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1.
BJOG ; 130(7): 750-758, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37078279

RESUMEN

OBJECTIVE: To evaluate the reasons for COVID-19 vaccine hesitancy during pregnancy. DESIGN: We used regular expressions to identify publicly available social media posts from pregnant people expressing at least one reason for their decision not to accept COVID-19 vaccine. SETTING: Two social media platforms - WhatToExpect and Twitter. SAMPLE: A total of 945 pregnant people in WhatToExpect (1017 posts) and 345 pregnant people in Twitter (435 tweets). METHODS: Two annotators manually coded posts according to the Scientific Advisory Group for Emergencies (SAGE) working group's 3Cs vaccine hesitancy model (confidence, complacency and convenience barriers). Within each 3Cs we created subthemes that emerged from the data. MAIN OUTCOME MEASURES: Subthemes were derived according to the people's posting own words. RESULTS: Safety concerns were most common and largely linked to the perceived speed at which the vaccine was created and the lack of data about its safety in pregnancy. This led to a preference to wait until after the baby was born or to take other precautions instead. Complacency surrounded a belief that they are young and healthy or already had COVID-19. Misinformation led to false safety and efficacy allegations, or even conspiracy theories, and fed into creating confidence and complacency barriers. Convenience barriers (such as availability) were uncommon. CONCLUSION: The information in this study can be used to highlight the questions, fears and hesitations pregnant people have about the COVID-19 vaccine. Highlighting these hesitations can help public health campaigns and improve communication between healthcare professionals and patients.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , Femenino , Embarazo , Humanos , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Vacilación a la Vacunación , Vacunación
2.
J Dairy Sci ; 104(4): 4206-4222, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33612226

RESUMEN

We determined if a microbial inoculant could improve the fermentation and aerobic stability of corn silage subjected to various challenges during storage that included an air stress challenge and low packing density. In Experiment 1, whole-plant corn was untreated (CTR) or treated (INO, Lactobacillus buchneri 40788 and Pediococcus pentosaceus 12455. Five individually replicated 7.5-L silos, at a density of 240 kg of dry matter (DM)/m3, for each treatment were kept sealed (NAS) for 19 wk, air stressed early (ES, 3 h/wk for wk 1-9), or air stressed late during storage (LS, 3 h/wk for wk 10-19). Inoculation increased the number of agar-culturable lactic acid bacteria regardless of air stress status, but it did not affect the relative abundance of Lactobacillus. Early, but not late air stress, resulted in silages with a higher relative abundance of Acetobacter when compared with NAS. Silages treated with INO had greater concentrations of acetic acid than CTR. Numbers of yeasts were lowest for INO regardless of air stress and CTR-LS had the most yeasts among all treatments. Silages that were not air stressed had a higher relative abundance of Candida tropicalis than air stressed silages. Monascus purpureus was detected in ES and LS but not in NAS, and its relative abundance was numerically higher in CTR-ES than in INO-ES and statistically higher in CTR-LS compared with INO-LS. Early air stress numerically reduced aerobic stability compared with NAS, and there was a statistical tendency for lower stability in LS compared with NAS. Inoculation improved aerobic stability regardless of when the air stress occurred. In Experiment 2, corn silage was prepared with the same primary treatments of CTR and INO but was packed at a low (LD; 180 kg of DM/m3) or a normal (ND; 240 kg of DM/m3) density and sealed (NAS) or air stressed (AS; 24 h on d 28, 42, and 89) for 92 d of storage. The concentration of acetic acid was greater in INO compared with CTR and in AS compared with NAS. Numbers of yeasts were lower in NAS compared with AS regardless of inoculation and they were lower in INO-AS compared with CTR-AS. Treatment with INO improved aerobic stability but the improvement was better in NAS versus AS and better in ND versus LD. Overall, our experiments corroborate past findings showing that INO markedly improves the aerobic stability of corn silage but they are the first to show that improvement can be sustained even when the silage was exposed to regular air stresses and when packed at a low density.


Asunto(s)
Ensilaje , Zea mays , Aerobiosis , Animales , Fermentación , Lactobacillus , Ensilaje/análisis
3.
J Dairy Sci ; 99(9): 7669-7678, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27320670

RESUMEN

Nitrogen excretion in dairy manure is a precursor for N2O and NH3 formation in livestock housing, manure storage facilities, and after manure is applied to land. Nitrous oxide is a major contributor to greenhouse gas emissions, and reducing N output from dairy production facilities can reduce the amount of anthropogenic N2O entering the atmosphere. The objective of the study was to conduct a comprehensive evaluation of extant prediction models for N excretion in feces and urine using extensive literature data. A total of 45 N excretion equations were evaluated for lactating cows, heifers, and nonlactating cows and steers. These equations were evaluated with 215 treatment means from 69 published studies collected over 20 yr from 1995 to 2015. Two evaluation methods were used: the root mean square prediction error and the concordance correlation coefficient. Equations constructed using a more rigorous development process fared better than older extant equations. Equations for heifers and nonlactating cows had greater error of prediction compared with equations used for lactating cows. This could be due to limited amount of data available for construction and evaluation of the equations. Urinary N equations had greater prediction errors than other forms of excretion, possibly due to high variability in urinary N excretion and challenges in urine collection. Fecal N equations had low error bias and reached an acceptable level of precision and accuracy.


Asunto(s)
Bovinos/metabolismo , Industria Lechera , Nitrógeno/metabolismo , Animales , Heces/química , Femenino , Lactancia , Masculino , Modelos Biológicos , Nitrógeno/orina
4.
Genes Immun ; 15(3): 153-61, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24477163

RESUMEN

Most systemic autoimmune diseases occur more frequently in females than in males. This is particularly evident in Sjögren's syndrome, systemic lupus erythromatosis (SLE) and thyroid autoimmunity, where the ratio of females to males ranges from 20:1 to 8:1. Our understanding of the etiology of SLE implies important roles for genetics, environmental factors and sex hormones, but the relative significance of each remains unknown. Using the New Zealand hybrid mouse model system of SLE, we present here a new fetal liver chimera-based system in which we can segregate effects of immune system genes from that of sex hormones in vivo. We show that female hematopoietic cells express an intrinsic capacity to drive lupus-like disease in both male and female recipient mice, suggesting that this capacity is hormone independent. Particularly, only chimeric mice with a female hematopoietic system showed significantly increased numbers of germinal center B cells, memory B cells and plasma cells followed by a spontaneous loss of tolerance to nuclear components and hence elevated serum antinuclear autoantibodies. A protective effect of testosterone was noted with regard to disease onset, but not disease incidence. Thus, genetic factors encoded within the female hematopoietic system can effectively drive lupus-like disease even in male recipients.


Asunto(s)
Autoinmunidad , Células Madre Hematopoyéticas , Hibridación Genética , Animales , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/etiología , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Células de la Médula Ósea , Trasplante de Médula Ósea , Femenino , Feto , Hormonas Esteroides Gonadales/metabolismo , Hepatocitos/metabolismo , Hepatocitos/trasplante , Interferón-alfa/sangre , Enfermedades Renales/etiología , Activación de Linfocitos/inmunología , Masculino , Ratones , Embarazo , Quimera por Trasplante
5.
Neurobiol Stress ; 28: 100590, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38075024

RESUMEN

Introduction: Behavioral therapies, including cognitive behavioral therapy, hypnotherapy and stress management activities, have emerged as effective treatments for irritable bowel syndrome (IBS), a female predominant disorder of the brain-gut axis. IBS, affecting over 10% of the global population, typically presents with abnormal bowel habits and abdominal pain due to visceral hypersensitivity. While the mechanisms underlying how behavioral therapies treat IBS are still elusive, we had previously shown that chronic stress alters gene expression in brain regions critical for stress processing and nociception. We found that exposure to an enriched environment (EE), the rodent analogue of behavioral therapies, prior to and during the stressor was sufficient to prevent stress-induced changes in glucocorticoid receptor (GR) expression in the central nucleus of the amygdala (CeA) and hippocampus. Pre-exposure to EE also inhibited stress-induced increased colonic permeability and was able to block the induction of stress-induced visceral and somatic hypersensitivity. However, it remains unknown if EE can reverse chronic viscerosomatic hypersensitivity that persists following exposure to stress. We hypothesized that EE after chronic stress would be sufficient to reverse stress-induced changes in i) GR expression in the CeA and hippocampus, ii) ameliorate stress-induced colonic hyperpermeability and iii) restore normal visceral and somatic sensitivity in male and female rats. Methods: Male and female rats were exposed to daily water avoidance stress (WAS). After confirming the rats had developed visceral hypersensitivity, 50% of the animals were housed in EE for 2 weeks while the other 50% remained in standard housing (SH). At the end of this period, we assessed visceral and somatic sensitivity. We also collected colon tissue to measure colonic permeability. Micro-punches of tissue from the CeA and hippocampus were isolated to measure GR expression. Control animals not exposed to WAS were kept in SH for the duration of the study (n = 8 per group). Results: In both male and female rats, EE reversed stress-induced visceral (p < 0.001) and somatic (p < 0.01) hypersensitivity when compared to WAS animals housed in SH to levels comparable to control animals. EE exposure also reversed changes in GR expression in both the hippocampus (p < 0.01) and CeA (p < 0.01), normalizing GR expression to control levels. EE exposure ameliorated stress-induced colonic hyperpermeability in both male (p < 0.01) and female (p < 0.01) rats compared to WAS rats in SH. Conclusion: Our findings suggest that behavioral therapies are viable therapeutic options for IBS as they can counter the stress-induced pathophysiology underlying IBS symptoms including visceral hypersensitivity, increased colonic permeability and altered gene expression.

6.
Mult Scler Relat Disord ; 65: 104022, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35816953

RESUMEN

BACKGROUND: Current guidelines recommend vaccination against SARS-CoV2 for people with multiple sclerosis (pwMS). The long-term review of the safety and effectiveness of COVID-19 vaccines in pwMS is limited. METHODS: Service re-evaluation. PwMS using the MS service at Barts Health National Health Service Trust were sent questionnaires via email to report symptoms following first and second COVID-19 vaccinations (n = 570). A retrospective review of electronic health records was conducted for clinical and safety data post-vaccination(s); cut-off was end of September 2021. Separate logistic regressions were carried out for symptoms experienced at each vaccination. Two sets of regressions were fitted with covariates: (i) Disease-modifying therapy type and (ii) patient characteristics for symptoms experienced. RESULTS: 193/570 pwMS responded. 184 pwMS had both vaccinations. 144 received the AZD1222 and 49 the BNT162b2 vaccine. 87% and 75% of pwMS experienced any symptoms at first and second vaccinations, respectively. The majority of symptoms resolved within a short timeframe. No severe adverse effects were reported. Two pwMS subsequently died; one due to COVID-19 and one due to aspiration pneumonia. Males were at a reduced risk of reporting symptoms at first vaccination. There was evidence that pwMS in certain treatment groups were at reduced risk of reporting symptoms at second vaccination only. CONCLUSIONS: Findings are consistent with our preliminary data. Symptoms post-vaccination were similar to the non-MS population and were mostly temporary. It is important to inform the MS community of vaccine safety data.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Esclerosis Múltiple , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , Humanos , Masculino , ARN Viral , SARS-CoV-2 , Medicina Estatal , Vacunación/efectos adversos
7.
Sci Total Environ ; 843: 157014, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35772542

RESUMEN

We explore the oft-repeated claim that river water quality in Great Britain is "better now than at any time since the Industrial Revolution". We review available data and ancillary evidence for seven different categories of water pollutants: (i) biochemical oxygen demand (BOD) and ammonia; (ii) heavy metals; (iii) sewage-associated organic pollutants (including hormone-like substances, personal care product and pharmaceutical compounds); (iv) macronutrients (nitrogen and phosphorus); (v) pesticides; (vi) acid deposition and (vii) other variables, including natural organic matter and pathogenic micro-organisms. With a few exceptions, observed data are scarce before 1970. However, we can speculate about some of the major water quality pressures which have existed before that. Point-source pollutants are likely to have increased with population growth, increased connection rates to sewerage and industrialisation, although the increased provision of wastewater treatment during the 20th century will have mitigated this to some extent. From 1940 to the 1990s, pressures from nutrients and pesticides associated with agricultural intensification have increased in many areas. In parallel, there was an increase in synthetic organic compounds with a "down-the-drain" disposal pathway. The 1990s saw general reductions in mean concentrations of metals, BOD and ammonia (driven by the EU Urban Waste Water Treatment Directive), a levelling out of nitrate concentrations (driven by the EU Nitrate Directive), a decrease in phosphate loads from both point-and diffuse-sources and some recovery from catchment acidification. The current picture is mixed: water quality in many rivers downstream of urban centres has improved in sanitary terms but not with respect to emerging contaminants, while river quality in catchments with intensive agriculture is likely to remain worse now than before the 1960s. Water quality is still unacceptably poor in some water bodies. This is often a consequence of multiple stressors which need to be better-identified and prioritised to enable continued recovery.


Asunto(s)
Plaguicidas , Contaminantes Químicos del Agua , Contaminantes del Agua , Amoníaco , Monitoreo del Ambiente , Nitratos , Compuestos Orgánicos , Contaminantes del Agua/análisis , Contaminantes Químicos del Agua/análisis , Calidad del Agua
8.
Nature ; 435(7044): 925-8, 2005 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-15944715

RESUMEN

The spin of a confined electron, when oriented originally in some direction, will lose memory of that orientation after some time. Physical mechanisms leading to this relaxation of spin memory typically involve either coupling of the electron spin to its orbital motion or to nuclear spins. Relaxation of confined electron spin has been previously measured only for Zeeman or exchange split spin states, where spin-orbit effects dominate relaxation; spin flips due to nuclei have been observed in optical spectroscopy studies. Using an isolated GaAs double quantum dot defined by electrostatic gates and direct time domain measurements, we investigate in detail spin relaxation for arbitrary splitting of spin states. Here we show that electron spin flips are dominated by nuclear interactions and are slowed by several orders of magnitude when a magnetic field of a few millitesla is applied. These results have significant implications for spin-based information processing.

9.
Noise Health ; 13(55): 432-43, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22122960

RESUMEN

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.


Asunto(s)
Pérdida Auditiva Provocada por Ruido/prevención & control , Micronutrientes/administración & dosificación , Personal Militar , Estrés Oxidativo/efectos de los fármacos , Adulto , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Ácido Ascórbico/fisiología , Audiometría de Tonos Puros , Estudios Cruzados , Femenino , Pérdida Auditiva Provocada por Ruido/sangre , Pérdida Auditiva Provocada por Ruido/fisiopatología , Humanos , Magnesio/administración & dosificación , Magnesio/sangre , Magnesio/fisiología , Masculino , Micronutrientes/sangre , Micronutrientes/fisiología , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Emisiones Otoacústicas Espontáneas/fisiología , Estrés Oxidativo/fisiología , Suecia , Vitamina E/administración & dosificación , Vitamina E/sangre , Vitamina E/fisiología , Adulto Joven , beta Caroteno/administración & dosificación , beta Caroteno/sangre , beta Caroteno/fisiología
10.
Curr Rev Musculoskelet Med ; 14(3): 214-223, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33864627

RESUMEN

PURPOSE OF REVIEW: Throwing athletes are vulnerable to elbow injuries, especially in the medial elbow, related to high stress and valgus load in both acute and chronic settings as a result of this complex biomechanical action. This current review details the relevant anatomy and imaging features of common elbow pathology identified with radiographs and MRI in throwing athletes. RECENT FINDINGS: Although elbow pathology in throwing athletes is well documented, advances in imaging technology and technique, particularly with MRI, have allowed for more detailed and accurate imaging description and diagnosis. Pathology of thrower's elbow occurs in predictable patterns and can be reliably identified radiologically. Clinical history and physical examination should guide radiologic evaluation initially with radiographs and followed by an MRI optimized to the clinical question. Constellation of clinical, physical, and radiologic assessments should be used to guide management.

11.
Mult Scler Relat Disord ; 52: 103028, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34049216

RESUMEN

BACKGROUND: Some people with multiple sclerosis (pwMS) are at increased risk of severe Coronavirus disease 19 (COVID-19) and should be rapidly vaccinated. However, vaccine supplies are limited, and there are concerns about side-effects, particularly with the ChAdOx1nCoV-19 (AstraZeneca) vaccine. OBJECTIVES: To report our first experience of pwMS receiving the AstraZeneca vaccine. METHODS: Service evaluation. pwMS using the MS service at Barts Health NHS Trust were sent questionnaires to report symptoms following vaccination. RESULTS: Thirty-three responses were returned, 29/33 pwMS received a first dose of AstraZeneca vaccine, the remaining four received a first dose of BioNTech/Pfizer vaccine. All but two patients (94%) reported any symptoms including a sore arm (70%), flu-like symptoms (64%), fever (21%), fatigue (27%), and headache (21%). In more than 2/3 patients, symptoms lasted up to 48 hours, and with the exception of two pwMS reporting symptom duration of 10 and 12 days, respectively, symptoms in the remainder resolved within seven days. No severe adverse effects occurred. CONCLUSIONS: pwMS report transient symptoms following AstraZeneca vaccination, characteristics of which were similar to those reported in the non-MS population. Symptoms may be more pronounced in pwMS due to the temperature-dependent delay in impulse propagation (Uhthoff's phenomenon) due to demyelination.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Esclerosis Múltiple , COVID-19/terapia , ChAdOx1 nCoV-19 , Humanos , Inmunización Pasiva , Esclerosis Múltiple/tratamiento farmacológico , SARS-CoV-2 , Vacunación
12.
Commun Biol ; 2: 10, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30623106

RESUMEN

Though often perceived as an environmentally-risky practice, biological control of invasive species can restore crop yields, ease land pressure and thus contribute to forest conservation. Here, we show how biological control against the mealybug Phenacoccus manihoti (Hemiptera) slows deforestation across Southeast Asia. In Thailand, this newly-arrived mealybug caused an 18% decline in cassava yields over 2009-2010 and an escalation in prices of cassava products. This spurred an expansion of cassava cropping in neighboring countries from 713,000 ha in 2009 to > 1 million ha by 2011: satellite imagery reveals 388%, 330%, 185% and 608% increases in peak deforestation rates in Cambodia, Lao PDR, Myanmar and Vietnam focused in cassava crop expansion areas. Following release of the host-specific parasitoid Anagyrus lopezi (Hymenoptera) in 2010, mealybug outbreaks were reduced, cropping area contracted and deforestation slowed by 31-95% in individual countries. Hence, when judiciously implemented, insect biological control can deliver substantial environmental benefits.


Asunto(s)
Conservación de los Recursos Naturales/métodos , Protección de Cultivos/métodos , Hemípteros , Control Biológico de Vectores/métodos , Bosque Lluvioso , Animales , Asia Sudoriental , Comercio , Producción de Cultivos , Productos Agrícolas/economía , Manihot/economía , Raíces de Plantas , Imágenes Satelitales , Avispas
13.
Oncogene ; 25(2): 278-87, 2006 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-16170359

RESUMEN

High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and site-directed mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Curcumina/farmacología , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Receptores ErbB/metabolismo , Sitios de Unión , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Proteína 1 de la Respuesta de Crecimiento Precoz/antagonistas & inhibidores , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Receptores ErbB/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica , Humanos , Mutagénesis Sitio-Dirigida , Fosforilación/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Elementos de Respuesta , Eliminación de Secuencia , Transducción de Señal , Activación Transcripcional , Proteína Elk-1 con Dominio ets
14.
Neurogastroenterol Motil ; 19(9): 754-60, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17539891

RESUMEN

Corticotropin releasing factor (CRF) is an important mediator in the stress response. Previous studies in rodent models demonstrated that stress-induced colonic hypersensitivity was inhibited by CRF1 receptor antagonism. As CRF(1)R-deficient mice have (+/+), CRF(1)R (+/-) and CRF(1)R (-/-) mice colonic sensitivity was assessed via a visceromotor behavioural response (VMR) induced by colorectal distension (CRD, 0-60 mmHg). In the CRF(1)R (+/+) mice there was a pressure-dependent increase in the VMR to CRD that was moderately attenuated in the CRF1R (+/-) mice. However in the CRF(1)R (-/-) mice a VMR to CRD was only observed at the highest distension pressure (60 mmHg). A CRF(1)R antagonist, NBI 30775 (30 mg kg(-1) i.p.) significantly decreased the VMR to CRD in CRF(1)R +/+ mice. An identical inhibitory effect of NBI 30775 was observed in 43% of the CRF(1)R +/- mice. This study provides pharmacological and genetic evidence for the importance of CRF(1)R in colonic sensitivity and suggests a link between stress and visceral perception.


Asunto(s)
Ansiedad/metabolismo , Colon/metabolismo , Receptores de Hormona Liberadora de Corticotropina/deficiencia , Animales , Ansiedad/fisiopatología , Colon/efectos de los fármacos , Colon/fisiopatología , Electromiografía , Femenino , Masculino , Manometría , Ratones , Ratones Noqueados , Umbral del Dolor/efectos de los fármacos , Pirimidinas/farmacología , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología
15.
Mol Cell Biol ; 8(10): 4174-84, 1988 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-2847030

RESUMEN

The epidermal growth factor (EGF) receptor is the functional target of the mitogen EGF and the cellular homolog of the avian erythroblastosis virus erbB oncogene product. Regulation of expression of the proto-oncogene encoding the EGF receptor can be elucidated by studying the structure and function of the gene promoter outside the confines of the cell. Previously, we reported the isolation of the human EGF receptor gene promoter. The promoter is highly GC rich, contains no TATA or CAAT box, and has multiple transcription start sites. An S1 nuclease-sensitive site has now been found 80 to 110 base pairs (bp) upstream from the major in vivo transcription initiation site. Two sets of direct repeat sequences were found in this area; both conform to the motif TCCTCCTCC. When deletion mutations were made in this region of the promoter by using either Bal 31 exonuclease or S1 nuclease, we found that in vivo activity dropped three- to fivefold, on the basis of transient-transfection analysis. Examination of nuclear protein binding to normal and mutated promoter DNAs by gel retardation analysis and DNase I footprinting revealed that two specific factors bind to the direct repeat region but cannot bind to the S1 nuclease-mutated promoter. One of the specific factors is the transcription factor Sp1. The results suggest that these nuclear trans-acting factors interact with the S1 nuclease-sensitive region of the EGF receptor gene promoter and either directly or indirectly stimulate transcription.


Asunto(s)
Endonucleasas/metabolismo , Receptores ErbB/genética , Regiones Promotoras Genéticas , Proto-Oncogenes , Animales , Línea Celular , Análisis Mutacional de ADN , Proteínas de Unión al ADN/fisiología , Desoxirribonucleasa I/metabolismo , Regulación de la Expresión Génica , Humanos , Proteínas Nucleares/fisiología , Proto-Oncogenes Mas , Secuencias Repetitivas de Ácidos Nucleicos , Endonucleasas Específicas del ADN y ARN con un Solo Filamento , Factores de Transcripción/fisiología , Transcripción Genética
16.
Environ Pollut ; 146(1): 155-65, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16905225

RESUMEN

An existing GIS hydrology water quality model, LF2000-WQX, was applied to predict the concentrations of the pharmaceuticals diclofenac and propranalol in catchments. As a practical exercise the predominantly rural Tamar (UK) catchment was chosen. Consumption, excretion, and fate data were used to estimate the pharmaceutical input load for the model. The predicted concentrations throughout most of the catchment were 1 ng/L or less under low flow (90th percentile) conditions. However, at a few locations, downstream of small sewage treatment plants, concentrations above 25 ng/L were predicted. This exercise shows that it is relatively straightforward to predict the concentrations of new and emerging organic microcontaminants in real catchments using existing GIS hydrology water quality models. Further testing will be required to establish their accuracy.


Asunto(s)
Simulación por Computador , Diclofenaco/análisis , Monitoreo del Ambiente/métodos , Modelos Teóricos , Propranolol/análisis , Contaminantes Químicos del Agua/análisis , Sistemas de Información Geográfica , Ríos , Aguas del Alcantarillado , Reino Unido , Movimientos del Agua , Purificación del Agua
17.
Neurogastroenterol Motil ; 18(5): 343-5, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16629860

RESUMEN

The 5-HT4 receptor agonist tegaserod is an effective prokinetic agent that increases gastrointestinal secretion and reduces visceral sensitivity. Tegaserod has both 5-HT4 receptor agonist and 5-HT2B receptor antagonist activity, the latter being a less potent effect of the drug. In a rat model of colonic hypersensitivity, selective 5-HT4 receptor antagonists only partially reversed the antihyperalgesic effect of tegaserod suggesting that non-5-HT4 receptor-mediated mechanisms may also be involved in its overall antihyperalgesic action. The objective of this study was to determine whether 5-HT2B receptors play a role in colonic hypersensitivity. A visceromotor response (VMR) in acutely sensitized animals (intracolonic acetic acid, 0.6%, 1.5 mL) quantified colonic hypersensitivity. Acetic acid produced an increase in the VMR at all distension pressures. However, neither the 5-HT2B receptor agonist BW 723C86, the 5-HT2B antagonist SB204741 or the 5-HT2B/2C antagonist SB 206553 caused any significant inhibition of the VMR. In summary, in the same rodent model in which tegaserod has previously been shown to produce a potent antihyperalgesic effect, 5-HT2B receptors do not appear to mediate colonic hypersensitivity. We conclude that 5-HT2B receptor-mediated mechanisms are unlikely to play a role in the antihyperalgesic action of tegaserod in man.


Asunto(s)
Motilidad Gastrointestinal/fisiología , Enfermedades Intestinales/fisiopatología , Receptor de Serotonina 5-HT2B/metabolismo , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Animales , Colon/efectos de los fármacos , Colon/metabolismo , Dilatación Patológica , Motilidad Gastrointestinal/efectos de los fármacos , Hiperalgesia/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT2B/efectos de los fármacos , Recto/efectos de los fármacos , Recto/metabolismo
18.
Neurogastroenterol Motil ; 18(6): 464-71, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16700726

RESUMEN

Serotonin-selective reuptake transporter (SERT) expression is decreased in animal models of intestinal inflammation and in individuals with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS), and it is possible that resultant changes in intestinal serotonin signalling contribute to the manifestation of clinical features associated with these disorders. The objective of this investigation was to determine whether inhibition of SERT function leads to changes in gut motility and sensitivity. Mice underwent a 14-day treatment with the SERT inhibitor, paroxetine (20 mg kg(-1)), or vehicle (saline/propylene glycol). Gastrointestinal (GI) transit following charcoal gavage, colonic motility, stool frequency and visceromotor responses to colorectal distension were evaluated. In mice treated with paroxetine, stool output was decreased, upper GI transit was delayed, and colonic sensitivity to a nociceptive stimulus was attenuated. These results demonstrate that reduced SERT function (via pharmacological blockade) significantly alters GI motility and sensitivity in mice, and support the concept that altered SERT expression and function could contribute to symptoms associated with IBS and IBD.


Asunto(s)
Colon/metabolismo , Motilidad Gastrointestinal/fisiología , Umbral del Dolor/fisiología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Animales , Colon/efectos de los fármacos , Electromiografía , Motilidad Gastrointestinal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/fisiopatología , Síndrome del Colon Irritable/fisiopatología , Masculino , Ratones , Umbral del Dolor/efectos de los fármacos , Paroxetina/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología
19.
Sci Total Environ ; 362(1-3): 166-78, 2006 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-16055169

RESUMEN

The combined farm animal population is considerably larger than the human one in the United Kingdom, implying a possibly important contribution to the environmental load of steroid hormones entering water. To make comparisons on the amount of steroid hormones produced by the different livestock, information was gathered on the structure of the UK farm animal populations and the amount of hormones excreted by animals at each of their life stages. An individual normalised dairy cow excretes two orders of magnitude more, and a normalised pig excretes more than one order of magnitude more steroid oestrogens than a normalised human. In terms of excretion, the combined farm animal population (including sheep and poultry) probably generates around four times more oestrogens than the human population in the UK. The biggest contributor on the animal side is the relatively small dairy cow population. If steroid oestrogens behave like herbicides, in which a worst case loss to surface waters is around 1%, then it could be argued that farm animals are responsible for 15% of all the oestrogens in UK waters. When simulations were made with the MACRO pesticide leaching model, predicted concentrations for field drains failed to exceed 1 ng/L. The rapid biodegradation rates, and high sorption rates taken from the literature and used in the model suggested less than 0.001% of oestrogens would reach the field drains. This survey suggests that direct excretion of steroid hormones by animals into water courses, or discharges from farmyard drains, are likely to be more important sources of contamination rather than via normal agricultural scenarios.


Asunto(s)
Animales Domésticos , Estradiol/análisis , Estrona/análisis , Contaminantes Químicos del Agua/análisis , Animales , Disruptores Endocrinos , Monitoreo del Ambiente , Estradiol/orina , Estrona/orina , Peces , Agua Dulce , Estiércol , Contaminantes del Suelo/análisis , Reino Unido , Movimientos del Agua
20.
Sci Total Environ ; 367(2-3): 616-30, 2006 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-16542709

RESUMEN

Most studies of hormonal activity in rivers have focused on inputs from sewage treatment works (STW), and their consequences for endocrine disruption in fish. It is possible that livestock is contributing to this hormonal activity in rivers. This study represents a search for evidence of steroid hormone contamination in streams associated with livestock farms. The majority of the 10 sites selected were streams running through dairy farms, although some examples of beef, sheep and pigs were included. Passive water samplers (Polar Organic Chemical Integrative Samplers-POCIS) were deployed up- (control) and down-stream of the farms for 3 to 10 weeks (mean=39 days) during the period November 2004 to January 2005. At one site, water samples were also taken automatically during rainfall events. All samples were solvent-extracted. Total oestrogenic activity in concentrates of the extracts was analysed using the Yeast Estrogen Screen (YES) calibrated against 17beta-oestradiol (E2), while oestrone (E1), E2 and 17alpha-ethinylestradiol (EE2) were analysed by liquid chromatography-mass spectrometry (LC-MS/MS). Stream water from the entirety of only one rainfall event was sampled directly, but this revealed background activity (E2 equivalents) of 0-0.3 ng/l, rising to a transient peak of 9.4 ng/l. Average oestrogenic activity at this site as estimated from the POCIS samplers was 1.8-2.7 ng E2 equiv./l. Estimated average oestrogenic activity across all sites (with one exception) lay in the range 0-26.5 ng E2 equiv./l (mean=2.0 ng/l; S.D.=5.1), based on the POCIS samples. The outlier was 292 ng/l, and this could not be specifically linked with livestock rearing. 92% of monitoring stations (at least one on each farm) contained some oestrogenic activity, and activity was higher at downstream sites in 50% of cases. Although no EE2 was detected analytically in any stream, E1 and E2 were almost ubiquitous, with E2 equivalents ranging from 0.04 to 3.6 ng/l across all sites. Furthermore, steroid concentrations downstream of livestock were higher than upstream in 60% of cases, more markedly so than for the YES data. In several cases, activity upstream was greater than downstream, and this tended to be associated with higher activity than could be accounted for by the hormone analyses. Both the YES and chemical analytical data suggest that fish in headwater streams on or near some livestock farms may be at risk of endocrine disruption.


Asunto(s)
Monitoreo del Ambiente/estadística & datos numéricos , Estrógenos/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Cromatografía Liquida , Industria Lechera , Espectrometría de Masas , Reino Unido , Levaduras
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