-5-HT or cisplatin. Thus, our findings demonstrate that activation of L-type calcium channels causes vomiting, whereas blockade of these ion channels by nifedipine-like antagonists not only provides broad-spectrum antiemetic activity but can also potentiate the antiemetic efficacy of well-established antiemetics such as palonosetron. L-type calcium channel antagonists should also provide antiemetic activity against drug

  10. Modulation of excitatory amino acid responses by tachykinins and selective tachykinin receptor agonists in the rat spinal cord.

    Science.gov (United States)

    Cumberbatch, M. J.; Chizh, B. A.; Headley, P. M.

    1995-01-01

    1. The effects of tachykinins and agonists selective for the three subtypes of neurokinin (NK) receptor have been tested on spinal neuronal responses both to the excitatory amino acids (EAAs) NMDA, AMPA and kainate, and to noxious heat stimuli. The agonists were applied by microiontophoresis in in vivo experiments in alpha-chloralose-anaesthetized, spinalized rats. 2. The NK1-selective agonist, GR 73632, enhanced responses to all three EAAs similarly, whilst the NK2-selective agonist, GR64349, reduced responses to AMPA and kainate without affecting those to NMDA, and the NK3 selective agonist, senktide, enhanced responses to AMPA and kainate. 3. The endogenous ligands substance P (SP) and neurokinin A (NKA) both enhanced responses to NMDA with little effect on responses to kainate, whereas neurokinin B (NKB) selectively enhanced responses to kainate without affecting those to NMDA. 4. The effects of GR73632 on EAA responses showed some differences between the dorsal and ventral horn, with more selectivity towards enhancement of NMDA responses in the ventral horn, but a smaller maximum effect. 5. Background activity was significantly enhanced by GR73632, GR64349, SP and NKA but not by senktide or NKB. GR73632 had the greatest effect on background firing, but this action was variable between cells and was related both to the location within the spinal cord and to the degree of spontaneous activity prior to GR73632 administration. 6. Responses to noxious heat were enhanced consistently only by NKA. 7. These data show that selective agonists for the tachykinin receptors are capable of modulating EAA responses differentially.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582496

  11. A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Spiess, S

    1995-01-01

    We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were p...

  12. Tachykinins and tachykinin receptors: a growing family.

    Science.gov (United States)

    Pennefather, Jocelyn N; Lecci, Alessandro; Candenas, M Luz; Patak, Eva; Pinto, Francisco M; Maggi, Carlo Alberto

    2004-02-06

    The peptides of the tachykinin family are widely distributed within the mammalian peripheral and central nervous systems and play a well-recognized role as excitatory neurotransmitters. Currently, the concept that tachykinins act exclusively as neuropeptides is being challenged, since the best known members of the family, substance P, neurokinin A and neurokinin B, are also present in non-neuronal cells and in non-innervated tissues. Moreover, the recently cloned mammalian tachykinins hemokinin-1 and endokinins are primarily expressed in non-neuronal cells, suggesting a widespread distribution and important role for these peptides as intercellular signaling molecules. The biological actions of tachykinins are mediated through three types of receptors denoted NK(1), NK(2) and NK(3) that belong to the family of G protein-coupled receptors. The identification of additional tachykinins has reopened the debate of whether more tachykinin receptors exist. In this review, we summarize the current knowledge of tachykinins and their receptors.

  13. The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis

    DEFF Research Database (Denmark)

    Waldhoer, Maria; Casarosa, Paola; Rosenkilde, Mette M

    2003-01-01

    US28 is one of four 7 transmembrane (7TM) chemokine receptors encoded by human cytomegalovirus and has been shown to both signal and endocytose in a ligand-independent, constitutively active manner. Here we show that the constitutive activity and constitutive endocytosis properties of US28...... that the cytoplasmic tail domain of US28 per se regulates receptor endocytosis, independent of the signaling ability of the core domain of US28. The constitutive endocytic property of the US28 c-tail was transposable to other 7TM receptors, the herpes virus 8-encoded ORF74 and the tachykinin NK1 receptor (ORF74-US28...

  14. The N-terminal domain of human hemokinin-1 influences functional selectivity property for tachykinin receptor neurokinin-1.

    Science.gov (United States)

    Mou, Lingyun; Xing, Yanhong; Kong, Ziqing; Zhou, Ying; Chen, Zongyao; Wang, Rui

    2011-03-01

    Human hemokinin-1 (hHK-1) is a substance P-like tachykinin peptide preferentially expressed in non-neuronal tissues. It is involved in multiple physiological functions such as inflammation, hematopoietic cells development and vasodilatation via the interaction with tachykinin receptor neurokinin-1 (NK1). To further understand the intracellular signal transduction mechanism under such functional multiplicity, current study was focused on the differential activation of Gs and Gq pathways by hHK-1 and its C-terminal fragments, which is termed as functional selectivity. We demonstrated these hHK-1 and related peptide fragments can independently activate Gs and Gq pathways, showing a relative bias toward Gq over Gs pathway. The T1, K3 and Q6 of hHK-1 might play roles in the activation of adenylate cyclase mediated by Gs, while having negligible effect on Gq mediated intracellular calcium release. The stepwise truncation of N-terminal amino acid of hHK-1 caused gradual decrease in ERK1/2 phosphorylation level and NF-κB activity. However, it had little influence on the induction of NK1 receptor desensitization and internalization. Taken together these data support that hHK-1 and its C-terminal fragments are human NK1 receptor agonists with different functional selectivity properties and that such functional selectivity leads to differential activation of downstream signaling and receptor trafficking. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of Dr+ Escherichia coli receptor protein decay accelerating factor (DAF or CD55) by nitric oxide.

    Science.gov (United States)

    Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

    2013-02-01

    We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr(+) ). The epithelial invasion of Dr(+) E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by downregulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5'-untranslated region and mapped the NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5'-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3'-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to the AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. © 2012 The Authors Journal compilation © 2012 FEBS.

  16. Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Grunberg, Steven M; Rolski, Janusz; Strausz, Janos

    2009-01-01

    intravenous plus oral casopitant mesylate (90 mg intravenous on day 1 plus 50 mg oral on days 2 and 3, n=270). Randomisation was done using a central telephone system at the study level, because some centres were expected to recruit only a few patients during the study period. The primary endpoint...

  17. Inmunolocalización de la sustancia p y receptor nk1 en el intestino normal de recién nacidos prematuros y en prematuros con enterocolitis necrotizante

    OpenAIRE

    Solo De Zaldívar Tristancho, María

    2016-01-01

    La ECN es una enfermedad inflamatoria devastadora del TGI que afecta a un 4% a 11% de los RN de MBPN y es una causa importante de morbilidad y mortalidad en esta población. Se caracterizada por inflamación e isquemia de intestino delgado y colon que progresa hacia la necrosis transmural y perforación. Constituye la principal emergencia gastrointestinal en el prematuro y, junto con la prematuridad y el distrés respiratorio, es una de las causas más importantes de estancia hospitalaria prolonga...

  18. Characterization of receptors mediating contraction induced by tachykinins in the guinea-pig isolated common bile duct

    Science.gov (United States)

    Patacchini, Riccardo; Barthó, Lorand; Alberto Maggi, Carlo

    1997-01-01

    We studied the effect of the natural tachykinins and of synthetic agonists selective for the tachykinin NK1, NK2 and NK3 receptors, on the motility of guinea-pig isolated common bile duct longitudinally-oriented smooth muscle. All the tachykinins tested (both natural and synthetic) produced a concentration-dependent contractile response of the guinea-pig isolated common bile duct: these effects underwent a marked tachyphylaxis, especially the responses elicited by NK1 and NK3 receptor-selective agonists. Among the natural tachykinins neurokinin B (EC50=3.2 nM; 95% c.l.=2.0–5.1; n=4) was the most potent, being about 40 and 25 fold more potent than substance P (EC50=121.6 nM; 95% c.l.=94–157; Ptachykinins (natural or synthetic receptor agonists) produced a similar Emax, averaging about 50% of that produced by KCl (80 mM). Atropine (1 μM) did not affect the responses to either NK1 or NK2 receptor-selective agonists, whereas it reduced the Emax of senktide by about 50%, without affecting its potency (EC50). Tetrodotoxin (1 μM) totally blocked senktide-induced contractions, as did the combined pretreatment with atropine plus the tachykinin NK1 and NK2 receptor-selective antagonists GR 82334 and MEN 11420 (1 μM each), respectively. GR 82334 (1 μM) blocked with apparent competitive kinetics septide- (apparent pKB=7.46±0.10; n=5) and [Sar9]substance P sulfone- (apparent pKB=6.80±0.04; n=4) induced contractions. MEN 11420 (30–300 nM), a novel potent NK2 receptor antagonist, potently antagonized [βAla8]NKA (4–10), with competitive kinetics (pKB=8.25±0.08; n=12: Schild plot slope=−0.90; 95% c.l.=−1.4; −0.35). The NK3 receptor-selective antagonist SR 142801 (30 nM) produced insurmountable antagonism of the senktide-induced contractions (Emax inhibited by 64%). None of the above antagonists, tested at the highest concentrations employed against tachykinins, affected the concentration–response curve to methacholine (0.1–300

  19. Phosphorylation of ERK in neurokinin 1 receptor-expressing neurons in laminae III and IV of the rat spinal dorsal horn following noxious stimulation

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiko

    2007-02-01

    Full Text Available Abstract Background There is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r and have dendrites that enter the superficial laminae. Although it has been shown that these are all projection neurons and that they are innervated by substance P-containing (nociceptive primary afferents, we know little about their responses to noxious stimuli. In this study we have looked for phosphorylation of extracellular signal-regulated kinases (ERKs in these neurons in response to different types of noxious stimulus applied to one hindlimb of anaesthetised rats. The stimuli were mechanical (repeated pinching, thermal (immersion in water at 52°C or chemical (injection of 2% formaldehyde. Results Five minutes after each type of stimulus we observed numerous cells with phosphorylated ERK (pERK in laminae I and IIo, together with scattered positive cells in deeper laminae. We found that virtually all of the lamina III/IV NK1r-immunoreactive neurons contained pERK after each of these stimuli and that in the great majority of cases there was internalisation of the NK1r on the dorsal dendrites of these cells. In addition, we also saw neurons in lamina III that were pERK-positive but lacked the NK1r, and these were particularly evident in animals that had had the pinch stimulus. Conclusion Our results demonstrate that lamina III/IV NK1r-immunoreactive neurons show receptor internalisation and ERK phosphorylation after mechanical, thermal or chemical noxious stimuli.

  20. Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of the Neurokinin-1 Receptor System.

    Science.gov (United States)

    Berger, Michael; VON Schweinitz, Dietrich

    2017-11-01

    Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon. To this repεrtoirε, the neurokinin-1 receptor (NK1R) system was recently added. The present article explores the most recent developments in targeting neuroblastoma cells via the NK1R and how this new knowledge could be helpful to create new anticancer therapies agains neuroblastoma and other cancers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. From the Cover: Prenatal Nicotinic Exposure Attenuates Respiratory Chemoreflexes Associated With Downregulation of Tyrosine Hydroxylase and Neurokinin 1 Receptor in Rat Pup Carotid Body.

    Science.gov (United States)

    Zhao, Lei; Zhuang, Jianguo; Gao, Xiuping; Ye, Chunyan; Lee, Lu-Yuan; Xu, Fadi

    2016-09-01

    Maternal cigarette smoke is the major risk of sudden infant death syndrome (SIDS). A depressed ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) is thought to be responsible for the pathogenesis of SIDS and the carotid body is critically involved in these responses. We have recently reported that prenatal nicotinic exposure (PNE) over the full gestation induces depressed HVR in rat pups. Here, we asked whether PNE (1) depressed not only HVR but also HCVR that were dependent on the carotid body, (2) affected some important receptors and neurochemicals expressed in the carotid body, such as tyrosine hydroxylase (TH), neurokinin-1 receptor (NK1R), and α7 nicotinic acetylcholine receptor (α7nAChR), and (3) blunted the ventilatory responses to activation of these receptors. To this end, HVR and HCVR in Ctrl and PNE pups were measured with plethysmography before and after carotid body ablation (Series I), mRNA expression and/or immunoreactivity (IR) of TH, NK1R, and α7nAChR in the carotid body were examined by RT-PCR and immunohistochemistry (Series II), and the ventilatory responses were tested before and after intracarotid injection of substance P (NK1R agonist) and AR-R17779 (α7nAChR agonist) (Series III). Our results showed that PNE (1) significantly depressed both HVR and HCVR and these depressions were abolished by carotid body ablation, (2) reduced the relative population of glomus cells, mRNA NK1R, and α7nAChR and IR of NK1R and TH in the carotid body, and (3) decreased ventilatory responses to intracarotid injection of substance P or AR-R17779. These results suggest that PNE acting via the carotid body could strikingly blunt HVR and HCVR, likely through downregulating TH and NK1R. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Discovery of Indazoles as Potent, Orally Active Dual Neurokinin 1 Receptor Antagonists and Serotonin Transporter Inhibitors for the Treatment of Depression.

    Science.gov (United States)

    Degnan, Andrew P; Tora, George O; Huang, Hong; Conlon, David A; Davis, Carl D; Hanumegowda, Umesh M; Hou, Xiaoping; Hsiao, Yi; Hu, Joanna; Krause, Rudolph; Li, Yu-Wen; Newton, Amy E; Pieschl, Rick L; Raybon, Joseph; Rosner, Thorsten; Sun, Jung-Hui; Taber, Matthew T; Taylor, Sarah J; Wong, Michael K; Zhang, Huiping; Lodge, Nicholas J; Bronson, Joanne J; Macor, John E; Gillman, Kevin W

    2016-12-21

    Combination studies of neurokinin 1 (NK1) receptor antagonists and serotonin-selective reuptake inhibitors (SSRIs) have shown promise in preclinical models of depression. Such a combination may offer important advantages over the current standard of care. Herein we describe the discovery and optimization of an indazole-based chemotype to provide a series of potent dual NK1 receptor antagonists/serotonin transporter (SERT) inhibitors to overcome issues of ion channel blockade. This effort culminated in the identification of compound 9, an analogue that demonstrated favorable oral bioavailability, excellent brain uptake, and robust in vivo efficacy in a validated depression model. Over the course of this work, a novel heterocycle-directed asymmetric hydrogenation was developed to facilitate installation of the key stereogenic center.

  3. Neurokinin-1 receptor antagonism in a rat model of subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Ansar, Saema; Svendgaard, Niels-Aage; Edvinsson, Lars

    2007-01-01

    was injected intracisternally 30 minutes and 24 hours after the induction of SAH. Two days after SAH induction, the basilar arteries were harvested, and contractile responses to endothelin-1 (ET-I, an ETA- and ETB-receptor agonist) and 5-carboxamidotryptamine (a 5-hydroxytryptamine- I1 [5-HT1]-receptor agonist......) were investigated using sensitive myographs. To determine whether NKIR inhibition had an influence on local CBF after post-SAH, a quantitative autoradiographic technique was used. After SAH, the vascular receptor phenotype was changed in cerebral arteries through upregulation of contractile ET, and 5......-HT1B receptors, while regional and total CBF were markedly reduced. Treatment with the selective NK1R inhibitor L-822429 prevented both the receptor upregulation and the reduction in regional and global CBF. CONCLUSIONS: The data reveal the coregulation of vascular receptor changes and blood flow...

  4. SP. Pescado

    Directory of Open Access Journals (Sweden)

    Renato Gendre

    2003-12-01

    Full Text Available Nell'occhiello di un articolo dal titolo Il Peru dei de[Jini rosa e de/la grande pioggia si legge: "da una partenza  in aereo al «pescado»  che ti  sfamera."1 Questa parola spagnola, giustamente chiusa tra caporali, a noi pare molto interes­ sante, perche, nonostante l'apparenza, non ha nulla da spartire sotto i1 profilo se­ mantico con l'it. pescato. lnfatti, tutti i piu importanti dizionari della lingua italiana, di ieri e di oggi, etimologici e non 2, registrano  accanto a pescata,  ii lemma pescato, 3 ma lo spiegano come "quantita di pesce catturato nel corso di una battuta o di una stagione di pesca",4 mentre lo sp. pescado  indica i1 "pesce (solo nel senso di: pesGe pescato da mangiare [...]".s

  5. Transgenic expression of the rice Xa21 pattern-recognition receptor in banana (Musa sp.) confers resistance to Xanthomonas campestris pv. musacearum.

    Science.gov (United States)

    Tripathi, Jaindra N; Lorenzen, Jim; Bahar, Ofir; Ronald, Pamela; Tripathi, Leena

    2014-08-01

    Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum (Xcm), is the most devastating disease of banana in east and central Africa. The spread of BXW threatens the livelihood of millions of African farmers who depend on banana for food security and income. There are no commercial chemicals, biocontrol agents or resistant cultivars available to control BXW. Here, we take advantage of the robust resistance conferred by the rice pattern-recognition receptor (PRR), XA21, to the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). We identified a set of genes required for activation of Xa21-mediated immunity (rax) that were conserved in both Xoo and Xcm. Based on the conservation, we hypothesized that intergeneric transfer of Xa21 would confer resistance to Xcm. We evaluated 25 transgenic lines of the banana cultivar 'Gonja manjaya' (AAB) using a rapid bioassay and 12 transgenic lines in the glasshouse for resistance against Xcm. About 50% of the transgenic lines showed complete resistance to Xcm in both assays. In contrast, all of the nontransgenic control plants showed severe symptoms that progressed to complete wilting. These results indicate that the constitutive expression of the rice Xa21 gene in banana results in enhanced resistance against Xcm. Furthermore, this work demonstrates the feasibility of PRR gene transfer between monocotyledonous species and provides a valuable new tool for controlling the BXW pandemic of banana, a staple food for 100 million people in east Africa. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  6. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

    Directory of Open Access Journals (Sweden)

    John Meshki

    Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

  7. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-05-16

    The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Inhibition of substance P-mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects.

    Science.gov (United States)

    Stathis, Marigo; Pietra, Claudio; Rojas, Camilo; Slusher, Barbara S

    2012-08-15

    Netupitant is a potent and selective NK(1) receptor antagonist under development in combination with a fixed dose of palonosetron for the prevention of chemotherapy induced nausea and vomiting. Palonosetron is a 5-HT(3) receptor antagonist approved for both the prevention of acute and delayed chemotherapy induced nausea and vomiting after moderately emetogenic chemotherapy. Accumulating evidence suggests that substance P (SP), a ligand acting largely on tachykinin (NK(1)) receptors, is the dominant mediator of delayed emesis. Interestingly, palonosetron does not bind to the NK(1) receptor so that the mechanism behind palonosetron's unique efficacy against delayed emesis is not clear. Palonosetron exhibits a distinct ability among 5-HT(3) receptor antagonists to inhibit crosstalk between NK(1) and 5-HT(3) receptor signaling pathways. The objective of the current work was to determine if palonosetron's ability to inhibit receptor signaling crosstalk would influence netupitant's inhibition of the SP-mediated response when the two drugs are dosed together. We first studied the inhibition of SP-induced Ca(2+) mobilization in NG108-15 cells by palonosetron, ondansetron and granisetron. Unexpectedly, in the absence of serotonin, palonosetron inhibited the SP-mediated dose response 15-fold; ondansetron and granisetron had no effect. Netupitant also dose-dependently inhibited the SP response as expected from an NK1 receptor antagonist. Importantly, when both palonosetron and netupitant were present, they exhibited an enhanced inhibition of the SP response compared to either of the two antagonists alone. The results further confirm palonosetron's unique pharmacology among 5-HT(3) receptor antagonists and suggest that it can enhance the prevention of delayed emesis provided by NK(1) receptor antagonists. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice

    Directory of Open Access Journals (Sweden)

    Eszter Pakai

    2018-02-01

    Full Text Available Neurokinin (NK signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS. A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally to mice with the Tacr1 gene, i.e., the gene encoding the NK1 receptor, either present (Tacr1+/+ or absent (Tacr1−/− and measured their thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX-2 expression, and prostaglandin (PG E2 concentration. We found that the LPS-induced febrile response was attenuated in Tacr1−/− compared to their Tacr1+/+ littermates starting from 40 min postinfusion. The febrigenic effect of intracerebroventricularly administered PGE2 was not suppressed in the Tacr1−/− mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1−/− and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in amplification of COX-2 mRNA expression in the lungs, liver, and brain of the mice, which was statistically indistinguishable between the genotypes. In contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated in the lungs and tended to be suppressed in the liver of Tacr1−/− mice compared with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge of PGE2 production in the lungs, whereas Tacr1−/− mice did not. In conclusion, the NK1 receptor is necessary for normal fever genesis. Our results suggest that the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing COX-2 protein expression in the periphery. These findings advance the understanding of the crosstalk between NK signaling and the “cytokine-COX-2

  10. Draft genome sequences of six neonatal meningitis-causing escherichia coli isolates (SP-4, SP-5, SP-13, SP-16, SP-46, and SP-65)

    Science.gov (United States)

    Neonatal meningitis Escherichia coli isolates (SP-4, SP-5, SP-13, SP-16, SP-46, and SP-65) were recovered from infants in the Netherlands from 1989 to 1997. Here, we report the draft genome sequences for these six E. coli isolates, which are currently being used to validate food safety processing te...

  11. Contractile effect of tachykinins on rabbit small intestine.

    Science.gov (United States)

    Valero, Marta Sofía; Fagundes, Diego Santos; Grasa, Laura; Arruebo, María Pilar; Plaza, Miguel Ángel; Murillo, María Divina

    2011-04-01

    To study the role of the tachykinin receptors in spontaneous contractions of longitudinal and circular smooth muscle from rabbit small intestine and to determine the mechanism of action of Substance P (SP). Rabbit duodenum, jejunum and ileum segments were prepared. The spontaneous contractions of longitudinal and circular smooth muscle were recorded using a computer via an isometric force transducer. The specific agonists and antagonists of tachykinin receptors were added into the organ bath. The agonists of tachykinin NK1 receptor (SP and [Sar9] SP), NK2 receptor (NKA and (β-Ala8)-NKA), and NK3 receptor (NKB and Senktide) all induced contractions in the small intestine. The contractions were diminished by NK1 receptor antagonist L-733,060, NK2 receptor antagonist GR-94800, and NK3 receptor antagonist SB 218795. Contractions caused by SP were also reduced by atropine, verapamil, PKC inhibitor staurosporine, and PLC inhibitor U73122. Ttachykinin NK1, NK2, and NK3 receptors mediate the contractions of the smooth muscle in rabbit intestine. Furthermore, SP acts directly on smooth muscle cells through the tachykinin NK1 receptor.

  12. A library of 7TM receptor C-terminal tails - Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, A.; Sondergaard, B.P.; Ersbøll, Bjarne Kjær

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor......-coupled receptor-associated sorting protein bound 23 of the 59 tail proteins. Surface plasmon resonance analysis of the binding kinetics of selected hits from the glutathione S-transferase pull-down experiments, i.e. the tails of the virally encoded receptor US28 and the delta-opioid receptor, confirmed...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK1 receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  13. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, Arne; Søndergaard, Birgitte P; Ersbøll, Bjarne

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor......-coupled receptor-associated sorting protein bound 23 of the 59 tail proteins. Surface plasmon resonance analysis of the binding kinetics of selected hits from the glutathione S-transferase pull-down experiments, i.e. the tails of the virally encoded receptor US28 and the delta-opioid receptor, confirmed...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1) receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  14. The expression of tachykinin receptors in the human lower esophageal sphincter.

    Science.gov (United States)

    Zhang, Ke; Chen, Que T; Li, Jing H; Geng, Xian; Liu, Jun F; Li, He F; Feng, Yong; Li, Jia L; Drew, Paul A

    2016-03-05

    Mammalian tachykinins are a family of neuropeptides which are potent modulators of smooth muscle function with a significant contractile effect on human smooth muscle preparations. Tachykinins act via three distinct G protein-coupled neurokinin (NK) receptors, NK1, NK2 and NK3, coded by the genes TACR1, TACR2 and TACR3 respectively. The purpose of this paper was to measure the mRNA and protein expression of these receptors and their isoforms in the clasp and sling fibers of the human lower esophageal sphincter complex and circular muscle from the adjacent distal esophagus and proximal stomach. We found differences in expression between the different receptors within these muscle types, but the rank order of the receptor expression did not differ between the different muscle types. The rank order of the mRNA expression was TACR2 (α isoform)>TACR2 (β isoform)>TACR1 (short isoform)>TACR1 (long isoform)>TACR3. The rank order of the protein expression was NK2>NK1>NK3. This is the first report of the measurement of the transcript and protein expression of the tachykinin receptors and their isoforms in the muscles of the human lower esophageal sphincter complex. The results provide evidence that the tachykinin receptors could contribute to the regulation of the human lower esophageal sphincter, particularly the TACR2 α isoform which encodes the functional isoform of the tachykinin NK2 receptor was the most highly expressed of the tachykinin receptors in the muscles associated with the lower esophageal sphincter. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Structure-activity relationship study of tachykinin peptides for the development of novel neurokinin-3 receptor selective agonists.

    Science.gov (United States)

    Misu, Ryosuke; Noguchi, Taro; Ohno, Hiroaki; Oishi, Shinya; Fujii, Nobutaka

    2013-04-15

    Neurokinin B (NKB) is a potential regulator of pulsatile gonadotropin-releasing hormone (GnRH) secretion via activation of the neurokinin-3 receptor (NK3R). NKB with the consensus sequence of the tachykinin peptide family also binds to other tachykinin receptors [neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R)] with low selectivity. In order to identify the structural requirements for the development of novel potent and selective NK3R agonists, a structure-activity relationship (SAR) study of [MePhe(7)]-NKB and other naturally occurring tachykinin peptides was performed. The substitutions to naturally occurring tachykinins with Asp and MePhe improved the receptor binding and agonistic activity for NK3R. The corresponding substitutions to NKB provided an NK3R selective analog. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. SP-R210 (Myo18A Isoforms as Intrinsic Modulators of Macrophage Priming and Activation.

    Directory of Open Access Journals (Sweden)

    Linlin Yang

    Full Text Available The surfactant protein (SP-A receptor SP-R210 has been shown to increase phagocytosis of SP-A-bound pathogens and to modulate cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. Alternative splicing of the Myo18A gene results in two isoforms: SP-R210S and SP-R210L, with the latter predominantly expressed in alveolar macrophages. In this study we show that SP-A is required for optimal expression of SP-R210L on alveolar macrophages. Interestingly, pre-treatment with SP-A prepared by different methods either enhances or suppresses responsiveness to LPS, possibly due to differential co-isolation of SP-B or other proteins. We also report that dominant negative disruption of SP-R210L augments expression of receptors including SR-A, CD14, and CD36, and enhances macrophages' inflammatory response to TLR stimulation. Finally, because SP-A is known to modulate CD14, we used a variety of techniques to investigate how SP-R210 mediates the effect of SP-A on CD14. These studies revealed a novel physical association between SP-R210S, CD14, and SR-A leading to an enhanced response to LPS, and found that SP-R210L and SP-R210S regulate internalization of CD14 via distinct macropinocytosis-like mechanisms. Together, our findings support a model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages.

  17. Preparation of {sup 99m}Tc labeled substance P (SP)

    Energy Technology Data Exchange (ETDEWEB)

    Ozker, S.K. E-mail: ozker@mcw.edu; Hellman, Robert S.; Krasnow, Arthur Z

    2002-11-01

    Substance P (SP) is an ll-amino acid neuropeptide of the tachykinin family. This study investigated the preparation of an SP analog labeled with {sup 99m}Tc for imaging SP receptor positive tissue (inflammatory diseases and neoplasms with increased expression of SP receptors). High specific activity {sup 99m}Tc-SP was prepared using the 1-imino-4-mercaptobutyl (IMB) group as a bifunctional chelator. Biological distribution in mice showed increased {sup 99m}Tc-SP uptake in the salivary glands (which have a high concentration of SP receptors), but this activity was displaced in animals pre-treated with excess non-radioactive SP. These data show that the uptake of {sup 99m}Tc-SP is receptor specific. IMB derivatization at the N-terminal location is suitable for labeling of SP analogues with {sup 99m}Tc. Synthetic analogues of SP labeled with {sup 99m}Tc may be an attractive alternative to {sup 111}In labeled molecules and merit further investigation.

  18. Targeting classical but not neurogenic inflammation reduces peritumoral oedema in secondary brain tumours.

    Science.gov (United States)

    Lewis, Kate M; Harford-Wright, Elizabeth; Vink, Robert; Ghabriel, Mounir N

    2012-09-15

    Dexamethasone, the standard treatment for peritumoral brain oedema, inhibits classical inflammation. Neurogenic inflammation, which acts via substance P (SP), has been implicated in vasogenic oedema in animal models of CNS injury. SP is elevated within and outside CNS tumours. This study investigated the efficacy of NK1 receptor antagonists, which block SP, compared with dexamethasone treatment, in a rat model of tumorigenesis. Dexamethasone reverted normal brain water content and reduced Evans blue and albumin extravasation, while NK1 antagonists did not ameliorate oedema formation. We conclude that classical inflammation rather than neurogenic inflammation drives peritumoral oedema in this brain tumour model. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Neurokinin-1 receptor activation in globus pallidus

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2009-10-01

    Full Text Available The undecapeptide substance P has been demonstrated to modulate neuronal activity in a number of brain regions by acting on neurokinin-1 receptors. Anatomical studies revealed a moderate level of neurokinin-1 receptor in rat globus pallidus. To determine the electrophysiological effects of neurokinin-1 receptor activation in globus pallidus, whole-cell patch-clamp recordings were performed in the present study. Under current-clamp recordings, neurokinin-1 receptor agonist, [Sar9, Met(O211] substance P (SM-SP at 1 μM, depolarized globus pallidus neurons and increased their firing rate. Consistently, SM-SP induced an inward current under voltage-clamp recording. The depolarization evoked by SM-SP persisted in the presence of tetrodotoxin, glutamate and GABA receptor antagonists, indicating its direct postsynaptic effects. The neurokinin-1 receptor antagonist, SR140333B, could block SM-SP-induced depolarization. Further experiments showed that suppression of potassium conductance was the predominant ionic mechanism of SM-SP-induced depolarization. To determine if neurokinin-1 receptor activation exerts any effects on GABAergic and glutamatergic neurotransmission, the action of SM-SP on synaptic currents was studied. SM-SP significantly increased the frequency of spontaneous inhibitory postsynaptic currents, but only induced a transient increase in the frequency of miniature inhibitory postsynaptic currents. No change was observed in both spontaneous and miniature excitatory postsynaptic currents. Based on the direct excitatory effects of SM-SP on pallidal neurons, we hypothesize that neurokinin-1 receptor activation in globus pallidus may be involved in the beneficial effect of substance P in Parkinson’s disease.

  20. Tachykinins and tachykinin receptors: effects in the genitourinary tract.

    Science.gov (United States)

    Candenas, Luz; Lecci, Alessandro; Pinto, Francisco M; Patak, Eva; Maggi, Carlo Alberto; Pennefather, Jocelyn N

    2005-01-07

    Tachykinins (TKs) are a family of peptides involved in the central and peripheral regulation of urogenital functions through the stimulation of TK NK1, NK2 and NK3 receptors. At the urinary system level, TKs locally stimulate smooth muscle tone, ureteric peristalsis and bladder contractions, initiate neurogenic inflammation and trigger local and spinal reflexes aimed to maintain organ functions in emergency conditions. At the genital level, TKs are involved in smooth muscle contraction, in inflammation and in the modulation of steroid secretion by the testes and ovaries. TKs produce vasodilatation of maternal and fetal placental vascular beds and appear to be involved in reproductive function, stress-induced abortion, and pre-eclampsia. The current data suggest that the genitourinary tract is a primary site of action of the tachykininergic system.

  1. Synergistic effect of 5-hydroxytryptamine 3 and neurokinin 1 receptor antagonism in rodent models of somatic and visceral pain.

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Mohammadi, Ehsan; Tyler, Karl; Pietra, Claudio; Bee, Lucy A; Dickenson, Anthony

    2014-10-01

    Synergistic activity has been observed between serotonergic 5-hydroxytryptamine 3 (5-HT3) and tachykinergic neurokinin 1 (NK1) receptor-mediated responses. This study investigated the efficacy of a 5-HT3 antagonist, palonosetron, and a NK1 antagonist, netupitant, alone or in combination in rodent models of somatic and visceral colonic hypersensitivity. In a rat model of experimental neuropathic pain, somatic hypersensitivity was quantified by the number of ipsilateral paw withdrawals to a von Frey filament (6g). Electrophysiologic responses were recorded in the dorsal horn neurons after mechanical or thermal stimuli. Acute colonic hypersensitivity was induced experimentally in rats by infusing dilute acetic acid (0.6%) directly into the colon. Colonic sensitivity was assessed by a visceromotor behavioral response quantified as the number of abdominal contractions in response to graded isobaric pressures (0-60 mm Hg) of colorectal distension. Palonosetron or netupitant was administered alone or in combination via oral gavage. When dosed alone, both significantly reduced somatic sensitivity, decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation, and caused significant (P netupitant at doses that were ineffective alone significantly reduced both somatic and visceral sensitivity and decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation. In summary, the combination of palonosetron with a NK1 receptor antagonist showed synergistic analgesic activity in rodent models of somatic and visceral hypersensitivity, and may prove to be a useful therapeutic approach to treat pain associated with irritable bowel syndrome. U.S. Government work not protected by U.S. copyright.

  2. ExaSP2

    Energy Technology Data Exchange (ETDEWEB)

    2017-09-08

    ExaSP2 is a reference implementation of typical linear algebra algorithms and workloads for a quantum molecular dynamics (QMD) electronic structure code. The algorithm is based on a recursive second-order Fermi-Operator expansion method (SP2) and is tailored for density functional based tight-binding calculations of material systems.

  3. Evaluating the role of substance P in the growth of brain tumors.

    Science.gov (United States)

    Harford-Wright, E; Lewis, K M; Vink, R; Ghabriel, M N

    2014-03-07

    Recent research has investigated the expression and secretion of neuropeptides by tumors, and the potential of these peptides to facilitate tumor growth and spread. In particular, substance P (SP) and its receptor NK1 have been implicated in tumor cell growth and evasion of apoptosis, although few studies have examined this relationship in vivo. The present study used both in vitro and in vivo models to characterize the role of SP in tumor pathogenesis. Immunohistochemical assessment of human primary and secondary brain tumor tissue demonstrated a marked increase in SP and its NK1 receptor in all tumor types investigated. Of the metastatic tumors, melanoma demonstrated particularly elevated SP and NK1 receptor staining. Subsequently, A-375 human melanoma cell line was examined in vitro and found to express both SP and the NK1 receptor. Treatment with the NK1 receptor antagonist Emend IV resulted in decreased cell viability and an increase in cell death in this cell line in vitro. An animal model of brain tumors using the same cell line was employed to assess the effect of Emend IV on tumor growth in vivo. Administration of Emend IV was found to decrease tumor volume and decrease cellular proliferation indicating that SP may play a role in tumor pathogenesis within the brain. We conclude that SP may provide a novel therapeutic target in the treatment of certain types of brain tumors, with further research required to determine whether the role of SP in cancer is tumor-type dependent. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. The nuclear receptor NR4A1 induces a form of cell death dependent on autophagy in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Jimena Bouzas-Rodríguez

    Full Text Available The control of cell death is a biological process essential for proper development, and for preventing devastating pathologies like cancer and neurodegeneration. On the other hand, autophagy regulation is essential for protein and organelle degradation, and its dysfunction is associated with overlapping pathologies like cancer and neurodegeneration, but also for microbial infection and aging. In the present report we show that two evolutionarily unrelated receptors--Neurokinin 1 Receptor (NK(1R, a G-protein coupled receptor, and Insulin-like Growth Factor 1 Receptor (IGF1R, a tyrosine kinase receptor--both induce non-apoptotic cell death with autophagic features and requiring the activity of the autophagic core machinery proteins PI3K-III, Beclin-1 and Atg7. Remarkably, this form of cell death occurs in apoptosis-competent cells. The signal transduction pathways engaged by these receptors both converged on the activation of the nuclear receptor NR4A1, which has previously been shown to play a critical role in some paradigms of apoptosis and in NK(1R-induced cell death. The activity of NR4A1 was necessary for IGF1R-induced cell death, as well as for a canonical model of cell death by autophagy induced by the presence of a pan-caspase inhibitor, suggesting that NR4A1 is a general modulator of this kind of cell death. During cell death by autophagy, NR4A1 was transcriptionally competent, even though a fraction of it was present in the cytoplasm. Interestingly, NR4A1 interacts with the tumor suppressor p53 but not with Beclin-1 complex. Therefore the mechanism to promote cell death by autophagy might involve regulation of gene expression, as well as protein interactions. Understanding the molecular basis of autophagy and cell death mediation by NR4A1, should provide novel insights and targets for therapeutic intervention.

  5. High-level expression of soluble form of mouse natural killer cell receptor NKR-P1C(B6) in Escherichia coli

    Czech Academy of Sciences Publication Activity Database

    Rozbeský, Daniel; Kavan, Daniel; Chmelík, Josef; Novák, Petr; Vaněk, Ondřej; Bezouška, Karel

    2011-01-01

    Roč. 77, č. 2 (2011), s. 178-184 ISSN 1046-5928 R&D Projects: GA ČR GA303/09/0477; GA ČR GD305/09/H008; GA ČR GAP207/10/1040; GA AV ČR IAA500200620; GA MŠk LC07017; GA MŠk LC545; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50200510 Keywords : Natural killer cell * NKR-P1C receptor * NK1.1 antigen Subject RIV: EC - Immunology Impact factor: 1.587, year: 2011

  6. Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis.

    Science.gov (United States)

    Zhang, Zhonghan; Zhang, Yaxiong; Chen, Gang; Hong, Shaodong; Yang, Yunpeng; Fang, Wenfeng; Luo, Fan; Chen, Xi; Ma, Yuxiang; Zhao, Yuanyuan; Zhan, Jianhua; Xue, Cong; Hou, Xue; Zhou, Ting; Ma, Shuxiang; Gao, Fangfang; Huang, Yan; Chen, Likun; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2018-01-12

    The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear. We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed. Olanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens. Olanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea. According to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed

  7. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  8. Fuzzy SP-irresolute functions

    International Nuclear Information System (INIS)

    Abbas, S.E.

    2004-01-01

    In this paper, fuzzy SP-irresolute, fuzzy SP-irresolute open and fuzzy SP-irresolute closed functions between fuzzy topological spaces in Sostak sense are defined. Their properties and the relationships between these functions and other functions introduced previously are investigated. Next fuzzy SP-connectedness is introduced and studied with the help of r-fuzzy strongly preopen sets

  9. Tachykinin NK2 receptor antagonists. A patent review (2006 - 2010).

    Science.gov (United States)

    Altamura, Maria

    2012-01-01

    Tachykinins are endogenous peptide neurotransmitters, acting through the NK1, NK2 and NK3 receptors, at central and peripheral level. At peripheral level, they are involved in contraction of smooth muscle, secretion of water and ion from epithelia, as well as modulation of visceral pain sensitivity. Tachykinin NK2 receptor antagonists have the potential to be useful in the treatment of various gastrointestinal, genitourinary and CNS diseases. In this review, an overview of the patenting activity in the last 5 years is provided. Patents from different companies and research groups are discussed for their novelty and evaluated in relation to proposed indications and clinical studies. Relevant biological data are also presented. Patents claiming new therapeutic indications are included in a dedicated section. Although there is still no tachykinin NK2 receptor antagonist approved for use in human therapy, research in the field is still proposing new compounds and possible uses. A number of candidates are being evaluated in Phase II clinical studies, in indications ranging from gastrointestinal disorders to inflammatory diseases. The results of these studies will indicate the role of tachykinin NK2 receptor antagonists in human therapy.

  10. Tachykinin receptors antagonism for asthma: a systematic review

    Directory of Open Access Journals (Sweden)

    Couto Nuno

    2011-08-01

    Full Text Available Abstract Background Tachykinins substance P, neurokinin A and neurokinin B seem to account for asthma pathophysiology by mediating neurogenic inflammation and several aspects of lung mechanics. These neuropeptides act mainly by their receptors NK1, NK2 and NK3, respectively which may be targets for new asthma therapy. Methods This review systematically examines randomized controlled trials evaluating the effect of tachykinins receptors antagonism on asthma. Symptoms, airway inflammation, lung function and airway inflammation were considered as outcomes. We searched the Cochrane Airways Group Specialized Register of Asthma Trials, Cochrane Database of Systematic Reviews, MEDLINE/PubMed and EMBASE. The search is as current as June 2010. Quality rating of included studies followed the Cochrane Collaboration and GRADE Profiler approaches. However, data were not pooled together due to different measures among the studies. Results Our systematic review showed the potential of NK receptor antagonist to decrease airway responsiveness and to improve lung function. However, effects on airway inflammation and asthma symptoms were poorly or not described. Conclusion The limited available evidence suggests that tachykinin receptors antagonists may decrease airway responsiveness and improve lung function in patients with asthma. Further large randomized trials are still required.

  11. Absence of torsion for NK_1(R) over associative rings

    OpenAIRE

    Basu, Rabeya

    2010-01-01

    When R is a commutative ring with identity, and if k is a natural number with kR = R, then C. Weibel proved that SK_1(R[X]) has no k-torsion. We reprove his result for any associative ring R with identity in which kR = R.

  12. Tachykinins and their receptors in human malignancies.

    Science.gov (United States)

    Palma, Carla

    2006-08-01

    The possibility of links between psychosocial factors and cancer incidence and progression has generated considerable scientific and public interest. Tachykinins, including substance P, neurokinin A and B, hemokinin-1 and endokinins, are a family of neuropeptides, acting through three types of transmembrane G-protein coupled receptors denoted NK1, NK2 and NK3. Besides their role as neurotransmitters in peripheral and central nervous system, tachykinins and their receptors are also expressed in several non neuronal cells contributing to the fine connections between nervous systems and peripheral organ system such as respiratory, cardiovascular, immune, endocrine, gastrointestinal and genitourinary. Being so much involved in regulating physiological functions, they, of course, can concur to pathological conditions including cancer. Tachykinins can act on different steps of carcinogenesis. Tumors expressing NK receptors, such as astrocytoma, glioma, neuroblastoma, pancreatic cancer and melanoma, can misuse tachykinin-induced signaling, operating in normal cells, to promote proliferation and survival of cancer cells and to release cytokines and soluble mediators favoring tumor growth. In neuroblastoma, breast and prostate carcinomas tachykinins facilitate tumor metastatic infiltration in the bone marrow. In neuroendocrine carcinoma, tachykinins are responsible of symptoms associated with these pathologies including flushing, diarrhea, wheezing and right heart disease. In addition, regardless tumor histology, tachykinins may favor cancer incidence and metastatic progression by influencing blood flux and neovascularization in tumor formation as well as inducing immunosuppression mediated by neurogenic inflammation due to stress or surgery. However, the precise involvement of tachykinins in cancer pathologies and the potentiality to become effective pharmacological drug targets remain to be fully defined.

  13. Cryptosporidium sp. in lizards

    Czech Academy of Sciences Publication Activity Database

    Koudela, Břetislav; Modrý, D.

    1998-01-01

    Roč. 45, č. 1 (1998), s. 8 ISSN 1066-5234. [ Cryptosporidium sp. in lazards. 01.01.1998-02.01.1998, Praha] R&D Projects: GA ČR GA508/95/0273; GA AV ČR IPP2020702 Subject RIV: fp - Other Medical Disciplines

  14. Increasing substance P levels in serum and synovial tissues from patients with developmental dysplasia of the hip (DDH).

    Science.gov (United States)

    Wang, Hui; Zheng, Xin-Feng; Zhang, Xiang; Li, Zheng; Shen, Chao; Zhu, Jun-Feng; Cui, Yi-Min; Chen, Xiao-Dong

    2014-03-19

    The tachykininergic neurotransmitters have been proved to be involved in the inflammatory progress and chronic pain in series of disease. The present study was undertaken to evaluate the levels of substance P (SP) and its receptors NK-1 receptor (NK-1R) in both serum and synovial tissues of hip joint from patients with different stages of DDH, and to detect the possible correlation of serum SP levels with pain sensation and dysfunction of the hip joint. SP levels in serum and synovial tissues from patients with DDH and DDH combined with osteoarthritis (DDH&OA) group were compared through immunohistochemistry (IHC), ELISA, and 2-step acetic acid extraction method respectively. Expression of NK-1R in synovial tissues was compared through IHC, quantitive Real-Time PCR (QRT-PCR) and Western-Blot. The severities of pain sensation and the functional activities of hip joint were assessed by Visual analogue scale (VAS) and Harris hip score (HHS). Correlations of serum SP levels with VAS, HHS and erythrocyte sedimentation rate (ESR) were evaluated respectively in these groups. Significantly elevated serum SP levels were detected in group of DDH and DDH&OA compared to that in normal group. IHC, QRT-PCR as well as tissue Elisa showed that SP levels in synovial tissue of DDH&OA group is stronger than that in DDH group. Serum SP levels in each group have no gender differences. The enhanced SP levels in synovial tissue mainly came from the segregation of peripheral nerve endings. Serum SP correlated with VAS and HHS in patients with DDH&OA (Male + Female). Serum SP correlated with HHS in patients with DDH (Male). Serum SP levels also correlated with erythrocyte sedimentation rate (ESR) in patients with DDH&OA (Male + Female). Up-regulated expression of NK-1R was also observed in synovial tissue of patients with DDH&OA compared to patients with DDH, through western-blot, IHC, and QRT-PCR. These findings indicated that the increasing SP levels in serum and synovial tissues

  15. The receptor-like MLO protein and the RAC/ROP family G-protein RACB modulate actin reorganization in barley attacked by the biotrophic powdery mildew fungus Blumeria graminis f.sp. hordei.

    Science.gov (United States)

    Opalski, Krystina S; Schultheiss, Holger; Kogel, Karl-Heinz; Hückelhoven, Ralph

    2005-01-01

    Cytoskeleton remodelling is a crucial process in determining the polarity of dividing and growing plant cells, as well as during interactions with the environment. Nothing is currently known about the proteins, which regulate actin remodelling during interactions with invading pathogens. The biotrophic powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh) invades susceptible barley (Hordeum vulgare L.) by penetrating epidermal cells, which remain intact during fungal development. In contrast, resistant host plants prevent infection by inhibiting penetration through apoplastic mechanisms, which require focusing defence reactions on the site of attack. We stained actin filaments in a susceptible Mlo-genotype and a near-isogenic race-non-specifically resistant barley mlo5-mutant genotype using fluorescence-labelled phalloidin after chemical fixation. This revealed that the actin cytoskeleton is differentially reorganized in susceptible and resistant hosts challenged by Bgh. Actin filaments were polarized towards the sites of attempted penetration in the resistant host, whereas when susceptible hosts were penetrated, a more subtle reorganization took place around fungal haustoria. Strong actin filament focusing towards sites of fungal attack was closely associated with successful prevention of penetration. Actin focusing was less frequent and seemingly delayed in susceptible wild-type barley expressing the susceptibility factor MLO. Additionally, single cell overexpression of a constitutively activated RAC/ROP G-protein, CA RACB, another potential host susceptibility factor and hypothetical actin cytoskeleton regulator, partly inhibited actin reorganization when under attack from Bgh, whereas knockdown of RACB promoted actin focusing. We conclude that RACB and, potentially, MLO are host proteins involved in the modulation of actin reorganization and cell polarity in the interaction of barley with Bgh.

  16. Tsukamurella inchonensis sp. nov.

    Science.gov (United States)

    Yassin, A F; Rainey, F A; Brzezinka, H; Burghardt, J; Lee, H J; Schaal, K P

    1995-07-01

    Chemotaxonomic and genomic 16S ribosomal DNA sequence analyses of two isolates obtained from two different clinical materials clearly delineated a new species of the genus Tsukamurella. This new species can be identified by its 16S ribosomal DNA similarity values, as well as its physiological characteristics. The name Tsukamurella inchonensis sp. nov. is proposed for these isolates, which are represented by strain IMMIB D-771T (= DSM 44067T) (T = type strain). This strain exhibits only 45% DNA relatedness to Tsukamurella paurometabola.

  17. SP-100 surety evaluation

    International Nuclear Information System (INIS)

    1985-06-01

    This report describes surety evaluations conducted during GFY 1985 in support of the General Electric design for a Space Nuclear Power System - SP-100. Those surety evaluations address both safety and safeguards requirements, which are derived from OSNP-1 and supporting documents. The report includes results of neutronics (criticality) calculations performed by Los Alamos. The results have been benchmarked against independent calculations performed by General Electric with different codes. These comparisons show close agreement, and are summarized. Los Alamos has also provided specifications of explosion and fire environments, which have been used in evaluation of the GE SP-100 concept. Following the summary of key results, surety requirements are given and recommendations toward specification of requirements for later SP-100 project phases are presented. A conceptual design summary is presented. To establish a comprehensive background for surety evaluations, a reference mission profile and potential accidents for each phase of the mission are identified. The main body of the report addresses surety of the General Electric Thermoelectric Conversion design. GE has also developed a Stirling Engine concept, and performed comprehensive surety evaluations for it. These evaluations are reported

  18. Transcriptional Regulation of Frizzled-1 in Human Osteoblasts by Sp1.

    Directory of Open Access Journals (Sweden)

    Shibing Yu

    Full Text Available The wingless pathway has a powerful influence on bone metabolism and is a therapeutic target in skeletal disorders. Wingless signaling is mediated in part through the Frizzled (FZD receptor family. FZD transcriptional regulation is poorly understood. Herein we tested the hypothesis that Sp1 plays an important role in the transcriptional regulation of FZD1 expression in osteoblasts and osteoblast mineralization. To test this hypothesis, we conducted FZD1 promoter assays in Saos2 cells with and without Sp1 overexpression. We found that Sp1 significantly up-regulates FZD1 promoter activity in Saos2 cells. Chromatin immunoprecipitation (ChIP and electrophoretic mobility shift (EMSA assays identified a novel and functional Sp1 binding site at -44 to -40 from the translation start site in the FZD1 promoter. The Sp1-dependent activation of the FZD1 promoter was abolished by mithramycin A (MMA, an antibiotic affecting both Sp1 binding and Sp1 protein levels in Saos2 cells. Similarly, down-regulation of Sp1 in hFOB cells resulted in less FZD1 expression and lower alkaline phosphatase activity. Moreover, over-expression of Sp1 increased FZD1 expression and Saos2 cell mineralization while MMA decreased Sp1 and FZD1 expression and Saos2 cell mineralization. Knockdown of FZD1 prior to Sp1 overexpression partially abolished Sp1 stimulation of osteoblast differentiation markers. Taken together, our results suggest that Sp1 plays a role in human osteoblast differentiation and mineralization, which is at least partially mediated by Sp1-dependent transactivation of FZD1.

  19. Control of Branchionus sp. and Amoeba sp. in cultures of Arthrospira sp. Control de Branchionus sp. y Amoeba sp. en cultivos de Arthrospira sp.

    Directory of Open Access Journals (Sweden)

    Carlos Méndez

    2012-09-01

    Full Text Available Cultivation of cyanobacterium Arthrospira sp. has been developed in many countries for the production of proteins, pigments and other compounds. Outdoor mass cultures are often affected by biological contamination, drastically reducing productivity as far as bringing death. This study evaluates the control of Branchionus sp. and Amoeba sp. with two chemical compounds: urea (U and ammonium bicarbonate (AB, in laboratory conditions and outdoor mass culture of Arthrospira sp. The lethal concentration 100 (LC100 at 24 h for Branchionus sp. and Amoeba sp. determined was of 60-80 mg L-1 (U and 100-150 mg L-1 (AB. The average effective inhibition concentration for 50% of the population (IC50 in Arthrospira sp., after 72 h, was 80 mg L-1 (U and 150 mg L-1 (AB. The application of doses of 60 mg L-1 (U or 100 mg L-1 (AB in the outdoor mass culture of this contaminated microalga, completely inhibited grazing and did not affect the growth of Arthrospira sp. but rather promoted rapid recovery of algal density at levels prior to infestation. These compounds provided an economical and effective control of predators in cultures of Arthrospira sp.El cultivo de la cianobacteria Arthrospira sp. ha sido desarrollado en muchos países para la obtención de proteínas, pigmentos y otros compuestos. Cultivo que a nivel industrial se ve afectado frecuentemente por contaminación biológica, reduciendo drásticamente la productividad hasta causar la muerte. Este estudio evalúa el control de Branchionus sp. y de Amoeba sp. con dos compuestos químicos, la urea (U y bicarbonato de amonio (AB en cultivos de Arthrospira sp. La concentración letal 100 (LC100 determinada a las 24 h para Branchionus sp. y Amoeba sp. fue de 60-80 mg L-1 (U y 100-150 mg L-1 (AB. La concentración media de inhibición efectiva, después de 72 h, para el 50% de la población (IC50 en Arthrospira fue de 80 mg L-1 (U y 150 mg L-1 (AB. La aplicación de dosis de 60 mg L-1 (U ó 100 mg L-1 (AB en

  20. Activation of PAR2 receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint

    Science.gov (United States)

    Russell, FA; Schuelert, N; Veldhoen, VE; Hollenberg, MD; McDougall, JJ

    2012-01-01

    Background and Purpose The PAR2 receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR2 activation in the rat knee joint. Experimental Approach PAR2 in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR2 with its activating peptide, 2-furoyl-LIGRLO-NH2 (1–100 nmol·100 μL−1, via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR2 activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR2 activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH2 or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK1) receptors in the PAR2 responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. Key Results PAR2 were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH2 increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH2 also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P knee joint via TRPV1- and NK1-dependent mechanisms involving both PAR2-mediated neuronal sensitization and leukocyte trafficking. PMID:22849826

  1. Tsukamurella pulmonis sp. nov.

    Science.gov (United States)

    Yassin, A F; Rainey, F A; Brzezinka, H; Burghardt, J; Rifai, M; Seifert, P; Feldmann, K; Schaal, K P

    1996-04-01

    Chemotaxonomic and 16S ribosomal DNA sequence analyses of an isolate from the sputum of a patient with a mycobacterial lung infection clearly delineated a new species of the genus Tsukamurella. This new species can be defined on the basis of genotypic and phenotypic data. The name Tsukamurella pulmonis sp. nov. is proposed for this organism; the type strain is IMMIB D-1321T (= DSM 44142T). This isolate shows 44.2 and 36.2% DNA relatedness to Tsukamurella paurometabola DSM 20162T (T = type strain) and Tsukamurella inchonensis DSM 44067T, respectively.

  2. The Transmodulation of HER2 and EGFR by Substance P in Breast Cancer Cells Requires c-Src and Metalloproteinase Activation.

    Directory of Open Access Journals (Sweden)

    Susana Garcia-Recio

    Full Text Available Substance P (SP is a pleiotropic cytokine/neuropeptide that enhances breast cancer (BC aggressiveness by transactivating tyrosine kinase receptors like EGFR and HER2. We previously showed that SP and its cognate receptor NK-1 (SP/NK1-R signaling modulates the basal phosphorylation of HER2 and EGFR in BC, increasing aggressiveness and drug resistance. In order to elucidate the mechanisms responsible for NK-1R-mediated HER2 and EGFR transactivation, we investigated the involvement of c-Src (a ligand-independent mediator and of metalloproteinases (ligand-dependent mediators in HER2/EGFR activation.Overexpression of NK-1R in MDA-MB-231 and its chemical inhibition in SK-BR-3, BT-474 and MDA-MB-468 BC cells significantly modulated c-Src activation, suggesting that this protein is a mediator of NK-1R signaling. In addition, the c-Src inhibitor 4-(4'-phenoxyanilino-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2. On the other hand, SP-dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1-10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR. Moreover, the use of these inhibitors demonstrated that this Src and MMP-dependent signaling is important to the cell viability and migration capacity of HER2+ and EGFR+ cell lines.Our results indicate that the transactivation of HER2 and EGFR by the pro-inflammatory cytokine/neuropeptide SP in BC cells is a c-Src and MMP-dependent process.

  3. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  4. Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs.

    Science.gov (United States)

    Nabe, T; Tsuzuike, N; Ohtani, Y; Mizutani, N; Watanabe, S; Fujii, M; Yoshimura, M; Nagasawa, M; Kohno, S

    2009-01-01

    Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists. SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.

  5. Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs

    International Nuclear Information System (INIS)

    Gandhy, Shruti U; Kim, KyoungHyun; Larsen, Lesley; Rosengren, Rhonda J; Safe, Stephen

    2012-01-01

    Curcumin inhibits growth of several cancer cell lines, and studies in this laboratory in bladder and pancreatic cancer cells show that curcumin downregulates specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and pro-oncogenic Sp-regulated genes. In this study, we investigated the anticancer activity of curcumin and several synthetic cyclohexanone and piperidine analogs in colon cancer cells. The effects of curcumin and synthetic analogs on colon cancer cell proliferation and apoptosis were determined using standardized assays. The changes in Sp proteins and Sp-regulated gene products were analysed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a), miR-20a, miR-17-5p and ZBTB10 and ZBTB4 mRNA expression. The IC 50 (half-maximal) values for growth inhibition (24 hr) of colon cancer cells by curcumin and synthetic cyclohexanone and piperidine analogs of curcumin varied from 10 μM for curcumin to 0.7 μM for the most active synthetic piperidine analog RL197, which was used along with curcumin as model agents in this study. Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis, and this was accompanied by downregulation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and Sp-regulated genes including the epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), survivin, bcl-2, cyclin D1 and NFκB (p65 and p50). Curcumin and RL197 also induced reactive oxygen species (ROS), and cotreatment with the antioxidant glutathione significantly attenuated curcumin- and RL197-induced growth inhibition and downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes. The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR)-27a, miR-20a and miR-17-5p that regulate these repressors. These results identify a new and highly potent

  6. mRNA expression of tachykinins and tachykinin receptors in different human tissues.

    Science.gov (United States)

    Pinto, Francisco M; Almeida, Teresa A; Hernandez, Mariano; Devillier, Philippe; Advenier, Charles; Candenas, M Luz

    2004-06-28

    The tachykinins substance P, neurokinin A and neurokinin B are involved in many pathophysiological processes. A reverse transcription-polymerase chain reaction (RT-PCR) assay was used to analyse the expression of TAC1 and TAC3, the genes that encode substance P/neurokinin A and neurokinin B, respectively, and the genes encoding the tachykinin NK(1), NK(2) and NK(3) receptors in different human tissues. The data show that tachykinins and their receptors mRNAs are broadly distributed in different human tissues being present in neuronal and non-neuronal types of cells. The presence of TAC3 and the tachykinin NK(3) receptor (TACR3) in a wide variety of peripheral tissues argue for a still unexplored role of this ligand-receptor pair in mediating visceral effects of tachykinins. We found, for the first time, that TAC3 and TACR3 mRNAs are expressed in human airways and pulmonary arteries and veins, providing further evidence for the involvement of this system in lung physiopathology.

  7. Analysis of the Expression of Tachykinins and Tachykinin Receptors in the Rat Uterus During Early Pregnancy.

    Science.gov (United States)

    Pinto, Francisco M; Bello, Aixa R; Gallardo-Castro, Manuel; Valladares, Francisco; Almeida, Teresa A; Tena-Sempere, Manuel; Candenas, Luz

    2015-08-01

    The peptides of the tachykinin family participate in the regulation of reproductive function acting at both central and peripheral levels. Our previous data showed that treatment of rats with a tachykinin NK3R antagonist caused a reduction of litter size. In the present study, we analyzed the expression of tachykinins and tachykinin receptors in the rat uterus during early pregnancy. Uterine samples were obtained from early pregnant rats (Days 1-9 of pregnancy) and from nonpregnant rats during the proestrus stage of the ovarian cycle, and real-time quantitative RT-PCR, immunohistochemistry, and Western blot studies were used to investigate the pattern of expression of tachykinins and tachykinin receptors. We found that all tachykinins and tachykinin receptors were locally synthesized in the uterus of early pregnant rats. The expression of substance P, neurokinin B, and the tachykinin receptors NK1R and NK3R mRNAs and proteins underwent major changes during the days around implantation and they were widely distributed in implantation sites, being particularly abundant in decidual cells. These findings support the involvement of the tachykinin system in the series of uterine events that occur around embryo implantation in the rat. © 2015 by the Society for the Study of Reproduction, Inc.

  8. Acetobacter intermedius, sp. nov.

    Science.gov (United States)

    Boesch, C; Trcek, J; Sievers, M; Teuber, M

    1998-03-01

    Strains of a new species in the genus Acetobacter, for which we propose the name A. intermedius sp. nov., were isolated and characterized in pure culture from different sources (Kombucha beverage, cider vinegar, spirit vinegar) and different countries (Switzerland, Slovenia). The isolated strains grow in media with 3% acetic acid and 3% ethanol as does A. europaeus, do, however, not require acetic acid for growth. These characteristics phenotypically position A. intermedius between A. europaeus and A. xylinus, DNA-DNA hybridizations of A. intermedius-DNA with DNA of the type strains of Acetobacter europaeus, A. xylinus, A. aceti, A. hansenii, A. liquefaciens, A. methanolicus, A. pasteurianus, A. diazotrophicus, Gluconobacter oxydans and Escherichia coli HB 101 indicated less than 60% DNA similarity. The important features of the new species are described. Acetobacter intermedius strain TF2 (DSM11804) isolated from the liquid phase of a tea fungus beverage (Kombucha) is the type strain.

  9. Tsukamurella tyrosinosolvens sp. nov.

    Science.gov (United States)

    Yassin, A F; Rainey, F A; Burghardt, J; Brzezinka, H; Schmitt, S; Seifert, P; Zimmermann, O; Mauch, H; Gierth, D; Lux, I; Schaal, K P

    1997-07-01

    Chemotaxonomic and 16S ribosomal DNA sequence analyses of four bacterial isolates from blood cultures from patients with cardiac pacemaker implants and sputa of patients with chronic lung infections clearly demonstrated that these bacteria belong to the genus Tsukamurella. DNA-DNA hybridization data, as well as the physiological characteristics of the isolates, indicate that they are closely related and belong to a single species that differs from previously described members of the genus Tsukamurella. The name Tsukamurella tyrosinosolvens sp. nov. is proposed for these isolates, and the new species is represented by strain IMMIB D-1397T (= DSM 44234T). Strain IMMIB D-1397T exhibits 53.4, 53.5, and 54.7% DNA-DNA relatedness to Tsukamurella paurometabola DSM 20162T, Tsukamurella inchonensis DSM 44067T, and Tsukamurella pulmonis DSM 44142T, respectively.

  10. New tachykinin peptides and nociception

    Directory of Open Access Journals (Sweden)

    Toshikazu Nishimori

    2013-02-01

    Full Text Available Hemokinin-1 (HK-1 and endokinins are peptides predicted from a new mammalian tachykinin gene, TAC4. The amino acid sequences derived from rat/mouse HK-1 and human HK-1 are not identical; however, the effects induced by intracerebroventricular or intrathecal administration of HK-1 are attenuated by treatment with antagonists of neurokinin 1 (NK1 receptor, substance P (SP receptor, indicating that HK-1 is an agonist of the NK1 receptor. On the other hand, a growing body of evidence indicates that pharmacological characteristics of HK-1 and SP are always not identical, suggesting that the HK-1-preferred receptor may be involved in the effects of HK-1. Endokinins are derived from human TAC4 and consist of four endokinins, endokinin A (EKA, endokinin B (EKB, endokinin C (EKC and endokinin D (EKD. Effects induced by intrathecal administration of EKA/B (the common C-terminal decapeptide in EKA and EKB and SP were very similar, while the effects of SP and EKA/B were inhibited by EKC/D (the common C-terminal duodecapeptide in EKC and EKD. This inhibitory effect of EKC/D was derived from leucine at the carboxyl-terminus. These findings suggest that HK-1 and EKA/B have an agonistic effect, while EKC/D has an antagonistic effect on the NK1 receptor in nociceptive processing.

  11. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing......- and heterodimerisation, let alone oligomerisation. Theoretically, this phenomenon adds a novel series of functional megareceptors/super-receptors, with varied pharmacological profiles, to the catalogue of monomeric receptor subtypes isolated and cloned in the past. SRIF analogues include both peptides and non......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  12. Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature.

    Science.gov (United States)

    Patacchini, Riccardo; Lecci, Alessandro; Holzer, Peter; Maggi, Carlo Alberto

    2004-01-01

    The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tachykinin-like peptides such as C14TKL-1 and virokinin raise many questions about the roles played by tachykinins in peripheral tissues and render terms such as 'neurokinins' and 'SP receptor' inappropriate.

  13. Genetic construction and properties of a diphtheria toxin-related substance P fusion protein: in vitro destruction of cells bearing substance P receptors.

    Science.gov (United States)

    Fisher, C E; Sutherland, J A; Krause, J E; Murphy, J R; Leeman, S E; vanderSpek, J C

    1996-01-01

    We have genetically replaced the native receptor binding domain of diphtheria toxin with an extended form of substance P (SP): SP-glycine (SP-Gly). The resulting fusion protein, DAB389SP-Gly, is composed of the catalytic and transmembrane domains of diphtheria toxin genetically coupled to SP-Gly. Because native SP requires a C-terminal amide moiety to bind with high affinity to the SP receptor, the precursor form of the fusion toxin, DAB389SP-Gly, was converted to DAB389SP by treatment with peptidylglycine-alpha-amidating monooxygenase. We demonstrate that following conversion, DAB389SP is selectively cytotoxic for cell lines that express either the rat or the human SP receptor. We also demonstrate that the cytotoxic action of DAB389SP is mediated via the SP receptor and dependent upon passage through an acidic compartment. To our knowledge, this is the first reported use of a neuropeptide as the targeting ligand for a fusion toxin; and the first instance in which an inactive precursor form of a fusion toxin is converted to the active form by a posttranslational modification. Images Fig. 2 PMID:8692995

  14. Efficacy and safety of repeated dosing of netupitant, a neurokinin-1 receptor antagonist, in treating overactive bladder.

    Science.gov (United States)

    Haab, F; Braticevici, B; Krivoborodov, G; Palmas, M; Zufferli Russo, M; Pietra, C

    2014-03-01

    NK-1 receptors in sensory nerves, the spinal cord and bladder smooth muscle participate in complex sensory mechanisms that regulate bladder activity. This study was designed to assess the efficacy and safety of a new NK-1 receptor antagonist, netupitant, in patients with OAB. This was a phase II, multicenter, double-blind study in which adults with OAB symptoms >6 months were randomized to receive 1 of 3 doses of netupitant (50, 100, 200 mg) or placebo once daily for 8 weeks. The primary efficacy endpoint was percentage change from baseline in average number of daily micturitions at week 8. Urinary incontinence, urge urinary incontinence (UUI), and urgency episodes were also assessed. The primary efficacy endpoint was similar in the treatment groups (-13.85 for placebo to -16.17 in the netupitant 200 mg group) with no statistically significant differences between netupitant and placebo. The same was true for most secondary endpoints although a significant difference for improvement in UUI episodes and a trend for the greatest decrease in urgency episodes were seen in the netupitant 100 mg group. Netupitant was well tolerated with most treatment emergent adverse events (AEs) being mild. While the overall incidence of AEs increased with netupitant dose, there was no evidence for this dose dependency based on relationship to treatment, intensity, or time to onset. The study failed to demonstrate superiority of netupitant versus placebo in decreasing OAB symptoms, despite a trend favoring netupitant 100 mg. There were no safety concerns with daily administration of netupitant over 8 weeks. © 2013 Wiley Periodicals, Inc.

  15. A role for tachykinins in the regulation of human sperm motility.

    Science.gov (United States)

    Ravina, C G; Seda, M; Pinto, F M; Orea, A; Fernández-Sánchez, M; Pintado, C O; Candenas, M Luz

    2007-06-01

    Tachykinins and tachykinin receptors are widely distributed in the male reproductive tract and appear to be involved in reproduction. However, the function and expression of tachykinins and their receptors in human spermatozoa remain poorly studied. We analysed the effects of tachykinins on sperm motility and characterized the population of tachykinin receptors in human spermatozoa. Motility analysis was performed following World Health Organization guidelines and we found that substance P (SP), human hemokinin-1 (hHK-1), neurokinin A (NKA) and neurokinin B (NKB) produced concentration-dependent increases in sperm progressive motility. The effects of tachykinins were antagonized by the NK(1) receptor-selective antagonist SR 140333, the NK(2) receptor-selective antagonist, SR 48968 and, to a lesser extent, also by the NK(3) receptor-selective antagonist SR 142801. Immunocytochemistry studies showed expression of the NK(1), NK(2) and NK(3) tachykinin receptor proteins in spermatozoa with different major sites of localization for each receptor. Western blot analysis confirmed the presence of tachykinin receptors in sperm cell homogenates. RT-PCR demonstrated expression of the genes that encode SP/NKA (TAC1), NKB (TAC3) and hHK-1 (TAC4) but not the genes TACR1, TACR2 and TACR3 encoding NK(1), NK(2) and NK(3) receptors, respectively. These results show for the first time that the NK(1), NK(2) and NK(3) tachykinin receptor proteins are present in human spermatozoa. Our findings suggest that tachykinins, probably acting through these three tachykinin receptors, play a role in the regulation of human sperm motility.

  16. Bradysia sp. em morangueiro Bradysia sp. in strawberry

    Directory of Open Access Journals (Sweden)

    Bernadete Radin

    2009-04-01

    Full Text Available No trabalho, relatam-se os primeiros registros de Bradysia sp. (Insecta: Diptera: Sciaridae em morangueiro (Fragaria x ananassa Duch., cultivado no Município de Eldorado do Sul, RS. O cultivo foi realizado em sacolas com três metros de comprimento, preenchidas com substrato composto de casca de arroz e turfa, dispostas horizontalmente sobre bancadas de madeira, em ambiente protegido. A presença de Bradysia sp. foi observada na segunda quinzena de agosto de 2005. Neste trabalho, estão descritos os sintomas apresentados no morangueiro pela praga, prováveis conseqüências sobre o aparecimento de doenças e uma breve descrição morfológica da Bradysia sp., adulto e fase larval.This paper describes the first record of Bradysia sp. (Insecta; Diptera; Sciaridae in strawberry (Fragaria x ananassa, cultivated in the city of Eldorado do Sul, RS, Brazil. Strawberry was planted in plastic bags filled with a mixture of burnt rice hulls and peat and cultivated in a greenhouse. The presence of Bradysia sp was noticed in the second fortnight of August, 2005. The symptoms in strawberry and the probable consequences in terms of disease arising were described in the present study, as well as the morphological characterization of Bradysia sp. and its illustrations.

  17. SP-100 reactor design

    International Nuclear Information System (INIS)

    Armijo, J.S.; Atwell, J.; Pluta, P.R.; Smith, M.A.; Solorzano, E.R.

    1987-01-01

    The SP-100 space reactor power system is being designed and developed as part of the Ground Engineering System (GES) contract between General Electric Company as the system developer and the Department of Energy. Other key participants in the GES program include Westinghouse Hanford Company (site operator), Los Alamos National Laboratory (fuel development and production), Oak Ridge National Laboratory (materials), and Westinghouse, Advanced Energy Systems Division (shield, HTS equipment). The GES Program includes two major elements. First, the development of a Reference Flight System design at 100 kWe output to the user, and second the validation of the Reference Flight System design by analysis and by testing. Development of key technologies along with component and system testing is an essential part of the validation program. The nuclear subsystem validation includes the design, manufacture, assembly and operational testing of a Ground Reactor Test Assembly. The subject of this paper is the reactor design for the Reference Flight System. The reference flight design is in the preliminary design stage and will evolve over the next year

  18. Gene expression of muscarinic, tachykinin and purinergic receptors in porcine bladder: comparison with cultured cells

    Directory of Open Access Journals (Sweden)

    Forough eBahadory

    2013-11-01

    Full Text Available Urothelial cells, myofibroblasts, and smooth muscle cells are important cell types contributing to bladder function. Multiple receptors including muscarinic (M3/M5, tachykinin (NK1/NK2 and purinergic (P2X1/P2Y6 receptors are involved in bladder motor and sensory actions. Using female pig bladder, our aim was to differentiate between various cell types in bladder by genetic markers. We compared the molecular expression pattern between the fresh tissue layers and their cultured cell counterparts. We also examined responses to agonists for these receptors in cultured cells. Urothelial, suburothelial (myofibroblasts and smooth muscle cells isolated from pig bladder were cultured (10-14 days and identified by marker antibodies. Gene (mRNA expression level was demonstrated by real-time PCR. The receptor expression pattern was very similar between suburothelium and detrusor, and higher than urothelium. The gene expression of all receptors decreased in culture compared with the fresh tissue, although the reduction in cultured urothelial cells appeared less significant compared to suburothelial and detrusor cells. Cultured myofibroblasts and detrusor cells did not contract in response to the agonists acetylcholine, neurokinin A and β,γ-MeATP, up to concentrations of 0.1 and 1 mM. The significant reduction of M3, NK2 and P2X1 receptors under culture conditions may be associated with the unresponsiveness of cultured suburothelial and detrusor cells to their respective agonists. These results suggest that under culture conditions, bladder cells lose the receptors that are involved in contraction, as this function is no longer required. The study provides further evidence that cultured cells do not necessarily mimic the actions exerted by intact tissues.

  19. New challenges in the study of the mammalian tachykinins.

    Science.gov (United States)

    Page, Nigel M

    2005-08-01

    There is an expanding repertoire of mammalian tachykinins produced by a variety of tachykinin genes, gene splicing events and peptide processing. Novel tachykinin-binding molecules/receptors are proposed, but only, three tachykinin receptors are identified with certainty. The question remains - do more tachykinin receptors exist or is there just the need to reappraise our understanding of the known receptors? The tachykinin NK1 receptor, the preferred receptor for both substance P and the peripheral SP-like endokinins, exists in several tissue-specific conformations and isoforms and may provide some clues. This review addresses recent advances in this exciting field and raises challenging new concepts.

  20. Pharmacological profile of the novel mammalian tachykinin, hemokinin 1

    Science.gov (United States)

    Bellucci, Francesca; Carini, Francesca; Catalani, Claudio; Cucchi, Paola; Lecci, Alessandro; Meini, Stefania; Patacchini, Riccardo; Quartara, Laura; Ricci, Renzo; Tramontana, Manuela; Giuliani, Sandro; Maggi, Carlo Alberto

    2002-01-01

    The effects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in vivo experiments.Similar to SP (Ki=0.13 nM), HEK-1 inhibited in a concentration-dependent manner and with high affinity [3H]-substance P (SP) binding to human NK1 receptor (Ki=0.175 nM) while its affinity for [125I]-neurokinin A (NKA) binding at human NK2 receptor was markedly lower (Ki=560 nM).In isolated bioassays HEK-1 was a full agonist at tachykinin NK1, NK2 and NK3 receptors. In the rat urinary bladder (RUB) HEK-1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK-1 and in the guinea-pig ileum (GPI), HEK-1 was about 500 fold less potent than NKA and NKB, respectively.The responses to HEK-1 were antagonized by GR 82334 in RUB (pKB=5.6±0.07), by nepadutant in RPA (pKB=8.6±0.04) and by SR 142801 in GPI (pKB=9.0±0.2) with apparent affinities comparable to that measured against tachykinin NK1, NK2 and NK3 receptor-selective agonists, respectively.Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guinea-pigs (ED50=0.1 nmol kg−1) and salivary secretion in anaesthetized rats (ED50=6 nmol kg−1) with potencies similar to that of SP. All these effects were blocked by the selective tachykinin NK1 receptor antagonist, SR 140333.We conclude that HEK-1 is a full agonist at tachykinin NK1, NK2 and NK3 receptors, possesses a remarkable selectivity for NK1 as compared to NK2 or NK3 receptors and acts in vivo experiments with potency similar to that of SP. PMID:11786503

  1. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Riesner, Anica [Department of Gastroenterology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jahn, Patrick [Nursing Research Unit, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Sieker, Frank; Vordermark, Dirk [Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jordan, Karin [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany)

    2015-08-01

    Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

  2. Penicillium araracuarense sp. nov., Penicillium elleniae sp. nov., Penicillium penarojense sp. nov., Penicillium vanderhammenii sp. nov. and Penicillium wotroi sp. nov., isolated from leaf litter

    DEFF Research Database (Denmark)

    Houbraken, Jos; López-Quintero, Carlos A.; Frisvad, Jens Christian

    2011-01-01

    Several species of the genus Penicillium were isolated during a survey of the mycobiota of leaf litter and soil in Colombian Amazon forest. Five species, Penicillium penarojense sp. nov. (type strain CBS 113178T = IBT 23262T), Penicillium wotroi sp. nov. (type strain CBS 118171T = IBT 23253T......), Penicillium araracuarense sp. nov. (type strain CBS 113149T = IBT 23247T), Penicillium elleniae sp. nov. (type strain CBS 118135T = IBT 23229T) and Penicillium vanderhammenii sp. nov. (type strain CBS 126216T = IBT 23203T) are described here as novel species. Their taxonomic novelty was determined using......, andrastin A, pulvilloric acid, paxillin, paspaline and janthitrem, were commonly produced by these phylogenetically related species. The novel species had a high growth rate on agar media, but could be distinguished from each other by several macro- and microscopical characteristics....

  3. Uji Fitokimia, Kandungan Total Fenol dan Aktivitas Antioksidan Mikroalga Spirulina sp., Chlorella sp., dan Nannochloropsis sp.

    Directory of Open Access Journals (Sweden)

    Diini Fithriani

    2015-12-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui kandungan fitokimia, total fenol, dan aktivitas antioksidan dari mikroalga Spirulina sp., Nannochloropsis sp., dan Chlorella sp. Mikroalga diekstrak dengan ekstraksi tunggal menggunakan etanol. Skrining fitokimia dilakukan secara kualitatif. Analisis total fenol dilakukan secara spektrofotometri dengan metode Folin-Ciocalteu. Analisis antioksidan dilakukan dengan metode 2,2-diphenyl-1-picrylhydrazyl (DPPH dan Ferric Reducing Antioxidant Power (FRAP. Skrining fitokimia menunjukkan keberadaan tanin, flavonoid, steroid, glikosida, dan alkaloid pada ekstrak etanol ketiga jenis mikroalga, sedangkan saponin hanya terdeteksi pada ekstrak etanol Spirulina sp. dan Chlorella sp., adapun triterpenoid tidak terdeteksi pada ekstrak etanol ketiga jenis mikroalga. Hasil penelitian menunjukkan bahwa kandungan total fenol, aktivitas antioksidan (IC50, dan kapasitas antioksidan (FRAP tertinggi diperoleh pada ekstrak etanol Spirulina sp. dengan nilai berturut turut sebesar 0,32 ± 0,025 mg GAE g-1D.W., 518,94 ppm, dan  49,95 ± 2,02 (mmol Fe2+ eq.g-1D.W. Dalam penelitian ini diketahui bahwa kandungan fenol total memiliki korelasi  yang kuat  dengan kapasitas antioksidan metode FRAP (R2= 0,84, dan aktivitas antioksidan metode DPPH (R2= 0,79.

  4. Uji Fitokimia, Kandungan Total Fenol Dan Aktivitas Antioksidan Mikroalga Spirulina Sp., Chlorella Sp., dan Nannochloropsis Sp.

    Directory of Open Access Journals (Sweden)

    Diini Fithriani

    2015-12-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui kandungan fitokimia, total fenol, dan aktivitas antioksidan dari mikroalga Spirulina sp., Nannochloropsis sp., dan Chlorella sp. Mikroalga diekstrak dengan ekstraksi tunggal menggunakan etanol. Skrining fitokimia dilakukan secara kualitatif. Analisis total fenol dilakukan secara spektrofotometri dengan metode Folin-Ciocalteu. Analisis antioksidan dilakukan dengan metode 2,2-diphenyl-1-picrylhydrazyl (DPPH dan Ferric Reducing Antioxidant Power (FRAP. Skrining fitokimia menunjukkan keberadaan tanin, flavonoid, steroid, glikosida, dan alkaloid pada ekstrak etanol ketiga jenis mikroalga, sedangkan saponin hanya terdeteksi pada ekstrak etanol Spirulina sp. dan Chlorella sp., adapun triterpenoid tidak terdeteksi pada ekstrak etanol ketiga jenis mikroalga. Hasil penelitian menunjukkan bahwa kandungan total fenol, aktivitas antioksidan (IC50, dan kapasitas antioksidan (FRAP tertinggi diperoleh pada ekstrak etanol Spirulina sp. dengan nilai berturut turut sebesar 0,32 ± 0,025 mg GAE g-1D.W., 518,94 ppm, dan  49,95 ± 2,02 (mmol Fe2+ eq.g-1D.W. Dalam penelitian ini diketahui bahwa kandungan fenol total memiliki korelasi  yang kuat  dengan kapasitas antioksidan metode FRAP (R2= 0,84, dan aktivitas antioksidan metode DPPH (R2= 0,79.

  5. Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition

    OpenAIRE

    Gao, Lu; Rabbitt, Elizabeth H.; Condon, Jennifer C.; Renthal, Nora E.; Johnston, John M.; Mitsche, Matthew A.; Chambon, Pierre; Xu, Jianming; O’Malley, Bert W.; Mendelson, Carole R.

    2015-01-01

    The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process...

  6. Peptide-evoked release of amylase from isolated acini of the rat parotid gland

    DEFF Research Database (Denmark)

    Goll, R; Poulsen, J H; Schmidt, P

    1994-01-01

    on isolated acini of the rat parotid gland. Furthermore, the occurrence and location of the peptides in the gland was studied. Finally, binding of 125I-BH-SP to isolated acini were studied in order to characterize their tachykinin receptor(s) and their binding kinetics. Only SP, NKA, NPK and VIP stimulated...... of NK1-receptors. Thus, the results of the present study support previous suggestions that the tachykinins and VIP are likely to be involved in amylase secretion in the rat parotid gland....

  7. The reliability of rabbit monoclonal antibodies in the immunohistochemical assessment of estrogen receptors, progesterone receptors, and HER2 in human breast carcinomas

    OpenAIRE

    Rhodes, A.; Sarson, J.; Assam, E. E.; Dean, S. J.; Cribb, E. C.; Parker, A.

    2010-01-01

    The reliability of the rabbit monoclonal antibodies SP1, SP2, SP3, and 4B5 was immunohistochemically assessed on a range of 96 invasive breast and carcinomas and the results compared with those achieved with established antibody markers for estrogen receptors (6F11), progesterone receptors (PgR636), and HER2 (polyclonal A0485 and clone CB11), with HER2 status validated by fluorescence in situ hybridization (FISH) and silver in situ hybridization. Optimal results depended on the duration of mi...

  8. Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model.

    Science.gov (United States)

    Andersson, Gustav; Backman, Ludvig J; Scott, Alexander; Lorentzon, Ronny; Forsgren, Sture; Danielson, Patrik

    2011-10-01

    Tenocytes produce substance P (SP), and its receptor (neurokinin-1 receptor (NK-1R)) is expressed throughout the tendon tissue, especially in patients with tendinopathy and tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering the known effects of SP, one might ask whether SP contributes to these changes. To test whether development of tendinosis-like changes (hypercellularity and angiogenesis) is accelerated during a 1-week course of exercise with local administration of SP in an established Achilles tendinopathy model. Rabbits were subjected to a protocol of Achilles tendon overuse for 1 week, in conjunction with SP injections in the paratenon. Exercised control animals received NaCl injections or no injections, and unexercised, uninjected controls were also used. Tenocyte number and vascular density, as well as paratendinous inflammation, were evaluated. Immunohistochemistry and in situ hybridisation to detect NK-1R were conducted. Results There was a significant increase in tenocyte number in the SP-injected and NaCl-injected groups compared with both unexercised and exercised, uninjected controls. Tendon blood vessels increased in number in the SP-injected group compared with unexercised controls, a finding not seen in NaCl-injected controls or in uninjected, exercised animals. Paratendinous inflammation was more pronounced in the SP-injected group than in the NaCl controls. NK-1R was detected in blood vessel walls, nerves, inflammatory cells and tenocytes. SP accelerated the development of tendinosis-like changes in the rabbit Achilles tendon, which supports theories of a potential role of SP in tendinosis development; a fact of clinical interest since SP effects can be effectively blocked. The angiogenic response to SP injections seems related to paratendinitis.

  9. Astaxanthin Suppresses MPP+-Induced Oxidative Damage in PC12 Cells through a Sp1/NR1 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiaochun Chen

    2013-03-01

    Full Text Available Objective: To investigate astaxanthin (ATX neuroprotection, and its mechanism, on a 1-methyl-4-phenyl-pyridine ion (MPP+-induced cell model of Parkinson’s disease. Methods: Mature, differentiated PC12 cells treated with MPP+ were used as an in vitro cell model. The MTT assay was used to investigate cell viability after ATX treatment, and western blot analysis was used to observe Sp1 (activated transcription factor 1 and NR1 (NMDA receptor subunit 1 protein expression, real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1. Results: PC12 cell viability was significantly reduced by MPP+ treatment. The expression of Sp1 and NR1 mRNA and protein were increased compared with the control (p < 0.01. Following co-treatment with ATX and MPP+, cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were decreased, compared with the MPP+ groups (p < 0.01. In addition, mithracycin A protected PC12 cells from oxidative stress caused by MPP+ by specifically inhibiting the expression of Sp1. Moreover, cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer. Conclusion: ATX inhibited oxidative stress induced by MPP+ in PC12 cells, via the SP1/NR1 signaling pathway.

  10. Lactobacillus apinorum sp. nov., Lactobacillus mellifer sp. nov., Lactobacillus mellis sp. nov., Lactobacillus melliventris sp. nov., Lactobacillus kimbladii sp. nov., Lactobacillus helsingborgensis sp. nov. and Lactobacillus kullabergensis sp. nov., isolated from the honey stomach of the honeybee Apis mellifera

    Science.gov (United States)

    Alsterfjord, Magnus; Nilson, Bo; Butler, Èile; Vásquez, Alejandra

    2014-01-01

    We previously discovered a symbiotic lactic acid bacterial (LAB) microbiota in the honey stomach of the honeybee Apis mellifera. The microbiota was composed of several phylotypes of Bifidobacterium and Lactobacillus. 16S rRNA gene sequence analyses and phenotypic and genetic characteristics revealed that the phylotypes isolated represent seven novel species. One grouped with Lactobacillus kunkeei and the others belong to the Lactobacillus buchneri and Lactobacillus delbrueckiisubgroups of Lactobacillus. We propose the names Lactobacillus apinorum sp. nov., Lactobacillus mellifer sp. nov., Lactobacillus mellis sp. nov., Lactobacillus melliventris sp. nov., Lactobacillus kimbladii sp. nov., Lactobacillus helsingborgensis sp. nov. and Lactobacillus kullabergensis sp. nov. for these novel species, with the respective type strains being Fhon13NT ( = DSM 26257T = CCUG 63287T), Bin4NT ( = DSM 26254T = CCUG 63291T), Hon2NT ( = DSM 26255T = CCUG 63289T), Hma8NT ( = DSM 26256T = CCUG 63629T), Hma2NT ( = DSM 26263T = CCUG 63633T), Bma5NT ( = DSM 26265T = CCUG 63301T) and Biut2NT ( = DSM 26262T = CCUG 63631T). PMID:24944337

  11. Tachykinins stimulate a subset of mouse taste cells.

    Science.gov (United States)

    Grant, Jeff

    2012-01-01

    The tachykinins substance P (SP) and neurokinin A (NKA) are present in nociceptive sensory fibers expressing transient receptor potential cation channel, subfamily V, member 1 (TRPV1). These fibers are found extensively in and around the taste buds of several species. Tachykinins are released from nociceptive fibers by irritants such as capsaicin, the active compound found in chili peppers commonly associated with the sensation of spiciness. Using real-time Ca(2+)-imaging on isolated taste cells, it was observed that SP induces Ca(2+) -responses in a subset of taste cells at concentrations in the low nanomolar range. These responses were reversibly inhibited by blocking the SP receptor NK-1R. NKA also induced Ca(2+)-responses in a subset of taste cells, but only at concentrations in the high nanomolar range. These responses were only partially inhibited by blocking the NKA receptor NK-2R, and were also inhibited by blocking NK-1R indicating that NKA is only active in taste cells at concentrations that activate both receptors. In addition, it was determined that tachykinin signaling in taste cells requires Ca(2+)-release from endoplasmic reticulum stores. RT-PCR analysis further confirmed that mouse taste buds express NK-1R and NK-2R. Using Ca(2+)-imaging and single cell RT-PCR, it was determined that the majority of tachykinin-responsive taste cells were Type I (Glial-like) and umami-responsive Type II (Receptor) cells. Importantly, stimulating NK-1R had an additive effect on Ca(2+) responses evoked by umami stimuli in Type II (Receptor) cells. This data indicates that tachykinin release from nociceptive sensory fibers in and around taste buds may enhance umami and other taste modalities, providing a possible mechanism for the increased palatability of spicy foods.

  12. Tachykinins stimulate a subset of mouse taste cells.

    Directory of Open Access Journals (Sweden)

    Jeff Grant

    Full Text Available The tachykinins substance P (SP and neurokinin A (NKA are present in nociceptive sensory fibers expressing transient receptor potential cation channel, subfamily V, member 1 (TRPV1. These fibers are found extensively in and around the taste buds of several species. Tachykinins are released from nociceptive fibers by irritants such as capsaicin, the active compound found in chili peppers commonly associated with the sensation of spiciness. Using real-time Ca(2+-imaging on isolated taste cells, it was observed that SP induces Ca(2+ -responses in a subset of taste cells at concentrations in the low nanomolar range. These responses were reversibly inhibited by blocking the SP receptor NK-1R. NKA also induced Ca(2+-responses in a subset of taste cells, but only at concentrations in the high nanomolar range. These responses were only partially inhibited by blocking the NKA receptor NK-2R, and were also inhibited by blocking NK-1R indicating that NKA is only active in taste cells at concentrations that activate both receptors. In addition, it was determined that tachykinin signaling in taste cells requires Ca(2+-release from endoplasmic reticulum stores. RT-PCR analysis further confirmed that mouse taste buds express NK-1R and NK-2R. Using Ca(2+-imaging and single cell RT-PCR, it was determined that the majority of tachykinin-responsive taste cells were Type I (Glial-like and umami-responsive Type II (Receptor cells. Importantly, stimulating NK-1R had an additive effect on Ca(2+ responses evoked by umami stimuli in Type II (Receptor cells. This data indicates that tachykinin release from nociceptive sensory fibers in and around taste buds may enhance umami and other taste modalities, providing a possible mechanism for the increased palatability of spicy foods.

  13. Ecdysteroids from a Zoanthus sp.

    Science.gov (United States)

    Suksamrarn, Apichart; Jankam, Aroon; Tarnchompoo, Bongkoch; Putchakarn, Sumaitt

    2002-08-01

    A new ecdysteroid, zoanthusterone, has been isolated from a marine zoanthid, Zoanthus sp. Ten known ecdysteroids, ponasterone A, 20-hydroxyecdysone 2-acetate, viticosterone E, integristerone A 25-acetate, 2-deoxy-20-hydroxyecdysone, ecdysone, ajugasterone C, dacryhainansterone, inokosterone, and 20-hydroxyecdysone, have also been isolated. This is the first report of ecdysteroids in a Zoanthus species.

  14. Sporulation of Cyclospora sp. oocysts.

    OpenAIRE

    Smith, H V; Paton, C A; Mitambo, M M; Girdwood, R W

    1997-01-01

    Cyclospora sp. oocysts sporulated maximally at 22 and 30 degrees C for 14 days retarded sporulation. Up to 12% of human- and baboon-derived oocysts previously stored at 4 degrees C for 1 to 2 months sporulated when stored for 6 to 7 days at 30 degrees C.

  15. Substance P Promotes the Proliferation, but Inhibits Differentiation and Mineralization of Osteoblasts from Rats with Spinal Cord Injury via RANKL/OPG System.

    Directory of Open Access Journals (Sweden)

    Hai-Juan Liu

    Full Text Available Spinal cord injury (SCI causes a significant amount of bone loss, which results in osteoporosis (OP. The neuropeptide substance P (SP and SP receptors may play important roles in the pathogenesis of OP after SCI. To identify the roles of SP in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB in SCI rats, we investigated the expression of neurokinin-1 receptors (NK1R in BMSC-OB and the effects of SP on bone formation by development of BMSC-OB cultures. Sixty young male Sprague-Dawley rats were randomized into two groups: SHAM and SCI. The expression of NK1R protein in BMSC-OB was observed using immunohistochemistry and Western blot analysis. The dose- and time-dependent effects of SP on the proliferation, differentiation and mineralization of BMSC-OB and the expression of osteoblastic markers by in vitro experiments. The expression of NK1R in BMSC-OB was observed on plasma membranes and in cytoplasm. One week after osteogenic differentiation, the expression of NK1R was significantly increased after SCI at mRNA and protein levels. However, this difference was gradually attenuated at 2 or 3 weeks later. SP have the function to enhance cell proliferation, inhibite cell differentiation and mineralization at a proper concentration and incubation time, and this effect would be inhibited by adding SP or NK1R antagonist. The expression of RANKL/OPG was significantly increased in tibiae after SCI. Similarly, the RANKL/OPG expression in SCI rats was significantly increased when treating with 10-8 M SP. SP plays a very important role in the pathogenesis of OP after SCI. The direct effect of SP may lead to increased bone resorption through the RANKL/OPG axis after SCI. In addition, high expression of SP also results in the suppression of osteogenesis in SCI rats. Then, the balance between bone resorption and bone formation was broken and finally osteoporosis occurred.

  16. Extracellular Expression in Aspergillus niger of an Antibody Fused to Leishmania sp. Antigens.

    Science.gov (United States)

    Magaña-Ortíz, Denis; Fernández, Francisco; Loske, Achim M; Gómez-Lim, Miguel A

    2018-01-01

    Nucleoside hydrolase and sterol 24-c-methyltransferase, two antigenic proteins of Leishmania sp., were expressed in Aspergillus niger. Genetic transformation of conidia was achieved using underwater shock waves. scFv antibody addressed to DEC205, a receptor of dendritic cells, was fused to two proteins of Leishmania sp. Receptor 205 has a relevant role in the immune system in mammals; it can modulate T cell response to different antigens. Extracellular expression strategy of recombinant antibody was achieved using a fragment of native glucoamylase A (514 aa) as a carrier. Fermentations in shake flasks showed that the recombinant protein (104 kDa) was expressed and secreted only when maltose was used as carbon source; on the contrary, the expression was highly repressed in presence of xylose. Noteworthy, recombinant protein was secreted without glucoamylase-carrier and accumulation at intracellular level was not observed. The results presented here demonstrate the high value of Aspergillus niger as biotechnological platform for recombinant antibodies against Leishmania sp. at low cost. To the best of our knowledge, this is the first report about the recombinant expression of antigenic proteins of Leishmania sp. in filamentous fungi. The protein obtained can be used to explore novel strategies to induce immunity against Leishmania sp. or it can be employed in diagnostic kits to detect this neglected disease.

  17. An Sp1/Sp3 binding polymorphism confers methylation protection.

    Directory of Open Access Journals (Sweden)

    Yanis A Boumber

    2008-08-01

    Full Text Available Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001. Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001. The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001, suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.

  18. Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography

    International Nuclear Information System (INIS)

    Gates, T.S.; Zimmerman, R.P.; Mantyh, C.R.; Vigna, S.R.; Maggio, J.E.; Welton, M.L.; Passaro, E.P. Jr.; Mantyh, P.W.

    1988-01-01

    Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125 I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: (1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; (2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; (3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and (4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells

  19. Advancing drug therapy for brain tumours: a current review of the pro-inflammatory peptide Substance P and its antagonists as anti-cancer agents.

    Science.gov (United States)

    Mander, Kimberley; Harford-Wright, Elizabeth; Lewis, Kate M; Vink, Robert

    2014-01-01

    Evidence for the involvement of the Substance P (SP)/NK1 receptor system in the development and progression of cancer strongly supports its potential as a therapeutic target in malignancies. Novel strategies for approaching cancer treatment are urgently required particularly with regard to tumours of the central nervous system (CNS), which are notoriously difficult to effectively treat and associated with extremely poor prognosis for many patients. This is due, in part, to the presence of the highly specialised blood-brain barrier, which is known to restrict common treatments such as chemotherapy and hinder early tumour diagnosis. Additionally, tumours of the CNS are difficult to surgically resect completely, often contributing to the resurgence of the disease many years later. Interestingly, despite the presence of the blood-brain barrier, circulating tumour cells are able to gain entry to the brain and form secondary brain tumours; however, the underlying mechanisms of this process remain unclear. Tachykinins, in particular Substance P, have been implicated in early blood-brain barrier disruption via neurogenic inflammation in a number of other CNS pathologies. Recent evidence also suggests that Substance P may play a central role in the development of CNS tumours. It has been well established that a number of tumour cells express Substance P, NK1 receptors and mRNA for the tachykinin NK1 receptor. This increase in the Substance P/NK1 receptor system is known to induce proliferation and migration of tumour cells as well as stimulate angiogenesis, thus contributing to tumour progression. Accordingly, the NK1 receptor antagonist presents a novel target for anti-cancer therapy for which a number of patents have been filed. This review will examine the role of Substance P in the development of CNS tumours and its potential application as an anti-cancer agent.

  20. Glutamate receptors

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Geballe, Matthew T; Snyder, James P

    2006-01-01

    Fast excitatory synaptic transmission in the CNS relies almost entirely on the neurotransmitter glutamate and its family of ion channel receptors. An appreciation of the coupling between agonist binding and channel opening has advanced rapidly during the past five years, largely as a result of ne...

  1. Antioxidant capacity, polyphenol content and iron bioavailability from algae (Ulva sp., Sargassum sp. and Porphyra sp.) in human subjects.

    Science.gov (United States)

    García-Casal, Maria N; Ramírez, José; Leets, Irene; Pereira, Ana C; Quiroga, Maria F

    2009-01-01

    Marine algae are easily produced and are good sources of Fe. If this Fe is bioavailable, algae consumption could help to combat Fe deficiency and anaemia worldwide. The objective of the present study was to evaluate Fe bioavailability, polyphenol content and antioxidant capacity from three species of marine algae distributed worldwide. A total of eighty-three subjects received maize- or wheat-based meals containing marine algae (Ulva sp., Sargassum sp. and Porphyra sp.) in different proportions (2.5, 5.0 and 7.5 g) added to the water to prepare the dough. All meals administered contained radioactive Fe. Absorption was evaluated calculating radioactive Fe incorporation in subjects' blood. The three species of marine algae were analysed for polyphenol content and reducing power. Algae significantly increased Fe absorption in maize- or wheat-based meals, especially Sargassum sp., due to its high Fe content. Increases in absorption were dose-dependent and higher in wheat- than in maize-based meals. Total polyphenol content was 10.84, 18.43 and 80.39 gallic acid equivalents/g for Ulva sp., Porphyra sp. and Sargassum sp., respectively. The antioxidant capacity was also significantly higher in Sargassum sp. compared with the other two species analysed. Ulva sp., Sargassum sp. and Porphyra sp. are good sources of bioavailable Fe. Sargassum sp. resulted in the highest Fe intake due to its high Fe content, and a bread containing 7.5 g Sargassum sp. covers daily Fe needs. The high polyphenol content found in Sargassum sp. could be partly responsible for the antioxidant power reported here, and apparently did not affect Fe absorption.

  2. Monocyte CD64 or CD89 targeting by surfactant protein D/anti-Fc receptor mediates bacterial uptake.

    NARCIS (Netherlands)

    Tacken, P.J.; Batenburg, J.J.

    2006-01-01

    We recently showed that a chimeric protein, consisting of a recombinant fragment of human surfactant protein D (rfSP-D) coupled to a Fab' fragment directed against the human Fcalpha receptor (CD89), effectively targets pathogens recognized by SP-D to human neutrophils. The present study evaluates

  3. Keratinocyte expression of inflammatory mediators plays a crucial role in substance P-induced acute and chronic pain

    Directory of Open Access Journals (Sweden)

    Wei Tzuping

    2012-07-01

    Full Text Available Abstract Tibia fracture in rats followed by cast immobilization leads to nociceptive, trophic, vascular and bone-related changes similar to those seen in Complex Regional Pain Syndrome (CRPS. Substance P (SP mediated neurogenic inflammation may be responsible for some of the signs of CRPS in humans. We therefore hypothesized that SP acting through the SP receptor (NK1 leads to the CRPS-like changes found in the rat model. In the present study, we intradermally injected rats with SP and monitored hindpaw mechanical allodynia, temperature, and thickness as well as tissue levels of tumor necrosis factor-α (TNF-α, interleukin 1β (IL-1β, interleukin 6 (IL-6, and nerve growth factor-β (NGF for 72 h. Anti-NGF antibody was utilized to block the effects of SP-induced NGF up-regulation. Fracture rats treated with the selective NK1 receptor antagonist LY303870 prior to cast removal were assessed for BrdU, a DNA synthesis marker, incorporation in skin cells to examine cellular proliferation. Bone microarchitecture was measured using micro computed tomography (μCT. We observed that: (1 SP intraplantar injection induced mechanical allodynia, warmth and edema as well as the expression of nociceptive mediators in the hindpaw skin of normal rats, (2 LY303870 administered intraperitoneally after fracture attenuated allodynia, hindpaw unweighting, warmth, and edema, as well as cytokine and NGF expression, (3 LY303870 blocked fracture-induced epidermal thickening and BrdU incorporation after fracture, (4 anti-NGF antibody blocked SP-induced allodynia but not warmth or edema, and (5 LY303870 had no effect on bone microarchitecture. Collectively our data indicate that SP acting through NK1 receptors supports the nociceptive and vascular components of CRPS, but not the bone-related changes.

  4. Interference with peroxisome proliferator-activated receptor-γ in vascular smooth muscle causes baroreflex impairment and autonomic dysfunction.

    Science.gov (United States)

    Borges, Giulianna R; Morgan, Donald A; Ketsawatsomkron, Pimonrat; Mickle, Aaron D; Thompson, Anthony P; Cassell, Martin D; Mohapatra, Durga P; Rahmouni, Kamal; Sigmund, Curt D

    2014-09-01

    S-P467L mice expressing dominant negative peroxisome proliferator-activated receptor-γ selectively in vascular smooth muscle exhibit impaired vasodilation, augmented vasoconstriction, hypertension, and tachycardia. We hypothesized that tachycardia in S-P467L mice is a result of baroreflex dysfunction. S-P467L mice displayed increased sympathetic traffic to the heart and decreased baroreflex gain and effectiveness. Carotid arteries exhibited inward remodeling but no changes in distensibility or stress/strain. Aortic depressor nerve activity in response to increased arterial pressure was blunted in S-P467L mice. However, the arterial pressure and heart rate responses to aortic depressor nerve stimulation were unaltered in S-P467L mice, suggesting that the central and efferent limbs of the baroreflex arc remain intact. There was no transgene expression in nodose ganglion and no change in expression of the acid-sensing ion channel-2 or -3 in nodose ganglion. There was a trend toward decreased expression of transient receptor potential vanilloid-1 receptor mRNA in nodose ganglion, but no difference in the immunochemical staining of transient receptor potential vanilloid-1 receptor in the termination area of the left aortic depressor nerve in S-P467L mice. Although there was no difference in the maximal calcium response to capsaicin in cultured nodose neurons from S-P467L mice, there was decreased desensitization of transient receptor potential vanilloid-1 receptor channels. In conclusion, S-P467L mice exhibit baroreflex dysfunction because of a defect in the afferent limb of the baroreflex arc caused by impaired vascular function, altered vascular structure, or compromised neurovascular coupling. These findings implicate vascular smooth muscle peroxisome proliferator activated receptor-γ as a critical determinant of neurovascular signaling. © 2014 American Heart Association, Inc.

  5. A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Spiess, S

    1995-01-01

    We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were......R alpha T-beta T+ cells were found in gut tissues of the immunodeficient host. Transplanted scid mice developed clinical and histological signs of IBD. An oligoclonal, gut-homing, memory/effector CD4+ CD44+ TcR beta T+ TcR alpha T-T cell subset from leaky tg scid mice thus has a pathogenic potential when...

  6. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Antje Brand

    Full Text Available Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP. In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1 SP, 2 an SP antagonist (GR-82334, and 3 an NMDA antagonist (APV on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  7. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Science.gov (United States)

    Brand, Antje; Smith, Ewan St J; Lewin, Gary R; Park, Thomas J

    2010-12-21

    Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  8. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    International Nuclear Information System (INIS)

    Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

    2011-01-01

    Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

  9. Pantoea rodasii sp. nov., Pantoea rwandensis sp. nov. and Pantoea wallisii sp. nov., isolated from Eucalyptus.

    Science.gov (United States)

    Brady, Carrie L; Cleenwerck, Ilse; van der Westhuizen, Lorinda; Venter, Stephanus N; Coutinho, Teresa A; De Vos, Paul

    2012-07-01

    Several Gram-negative-staining, facultatively anaerobic bacterial isolates were obtained from Eucalyptus seedlings showing symptoms of bacterial blight and dieback in Colombia, Rwanda and South Africa. Partial 16S rRNA gene sequencing, together with partial gyrB sequencing, placed the isolates in the genus Pantoea and indicated that they constituted three novel species. Multilocus sequence analysis (MLSA) based on partial sequences of gyrB, rpoB, infB and atpD revealed Pantoea dispersa, Pantoea eucrina and Pantoea cypripedii as their closest phylogenetic relatives. DNA-DNA hybridization studies confirmed the classification of the new isolates as three novel species and phenotypic tests allowed them to be differentiated from their closest phylogenetic neighbours. The names Pantoea rodasii sp. nov. [type strain LMG 26273(T)=BD 943(T) (deposited with the Plant Pathogenic and Plant Protecting Bacteria Collection, South Africa)=BCC 581(T) (deposited with the Bacterial Culture Collection, Forestry and Agricultural Institute, South Africa)], Pantoea rwandensis sp. nov. (type strain LMG 26275(T)=BD 944(T)=BCC 571(T)) and Pantoea wallisii sp. nov. (type strain LMG 26277(T)=BD 946(T)=BCC 682(T)) are proposed.

  10. DISTRIBUSI Solen sp DI PERAIRAN KABUPATEN BANGKALAN

    Directory of Open Access Journals (Sweden)

    Eva Ari Wahyuni

    2016-03-01

    Full Text Available DISTRIBUTION OF Solen sp IN BANGKALAN WATERSSolen sp potential needs to be developed on the island of Madura, particularly in Bangkalan. Solen sp utilization has increased which has the potential to overfishing. Therefore, this study aims to determine the density of Solen sp and their ecology in the waters Modung village, Modung District, Bangkalan. The experiment was conducted in April 2015 using the descriptive method. The materials used include Solen sp and physico-chemical parameters of the environment (temperature, salinity, pH, and substrate. The analyzes were conducted at the Laboratory of Marine Science, Department of Marine Sciences, Trunojoyo University of Madura by using the tool grabsampler, sieveshaker, and pipetting with gravimetric method. The analysis shows the range of values of temperature between 29-300C, salinity between 31-32 ppt, pH were 7.9-8.0 and the type of substrate in the form of sandy mud, as well as the density of Solen sp from 8-10 individuals/m2. All measurement results indicate normal conditions and in accordance with the sea water quality standard for marine life, which can be a suitable habitat for the growth and development of Solen sp. This condition is thought to affect the density of Solen sp.Keywords: Bangkalan, density, distribution, Solen sp, substrate.ABSTRAKPotensi Solen sp perlu dikembangkan di pulau Madura, khususnya di Kabupaten Bangkalan. Pemanfaatan Solen sp mengalami peningkatan sehingga berpotensi overfishing. Untuk itu, penelitian ini bertujuan untuk mengetahui kepadatan Solen sp dan ekologinya di perairan desa Modung, Kecamatan Modung, Kabupaten Bangkalan. Penelitian dilaksanakan pada bulan April 2015 dengan metode deskriptif. Materi dan bahan yang digunakan diantaranya Solen sp dan parameter fisika-kimia lingkungan (suhu, salinitas, pH, dan substrat. Analisa dilakukan di Laboratorium Ilmu Kelautan, Program studi/Jurusan Ilmu Kelautan Universitas Trunojoyo Madura dengan menggunakan alat

  11. Especificidad del hongo micorrizico (Rhizoctonia sp.) en Phalaenopsis sp., Cymbidium sp., Trichoceros antenifer, Oncidium excavatum, y Cyrtochilum sp.

    OpenAIRE

    Ordoñez, Silvia L.; Pillacela Zhunio, Dora Priscila; Salazar, Jazmín M.; Peña Tapia, Denisse Fabiola

    2016-01-01

    Las orquídeas producen abundantes semillas pequeñas, careciendo de endospermo, cotiledones y sustancias de reserva para llevar a cabo su germinación. Es por esto que estratégicamente las semillas establecen una relación simbiótica con un hongo micorrízico que favorece a su germinación y desarrollo. El objetivo de este estudio fue determinar la especificidad del hongo micorrízico (Rhizoctonia sp.) en la germinación de cinco géneros de orquídeas. Se usaron dos medios de cultivo: 1) PhytamaxTM y...

  12. Interaction of tachykinins with their receptors studied with cyclic analogues of substance P and neurokinin B

    Energy Technology Data Exchange (ETDEWEB)

    Ploux, O.; Lavielle, S.; Chassaing, G.; Julien, S.; Marquet, A.; D' Orleans-Juste, P.; Dion, S.; Regoli, D.; Beaujouan, J.C.; Bergstroem, L.

    1987-11-01

    The activities of two groups of cyclic agonists of substance P (SP) have been studied. The disulfide bridge constraints have been designed on the basis of conformational studies on SP and physalaemin indicating an ..cap alpha..-helical structure for the core of these two tachykinins (group I) and a folding of the C-terminal carboxamide towards the side chains of the glutamines 5 and 6 (group II). Only peptides simulating the ..cap alpha..-helix present substantial potencies. (Cys/sup 3,6/)SP is as active as SP in inhibiting /sup 125/I-labeled Bolton and Hunter SP-specific binding on rat brain synaptosomes and on dog carotid bioassay, two assays specific for the neurokinin 1 receptor. Moreover, (Cys/sup 3,6/)SP is a potent as neurokinin B in inhibiting /sup 125/I-labeled Bolton and Hunter eledoisin-specific binding on rat cortical synaptosomes as well as in stimulating rat portal vein, two tests specific for the neurokinin 3 receptor. Interestingly, in contrast to neurokinin B, (Cys/sup 3,6/)SP is a weak agonist of the neurokinin 2 receptor subtype, as evidenced by its binding potency in inhibiting /sup 3/H-labeled neurokinin A-specific binding on rat duodenum and in inducing the contractions of the rabbit pulmonary artery, a neurokinin 2-type bioassay. To increase the specificity of the cyclic analogue (Cys/sup 3,6/)SP positions 8 and 9 were modified. Collectively, these results suggest that the neurokinin 1 and neurokinin 3 tachykinin receptors may recognize a similar three-dimensional structure of the core of the tachykinins. Different orientations of the common C-terminal tripeptide may be related to the selectivity for the different receptor subtypes.

  13. Rodentibacter gen. nov including Rodentibacter pneumotropicus comb. nov., Rodentibacter heylii sp nov., Rodentibacter myodis sp nov., Rodentibacter ratti sp nov., Rodentibacter heidelbergensis sp nov., Rodentibacter trehalosifermentans sp nov., Rodentibacter rarus sp nov., Rodentibacter mrazii

    DEFF Research Database (Denmark)

    Adhikary, Sadhana; Nicklas, Werner; Bisgaard, Magne

    2017-01-01

    genomic comparison allowed the estimation of DNA–DNA renaturation. Rodentibacter heylii sp. nov. was proposed for a group that included the biovar Heyl of [ Pasteurella ] pneumotropica with the type strain ATCC 12555T (=CCUG 998T). A group was proposed as Rodentibacter ratti sp. nov., which included...

  14. Radio-peptides targeting g-protein coupled receptors in cancer: from bench to bed

    International Nuclear Information System (INIS)

    Maecke, H.R.

    2015-01-01

    Full text of publication follows. In the development of targeted imaging and therapy agents the most important challenge and prerequisite is to identify and validate the molecular targets of any disease. The targets should be specific, relevant, easily accessible and highly expressed. In addition they should have no or at least very low expression in normal tissue. Among the many drug targets is the large family of G-protein coupled receptors (GPCRs). It is the most important family of marketed drugs and the basic accomplishments in the field were recognised by the award of the recent Nobel price in chemistry. GPCRs also play a role in cancer. Several of these receptors are massively over-expressed in different human tumors such as neuroendocrine tumors (over-expression of the somatostatin receptor family), prostate and breast tumors (bombesin receptor family), brain tumors (NK1 receptor) etc.. This allows to develop (nuclear, MRI, optical) probes for imaging and potentially targeted therapy (theragnostics). Natural ligands targeting GPCRs are often peptides. They need to be modified for metabolic stability, modified for labeling with radio-metals (conjugation of bifunctional chelators) or radio-halogens (prosthetic groups). Preserved biological integrity after modification and labeling needs to be assured, long retention times in the tumor is important, conferred by internalisation. Radio-metal labeling in particular needs to be reasonably fast and the radio metal complexes have to show high stability with regard to radio-metal release. These prerequisites will be discussed for somatostatin receptor based radio-peptides in particular. For a successful clinical application preclinical imaging and biodistribution in adequate animal models are mandatory. New tracers for positron emission tomography (PET) and single photon emission computed tomography (SPECT) will be presented for neuroendocrine tumors and prostate cancer. In particular radiolabeled antagonists will

  15. Xylanolytic enzyme systems in Arthrobacter sp MTCC 5214 and Lactobacillus sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Khandeparker, R.; Jalal, T.

    The production of extracellular xylanolytic enzymes such as xylanase, alfa-L-arabinofuranosidase (alfa-l-AFase), and acetyl xylan esterase (Axe) by marine Arthrobacter sp and Lactobacillus sp was investigated using different carbon sources Induction...

  16. Evaluation of antioxidant and cytotoxic properties of Cynobacteria, Limnothrix sp. and Leptolyngbya sp. from Arabian sea

    Digital Repository Service at National Institute of Oceanography (India)

    Anas, A.; Vinothkumar, S.; Gupta, S.; Jasmin, C.; Joseph, V.; Parameswaran, P.S.; Nair, S.

    The hexane fractions of the marine cyanobacteria: Leptolyngbya sp. and Limnothrix sp., collected from Arabian Sea were found to display promising antioxidant properties than their ethyl acetate fraction during radical scavenging ABTS/DPPH assays (IC...

  17. Structure of a tetrameric galectin from Cinachyrella sp. (ball sponge)

    Energy Technology Data Exchange (ETDEWEB)

    Freymann, Douglas M., E-mail: freymann@northwestern.edu [Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611 (United States); Nakamura, Yuka [Hokkaido University, 3-1-1 Minato-cho, Hakodate 041-8611 (Japan); Focia, Pamela J. [Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611 (United States); Sakai, Ryuichi [Hokkaido University, 3-1-1 Minato-cho, Hakodate 041-8611 (Japan); Swanson, Geoffrey T. [Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611 (United States)

    2012-09-01

    The structure of a tetrameric sponge galectin suggests a basis for glutamate receptor potentiation. The galectins are a family of proteins that bind with highest affinity to N-acetyllactosamine disaccharides, which are common constituents of asparagine-linked complex glycans. They play important and diverse physiological roles, particularly in the immune system, and are thought to be critical metastatic agents for many types of cancer cells, including gliomas. A recent bioactivity-based screen of marine sponge (Cinachyrella sp.) extract identified an ancestral member of the galectin family based on its unexpected ability to positively modulate mammalian ionotropic glutamate receptor function. To gain insight into the mechanistic basis of this activity, the 2.1 Å resolution X-ray structure of one member of the family, galectin CchG-1, is reported. While the protomer exhibited structural similarity to mammalian prototype galectin, CchG-1 adopts a novel tetrameric arrangement in which a rigid toroidal-shaped ‘donut’ is stabilized in part by the packing of pairs of vicinal disulfide bonds. Twofold symmetry between binding-site pairs provides a basis for a model for interaction with ionotropic glutamate receptors.

  18. Substance P stimulates Growth Hormone (GH) and GH-Releasing Hormone (GHRH) secretions through tachykinin NK2 receptors in sheep.

    Science.gov (United States)

    Lemamy, Guy-Joseph; Guillaume, Viviane; Ndéboko, Bénédicte; Mouecoucou, Justine; Oliver, Charles

    2012-05-01

    Substance P is ubiquitous undecapeptide belonging to the tachykinins family. It has been found in the hypothalamus and is involved in the hypothalamo-hypophysial axis in several mammals, including human. Previous studies have shown that substance P increases GH secretions in rats and human. In this study, we have shown that intravenously infused substance P in sheep caused an increased level of Growth Hormone (GH) and GH-Releasing Hormone (GHRH), and decreased Somatotropin Release Inhibiting Hormone (SRIH) secretions. GH was obtained from peripheral blood. GHRH and SRIH were directly collected from hypophysial portal blood, using a trans-nasal surgery technique in a vigil sheep that allowed accessing to hypothalamo-hypophysial portal vessels. Hormones assays were performed by radioimmunoassay (RIA). Moreover, we showed that substance P-induced GH and GHRH secretion appears to be mediated by NK2 tachykinin receptors, since it is specifically blocked by a non peptidic tachykinin NK2 receptor antagonist (SR48968, Sanofi, Montpellier, France) whereas a non peptidic tachykinin NK1 antagonist (SR140333, Sanofi, Montpellier, France) failed to modify GH and GHRH hormones secretions. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Scopranones with Two Atypical Scooplike Moieties Produced by Streptomyces sp. BYK-11038.

    Science.gov (United States)

    Uchida, Ryuji; Lee, Daiki; Suwa, Ibuki; Ohtawa, Masaki; Watanabe, Nozomu; Demachi, Ayumu; Ohte, Satoshi; Katagiri, Takenobu; Nagamitsu, Tohru; Tomoda, Hiroshi

    2017-11-03

    Three new compounds, designated scopranones A-C, were isolated from the culture broth of a soil isolate, Streptomyces sp. BYK-11038, and shown to be inhibitors of bone morphogenetic protein (BMP) induced alkaline phosphatase activity in a BMP receptor mutant cell line. The structures were elucidated using NMR and other spectral data. The scopranones have an unusual structure with two atypical scooplike moieties linked at the tails to form part of a unique 3-furanone ring.

  20. First report of Anisakis sp. in Epinephelus sp. in East Indonesia

    OpenAIRE

    Annytha Ina Rohi Detha; Diana Agustiani Wuri; Julianty Almet; Yuni Riwu; Christin Melky

    2018-01-01

    Objective: The present research was conducted to identify the prevalence of Anisakis sp. as fish-borne zoonoses in Epinephelus sp. in territorial waters of East Nusa Tenggara, Indonesia. Materials and methods: A total of 50 fish (Epinephelus sp.) were collected from Kupang Fish Market in East Nusa Tenggara. Identification of Anisakis sp. was performed based on morphological observations considering shape of ventriculus, boring tooth, and mucron using binocular microscope. Results: Prev...

  1. Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi.

    Science.gov (United States)

    Chauhan, Vinita S; Sterka, David G; Gray, David L; Bost, Kenneth L; Marriott, Ian

    2008-06-15

    Although glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation of the ability of resident CNS cells to initiate and/or augment inflammation following trauma or infection. The tachykinin, substance P (SP), is well known to augment inflammatory responses at peripheral sites and its presence throughout the CNS raises the possibility that this neuropeptide might serve a similar function within the brain. In support of this hypothesis, we have recently demonstrated the expression of high affinity receptors for SP (Neurokinin-1 (NK-1) receptors) on microglia and shown that this tachykinin can significantly elevate bacterially induced inflammatory prostanoid production by isolated cultures of these cells. In the present study, we demonstrate that endogenous SP/NK-1R interactions are an essential component in the initiation and/or progression of CNS inflammation in vivo following exposure to two clinically relevant bacterial CNS pathogens, Neisseria meningitidis and Borrelia burgdorferi. We show that in vivo elevations in inflammatory cytokine production and decreases in the production of an immunosuppressive cytokine are markedly attenuated in mice genetically deficient in the expression of the NK-1R or in mice treated with a specific NK-1R antagonist. Furthermore, we have used isolated cultures of microglia and astrocytes to demonstrate that SP can augment inflammatory cytokine production by these resident CNS cell types following exposure to either of these bacterial pathogens. Taken together, these studies indicate a potentially important role for neurogenic exacerbation of resident glial immune responses in CNS inflammatory diseases, such as bacterial meningitis.

  2. The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis

    Directory of Open Access Journals (Sweden)

    Jansen Sandra

    2011-02-01

    Full Text Available Abstract Background Recent studies have suggested that the scavenger receptor MARCO (macrophage receptor with collagenous structure mediates activation of the immune response in bacterial infection of the central nervous system (CNS. The chemotactic G-protein-coupled receptor (GPCR formyl-peptide-receptor like-1 (FPRL1 plays an essential role in the inflammatory responses of host defence mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD. Expression of the antimicrobial peptide cathelicidin CRAMP/LL-37 is up-regulated in bacterial meningitis, but the mechanisms underlying CRAMP expression are far from clear. Methods Using a rat meningitis model, we investigated the influence of MARCO and FPRL1 on rCRAMP (rat cathelin-related antimicrobial peptide expression after infection with bacterial supernatants of Streptococcus pneumoniae (SP and Neisseria meningitides (NM. Expression of FPRL1 and MARCO was analyzed by immunofluorescence and real-time RT-PCR in a rat meningitis model. Furthermore, we examined the receptor involvement by real-time RT-PCR, extracellular-signal regulated kinases 1/2 (ERK1/2 phosphorylation and cAMP level measurement in glial cells (astrocytes and microglia and transfected HEK293 cells using receptor deactivation by antagonists. Receptors were inhibited by small interference RNA and the consequences in NM- and SP-induced Camp (rCRAMP gene expression and signal transduction were determined. Results We show an NM-induced increase of MARCO expression by immunofluorescence and real-time RT-PCR in glial and meningeal cells. Receptor deactivation by antagonists and small interfering RNA (siRNA verified the importance of FPRL1 and MARCO for NM- and SP-induced Camp and interleukin-1β expression in glial cells. Furthermore, we demonstrated a functional interaction between FPRL1 and MARCO in NM-induced signalling by real-time RT-PCR, ERK1/2 phosphorylation and cAMP level measurement and show differences between

  3. Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy-peptidergic elevation preceding tendinosis-like tissue changes.

    Science.gov (United States)

    Backman, L J; Andersson, G; Wennstig, G; Forsgren, S; Danielson, P

    2011-06-01

    To quantify the intratendinous levels of substance P (SP) at different stages of overload in an established model for Achilles tendinopathy (rabbit). Also, to study the distribution of the SP-receptor, the NK-1R, and the source of SP, in the tendon. Animals were subjected to the overuse protocol for 1, 3 or 6 weeks. One additional group served as unexercised controls. Immunoassay (EIA), immunohistochemistry (IHC), and in situ hybridisation (ISH) were performed. EIA revealed increased SP-levels in the Achilles tendon of the exercised limb in all the experimental groups as compared to in the controls (statistically significant; p=0.01). A similar trend in the unexercised Achilles tendon was observed but was not statistically significant (p=0.14). IHC and in ISH illustrated reactions of both SP and NK-1R mainly in blood vessel walls, but the receptor was also found on tenocytes. Achilles tendon SP-levels are elevated already after 1 week of loading. This shows that increased SP-production precedes tendinosis, as tendinosis-like changes occur only after a minimum of 3 weeks of exercise, as shown in a recent study using this model. We propose that central neuronal mechanism may be involved as similar trends were observed in the contralateral Achilles tendon.

  4. Detection of Sp110 by Flow Cytometry and Application to Screening Patients for Veno-occlusive Disease with Immunodeficiency.

    Science.gov (United States)

    Marquardsen, Florian A; Baldin, Fabian; Wunderer, Florian; Al-Herz, Waleed; Mikhael, Raymond; Lefranc, Gérard; Baz, Zeina; Rezaee, Fariba; Hanna, Rabi; Kfir-Erenfeld, Shlomit; Stepensky, Polina; Meyer, Benedikt; Jauch, Annaise; Bigler, Marc B; Burgener, Anne-Valérie; Higgins, Rebecca; Navarini, Alexander A; Church, Joeseph A; Chou, Janet; Geha, Raif; Notarangelo, Luigi D; Hess, Christoph; Berger, Christoph T; Bloch, Donald B; Recher, Mike

    2017-10-01

    Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC). This approach will fail to identify VODI patients because the disease is not associated with severe T cell lymphopenia at birth; (2) the SP110 gene contains 17 exons, making it a challenge for Sanger sequencing. The recently developed next-generation sequencing (NGS) platforms that can rapidly determine the sequence of all 17 exons are available in only a few laboratories; (3) there is no standard functional assay to test for the effects of novel mutations in Sp110; and (4) it has been difficult to use flow cytometry to identify patients who lack Sp110 because of the low level of Sp110 protein in peripheral blood lymphocytes. We report here a novel flow cytometric assay that is easily performed in diagnostic laboratories and might thus become a standard assay for the evaluation of patients who may have VODI. In addition, the assay will facilitate investigations directed at understanding the function of Sp110.

  5. Specialised predation by Palpimanus sp. (Araneae: Palpimanidae ...

    African Journals Online (AJOL)

    This is the first detailed report on the natural prey and the prey-capture tactics of a Palpimanus sp. from Entebbe (Uganda). Although this species fed occasionally on insects, its dominant prey in the field was other spiders, especially jumping spiders (Salticidae) and their eggs. Encounters between Palpimanus sp. and ...

  6. Receptors for substance P on isolated intestinal smooth muscle cells of the guinea pig

    Energy Technology Data Exchange (ETDEWEB)

    Souquet, J.C.; Bitar, K.N.; Grider, J.R.; Makhlouf, G.M.

    1987-11-01

    Two radioligands, /sup 125/I-labeled substance P (/sup 125/I-SP) and /sup 125/I-labeled substance K (/sup 125/I-SK), were used to characterize the kinetics and stoichiometry of binding of mammalian tachykinins (substance P (SP), substance K (SK), and neuromedin K (NK)) to smooth muscle cells isolated from the longitudinal muscle layer of guinea pig intestine. Specific binding of /sup 125/I-SP and /sup 125/I-SK was rapid, saturable, reversible, and temperature dependent. Binding attained 63-70% of steady-state binding within 1 min, coincidentally with the time of optimal contraction. The order of potency with which mammalian tachykinins and the SP antagonist, (D-Pro2, D-Trp7,9)SP, inhibited the binding of both radioligands was identical: SP greater than SK greater than NK greater than (D-Pro2, D-Trp7,9)SP, implying preferential interaction with a site that had highest affinity for SP. SK was 2-3 times, NK 3-4 times, and (D-Pro2, D-Trp7,9)SP 7-23 times less potent than SP (IC50 0.36 nM). Except for NK, the order of potency was similar to that for contraction of isolated muscle cells. The existence of binding sites with even higher affinity was suggested by the ability of muscle cells to contract in response to concentrations as low as 10(-13) M. These binding sites were not detectable at the concentration of radioligands used. It was concluded that a SP receptor is the only tachykinin receptor subtype present on intestinal muscle cells of the guinea pig.

  7. Guide til gode spørgeskemaer

    DEFF Research Database (Denmark)

    Olsen, Henning

    Spørgeskemaundersøgelser bliver ofte brugt til at dokumentere forskellige forhold og begrunde politiske beslutninger. Men resultaterne kan være forbundet med stor usikkerhed. Det kræver omhu og stor sproglig formåen at udarbejde spørgeskemaer. Seniorforsker Henning Olsen har i flere år arbejdet med...... viden om, hvordan folk forstår sproglige meddelelser og genkalder sig informationer. I guiden behandles emner som fx styrende problemstillinger og spørgsmåls fokus og neutralitet, formulering af åbne eller lukkede spørgsmål og svarkategorier, tematiske spørgeforløb, aflastning af svarpersoners...

  8. Listeria floridensis sp. nov., Listeria aquatica sp. nov., Listeria cornellensis sp. nov., Listeria riparia sp. nov. and Listeria grandensis sp. nov., from agricultural and natural environments.

    Science.gov (United States)

    den Bakker, Henk C; Warchocki, Steven; Wright, Emily M; Allred, Adam F; Ahlstrom, Christina; Manuel, Clyde S; Stasiewicz, Matthew J; Burrell, Angela; Roof, Sherry; Strawn, Laura K; Fortes, Esther; Nightingale, Kendra K; Kephart, Daniel; Wiedmann, Martin

    2014-06-01

    Sampling of agricultural and natural environments in two US states (Colorado and Florida) yielded 18 Listeria-like isolates that could not be assigned to previously described species using traditional methods. Using whole-genome sequencing and traditional phenotypic methods, we identified five novel species, each with a genome-wide average BLAST nucleotide identity (ANIb) of less than 85% to currently described species. Phylogenetic analysis based on 16S rRNA gene sequences and amino acid sequences of 31 conserved loci showed the existence of four well-supported clades within the genus Listeria; (i) a clade representing Listeria monocytogenes, L. marthii, L. innocua, L. welshimeri, L. seeligeri and L. ivanovii, which we refer to as Listeria sensu stricto, (ii) a clade consisting of Listeria fleischmannii and two newly described species, Listeria aquatica sp. nov. (type strain FSL S10-1188(T) = DSM 26686(T) = LMG 28120(T) = BEI NR-42633(T)) and Listeria floridensis sp. nov. (type strain FSL S10-1187(T) = DSM 26687(T) = LMG 28121(T) = BEI NR-42632(T)), (iii) a clade consisting of Listeria rocourtiae, L. weihenstephanensis and three novel species, Listeria cornellensis sp. nov. (type strain TTU A1-0210(T) = FSL F6-0969(T) = DSM 26689(T) = LMG 28123(T) = BEI NR-42630(T)), Listeria grandensis sp. nov. (type strain TTU A1-0212(T) = FSL F6-0971(T) = DSM 26688(T) = LMG 28122(T) = BEI NR-42631(T)) and Listeria riparia sp. nov. (type strain FSL S10-1204(T) = DSM 26685(T) = LMG 28119(T) = BEI NR- 42634(T)) and (iv) a clade containing Listeria grayi. Genomic and phenotypic data suggest that the novel species are non-pathogenic. © 2014 IUMS.

  9. Predictive value of Sp1/Sp3/FLIP signature for prostate cancer recurrence.

    Directory of Open Access Journals (Sweden)

    Roble G Bedolla

    Full Text Available Prediction of prostate cancer prognosis is challenging and predictive biomarkers of recurrence remain elusive. Although prostate specific antigen (PSA has high sensitivity (90% at a PSA level of 4.0 ng/mL, its low specificity leads to many false positive results and considerable overtreatment of patients and its performance at lower ranges is poor. Given the histopathological and molecular heterogeneity of prostate cancer, we propose that a panel of markers will be a better tool than a single marker. We tested a panel of markers composed of the anti-apoptotic protein FLIP and its transcriptional regulators Sp1 and Sp3 using prostate tissues from 64 patients with recurrent and non-recurrent cancer who underwent radical prostatectomy as primary treatment for prostate cancer and were followed with PSA measurements for at least 5 years. Immunohistochemical staining for Sp1, Sp3, and FLIP was performed on these tissues and scored based on the proportion and intensity of staining. The predictive value of the FLIP/Sp1/Sp3 signature for clinical outcome (recurrence vs. non-recurrence was explored with logistic regression, and combinations of FLIP/Sp1/Sp3 and Gleason score were analyzed with a stepwise (backward and forward logistic model. The discrimination of the markers was identified by sensitivity-specificity analysis and the diagnostic value of FLIP/Sp1/Sp3 was determined using area under the curve (AUC for receiver operator characteristic curves. The AUCs for FLIP, Sp1, Sp3, and Gleason score for predicting PSA failure and non-failure were 0.71, 0.66, 0.68, and 0.76, respectively. However, this increased to 0.93 when combined. Thus, the "biomarker signature" of FLIP/Sp1/Sp3 combined with Gleason score predicted disease recurrence and stratified patients who are likely to benefit from more aggressive treatment.

  10. Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees.

    Science.gov (United States)

    Borbély, Éva; Sándor, Katalin; Markovics, Adrienn; Kemény, Ágnes; Pintér, Erika; Szolcsányi, János; Quinn, John P; McDougall, Jason J; Helyes, Zsuzsanna

    2016-09-01

    Mast cell tryptase (MCT) is elevated in arthritic joints, but its direct effects are not known. Here, we investigated MCT-evoked acute inflammatory and nociceptive mechanisms with behavioural, in vivo imaging and immunological techniques. Neurogenic inflammation involving capsaicin-sensitive afferents, transient receptor potential vanilloid 1 receptor (TRPV1), substance P (SP), neurokinin A (NKA) and their NK1 tachykinin receptor were studied using gene-deleted mice compared to C57Bl/6 wildtypes (n = 5-8/group). MCT was administered intraarticularly or topically (20 μl, 12 μg/ml). Capsaicin-sensitive afferents were defunctionalized with the TRPV1 agonist resiniferatoxin (RTX; 30-70-100 μg/kg s.c. pretreatment). Knee diameter was measured with a caliper, synovial perfusion with laser Doppler imaging, mechanonociception with aesthesiometry and weight distribution with incapacitance tester over 6 h. Cytokines and neuropeptides were determined with immunoassays. MCT induced synovial vasodilatation, oedema, impaired weight distribution and mechanical hyperalgesia, but cytokine or neuropeptide levels were not altered at the 6-h timepoint. Hyperaemia was reduced in RTX-treated and TRPV1-deleted animals, and oedema was absent in NK1-deficient mice. Hyperalgesia was decreased in SP/NKA- and NK1-deficient mice, weight bearing impairment in RTX-pretreated, TRPV1- and NK1-deficient animals. MCT evokes synovial hyperaemia, oedema, hyperalgesia and spontaneous pain. Capsaicin-sensitive afferents and TRPV1 receptors are essential for vasodilatation, while tachykinins mediate oedema and pain.

  11. Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro.

    Science.gov (United States)

    Hillaire, Marine L B; van Eijk, Martin; van Trierum, Stella E; van Riel, Debby; Saelens, Xavier; Romijn, Roland A; Hemrika, Wieger; Fouchier, Ron A M; Kuiken, Thijs; Osterhaus, Albert D M E; Haagsman, Henk P; Rimmelzwaan, Guus F

    2011-01-01

    The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.

  12. Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro.

    Directory of Open Access Journals (Sweden)

    Marine L B Hillaire

    Full Text Available The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.

  13. Regulation of Na(+)/K(+)-ATPase by neuron-specific transcription factor Sp4: implication in the tight coupling of energy production, neuronal activity and energy consumption in neurons.

    Science.gov (United States)

    Johar, Kaid; Priya, Anusha; Wong-Riley, Margaret T T

    2014-02-01

    A major source of energy demand in neurons is the Na(+)/K(+)-ATPase pump that restores the ionic gradient across the plasma membrane subsequent to depolarizing neuronal activity. The energy comes primarily from mitochondrial oxidative metabolism, of which cytochrome c oxidase (COX) is a key enzyme. Recently, we found that all 13 subunits of COX are regulated by specificity (Sp) factors, and that the neuron-specific Sp4, but not Sp1 or Sp3, regulates the expression of key glutamatergic receptor subunits as well. The present study sought to test our hypothesis that Sp4 also regulates Na(+)/K(+)-ATPase subunit genes in neurons. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutational analysis, over-expression, and RNA interference studies, we found that Sp4, with minor contributions from Sp1 and Sp3, functionally regulate the Atp1a1, Atp1a3, and Atp1b1 subunit genes of Na(+)/K(+)-ATPase in neurons. Transcripts of all three genes were up-regulated by depolarizing KCl stimulation and down-regulated by the impulse blocker tetrodotoxin (TTX), indicating that their expression was activity-dependent. Silencing of Sp4 blocked the up-regulation of these genes induced by KCl, whereas over-expression of Sp4 rescued them from TTX-induced suppression. The effect of silencing or over-expressing Sp4 on primary neurons was much greater than those of Sp1 or Sp3. The binding sites of Sp factors on these genes are conserved among mice, rats and humans. Thus, Sp4 plays an important role in the transcriptional coupling of energy generation and energy consumption in neurons. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Antibacterial Actions and Potential Phototoxic Effects of Volatile oils of Foeniculum sp. (fennel, Salvia sp. (sage, Vitis sp. (grape, Lavandula sp. (lavender

    Directory of Open Access Journals (Sweden)

    Elif Ayse Erdogan Eliuz

    2016-09-01

    Full Text Available In the present study, the volatile compounds of essential oil of Foeniculum vulgare (fennel, Salvia officinalis (sage, Vitis vinifera (grape, Lavandula angustifolia (lavender were analysed by gas chromatography-mass spectrometry (GC-MS using the Nist and Willey libraries. It was determined that the main components of Foeniculum sp. were anethole (41.11%, carvacrol (9.18%. whereas main components of Salvia sp were 1.8 cineole (34.09%, caryophyllene (10.95%, camphor (9.44%, α-pinene (8.42%. Vitis sp. contained linoleic acid (36.98%, 2,4-decadienal (30.79%. Finally, volatile component of Lavandula sp. was linalool (33.57%, linalyl acetate (30.74%. Photoxic antibacterial activity of volatile oil of those plants against Escherichia coli (ATCC 25293, Klebsiella pneumoniae (10031, Salmonella thyphimurium, Bacillus subtilis (ATCC 6633, Staphylococcus aureus (ATCC 25925, Enterococcus feacalis (ATCC 29212 were examined by using disc diffusion method. We demonstrated that volatile oil effectively can be activated by a standard LED light. In vitro, significant phototoxicity was demonstrated by volatile oil of Foeniculum sp. and Vitis sp. (P < 0.05, while minor phototoxicity was induced by Lavandula sp. Therefore, volatile oil of plant can be considered as a potential photosensitizer in the photochemical therapy.

  15. TurboSP and the Topological Trigger

    CERN Document Server

    Belavin, Vladislav

    2016-01-01

    TurboSP was originally proposed as an alternative to Full stream in LHCb data flow. TurboSP is a data flow strategy which not only selects events that should be preserved, like in Full stream, but also provides selective persistence. This is achieved by saving candidates and subset of the reconstruction. During this summer project we investigated the physics viability of using TurboSP with the topological lines and found out a possibility to reduce the number of kept tracks per event by two times while keeping a ratio of fully picked up interesting decay modes on $\\sim 97 \\%$ level.

  16. Spotlight on the perioperative use of maropitant citrate

    Directory of Open Access Journals (Sweden)

    Hay Kraus BL

    2017-08-01

    Full Text Available Bonnie L Hay Kraus Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, USA Abstract: Neurokinin-1 (NK-1 receptors are present in both the central nervous system and peripheral tissues. Substance P (SP is the major ligand and is involved in multiple processes including pain transmission, vasodilation, modulation of the inflammatory response, as well as the sensory neuronal transmission involved in stress, anxiety, and emesis. The involvement of NK-1 and SP in the vomiting reflex has led to the development of NK-1 antagonists to prevent and treat vomiting in human and veterinary medicine. Maropitant is a potent, selective neurokinin (NK-1 receptor antagonist that blocks the pharmacologic action of SP in the central nervous system. Maropitant is available in both an injectable and tablet formulation and approved for use in dogs and cats for the treatment and prevention of vomiting from a variety of clinical causes and motion sickness. When administered prior to anesthetic premedication, maropitant prevents or significantly decreases the incidence of opioid-induced vomiting and signs of nausea in dogs and cats. Maropitant has also been shown to improve postoperative return to feeding and food intake in dogs. The minimum alveolar concentration of sevoflurage is decreased in both dogs and cats by maropitant, indicating a potential role as an adjunct analgesic, especially for visceral pain. This article will review the background information and literature, including clinical recommendations with respect to the perioperative use of maropitant in canine and feline veterinary patients. Keywords: maropitant, perioperative nausea and vomiting, neurokinin-1 antagonist, Substance P

  17. The Role of Substance P in Secondary Pathophysiology after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Robert Vink

    2017-06-01

    Full Text Available It has recently been shown that substance P (SP plays a major role in the secondary injury process following traumatic brain injury (TBI, particularly with respect to neuroinflammation, increased blood–brain barrier (BBB permeability, and edema formation. Edema formation is associated with the development of increased intracranial pressure (ICP that has been widely associated with increased mortality and morbidity after neurotrauma. However, a pharmacological intervention to specifically reduce ICP is yet to be developed, with current interventions limited to osmotic therapy rather than addressing the cause of increased ICP. Given that previous publications have shown that SP, NK1 receptor antagonists reduce edema after TBI, more recent studies have examined whether these compounds might also reduce ICP and improve brain oxygenation after TBI. We discuss the results of these studies, which demonstrate that NK1 antagonists reduce posttraumatic ICP to near normal levels within 4 h of drug administration, as well as restoring brain oxygenation to near normal levels in the same time frame. The improvements in these parameters occurred in association with an improvement in BBB integrity to serum proteins, suggesting that SP-mediated increases in vascular permeability significantly contribute to the development of increased ICP after acute brain injury. NK1 antagonists may therefore provide a novel, mechanistically targeted approach to the management of increased ICP.

  18. Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral contraceptives.

    Science.gov (United States)

    Calcagnile, Selma; Lanzarotti, Corinna; Rossi, Giorgia; Henriksson, Anders; Kammerer, Klaus Peter; Timmer, Wolfgang

    2013-10-01

    Neurokinin-1 receptor antagonists (NK1 RAs) are commonly coadministered with a 5-HT3 RA such as palonosetron to prevent nausea and vomiting induced by chemotherapy. Netupitant, a new highly selective NK1 RA, is both a substrate for and a moderate inhibitor of CYP3A4. Three studies were designed to evaluate the potential drug-drug interaction of netupitant with palonosetron and of the fixed dose combination of netupitant and palonosetron, NEPA, with an inhibitor (ketoconazole), an inducer (rifampicin) and a substrate (oral contraceptives) of CYP3A4. Study 1 was a three-way crossover in 18 healthy subjects receiving netupitant alone, palonosetron alone, and the combination of both antiemetics. Studies 2 and 3 were two-way crossover trials where healthy subjects received NEPA (the fixed dose combination of netupitant and palonosetron). In study 2, 36 subjects received NEPA alone (day 1) and in combination with ketoconazole or rifampicin. In study 3, 24 healthy women received ethinylestradiol/levonorgestrel alone or in combination with NEPA (day 1). There were no significant pharmacokinetic interactions between netupitant and palonosetron. Ketoconazole increased netupitant area under curve (AUC) by 140 % and C max by 25 %. Rifampicin decreased netupitant AUC by 83 % and C max by 62 %. NEPA did not significantly affect exposure to ethinylestradiol, while systemic exposure to levonorgestrel increased by 40 %, but this was not considered clinically relevant. There were no clinically relevant interactions between netupitant and palonosetron, or between NEPA and oral contraceptives. The coadministration of NEPA with inhibitors or inducers of CYP3A4 may require dose adjustments. Treatments were well tolerated.

  19. Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

    LENUS (Irish Health Repository)

    O'Connor, Terence M

    2012-02-03

    Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1\\/9 bronchoalveolar lavage cells of controls compared with 8\\/10 patients with sarcoidosis (p = 0.012) and 2\\/9 biopsies of controls compared with 9\\/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.

  20. Amphibian (Xenopus sp.) iodothyronine deiodinase ...

    Science.gov (United States)

    The U.S. EPA-MED amphibian thyroid group is currently screening chemicals for inhibition of human iodothyronine deiodinase activity as components of the thyroid system important in human development. Amphibians are a bellwether taxonomic group to gauge toxicity of chemicals in the environment. Amphibian thyroid function is not only important in development but also metamorphosis. Xenopus sp. have been used extensively as model organisms and are well characterized genetically. We propose to screen a list of chemicals (selected from the human DIO screening results) to test for inhibition of Xenopus deiodinases. Large quantities of the enzymes will be produced using an adenovirus system. Our preliminary results show that there may be catalytic differences between human and Xenopus deiodinases. The Twin Ports Early Career Scientists is a new group formed within the Duluth-Superior scientific community. This presentation will provide a basic introduction to my research and our mission at EPA, and help to establish networking and collaboration relationships across disciplines and institutions.

  1. Detection of Salmonella sp., Vibrio sp. and total plate count bacteria on blood cockle (Anadara granosa)

    Science.gov (United States)

    Ekawati, ER; Yusmiati, S. N. H.

    2018-01-01

    Blood cockle (Anadara granosa) has high level of zinc and protein, which is beneficial for therapeutic function for malnourished particularly stunting case in children. Zinc in animal foods is more absorbable than that from vegetable food. Blood cockle (Anadara granosa) is rich in nutrient and an excellent environment for the growth of microorganisms. This research aimed to identify the contamination of Salmonella sp., Vibrio sp. and total plate count bacteria on blood cockle (Anadara granosa). This was observation research with laboratory analysis. Salmonella sp. and Vibrio sp. were detected from blood cockle. Total plate count was determine of the total amount of the bacteria. Results detected from 20 samples of blood cockle showed that all samples were negative of Salmonella sp. and 1 sample positive Vibrio sp. The result of total plate count bacteria was sample.

  2. Helicotylenchus stylocercus n. sp. and Rotylenchus phaliurus n. sp. (Nematoda: Hoplolaimidae) from Costa Rica.

    Science.gov (United States)

    Siddiqi, M R; Pinochet, J

    1979-10-01

    Two new species of plant-parasitic nematodes from Costa Rica are described. Helicotygenchus styloeercus n. sp., from soil around roots of banana at Coto, is distinguished hy the female tail, which bears a large pillarlike ventral projection. Rotylenchus phaliurus n. sp., from soil artmnd roots of Dioscoroea sp. at Sixaola, differs from R. caudaphasmidius in having the conus equal to or more than half the spear length, and large terminal annules on the female tail.

  3. SP (4,R) symmetry in light nuclei

    International Nuclear Information System (INIS)

    Peterson, D.R.

    1979-01-01

    A classification of nuclear states according to the noncompact sympletic Lie algebras sp(2n,R), n = 1, 2, 3, is investigated. Such a classification has recently been shown to be physically meaningful. This classification scheme is the appropriate generalization fo Elliott's SU 3 model of rotational states in deformed light nuclei to include core excitations. A restricted classification according to the Lie algebra, sp(4,R), is motivated. Truncation of the model space to a single sp(4,R) irreducible representation allows the inclusion of states possessing very high excitation energy. An sp(4,R) model study is performed on S = T = 0 positive-parity rotational bands in the deformed light nuclei 16 O and 24 Mg. States are included in the model space that possess up to 10h ω in excitation energy. Results for the B(E2) transition rates compare favorable with experiment, without resort to effective charges

  4. EOP Gold Coral (Gerardia sp.) Growth Measurements

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Gold coral (Gerardia sp.) trees that were inspected years earlier on Pisces submersible dives were revisited and their change in size measured. The fishery for...

  5. Silencing the SpMPK1, SpMPK2, and SpMPK3 Genes in Tomato Reduces Abscisic Acid—Mediated Drought Tolerance

    Directory of Open Access Journals (Sweden)

    Yan Liang

    2013-11-01

    Full Text Available Drought is a major threat to agriculture production worldwide. Mitogen-activated protein kinases (MAPKs play a pivotal role in sensing and converting stress signals into appropriate responses so that plants can adapt and survive. To examine the function of MAPKs in the drought tolerance of tomato plants, we silenced the SpMPK1, SpMPK2, and SpMPK3 genes in wild-type plants using the virus-induced gene silencing (VIGS method. The results indicate that silencing the individual genes or co-silencing SpMPK1, SpMPK2, and SpMPK3 reduced the drought tolerance of tomato plants by varying degrees. Co-silencing SpMPK1 and SpMPK2 impaired abscisic acid (ABA-induced and hydrogen peroxide (H2O2-induced stomatal closure and enhanced ABA-induced H2O2 production. Similar results were observed when silencing SpMPK3 alone, but not when SpMPK1 and SpMPK2 were individually silenced. These data suggest that the functions of SpMPK1 and SpMPK2 are redundant, and they overlap with that of SpMPK3 in drought stress signaling pathways. In addition, we found that SpMPK3 may regulate H2O2 levels by mediating the expression of CAT1. Hence, SpMPK1, SpMPK2, and SpMPK3 may play crucial roles in enhancing tomato plants’ drought tolerance by influencing stomatal activity and H2O2 production via the ABA-H2O2 pathway.

  6. Netupitant PET imaging and ADME studies in humans

    OpenAIRE

    Spinelli, Tulla; Calcagnile, Selma; Giuliano, Claudio; Rossi, Giorgia; Lanzarotti, Corinna; Mair, Stuart; Stevens, Lloyd; Nisbet, Ian

    2013-01-01

    Netupitant is a new, selective NK1 receptor antagonist under development for the prevention of chemotherapy-induced nausea and vomiting. Two studies were conducted to evaluate the brain receptor occupancy (RO) and disposition (ADME) of netupitant in humans. Positron emission tomography (PET) imaging with the NK1 receptor-binding?selective tracer [11C]-GR205171 was used to evaluate the brain penetration of different doses of netupitant (100, 300, and 450?mg) and to determine the NK1-RO duratio...

  7. SP-D impedes transfer of HIV-1 from multi-layered vaginal epithelium with a distinct gene signature

    Directory of Open Access Journals (Sweden)

    Hrishikesh Pandit

    2017-12-01

    Full Text Available Surfactant Protein (SP D is a member of the collectin family of soluble pattern recognition receptors. We have previously shown that a recombinant fragment of SP-D (rhSP-D inhibits gp120-CD4 interaction and HIV-1 entry in target cells. To potentiate its prophylactic use as a vaginal microbicide, we determined ex vivo efficacy using organotypic human vaginal-ectocervical epithelia (VEC-100 that closely resemble the native tissues of origin. VEC-100, stratified human vaginal-ectocervical tissues grown on membrane inserts were treated with rhSP-D followed by a challenge with HIV-1 to assess the transfer of HIV-1 through the VEC-100 tissues to PBMCs in the basal submucosal compartment. Treated VEC tissues were subjected to mRNA Illumina microarray analysis. Levels of transcripts encoding for immune mediators, adhesion and tight junction proteins were also evaluated. Effect of rhSP-D on viability, NFκB activation, cytokine secretion and bacterial colonization of cervical vaginal epithelial cells was determined. rhSP-D significantly inhibited HIV-1 transfer from the multi-layered epithelial tissues to the basal PBMCs as compared to HIV-1 alone. Global gene expression profile of HIV-1 challenged VEC-100 tissues revealed differential regulation of genes and pathways majorly involved in inflammation, cell survival and transcription factors. Levels of Guanylate-binding proteins (GBPs and interferon-inducible proteins were significantly upregulated suggesting an interferon host defense response. rhSP-D showed an inhibition in the levels of GBPs and rescued the cell adhesion molecules such as Claudin 2, 3, 4, 5 and Occludin, known to be down regulated by HIV-1 in primary vaginal cells. Importantly, rhSP-D conditioned VEC tissue supernatants did not enhance susceptibility of target cells to HIV-1. rhSP-D treated vaginal epithelial cells did not show any significant alteration in viability, NFκB activation and levels of immune mediators like IL-1RA, Elafin

  8. CADM1 is a key receptor mediating human mast cell adhesion to human lung fibroblasts and airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Elena P Moiseeva

    Full Text Available Mast cells (MCs play a central role in the development of many diseases including asthma and pulmonary fibrosis. Interactions of human lung mast cells (HLMCs with human airway smooth muscle cells (HASMCs are partially dependent on adhesion mediated by cell adhesion molecule-1 (CADM1, but the adhesion mechanism through which HLMCs interact with human lung fibroblasts (HLFs is not known. CADM1 is expressed as several isoforms (SP4, SP1, SP6 in HLMCs, with SP4 dominant. These isoforms differentially regulate HLMC homotypic adhesion and survival.In this study we have investigated the role of CADM1 isoforms in the adhesion of HLMCs and HMC-1 cells to primary HASMCs and HLFs.CADM1 overexpression or downregulation was achieved using adenoviral delivery of CADM1 short hairpin RNAs or isoform-specific cDNAs respectively.Downregulation of CADM1 attenuated both HLMC and HMC-1 adhesion to both primary HASMCs and HLFs. Overexpression of either SP1 or SP4 isoforms did not alter MC adhesion to HASMCs, whereas overexpression of SP4, but not SP1, significantly increased both HMC-1 cell and HLMC adhesion to HLFs. The expression level of CADM1 SP4 strongly predicted the extent of MC adhesion; linear regression indicated that CADM1 accounts for up to 67% and 32% of adhesion to HLFs for HMC-1 cells and HLMCs, respectively. HLFs supported HLMC proliferation and survival through a CADM1-dependent mechanism. With respect to CADM1 counter-receptor expression, HLFs expressed both CADM1 and nectin-3, whereas HASMCs expressed only nectin-3.Collectively these data indicate that the CADM1 SP4 isoform is a key receptor mediating human MC adhesion to HASMCs and HLFs. The differential expression of CADM1 counter-receptors on HLFs compared to HASMCs may allow the specific targeting of either HLMC-HLF or HLMC-HASMC interactions in the lung parenchyma and airways.

  9. Penggunaan Jamur Antagonis Trichoderma SP. Dan Gliocladium SP. Untuk Mengendalikan Penyakit Layu Fusarium Pada Tanaman Bawang Merah (Allium Ascalonicum L.)

    OpenAIRE

    Arie Ramadhina, Arie Ramadhina; Lisnawita, Lisnawita; Lubis, Lahmuddin

    2013-01-01

    The use of antagonism fungus of Trichoderma sp. and Gliocladium sp. for controlling wilt(Fusarium oxysporum) in red onion plants. The aim of the research was to know the effectiviness ofantagonism fungus of Trichoderma sp. and Gliocladium sp. in controlling wilt in red onion plants.The research used non-factorial RAK (random group design) with eight treatments: control, 10grams of F. oxysporum, 12 grams of Trichoderma sp., 18 grams of Trichoderma sp., 24 grams ofTrichoderma sp., and 12 grams ...

  10. Ligand-directed trafficking of receptor stimulus.

    Science.gov (United States)

    Chilmonczyk, Zdzisław; Bojarski, Andrzej J; Sylte, Ingebrigt

    2014-12-01

    GPCRs are seven transmembrane-spanning receptors that convey specific extracellular stimuli to intracellular signalling. They represent the largest family of cell surface proteins that are therapeutically targeted. According to the traditional two-state model of receptor theory, GPCRs were considered as operating in equilibrium between two functional conformations, an active (R*) and inactive (R) state. Thus, it was assumed that a GPCR can exist either in an "off" or "on" conformation causing either no activation or equal activation of all its signalling pathways. Over the past several years it has become evident that this model is too simple and that GPCR signalling is far more complex. Different studies have presented a multistate model of receptor activation in which ligand-specific receptor conformations are able to differentiate between distinct signalling partners. Recent data show that beside G proteins numerous other proteins, such as β-arrestins and kinases, may interact with GPCRs and activate intracellular signalling pathways. GPCR activation may therefore involve receptor desensitization, coupling to multiple G proteins, Gα or Gβγ signalling, and pathway activation that is independent of G proteins. This latter effect leads to agonist "functional selectivity" (also called ligand-directed receptor trafficking, stimulus trafficking, biased agonism, biased signalling), and agonist intervention with functional selectivity may improve the therapy. Many commercially available drugs with beneficial efficacy also show various undesirable side effects. Further studies of biased signalling might facilitate our understanding of the side effects of current drugs and take us to new avenues to efficiently design pathway-specific medications. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors

    Directory of Open Access Journals (Sweden)

    Chen Yuzhi

    2009-05-01

    Full Text Available Abstract The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NFκB transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NFκB that is nonetheless expressed at reasonable levels. A subset of the κB cis elements are instead bound by members of the Sp1 family in neurons. Also surprising was our discovery that Sp1 itself, typically described as ubiquitous, is severely restricted in expression within forebrain neurons; Sp4 seems to be substituted during neuronal differentiation. These findings and their implications for neuronal differentiation – as well as potential dedifferentiation during degenerative processes – are discussed here.

  12. Role of vascular smooth muscle PPARγ in regulating AT1 receptor signaling and angiotensin II-dependent hypertension.

    Directory of Open Access Journals (Sweden)

    Maria Alicia Carrillo-Sepulveda

    Full Text Available Peroxisome proliferator activated receptor γ (PPARγ has been reported to play a protective role in the vasculature; however, the underlying mechanisms involved are not entirely known. We previously showed that vascular smooth muscle-specific overexpression of a dominant negative human PPARγ mutation in mice (S-P467L leads to enhanced myogenic tone and increased angiotensin-II-dependent vasoconstriction. S-P467L mice also exhibit increased arterial blood pressure. Here we tested the hypotheses that a mesenteric smooth muscle cells isolated from S-P467L mice exhibit enhanced angiotensin-II AT1 receptor signaling, and b the increased arterial pressure of S-P467L mice is angiotensin-II AT1 receptor dependent. Phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase (ERK1/2 was robustly increased in mesenteric artery smooth muscle cell cultures from S-P467L in response to angiotensin-II. The increase in ERK1/2 activation by angiotensin-II was blocked by losartan, a blocker of AT1 receptors. Angiotensin-II-induced ERK1/2 activation was also blocked by Tempol, a scavenger of reactive oxygen species, and correlated with increased Nox4 protein expression. To investigate whether endogenous renin-angiotensin system activity contributes to the elevated arterial pressure in S-P467L, non-transgenic and S-P467L mice were treated with the AT1 receptor blocker, losartan (30 mg/kg per day, for 14-days and arterial pressure was assessed by radiotelemetry. At baseline S-P467L mice showed a significant increase of systolic arterial pressure (142.0 ± 10.2 vs 129.1 ± 3.0 mmHg, p<0.05. Treatment with losartan lowered systolic arterial pressure in S-P467L (132.2 ± 6.9 mmHg to a level similar to untreated non-transgenic mice. Losartan also lowered arterial pressure in non-transgenic (113.0 ± 3.9 mmHg mice, such that there was no difference in the losartan-induced depressor response between groups (-13.53 ± 1.39 in S-P467L vs -16.16 ± 3

  13. Chaenorhinum semispeluncarum sp. nov. and C. yildirimlii sp. nov. (Scrophulariaceae) from east Anatolia, Turkey

    DEFF Research Database (Denmark)

    Yildirim, Hasan; Tan, Kit; Senol, Serdar

    2010-01-01

    Chaenorhinum semispeluncarum H. Yildirim, Kit Tan, S. Senol & A. Pirhan sp. nov. and C. yildirimlii Kit Tan, H. Yildirim, S. Senol & A. Pirhan sp. nov. (Scrophulariaceae, C. sect. Microrrhinum) from east Anatolia are described and illustrated. They are both narrow endemics related to the rare C...

  14. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    physiology and develop- mental biology of silkworms, and use of silk in industrial applications. The low-density lipoprotein receptor (LDLR), one of the best characterized cell-surface receptors, mediates cholesterol ho- meostasis and other functions in mammals. The members of the LDLR superfamily are structurally related ...

  15. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    Permanent link: http://www.ias.ac.in/article/fulltext/reso/018/08/0748-0755. Keywords. Low-density lipoprotein receptor; lipophorin; lipophorin receptor; insects. Author Affiliations. G Ravikumar1 N B Vijayaprakash1. Seri-biotech Research Laboratory Central Silk Board Kodathi, Carmelaram Post Bangalore 560 035, India.

  16. Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

    Directory of Open Access Journals (Sweden)

    Celso Almeida

    2011-12-01

    Full Text Available The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3, and the known compound silvaticol (4. The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1 was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC50 of 12.1 µM. Marilone B (2 showed selective antagonistic activity towards the serotonin receptor 5-HT2B with a Ki value of 7.7 µM.

  17. Acetylcholine receptor antibody

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  18. Metallaphotoredox-catalysed sp3-sp3 cross-coupling of carboxylic acids with alkyl halides

    Science.gov (United States)

    Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

    2016-08-01

    In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3-sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3-sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3-sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3-sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for

  19. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of

  20. Androgen receptor abnormalities

    NARCIS (Netherlands)

    Brinkmann, A. O.; Kuiper, G. G.; Ris-Stalpers, C.; van Rooij, H. C.; Romalo, G.; Trifiro, M.; Mulder, E.; Pinsky, L.; Schweikert, H. U.; Trapman, J.

    1991-01-01

    The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of the genomic organization of the

  1. Five novel Wickerhamomyces- and Metschnikowia-related yeast species, Wickerhamomyces chaumierensis sp. nov., Candida pseudoflosculorum sp. nov., Candida danieliae sp. nov., Candida robnettiae sp. nov. and Candida eppingiae sp. nov., isolated from plants

    NARCIS (Netherlands)

    Groenewald, Marizeth; Robert, Vincent; Smith, Maudy Th

    On the basis of nucleotide divergences in the D1/D2 domain of the 26S rRNA gene and the internal transcribed spacers (ITS) domain of the rRNA gene, five novel yeast species, Wickerhamomyces chaumierensis sp. nov. (CBS 8565(T)  = JCM 17246(T)), Candida pseudoflosculorum sp. nov. (CBS 8584(T)  = JCM

  2. SP-100/Brayton power system concepts

    International Nuclear Information System (INIS)

    Owen, D.F.

    1989-01-01

    Use of closed Brayton cycle (CBC) power conversion technology has been investigated for use with SP-100 reactors for space power systems. The CBC power conversion technology is being developed by Rockwell International under the Dynamic Isotype Power System (DIPS) and Space Station Freedom solar dynamic power system programs to provide highly efficient power conversion with radioisotype and solar collector heat sources. Characteristics including mass, radiator area, thermal power, and operating temperatures for systems utilizing SP-100 reactor and CBC power conversion technology were determined for systems in the 10-to 100-kWe power range. Possible SP-100 reactor/CBC power system configurations are presented. Advantages of CBC power conversion technology with regard to reactor thermal power, operating temperature, and development status are discussed

  3. Modulation of cardiac activity by tachykinins in the rat substantia nigra

    Science.gov (United States)

    Lessard, Andrée; Couture, Réjean

    2001-01-01

    The effects of tachykinin NK1, NK2 and NK3 receptor agonists and antagonists were measured on blood pressure (MAP) and heart rate (HR) after bilateral microinjection into the substantia nigra (SN) of awake, unrestrained rats. Increasing doses (25 pmol – 1 nmol) of selective agonists at NK1 ([Sar9,Met(O2)11]SP), NK2 ([β-Ala8]NKA(4 – 10)) and NK3 (senktide) receptors into the SN produced tachycardia which was selectively and reversibly blocked by the prior injection of tachykinin antagonists at NK1 (RP67580, 250 pmol), NK2 (SR48968, 250 pmol) and NK3 (R-820, 500 pmol) receptor. A rapid fall in MAP followed by a pressor response was seen with 1 nmol of [Sar9,Met(O2)11]SP. Behavioural activity was elicited by 1 nmol of [Sar9,Met(O211]SP (sniffing>face washing=grooming) and senktide (sniffing>wet dog shake>rearing=locomotion). Tachykinin antagonists had no direct cardiovascular or behavioural effects. The tachycardia produced by 100 pmol of [β-Ala8]NKA(4 – 10) or senktide was abolished by an i.v. treatment with atenolol (β1-adrenoceptor antagonist, 5 mg kg−1) while that evoked by [Sar9,Met(O2)11]SP was reduced. A combination of atenolol (5 mg kg−1) and atropine (muscarinic antagonist, 1 mg kg−1) blocked the response evoked by [Sar9,Met(O2)11]SP. These data suggest that the SN is a potential site of modulation of cardiac activity by tachykinins. In addition to the withdrawal of the cardiovagal activity by NK1 receptor, the three tachykinin receptors appear to increase the sympatho/adrenal drive to the heart. This occurs independently of changes in MAP and behaviour. Hence, this study highlights a new central regulatory mechanism of cardiac autonomic activity. PMID:11739252

  4. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Mosbacher, Johannes; Elg, Susanne

    2002-01-01

    The actions of the anticonvulsant gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin] have been somewhat enigmatic until recently, when it was claimed to be a gamma-aminobutyric acid-B (GABA(B)) receptor agonist acting exclusively at a heterodimeric complex containing the GABA(B(1a)) sp...

  5. Mycobacterium arosiense sp. nov., a slowly growing, scotochromogenic species causing osteomyelitis in an immunocompromised child

    DEFF Research Database (Denmark)

    Bang, D.; Herlin, T.; Stegger, M.

    2008-01-01

    A yellow-pigmented, scotochromogenic, slowly growing mycobacterial strain, designated T1921(T), was isolated from the disseminated osteomyelitic lesions of a 7-year-old child with an underlying partial gamma interferon receptor alpha-1 deficiency. Hybridization by the line probe assay indicated t...... mycobacteria. Strain T1921(T) is considered to represent a novel species of the genus Mycobacterium, for which the name Mycobacterium arosiense sp. nov. is proposed. The type strain is T1921(T) (=DSM 45069(T) =ATCC BAA-1401(T)) Udgivelsesdato: 2008/10...

  6. Characterization of a neurokinin B receptor site in rat brain using a highly selective radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Laufer, R.; Gilon, C.; Chorev, M.; Selinger, Z.

    1986-08-05

    We have recently characterized a tachykinin receptor subtype (SP-N) whose preferred ligand is the mammalian neuropeptide, neurokinin B. To investigate this novel tachykinin receptor, we have now prepared a radiolabeled peptide, N alpha-(( /sup 125/I)desamino-3-iodotyrosyl)-(Asp5,6, N-methyl-Phe8)substance P (5-11) heptapeptide (/sup 125/I-BH-NH-Senktide), which selectively interacts with the SP-N receptor subtype. The binding of /sup 125/I-BH-NH-Senktide to rat cerebral cortex membranes was studied under conditions that minimized nonspecific binding. Unlike other tachykinin receptor probes, this radioligand is not degraded during the binding experiment. Binding of /sup 125/I-BH-NH-Senktide is reversible, saturable, and of high affinity (KD = 0.9 nM). The radioligand labels a single class of binding site (122 fmol binding sites/mg of protein), as indicated by a linear Scatchard plot and a Hill coefficient close to unity (nH = 1.05). The pharmacological specificity of this binding site corresponds to that of the neuronal SP-N receptor in guinea pig ileum myenteric plexus, which was determined by a functional bioassay. Among various rat brain regions, the highest binding was observed in the cerebral cortex, olfactory bulb, hypothalamus, and hippocampus. These results suggest the existence and specific distribution of a neurokinin B receptor site of the SP-N type in rat brain. /sup 125/I-BH-NH-Senktide is the first selective and potent probe for this receptor and is thus an important tool for further studies of its distribution, regulation, and functional role.

  7. Ovos de Toxocara sp. e larvas de Ancylostoma sp. em praça pública de Lavras, MG Toxocara sp. eggs and Ancylostoma sp. larva in public parks, Brazil

    Directory of Open Access Journals (Sweden)

    Antônio Marcos Guimarães

    2005-04-01

    Full Text Available Larva migrans visceral e cutânea são zoonoses parasitárias causadas pela infecção da larva de Toxocara sp. e Ancylostoma sp., respectivamente. O objetivo do estudo foi verificar a contaminação por ovos de Toxocara sp. e ovos e larvas de Ancylostoma sp. em amostras de solos coletadas de praças públicas e de áreas de recreação infantil de Lavras, Estado de Minas Gerais, por meio da técnica de centrífugo-flutuação e do método de Baermann. A ocorrência de ovos de Toxocara sp. e, ovos e larvas de Ancylostoma sp. foi observada em 69,6% (16/23 das amostras de solo coletadas de praças públicas. A contaminação somente por ovos de Ancylostoma sp. em amostras de solo coletadas em escolas/creches foi de 22,2% (4/18. A percentagem de amostras de areia coletadas de escolas/creches contaminadas somente com larvas de Ancylostoma sp. foi de 11,1% (2/18. Praças públicas são as áreas com maior risco potencial de infecção por Toxocara sp. e Ancylostoma sp. Exame coproparasitológico realizado em 174 amostras de fezes de cães observou 58% e 23%, respectivamente, com ovos de Ancylostoma sp. e Toxocara sp.Visceral and cutaneous larva migrans are parasitic zoonoses caused by the infection of larval nematodes Toxocara sp. and Ancylostoma sp. respectively. The objective of this study was to investigate the contamination by Toxocara sp. eggs and Ancylostoma sp. eggs and larva of soil samples collected from public parks and children's playground areas in state of Minas Gerais, Brazil, using both Baermann's method and centrifugal flotation technique. Toxocara sp. and Ancylostoma sp. eggs were observed in soil samples collected from public squares in 17.4% (4/23 and 69.6 (16/23 respectively. In schools and child day care settings the contamination by Ancylostoma sp. larva in sand samples was 11.1% (2/18. Public parks are settings of more potential risk of Toxocara sp. eggs and Ancylostoma sp. infection. Stool parasitology testing of 174 stool

  8. Receptor binding sites for substance P in surgical specimens obtained from patients with ulcerative colitis and Crohn disease

    Energy Technology Data Exchange (ETDEWEB)

    Mantyh, C.R.; Gates, T.S.; Zimmerman, R.P.; Welton, M.L.; Passaro, E.P. Jr.; Vigna, S.R.; Maggio, J.E.; Kruger, L.; Mantyh, P.W.

    1988-05-01

    Several lines of evidence indicate that tachykinin neuropeptides (substance P (SP), substance K (SK), and neuromedin K (NK)) play a role in regulating the inflammatory and immune responses. To test this hypothesis in a human inflammatory disease, quantitative receptor autoradiography was used to examine possible abnormalities in tachykinin binding sites in surgical specimens from patients with inflammatory bowel disease. In all cases, specimens were processed for quantitative receptor autoradiography by using /sup 125/I-labeled Bolton-Hunter conjugates of NK, SK, and SP. In colon tissue obtained from ulcerative colitis and Crohn disease patients, very high concentrations of SP receptor binding sites are expressed by arterioles and venules located in the submucosa, muscalairs mucosa, external circular muscle, external longitudinal muscle, and serosa, in contrast to control patients. These results demonstrate that receptor binding sites for SP, but not SK or NK, are ectopically expressed in high concentrations by cells involved in mediating inflammatory and immune responses. These data suggest that SP may be involved in the pathophysiology of inflammatory bowel disease and might provide some insight into the interaction between the nervous system and the regulation of inflammation and the immune response in human inflammatory disease.

  9. Nitrogen fixation in Asaia sp. (family Acetobacteraceae).

    Science.gov (United States)

    Samaddar, Neeloy; Paul, Arundhati; Chakravorty, Somnath; Chakraborty, Writachit; Mukherjee, Joydeep; Chowdhuri, Debarati; Gachhui, Ratan

    2011-08-01

    The genus Asaia (family Acetobacteraceae) was first introduced with a single species-Asaia bogorensis and later six more species were described namely A. siamensis, A. krungthepensis, A. lannaensis, A. platycodi, A. prunellae, and A. astilbes. Acetobacteraceae family has been divided into ten genera but, only three of them include nitrogen fixing species: Gluconacetobacter, Acetobacter, and Swaminathania. This article originated from our study primarily aimed to isolate new endosymbiotic nitrogen fixer among Acetobacteraceae during which we have isolated, for the first time in India, four different strains of Asaia sp. from three different sources: Michalia champaca flower, Anopheles mosquito, and ant Tetraponera rufonigra. All the endosymbiotic strains isolated possess the ability to fix nitrogen. Evidence for both nitrogenase activity and the presence of nifH gene in isolated Asaia sp. is presented. Asaia bogorensis (MTCC 4041(T)) and A. siamensis (MTCC 4042(T)), two of the validated type strains available from the repository, were tested positive for the presence of functional nitrogenase. The nifH gene sequences from these type strains were also confirmed and compared with other nitrogen fixing members of the family Acetobacteraceae. Our result corroborate with the previous reports that Asaia sp. are indeed widely distributed in nature but this is the first time demonstration of their functional nitrogenase activity. This study shows Asaia sp. as fourth genera of nitrogen fixing bacteria in the family Acetobacteraceae.

  10. Molecular characterization of Trichoderma sp. isolated from ...

    African Journals Online (AJOL)

    The genetic relatedness among 15 isolates of Trichoderma sp. was analyzed with six micro-satellite primers. ISSR profiles showed 83.7% genetic diversity among the isolates with the formation of four clusters. Analysis of dendrogram revealed that similarity coefficient ranged from 0.27 to 0.95. ITS-PCR of rDNA region with ...

  11. Som man spørger

    DEFF Research Database (Denmark)

    Bjerg, Lars

    Indhold: Input og outputinterview ; Tre interviewtyper ; Tre grundprincipper ; De syv dødssynder ; Åbne, simple og neutrale spørgsmål ; Skuffespørgsmål ; Fokus ; Aktiv lytning ; Mål ; Strategi ; Abstrakt og konkret ; Det kritiske interview ; Kilder med et budskab ; Oldfruens fif ; Resumé i punktform...

  12. POTENSI MELANOTUS SP. DALAM MENDEGRADASI LIGNIN

    Directory of Open Access Journals (Sweden)

    NUNIK SULISTINAH

    2008-06-01

    Full Text Available Ten isolates of fungus were isolated from oil palm stem at oil palm plantation in Medan All of them were tested its abilities to degrade lignin. The results showed that one of them was able to grow on ligninase media and the fungi has the ability to degrade ligin. The fungi is identified as Melanotus sp.

  13. Biosorption of uranium by Azolla, SP, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, Ludmila C.; Alves, Eliakim G.; Marumo, Julio T., E-mail: lcvieira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Ferreira, Rafael V. de P., E-mail: rafael@itatijuca.com [Itatijuca Biotech, Sao Paulo, SP (Brazil); Canevesi, Rafael L.S.; Silva, Edson A., E-mail: edson.silva2@unioeste.br [Universidade Estadual do Oeste Parana (UNIOESTE), Toledo, PR (Brazil)

    2015-07-01

    Radioactive liquid waste needs special attention and requires suitable treatment before deposition. Among the potential technologies under development for the treatment of liquid radioactive wastes the biosorption has been highlighted by being an efficient and low cost technique. Biosorption process involves the exchange of ions contained in the biomass matrix by others present in solution. There are many biomasses that could be applied in treatment of radioactive wastes, for example, agricultural residues and macrophyte. The aim of this study is evaluate the ability of the Azolla sp., a floating aquatic plant, to absorb uranium in solution. Azolla sp. is a macrophyte that has been used to treat effluents containing heavy metals. The biosorption capacity of uranium by Azolla sp. was experimentally determined and modeled by isotherms. Experiments were performed to determine metal uptake, and then the solutions were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES). The isotherms applied to model the data was Langmuir, Freundlich, Sips Toth, Redlich Peternson, Two-Site-Langmuir, Radke Prausnitz to develop a technique for the treatment of radioactive liquid waste generated at the Nuclear and Energy Research Institute (IPEN-CNEN/SP), Brazil. (author)

  14. Biosorption of uranium by Azolla, SP, Brazil

    International Nuclear Information System (INIS)

    Vieira, Ludmila C.; Alves, Eliakim G.; Marumo, Julio T.; Ferreira, Rafael V. de P.; Canevesi, Rafael L.S.; Silva, Edson A.

    2015-01-01

    Radioactive liquid waste needs special attention and requires suitable treatment before deposition. Among the potential technologies under development for the treatment of liquid radioactive wastes the biosorption has been highlighted by being an efficient and low cost technique. Biosorption process involves the exchange of ions contained in the biomass matrix by others present in solution. There are many biomasses that could be applied in treatment of radioactive wastes, for example, agricultural residues and macrophyte. The aim of this study is evaluate the ability of the Azolla sp., a floating aquatic plant, to absorb uranium in solution. Azolla sp. is a macrophyte that has been used to treat effluents containing heavy metals. The biosorption capacity of uranium by Azolla sp. was experimentally determined and modeled by isotherms. Experiments were performed to determine metal uptake, and then the solutions were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES). The isotherms applied to model the data was Langmuir, Freundlich, Sips Toth, Redlich Peternson, Two-Site-Langmuir, Radke Prausnitz to develop a technique for the treatment of radioactive liquid waste generated at the Nuclear and Energy Research Institute (IPEN-CNEN/SP), Brazil. (author)

  15. Carbon sp chains in graphene nanoholes

    DEFF Research Database (Denmark)

    Castelli, Ivano Eligio; Ferri, Nicola; Onida, Giovanni

    2012-01-01

    Nowadays sp carbon chains terminated by graphene or graphitic-like carbon are synthesized routinely in several nanotech labs. We propose an ab initio study of such carbon-only materials, by computing their structure and stability, as well as their electronic, vibrational and magnetic properties. We...

  16. Lipid contents of the sponge Haliclona sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Parameswaran, P.S.; Das, B.; Kamat, S.Y.

    Several fatty acids, sterols, batyl alcohol and its analogs and an N-acylated sphingosine (ceramide) have been isolated from the lipid fraction of the extract of the sponge Haliclona sp. The major sterol is found to be cholesterol (54%), followed...

  17. Test af spørgeskema

    DEFF Research Database (Denmark)

    Hermansen, Jonathan

    2017-01-01

    Denne bog gennemgår alle surveyarbejdets faser og giver en praktisk indføring i •design af undersøgelsen og udvælgelse af stikprøver, •formulering af spørgeskemaer samt indsamling og kodning af data, •metoder til at analysere resultaterne....

  18. Botrallin from the endophytic fungus Hyalodendriella sp ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... Bioassay-guided fractionation of the crude methanol extract of the mycelia from the endophytic fungus. Hyalodendriella sp. Ponipodef12, associated with the hybrid 'Neva' of Populus deltoides Marsh × P. nigra L., led to the isolation of one compound coded as P12-1 which was identified as botrallin (1,7-.

  19. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  20. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  1. C (sp2)–C (sp2) cross coupling reaction catalyzed by a palladacycle ...

    Indian Academy of Sciences (India)

    (sp2) cross coupling reaction catalyzed by a palladacycle phosphine complex: A simple and sustainable protocol in aqueous media. Seyyed Javad Sabounchei Marjan Hosseinzadeh. Articles Volume 127 Issue 11 November 2015 pp 1919- ...

  2. Nanocrystalline sp{sup 2} and sp{sup 3} carbons: CVD synthesis and applications

    Energy Technology Data Exchange (ETDEWEB)

    Terranova, M. L. [Università degli Studi di Roma “Tor Vergata,” via Della Ricerca Scientifica, Dipartimento di Scienze e Tecnologie Chimiche—MinimaLab (Italy); Rossi, M. [Università degli Studi di Roma “Sapienza,” via A. Scarpa, Dipartimento di Scienze di Base e Applicate per l’Ingegneria and Centro di Ricerca per le Nanotecnologie Applicate all’Ingegneria (CNIS) (Italy); Tamburri, E., E-mail: emanuela.tamburri@uniroma2.it [Università degli Studi di Roma “Tor Vergata,” via Della Ricerca Scientifica, Dipartimento di Scienze e Tecnologie Chimiche—MinimaLab (Italy)

    2016-11-15

    The design and production of innovative materials based on nanocrystalline sp{sup 2}- and sp{sup 3}-coordinated carbons is presently a focus of the scientific community. We present a review of the nanostructures obtained in our labs using a series of synthetic routes, which make use of chemical vapor deposition (CVD) techniques for the selective production of non-planar graphitic nanostructures, nanocrystalline diamonds, and hybrid two-phase nanostructures.

  3. Analisis Fosfor pada Cacing Tanah (Megascolex sp. dan Fridericia sp.) Secara Spektrofotometri Sinar Tampak

    OpenAIRE

    Safira, Cut Shafa

    2015-01-01

    Earthworm is natural resource which can be used for medication due to its highly amount of minerals. One of these minerals is phosphorus. The aim of this research are to identify, determine and know the difference content of phosphorus in Megascolex sp. and Fridericia sp. Qualitative analysis shows positive results with addition of ammonium molybdate 4% and BaCl2 5%. Quantitative analysis was done using visible spectrophotometer with ascorbic acid method, measuring blu-colored molybdenum ...

  4. Differences in nutrient uptake capacity of the benthic filamentous algae Cladophora sp., Klebsormidium sp. and Pseudanabaena sp. under varying N/P conditions.

    Science.gov (United States)

    Liu, Junzhuo; Vyverman, Wim

    2015-03-01

    The N/P ratio of wastewater can vary greatly and directly affect algal growth and nutrient removal process. Three benthic filamentous algae species Cladophora sp., Klebsormidium sp. and Pseudanabaena sp. were isolated from a periphyton bioreactor and cultured under laboratory conditions on varying N/P ratios to determine their ability to remove nitrate and phosphorus. The N/P ratio significantly influenced the algal growth and phosphorus uptake process. Appropriate N/P ratios for nitrogen and phosphorus removal were 5-15, 7-10 and 7-20 for Cladophora sp., Klebsormidium sp. and Pseudanabaena sp., respectively. Within these respective ranges, Cladophora sp. had the highest biomass production, while Pseudanabaena sp. had the highest nitrogen and phosphorus contents. This study indicated that Cladophora sp. had a high capacity of removing phosphorus from wastewaters of low N/P ratio, and Pseudanabaena sp. was highly suitable for removing nitrogen from wastewaters with high N/P ratio. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Anomalous self potential (sp) log signatures observed in a water ...

    African Journals Online (AJOL)

    Geophysical logging was done after drilling had been completed in a water well at Okwudor, South Eastern Nigeria. Three electric logs were run viz: Self Potential (SP), Resistivity N16″ and N64″ logs. An anomaly was observed in the SP log. The SP results from this well show some deviation from the standard norm.

  6. Biosorption of chromium by mangrove-derived Aplanochytrium sp ...

    African Journals Online (AJOL)

    The microbial dried biomass of Thraustochytrids is used as bioadsorbent for the removal of the chromium in aqueous solution. In this investigation, three species of Thraustochydrids namely Aplanochytrium sp., Thraustochytrium sp. and Schizochytrium sp. were tested for the efficiency of chromium accumulation by culturing ...

  7. Babesia peircei sp. nov. from the jackass penguin

    African Journals Online (AJOL)

    1992-01-09

    Jan 9, 1992 ... An avian piroplasm, Babesia peircei sp. nov. is described from the jackass penguin Spheniscus demersus. Morphological differences between Babesia peircei sp. nov. and the other valid Babesia spp. are discussed together with the possible vectors. 'n Voal-piroplasma, Babesia peircei sp. nov. afkomstig ...

  8. Occurrence of Aspergillus sp., Fusarium sp., and aflatoxins in corn hybrids with different systems of storage

    Directory of Open Access Journals (Sweden)

    Adriana Sbardelotto Di Domenico

    2016-01-01

    Full Text Available The aim of this study was to assess alternatives for viable corn storage for small rural properties in two annual storage experiments. A 4×5 factorial design was used with four types of storage (conventional bags, hermetic bags, metal silos and corncobs and five periods of storage (0, 3, 6, 9 and 12 months. We used corn hybrids 2B688RR and 30K73Hx cultivated in winter 2012 and summer 2012/2013 in the city of Dois Vizinhos, Paraná, Brazil. The moisture contents, counts of Aspergillus sp. and Fusarium sp., and the occurrence of aflatoxins (B1, B2, G1 and G2 were assessed. The kernels stored in hermetic bags had lower moisture contents. Aspergillus sp. and Fusarium sp. were observed in 20.37 and 86.11% of winter storage samples, respectively, and in 83.3 and 91.6% of summer storage samples, respectively. The storage system and time of storage had no influence on the occurrence of Aspergillus sp. and aflatoxins in the winter crop samples. The corncobs from the summer crop samples had the lowest counts of Aspergillus sp. and did not have aflatoxins. We detected aflatoxins at concentrations of 2.8-14.5 and 3-197.5 µg kg-1 in the winter and summer crop samples, respectively.

  9. Two new species of suctorians, Acineta satyanandani sp. nov. and Paracineta karunakarani sp. nov. epizoic on ostracods

    Digital Repository Service at National Institute of Oceanography (India)

    Santhakumari, V.

    Two, species of protozoic suctorians, Acineta satyanandani sp. nov. and Paracineta karunakarani sp. nov., are described. These were found attached on the body of the marine ostracod, Cypridina dentata (Muller), collected from the shelf and slope...

  10. The family Carabodidae (Acari, Oribatida) VIII. The genus Machadocepheus (first part) Machadocepheusleoneae sp. n. and Machadocepheusrachii sp. n. from Gabon.

    Science.gov (United States)

    Fernandez, Nestor; Theron, Pieter; Rollard, Christine; Leiva, Sergio

    2014-01-01

    The genus Machadocepheus, being one of the more complex genera of the Carabodidae family, is briefly outlined to demonstrate this complexity. Descriptions of two new species from Gabon, Machadocepheusleoneae sp. n. and Machadocepheusrachii sp. n. are given.

  11. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Udai P.; Singh, Narendra P. [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Singh, Balwan [National Primate Research Center, Emory University, Atlanta GA 30329 (United States); Price, Robert L. [Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Mitzi [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)

    2012-01-15

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and

  12. Bilateral muscle fiber and nerve influences by TNF-alpha in response to unilateral muscle overuse - studies on TNF receptor expressions.

    Science.gov (United States)

    Renström, Lina; Stål, Per; Song, Yafeng; Forsgren, Sture

    2017-11-28

    TNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition. A rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated. In situ hybridization and immunofluorescence were utilized. Immunostainings for desmin, NK-1R and CD31 were made in parallel. Immunoreactions (IR) for TNF receptors were clearly observed in white blood cells, fibroblasts and vessel walls, and most interestingly also in muscle fibers and nerve fascicles in the myositis muscles. There were very restricted reactions for these in the muscles of controls. The upregulation of TNF receptors was for all types of structures seen for both the experimental side and the contralateral nonexperimental side. TNF receptor expressing muscle fibers were present in myositis muscles. They can be related to attempts for reparation/regeneration, as evidenced from results of parallel stainings. Necrotic muscle fibers displayed TNFR1 mRNA and TNFR2 immunoreaction (IR) in the invading white blood cells. In myositis muscles, TNFR1 IR was observed in both axons and Schwann cells while TNFR2 IR was observed in Schwann cells. Such observations were very rarely made for control animals. The findings suggest that there is a pronounced involvement of TNF-alpha in the developing myositis process. Attempts for reparation of the muscle tissue seem to occur via both TNFR1 and TNFR2. As the myositis process also occurs in the nonexperimental side and as TNF receptors are confined to nerve fascicles bilaterally it can be asked whether TNF-alpha is involved in the spreading of the myositis process to the contralateral side via the

  13. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  14. Therapeutic androgen receptor ligands

    Science.gov (United States)

    Allan, George F.; Sui, Zhihua

    2003-01-01

    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs). PMID:16604181

  15. First report of Giardia sp. and Cryptosporidium sp. in fecal samples in blue macaw (Anodorhynchus hyacinthinus) in southern Brazil

    OpenAIRE

    Matheus Hillard Farret; Vinicius da Rosa Fanfa; Luisa Ragagnin; Aleksandro Schafer da Silva; Silvia Gonzalez Monteiro

    2010-01-01

    This study reports the gastrointestinal parasitism by Giardia sp. and Cryptosporidium sp. in blue macaw (Anodorhynchus hyacinthinus) in the southern region of Brazil. Fecal samples of two species kept in captivity in the state of Rio Grande do Sul were analyzed by the direct smear method, centrifugal flotation technique with zinc sulfate and Kinyoun staining technique for research of parasites. Mixed infection by eggs of Capillaria, cysts of Giardia sp. and oocysts of Cryptosporidium sp. was ...

  16. Pharmacological characterization of tachykinin tetrabranched derivatives.

    Science.gov (United States)

    Ruzza, Chiara; Rizzi, Anna; Malfacini, Davide; Cerlesi, Maria Camilla; Ferrari, Federica; Marzola, Erika; Ambrosio, Caterina; Gro, Cristina; Severo, Salvadori; Costa, Tommaso; Calo, Girolamo; Guerrini, Remo

    2014-09-01

    Peptide welding technology (PWT) is a novel chemical strategy that allows the synthesis of multibranched peptides with high yield, purity and reproducibility. Using this technique, we have synthesized and pharmacologically characterized the tetrabranched derivatives of the tachykinins, substance P (SP), neurokinin A (NKA) and B (NKB). The following in vitro assays were used: calcium mobilization in cells expressing human recombinant NK receptors, BRET studies of G-protein - NK1 receptor interaction, guinea pig ileum and rat urinary bladder bioassays. Nociceptive behavioural response experiments were performed in mice following intrathecal injection of PWT2-SP. In calcium mobilization studies, PWT tachykinin derivatives behaved as full agonists at NK receptors with a selectivity profile similar to that of the natural peptides. NK receptor antagonists display similar potency values when tested against PWT2 derivatives and natural peptides. In BRET and bioassay experiments PWT2-SP mimicked the effects of SP with similar potency, maximal effects and sensitivity to aprepitant. After intrathecal administration in mice, PWT2-SP mimicked the nociceptive effects of SP, but with higher potency and a longer-lasting action. Aprepitant counteracted the effects of PWT2-SP in vivo. The present study has shown that the PWT technology can be successfully applied to the peptide sequence of tachykinins to generate tetrabranched derivatives characterized with a pharmacological profile similar to the native peptides. In vivo, PWT2-SP displayed higher potency and a marked prolongation of action, compared with SP. © 2014 The British Pharmacological Society.

  17. PET evaluation of the uptake of N-[{sup 11}C]methyl CP-643,051, an NK{sub 1} receptor antagonist, in the living porcine brain

    Energy Technology Data Exchange (ETDEWEB)

    Bender, D. E-mail: dirk@pet.auh.dk; Olsen, A.K.; Marthi, M.K.; Smith, D.F.; Cumming, P

    2004-08-01

    Antagonists of neurokinin receptors such as CP-643,051 are presently under investigation as potential antidepressants, but little is known about the brain uptake and distribution of these agents. We developed a method for the efficient N-[{sup 11}C]methylation of CP-122,721, yielding the NK{sub 1} antagonist N-[{sup 11}C]methyl CP-643,051. The brain uptake and distribution of N-[{sup 11}C]methyl CP-643,051 were studied by positron emission tomography (PET) in the anaesthetized pig, first in a baseline condition, and again after displacement of specific binding with the NK{sub 1} receptor antagonist L-732,138 (0.6 mg/kg, i.v.). In order to validate this displacement procedure, we tested the effects of L-732,138 on cerebral blood flow (CBF) in one pig. We found that N-[{sup 11}C]methyl CP-643,051 had a distribution volume close to 3 ml g{sup -1}, and a binding potential (pB) of 0.3 in the pig striatum; this binding was displaceable by the L-732,138 pre-treatment, which evoked a small (10-20%) global increase in CBF. We conclude that of N-[{sup 11}C]methyl CP-643,051 may serve as a lead structure for the development of PET NK-1 ligands of higher specific binding in vivo.

  18. PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1

    International Nuclear Information System (INIS)

    Rankin, Sherri L.; Guy, Clifford S.; Mearow, Karen M.

    2009-01-01

    p75NTR is expressed throughout the nervous system and its dysregulation is associated with pathological conditions. We have recently demonstrated a signalling cascade initiated by laminin (LN), which upregulates PTEN and downregulates p75NTR. Here we investigate the mechanism by which PTEN modulates p75NTR. Studies using PTEN mutants show that its protein phosphatase activity directly modulates p75NTR protein expression. Nuclear relocalization of PTEN subsequent to LN stimulation suggests transcriptional control of p75NTR expression, which was confirmed following EMSA and ChIP analysis of Sp1 transcription factor binding activity. LN and PTEN independently decrease the DNA-binding ability of PTEN to the p75NTR promoter. Sp1 regulation of p75NTR occurs via dephosphorylation of Sp1, thus reducing p75NTR transcription and protein expression. This mechanism represents a novel regulatory pathway which controls the expression level of a receptor with broad implications not only for the development of the nervous system but also for progression of pathological conditions.

  19. Inhibition of marine Vibrio sp. by pyoverdine from Pseudomonas aeruginosa PA1.

    Science.gov (United States)

    Zhang, Weiwei; Liang, Weikang; Li, Chenghua

    2016-01-25

    Siderophores are low-molecular-weight chemicals that are secreted by many microorganisms to chelate iron from the external environment in order to facilitate their growth and diverse metabolisms. In this study, a fluorescent siderophore, pyoverdine, secreted by Pseudomonas aeruginosa PA1 was purified by affinity chromatography using Cu-sepharose. Pyoverdine was determined to have a molecular mass of 1333.54 Da, as determined by MALDI-TOF/TOF, and belong to type I pyoverdine, as determined by PCR analysis of its corresponding outer membrane ferri-pyoverdine receptor. Pyoverdine showed different degrees of inhibitory effects on the growth of marine Vibrio sp. strains. It was also shown that the biofilm developed by Vibrio parahaemolyticus WzW1 and Wz2121 and Vibrio cyclitrophicus HS12 was significantly reduced, alone with the repressed growth in the presence of pyoverdine. Siderophore production was determined in the strains of Vibrio sp. in response to the pyoverdine-induced iron-limited conditions. The siderophore production of most Vibrio sp. was up-regulated, with the exception of the bacteria that produced little siderophore. Furthermore, Apostichopus japonicus cultured in pyoverdine pretreated seawater showed a relative percent of survival of 89% when they were challenged by Vibrio splendidus. Our results demonstrated that pyoverdine may be a promising agent that could be potentially applied to treat vibriosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Agromyces italicus sp. nov., Agromyces humatus sp. nov. and Agromyces lapidis sp. nov., isolated from Roman catacombs.

    Science.gov (United States)

    Jurado, Valme; Groth, Ingrid; Gonzalez, Juan M; Laiz, Leonila; Schuetze, Barbara; Saiz-Jimenez, Cesareo

    2005-03-01

    A polyphasic study was carried out to clarify the taxonomic positions of three Gram-positive isolates from the Catacombs of Domitilla, Rome (Italy). 16S rRNA gene sequence comparisons placed these strains within the genus Agromyces. The morphological and chemotaxonomic characteristics of these isolates were consistent with the description of the genus Agromyces. The three isolates could be readily distinguished from one another and from representatives of all Agromyces species with validly published names by a broad range of phenotypic characteristics and DNA-DNA relatedness studies. Therefore, these isolates are proposed to represent three novel species of the genus Agromyces, Agromyces italicus sp. nov. (type strain CD1(T)=HKI 0325(T)=DSM 16388(T)=NCIMB 14011(T)), Agromyces humatus sp. nov. (type strain CD5(T)=HKI 0327(T)=DSM 16389(T)=NCIMB 14012(T)) and Agromyces lapidis sp. nov. (type strain CD55(T)=HKI 0324(T)=DSM 16390(T)=NCIMB 14013(T)).

  1. Cryptotrichosporon argae sp. nov., Cryptotrichosporon brontae sp. nov. and Cryptotrichosporon steropae sp. nov., isolated from forest soils.

    Science.gov (United States)

    Pontes, Ana; Röhl, Oliver; Maldonado, Cristina; Yurkov, Andrey M; Sampaio, José Paulo

    2017-09-01

    Yeast strains belonging to the basidiomycetous genus Cryptotrichosporon were isolated from forest soils in Serra da Arrábida Natural Park in Portugal. Similar to the already-known representatives of this genus, the new isolates formed pigmented colonies of a distinctive pale orange colour. Phylogenetic analyses employing concatenated sequences of the D1/D2 domains of the 26S (large subunit) rRNA gene and the internal transcribed spacer (ITS) region supported the recognition of three novel species: Cryptotrichosporon argae sp. nov. (type strain CM 19T=CBS 14376T=PYCC 7010T=DSM 104550T; MycoBank accession number MB 817168), Cryptotrichosporon brontae sp. nov. (type strain CM 1562T=CBS 14303T=PYCC 7011T=DSM 104551T; MycoBank accession number MB 817077) and Cryptotrichosporon steropae sp. nov. (type strain OR 395T=CBS 14302T=PYCC 7012T=DSM 104552T; MycoBank accession number MB 817078).

  2. Fitoremediasi limbah budidaya sidat menggunakan filamentous algae (Spirogyra sp.

    Directory of Open Access Journals (Sweden)

    Tri Apriadi

    2014-09-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui potensi dari filamentous algae (Spirogyra sp. sebagai agen bioremediasi dalam mereduksi kandungan bahan organik limbah budidaya sidat. Penelitian menggunakan rancangan acak lengkap dengan perlakuan perbedaan dosis limbah (25 %, 50 %, 75 %, 100%. Wadah penelitian berupa akuarium resirkulasi menggunakan sistem carrousel. Dilakukan pengukuran secara rutin terhadap beberapa parameter kualitas air serta perubahan bobot Spirogyra sp. selama dua minggu retensi. Diperoleh hasil bahwa penurunan konsentrasi bahan organik menggunakan Spirogyra sp. berlangsung efektif hingga hari keenam. Spirogyra sp. mampu mentolelir limbah budidaya sidat pada dosis limbah 25% dan 50%. Spirogyra sp. pada perlakuan dosis limbah 50% memiliki kemampuan yang lebih baik dalam menurunkan bahan organik limbah budidaya sidat.

  3. A superhard sp3 microporous carbon with direct bandgap

    Science.gov (United States)

    Pan, Yilong; Xie, Chenlong; Xiong, Mei; Ma, Mengdong; Liu, Lingyu; Li, Zihe; Zhang, Shuangshuang; Gao, Guoying; Zhao, Zhisheng; Tian, Yongjun; Xu, Bo; He, Julong

    2017-12-01

    Carbon allotropes with distinct sp, sp2, and sp3 hybridization possess various different properties. Here, a novel all-sp3 hybridized tetragonal carbon, namely the P carbon, was predicted by the evolutionary particle swarm structural search. It demonstrated a low density among all-sp3 carbons, due to the corresponding distinctive microporous structure. P carbon is thermodynamically stable than the known C60 and could be formed through the single-walled carbon nanotubes (SWCNTs) compression. P carbon is a direct bandgap semiconductor displaying a strong and superhard nature. The unique combination of electrical and mechanical properties constitutes P carbon a potential superhard material for semiconductor industrial fields.

  4. Tachykinins and tachykinin-receptors in the rat pineal gland

    DEFF Research Database (Denmark)

    Mukda, S; Chetsawang, B; Govitrapong, P

    2005-01-01

    High-pressure liquid chromatography of extracts of rat pineal glands, followed by radio immunological analysis with antibodies against tachykinins, demonstrated the presence of substance P, neurokinin A and neurokinin B in the superficial rat pineal gland. Immunohistochemistry on perfusion...... hybridization using radioactively labeled antisense oligonucleotide probes. Double immunohistochemical stainings showed that the NK1-immunoreactive cells were not a part of the macrophages or antigen-presenting cells of the gland. Our study suggests that tachykinins, after release from intrapineal nerve fibers...

  5. Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

    International Nuclear Information System (INIS)

    Silva, S.C.; Baggio-Zappia, G.L.; Brunialti, M.K.C.; Assunçao, M.S.C.; Azevedo, L.C.P.; Machado, F.R.; Salomao, R.

    2014-01-01

    Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated

  6. Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Silva, S.C.; Baggio-Zappia, G.L.; Brunialti, M.K.C. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Hospital São Paulo, Disciplina de Infectologia, Departamento de Medicina, São Paulo, SP, Brasil, Disciplina de Infectologia, Departamento de Medicina, Hospital São Paulo, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Assunçao, M.S.C. [Hospital Israelita Albert Einstein, Unidade de Terapia Intensiva, São Paulo, SP, Brasil, Unidade de Terapia Intensiva, Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Azevedo, L.C.P. [Hospital Sírio Libanês, Unidade de Terapia Intensiva, São Paulo, SP, Brasil, Unidade de Terapia Intensiva, Hospital Sírio Libanês, São Paulo, SP (Brazil); Machado, F.R. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Hospital São Paulo, Disciplina de Anestesiologia, Departamento de Cirurgia, São Paulo, SP, Brasil, Disciplina de Anestesiologia, Departamento de Cirurgia, Hospital São Paulo, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Salomao, R. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Hospital São Paulo, Disciplina de Infectologia, Departamento de Medicina, São Paulo, SP, Brasil, Disciplina de Infectologia, Departamento de Medicina, Hospital São Paulo, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-04-11

    Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.

  7. Sp6 and Sp8 Transcription Factors Control AER Formation and Dorsal-Ventral Patterning in Limb Development

    Science.gov (United States)

    Haro, Endika; Delgado, Irene; Junco, Marisa; Yamada, Yoshihiko; Mansouri, Ahmed; Oberg, Kerby C.; Ros, Marian A.

    2014-01-01

    The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6−/−;Sp8+/−) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/βcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning. PMID:25166858

  8. Bioakumulasi logam berat Cu oleh Bacillus sp

    Directory of Open Access Journals (Sweden)

    Riesta Primaharinastiti

    2012-02-01

    Full Text Available The research was conducted to investigate the ability of Bacillus sp in accumulating Cu and how much it can be acumulated. Themedium used to growth the bacterium was Nutrient Broth and Atomic Absorption Spectrophotometry methods was used to assay theCu, both in the cells and medium. The result of this study showed that Bacillus sp incubated in the Nutrient Broth medium containing10 ppm of Cu, with continuous stirring in the room temperature was able to reduce Cu in the medium 8.912–12.623% and accumulateCu in the cell 0.1149–0.1400 %/mg cells. Based on this result, it is necessary to develop more studies to find out what factors thatinfluence the accumulation process and to optimize the bioprocess.

  9. Analysis list: SP2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SP2 Blood,Liver,Pluripotent stem cell + hg19 http://dbarchive.biosciencedbc.jp/kyus...hu-u/hg19/target/SP2.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/SP2.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/SP2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/SP2.B...lood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/SP2.Liver.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/SP2.Pluripotent_stem_cell.tsv http://dbarchive.biosciencedbc

  10. Hepatites pós-transfusionais na cidade de Campinas, SP, Brasil: II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo vírus C nos receptores de sangue ou derivados Post-transfusional hepatitis in the city of Campinas, SP, Brazil: II- Presence of anti-HBc and anti-HCV antibodies in blood donors and occurrence of post-transfusional hepatitis C virus in recipients of blood or derivates

    Directory of Open Access Journals (Sweden)

    Fernando Lopes Gonçales Júnior

    1993-02-01

    Full Text Available Pesquisamos os anticorpos anti-HBc e anti-HCV em amostras de soros provenientes de 799 candidatos a doadores, que tiveram suas unidades de sangue ou derivados transfundidas a 111 receptores. O anti-HBc e o anti-HCV foram reagentes, em respectivamente 9 e 2,1% dos doadores testados. Observamos que entre os 111 receptores, 44 haviam recebido pelo menos uma unidade anti-HBc positiva e 67 haviam sido transfundidos somente com unidades anti-HBc negativas. Houve um risco 4,5 vezes maior de aquisição de hepatite por vírus C pelos receptores que receberam pelo menos uma unidade anti-HBc positiva Se a pesquisa do anti-HBc fosse realizada na triagem sorológica dos doadores de sangue, cerca de 56% dos casos de HVC nos receptores saiam evitados. A população de receptores que recebeu pelo menos uma unidade anti-HCV reagente, apresentou um risco 29 vezes maior de adquirir esta hepatite, quando comparada aos receptores transfundidos com todas as unidades anti-HCV negativas. A realização do teste para a pesquisa do anti-HCV na triagem dos doadores de sangue, preveniria 79% dos casos de HVC pós-transfusionais. Os candidatos a doadores brasileiros parecem ser acometidos simultânea ou sequencialmente, pelos vírus B e C das hepatites, pois, 44,4% dos doadores anti-HCV positivos, também foram anti-HBc positivos. A realização dos testes para as pesquisas dos anticorpos anti-HBc e anti-HCV, nas triagens hemoterápicas, está indicada para prevenir a transmissão de hepatites pós-transfusionais, em nosso meio.We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799 donors which had their blood or derivates transfused to 111 recipients. Anti-HBc and anti-HCV were reactive in respectively 9 and 2.1% of the donors tested. We have observed that among the 111 recipients, 44 had received at least one positive anti-HBc unit and 67 had been transfused only with negative anti-HBc, units. The risk of developing hepatitis C virus was 4.5 times

  11. Superfield quantization in Sp(2) covariant formalism

    CERN Document Server

    Lavrov, P M

    2001-01-01

    The rules of the superfield Sp(2) covariant quantization of the arbitrary gauge theories for the case of the introduction of the gauging with the derivative equations for the gauge functional are generalized. The possibilities of realization of the expanded anti-brackets are considered and it is shown, that only one of the realizations is compatible with the transformations of the expanded BRST-symmetry in the form of super translations along the Grassmann superspace coordinates

  12. Carbon sp chains in graphene nanoholes

    Science.gov (United States)

    Castelli, Ivano E.; Ferri, Nicola; Onida, Giovanni; Manini, Nicola

    2012-03-01

    Nowadays sp carbon chains terminated by graphene or graphitic-like carbon are synthesized routinely in several nanotech labs. We propose an ab initio study of such carbon-only materials, by computing their structure and stability, as well as their electronic, vibrational and magnetic properties. We adopt a fair compromise of microscopic realism with a certain level of idealization in the model configurations, and predict a number of properties susceptible to comparison with experiment.

  13. Commercial technologies from the SP-100 program

    International Nuclear Information System (INIS)

    Truscello, V.C.; Fujita, T.; Mondt, J.F.

    1995-01-01

    For more than a decade, Jet Propulsion Labortory and Los Alamos have managed a multi-agency funded effort to develop a space reactor power system. This SP-100 Program has developed technologies required for space power systems that can be implemented in the industrial and commercial sectors to improve competitiveness in the global economy. Initial steps taken to transfer this technology from the laboratories to industrial and commercial entities within United States include: (1) identifying specific technologies having commercial potential; (2) distributing information describing the identified technologies and interacting with interested commercial and industrial entities to develop application-specific details and requirements; and (3) providing a technological data base that leads to transfer of technology or the forming of teaming arrangements to accomplish the transfer by tailoring the technology to meet application-specific requirements. SP-100 technologies having commercial potential encompass fabrication processes, devices, and components. Examples: a process for bonding refractory metals to graphite, a device to sense the position of an actuator and a component to enable rotating machines to operate without supplying lubrication (self-lubricating ball bearing). Shortly after the NASA Regional Technology Transfer Centers widely disseminated information covering SP-100 technologies, over one hundred expressions of interest were received, which indicate that there is a large potential benefit in transferring SP-100 technology. Interactions with industrial and commercial entities have identified a substantial need for creating teaming arrangements involving the interested entity and personnel from laboratories and their contractors, who have the knowledge and ability to tailor the technology to meet application-specific requirements. copyright 1995 American Institute of Physics

  14. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...

  15. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  16. Sterols from the Madagascar sponge Fascaplysinopsis sp.

    Science.gov (United States)

    Aknin, Maurice; Gros, Emmanuelle; Vacelet, Jean; Kashman, Yoel; Gauvin-Bialecki, Anne

    2010-12-17

    The sponge Fascaplysinopsis sp. (order Dictyoceratida, Family Thorectidae) from the west coast of Madagascar (Indian Ocean) is a particularly rich source of bioactive nitrogenous macrolides. The previous studies on this organism led to the suggestion that the latter should originate from associated microsymbionts. In order to evaluate the influence of microsymbionts on lipid content, 10 samples of Fascaplysinopsis sp. were investigated for their sterol composition. Contrary to the secondary metabolites, the sterol patterns established were qualitatively and quantitatively stable: 14 sterols with different unsaturated nuclei, Δ(5), Δ(7) and Δ(5,7), were identified; the last ones being the main sterols of the investigated sponges. The chemotaxonomic significance of these results for the order Dictyoceratida is also discussed in the context of the literature. The conjugated diene system in Δ(5,7) sterols is known to be unstable and easily photo-oxidized during storage and/or experiments to produce 5α,8α-epidioxy sterols. However, in this study, no 5α,8α-epidioxysterols (or only trace amounts) were observed. Thus, it was supposed that photo-oxidation was avoided thanks to the natural antioxidants detected in Fascaplysinopsis sp. by both the DPPH and β-caroten bleaching assays.

  17. Sterols from the Madagascar Sponge Fascaplysinopsis sp.

    Directory of Open Access Journals (Sweden)

    Yoel Kashman

    2010-12-01

    Full Text Available The sponge Fascaplysinopsis sp. (order Dictyoceratida, Family Thorectidae from the west coast of Madagascar (Indian Ocean is a particularly rich source of bioactive nitrogenous macrolides. The previous studies on this organism led to the suggestion that the latter should originate from associated microsymbionts. In order to evaluate the influence of microsymbionts on lipid content, 10 samples of Fascaplysinopsis sp. were investigated for their sterol composition. Contrary to the secondary metabolites, the sterol patterns established were qualitatively and quantitatively stable: 14 sterols with different unsaturated nuclei, D5, D7 and D5,7, were identified; the last ones being the main sterols of the investigated sponges. The chemotaxonomic significance of these results for the order Dictyoceratida is also discussed in the context of the literature. The conjugated diene system in D5,7 sterols is known to be unstable and easily photo-oxidized during storage and/or experiments to produce 5a,8a-epidioxy sterols. However, in this study, no 5a,8a-epidioxysterols (or only trace amounts were observed. Thus, it was supposed that photo-oxidation was avoided thanks to the natural antioxidants detected in Fascaplysinopsis sp. by both the DPPH and b-caroten bleaching assays.

  18. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  19. Syrian hamsters (Mesocricetus auratus) with simultaneous intestinal Giardia sp., Spironucleus sp., and trichomonad infections.

    Science.gov (United States)

    Sheppard, Barbara J; Stockdale Walden, Heather D; Kondo, Hirotaka

    2013-11-01

    A commercial facility producing hamsters with a history of infection by dwarf tapeworm (Hymenolepis nana) submitted 15 animals for necropsy and postmortem parasitological and microscopic examination. No tapeworms were detected grossly or microscopically. Fecal examination including gastrointestinal mucosal smears demonstrated mixed intestinal bacteria and low numbers of Giardia sp. Histologic examination of small intestine demonstrated filling of the small intestinal crypts by large numbers of 7-9 µm × 3 µm, rod to crescent or teardrop-shaped flagellates consistent with Spironucleus sp. These organisms had two 1-µm, basophilic, oval nuclei and multiple superficial flagella-like structures. Much larger 10-15 µm × 8-10 µm, oval to pear-shaped organisms were also present in lower numbers and usually located with the crypts. These larger flagellates had multiple flagella and a basophilic rod-shaped nucleus. The larger flagellates included Giardia sp., which had an intimate interface with the surface of the mucosal epithelium, bilaterally symmetry, and binucleation. Lower numbers of trichomonads were also present and were distinguished by an undulating surface membrane and a single nucleus. The mucosa was hyperplastic and moderately inflamed. Although the tapeworm infection was resolved, diagnosis of multiple intestinal flagellates by fecal examination is complicated by the varying sensitivity and diagnostic accuracy of different types of fecal analysis for different flagellate types. Key differences in the morphology and location of the different types of flagellates as observed by histology of intestinal tissues provide important additional diagnostic information to distinguish trichomonads, Spironucleus sp., and Giardia sp.

  20. Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov. prevail in diverse enzootic transmission cycles

    Science.gov (United States)

    Margos, Gabriele; Lane, Robert S.; Fedorova, Natalia; Koloczek, Johannes; Piesman, Joseph; Hojgaard, Andrias; Sing, Andreas; Fingerle, Volker

    2018-01-01

    Two species of the genus Borrelia, Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov., were first described by Postic and co-workers on the basis of genetic analyses of several loci. Multilocus sequence analysis of eight housekeeping loci confirmed that these two Borrelia genomospecies are distinct members of the Borrelia burgdorferi sensu lato complex. B. bissettiae sp. nov. was initially described in transmission cycles involving Neotoma fuscipes wood rats and Ixodes pacificus ticks in California, and Neotoma mexicana and Ixodes spinipalpis in Colorado. The preferred host of B. californiensis sp. nov. appears to be the California kangaroo rat, Dipodomys californicus; Ixodes jellisoni, I. spinipalipis and I. pacificus ticks are naturally infected with it. Thus, the ecological associations of the two genomospecies and their genetic distance from all other known Borrelia genomospecies species justify their description as separate genomospecies: B. bissettiae sp. nov. (type strain DN127T=DSM 17990T= CIP 109136T) and B. californiensis (type strain CA446T=DSM 17989T=ATCC BAA-2689T). PMID:26813420

  1. P2X receptors.

    Science.gov (United States)

    North, R Alan

    2016-08-05

    Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. In the central nervous system, activation of P2X receptors allows calcium to enter neurons and this can evoke slower neuromodulatory responses such as the trafficking of receptors for the neurotransmitter glutamate. In primary afferent nerves, P2X receptors are critical for the initiation of action potentials when they respond to ATP released from sensory cells such as taste buds, chemoreceptors or urothelium. In immune cells, activation of P2X receptors triggers the release of pro-inflammatory cytokines such as interleukin 1β. The development of selective blockers of different P2X receptors has led to clinical trials of their effectiveness in the management of cough, pain, inflammation and certain neurodegenerative diseases.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Author(s).

  2. EFEKTIFITAS DAYA HAMBAT BAKTERI Streptomyces sp TERHADAP Erwinia sp PENYEBAB PENYAKIT BUSUK REBAH PADA TANAMAN LIDAH BUAYA (Aloe barbadensis Mill

    Directory of Open Access Journals (Sweden)

    SARMILA TASNIM

    2013-05-01

    Full Text Available Streptomyces sp was conducted from December 2010 - June 2011 at the Laboratoryof Microbiology, Biology Department, Math and Science Faculty, UdayanaUniversity Bukit Jimbaran-Bali. Implementation stages of the research consisted ofisolation and testing of the antibiotic activity Streptomyces sp to inhibit growthbacterial pathogens Erwinia sp as a cause of disease in plants fallen foul (Soft rot ofAloe barbadensis Mill.The results of this study have eight isolates of Streptomyces spwith macroscopic and microscopic characters are varied. Furthermore, all isolateswere obtained and then tested against antibiotic activity to inhibit growth the bacteriaErwinia sp. Test results obtained by Streptomyces sp that has the most effective ininhibiting the ability of the bacteria Erwinia sp isolates are Streptomyces sp2for (45%.

  3. Detección de una mutación puntual en el gen receptor Ryanodina (Ryr 1 en cerdos criollos colombianos Detection of a single mutation point in Ryanodine receptor gene (Ryr 1 in colombian creole pigs

    Directory of Open Access Journals (Sweden)

    Darwin Y Hernández

    2008-12-01

    Full Text Available El síndrome de estrés porcino (PSS es una enfermedad hereditaria monogénica recesiva relacionada con el gen receptor ryanodina (Ryr1. Utilizando PCR-SSCP y PCR-RFLP se tipificaron genéticamente 14 individuos de cerdos comerciales con el rasgo sindactilia (Casco de Mula-CM, 21 San Pedreños -SP y 100 Zungos- ZN. Las razas CM y SP tuvieron las mismas frecuencias alélicas (F(H = 0.79 y F(h = 0.21, mientras que en los cerdos ZN no se encontró el alelo recesivo (h. La heterocigosidad (He fue de 0.28% para los cerdos CM y 0.23% para los SP. La He para la muestra poblacional fue de 0.066.The Porcine Stress Syndrome is a hereditary monogenic recessive disease related with Ryanodine Receptor gen (Ryr1. Using PCR-SSCP and PCR-RFLP 14 animals of commercial breed with Mule foot characteristic (CM, 21 San Pedreño breed (SP and 100 Zungo breed (ZN were genotipificated. Allelic frequency for CM and SP was the same (F(H = 0.79 y F(h = 0.21, while in ZN there was no evidence of recessive allele (h. Heterocigosity (He was 0.28% for CM and 0.23% for SP. He value for population sample was 0.066.

  4. Transcriptional regulation of renal dopamine D1 receptor function during oxidative stress.

    Science.gov (United States)

    Banday, Anees A; Lokhandwala, Mustafa F

    2015-05-01

    There exists a strong link between oxidative stress, renal dopaminergic system, and hypertension. It is reported that reactive oxygen species attenuate renal proximal tubular dopamine receptor (D1R) function, which disrupts sodium regulation and leads to hypertension. However, the mechanisms for renal D1R dysfunction are not clear. We investigated the role of redox-sensitive transcription factors AP1 and SP3 in transcriptional suppression of D1R gene and subsequent D1R signaling. Human kidney proximal tubular cells were treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol. In human kidney cells, BSO caused oxidative stress and reduced D1R mRNA and membrane receptor expression. Incubation of human kidney cells with SKF38393, a D1R agonist, caused a concentration-dependent inhibition of Na/K-ATPase. However, SKF38393 failed to inhibit Na/K-ATPase in BSO-treated cells. BSO increased AP1 and SP3 nuclear expression. Transfection with AP1- or SP3-specific siRNA abolished BSO-induced D1R downregulation. Treatment of rats with BSO for 4 weeks increased oxidative stress and SP3-AP1 expression and reduced D1R numbers in renal proximal tubules. These rats exhibited high blood pressure, and SKF38393 failed to inhibit proximal tubular Na/K-ATPase activity. Control rats were kept on tap water. Tempol per se had no effect on D1R expression or other signaling molecules but prevented BSO-induced oxidative stress, SP3-AP1 upregulation, and D1R dysfunction in both human kidney cells and rats. These data show that oxidative stress via AP1-SP3 activation suppresses D1R transcription and function. Tempol mitigates oxidative stress, blocks AP1-SP3 activation, and prevents D1R dysfunction and hypertension. © 2015 American Heart Association, Inc.

  5. SpAHA1 and SpSOS1 Coordinate in Transgenic Yeast to Improve Salt Tolerance.

    Directory of Open Access Journals (Sweden)

    Yang Zhou

    Full Text Available In plant cells, the plasma membrane Na+/H+ antiporter SOS1 (salt overly sensitive 1 mediates Na+ extrusion using the proton gradient generated by plasma membrane H+-ATPases, and these two proteins are key plant halotolerance factors. In the present study, two genes from Sesuvium portulacastrum, encoding plasma membrane Na+/H+ antiporter (SpSOS1 and H+-ATPase (SpAHA1, were cloned. Localization of each protein was studied in tobacco cells, and their functions were analyzed in yeast cells. Both SpSOS1 and SpAHA1 are plasma membrane-bound proteins. Real-time polymerase chain reaction (PCR analyses showed that SpSOS1 and SpAHA1 were induced by salinity, and their expression patterns in roots under salinity were similar. Compared with untransformed yeast cells, SpSOS1 increased the salt tolerance of transgenic yeast by decreasing the Na+ content. The Na+/H+ exchange activity at plasma membrane vesicles was higher in SpSOS1-transgenic yeast than in the untransformed strain. No change was observed in the salt tolerance of yeast cells expressing SpAHA1 alone; however, in yeast transformed with both SpSOS1 and SpAHA1, SpAHA1 generated an increased proton gradient that stimulated the Na+/H+ exchange activity of SpSOS1. In this scenario, more Na+ ions were transported out of cells, and the yeast cells co-expressing SpSOS1 and SpAHA1 grew better than the cells transformed with only SpSOS1 or SpAHA1. These findings demonstrate that the plasma membrane Na+/H+ antiporter SpSOS1 and H+-ATPase SpAHA1 can function in coordination. These results provide a reference for developing more salt-tolerant crops via co-transformation with the plasma membrane Na+/H+ antiporter and H+-ATPase.

  6. Muscarinic receptor oligomerization.

    Science.gov (United States)

    Marsango, Sara; Ward, Richard J; Alvarez-Curto, Elisa; Milligan, Graeme

    2017-11-14

    G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization remain topics of intense speculation. Muscarinic acetylcholine receptors belong to class A of the GPCR family. Each muscarinic receptor subtype has its own particular distribution throughout the central and peripheral nervous systems. In the central nervous system, muscarinic receptors regulate several sensory, cognitive, and motor functions while, in the peripheral nervous system, they are involved in the regulation of heart rate, stimulation of glandular secretion and smooth muscle contraction. Muscarinic acetylcholine receptors have long been used as a model for the study of GPCR structure and function and to address aspects of GPCR dimerization using a broad range of approaches. In this review, the prevailing knowledge regarding the quaternary arrangement for the various muscarinic acetylcholine receptors has been summarized by discussing work ranging from initial results obtained using more traditional biochemical approaches to those generated with more modern biophysical techniques. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Copper resistance of different ectomycorrhizal fungi such as Pisolithus microcarpus, Pisolithus sp., Scleroderma sp. and Suillus sp.

    Directory of Open Access Journals (Sweden)

    R.F. Silva

    2013-01-01

    Full Text Available Environments contaminated with heavy metals negatively impact the living organisms. Ectomycorrhizal fungi have shown important role in these impacted sites. Thus, this study aimed to evaluate the copper-resistance of ectomycorrhizal fungi isolates Pisolithus microcarpus - UFSC-Pt116; Pisolithus sp. - UFSC-PT24, Suillus sp. - UFSM RA 2.8 and Scleroderma sp. - UFSC-Sc124 to different copper doses in solid and liquid media. The copper doses tested were: 0.00, 0.25, 0.5, 0.75, 1.0 and 1.25 mmol L-1 in the solid medium and 0.00, 0.32, 0.64 and 0.96 mmol L-1 in the liquid medium. Copper was amended as copper sulphate in order to supplement the culture medium MNM at pH 4.8, with seven replicates to each fungus-dose combination. The fungal isolates were incubated for 30 days at 28 °C. UFSC-Pt116 showed high copper-resistance such as accessed by CL50 determinations (concentration to reduce 50% of the growth as while as UFSC-PT24 displayed copper-resistance mechanism at 0.50 mmol L-1 in solid medium. The UFSC-PT24 and UFSC-Sc124 isolates have increased copper-resistance in liquid medium. The higher production of extracellular pigment was detected in UFSC-Pt116 cultures. The UFSC-Pt116 and UFSC-PT24 isolates showed higher resistance for copper and produced higher mycelium biomass than the other isolates. In this way, the isolates UFSG-Pt116 and UFSC-PT24 can be important candidates to survive in copper-contaminated areas, and can show important role in plants symbiosis in these contaminated sites.

  8. Isolation of C11 Cyclopentenones from Two Didemnid Species, Lissoclinum sp. and Diplosoma sp.

    Directory of Open Access Journals (Sweden)

    Katsuhiro Ueda

    2009-12-01

    Full Text Available A series of new C11 cyclopentenones 1-7 was isolated, together with four known metabolites 9/10, 12 and 13, from the extract of the didemnid ascidian Lissoclinum sp. The other didemnid ascidian Diplosoma sp. contained didemnenones 1, 2 and 5, and five known metabolites 8-12. The structures of 1-7 were elucidated by spectroscopic analyses. Cytotoxicity of the isolated compounds was evaluated against three human cancer cell lines (HCT116, A431 and A549.

  9. Construction of human MASP-2-CCP1/2SP, CCP2SP, SP plasmid DNA nanolipoplexes and the effects on tuberculosis in BCG-infected mice.

    Science.gov (United States)

    Gao, Qi; Dong, Xinfang; Luo, Yanping; Zhang, Guochao; Shan, Jinyu; Wang, Qian; He, Qi; Zhang, Lifeng; Wang, Jingqiu; Zhu, Bingdong; Ma, Xingming

    2017-08-01

    The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. The serine protease of MASP-2 plays an essential role in complement activation of the lectin pathway. The C-terminal segment of MASP-2 is comprised of the CCP1-CCP2-SP domains, and is the crucial catalytic segment. However, what is the effect of CCP1-CCP2-SP domains in controlling chronic infection is unknown. In order to evaluate the potential impact of CCP1-CCP2-SP domains on tuberculosis, we constructed the human MASP-2 CCP1/2SP, CCP2SP and SP recombinant plasmids, and delivered these plasmids by DNA-DOTAP:cholesterol cationic nanolipoplexes to BCG-infected mice. After 21 days post DNA-DOTAP:chol nanolipoplexes application, we analyzed bacteria loads of pulmonary, pathology of granuloma, lymphocyte subpopulations. The C3a, C4a and MASP-2 levels in serum were measured with enzyme-linked immunosorbent assays. Compared to the control group that received GFP DNA-DOTAP:chol nanolipoplexes, MASP-2 CCP1/2SP DNA-DOTAP:chol nanolipoplexes treated group showed significantly enlarged pulmonary granulomas lesion (P  0.05). These findings provided experimental evidence that MASP-2 CCP1/2SP DNA nanolipoplexes shown the negative efficacy in controlling Mycobacterium tuberculosis infection, and displayed a potential role of down-regulating T-cell-mediated immunity in tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  11. P2X receptors

    OpenAIRE

    North, R. Alan

    2016-01-01

    Extracellular adenosine 5′-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2...

  12. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  13. Quality improvement on half-fin anchovy (Setipinna taty) fish sauce by Psychrobacter sp. SP-1 fermentation.

    Science.gov (United States)

    Zheng, Bin; Liu, Yu; He, Xiaoxia; Hu, Shiwei; Li, Shijie; Chen, Meiling; Jiang, Wei

    2017-10-01

    A method of improving fish sauce quality during fermentation was investigated. Psychrobacter sp. SP-1, a halophilic protease-producing bacterium, was isolated from fish sauce with flavor-enhancing properties and non-biogenic amine-producing activity. The performance of Psychrobacter sp. SP-1 in Setipinna taty fish sauce fermentation was investigated further. The inoculation of Psychrobacter sp. SP-1 did not significantly affect pH or NaCl concentration changes (P > 0.05), although it significantly increased total moderately halophilic microbial count, protease activity, total soluble nitrogen content and amino acid nitrogen content, and also promoted the umami taste and meaty aroma (P < 0.05). Furthermore, the inoculation of Psychrobacter sp. SP-1 significantly decreased total volatile basic nitrogen content and biogenic amines content (P < 0.05), which were regarded as harmful compounds in foods. The results of the present study demonstrate that Psychrobacter sp. SP-1 can be used as a potential starter culture for improving fish sauce quality by fermentation. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. Dominancy of Trichodesmium sp. in the Biawak Island

    Science.gov (United States)

    Prihadi, D. J.

    2018-03-01

    The Biawak Island is one of the small islands in West Java Province with an abundance of marine biological resources. This research was conducted to collect the primary producer zooplankton and water quality parameters. Direct observation is done by field surveys and measurement in situ for plankton and environmental parameters such as temperature, water transparency, water current, salinity, dissolved oxygen, and pH. Trichodesmium sp. was found dominance in where some other types of zooplankton were found in the area, like Scenedesmus sp., Sagitta sp., Acartia sp. also occurred. Further, the most abundance of Trichodesmium sp. was found in southern of Biawak Island where mangroves, coral and seagrass ecosystem provide nutrients which indirectly support the abundance of planktons. Trichodesmium sp. is plankton that can survive in water with minimum nutrient.

  15. The SP Theory of Intelligence: An Overview

    Directory of Open Access Journals (Sweden)

    J Gerard Wolff

    2013-08-01

    Full Text Available This article is an overview of the SP theory of intelligence, which aims to simplify and integrate concepts across artificial intelligence, mainstream computing and human perception and cognition, with information compression as a unifying theme. It is conceived of as a brain-like system that receives "New" information and stores some or all of it in compressed form as "Old" information; and it is realised in the form of a computer model, a first version of the SP machine. The matching and unification of patterns and the concept of multiple alignment are central ideas. Using heuristic techniques, the system builds multiple alignments that are "good" in terms of information compression. For each multiple alignment, probabilities may be calculated for associated inferences. Unsupervised learning is done by deriving new structures from partial matches between patterns and via heuristic search for sets of structures that are "good" in terms of information compression. These are normally ones that people judge to be "natural", in accordance with the "DONSVIC" principle—the discovery of natural structures via information compression. The SP theory provides an interpretation for concepts and phenomena in several other areas, including "computing", aspects of mathematics and logic, the representation of knowledge, natural language processing, pattern recognition, several kinds of reasoning, information storage and retrieval, planning and problem solving, information compression, neuroscience and human perception and cognition. Examples include the parsing and production of language with discontinuous dependencies in syntax, pattern recognition at multiple levels of abstraction and its integration with part-whole relations, nonmonotonic reasoning and reasoning with default values, reasoning in Bayesian networks, including "explaining away", causal diagnosis, and the solving of a geometric analogy problem.

  16. Early SP-100 flight mission designs

    International Nuclear Information System (INIS)

    Josloff, A.T.; Shepard, N.F.; Kirpich, A.S.; Murata, R.; Smith, M.A.; Stephen, J.D.

    1993-01-01

    Early flight mission objectives can be met with a Space Reactor Power System (SRPS) using thermoelectric conversion in conjunction with fast spectrum, lithium-cooled reactors. This paper describes two system design options using thermoelectric technology to accommodate an early launch. In the first of these options, radiatively coupled Radioiosotope Thermoelectric Generator (RTG) unicouples are adapted for use with a SP-100-type reactor heat source. Unicouples have been widely used as the conversion technology in RTGs and have demonstrated the long-life characteristics necessary for a highly relible SRPS. The thermoelectric leg height is optimized in conjunction with the heat rejection temperature to provide a mass optimum 6-kW e system configured for launch on a Delta II launch vehicle. The flight-demonstrated status of this conversion technology provides a high confidence that such a system can be designed, assembled, tested, and launched by 1997. The use of a SP-100-type reactor assures compliance with safety requirements and expedites the flight safety approval process while, at the same time, providing flight performance verification for a heat source technology with the growth potential to meet future national needs for higher power levels. A 15-kW 2 , Atlas IIAS-launched system using the compact, conductively coupled multicouple converters being developed under the SP-100 program to support an early flight system launch also described. Both design concepts have been scaled to 20-kW e in order to support recent studies by DOE/NASA for higher power early launch missions

  17. Dosimetric Studies in Normal Mice of 177Lu-DOTA-SP and 177Lu-DOTA-His2-MG

    International Nuclear Information System (INIS)

    Puerta Yepes, N.; Rojo, A.M.; Lopez Bularte, A.C.; Nevares, N.; Zapata, M.; Perez, J.H.; Crudo, J.

    2010-01-01

    DOTA-Substance-P (SP) and DOTA-minigastrin (His2-MG) labeled with 177 Lu could be used in peptide receptor radionuclide therapy (PRRT) for treatment of various tumour species. Biodistribution studies of both radiopharmaceuticals in normal mice were performed at different times. Absorbed doses in mouse organs were estimated and extrapolated to humans. Dosimetric calculations showed that kidneys received the highest dose, for both radiopharmaceuticals. The Maximum Tolerated Activity (MTA) of 177 Lu-DOTA-SP that can be administered without kidney toxicity are 414 and 422 MBq/kg for the standard adult man and woman, respectively. In the same way, the MTA of 177 Lu-DOTA-His2-MG are 488 and 518 MBq/kg for the standard adult man and woman, respectively. (authors)

  18. Somatostatin receptor skintigrafi

    DEFF Research Database (Denmark)

    Rasmussen, Karin; Nielsen, Jørn Theil; Rehling, Michael

    2005-01-01

    Somatostatin receptor scintigraphy (SRS) is a very valuable imaging technique for visualisation of a diversity of neuroendocrine tumours. The sensitivity for localisation of carcinoid tumours is high, but somewhat lower for other neuroendocrine tumours. The methodology, multiple clinical aspects ...

  19. Amino Alcohols from the Ascidian Pseudodistoma sp.

    Directory of Open Access Journals (Sweden)

    Tae Hyung Won

    2014-06-01

    Full Text Available Seven new amino alcohol compounds, pseudoaminols A–G (1–7, were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion. The presence of an N-carboxymethyl group in two of the new compounds (6 and 7 is unprecedented among amino alcohols. Several of these compounds exhibited moderate antimicrobial activity and cytotoxicity, as well as weak inhibitory activity toward Na+/K+-ATPase.

  20. SP-100 control drive assembly development

    Science.gov (United States)

    Gleason, Thomas; Gilchrist, A. Richard; Schuster, Gary

    1993-01-01

    The SP-100 is an electrical generating nuclear power system for space operation. This paper describes the nuclear reactor control systems and the methods used to assure reliable performance for the 10-year design life. Reliable performance is achieved by redundancy and by selecting highly reliable components and design features. Reliability is quantified by analysis using established reliability data. Areas lacking reliability data are identified for development testing. A specific development test description is provided as an example to demonstrate how this process is meeting the system reliability goals.

  1. ANCAMAN DARI NYAMUK Culex sp YANG TERABAIKAN

    Directory of Open Access Journals (Sweden)

    Zumrotus Sholichah

    2012-11-01

    Full Text Available Nyamuk Culex sp lebih menyukai meletakkan telurnya pada genangan air berpolutan tinggi, berkembang biak di air keruh dan lebih menyukai genangan air yang sudah lama daripada genangan air yang baru. Aktif menggigit pada malam hari. Tempat yang gelap, sejuk dan lembab merupakan tempat yang disukai untuk beristirahat. Nyamuk betina dewasa menggigit dengan abdomen terletak sejajar dengan permukaan induk semang yang sedang digigit.Gangguan yang ditimbulkan oleh nyamuk selain dapat menularkan penyakit juga dapat sangat mengganggu dengan dengungan dan gigitannya sehingga bagi orang-orang tertentu dapat menimbulkan phobi (entomopobhia serta dapat menyebabkan dermatitis dan urticaria.

  2. Methyl (Sp-2-(diphenylphosphinoferrocene-1-carboxylate

    Directory of Open Access Journals (Sweden)

    Petr Štěpnička

    2009-10-01

    Full Text Available The title compound, [Fe(C5H5(C19H16O2P], obtained serendipitously during recrystallization of 1-hydroxybenzotriazolyl (Sp-2-(diphenylphosphinoferrocene-1-carboxylate from methanol, crystallizes in the chiral space group P212121. Its crystal structure not only confirms the anticipated absolute configuration but also establishes a rather regular geometry for the ferrocene unit, devoid of any significant deformation due to the attached substituents. In the crystal, symmetry-related molecules are linked via weak C—H...O interactions.

  3. Genome Sequence of Streptomyces sp. Strain Tü6071▿

    OpenAIRE

    Erxleben, Anika; Wunsch-Palasis, Julia; Grüning, Björn A.; Luzhetska, Marta; Bechthold, Andreas; Günther, Stefan

    2011-01-01

    Streptomyces sp. Tü6071 is a soil-dwelling bacterium which has a highly active isoprenoid biosynthesis. Isoprenoids are important precursors for biopharmaceutical molecules such as antibiotics or anticancer agents, e.g., landomycin. Streptomyces sp. Tü6071 produces the industrially important terpene glycosides phenalinolactones, which have antibacterial activity against several Gram-positive bacteria. The availability of the genome sequence of Streptomyces sp. Tü6071 allows for understanding ...

  4. Muscarinic receptor oligomerization

    OpenAIRE

    Marsango, Sara; Ward, Richard J.; Alvarez-Curto, Elisa; Milligan, Graeme

    2017-01-01

    G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization...

  5. Screening of biodiesel production from waste tuna oil (Thunnus sp.), seaweed Kappaphycus alvarezii and Gracilaria sp.

    Science.gov (United States)

    Alamsjah, Mochammad Amin; Abdillah, Annur Ahadi; Mustikawati, Hutami; Atari, Suci Dwi Purnawa

    2017-09-01

    Biodiesel has several advantages over solar. Compared to solar, biodiesel has more eco-friendly characteristic and produces lower greenhouse gas emissions. Biodiesel that is made from animal fats can be produced from fish oil, while other alternative sources from vegetable oils are seaweed Kappaphycus alvarezii and Gracilaria sp. Waste tuna oil (Thunnus sp.) in Indonesia is commonly a side product of tuna canning industries known as tuna precook oil; on the other hand, seaweed Gracilaria sp. and Kappaphycus alvarezii are commonly found in Indonesia's seas. Seaweed waste that was used in the present study was 100 kg and in wet condition, and the waste oil was 10 liter. The seaweed was extracted with soxhletation method that used n-hexane as the solvent. To produce biodiesel, trans esterification was performed on the seaweed oil that was obtained from the soxhletation process and waste tuna oil. Biodiesel manufactured from seaweed K. alvarezii obtained the best score in flash point, freezing point, and viscosity test. However, according to level of manufacturing efficiency, biodiesel from waste tuna oil is more efficient and relatively easier compared to biodiesel from waste K. alvarezii and Gracilaria sp.

  6. SHEAR STRENGTH IN THE GLUE LINE OF Eucalyptus sp. AND Pinus sp.WOOD

    Directory of Open Access Journals (Sweden)

    Juliana Jerásio Bianche

    Full Text Available ABSTRACT To evaluate the adhesive efficiency on the union of glued joints in a particular temperature and humidity conditions for a specified time the adhesive must be submitted to specific load tests, such as shear in the glue line. The objective of this study was to evaluate the shear strength in the glue line of Eucalyptus sp and Pinus sp.woods. Five adhesives (castor oil, sodium silicate, modified silicate, , PVA and resorcinol-formaldehyde, three weights (150 g/m2, 200 g/m2, and 250 g/m2 and two species (Eucalyptus sp. and Pinus sp. of wood were used. Twelve specimens were obtained from each repetition per treatment, corresponding to 108 specimens that were conditioned at a temperature of 23 ± 1°C and relative humidity of 50 ± 2%. The interaction between the weight and type of adhesive was significant for the shear strength in the glue line of eucalyptus wood. However, no interaction between the weight and the adhesive was found for pinus, only the isolated from the adhesive effect. Chemical bonds originated in the polymerization of resorcinol-formaldehyde adhesives and castor bi-component conferred upon these adhesives the greatest resistance in the glue line. Castor and resorcinol-formaldehyde adhesives showed the highest shear strength values in the line of glue and wood failure. Castor adhesive presented satisfactory performance for bonding of eucalyptus and pine woods.

  7. Genetic diversity in Fusarium oxysporum f.sp. dianthi and F. redolens f.sp. dianthi

    NARCIS (Netherlands)

    Baayen, R.P.; Dreven, van F.; Krijger, M.C.; Waalwijk, C.

    1997-01-01

    Pathogenic isolates were selected representing all known vegetative compatibility groups (VCGs) and races of Fusarium oxysporum sensu lato from Dianthus spp. On basis of differences in the internal transcribed spacer region of the ribosomal DNA, six VCGs were classified as F. oxysporum f.sp. dianthi

  8. Biodegradation of hexavalent chromium (Cr+6) in wastewater using Pseudomonas sp. and Bacillus sp. bacterial strains

    Energy Technology Data Exchange (ETDEWEB)

    Qasim, Muhammad [Department of Chemical Engineering, American University of Sharjah (United Arab Emirates)

    2013-07-01

    The recovery of toxic metal compounds is a deep concern in all industries. Hexavalent chromium is particularly worrying because of its toxic influence on human health. In this paper, biodegradation of hexavalent chromium (Cr+6) present in wastewater has been studied using two different bacterial strains; Pseudomonas sp. and Bacillus sp. A chemostat (with and without recycle of cells) with 10 L liquid culture volume was used to study the substrate and the biomass cell concentrations with time. Also, the degree of substrate conversion was studied by the varying the dilution rate as an independent parameter. The dilution rate (ratio of feed flow rate to the culture volume) was varied by varying the feed volumetric rate from 110-170 mL/h for inlet hexavalent chromium concentrations of 70 mg/dm3. The results show that a chemostat with recycle gives a better performance in terms of substrate conversion than a chemostat without a recycle. Moreover, the degree of substrate conversion decreases as the dilution rate is increased. Also, Bacillus sp. was found to give higher conversions compared to pseudomonas sp.

  9. Adenosine receptor neurobiology: overview.

    Science.gov (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases. © 2014 Elsevier Inc. All rights reserved.

  10. Genetics of taste receptors.

    Science.gov (United States)

    Bachmanov, Alexander A; Bosak, Natalia P; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R; Nelson, Theodore M

    2014-01-01

    Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical "tastes" as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications.

  11. Sp(2) covariant quantisation of general gauge theories

    International Nuclear Information System (INIS)

    Vazquez-Bello, J.L.

    1994-11-01

    The Sp(2) covariant quantization of gauge theories is studied. The geometrical interpretation of gauge theories in terms of quasi principal fibre bundles Q(M s , G s ) is reviewed. It is then described the Sp(2) algebra of ordinary Yang-Mills theory. A consistent formulation of covariant Lagrangian quantisation for general gauge theories based on Sp(2) BRST symmetry is established. The original N = 1, ten dimensional superparticle is considered as an example of infinitely reducible gauge algebras, and given explicitly its Sp(2) BRST invariant action. (author). 18 refs

  12. Lagenidium callinectes INFECTION ON ROTIFERS Brachionus sp.

    Directory of Open Access Journals (Sweden)

    Des Roza

    2007-06-01

    Full Text Available Milkfish, Chanos chanos and humpback grouper, Cromileptes altivelis hatcheries have developed at Gondol, Bali since 1995 and until now still rely on rotifers, the main natural food, supply. Recent problem on mass culture of rotifer, Brachionus sp. is harvest failure caused by fungus infection. Under light microscope, infected eggs and bodies of the rotifers was filled with numerous aseptate hyphae. Two isolates of fungi were isolated from rotifer eggs and carcass on June 21st, 2004 and on June 25th, 2004 obtained from milkfish and humpback grouper hatcheries at Gondol. Based on its morphological characteristics, the pathogenic fungus was identified as Lagenidium callinectes which grows optimally at 25°C and survives in 1.0%, 2.5%, and 5.0% NaCl as well as in 1.0% and 2.5% KCl. Both of the present isolates utilize only 8 out of 26 carbohydrates and derivatives tested as carbon, nutrition and energy sources. This finding is the first report on rotifer, Brachionus sp. infected with L. callinectes causing up to 100% mortality.

  13. Polyhydroxybutyrate by Streptomyces sp.: Production and characterization.

    Science.gov (United States)

    Krishnan, Sivakumar; Chinnadurai, Gandhi Shree; Perumal, Palani

    2017-11-01

    A total number of 20 actinomycetes isolates were isolated from soil sediments obtained from Semmancheri coastal areas of Bay of Bengal, India and they were qualitatively screened for the production of polyhydroxybutyrate (PHB) on a medium containing Sudan black stain. Nine of the 20 isolates produced PHB and the quantity of PHB produced varied from 1.79 to 4.26g -L . Among the positive isolates an actinomycete isolate which was identified as Streptomyces sp. through 16S rRNA sequencing analysis (Accession No: KF667247) produced relatively higher PHB than other positive isolates. Subsequently, the growth conditions were optimized for the maximum PHB production by the chosen organism. Attempt was also made to utilize natural carbon sources such as paddy straw, wheat bran, rice bran, sugarcane molasses and oil cake for the production of PHB in an attempt to reduce the cost production of PHB. The purified PHB was analyzed by Solid-State 13 C NMR, Fourier Transformed Infrared spectroscopy, Powder X-ray diffraction, Thermogravimetric Analysis, Scanning and Transmission Electron Microscopic analyses to determine the structure, crystallinity, purity and thermal stability. The present investigation has revealed that Streptomyces sp. could be a potential source for the production of PHB with desirable characteristics and could also be exploited for the industrial production. Copyright © 2017. Published by Elsevier B.V.

  14. Fluorescence Properties of Chlorella sp. Algae

    Directory of Open Access Journals (Sweden)

    Tibor Teplicky

    2017-01-01

    Full Text Available Water quality and its fast and reliable monitoring is the challenge of the future. Design of appropriate biosensors that would be capable of non-invasive identification of water pollution is an important prerequisite for such challenge. Chlorophylls are pigments, naturally presented in all plants that absorb light. The main forms of chlorophyll in algae are chlorophyll a and chlorophyll b, other pigments include xantophylls and beta-carotenes. Our aim was to characterize endogenous fluorescence of the Chlorella sp. algae, present naturally in drinking water. We recorded spatial, spectral and lifetime fluorescence distribution in the native algae. We noted that the fluorescence was evenly distributed in the algae cytosol, but lacked in the nucleus and reached maximum at 680-690 nm. Fluorescence decay of chlorella sp. was double-exponential, and clearly shorter than that of its isolated pigments. For the first time, fluorescence lifetime image of the algae is presented. Study of the fluorescence properties of algae is aimed at the improvement of water supply contamination detection and cleaning.

  15. Karakterisasi protease Bacillus sp. UGM5

    Directory of Open Access Journals (Sweden)

    Titik Purwati Widowati

    1999-07-01

    Full Text Available The objective of this experiment is to indentify the characters of proetease produced by Bacillus sp.UGM5.the protease secreted by Bacillus sp.UGM5 was first isolated,purified and then charactirezed.The crude enzyme has spesific actifity of 1.14 U/mg,however,the spesific activity of purified enzyme was increased by 23.8 times fold and recovery was 33.69%.The Page of nondenatured crude enzymes showes two type of proreases,however ,the SDS-Page of denatured purified enzyme showed four protein-bends with molecular weights of 55.5 kDa,18kDa respecetively.The optimum pH and temperature for the enzyme acrivity are 8.5 and 420C and belongs to serin protease type,with Km 3 X 10-3mM and Vmax 0.0890mM/30 minutes.The activity is not inhibited by Ca+2,Fe+2 and EDTA.

  16. UTILIZAÇÃO DE ADESIVO PVA EM COMPENSADOS DE Pinus sp. E Eucalyptus sp. / UTILIZATION OF PVA ADHESIVES IN Pinus sp. and Eucalyptus sp. PLYWOOD

    Directory of Open Access Journals (Sweden)

    C. I. De Campos

    2014-12-01

    Full Text Available Estudos sobre novos adesivos ou resinas para colagem de madeira e derivados estão sendo realizados com a intenção de diminuir o impacto ambiental sem alterar suas propriedades. Por este motivo, novas formulações de adesivos PVA (Acetato de Polivinila vêm sendo desenvolvidas. Este trabalho testou a utilização deste adesivo na produção de compensado de Eucalyptus sp. e Pinus sp., com tempo e temperatura de prensagem, respectivamente, de 10 minutos e90°C. Foram realizados os ensaios físicos de densidade, teor de umidade e absorção, e os ensaios mecânicos de flexão estática e de resistência ao cisalhamento na linha de cola, todos de acordo com as normas ABNT. Obtiveram-se bons resultados com relação à resistência ao cisalhamento na linha de cola, a qual foi superior para os adesivos PVA, se comparados com compensados produzidos com ureia-formaldeído e o fenol-formaldeído, enquanto que os resultados de MOE e MOR apresentaram-se inferiores em ambos os casos. 

  17. Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

    Directory of Open Access Journals (Sweden)

    Vidlak Debbie

    2012-06-01

    Full Text Available Abstract Although IL-17A (commonly referred to as IL-17 has been implicated in the pathogenesis of central nervous system (CNS autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R knockout (KO mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25. In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT cell and gamma-delta (γδ T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

  18. The Effect of Acupuncture to SP6 on Skin Temperature Changes of SP6 and SP10: An Observation of “Deqi”

    Directory of Open Access Journals (Sweden)

    Jia-Min Yang

    2014-01-01

    Full Text Available Background. Deqi sensation is a complex but an important component for acupuncture effect. In this study, we tried to observe the relationship between Deqi and skin temperature changes and whether there was some relativity between Deqi and needle stimulations on cold congealing and dysmenorrhea rat model. Thirty-two female Sprague Dawley (SD rats were randomly divided into four groups (Saline Control Group, Model Group, Group A with strong stimulation, and Group B with small stimulation. Group A and Group B were performed with different stimulations. We found that, compared with saline control group, model group, and Group B, Group A showed that the skin temperature changes on right acupoint SP6 and SP10 increased significantly at 5 min–10 min interval. The skin temperature changes on left SP6 decreased at instant–5 min interval. The skin temperature changes on right SP10 decreased significantly at instant–5 min interval and 10 min–20 min interval. Thermogenic action along Spleen Meridian of Foot Greater Yin was manifested as simultaneous skin temperature increase on right SP6 and SP10 at 5 min–10 min interval after needling SP6, which was helpful to illustrate the relationship between the characteristic of Deqi and needle stimulations.

  19. Δ9-tetrahydrocannabinol impairs the inflammatory response to influenza infection: role of antigen-presenting cells and the cannabinoid receptors 1 and 2.

    Science.gov (United States)

    Karmaus, Peer W F; Chen, Weimin; Crawford, Robert; Kaplan, Barbara L F; Kaminski, Norbert E

    2013-02-01

    Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has potent immune modulatory properties and can impair pathogen-induced immune defenses, which in part have been attributed to ligation of the cannabinoid receptors 1 (CB(1)) and 2 (CB(2)). Most recently, dendritic cells (DC) were identified for their potential to enhance influenza-induced immunopathology in mice lacking CB(1) and CB(2) (CB(1) (-/-)CB(2) (-/-)). This study focused on the modulation of the inflammatory immune response to influenza by Δ(9)-THC and the role of CB(1) and/or CB(2) as receptor targets for Δ(9)-THC. C57Bl/6 (wild type) and CB(1) (-/-)CB(2) (-/-) mice were administered Δ(9)-THC (75 mg/kg) surrounding the intranasal instillation of A/PR/8/34 influenza virus. Three days post infection (dpi), Δ(9)-THC broadly decreased expression levels of mRNA induced by the innate immune response to influenza, suppressed the percentage of interferon-gamma (IFN-γ)-producing CD4(+) and interleukin-17-producing NK1.1(+) cells, and reduced the influx of antigen-presenting cells (APC), including inflammatory myeloid cells and monocytes/macrophages, into the lung in a CB(1)- and/or CB(2)-dependent manner. Δ(9)-THC had little effect on the expression of CD86, major histocompatibility complex I (MHC I), and MHC II by APC isolated from the lung. In vitro studies demonstrated that lipopolysaccharide (LPS)-induced maturation was suppressed by Δ(9)-THC in bone marrow-derived DC (bmDC). Furthermore, antigen-specific IFN-γ production by CD8(+) T cells after coculture was reduced by Δ(9)-THC treatment of bmDC in a CB(1)- and/or CB(2)-dependent manner. Collectively, these studies suggest that Δ(9)-THC potently suppresses myeloid cell immune function, in a manner involving CB(1) and/or CB(2), thereby impairing immune responses to influenza infection.

  20. Brain kinin B1 receptor is upregulated by the oxidative stress and its activation leads to stereotypic nociceptive behavior in insulin-resistant rats.

    Science.gov (United States)

    Dias, Jenny Pena; Gariépy, Helaine De Brito; Ongali, Brice; Couture, Réjean

    2015-07-01

    Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it is highly expressed in models of diabetes mellitus. This study aims at determining: (1) whether B1R is induced in the brain of insulin-resistant rat through the oxidative stress; (2) the consequence of B1R activation on stereotypic nocifensive behavior; (3) the role of downstream putative mediators in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% D-glucose in their drinking water or tap water (controls) for 4 or 12 weeks, combined either with a standard chow diet or a diet enriched with α-lipoic acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding sites were assessed by autoradiography. Behavioral activity evoked by i.c.v. injection of the B1R agonist Sar-[D-Phe(8)]-des-Arg(9)-BK (10 μg) was measured before and after i.c.v. treatments with selective antagonists (10 μg) for kinin B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5) receptors or with the inhibitor of NOS (L-NNA). Results showed significant increases of B1R binding sites in various brain areas of glucose-fed rats that could be prevented by the diet containing α-lipoic acid. The B1R agonist elicited head scratching, grooming, sniffing, rearing, digging, licking, face washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which were absent after treatment with α-lipoic acid or antagonists/inhibitors. Data suggest that kinin B1R is upregulated by the oxidative stress in the brain of insulin-resistant rats and its activation causes stereotypic nocifensive behavior through the release of substance P, glutamate and NO. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Genetic association of the tachykinin receptor 1 TACR1 gene in bipolar disorder, attention deficit hyperactivity disorder, and the alcohol dependence syndrome.

    Science.gov (United States)

    Sharp, Sally I; McQuillin, Andrew; Marks, Michael; Hunt, Stephen P; Stanford, S Clare; Lydall, Greg J; Morgan, Marsha Y; Asherson, Philip; Curtis, David; Gurling, Hugh M D

    2014-06-01

    Single nucleotide polymorphisms (SNPs) in the tachykinin receptor 1 gene (TACR1) are nominally associated with bipolar affective disorder (BPAD) in a genome-wide association study and in several case-control samples of BPAD, alcohol dependence syndrome (ADS) and attention-deficit hyperactivity disorder (ADHD). Eighteen TACR1 SNPs were associated with BPAD in a sample (506 subjects) from University College London (UCL1), the most significant being rs3771829, previously associated with ADHD. To further elucidate the role of TACR1 in affective disorders, rs3771829 was genotyped in a second BPAD sample of 593 subjects (UCL2), in 997 subjects with ADS, and a subsample of 143 individuals diagnosed with BPAD and comorbid alcohol dependence (BPALC). rs3771829 was associated with BPAD (UCL1 and UCL2 combined: P = 2.0 × 10(-3)), ADS (P = 2.0 × 10(-3)) and BPALC (P = 6.0 × 10(-4)) compared with controls screened for the absence of mental illness and alcohol dependence. DNA sequencing in selected cases of BPAD and ADHD who had inherited TACR1-susceptibility haplotypes identified 19 SNPs in the promoter region, 5' UTR, exons, intron/exon junctions and 3' UTR of TACR1 that could increase vulnerability to BPAD, ADS, ADHD, and BPALC. Alternative splicing of TACR1 excludes intron 4 and exon 5, giving rise to two variants of the neurokinin 1 receptor (NK1R) that differ in binding affinity of substance P by 10-fold. A mutation in intron four, rs1106854, was associated with BPAD, although a regulatory role for rs1106854 is unclear. The association with TACR1 and BPAD, ADS, and ADHD suggests a shared molecular pathophysiology between these affective disorders. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

  2. First report of Giardia sp. and Cryptosporidium sp. in fecal samples in blue macaw (Anodorhynchus hyacinthinus in southern Brazil

    Directory of Open Access Journals (Sweden)

    Matheus Hillard Farret

    2010-09-01

    Full Text Available This study reports the gastrointestinal parasitism by Giardia sp. and Cryptosporidium sp. in blue macaw (Anodorhynchus hyacinthinus in the southern region of Brazil. Fecal samples of two species kept in captivity in the state of Rio Grande do Sul were analyzed by the direct smear method, centrifugal flotation technique with zinc sulfate and Kinyoun staining technique for research of parasites. Mixed infection by eggs of Capillaria, cysts of Giardia sp. and oocysts of Cryptosporidium sp. was observed. This is the first report this protozoa in blue macaw.

  3. Integrative Gene Cloning and Expression System for Streptomyces sp. US 24 and Streptomyces sp. TN 58 Bioactive Molecule Producing Strains

    Directory of Open Access Journals (Sweden)

    Samiha Sioud

    2009-01-01

    Full Text Available Streptomyces sp. US 24 and Streptomyces sp. TN 58, two strains producing interesting bioactive molecules, were successfully transformed using E. coli ET12567 (pUZ8002, as a conjugal donor, carrying the integrative plasmid pSET152. For the Streptomyces sp. US 24 strain, two copies of this plasmid were tandemly integrated in the chromosome, whereas for Streptomyces sp. TN 58, the integration was in single copy at the attB site. Plasmid pSET152 was inherited every time for all analysed Streptomyces sp. US 24 and Streptomyces sp. TN 58 exconjugants under nonselective conditions. The growth, morphological differentiation, and active molecules production of all studied pSET152 integrated exconjugants were identical to those of wild type strains. Consequently, conjugal transfer using pSET152 integration system is a suitable means of genes transfer and expression for both studied strains. To validate the above gene transfer system, the glucose isomerase gene (xylA from Streptomyces sp. SK was expressed in strain Streptomyces sp. TN 58. Obtained results indicated that heterologous glucose isomerase could be expressed and folded effectively. Glucose isomerase activity of the constructed TN 58 recombinant strain is of about eighteenfold higher than that of the Streptomyces sp. SK strain. Such results are certainly of importance due to the potential use of improved strains in biotechnological process for the production of high-fructose syrup from starch.

  4. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene

    Science.gov (United States)

    Berryman, Orion B.; Johnson, Charles A.; Vonnegut, Chris L.; Fajardo, Kevin A.; Zakharov, Lev N.; Johnson, Darren W.; Haley, Michael M.

    2015-01-01

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)–C(sp2) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2′-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N–H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF4− or HSO4−, where the sulfonamide arms rotate to the side opposite the pyridine N atom. PMID:26405435

  5. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene.

    Science.gov (United States)

    Berryman, Orion B; Johnson, Charles A; Vonnegut, Chris L; Fajardo, Kevin A; Zakharov, Lev N; Johnson, Darren W; Haley, Michael M

    2015-03-04

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)-C(sp 2 ) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2'-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N-H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF 4 - or HSO 4 - , where the sulfonamide arms rotate to the side opposite the pyridine N atom.

  6. Microfungi on the Pandanaceae: Linocarpon lammiae sp. nov., L. siamensis sp. nov. and L. suthepensis sp. nov. are described with a key to Linocarpon species from the Pandanaceae.

    Science.gov (United States)

    Thongkantha, S; Lumyong, S; Lumyong, P; Whitton, S R; McKenzie, E H C; Hyde, K D

    2003-01-01

    Linocarpon species are reported from Pandanaceae in Australia, Brunei, Hong Kong, Nepal, New Zealand, Philippines, Seychelles, Thailand and Vanuatu. Linocarpon lammiae sp. nov. were collected on decaying leaves of Pandanus tectorius in Hong Kong. Linocarpon siamensis sp. nov. and L. suthepensis sp. nov. were collected from decaying leaves of P. penetrans in Thailand. These taxa are described, illustrated and compared with Linocarpon species with similar ascospore morphology and dimensions. Included are a synoptic table, which compares the new species to similar known species, and a dichotomous key to species of Linocarpon known from members of the Pandanaceae.

  7. Synergistic Effect of Caffeine and Glucocorticoids on Expression of Surfactant Protein B (SP-B) mRNA

    Science.gov (United States)

    Fehrholz, Markus; Bersani, Iliana; Kramer, Boris W.; Speer, Christian P.; Kunzmann, Steffen

    2012-01-01

    Administration of glucocorticoids and caffeine is a common therapeutic intervention in the neonatal period, but possible interactions between these substances are still unclear. The present study investigated the effect of caffeine and different glucocorticoids on expression of surfactant protein (SP)-B, crucial for the physiological function of pulmonary surfactant. We measured expression levels of SP-B, various SP-B transcription factors including erythroblastic leukemia viral oncogene homolog 4 (ErbB4) and thyroid transcription factor-1 (TTF-1), as well as the glucocorticoid receptor (GR) after administering different doses of glucocorticoids, caffeine, cAMP, or the phosphodiesterase-4 inhibitor rolipram in the human airway epithelial cell line NCI-H441. Administration of dexamethasone (1 µM) or caffeine (5 mM) stimulated SP-B mRNA expression with a maximal of 38.8±11.1-fold and 5.2±1.4-fold increase, respectively. Synergistic induction was achieved after co-administration of dexamethasone (1 mM) in combination with caffeine (10 mM) (206±59.7-fold increase, pglucocorticoids and caffeine, achieved by accumulation of intracellular cAMP. This effect was mediated by a caffeine-dependent phosphodiesterase inhibition and by upregulation of both ErbB4 and the GR. These results suggested that caffeine is able to induce the expression of SP-transcription factors and affects the signaling pathways of glucocorticoids, amplifying their effects. Co-administration of caffeine and corticosteroids may therefore be of benefit in surfactant homeostasis. PMID:23272120

  8. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  9. 75 FR 42411 - Orders Finding That the SP-15 Financial Day-Ahead LMP Peak Daily Contract; SP-15 Financial Day...

    Science.gov (United States)

    2010-07-21

    ... COMMODITY FUTURES TRADING COMMISSION Orders Finding That the SP-15 Financial Day-Ahead LMP Peak Daily Contract; SP-15 Financial Day-Ahead LMP Off-Peak Daily Contract; SP-15 Financial Swap Real Time...-Peak Daily (``SQP'') contract; SP-15 Financial Swap Real Time LMP-Peak Daily (``SRP'') contract; NP-15...

  10. Kroyeria deetsi n.sp. (Kroyeriidae: Siphonostomatoida), a parasitic ...

    African Journals Online (AJOL)

    Kroyeria deetsi n.sp. (Kroyeriidae: Siphonostomatoida) is described from both sexes collected from the gills of spinner sharks, Carcharhinus brevipinna (Müller & Henle, 1839), captured in the Indian Ocean off the coast of South Africa. Kroyeria deetsi n.sp. can easily be distinguished from all of its congeners because the ...

  11. Evaluation of Cr (VI) remediation potential of Eichornia sp in ...

    African Journals Online (AJOL)

    Purpose: Evaluation of Cr (VI) removal by indigenous chromium resistant bacterial strains alone and in combination with Eichornia sp. Methods: Three chromium resistant bacterial strains S-4 Ochrobactrum grignonense, SF-5 Bacillus sp. and S-6 Ochrobactrum pseudogrignonenses were isolated from industrial effluent.

  12. Antibiotic Resistance in Salmonella sp and Escherichia coli Isolated ...

    African Journals Online (AJOL)

    Strains of Salmonella sp and E. coli isolated were significantly resistant to gentamicin, erythromycin, chloramphenicol, tetracycline, streptomycin, cefixine and ampicillin. Resistance to gentamicin was the least with 33-71% in Salmonella sp and 25-80% in E. coli. The level of drug resistance in these organisms is ascribed to ...

  13. Biochemical characterization of Fusarium oxysporum f . sp. cubense ...

    African Journals Online (AJOL)

    The Fusarium wilt caused by Fusarium oxyspoum f. sp. cubense (Foc) is a major biotic constraint for banana production. The characteristics of F. oxyspoum f. sp. cubense isolates were investigated using electrophoretic studies of isozyme and whole-cell protein. The morphological characteristics of the isolates were very ...

  14. LOCALIZATION OF SP22 ON HUMAN SPERM OF DIFFERING QUALITY

    Science.gov (United States)

    LOCALIZATION OF SP22 ON HUMAN SPERM OF DIFFERING QUALITY. AE Lavers*1, GR Klinefelter2, DW Hamilton1, KP Roberts1, 1University of Minnesota, Minneapolis, MN and 2US EPA, Research Triangle Park, NC. SP22 is a sperm membrane protein that has been implicated in sperm function d...

  15. Biochemical characterization of Fusarium oxysporum f. sp. cubense ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-25

    Jan 25, 2010 ... Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore – 570 006, India. Accepted 24 November, 2009. The Fusarium wilt caused by Fusarium oxyspoum f. sp. cubense (Foc) is a major biotic constraint for banana production. The characteristics of F. oxyspoum f. sp. cubense ...

  16. Effects of phosphate solubilizing microorganisms and Rhizobium sp ...

    African Journals Online (AJOL)

    Effects of Phosphate solubilizing microorganisms ( Glomus intraradices, Pseudomonas putida, P. alcaligenes, P. aeruginosa (Pa28), A. awamori) and Rhizobium sp. was observed on the growth, nodulation yield and root-rot disease complex of chickpea under field condition. Inoculation of Rhizobium sp. caused a greater ...

  17. HANSENULA WICKERHAMII SP. N., A NEW YEAST FROM FINNISH SOIL

    Science.gov (United States)

    Capriotti, Augusto

    1961-01-01

    Capriotti, Augusto (l'Università di Perugia, Perugia, Italy). Hansenula wickerhamii sp. n., a new yeast from Finnish soil. J. Bacteriol. 82:259–360. 1961.—Hansenula wickerhamii sp. n. is described; it was isolated from a Finnish soil, and is named in honor of Lynferd J. Wickerham. Images PMID:13690638

  18. Linking surfactant protein SP-D and IL-13

    DEFF Research Database (Denmark)

    Qaseem, Asif S; Sonar, Sanchaita; Mahajan, Lakshna

    2012-01-01

    Surfactant protein D (SP-D) is an innate immune molecule that plays a protective role against lung infection, allergy, asthma and inflammation. In vivo experiments with murine models have shown that SP-D can protect against allergic challenge via a range of mechanisms including inhibition...

  19. Biofixation of carbon dioxide by Chlorococcum sp. in a ...

    African Journals Online (AJOL)

    In this study, Chlorococcum sp. was cultured in a photobioreactor with a polytetrafluoroethene membrane sparger (PTFE) to study CO2 biofixation and microalgae growth. Daily variations of dissolved oxygen (DO), pH and dissolved CO2 were analyzed during batch culture of Chlorococcum sp. in the photobioreactor.

  20. Production of mycelium and blastospores of sp. in submerged culture

    African Journals Online (AJOL)

    Hirsutella sp. was grown in four liquid media containing either casamino acids, corn steep liquor, collagen peptone or casein peptone. These media were inoculated with a 7 day-old culture of mycelia and blastospores of Hirsutella sp. and the cultures incubated with shaking at 250 rpm at 26°C. The media containing corn ...

  1. Brachystelma nallamalayana sp. Nov. (Apocynaceae: Asclepiadoideae: Ceropegieae from India

    Directory of Open Access Journals (Sweden)

    K. Prasad

    2014-10-01

    Full Text Available Brachystelma nallamalayana sp. nov., collected from Nallamalais, the Eastern Ghats of Andhra Pradesh, India is described and illustrated. The new species is compared to its closest species, Brachystelma maculatum Hook. f. Brachystelma nallamalayana, sp. nov. is distinct from other species of Brachystelma in having ca 80cm high glabrous stems, peduncled cymes, basally united calyx lobes and biseriate corona.

  2. Effects of phosphate solubilizing microorganisms and Rhizobium sp ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... Effects of Phosphate solubilizing microorganisms (Glomus intraradices, Pseudomonas putida, P. alcaligenes, P. aeruginosa (Pa28), A. awamori) and Rhizobium sp. was observed on the growth, nodulation yield and root-rot disease complex of chickpea under field condition. Inoculation of. Rhizobium sp.

  3. Antioxidant activity of aqueous extract of a Tolypocladium sp ...

    African Journals Online (AJOL)

    Tolypocladium sp. Ts-1 was isolated from the fruiting body of a wild Cordyceps sinensis, one of the best known traditional Chinese medicine and health foods. The antioxidant activities of hot-water extracts from cultured mycelia of Tolypocladium sp. were assessed in different in vitro systems. The extracts showed ...

  4. Antioxidant activity of aqueous extract of a Tolypocladium sp. fungus ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-03

    Sep 3, 2008 ... Tolypocladium sp. Ts-1 was isolated from the fruiting body of a wild Cordyceps sinensis, one of the best known traditional Chinese medicine and health foods. The antioxidant activities of hot-water extracts from cultured mycelia of Tolypocladium sp. were assessed in different in vitro systems. The extracts ...

  5. Oncholaim~ jessicae n.sp. (Nematoda: Oncholaimidae) from fresh ...

    African Journals Online (AJOL)

    Oncholaim~ jessicae n.sp. (Nematoda: Oncholaimidae) from fresh water in the Transvaal. A. Coomans. Instituut voor Dierkunde, Rijksuniversiteit Gent, Gent, Belgium. J. Heyns. Department of Zoology, Rand Afrikaans University, Johannesburg. Oncholaimus jessicae n.sp. is described from several sites in the Blyde River ...

  6. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice

    Directory of Open Access Journals (Sweden)

    Mühlfeld Christian

    2007-10-01

    Full Text Available Abstract Background Surfactant protein D (SP-D deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. Methods SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. Main Results After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. Conclusion Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are

  7. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice.

    Science.gov (United States)

    Knudsen, Lars; Ochs, Matthias; Mackay, Rosemarie; Townsend, Paul; Deb, Roona; Mühlfeld, Christian; Richter, Joachim; Gilbert, Fabian; Hawgood, Samuel; Reid, Kenneth; Clark, Howard

    2007-10-03

    Surfactant protein D (SP-D) deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D) has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are characterized by decreased SP-D levels in the lung.

  8. Effects of substance P on identified neurons of the rat dorsal motor nucleus of the vagus.

    Science.gov (United States)

    Lewis, M W; Travagli, R A

    2001-07-01

    Previous evidence suggests that substance P (SP) activates subpopulations of neurons within the dorsal motor nucleus of the vagus (DMV). In this study we aimed at identifying these subpopulations in relation to their gastrointestinal projection organs or vagal branches and characterizing pharmacologically the SP response. Using whole cell patch-clamp recordings from identified gastrointestinal-projecting vagal motoneurons, we found that SP induced an inward current in all neuronal groups except for cecum-projecting cells. The lowest percentage of SP-responding neurons was found in fundus-projecting cells, where SP also had a concentration-response curve that was shifted to the left (P < 0.05). Independently from the projections, the SP response was reduced by sendide and MEN 10,376 and mimicked by a combination of [Sar(9)-Met(O(2))(11)]SP and alpha-neurokinin. SP and alpha-neurokinin also increased the frequency, but not the amplitude, of postsynaptic currents. In conclusion, we demonstrated that SP induces both pre- and postsynaptic effects on DMV neurons via activation of neurokinin NK(1) and NK(2) receptors. The magnitude of the SP response was correlated to the peripheral target organ.

  9. Post-neonatal drop in alveolar SP-A expression

    DEFF Research Database (Denmark)

    Stray-Pedersen, Arne; Vege, Ashild; Stray-Pedersen, Asbjorg

    2008-01-01

    BACKGROUND: Surfactant protein A (SP-A) is synthesized in the lung and is a part of the innate immune system. The aim of this study was to evaluate the expression of SP-A in lung tissue from fetuses, infants, children and adults with special regard to sudden infant death syndrome (SIDS). METHODS......: A total of 160 cases were studied; 19 fetuses and neonates, 59 SIDS and 49 explained infant deaths below 1 year of age, 19 toddlers and 14 adults. Immunohistochemical detection of SP-A using monoclonal antibodies was performed by microscopy of lung tissue specimens collected at autopsy. A scoring system...... was developed enabling semi-quantitative estimation of staining intensity and distribution. RESULTS: SP-A was detected in the terminal bronchioles and alveolar spaces of fetuses >35 weeks gestation. The intra-alveolar SP-A expression increased in the perinatal period followed by a marked drop in infants aged...

  10. SP-100 space reactor power system

    International Nuclear Information System (INIS)

    Kirpich, A.; Kruger, G.; Matteo, D.; Stephen, J.

    1990-01-01

    A generic flight system (GFS) design for a 100-kWe space reactor power (SP-100) system is presented. The design has evolved around issues such as the selection of a lithium liquid-metal-cooled reactor built of refractory metals and permitting operation in the range of 1300-1400 K; heat transport by lithium circulation using thermoelectrically driven liquid-metal pumps; thermoelectric power conversion; and waste heat rejection at approximately 800 K through lithium circulation to potassium heat pipe radiators. Various thermal-hydraulic analytical procedures have been utilized in the design of the reactor, ducting, hot-side and cold-side heat exchangers, circulating pumps, and heat pipe radiators. The physical and performance characteristics of the GFS and its power margins are estimated as a function of mission time

  11. Thermoelectric electromagnetic pump design for SP-100

    International Nuclear Information System (INIS)

    Collett, J.; Kugler, W.; Sinha, U.; Surjadi, T.

    1988-01-01

    This paper describes the design of the Thermoelectric Electromagnetic (TEM) pump used in the SP-100 space power system. The TEM pump is designed to pump liquid (molten) lithium (Li) coolant in the Primary Heat Transport Subsystem (PHTS) and Heat Rejection Subsystem (HRSS). The pump utilizes advanced Thermoelectric (TE) cells to generate electric current that induces magnetic flux in a Z-shaped magnetic structure. The electric current and magnetic flux pass through the liquid Li perpendicular to each other to create the pumping force. The TE cells are semiconductors located between rectangular ducts connected to the reactor hot PHTS piping and the cooler HRSS piping. The temperature difference (ΔT) across the TE cells generates the voltage to power the pump. The design provides a minimum mass, self-regulated pump, with no moving parts and self-powered by an internal temperature gradient

  12. SP-100 status and technology accomplishments

    International Nuclear Information System (INIS)

    Armijo, J.S.

    1989-01-01

    There are many space missions that require electric power in the 10-kW(electric) to 1-MW(electric) range. The SP-100 program will provide technology that demonstrates that a nuclear reactor heat source and passive thermoelectric conversion can reliably provide electrical power over this full range for 10 yr. Based on the generic flight system (GFS) design at 100 kW(electric), tests will be conducted to demonstrate that technologies required for the GFS have been validated. In addition, system-level tests will show that the GFS design and predictive capability to design at other power levels are well understood and meet an enveloping set of requirements. Technology and component testing has begun at General Electric (GE), its subcontractors, and several national laboratories. This paper reviews the significant progress made to date and major planned future tests with respect to the reference flight system, technology and component achievements, and nuclear assembly and integrated assembly tests

  13. Epitheliotropic lymphoma in a squirrel (Sciurus sp.).

    Science.gov (United States)

    Honnold, Shelley P; Arun, Iyampillai; Saturday, Greg; McLeod, Charles

    2007-09-01

    A 12-yr-old, intact male squirrel (Sciurus sp.) presented with a 15 mm-by-20 mm area of alopecia and plaque-like dermal thickening over the left caudolateral thorax. Routine diagnostic tests ruled out more common conditions that result in alopecia, such as dermatophytosis and acariasis. A punch biopsy was obtained under anesthesia and submitted for histopathologic evaluation. The diagnosis of epitheliotropic lymphoma was made, and follow-up surgical excision was performed. Histopathologic features were consistent with epitheliotropic lymphoma, and immunohistochemistry confirmed a T-cell origin. There was no local recurrence, new lesions, or evidence of metastasis 10 mo after surgical excision. To our knowledge, to date, epitheliotropic lymphoma has not been described in a squirrel.

  14. Chitinase Production by Streptomyces sp. ANU 6277

    Directory of Open Access Journals (Sweden)

    Kolla J.P. Narayana

    2009-12-01

    Full Text Available Chitinase production by a terrestrial Streptomyces sp. ANU 6277 was studied under sub-merged fermentation. Chitinase production started after 24 h of incubation and reached maximum levels after 60 h of cultivation. A high level of chitinase activity was observed in the culture medium with pH 6 at 35ºC. Culture medium amended with 1% chitin was found to be suitable for maximum production of chitinase. An optimum concentration of colloidal chitin for chitinase production was determined. Studies on the influence of additional carbon and nitrogen sources on chitinase production revealed that starch and yeast extract served as good carbon and nitrogen sources to enhance chitinase yield.Chitinase was purified from crude enzyme extract by single step gel filtration by Sephadex G-100. Purified chitinase of the strain exhibited a distinct protein band near 45 kDa by means of SDS-PAGE.

  15. Kinerja probiotik Bacillus sp. pada pendederan benih ikan lele Clarias sp. yang diinfeksi Aeromonas hydrophila

    Directory of Open Access Journals (Sweden)

    , Sukenda

    2016-12-01

    Full Text Available ABSTRACT This experiment was conducted to assess performance of Bacillus sp. probiotic on catfish juvenile Clarias sp. infected by Aeromonas hydrophila. The probiotic content in the diets were 0% (K+ and K-, 1%, and 2% in duplicates. This experiment used randomized design with four treatments and two replications. Juveniles with average body weight of 3.22±0.15 g/fish were reared in the 1.5×2.8×0.5 m3 pond with density of 800 fish/pond. Fish were reared for 30 days and fed three times a day at rate 8% of  total body weight. At day 31, catfish were challenged by A. hydrophila 0.1 mL (106 cfu/mL. Post infection observation was carried out ten days with density 10 fish/aquaria. The result showed that fish fed diet containing 2% probiotic gave the best probiotic performance with survival rate of catfish 83.33% after challenged, spesific growth rate 5.40%, and 0,75 of feed conversion ratio. The results of the blood profile showed significantly better results in the treatment of probiotics compared to the positive control after challenge test A. hydrophila. Probiotic Bacillus sp. has given as much as 2% on feed provides better performance on catfish juvenile. Keywords: probiotic, Bacillus sp., A. hydrophila, catfish juvenille, growth  ABSTRAK Penelitian ini bertujuan untuk menguji kinerja probiotik Bacillus sp. dalam pakan pada pendederan benih ikan lele Clarias sp. yang diinfeksi bakteri Aeromonas hydrophila. Penelitian ini menggunakan rancangan acak lengkap dengan empat perlakuan yaitu kandungan probiotik dalam pakan perlakuan yaitu 0% (K+ dan K-, 1%,  dan 2%, masing-masing dengan dua ulangan. Ikan lele yang digunakan memiliki bobot rata-rata 3,22±0,15 g/ekor, dipelihara dalam kolam terpal berukuran 1,5×2,8×0,5 m3 dengan kepadatan 800 ekor/kolam. Ikan dipelihara selama 30 hari dengan frekuensi pemberian pakan tiga kali sehari sebanyak 8% dari bobot tubuh ikan. Hari ke-31 benih lele diinjeksi bakteri A. hydrophila dosis 0,1 m

  16. The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1β, IL-23, and TNF-like 1A expression by monocytes.

    Science.gov (United States)

    Cunin, Pierre; Caillon, Antoine; Corvaisier, Murielle; Garo, Erwan; Scotet, Mari; Blanchard, Simon; Delneste, Yves; Jeannin, Pascale

    2011-04-01

    The nervous system influences immune responses through the release of neural factors such as neuropeptides. Among them, the tachykinin substance P (SP) signals via the neurokinin 1 receptor (NK-1R), which is expressed by various immune cells. We thereby analyzed in this paper whether tachykinins may participate in human CD4(+) Th cell polarization. We report that SP and hemokinin-1 (HK-1) upregulate IL-17A and IFN-γ production by human memory CD4(+) T cells without affecting IL-4 and IL-10 production. SP and HK-1 switch non-Th17-committed CD4(+) memory T cells into bona fide Th17 cells and Th1/Th17 cells. In contrast, SP and HK-1 do not modulate the polarization of naive CD4(+) T cells. SP- and HK-1-induced Th17 cell generation is mediated through NK-1R and requires the presence of monocytes. SP and HK-1 trigger IL-1β, IL-6, and TNF-α production, upregulate IL-23 production, and enhance TNF-like 1A expression on monocyte surface. Neutralization experiments demonstrated that IL-1β, IL-23, and TNF-like 1A are involved in the SP- and HK-1-induced Th17 cell. The other members of the tachykinin family, neurokinins A and B, have no effect on the differentiation of naive and memory T cells. These results thereby show that SP and HK-1 are novel Th17 cell-inducing factors that may act locally on memory T cells to amplify inflammatory responses.

  17. Neorickettsia risticii, Rickettsia sp. and Bartonella sp. in Tadarida brasiliensis bats from Buenos Aires, Argentina.

    Science.gov (United States)

    Cicuttin, Gabriel L; De Salvo, María N; La Rosa, Isabel; Dohmen, Federico E Gury

    2017-06-01

    Bats are potential reservoirs of many vector-borne bacterial pathogens. The aim of the present study was to detect species of Anaplasma, Ehrlichia, Neorickettsia, Rickettsia, Borrelia and Bartonella in Brazilian free-tailed bats (Tadarida brasiliensis, Molossidae) from Buenos Aires city, Argentina. Between 2012 and 2013, 61 T. brasiliensis from urban areas of Buenos Aires city were studied. The samples were molecularly screened by PCR and sequencing. Five bats (8.2%) were positive to Neorickettsia risticii, one (1.6%) was positive to Rickettsia sp. and three bats (4.9%) to Bartonella sp. For molecular characterization, the positive samples were subjected to amplification and sequencing of a fragment of p51 gene for N. risticii, a fragment of citrate synthase gene (gltA) for Rickettsia genus and a fragment of gltA for Bartonella genus. Phylogenetic tree was constructed using the maximum-likelihood method. Phylogenetic analysis of N. risticii detect in our study revealed that it relates to findings in the USA West Coast; Rickettsia sp. detected is phylogenetically within R. bellii group, which also includes many other Rickettsia endosymbionts of insects; and Bartonella sp. found is related to various Bartonella spp. described in Vespertilionidae bats, which are phylogenetically related to Molossidae. Our results are in accordance to previous findings, which demonstrate that insectivorous bats could be infected with vector-borne bacteria representing a potential risk to public health. Future research is necessary to clarify the circulation of these pathogens in bats from Buenos Aires. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  19. From spent graphite to amorphous sp2+sp3 carbon-coated sp2 graphite for high-performance lithium ion batteries

    Science.gov (United States)

    Ma, Zhen; Zhuang, Yuchan; Deng, Yaoming; Song, Xiaona; Zuo, Xiaoxi; Xiao, Xin; Nan, Junmin

    2018-02-01

    Today, with the massive application of lithium ion batteries (LIBs) in the portable devices and electric vehicles, to supply the active materials with high-performances and then to recycle their wastes are two core issues for the development of LIBs. In this paper, the spent graphite (SG) in LIBs is used as raw materials to fabricate two comparative high-capacity graphite anode materials. Based on a microsurgery-like physical reconstruction, the reconstructed graphite (RG) with a sp2+sp3 carbon surface is prepared through a microwave exfoliation and subsequent spray drying process. In contrast, the neural-network-like amorphous sp2+sp3 carbon-coated graphite (AC@G) is synthesized using a self-reconfigurable chemical reaction strategy. Compared with SG and commercial graphite (CG), both RG and AC@G have enhanced specific capacities, from 311.2 mAh g-1 and 360.7 mAh g-1 to 409.7 mAh g-1 and 420.0 mAh g-1, at 0.1C after 100 cycles. In addition, they exhibit comparable cycling stability, rate capability, and voltage plateau with CG. Because the synthesis of RG and AC@G represents two typical physical and chemical methods for the recycling of SG, these results on the sp2+sp3 carbon layer coating bulk graphite also reveal an approach for the preparation of high-performance graphite anode materials derived from SG.

  20. Phospholipids and protein adaptation of Pseudomonas sp. to the xenoestrogen tributyltin chloride (TBT).

    Science.gov (United States)

    Bernat, Przemysław; Siewiera, Paulina; Soboń, Adrian; Długoński, Jerzy

    2014-09-01

    A tributyltin (TBT)-resistant strain of Pseudomonas sp. isolated from an overworked car filter was tested for its adaptation to TBT. The isolate was checked for organotin degradation ability, as well as membrane lipid and cellular protein composition in the presence of TBT. The phospholipid profiles of bacteria, grown with and without increased amounts of TBT, were characterized using liquid chromatography/electrospray ionization/mass spectrometry. The strain reacted to the biocide by changing the composition of its phospholipids. TBT induced a twofold decline in the amounts of many molecular species of phosphatidylglycerol and an increase in the levels of phosphatidic acid (by 58%) and phosphatidylethanolamine (by 70%). An increase in the degree of saturation of phospholipid fatty acids of TBT exposed Pseudomonas sp. was observed. These changes in the phospholipid composition and concentration reflect the mechanisms which support optimal lipid ordering in the presence of toxic xenobiotic. In the presence of TBT the abundances of 16 proteins, including TonB-dependent receptors, porins and peroxidases were modified, which could indicate a contribution of some enzymes to TBT resistance.

  1. Wnt-mediated down-regulation of Sp1 target genes by a transcriptional repressor Sp5

    Czech Academy of Sciences Publication Activity Database

    Fujimura, Naoko; Vacík, Tomáš; Machoň, Ondřej; Vlček, Čestmír; Scalabrin, S.; Speth, M.; Diep, D.; Krauss, S.; Kozmik, Zbyněk

    2007-01-01

    Roč. 282, č. 2 (2007), s. 1225-1237 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z50520514 Keywords : Wnt -mediated signaling * Sp5 transcription factor * Sp1 target genes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.581, year: 2007

  2. Desulfuromonas svalbardensis sp nov and Desulfuromusa ferrireducens sp nov., psychrophilic, Fe(III)-reducing bacteria isolated from Arctic sediments, Svalbard

    DEFF Research Database (Denmark)

    Vandieken, V.; Mussmann, M.; Niemann, Hans Henrik

    2006-01-01

    succinoxidans Gylac(T) (95.9%) within the Deltaproteobacteria. Strains 112(T) and 102(T) therefore represent novel species, for which the names Desulfuromonas svalbardensis sp. nov. (type strain 112(T) = DSM 16958(T) = JCM 12927(T)) and Desulfuromusa ferrireducens sp. nov. (type strain 102(T) = DSM 16956 (T...

  3. Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers

    International Nuclear Information System (INIS)

    Chen Yongxin; Guo Yingqiu; Ge Xijin; Itoh, Hirotaka; Watanabe, Akira; Fujiwara, Takeshi; Kodama, Tatsuhiko; Aburatani, Hiroyuki

    2006-01-01

    In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Gal4-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer. To study the effects of the Sp5 protein on growth properties of human cancer cells and facilitate the identification of its downstream genes, we combined an inducible gene expression system with microarray analysis to screen for its transcriptional targets. Transfer of Sp5 into MCF-7 cells that expressed no detectable endogenous Sp5 protein elicited significant growth promotion activity. Several of the constitutively deregulated genes have been associated with tumorigenesis (CDC25C, CEACAM6, TMPRSS2, XBP1, MYBL1, ABHD2, and CXCL12) and Wnt/β-Catenin signaling pathways (BAMBI, SIX1, IGFBP5, AES, and p21 WAF1 ). This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against human cancers

  4. Direct transesterification of Oedogonium sp. oil be using immobilized isolated novel Bacillus sp. lipase.

    Science.gov (United States)

    Sivaramakrishnan, Ramachandran; Muthukumar, Karuppan

    2014-01-01

    This work emphasizes the potential of the isolated Bacillus sp. lipase for the production of fatty acid methyl ester by the direct transesterification of Oedogonium sp. of macroalgae. Dimethyl carbonate was used as the extraction solvent and also as the reactant. The effect of solvent/algae ratio, water addition, catalyst, temperature, stirring and time on the direct transesterification was studied. The highest fatty acid methyl ester yield obtained under optimum conditions (5 g Oedogonium sp. powder, 7.5 ml of solvent (dimethyl carbonate)/g of algae, 8% catalyst (%wt/wt of oil), distilled water 1% (wt/wt of algae), 36 h, 55°C and 180 rpm) was 82%. Final product was subjected to thermogravimetric analysis and (1)H NMR analysis. The results showed that the isolated enzyme has good potential in catalyzing the direct transesterification of algae, and the dimethyl carbonate did not affect the activity of the isolated lipase. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  5. PENGGUNAAN EKSTRAK BIOTA LAUTAGLAOPHENIA SP. UNTUK MENGENDALIKANFUSARIUM OXYSPORUM F.SP.VANILLAE PENYEBAB BUSUK BATANG VANILI

    Directory of Open Access Journals (Sweden)

    I KETUT SUADA

    2012-11-01

    Full Text Available The Use of Aglaophenia sp. Marine Biota Extract to Control Fusarium oxysporum f. sp. vanillae, a Pathogen of Vanilla Stem Rot The use of marine biota for organic fungicide material has enormous potential to be developed. The organic fungicide was directed to substitute synthetic fungicide for vanilla cultivation. Application of synthetic fungicide degraded environmental quality, therefore its applications does not support sustainable agriculture. The objective of this research was to know the potence of Aglaopheniain suppressing the growth of F. oxysporum f. sp.vanillae, the pathogen of vanilla stem rot. The research was done in green house in order to find the best substance for formulation of the extract. The substances screened were water, tween-80, and detergents with two different concentrations. Subsequently, two best formulas were chosen to apply in endemic area in Tabanan. The green house and field trial research used Randomized Completely Design with three and five replications respectively. Results showed that tween was the best substance used for formulation and concentration of 0.2% was better than other concentrations. The extract diluted in tween-80 on the concentration of 0.2% showed the lowest rot on stem, longest shoot, and the most leaves on vanilla shoot. Because of its significant performance, the 0.1% extract ofAglaopheniain 0.1% tween-80 was proposed to be the best formula to suppress the vanilla stem rot disease.

  6. Characterization of rabbit ileal receptors for Clostridium difficile toxin A. Evidence for a receptor-coupled G protein

    Energy Technology Data Exchange (ETDEWEB)

    Pothoulakis, C.; LaMont, J.T.; Eglow, R.; Gao, N.; Rubins, J.B.; Theoharides, T.C.; Dickey, B.F. (Boston Univ. School of Medicine, MA (USA))

    1991-07-01

    The purpose of this study was to characterize the surface receptor for toxin A, the enterotoxin from Clostridium difficile, on rabbit intestinal brush borders (BB) and on rat basophilic leukemia (RBL) cells. Purified toxin A was radiolabeled using a modified Bolton-Hunter method to sp act 2 microCi/micrograms, with retention of full biologic activity. 3H-Toxin A bound specifically to a single class of receptors on rabbit BB and on RBL cells with dissociation constants of 5.4 x 10(-8) and 3.5 x 10(-8) M, respectively. RBL cells were highly sensitive to toxin A (cell rounding) and had 180,000 specific binding sites per cell, whereas IMR-90 fibroblasts were far less sensitive to toxin A and lacked detectable specific binding sites. Exposure of BB to trypsin or chymotrypsin significantly reduced 3H-toxin A specific binding. Preincubation of BB with Bandeirea simplicifolia (BS-1) lectin also reduced specific binding, and CHAPS-solubilized receptors could be immobilized with WGA-agarose. The addition of 100 nM toxin A accelerated the association of 35S-GTP gamma S with rabbit ileal BB, and preincubation of BB with the GTP analogues GTP gamma S or Gpp(NH)p, significantly reduced 3H-toxin A specific binding. Our data indicate that the membrane receptor for toxin A is a galactose and N-acetyl-glucosamine-containing glycoprotein which appears to be coupled to a G protein.

  7. Kinetics of petroleum oil biodegradation by a consortium of three protozoan isolates (Aspidisca sp., Trachelophyllum sp. and Peranema sp.

    Directory of Open Access Journals (Sweden)

    L. Kachieng’a

    2017-09-01

    Full Text Available Petroleum oil is a complex mixture of substances, the majority of which are hydrocarbons; the latter represent an extremely important and heterogeneous group of compounds that find their way into water resources by anthropogenic or natural ways. The majority of toxic hydrocarbon components of petroleum are biodegradable, where bioremediation using microbial species has become an integral process for the restoration of oil-polluted areas. In this study, three bioremediation processes, namely natural attenuation, nutrient supplementation by adding glucose and biostimulation by adding Tween® 80, were carried out in various petroleum hydrocarbon concentrations in polluted water media using a consortium of three protozoan isolates (Aspidisca sp., Trachelophyllum sp. and Peranema sp.. A first-order kinetics model was fitted to the biodegradation data to evaluate the biodegradation rate and to determine the corresponding half-life time. First-order kinetics satisfactorily described the biodegradation of the petroleum-based contaminants under abiotic conditions. The results showed an increase in the percentage removal of petroleum oil at the lower petroleum concentrations and a gradual percentage decrease in removing petroleum oil residues occurred when there was an increase in the initial concentrations of the petroleum oil: 39%, 27%, 22%, 12%, 10% for various petroleum oil concentrations of 50, 100, 150, 200, 250 mg/L, respectively. A similar trend was also observed in the glucose-supplemented culture media where the reduction was 45% and 78% for petroleum concentrations of 250 mg/L and 50 mg/L, respectively. Biodegradation of between 33 and 90% was achieved at a Tween® 80 concentration of between 50 mg/L and 250 mg/L. The degradation rate constants for the natural attenuation process ranged between ≥0 to ≤0.50, ≥0 to ≤0.35, ≥0 to ≤0.25, ≥0 to ≤ 0.14 and ≥ 0 to ≤0.11 for petroleum oil concentrations varying from 50, 100, 150

  8. A sp2+sp3 hybridized carbon allotrope transformed from AB stacking graphyne and THD-graphene

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2018-01-01

    Full Text Available New carbon allotropes can be designed by combining sp, sp2 and sp3 three hybridization states. And the hybridization states or coordination numbers of carbon atoms can be changed by applying high pressure on carbon materials. In this study, a common high pressure phase (named as TBBC transformed from AB-stacking graphyne or THD-graphene is predicted. Its kinetic stability is examined using finite displacement method. We find that the sp2 and sp3 hybridized carbon atoms behave different vibration features at high frequency region. Both graphene-like and diamond-like vibration peaks occurs. Phase transition energy barriers from both graphyne and THD-graphene to TBBC are estimated. Electronic structure calculations show that the TBBC is an indirect semiconductor with a bandgap of 0.66 eV. The ideal tensile strength of TBBC is high in [0001] and [11¯00] directions, but is weak along [12¯10] direction.

  9. A sp2+sp3 hybridized carbon allotrope transformed from AB stacking graphyne and THD-graphene

    Science.gov (United States)

    Zhang, Yu; Shang, Jiacheng; Fu, Weida; Zeng, Li; Tang, Tao; Cai, Yingxiang

    2018-01-01

    New carbon allotropes can be designed by combining sp, sp2 and sp3 three hybridization states. And the hybridization states or coordination numbers of carbon atoms can be changed by applying high pressure on carbon materials. In this study, a common high pressure phase (named as TBBC) transformed from AB-stacking graphyne or THD-graphene is predicted. Its kinetic stability is examined using finite displacement method. We find that the sp2 and sp3 hybridized carbon atoms behave different vibration features at high frequency region. Both graphene-like and diamond-like vibration peaks occurs. Phase transition energy barriers from both graphyne and THD-graphene to TBBC are estimated. Electronic structure calculations show that the TBBC is an indirect semiconductor with a bandgap of 0.66 eV. The ideal tensile strength of TBBC is high in [0001] and [1 1 ¯ 00 ] directions, but is weak along [1 2 ¯ 10 ] direction.

  10. DAN IDENTIFIKASI PATOGEN POTENSIAL YANG MENGINFEKSI IKAN RAINBOW (Melanotaenia sp.

    Directory of Open Access Journals (Sweden)

    Lili Sholichah

    2014-03-01

    Full Text Available Pemeliharaan ikan rainbow (Melanotaenia sp. di Balai Penelitian dan Pengembangan Budidaya Ikan Hias selalu terjadi kematian secara bertahap mulai calon induk hingga proses pemijahan. Hal ini terjadi berulang kali sehingga ketersediaan induk Melanotaenia sp. sangat terancam. Ikan ini berasal dari Papua yang diperoleh mengandalkan penangkapan di alam. Tujuan dari penelitian ini adalah untuk menginventarisir dan mengidentifikasi berbagai patogen (parasit, jamur, bakteri potensial yang menginfeksi ikan rainbow yang dipelihara di dalam akuarium berukuran 50 cm x 50 cm x 50 cm dengan sistem aliran air stagnan. Tiga jenis rainbow yang dipelihara yaitu: rainbow Sungai Salawati, asal Sungai Sawiat, dan asal Danau Kurumoi. Setiap ikan masing-masing berjumlah 100 ekor dipelihara di akuarium dengan penambahan batu karang dan tanpa penambahan karang (kontrol ke dalam akuarium. Ikan diberi pakan sekenyangnya berupa jentik nyamuk dan cacing rambut beku setiap pagi dan sore hari. Sampling dilakukan secara random sebulan sekali dan secara unrandom setiap ada kejadian ikan sakit. Gejala klinis ikan yang sakit sebagai berikut: ikan berenang di permukaan dan menggosok-gosokkan badan di dinding akuarium, nafsu makan berkurang, gerakan berputar-putar, warna memudar menjadi putih, penekanan warna hitam pada sirip punggung dan perut meningkat, pendarahan pada perut, lendir berlebihan dan sangat berbau, serta sisik berdiri/terbuka. Diagnosa dan deteksi penyakit awal berupa pengamatan parasit baik ektoparasit maupun endoparasit, pengamatan dan isolasi jamur pada media selektif jamur, dan isolasi bakteri dilakukan untuk mengetahui jenis-jenis patogen yang menginfeksi ketiga jenis ikan rainbow. Selanjutnya dilakukan uji histologi dan analisa DNA beberapa patogen. Hasil pengamatan diperoleh patogen berupa parasit (Ichthyophthirius sp., Dactylogyrus sp., Gyrodactylus sp., dan Trichodina sp. dan bakteri (Aeromonas hydrophila, Acinetobacter sp

  11. adrenergic receptor with preeclampsia

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... expenditure and lipolysis. The mechanisms underlying lipolytic resistance to catecholamines in obesity are not clear and may include desensitization of ADRB2 function. (Yamada et al., 1999). Many studies have reported on the relationship between obesity and genetic variants in β-2 adrenergic receptors ...

  12. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  13. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...

  14. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  15. Genetic polymorphism of horse serum protein 3 (SP3).

    Science.gov (United States)

    Juneja, R K; Sandberg, K; Kuryl, J; Gahne, B

    1989-01-01

    Two-dimensional agarose gel (pH 8.6)-horizontal polyacrylamide gel (pH 9.0) electrophoresis of horse serum samples, followed by general protein staining, revealed genetic polymorphism of an unidentified protein tentatively designated serum protein 3 (SP3). The SP3 fractions appeared distinctly when a 14% concentration of acrylamide was used in the separation gels. The 2-D mobilities of SP3 fractions were quite similar to that of albumin. Family data were consistent with the hypothesis that the observed SP3 phenotypes were controlled by four co-dominant, autosomal alleles (D, F, I, S). Evidence was provided that the F allele can be further divided into two alleles (F1 and F2); the mobilities of F1 and F2 variants were very similar. Each of the SP3 alleles gave rise to one fraction and each of the heterozygous types showed two fractions. More than 600 horses representing five different breeds (Swedish Trotter, North-Swedish Trotter, Thoroughbred, Arab and Polish Tarpan) were typed for SP3, and allele frequency estimates were calculated. SP3 was highly polymorphic in all breeds studied.

  16. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking...... the phenomenon of blockade of angiotensin-(1-7) [Ang-(1-7)] actions by AT2R antagonists and vice versa. Such mechanisms may comprise dimerization of the receptors or dimerization-independent mechanisms such as lack of specificity of the receptor ligands used in the experiments or involvement of the Ang-(1...

  17. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia

    2012-01-01

    and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1), a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists), or the neuropeptide...... substance P (SP), which is released from sensory nerve terminals by capsaicin, acrolein or CS), produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue) in bronchoalveolar lavage (BAL...

  18. Cytotoxic effects of the anthraquinone derivatives 1'-deoxyrhodoptilometrin and (S)-(-)-rhodoptilometrin isolated from the marine echinoderm Comanthus sp.

    Science.gov (United States)

    Wätjen, Wim; Ebada, Sherif S; Bergermann, Anja; Chovolou, Yvonni; Totzke, Frank; Kubbutat, Michael H G; Lin, Wenhan; Proksch, Peter

    2017-03-01

    We investigated cytotoxic effects of the anthraquinone derivatives 1'-deoxyrhodoptilometrin (SE11) and (S)-(-)-rhodoptilometrin (SE16) isolated from the marine echinoderm Comanthus sp. in two tumor cell lines (C6 glioma, Hct116 colon carcinoma). Both compounds showed cytotoxic effects, with SE11 [IC 50 -value (MTT assay): 13.1 µM in Hct116 cells] showing a higher potency to induce apoptotic and necrotic cell death. No generation of oxidative stress was detectable (DCF assay), and also no modulation of Nrf2/ARE and NFκB signaling could be shown. Investigation of 23 protein kinases associated with cell proliferation, survival, metastasis, and angiogenesis showed that both compounds were potent inhibitors of distinct kinases, e.g., IGF1-receptor kinase, focal adhesion kinase, and EGF receptor kinase with SE11 being a more potent compound (IC 50 values: 5, 18.4 and 4 µM, respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the inhibition of EGF receptor kinase by this compound. Since an inhibition of the EGF receptor/MAPK pathway is an important target for diverse cytostatic drugs, we suggest that the anthraquinone derivative 1'-deoxyrhodoptilometrin (SE11) may be an interesting lead structure for the development of new anticancer drugs.

  19. HER2 evaluation using the novel rabbit monoclonal antibody SP3 and CISH in tissue microarrays of invasive breast carcinomas.

    Science.gov (United States)

    Ricardo, Sara Alexandra Vinhas; Milanezi, Fernanda; Carvalho, Sílvia Teresa; Leitão, Dina Raquel Aguilera; Schmitt, Fernando Carlos Lander

    2007-09-01

    Laboratory methods for HER2 assessment currently include immunohistochemical (IHC) methods (measuring protein overexpression) and fluorescence in situ hybridisation (FISH) (measuring gene amplification). The measure of HER2 protein by IHC is usually assessed by the mouse monoclonal antibody CB11, and polyclonal antibodies (Herceptest) directed against the internal portion of the receptor. Recently, chromogenic in situ hybridisation (CISH), in which HER2 is detected by a peroxidase reaction and the gene amplification can be determined by regular bright-field microscopy, has emerged as an alternative to FISH. To evaluate the status of HER2 in tissue microarrays (TMAs) of invasive breast cancer using the novel rabbit monoclonal antibody SP3 directed against the external portion of HER2, and correlate the results with CB11 and CISH. IHC was performed with two antibodies (CB11 and SP3) and CISH for HER2 in 10 TMA blocks with 190 formalin-fixed paraffin-embedded cases of invasive breast carcinomas. The correlation between SP3 and CB11 was significant (pCISH (pCISH, shows that this novel antibody is a reliable candidate to evaluate the expression of HER2 in breast cancer.

  20. Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

    Science.gov (United States)

    Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

    2013-12-01

    The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

  1. Efektivitas Ovitrap Bambu terhadap Jumlah Jentik Aedes sp yang Terperangkap

    Directory of Open Access Journals (Sweden)

    Wiwit Aditama

    2015-05-01

    places of 10 subdistricts. Data of trapped Aedes sp larvae numbers was collected four times repeatedly within one week time-lapse. Analysis was conducted using the mean number of larvae in ovitraps and ovitrap index. The number of Aedes sp larvae trapped was 1,265. The most effective ovitrap is piece of bamboo, mean = 123, p value = 0.006, HI = 10.01% (16.66 26.67%, CI = 36.8% (336.06 - 39.74%, BI = 29.97% (73.33 - 103.3%. Health authorities should promote bamboo ovitrap, especially to public as an effort to control Aedes sp.

  2. Pengaruh Perbedaan Konsentrasi Ekstrak Sargassum sp. dan Lama Penyimpanan terhadap Oksidasi Lemak pada Fillet Ikan Patin (Pangasius sp.

    Directory of Open Access Journals (Sweden)

    Fatin Hidayati

    2017-05-01

    Full Text Available ABSTRAK Ikan patin merupakan ikan air tawar yang mengandung lemak dan protein tinggi sehingga apabila dilakukan penyimpanan rentan terjadi oksidasi yang mengakibatkan ketengikan. Sargassum sp. dengan kandungan fenol dan flavonoid mampu menghambat terjadinya oksidasi pada fillet ikan patin. Penelitian ini bertujuan untuk mengetahui pengaruh perbedaan ekstrak Sargassum sp. dan lama penyimpanan dalam menghambat terjadinya oksidasi pada fillet ikan patin. Materi yang digunakan dalam penelitian ini adalah ekstrak Sargassum sp. dan fillet ikan patin. Metode penelitian yang digunakan adalah experimental laboratories dengan menggunakan Rancangan Acak Lengkap (RAL faktorial dengan 2 faktor yaitu konsentrasi ekstrak Sargassum sp. (0%, 1%, 1,5% dan 2% dan lama penyimpanan (hari ke-0, hari ke-2, hari ke-4, dan hari ke-6. Hasil penelitian menunjukkan bahwa perbedaan penambahan konsentrasi ekstrak Sargassum sp. dan lama penyimpanan memberikan pengaruh nyata terhadap nilai PV, nilai TBA, kadar lemak, kadar protein, kadar air serta organoleptik (P < 0,05. Hasil penelitian tahap I didapatkan rendemen Sargassum sp. dengan pelarut etanol 96% sebesar 1,39%, kandungan fenol 1,813%, flavonoid 0,278% dan aktivitas antioksidan 99,1659 ppm (kuat. Hasil penelitian tahap II didapatkan nilai PV berkisar antara 2,03 - 19,82 meq/kg, nilai TBA 0,63 - 6,72 mg.mal/kg. Konsentrasi 1,5% merupakan konsentrasi terbaik ekstrak Sargassum sp. dalam menghambat oksidasi lemak pada fillet ikan patin selama penyimpanan. Kata kunci: Antioksidan, Ekstrak Sargassum sp., Lama Penyimpanan, Oksidasi lemak, Fillet Ikan patin ABSTRACT Catfish is a freshwater fish that contain high fat and protein so that if its stored it will susceptible to oxidation process which leads to rancidity. Sargassum sp. with its phenolic and flavonoid content are able to inhibit the oxidation process in catfish fillet. This research was aimed to know the effects of different concentrations of Sargassum sp. extracts and

  3. Description of Pristina armata n. sp. (Clitellata: Naididae: Pristininae) from a carnivorous plant (Nepenthes sp.) in Borneo, Indonesia.

    Science.gov (United States)

    Schenková, Jana; Čermák, Václav

    2013-01-01

    A new clitellate species of Pristininae (Naididae), Pristina armata n. sp., found in the pitcher of the carnivorous plant Nepenthes sp., is reported from East Kalimantan, Indonesia. P. armata n. sp. is a very small clitellate, less than 1 mm long in fixed state, and without proboscis on the prostomium. Signs of reproduction by paratomy were observed, but the generic placement remains preliminary because sexually mature individuals were not found. P. armata n. sp. is characterized by giant hook-like dorsal chaetae at IV. The description of P. armata n. sp. was based on six fixed specimens of different size and stage of development. Noteworthy is the habitat of P. armata n. sp. in Nepenthes pitchers, this being the first clitellate species described from such a habitat. P. armata n. sp. may be a member of the nepenthebionts' community, realizing its life cycle inside the digestive fluid of the Nepenthes pitcher, or it belongs to nepenthephiles, species that commonly occur in this habitat but do not specialize on it.

  4. The antipsychotic-like effects in rodents of YQA31 involve dopamine D3 and 5-HT1A receptor.

    Science.gov (United States)

    Gou, Hong-Yan; Sun, Xue; Li, Fei; Wang, Zhi-Yuan; Wu, Ning; Su, Rui-Bin; Cong, Bin; Li, Jin

    2017-12-01

    We previously reported that YQA31 is a dopamine D3 receptor antagonist with modest 5-HT1A receptor affinity and that it exhibits antipsychotic properties in animal models of schizophrenia. However, the contributions of D3 and 5-HT1A receptors in the anti-psychotic effects of YQA31 are not clear. The current study evaluated the role of these two receptors in the effect of YQA31 on the hyperactivity and novel object recognition deficit in mice. We used dopamine D3 receptor knockout mice and 5-HT1A receptor antagonist WAY100635 pretreatment, respectively, to investigate the involvement of these receptors in the effects of YQA31. The anti-psychotic effects were tested by inducing hyperlocomotion with methamphetamine or MK-801 and by inducing novel object recognition deficit with MK-801, which are the animal models to represent a positive symptom and a cognitive disorder. YQA31 significantly inhibited MK-801-induced hyperlocomotion and novel object recognition deficit in WT mice, which was significantly inhibited by dopamine D3 receptor knockout. The 5-HT1A receptor antagonist, WAY100635, also blocked the effect of YQA31 in MK-801-induced novel object recognition deficit but not hyperlocomotion. The effect of YQA31 on methamphetamine-induced hyperlocomotion was not reversed by either dopamine D3 receptor knockout or WAY100635 pretreatment. These results demonstrate the different roles of dopamine D3 and 5-HT1A receptors in the anti-psychotic effects of YQA31. Both dopamine D3 and 5-HT1A receptors contributed to the effects of YQA31 on the inhibition of MK-801-induced novel object recognition deficit, and the dopamine D3 receptor mediated the inhibiting effect of YQA31 on hyperlocomotion induced by MK-801. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  5. The miR9863 family regulates distinct Mla alleles in barley to attenuate NLR receptor-triggered disease resistance and cell-death signaling

    Science.gov (United States)

    Barley Mla alleles encode coiled-coil (CC), nucleotide binding and leucine-rich repeat (NB-LRR) intracellular receptors that trigger isolate-specific immune responses against the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). How Mla or NB-LRR genes in grass species are regulated at p...

  6. Plant growth promoting properties of Halobacillus sp. and Halomonas sp. in presence of salinity and heavy metals.

    Science.gov (United States)

    Desale, Prithviraj; Patel, Bhargav; Singh, Sukrit; Malhotra, Aakshi; Nawani, Neelu

    2014-08-01

    Salinity and heavy metal stress are challenging problems in agriculture. Here we report the plant growth promoting ability of three moderate halophiles, Halobacillus sp. ADN1, Halomonas sp. MAN5, and Halobacillus sp. MAN6, in presence of both salinity and heavy metal stress. Halobacillus sp. ADN1, Halomonas sp. MAN5, and Halobacillus sp. MAN6 can tolerate 25, 21, and 29% NaCl, respectively and grow in presence of 1 mM cobalt, cadmium, and nickel and 0.04 mM mercury and 0.03 mM silver. Halobacillus sp. ADN1, Halomonas sp. MAN5, and Halobacillus sp. MAN6 produced 152.5, 95.3, and 167.3 µg/ml indole acetic acid (IAA) and could solubilize 61, 53, and 75 parts per million (ppm) phosphate, respectively in the presence of 15% NaCl. The production of IAA and solubilization of phosphate was well retained in the presence of salinity and heavy metals like 1 mM cadmium, 0.7 mM nickel, 0.04 mM mercury, and 0.03 mM silver. Besides, the strains showed amylase and protease activities and could produce hydrogen cyanide and ammonia in presence of salinity and heavy metals. A mixture of three strains enhanced the root growth of Sesuvium portulacastrum under saline and heavy metal stress, where the root length increased nearly 4.5 ± 0.6 times and root dry weight increased 5.4 ± 0.5 times as compared to control. These strains can thus be useful in microbial assisted phytoremediation of polluted saline soils. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Lactobacillus oeni sp. nov., from wine.

    Science.gov (United States)

    Mañes-Lázaro, Rosario; Ferrer, Sergi; Rosselló-Mora, Ramón; Pardo, Isabel

    2009-08-01

    Ten Lactobacillus strains, previously isolated from different Bobal grape wines from the Utiel-Requena Origin Denomination of Spain, were characterized phylogenetically, genotypically and phenotypically. The 16S rRNA genes were sequenced and phylogenetic analysis showed that they form a tight phylogenetic clade that is closely related to reference strains Lactobacillus satsumensis NRIC 0604T, 'Lactobacillus uvarum' 8 and Lactobacillus mali DSM 20444T. DNA-DNA hybridization results confirmed the separation of the strains from other Lactobacillus species. Genotypically, the strains could be differentiated from their closest neighbours by 16S amplified rDNA restriction analysis and random amplified polymorphic DNA patterns. The strains were Gram-staining-positive, facultatively anaerobic rods that did not exhibit catalase activity. Phenotypically, they could be distinguished from their closest relatives by several traits such as their inabilities to grow at pH 3.3, to ferment sucrose, amygdalin and arbutin or to hydrolyse aesculin. The characteristics of the ten wine isolates suggest that they represent a novel species, for which the name Lactobacillus oeni sp. nov. is proposed. The type strain is 59bT (=CECT 7334T=DSM 19972T).

  8. Cellulomonas bogoriensis sp. nov., an alkaliphilic cellulomonad.

    Science.gov (United States)

    Jones, Brian E; Grant, William D; Duckworth, A W; Schumann, Peter; Weiss, Norbert; Stackebrandt, Erko

    2005-07-01

    An alkaliphilic, slightly halotolerant, chemo-organotrophic, Gram-positive, rod-shaped bacterium, strain 69B4(T), was isolated from the sediment of the littoral zone of Lake Bogoria, Kenya. Phylogenetically, it is a member of the genus Cellulomonas, showing less than 97.5 % sequence similarity to the type strains of other Cellulomonas species. The highest level of similarity, albeit moderate, was found with respect to Cellulomonas cellasea DSM 20118(T). Chemotaxonomic properties confirm the 16S rRNA gene-based generic affiliation, i.e. a DNA G+C content of 71.5 mol%, anteiso-C(15:0) and C(16:0) as the major fatty acids, MK-9(H(4)) as the major isoprenoid quinone, a peptidoglycan containing L-ornithine as the diamino acid and D-aspartic acid in the interpeptide bridge and phosphatidylglycerol as the only identified main polar lipid. The strain is aerobic to facultatively anaerobic, being capable of growth under strictly anaerobic conditions. Optimal growth occurs between pH values 9.0 and 10.0. On the basis of its distinct phylogenetic position and metabolic properties, strain 69B4(T) represents a novel species of the genus Cellulomonas, for which the name Cellulomonas bogoriensis sp. nov. is proposed. The type strain is 69B4(T) (=DSM 16987(T)=CIP 108683(T)).

  9. Preliminary SP-100/Stirling heat exchanger designs

    International Nuclear Information System (INIS)

    Schmitz, P.; Tower, L.; Blue, B.; Dunn, P.

    1994-01-01

    Analytic modeling of several heat exchanger concepts to couple the SP-100 nuclear reactor lithium loop and the Space Stirling Power Convertor (SSPC) was performed. Four 25 kWe SSPC's are used to produce the required 100 kW of electrical power. This design work focused on the interface between a single SSPC and the primary lithium loop. Manifolding to separate and collect the four channel flow was not modeled. This work modeled two separate types of heat exchanger interfaces (conductive coupling and radiative coupling) to explore their relative advantages and disadvantages. The minimum mass design of the conductively coupled concepts was 18 kg or 0.73 kg/kWe for a single 25 kWe convertor. The minimum mass radiatively coupled concept was 41 kg or 1.64 kg/kWe. The direct conduction heat exchanger provides a lighter weight system because of its ability to operate the Stirling convertor evaporator at higher heat fluxes than those attainable by the radiatively coupled systems. Additionally the conductively coupled concepts had relatively small volumes and provide potentially simpler assembly. Their disadvantages were the tight tolerances and material joining problems associated with this refractory to superalloy interface. The advantages of the radiatively coupled designs were the minimal material interface problems

  10. Preliminary SP-100/Stirling heat exchanger designs

    International Nuclear Information System (INIS)

    Schmitz, P.; Tower, L.; Dawson, R.; Blue, B.; Dunn, P.

    1993-12-01

    Analytic modeling of several heat exchanger concepts to couple the SP-100 nuclear reactor primary lithium loop and the Space Stirling Power Convertor (SSPC) was performed. Four 25 kWe SSPC's are used to produce the required 100 kW of electrical power. This design work focused on the interface between a single SSPC and the primary lithium loop. Manifolding to separate and collect the four channel flow was not modeled. This work modeled two separate types of heat exchanger interfaces (conductive coupling and radiative coupling) to explore their relative advantages and disadvantages. The minimum mass design of the conductively coupled concepts was 18 kg or 0.73 kg/kWe for a single 25 kWe convertor. The minimum mass radiatively coupled concept was 41 kg or 1.64 kg/kWe. The direct conduction heat exchanger provides a lighter weight system because of its ability to operate the Stirling convertor evaporator at higher heat fluxes than those attainable by the radiatively coupled systems. Additionally the conductively coupled concepts had relatively small volumes and provide potentially simpler assembly. Their disadvantages were the tight tolerances and material joining problems associated with this refractory to superalloy interface. The advantages of the radiatively coupled designs were the minimal material interface problems

  11. Accomplishments and plans of SP-100 program

    International Nuclear Information System (INIS)

    Wright, W.E.

    1985-01-01

    The SP-100 program is proceeding toward concept definitions for a space nuclear reactor which is safe and suitable for civilian and military applications. The selection of a specific design and demonstration of the base technologies was scheduled for the end of 1985, to be followed by engineering development and ground testing in 1986. The main current uses/users thus far anticipated are communications satellites, both military and civilian, radar (and possibly laser) surveillance and remote sensing systems, and manufacturing and other extensions of a space station growth scenario. The reactor will weigh no more than 3000 kg and must fit into the Orbiter bay with a payload and OTV. Three concepts are still under evaluation: a lithium-cooled reactor with thermoelectrics; an in-core thermionic system with pumped sodium-potassium coolant; and a configuration with a Stirling engine to convert reactor heat into electricity. If the engineering analyses and base tests are successful, it is expected that the flight application phase can be reached by 1991 at the latest

  12. Phenotypic diversity of Xanthomonas sp. mangiferaeindicae.

    Science.gov (United States)

    Pruvost, O; Couteau, A; Perrier, X; Luisetti, J

    1998-01-01

    Carbohydrate utilization profiles by means of the API (Appareils et Procédés d'Identification) system and sensitivity to antibiotics and heavy metal salts of 68 Xanthomonas sp. mangiferaeindicae strains isolated in nine countries from mango (Mangifera indica L.) and other genera of the Anacardiaceae were examined to assess the variability of the taxon. The strains could be separated into 10 groups according to Ward clustering. Apigmented strains isolated from the pepper tree [syn. Brazilian pepper] (Schinus terebenthifolius Raddi) could not be clearly differentiated from most apigmented strains isolated from mango. Yellow-pigmented strains isolated from mango in Brazil and Reunion Island, apigmented strains isolated from mango in Brazil and from ambarella in the French West Indies, clustered in distinct groups. The results are consistent with those of other studies, based on isozyme analysis of esterase, phosphoglucomutase and superoxide dismutase, and hrp-RFLP analysis; they indicate the need for a comprehensive taxonomic evaluation of xanthomonads associated with Anacardiaceae.

  13. Kribbella sindirgiensis sp. nov. isolated from soil.

    Science.gov (United States)

    Ozdemir-Kocak, Fadime; Isik, Kamil; Saricaoglu, Salih; Saygin, Hayrettin; Inan-Bektas, Kadriye; Cetin, Demet; Guven, Kiymet; Sahin, Nevzat

    2017-12-01

    A Kribbella strain FSN23 T was isolated from soil sample which was collected from Caygoren Dam lakeside located in Sındırgı, Turkey. The isolate was investigated using a polyphasic approach consisting of numeric, chemotaxonomic and molecular analysis. The isolate indicated chemotaxonomic, morphological and phylogenetic properties associated with members of the genus Kribbella. Phylogenetic analysis based on the 16S rRNA sequence of the strain demonstrated that the strain forms a subclade with K. aluminosa HKI 0478 T and K. jejuensis HD9 T . The organism formed an extensively branched substrate and aerial hyphae which generated spiral chains of spores with smooth surfaces. The cell wall contained LL-diaminopimelic acid, and the whole cell sugars were glucose and ribose along with trace amounts of mannose. The polar lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, four unidentified lipids and five unidentified polar lipids. The predominant menaquinone was MK-9(H 4 ). The major cellular fatty acids were anteiso-C 15:0 and iso-C 16:0 . Polyphasic taxonomy properties confirm that strain FSN23 T represents a novel Kribbella taxon distinguished from closely related type strains. Hence, strain FSN23 T (=KCTC 29220 T  = DSM 27082 T ) is proposed as the type strain of a novel species with the name Kribbella sindirgiensis sp. nov.

  14. Campylobacter iguaniorum sp. nov., isolated from reptiles.

    Science.gov (United States)

    Gilbert, Maarten J; Kik, Marja; Miller, William G; Duim, Birgitta; Wagenaar, Jaap A

    2015-03-01

    During sampling of reptiles for members of the class Epsilonproteobacteria, strains representing a member of the genus Campylobacter not belonging to any of the established taxa were isolated from lizards and chelonians. Initial amplified fragment length polymorphism, PCR and 16S rRNA sequence analysis showed that these strains were most closely related to Campylobacter fetus and Campylobacter hyointestinalis. A polyphasic study was undertaken to determine the taxonomic position of five strains. The strains were characterized by 16S rRNA and atpA sequence analysis, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and conventional phenotypic testing. Whole-genome sequences were determined for strains 1485E(T) and 2463D, and the average nucleotide and amino acid identities were determined for these strains. The strains formed a robust phylogenetic clade, divergent from all other species of the genus Campylobacter. In contrast to most currently known members of the genus Campylobacter, the strains showed growth at ambient temperatures, which might be an adaptation to their reptilian hosts. The results of this study clearly show that these strains isolated from reptiles represent a novel species within the genus Campylobacter, for which the name Campylobacter iguaniorum sp. nov. is proposed. The type strain is 1485E(T) ( = LMG 28143(T) = CCUG 66346(T)). © 2015 IUMS.

  15. Taxonomic study of bacteria isolated from plants: proposal of Sphingomonas rosa sp. nov., Sphingomonas pruni sp. nov., Sphingomonas asaccharolytica sp. nov., and Sphingomonas mali sp. nov.

    Science.gov (United States)

    Takeuchi, M; Sakane, T; Yanagi, M; Yamasato, K; Hamana, K; Yokota, A

    1995-04-01

    The taxonomic positions of 10 strains of 3-ketolactose-forming bacteria which were isolated from the roots of plants (Rosa sp., Psychotria nairobiensis, Ardisia crispa, Prunus persica, and apple trees) were investigated. The DNA base compositions of these strains ranged from 64.0 to 65.7 mol%, the isoprenoid quinone of each strain was ubiquinone 10, 3-hydroxy fatty acids were lacking in the cellular fatty acids of these organisms, and all of the strains contained a sphingolipid with the long-chain base dihydrosphingosin. These are characteristics of the genus Sphingomonas. On the basis of morphological, physiological, and chemotaxonomic characteristics, together with DNA-DNA hybridization and 16S ribosomal DNA sequence comparison data, we propose the following four new species of the genus Sphingomonas: Sphingomonas rosa (type strain, IFO 15208) for the strains isolated from rose plants and formerly named [Agrobacterium rhizogenes]; Sphingomonas pruni (type strain, IFO 15498) for the strains isolated from Prunus persica; and Sphingomonas asaccharolytica (type strain, IFO 15499) and Sphingomonas mali (type strain, IFO 15500) for the strains isolated from apple trees. Two strains which were isolated from Psychotria nairobiensis and formerly named [Chromobacterium lividum] were identified as Sphingomonas yanoikuyae strains.

  16. Chryseobacterium solincola sp. nov., isolated from soil.

    Science.gov (United States)

    Benmalek, Yam; Cayol, Jean-Luc; Bouanane, Nabila A; Hacene, Hocine; Fauque, Guy; Fardeau, Marie-Laure

    2010-08-01

    A Gram-staining-negative, yellow-pigmented, strictly aerobic bacterium, designated strain 1YB-R12T, was isolated from a soil sample in western Algeria. The novel isolate was heterotrophic, chemoorganotrophic, halotolerant and psychrotolerant. The temperature and pH optima for growth were 28-30 degrees C and pH 7.3-8. The bacterium tolerated up to 6% (w/v) NaCl. Cells were non-motile, non-gliding and non-spore-forming, and were characterized by a variable morphological cycle. Flexirubin-type pigments were not detected. 16S rRNA gene sequence analysis showed that strain 1YB-R12T occupied a distinct lineage within the genus Chryseobacterium and shared highest sequence similarity with Chryseobacterium haifense LMG 24029T (96.5%). The DNA G+C content of strain 1YB-R12T was 40.9 mol%. The predominant cellular fatty acids were anteiso-C15:0 (41.4%) and iso-C15:0 (14.4%). On the basis of phenotypic properties and phylogenetic distinctiveness, strain 1YB-R12T is considered to represent a novel species of the genus Chryseobacterium, for which the name Chryseobacterium solincola sp. nov. is proposed. The type strain is 1YB-R12T (=DSM 22468T=CCUG 55604T).

  17. Production of biodiesel from Coelastrella sp. microalgae

    Science.gov (United States)

    Mansur, Dieni; Fitriady, Muhammad Arifuddin; Susilaningsih, Dwi; Simanungkalit, Sabar Pangihutan

    2017-11-01

    Microalgae have a wide area of usage and one of them it can be used for biodiesel production. In biodiesel production, lipids containing triglyceride or free fatty acid are converted into methyl ester through trans/esterification reactions. Lipids from microalgae can be extracted by acetone and dimethyl carbonate using homogenizer. Esterification of the lipids was investigated using various catalysts and source of methyl group. Activity of homogeneous catalyst such as HCl and H2SO4 and heterogeneous catalysts such as montmorillonit K-10 and ledgestone was investigated. Moreover, methanol and dimethyl carbonate as source of methyl group were also studied. Among of catalysts with methanol as source of methyl group, it was found that yield of crude biodiesel derived from Choelestrella Sp. microalgae was high over H2SO4 catalyst. On the other hand, over H2SO4 catalyst using dimethyl carbonate as source of methyl group, yield of crude biodiesel significant increase. However, FAME composition of crude biodiesel was high over HCl catalyst.

  18. Mycorrhizal dependency of laurel (Ocotea sp.)

    International Nuclear Information System (INIS)

    Sierra-Escobar, Jorge A; Castro Restrepo, Dagoberto; Osorio Vega, Walter

    2009-01-01

    A greenhouse experiment was carried out to determine the mycorrhizal dependency of laurel (>Ocotea sp.). In order to do this, a completely randomized experimental design was used, with six treatments in a factorial array of 3 x 2 and five repetitions. The treatments involved a combination of three Phosphorus (P) levels in soil solution (0.002, 0.02 and 0.2 mg L-1) and two levels of mycorrhizal inoculation, either inoculated or non-inoculated with Glomus aggregatum Schenck and Smith. The leaf P content as a function of time was used as an output variable. Shoot dry matter, shoot P content, mycorrhizal colonization of roots, and mycorrhizal dependence were measured at harvest. The results indicated that the leaf P content increased significantly when using the mycorrhizal inoculation in laurel at P level 0.2 mg L -1, but not in the other P levels, on some of the sampling days. Shoot dry weight and total plant P content did not increase at all levels of soil available P. Mycorrhizal dependency of laurel reached 28%, which allows this species to be classified as moderately dependent on mycorrhiza.

  19. Rolapitant for the treatment of chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Navari, Rudolph M

    2015-01-01

    Chemotherapy-induced nausea and vomiting is a significant clinical issue which affects patient's quality of life and treatment decisions. Significant improvements in the control of chemotherapy-induced nausea and vomiting have occurred in the past 15 years with the introduction of new antiemetic agents 5-HT3, receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and olanzapine. Aprepitant was the first NK-1 receptor antagonist introduced (2003) for the prevention of chemotherapy-induced nausea and vomiting in combination with a 5-HT3 receptor antagonist and dexamethasone. A second NK-1 receptor antagonist netupitant was approved for use in October 2014. Phase III clinical trials of an additional NK-1 receptor antagonist rolapitant have been completed, and the data have been submitted for regulatory approval. A description of rolapitant and its role in chemotherapy-induced nausea and vomiting will be presented, along with a comparison of the other neurolinin-1 receptor antagonists aprepitant and netupitant.

  20. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  1. The Growth of Monoraphidium sp. and Scenedesmus sp. Cells in the Presence of Thorium

    Directory of Open Access Journals (Sweden)

    Juliana Cristina de Queiroz

    2012-01-01

    Full Text Available Toxicity of thorium by Monoraphidium sp. and Scenedesmus sp. was studied. Microalgal cultures were inoculated in ASM-1 medium in presence and absence of thorium. Its effect was monitored by direct counting on Fuchs-Rosenthal chamber and with software. The toxicity of thorium over the species was observed for concentrations over 50.0 mg/L. After 30 days, Monoraphidium cells decreased their concentration from 4.23×106 to 4.27×105 and 8.57×105 cells/mL, in the presence of 50.0 and 100.0 mg/L of thorium, respectively. Scenedesmus sp. cells were more resistant to thorium: for an initial cell concentration of 7.65×104 cells/mL it was observed a change to 5.25×105 and 5.12×105 cells/mL, in the presence of thorium at 50.0 and 100.0 mg/L, respectively. This is an indication that low concentrations of the radionuclide favored the growth, and that Scenedesmus cells are more resistant to thorium than Monoraphidium cells. The software used for comparison with direct count method proved to be useful for the improvement of accuracy of the results obtained, a decrease in the uncertainty and allowed recording of the data. The presence of thorium suggests that low concentrations have a positive effect on the growth, due to the presence of the nitrate, indicating its potential for ecotoxicological studies.

  2. Aborto eqüino por Leptospira sp. Leptospira sp. as a cause of equine abortion

    Directory of Open Access Journals (Sweden)

    Caroline Argenta Pescador

    2004-02-01

    Full Text Available Descreve-se um caso de aborto eqüino por Leptospira sp