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Neil C Ford, Mark L Baccei
Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life...
October 14, 2016: Neuroscience
Wei-Jun Wu, Wan-Wan Jia, Xin-Hua Liu, Li-Long Pan, Qiu-Yan Zhang, Di Yang, Xiao-Yan Shen, Liang Liu, Yi Zhun Zhu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H2S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1β-induced human rheumatoid fibroblast-like synoviocytes MH7A...
October 6, 2016: Redox Biology
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
Our studies investigating the existence of tumor-initiating cell (TIC) populations in human esophageal squamous cell carcinoma (ESCC) had identified a subpopulation of cells isolated from ESCC patient-derived tumor specimens marked by an ALDH(bri+) phenotype bear stem cell-like features. Importantly, KDM4C, a histone demethylase was enhanced in ALDH(bri+) subpopulation, suggesting that strategies interfering with KDM4C may be able to target these putative TICs. In the present study, by genetic and chemical means, we demonstrated that, KDM4C blockade selectively decreased the ESCC ALDH(bri+) TICs population in vitro and specifically targeted the TICs in ALDH(bri+)-derived xenograft, retarding engraftment...
October 2016: Neoplasia: An International Journal for Oncology Research
Edoardo Torti, Stefano Protti, Daniele Merli, Daniele Dondi, Maurizio Fagnoni
The photochemical behavior of differently substituted N-arylsulfonimides was investigated. Homolysis of the S-N bond took place as the exclusive path from the singlet state to afford both N-arylsulfonamides and photo-Fries adducts, the amount of which depended on reaction conditions and aromatic substituents. Sulfinic and sulfonic acids were released upon irradiation under deaerated and oxygenated conditions, respectively. The nature of the excited states and intermediates involved were proved by laser flash photolysis and EPR experiments...
October 14, 2016: Chemistry: a European Journal
Halil Kara, Fatma Isli, Gokce Sevim Ozturk Fincan, Seniz Yildirim, Sevim Ercan, Yusuf Sarioglu
BACKGROUND: Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits. METHODS: An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer...
September 6, 2016: Pharmacological Reports: PR
L M Moura, P C S Carneiro, N M Vale, L D Barili, L C Silva, J E S Carneiro, C D Cruz
In this study, conducted in two different seasons, we aimed to choose parents to obtain promising segregating populations for the extraction of black bean (Phaseolus vulgaris L.) lines that are superior in terms of disease resistance, plant architecture, and grain yield. Twelve parents were arranged in two groups to compose a partial diallel in a 5 x 7 scheme. Group 1 was composed of parents with black grains and erect plant architecture, while group 2 was composed of parents that had carioca grains and were resistant to the main fungal diseases that occur in the common bean...
August 29, 2016: Genetics and Molecular Research: GMR
Maria L Breser, Ruben D Motrich, Leonardo R Sanchez, Virginia E Rivero
BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant...
October 4, 2016: Prostate
Hidenori Kamiguchi, Masashi Yamaguchi, Mika Murabayashi, Ikuo Mori, Akira Horinouchi
Urinary hippuric acid (HA) and phenylacetylglycine (PAG) are biomarker candidates for drug-induced phospholipidosis (PLD). To confirm their utility in preclinical and clinical settings, it is essential to develop and validate their quantification method in advance. In this study, we have applied liquid chromatography-tandem mass spectrometry (LC/MS/MS) for simultaneous quantification of HA and PAG in rat urine, and matrix based ion suppression was assessed by post-column infusion assay. Effective sample dilution reduced matrix effect of urine to be negligible level and calibration curves showed good correlation between those in urine diluent and buffer alone...
November 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Sun-A Im, Ji-Wan Kim, Hee-Suk Kim, Chan-Su Park, Eunju Shin, Seon-Gil Do, Young In Park, Chong-Kil Lee
The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200, or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80% and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated mice...
September 30, 2016: International Immunopharmacology
Ruiji Li, Takuya Nakashima, Rui Kanazawa, Olivier Galangau, Tsuyoshi Kawai
A series of highly sensitive neutral photoacid generators (PAGs) based on photochromic terarylenes was prepared. Like the example presented herein, these compounds show a subsequent thermal elimination of a Brønsted acid after a light-triggered 6π-electrocyclization, concomitant with the hexatriene aromatization. A novel type of molecular systems was developed, in which one thiazolyl moiety was replaced by a thienyl group. Depending on the solvents and on the nature of the acid source, the quantum yield (QY) for acid generation could reach up to 0...
November 2, 2016: Chemistry: a European Journal
Janine Thome, Maria Densmore, Paul A Frewen, Margaret C McKinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius
OBJECTIVES: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest...
September 20, 2016: Human Brain Mapping
Renato Leonardo de Freitas, Priscila Medeiros, Juliana Almeida da Silva, Rithiele Cristina de Oliveira, Ricardo de Oliveira, Farhad Ullah, Asmat Ullah Khan, Norberto Cysne Coimbra
It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia. The goal of this study was to examine if LC-opioid and serotonergic/noradrenergic mechanisms signal the post-ictal hypoalgesic responses to tonic-clonic seizures produced by intraperitoneal administration of pentylenetetrazole (PTZ at 64mg/kg), causing an ionophore γ-aminobutyric acid (GABA)-mediated Cl(-) influx antagonism...
November 12, 2016: Neuroscience
G L Farren, T Zhang, S B Martin, K T Thomas
OBJECTIVE: To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). PARTICIPANTS: 396 college students participated in this study in the summer 2013. METHODS: Students completed online questionnaires that assessed physical activity behaviors and psychosocial factors (i.e., self-efficacy, outcome expectancies, and social support). Students' physical activity profile was categorized as meeting no PAGs, meeting aerobic PAGs only, meeting muscle-strengthening PAGs only, or meeting both PAGs...
September 3, 2016: Journal of American College Health: J of ACH
R A R Drake, J L Leith, F Almahasneh, J Martindale, A W Wilson, B Lumb, L F Donaldson
UNLABELLED: Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase-prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kgaugelo Edward Lekota, Ayesha Hassim, Joseph Mafofo, Jasper Rees, Farai Catherine Muchadeyi, Henriette Van Heerden, Evelyn Madoroba
INTRODUCTION: Bacillus anthracis is the causative agent of anthrax, a disease endemic in regions of Northern Cape Province and Kruger National Park of South Africa. Accurate identification of virulent B. anthracis is essential but challenging due to its close relationship with other members of B. cereus group. This study characterized B. anthracis and Bacillus species that were recovered from animals and the environment where animals died of anthrax symptoms in southern Africa using a polyphasic approach...
2016: Journal of Infection in Developing Countries
Kyle N Campion, Kimber A Saville, Michael M Morgan
The dorsal raphe nucleus (DRN) is embedded in the ventral part of the caudal periaqueductal gray (PAG). Electrical or chemical activation of neurons throughout this region produces antinociception. The objective of this manuscript is to determine whether the ventrolateral PAG and DRN are distinct antinociceptive systems. This hypothesis was tested by determining the antinociceptive potency of microinjecting morphine into each structure (Experiment 1), creating a map of effective microinjection sites that produce antinociception (Experiment 2), and comparing the development of antinociceptive tolerance to repeated microinjections of morphine into the ventrolateral PAG and DRN (Experiment 3)...
August 26, 2016: European Journal of Neuroscience
Hugh Sims-Williams, Julian C Matthews, Peter S Talbot, Sarah Love-Jones, Jonathan Cw Brooks, Nikunj K Patel, Anthony E Pickering
Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [(11)C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or anaesthesia dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [(11)C]DPN and [(15)O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation...
August 20, 2016: NeuroImage
Valerie L Tryon, Sheri J Y Mizumori, Michael M Morgan
Microinjection of morphine into the periaqueductal gray (PAG) produces antinociception. In vitro slice recordings indicate that all PAG neurons are sensitive to morphine either by direct inhibition or indirect disinhibition. We tested the hypothesis that all PAG neurons respond to opioids in vivo by examining the extracellular activity of PAG neurons recorded in lightly anesthetized and awake rats. Spontaneous activity was less than 1Hz in most neurons. Noxious stimuli (heat, pinch) caused an increase in activity in 57% and 75% of the neurons recorded in anesthetized and awake rats, respectively...
October 29, 2016: Neuroscience
Santosh Kumar Adla, Barbora Slavikova, Marketa Smidkova, Eva Tloustova, Martin Svoboda, Vojtech Vyklicky, Barbora Krausova, Pavla Hubalkova, Michaela Nekardova, Kristina Holubova, Karel Vales, Milos Budesinsky, Ladislav Vyklicky, Hana Chodounska, Eva Kudova
Herein, we report a new class of amide-based inhibitors (1-4) of N-methyl-d-aspartate receptors (NMDARs) that were prepared as analogues of pregnanolone sulfate (PAS) and pregnanolone glutamate (PAG) - the steroidal neuroprotective NMDAR inhibitors. A series of experiments were conducted to evaluate their physicochemical and biological properties: (i) the inhibitory effect of compounds 3 and 4 on NMDARs was significantly improved (IC50=1.0 and 1.4μM, respectively) as compared with endogenous inhibitor - pregnanolone sulfate (IC50=24...
August 17, 2016: Steroids
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