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1.
Br J Surg ; 107(12): 1552-1557, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32996597

RESUMEN

The aim of this study was to compare the outcomes of robotic total mesorectal excision (TME) in obese versus non-obese patients. A total of 533 patients, of whom 161 were obese (30·2 per cent) underwent robotic proctectomy during the study interval. Patient obesity was not associated with adverse short-term clinical outcomes after robotic rectal cancer surgery. Indicated in the obese perhaps?


Asunto(s)
Obesidad/complicaciones , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/complicaciones , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento , Adulto Joven
2.
Colorectal Dis ; 22(1): 53-61, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31356721

RESUMEN

AIM: Complete mesocolic excision (CME) with central vascular ligation (CVL) has been advocated for right colon adenocarcinoma (RC), but the radicality of vascular dissection remains controversial. Our aim is to report outcomes of selective CVL (D3 lymphadenectomy) during minimally invasive CME for RC. METHOD: A prospective database identified patients who were treated for RC between 2009 and 2016. Minimally invasive CME was standard. The radicality of lymphadenectomy was defined as high ligation (HL) versus CVL based on operative reports and videos. Two blinded radiologists independently evaluated the pre- and postoperative CT scans for radiographically abnormal nodes. RESULTS: Of 197 patients who underwent CME, HL was performed in 56 (28%) and CVL in 141 (72%). There were no baseline differences in age, sex, body mass index, American Society of Anesthesiologists score or pathological staging, and there were no major intra-operative complications in either group (including no major vascular injuries). The median total number of nodes retrieved was 27 and 31 (P = 0.011) in HL and CVL groups, resepctively, with pathologically positive nodes identified in 33.9% and 39.8% (P = 0.704), respectively. Preoperative imaging identified abnormal cN3 nodes in 1.5% of patients; all of whom underwent CVL. No abnormal cN2 or cN3 nodes remained on postoperative imaging. The 60-day mortality was 0.5%, and major morbidity was 4%. One patient (0.5%) had an anastomotic recurrence after a median follow-up of 22 months. CONCLUSION: With imperfect preoperative clinical nodal staging, and in the absence of randomized data, the low morbidity and oncological outcomes observed support the approach of CME with HL as a minimum standard, with CVL (D3 lymphadenectomy) in selected cases.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias del Colon/cirugía , Ligadura/métodos , Escisión del Ganglio Linfático/métodos , Mesocolon/irrigación sanguínea , Adenocarcinoma/diagnóstico por imagen , Anciano , Colectomía/efectos adversos , Colectomía/métodos , Neoplasias del Colon/diagnóstico por imagen , Bases de Datos Factuales , Femenino , Humanos , Ligadura/efectos adversos , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Masculino , Arterias Mesentéricas/cirugía , Venas Mesentéricas/cirugía , Mesocolon/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
3.
Colorectal Dis ; 22(12): 2049-2056, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32892473

RESUMEN

AIM: There are limited outcome data for lateral pelvic lymph node dissection (LPLND) following neoadjuvant chemoradiotherapy (nCRT), particularly in the West. Our aim was to evaluate the short-term perioperative and oncological outcomes of robotic LPLND at a single cancer centre. METHOD: A retrospective analysis of a prospective database of consecutive patients undergoing robotic LPLND for rectal cancer between November 2012 and February 2020 was performed. The main outcomes were short-term perioperative and oncological outcomes. Major morbidity was defined as Clavien-Dindo grade 3 or above. RESULTS: Forty patients underwent robotic LPLND during the study period. The mean age was 54 years (SD ± 15 years) and 13 (31.0%) were female. The median body mass index was 28.6 kg/m2 (IQR 25.5-32.6 kg/m2 ). Neoadjuvant CRT was performed in all patients. Resection of the primary rectal cancer and concurrent LPLND occurred in 36 (90.0%) patients, whilst the remaining 4 (10.0%) patients had subsequent LPLND after prior rectal resection. The median operating time was 420 min (IQR 313-540 min), estimated blood loss was 150 ml (IQR 55-200 ml) and length of hospital stay was 4 days (IQR 3-6 days). The major morbidity rate was 10.0% (n = 4). The median lymph node harvest from the LPLND was 6 (IQR 3-9) and 13 (32.5%) patients had one or more positive LPLNs. The median follow-up was 16 months (IQR 5-33 months), with 1 (2.5%) local central recurrence and 7 (17.5%) patients developing distant disease, resulting in 3 (7.5%) deaths. CONCLUSION: Robotic LPLND for rectal cancer can be performed in Western patients to completely resect extra-mesorectal LPLNs and is associated with acceptable perioperative morbidity.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
4.
J Radiol Prot ; 40(3): N31-N38, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32408280

RESUMEN

We report on the retrofitting of a standard DP2 environmental radiation monitor replacing the photomultiplier tube with a silicon photomultiplier (SiPM). The use of a SiPM has several advantages for a hand-held radiation monitor, including convenient low-voltage operation and physical robustness. We report the detection efficiency and alpha/beta discrimination performance of the modified probe compared with an unmodified version.


Asunto(s)
Monitoreo de Radiación/instrumentación , Silicio/química , Diseño de Equipo
5.
Sensors (Basel) ; 19(18)2019 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-31487922

RESUMEN

In response to the Fukushima Daiichi Nuclear Power Plant accident, there has occurred the unabated growth in the number of airborne platforms developed to perform radiation mapping-each utilising various designs of a low-altitude uncrewed aerial vehicle. Alongside the associated advancements in the airborne system transporting the radiation detection payload, from the earliest radiological analyses performed using gas-filled Geiger-Muller tube detectors, modern radiation detection and mapping platforms are now based near-exclusively on solid-state scintillator detectors. With numerous varieties of such light-emitting crystalline materials now in existence, this combined desk and computational modelling study sought to evaluate the best-available detector material compatible with the requirements for low-altitude autonomous radiation detection, localisation and subsequent high spatial-resolution mapping of both naturally occurring and anthropogenically-derived radionuclides. The ideal geometry of such detector materials is also evaluated. While NaI and CsI (both elementally doped) are (and will likely remain) the mainstays of radiation detection, LaBr3 scintillation detectors were determined to possess not only a greater sensitivity to incident gamma-ray radiation, but also a far superior spectral (energy) resolution over existing and other potentially deployable detector materials. Combined with their current competitive cost, an array of three such composition cylindrical detectors were determined to provide the best means of detecting and discriminating the various incident gamma-rays.

6.
Ann Oncol ; 29(10): 2061-2067, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-30412224

RESUMEN

Background: Gene expression-based profiling of colorectal cancer (CRC) can be used to identify four molecularly homogeneous consensus molecular subtype (CMS) groups with unique biologic features. However, its applicability to colorectal premalignant lesions remains unknown. Patients and methods: We assembled the largest transcriptomic premalignancy dataset by integrating different public and proprietary cohorts of adenomatous and serrated polyps from sporadic (N = 311) and hereditary (N = 78) patient populations and carried out a comprehensive analysis of carcinogenesis pathways using the CMS random forest (RF) classifier. Results: Overall, transcriptomic subtyping of sporadic and hereditary polyps revealed CMS2 and CMS1 subgroups as the predominant molecular subtypes in premalignancy. Pathway enrichment analysis showed that adenomatous polyps from sporadic or hereditary cases (including Lynch syndrome) displayed a CMS2-like phenotype with WNT and MYC activation, whereas hyperplastic and serrated polyps with CMS1-like phenotype harbored prominent immune activation. Rare adenomas with CMS4-like phenotype showed significant enrichment for stromal signatures along with transforming growth factor-ß activation. There was a strong association of CMS1-like polyps with serrated pathology, right-sided anatomic location and BRAF mutations. Conclusions: Based on our observations made in premalignancy, we propose a model of pathway activation associated with CMS classification in colorectal carcinogenesis. Specifically, while adenomatous polyps are largely CMS2, most hyperplastic and serrated polyps are CMS1 and may transition into other CMS groups during evolution into carcinomas. Our findings shed light on the transcriptional landscape of premalignant colonic polyps and may help guide the development of future biomarkers or preventive treatments for CRC.


Asunto(s)
Adenoma/diagnóstico , Biomarcadores de Tumor/genética , Pólipos del Colon/diagnóstico , Neoplasias Colorrectales/clasificación , Neoplasias Colorrectales/diagnóstico , Mutación , Lesiones Precancerosas/diagnóstico , Adenoma/genética , Pólipos del Colon/genética , Neoplasias Colorrectales/genética , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Lesiones Precancerosas/genética , Valor Predictivo de las Pruebas , Pronóstico , Transcriptoma
7.
J Microsc ; 270(2): 217-234, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29333754

RESUMEN

Serial block face scanning electron microscopy (SBF-SEM) is a relatively new technique that allows the acquisition of serially sectioned, imaged and digitally aligned ultrastructural data. There is a wealth of information that can be obtained from the resulting image stacks but this presents a new challenge for researchers - how to computationally analyse and make best use of the large datasets produced. One approach is to reconstruct structures and features of interest in 3D. However, the software programmes can appear overwhelming, time-consuming and not intuitive for those new to image analysis. There are a limited number of published articles that provide sufficient detail on how to do this type of reconstruction. Therefore, the aim of this paper is to provide a detailed step-by-step protocol, accompanied by tutorial videos, for several types of analysis programmes that can be used on raw SBF-SEM data, although there are more options available than can be covered here. To showcase the programmes, datasets of skeletal muscle from foetal and adult guinea pigs are initially used with procedures subsequently applied to guinea pig cardiac tissue and locust brain. The tissue is processed using the heavy metal protocol developed specifically for SBF-SEM. Trimmed resin blocks are placed into a Zeiss Sigma SEM incorporating the Gatan 3View and the resulting image stacks are analysed in three different programmes, Fiji, Amira and MIB, using a range of tools available for segmentation. The results from the image analysis comparison show that the analysis tools are often more suited to a particular type of structure. For example, larger structures, such as nuclei and cells, can be segmented using interpolation, which speeds up analysis; single contrast structures, such as the nucleolus, can be segmented using the contrast-based thresholding tools. Knowing the nature of the tissue and its specific structures (complexity, contrast, if there are distinct membranes, size) will help to determine the best method for reconstruction and thus maximize informative output from valuable tissue.

8.
Conserv Biol ; 30(5): 1122-7, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26931376

RESUMEN

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful.


Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Diclofenaco/análogos & derivados , Diclofenaco/toxicidad , Falconiformes , Animales , Asia , Bovinos , Conservación de los Recursos Naturales , Diclofenaco/metabolismo , Diclofenaco/farmacocinética , Especies en Peligro de Extinción
9.
Environ Sci Technol ; 49(1): 423-31, 2015 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-25489920

RESUMEN

Traditional beach management that uses concentrations of cultivatable fecal indicator bacteria (FIB) may lead to delayed notification of unsafe swimming conditions. Predictive, nowcast models of beach water quality may help reduce beach management errors and enhance protection of public health. This study compares performances of five different types of statistical, data-driven predictive models: multiple linear regression model, binary logistic regression model, partial least-squares regression model, artificial neural network, and classification tree, in predicting advisories due to FIB contamination at 25 beaches along the California coastline. Classification tree and the binary logistic regression model with threshold tuning are consistently the best performing model types for California beaches. Beaches with good performing models usually have a rainfall/flow related dominating factor affecting beach water quality, while beaches having a deteriorating water quality trend or low FIB exceedance rates are less likely to have a good performing model. This study identifies circumstances when predictive models are the most effective, and suggests that using predictive models for public notification of unsafe swimming conditions may improve public health protection at California beaches relative to current practices.


Asunto(s)
Playas , Modelos Estadísticos , Microbiología del Agua , Calidad del Agua , California , Enterobacteriaceae , Enterococcus , Ambiente , Heces/microbiología , Gastroenteritis , Humanos , Análisis de los Mínimos Cuadrados , Modelos Lineales , Modelos Logísticos , Modelos Teóricos , Redes Neurales de la Computación , Sensibilidad y Especificidad , Agua
10.
bioRxiv ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39071342

RESUMEN

Drug discovery pipelines rely on the availability of isolated primary hepatocytes for investigating potential hepatotoxicity prior to clinical application. These hepatocytes are typically isolated from livers rejected for transplantation and subsequently cryopreserved for later usage. The gold-standard cryopreservation technique, slow-freezing, is a labor-intensive process, with significant post-storage viability loss. In this work, we introduce parallelized droplet vitrification, a technique for high-volumetric, rapid vitrification of suspended cells. We show the utility of this technique through the single-run vitrification of the whole-rate liver hepatocyte yield, resulting in a 1600% increase in single-batch vitrification and a 500% increase in droplet generation rate compared to previous droplet vitrification approaches. Additionally, we showed that these implementations maintained improved post-preservation outcomes in primary rat hepatocytes.

11.
Mol Hum Reprod ; 19(11): 727-36, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23775458

RESUMEN

Endothelial-dependent regulation of vascular tone occurs in part via protein kinase G1α-mediated changes in smooth muscle myofilament sensitivity to Ca(2+). Tissue-specific differences in PKG-dependent relaxation have been attributed to altered expression of myofilament-associated proteins that are substrates for PKG binding. These include the alternative splicing of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase to yield leucine zipper positive (LZ(+)) and negative (LZ(-)) isovariants, with the former being required for PKG-mediated relaxation, and/or altered expressions of telokin, vasodilator-stimulated phosphoprotein (VASP) or heat shock protein Hsp20. During human pregnancy the uterine and placental circulations remain distinct entities and, as such, their mechanisms of vascular tone regulation may differ. Indeed, the sensitivity of myometrial arteries to endothelial-dependent agonists has been suggested to be greater than that of placental arteries. We tested the hypothesis that this was related to tissue-specific changes in PKG-mediated myofilament Ca(2+)-desensitization and/or the expressions of PKG-interacting myofilament-associated proteins. Permeabilized human placental and myometrial arteries were constricted with maximal activating Ca(2+) (pCa 4.5), or sub-maximal Ca(2+) (pCa 6.7) and the thrombane mimetic U46619, and exposed to 8-Br-cGMP. In each case, relaxation was significantly greater in myometrial arteries (e.g. relaxation in pCa 4.5 to 8-Br-cGMP was 49 ± 9.7%, n = 7) than placental arteries (relaxation of 23 ± 6.6%, n = 6, P < 0.05). MYPT1 protein levels, or MYPT1 LZ(+)/LZ(-) mRNA ratios, were similar for both artery types. Of other proteins examined, only Hsp20 expression was significantly elevated in myometrial arteries than placental arteries. These results demonstrate that the reduced human placental artery relaxation to PKG stimulation lies partly at the level of myofilament (de)activation and may be related to a lower expression of Hsp20 than in myometrial arteries.


Asunto(s)
Calcio/metabolismo , Miofibrillas/metabolismo , Miometrio/irrigación sanguínea , Placenta/irrigación sanguínea , Arteria Uterina/fisiología , Vasodilatación/fisiología , Adulto , Biopsia , Femenino , Proteínas del Choque Térmico HSP20/genética , Proteínas del Choque Térmico HSP20/metabolismo , Humanos , Miofibrillas/patología , Miografía , Miometrio/metabolismo , Miometrio/patología , Fosfatasa de Miosina de Cadena Ligera/genética , Fosfatasa de Miosina de Cadena Ligera/metabolismo , Placenta/metabolismo , Placenta/patología , Embarazo , Adulto Joven
12.
Ecotoxicol Environ Saf ; 97: 183-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24008155

RESUMEN

When planning rodent eradications, that normally involve the use of the anticoagulant poison brodifacoum, it is imperative to minimise impacts on other "non-target" species that dwell alongside the targeted rodents and may indeed be the intended beneficiaries of the eradication. Such impacts can arise either from primary poisoning when the non-target species ingest bait pellets containing toxicant or by secondary poisoning when the non-target species eats prey that has itself eaten brodifacoum. Cockroaches and woodlice, likely to scavenge bait pellets, are widely distributed on tropical and sub-tropical islands where they are eaten by ground-dwelling birds. Combining work on Henderson Island, South Pacific, site of a recent rat eradication project, and UK laboratory experiments, our study first measured brodifacoum concentrations in cockroaches given temporary ad lib access to poison bait pellets, approximately mimicking the aftermath of bait distribution for a rodent eradication. In two separate experiments using different species/exposure times, the mean brodifacoum concentrations among cockroaches immediately after bait exposure was 262±s.e. 131 and 477±168µgkg(-1) wet weight. Values decreased quickly in the following 2 weeks, and then continued to decline at a slower rate over the following 4 weeks in the more prolonged laboratory experiment. A supplementary experiment with woodlice recorded a similar brodifacoum concentration in the animals at the end of the exposure period, 223±66µgkg(-1), and a similar time course for the post-exposure decline. In the context of rails (Rallidae), a group of birds known to be particularly susceptible to primary brodifacoum poisoning, these results suggested that, in terms of acute exposure, individual birds would need to eat a minimum of their own body weight (and more commonly 2-5 times that) of live cockroaches before facing a 50% risk of death. Therefore, we conclude that in eradication scenarios, acute secondary poisoning is of lower concern for these birds than primary poisoning.


Asunto(s)
4-Hidroxicumarinas/análisis , Cucarachas/química , Isópodos/química , Rodenticidas/análisis , Análisis de Varianza , Animales , Islas , Factores de Tiempo
13.
Ann Oncol ; 23(3): 652-658, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21653683

RESUMEN

BACKGROUND: Poorly differentiated and signet ring cell adenocarcinomas of the appendix represent a subset with aggressive tumor biology and poor outcomes with few studies evaluating the impact of systemic chemotherapy and cytoreductive surgery (CRS). PATIENTS AND METHODS: A retrospective chart review of patients with either poorly differentiated and signet ring cell appendiceal adenocarcinomas was completed from 1992 to 2010. RESULTS: One hundred forty-two patients were identified. Seventy-eight patients with metastatic disease received chemotherapy. Radiographic response was 44%, median progression-free survival (PFS) was 6.9 months, and median overall survival (OS) was 1.7 years. In multivariate analysis, response to chemotherapy [hazard ratio (HR) 0.5; P = 0.02] predicted improved PFS, and complete CRS (HR 0.3; P = 0.004) predicted improved OS. Patients who underwent complete CRS (n = 26) had a median relapse-free survival (RFS) of 1.2 years and a median OS of 4.2 years. In multivariate analysis for this subset, complete cytoreduction score of 0 was significantly correlated with improved RFS (HR 0.07; P = 0.01) and OS (HR 0.02; P = 0.01). CONCLUSIONS: Systemic chemotherapy appears to be a viable treatment option for patients with metastatic poorly differentiated and signet ring cell appendiceal adenocarcinomas. Complete CRS is associated with improved RFS and OS, though part of this benefit likely reflects the selection of good tumor biology.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Apéndice/tratamiento farmacológico , Neoplasias del Apéndice/cirugía , Carcinoma de Células en Anillo de Sello/tratamiento farmacológico , Carcinoma de Células en Anillo de Sello/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Apéndice/patología , Carcinoma de Células en Anillo de Sello/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
Phys Rev Lett ; 108(24): 242701, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-23004266

RESUMEN

The 18Ne(α,p) 21Na reaction provides one of the main HCNO-breakout routes into the rp process in x-ray bursts. The 18Ne(α,p0) 21Na reaction cross section has been determined for the first time in the Gamow energy region for peak temperatures T∼2 GK by measuring its time-reversal reaction 21Na(p,α) 18Ne in inverse kinematics. The astrophysical rate for ground-state to ground-state transitions was found to be a factor of 2 lower than Hauser-Feshbach theoretical predictions. Our reduced rate will affect the physical conditions under which breakout from the HCNO cycles occurs via the 18Ne(α,p) 21Na reaction.

15.
Arch Toxicol ; 84(10): 761-6, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20140424

RESUMEN

In a safety study, Cape Griffon vultures (Gyps coprotheres) were dosed with ketoprofen at single doses of ~1 mg/kg (n = 5) and 5 mg/kg (n = 11). No toxicity was reported in the 1 mg/kg group, with the AUC(inf), V(z) and Cl being 10.42 µg/ml h, 0.37 l/kg and 0.10 l/h kg, respectively. Toxicity occurred in the 5 mg/kg group, with 7 of the 11 birds dying. Clinical signs of toxicity included depression, loss of appetite and apparent coma. Animals died within 48 h of dosing. The AUC(inf), V(z) and Cl in the birds that survived were 52.26 µg/ml h, 0.45 l/kg and 0.10 l/h kg, respectively. The AUC(inf), V(z) and Cl in the birds those died were 207.90 µg/ml h, 0.26 l/kg and 0.02 l/h kg, respectively. Based on the increase in the AUC(inf) and C(max) in the birds that died, we surmise that toxicity resulted from saturation of the metabolic process. While the exact metabolic pathway remains unknown in these vultures, we believe that toxicity may be due to pharmacogenomic differences in the cytochrome P450 pathway.


Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Falconiformes/metabolismo , Cetoprofeno/toxicidad , Animales , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/farmacocinética , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Falconiformes/sangre , Cetoprofeno/sangre , Cetoprofeno/farmacocinética , Pruebas de Toxicidad
16.
Ultrasound Obstet Gynecol ; 33(3): 307-12, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19204911

RESUMEN

OBJECTIVES: Myometrial contractions are one of the most important aspects of effective labor. For cells within the myometrium to work efficiently they need to be well oxygenated and this requires an adequate blood supply. This study used quantitative three-dimensional (3D) power Doppler angiography to calculate the percentage change in myometrial blood flow during a relaxation-contraction-relaxation cycle of active labor. METHODS: Transabdominal 3D power Doppler ultrasound imaging was used to acquire volumetric data during the first stage of spontaneous labor in 20 term, nulliparous women. 3D datasets were acquired during a single cycle of uterine relaxation, contraction and subsequent relaxation for each subject. The resultant datasets were analyzed independently by two investigators on two occasions using Virtual Organ Computer-aided AnaLysis to define a volume of interest within the myometrium; the power Doppler signal within this volume was quantified to provide 3D indices of vascularity: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The percentage change in these indices, during a uterine contraction, was calculated from the baseline value during the initial uterine relaxation phase (taken as a maximum of 100%). RESULTS: Myometrial blood flow fell significantly during the uterine contraction and returned during the subsequent relaxation phase of the cycle (P < 0.001 for VI and VFI, P = 0.002 for FI). From the initial baseline relaxation value, VI dropped to 43.9%, FI to 85.5% and VFI to 40.8% during uterine contraction, and returned to 86.7%, 98.1% and 89.1%, respectively, during the subsequent relaxation. The intraclass correlation coefficients in blood flow measurements of 0.982-0.999 between the two investigators were indicative of good interobserver reliability. CONCLUSIONS: This study confirms that myometrial perfusion, as measured by quantitative 3D power Doppler angiography, significantly falls during uterine contractions, returns during the subsequent relaxation phase, and can be quantified reliably from stored datasets. Further work is now required to establish clinical applicability for this non-invasive investigation.


Asunto(s)
Miometrio/irrigación sanguínea , Contracción Uterina/fisiología , Adulto , Angiografía/métodos , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Edad Gestacional , Humanos , Imagenología Tridimensional/métodos , Primer Periodo del Trabajo de Parto/fisiología , Miometrio/diagnóstico por imagen , Miometrio/fisiopatología , Embarazo , Estudios Prospectivos , Ultrasonografía Prenatal/métodos
17.
Placenta ; 29(4): 356-65, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18336903

RESUMEN

Agonist-induced tone oscillations (rhythmic contractions and relaxations) occur in vascular beds to allow acute regulation of volume flow and thus the delivery of oxygen and nutrients to the tissue. Mechanisms responsible for the control of human placental vasomotor tone and blood flow are poorly characterized. This study aimed to characterise thromboxane-induced tone oscillations in human placental and myometrial arteries. Chorionic plate and myometrial arteries obtained from biopsies at term were mounted for isometric tension measurement. Tone oscillations were observed in chorionic arteries only when exposed to sub-maximal (<1 microM) concentrations of U46619. Slow (mean+/-SEM) frequency (2.6+/-0.5 per hour), large amplitude (39+/-7% of peak contraction) tone oscillations were elicited by 0.03 microM U46619 (n=18). In the presence of the nitric oxide synthase (NOS) inhibitor l-NNA (100 microM) the amplitude was significantly reduced (40+/-13% to 18+/-8%, P<0.05, n=6), frequency was unaltered and the bradykinin-dependent vasodilator response was reduced (68+/-13% to 40+/-19%, P<0.05, n=6). Myometrial arteries exposed to 1 microM U46619 developed tone oscillations within 10 min, which increased in amplitude over 30min occurring at relatively constant frequency. The mean amplitude of oscillations at 30 min (31+/-7%, n=16) was similar to that in chorionic arteries but the occurrence more frequent (42.8+/-9.7 per hour, P<0.001). Inhibition of NOS did not alter tone oscillations in myometrial arteries. Tone oscillations in chorionic arteries from pre-eclamptic and growth restricted (FGR) pregnancies were reduced in amplitude whereas those in myometrial arteries had increased frequency. Inhibition of NOS further reduced oscillation amplitude in chorionic arteries from FGR pregnancies. The alterations may contribute to the vasculopathology of these conditions, or, may represent compensatory mechanisms to maintain a matching of materno-placental blood flow.


Asunto(s)
Arterias/fisiología , Retardo del Crecimiento Fetal/fisiopatología , Tono Muscular/fisiología , Miometrio/irrigación sanguínea , Placenta/irrigación sanguínea , Preeclampsia/fisiopatología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Adolescente , Adulto , Arterias/efectos de los fármacos , Arterias/fisiopatología , Peso al Nacer , Presión Sanguínea/fisiología , Bradiquinina/farmacología , Corion/irrigación sanguínea , Femenino , Humanos , Tono Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Miografía , Óxido Nítrico/metabolismo , Nitroarginina/farmacología , Embarazo , Flujo Sanguíneo Regional/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos
18.
Hypertens Pregnancy ; 27(1): 29-38, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18293202

RESUMEN

OBJECTIVE: To investigate the effect of TNF-alpha on the endothelial function of human systemic arteries. METHODS: Omental arteries were obtained from healthy pregnant women undergoing Cesarean section and examined using isometric wire myography. RESULTS: Incubation with TNF-alpha (1nM) alone did not alter bradykinin-mediated endothelium-dependent relaxation of arteries. However, TNF-alpha did attenuate nitric oxide- (NO) and prostacyclin-independent endothelial-mediated relaxation. Similarly, in vessels constricted with a high potassium solution (60 mM), which inhibits vasodilatation via endothelial-derived hyperpolarising factor (EDHF), TNF-alpha incubation also attenuated bradykinin-induced vasodilatation. CONCLUSIONS: The vasorelaxant capacity of human systemic arteries is compromised by TNF-alpha incubation in the presence of NO/prostacyclin or EDHF-blockade.


Asunto(s)
Arterias/fisiología , Factores Biológicos/fisiología , Endotelio Vascular/fisiología , Óxido Nítrico/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Vasodilatación/fisiología , Adulto , Bradiquinina/fisiología , Epoprostenol/fisiología , Femenino , Humanos , Epiplón/irrigación sanguínea
19.
Sci Total Environ ; 406(1-2): 287-97, 2008 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-18625513

RESUMEN

Lead mining in the Sierra Madrona mountains and the valley of Alcudia in Southern Spain began in the 1st millennium B.C., and the area was intermittently exploited up until the end of the 20th century. The degree of contamination by Pb, Zn, Cd, Cu, As and Se of soil, water and sediment, and the transfer to 13 species of plants, and then to red deer (Cervus elaphus) have been studied. Mined areas had higher concentrations in stream sediments than control areas. The highest concentrations were observed for Pb (1481 microg g(-1) d.w.) and As (1880 microg g(-1)) in the sediment of a stream flowing beside the spoil dump at Mina de Horcajo. Plants from mining sites contained consistently higher levels of Pb and As, and their concentrations in plants were correlated. The highest concentrations of Pb were in Gramineae (Pb: 97.5, As: 2.4 microg g(-1) d.w.), and the lowest in elmleaf blackberry (Rubus ulmifolius). The highest mean liver concentrations were found in red deer from the mining sites for Pb (0.805 microg g(-1) d. w.), Cd (0.554 microg g(-1)), Se (0.327 microg g(-1)), and As (0.061 microg g(-1)), although these were well below the levels associated with clinical poisoning.


Asunto(s)
Ciervos/metabolismo , Monitoreo del Ambiente , Metales/análisis , Minería , Plantas/metabolismo , Contaminantes del Suelo/análisis , Contaminantes Químicos del Agua/análisis , Animales , Sedimentos Geológicos/análisis , Sedimentos Geológicos/química , Metales/metabolismo , Metales/toxicidad , Plantas/clasificación , Medición de Riesgo , Suelo/análisis , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , España , Especificidad de la Especie , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad
20.
Sci Total Environ ; 399(1-3): 193-201, 2008 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-18455757

RESUMEN

The Iberian lynx (Lynx pardinus) is the most endangered felid in the world with a wild population which probably stands at less than 200 individuals inhabiting two areas in Southern Spain (Doñana and Sierra Morena) that are known to have been contaminated by heavy metals and metalloids due to a long history of mining activities. This contamination may pose a threat to long term conservation efforts and hence, the concentrations of seven elements (As, Se, Cd, Zn, Cu, Pb, Hg) were determined in the liver, muscle and bone of 9 lynx, as well as 17 red foxes (Vulpes vulpes), 11 Egyptian mongooses (Herpestes ichneumon), 4 common genets (Genetta genetta) and 1 Eurasian badger (Meles meles). The mean concentrations found were below the threshold levels indicative of chronic intoxication in all the species studied. In general, genet and red fox were species with the highest concentrations of several elements in Doñana, whilst Iberian lynx had the lowest levels of most of them. Lynx from Sierra Morena had significantly higher concentrations of bone Pb (2.05 microg/g d.w.) than those from Doñana (0.13 microg/g d.w.), probably due to the mineralised underlying geology and/or the abandoned mine workings in Sierra Morena. Egyptian mongoose presented liver concentrations of Hg up to 9.7 microg/g d.w. A strong relationship between Hg and Se levels was found in liver and muscle samples of all the studied species, especially in mongoose. In conclusion, levels of the studied elements do not appear to represent a significant threat for the lynx or for the other carnivores studied. However, given the critical status of the Iberian lynx, a continuous monitoring scheme remains necessary.


Asunto(s)
Animales Salvajes , Hígado/efectos de los fármacos , Metales Pesados/toxicidad , Minería , Músculo Esquelético/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Carnívoros , Femenino , Zorros , Hígado/metabolismo , Lynx , Masculino , Metales Pesados/análisis , Metales Pesados/metabolismo , Músculo Esquelético/metabolismo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/química , Contaminantes del Suelo/metabolismo , España , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo
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