Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
J Public Health (Oxf) ; 44(2): 234-245, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-33200200

RESUMEN

BACKGROUND: Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff. METHODS: We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity. RESULTS: A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07-1.49 and Black: 2.42; 1.90-3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27-0.61). CONCLUSIONS: Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/epidemiología , Estudios Transversales , Demografía , Personal de Salud , Humanos , Inmunoglobulina G , Personal de Hospital , Estudios Seroepidemiológicos
2.
Sci Rep ; 7: 44169, 2017 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-28281561

RESUMEN

Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.


Asunto(s)
Endometriosis/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Indoles/farmacología , Subtipo EP2 de Receptores de Prostaglandina E/antagonistas & inhibidores , Animales , Modelos Animales de Enfermedad , Endometriosis/metabolismo , Endometriosis/patología , Femenino , Hiperalgesia/metabolismo , Hiperalgesia/patología , Ratones
3.
Neuropharmacology ; 79: 136-51, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24269608

RESUMEN

Effective relief from chronic hypersensitive pain states remains an unmet need. Here we report the discovery that the TRPM8 ion channel, co-operating with the 5-HT(1B) receptor (5-HT(1B)R) in a subset of sensory afferents, exerts an influence at the spinal cord level to suppress central hypersensitivity in pain processing throughout the central nervous system. Using cell line models, ex vivo rat neural tissue and in vivo pain models, we assessed functional Ca(2+) fluorometric responses, protein:protein interactions, immuno-localisation and reflex pain behaviours, with pharmacological and molecular interventions. We report 5-HT(1B)R expression in many TRPM8-containing afferents and direct interaction of these proteins in a novel multi-protein signalling complex, which includes phospholipase D1 (PLD1). We provide evidence that the 5-HT(1B)R activates PLD1 to subsequently activate PIP 5-kinase and generate PIP2, an allosteric enhancer of TRPM8, achieving a several-fold increase in potency of TRPM8 activation. The enhanced activation responses of synaptoneurosomes prepared from spinal cord and cortical regions of animals with a chronic inflammatory pain state are inhibited by TRPM8 activators that were applied in vivo topically to the skin, an effect potentiated by co-administered 5-HT(1B)R agonists and attenuated by 5-HT(1B)R antagonists, while 5-HT(1B)R agents alone had no detectable effect. Corresponding results are seen when assessing reflex behaviours in inflammatory and neuropathic pain models. Control experiments with alternative receptor/TRP channel combinations reveal no such synergy. Identification of this novel receptor/effector/channel complex and its impact on nociceptive processing give new insights into possible strategies for enhanced analgesia in chronic pain.


Asunto(s)
Dolor/metabolismo , Fosfolipasa D/metabolismo , Receptor de Serotonina 5-HT1B/metabolismo , Canales Catiónicos TRPM/metabolismo , Animales , Canales de Calcio/metabolismo , Células Cultivadas , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/fisiopatología , Células HEK293 , Humanos , Masculino , Proteínas del Tejido Nervioso/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Dolor/tratamiento farmacológico , Ratas , Ratas Wistar , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Antagonistas del Receptor de Serotonina 5-HT1/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatología , Canal Catiónico TRPA1 , Canales Catiónicos TRPV/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo
4.
Cell Signal ; 25(4): 814-21, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23314176

RESUMEN

The 5-HT2A receptor (5-HT2AR) is implicated in psychotropic changes within the central nervous system (CNS). A number of polymorphisms have been reported in the 5-HT2AR gene; one of these results in a non-synonymous change, H452Y, in the carboxy-terminal tail of the receptor protein. The minor allele (9% occurrence) has been statistically associated with CNS dysfunction such as impaired memory processing and resistance to neuroleptic treatment in schizophrenic patients. We investigated the impact of H452Y mutation of the 5-HT2AR expressed in COS7 cells on distinctly coupled intracellular signalling pathways from the receptor, focusing on the heterotrimeric G protein-independent phospholipase D (PLD) pathway, compared to the conventional Gq/11-linked phospholipase C (PLC) pathway. The H452Y mutation selectively attenuated PLD signalling, which as in the wild-type receptor, was mediated by a molecular complex involving PLD1 docked to the receptor's carboxy-terminal tail domain. Co-immunoprecipitation and GST-fusion protein experiments revealed that the H452Y mutation selectively reduced PLD1 binding to the receptor. Experiments with blocking peptides to mimic short sections of the 5-HT2AR tail sequence revealed that the peptide spanning residue 452 strongly reduced PLD but not PLC responses of the receptor. Similar observations were made when assessing both PLD responses and PLD-dependent cellular proliferation elicited by activation of 5-HT2ARs natively expressed in MCF-7 cells. Overall these findings indicate that the H452Y polymorphic variant of the 5-HT2AR displays selective disruption of its PLD signalling pathway. This may potentially play a role in the CNS dysfunction associated with the H452Y allele of the 5-HT2AR.


Asunto(s)
Fosfolipasa D/metabolismo , Receptor de Serotonina 5-HT2A/metabolismo , Animales , Células COS , Chlorocebus aethiops , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Humanos , Células MCF-7 , Fosfolipasa D/antagonistas & inhibidores , Polimorfismo de Nucleótido Simple , Isoformas de Proteínas/metabolismo , Receptor de Serotonina 5-HT2A/química , Receptor de Serotonina 5-HT2A/genética , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Transducción de Señal/efectos de los fármacos , Transfección , Fosfolipasas de Tipo C/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA