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1.
Phys Rev Lett ; 126(8): 083001, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33709752

RESUMEN

The first direct experimental observation of an electric quadrupole (E2) absorption transition between bound states of an atomic negative ion has been made. The transition was observed in the negative ion of bismuth by resonant (1+1) photon detachment from Bi^{-} via ^{3}P_{2}→^{3}P_{0} excitation. The E2 transition properties were completely independently calculated using a hybrid theoretical approach to account for the strong multilevel electron interactions and relativistic effects. The experimental and ab initio theoretical results are in excellent agreement, providing valuable new insight into this complex system and forbidden transitions in negative ions more generally.

2.
Regul Toxicol Pharmacol ; 75: 72-80, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26743742

RESUMEN

Profound immunosuppression (e.g., AIDS, transplant therapy) is epidemiologically associated with an increased cancer risk, and often with oncogenic viruses. It is currently unclear how broadly this association translates to therapeutics that modulate immunity. A workshop co-sponsored by the FDA and HESI examined how perturbing the immune system may contribute to carcinogenesis, and highlighted priorities for improving non-clinical risk assessment of targeted immunomodulatory therapies. Conclusions from the workshop were as follows. 1) While profound altered immunity can promote tumorigenesis, not all components of the immune system are equally important in defense against or promotion of cancer and a similar cancer risk for all immunomodulatory molecules should not be assumed. 2) Rodent carcinogenicity studies have limitations and are generally not reliable predictors of cancer risk associated with immunosuppression. 3) Cancer risk needs to be evaluated based on mechanism-based weight-of-evidence, including data from immune function tests most relevant to tumor immunosurveillance or promotion. 4) Information from nonclinical experiments, clinical epidemiology and immunomodulatory therapeutics show that immunosurveillance involves a complex network of cells and mediators. To support a weight-of-evidence approach, an increased focus on understanding the quantitative relationship between changes in relevant immune function tests and cancer risk is needed.


Asunto(s)
Factores Inmunológicos/efectos adversos , Neoplasias/inducido químicamente , Animales , Humanos , Neoplasias/epidemiología , Neoplasias/inmunología , Medición de Riesgo/legislación & jurisprudencia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología
3.
J Orthop Trauma ; 38(9): 477-483, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39150298

RESUMEN

OBJECTIVES: To identify factors that contribute to iatrogenic sciatic nerve palsy during acetabular surgery through a Kocher-Langenbeck approach and to evaluate if variation among individual surgeons exists. DESIGN: Retrospective cohort. SETTING: Level I trauma center. PATIENT SELECTION CRITERIA: Adults undergoing fixation of acetabular fractures (AO/OTA 62) through a posterior approach by 9 orthopaedic traumatologists between November 2010 and November 2022. OUTCOME MEASURES AND COMPARISONS: The prevalence of iatrogenic sciatic nerve palsy and comparison of the prevalence and risk of palsy between prone and lateral positions before and after adjusting for individual surgeon and the presence of transverse fracture patterns in logistic regression. Comparison of the prevalence of palsy between high-volume (>1 patient/month) and low-volume surgeons. RESULTS: A total of 644 acetabular fractures repaired through a posterior approach were included (median age 39 years, 72% male). Twenty of 644 surgeries (3.1%) resulted in iatrogenic sciatic nerve palsy with no significant difference between the prone (3.1%, 95% confidence interval [CI], 1.9%-4.9%) and lateral (3.3%, 95% CI, 1.3%-8.1%) positions (P = 0.64). Logistic regression adjusting for surgeon and transverse fracture pattern demonstrated no significant effect for positions (odds ratio 1.0, 95% CI, 0.3-3.9). Transverse fracture pattern was associated with increased palsy risk (odds ratio 3.0, 95% CI, 1.1-7.9). Individual surgeon was significantly associated with iatrogenic palsy (P < 0.02). CONCLUSIONS: Surgeon and the presence of a transverse fracture line predicted iatrogenic nerve palsy after a posterior approach to the acetabulum in this single-center cohort. Surgeons should perform the Kocher-Langenbeck approach for acetabular fixation in the position they deem most appropriate, as the position was not associated with the rate of iatrogenic palsy in this series. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Acetábulo , Fracturas Óseas , Enfermedad Iatrogénica , Neuropatía Ciática , Humanos , Acetábulo/lesiones , Acetábulo/cirugía , Masculino , Femenino , Enfermedad Iatrogénica/epidemiología , Adulto , Estudios Retrospectivos , Fracturas Óseas/cirugía , Neuropatía Ciática/etiología , Neuropatía Ciática/epidemiología , Persona de Mediana Edad , Posicionamiento del Paciente/métodos , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Nervio Ciático/lesiones , Prevalencia
4.
Sci Total Environ ; 898: 165474, 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37463626

RESUMEN

This study examines the simultaneous water-atmosphere exchange of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) on the continental shelf of the Gulf of Cadiz, as well as the effect it has in terms of the radiative balance in the atmosphere, between 2014 and 2016. The experimental database consists of new measurements of the spatial and seasonal distribution of CO2 partial pressure (pCO2) and N2O concentration in 2016. pCO2 shows a wide range of variation influenced mainly by seasonal thermal variations (8.0 µatm 0C-1), as well as with the relative intensity of biological activity. There is experimental evidence of a progressive increase of pCO2 over the last 2 decades, with an estimated gradient of 4.2 ± 0.7 µatm y-1. During 2016, the Gulf of Cadiz acted as a slight source of CO2 to the atmosphere, with a mean flux of 0.4 ± 2.2 mmol m-2 d-1. The analysis of concentration variations in the water column shows that nitrification is the main N2O production process in the study area, although in the more coastal zone there are signs of inputs related to continental and sediment contributions, most probably induced by denitrification processes. In 2016, the Gulf of Cadiz acted as a weak sink of atmospheric N2O, with a mean flux of -0.1 ± 0.9 µmol m-2 d-1. From previous studies, performed with a similar methodology, an interannual database (2014-2016) of water-atmosphere fluxes of CO2, CH4 and N2O, normalized to the mean wind speed in the area, has been generated. Considering their respective Global Warming Potential (GWP) a joint greenhouse gasses (GHG) flux, expressed in CO2 equivalents of 0.6 ± 2.0 mmol m-2 d-1, has been estimated, which extended to the area of study indicates an approximate emission of 67.9 Gg CO2 y-1. However, although there is a high uncertainty associated with the spatial, temporal and interannual variations of CO2, CH4 and N2O fluxes in the Gulf of Cadiz, the exchange of greenhouse gasses could be influencing a radiative forcing increase in the atmosphere. When considering the available information on local and global estimates, the uncertainty about the effect of the joint exchange of GHGs to the atmosphere from the coastal seas increases significantly.

5.
Front Plant Sci ; 14: 1278608, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37965003

RESUMEN

Climate change is one of the biggest threats that human society currently needs to face. Heat waves associated with global warming negatively affect plant growth and development and will increase in intensity and frequency in the coming years. Tomato is one of the most produced and consumed fruit in the world but remarkable yield losses occur every year due to the sensitivity of many cultivars to heat stress (HS). New insights into how tomato plants are responding to HS will contribute to the development of cultivars with high yields under harsh temperature conditions. In this study, the analysis of microsporogenesis and pollen germination rate of eleven tomato cultivars after exposure to a chronic HS revealed differences between genotypes. Pollen development was either delayed and/or desynchronized by HS depending on the cultivar considered. In addition, except for two, pollen germination was abolished by HS in all cultivars. The transcriptome of floral buds at two developmental stages (tetrad and pollen floral buds) of five cultivars revealed common and specific molecular responses implemented by tomato cultivars to cope with chronic HS. These data provide valuable insights into the diversity of the genetic response of floral buds from different cultivars to HS and may contribute to the development of future climate resilient tomato varieties.

6.
Braz J Biol ; 84: e264425, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36722676

RESUMEN

The ixodicidal activity of the methanolic extracts of Artemisia ludoviciana (Astereceae), Cordia boissieri (Boraginaceae) and Litchi chinensis (Sapindaceae) against two field populations of Rhipicephalus (Boophilus) microplus from the state of Nuevo Leon (NL) and Veracruz (VER) was evaluated. The extract of L. chinensis in the concentration of 150 mg/ml showed efficacies of 100% and 99% against engorged females and mortalities of 98% and 99% against larvae. C. boissieri in the same concentration showed efficacies of 71% and 37% against engorged adults and mortalities of 33.04% and 10.33% against larvae and A. ludoviciana had efficacies of 94% and 83% in adults and mortalities of 89.39% and 89.21% against larvae in both populations respectively. The enzymatic activity of Acetylcholinesterase (AChE), Carboxylesterase (CaE), Glutathione-S-Transferase (GST) and Alkaline Phosphatase (ALP) was measured in both populations of ticks. As a result, a significant difference between both populations was shown, being the VER population the one that exhibited a higher enzymatic activity (p ≤ 0.05). It can be concluded that the methanolic extract of the seed of L. chinensis shows potential ixodicidal activity and can be used as an alternative source of tick control, however, prior characterization, toxicity and formulation studies are necessary.


Asunto(s)
Artemisia , Cordia , Ixodidae , Litchi , Rhipicephalus , Femenino , Animales , Acetilcolinesterasa , Glutatión Transferasa , Larva , Metanol , Extractos Vegetales/farmacología
7.
Sci Total Environ ; 779: 146314, 2021 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-34030236

RESUMEN

The Mar Menor is a hypersaline coastal lagoon with salinity values ranging from 41.9 to 45.5. The system is subjected to a high anthropic pressure that causes an intense eutrophication process, followed by a recovery of the macrophyte meadows. This study focuses on the distribution of the main greenhouse gases (CO2, CH4 and N2O) and was carried out in the extreme seasonal conditions of winter and summer during the year 2018. Sediment-water-atmosphere exchanges and biochemical processes in the water column appeared to be the main factors to explain the variability of these gases. Dissolved Inorganic Carbon (DIC), CH4 and N2O benthic fluxes values obtained in this study, were of 91 ± 29 mmol m-2 d-1, 3.9 ± 1.9 µmol m-2 d-1 and -0.65 µmol m-2 d-1, respectively, along with an important seasonal variation observed, with an increase of DIC and CH4 benthic fluxes during the summer season. Mean values of partial pressure of CO2 (pCO2) in surface water were of 579 µatm in winter and 464 µatm in summer, therefore we can establish that the Mar Menor acts as a source of this gas emitting 3.3 ± 3.0 mmol CO2 m-2 d-1 to the atmosphere. In spite of this, the Mar Menor has a strong autotrophic behaviour partly due to the recovery of the macrophyte meadows, presenting an estimated NEP of 101 mmol m-2 d-1. Regarding to CH4, the mean fluxes to the atmosphere were of 8.0 ± 5.8 µmol m-2 d-1 and there was evidence of CH4 production in the water column that increased in summer. Last of all, in the case of N2O the system acts as a sink with values of -0.65 ± 0.5 µmol m-2 d-1, presenting an intake of N2O that is usually detected in pristine systems.

8.
Clin Exp Dermatol ; 34(4): 481-6, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19040507

RESUMEN

Disseminated cutaneous histoplasmosis is an opportunistic infection in patients with acquired immunodeficiency syndrome. We report a series of 23 cases (21 men, two women; median age 29 years) with disseminated cutaneous histoplasmosis seen at two hospital centres. Most of the patients (21/23) were classified as stage C3. The most common dermatological findings were papules, crusting plaques, nodules and ulcers, mainly located on the face and chest. Of the 23 cases, 15 (65%) had pulmonary involvement. Amphotericin B and itraconazole were the main drugs used for treatment. Treatment response was variable: four of the patients were cured, six improved and remain stable, nine patients died, and four patients were lost to follow-up.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/patología , VIH-1 , Histoplasmosis/patología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Femenino , Histoplasmosis/tratamiento farmacológico , Humanos , Itraconazol/uso terapéutico , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
9.
Stud Mycol ; 61: 77-82, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19287529

RESUMEN

Tinea nigra is a superficial mycosis caused by Hortaea werneckii. It is an infrequent asymptomatic infection that affects human palms and soles, and is mostly observed in tropical countries. We evaluate retrospectively twenty-two confirmed cases of tinea nigra from a total of eleven yr (1997-2007) and discuss the epidemiology, clinical features and treatment of this disease. In twelve cases, adults were involved, in 10, children. In nineteen cases the disorder was located on palms of hands and in three on soles of feet. In all cases, the obtained isolates were morphologically identified as Hortaea werneckii and the identification of ten isolates was retrospectively confirmed with the help of sequences of the internal transcribed spacer regions of the ribosomal DNA. The patients received topical treatment with Whitfield ointment, ketoconazole, bifonazole, or terbinafine. Treatment with keratolytic agents and topical antifungals was effective.

10.
Oral Dis ; 14(6): 569-74, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18248590

RESUMEN

OBJECTIVE: To present a clinical report of palatal zygomycosis, its epidemiological, mycological features, and our treatment experience. DESIGN: Retrospective report. SUBJECTS AND METHODS: This is a 25-year long retrospective trial of clinically and mycologically proven cases of zygomycosis. Some patients underwent a biopsy of the palatal lesion and autopsy. This study reports the treatment experience with amphotericin B alone and in combination with itraconazole and fluconazole. RESULTS: Twenty-one cases (18.75%) of zygomycosis with palatal involvement were included in the study, from a total of 112 cases screened. Mean age was 36.5 years, with 18 adults and three children. The associated pre-disposing factors were: ketoacidotic diabetes (five type-1 and 15 type-2), and acute leukaemia in one patient. The clinical varieties were as follows: 19 cases of rhinocerebral (RC) involvement and two disseminated cases. Palatal ulcers occurred in 3/21 early cases (14.3%) and in 16/21 cases after the nasal involvement. All patients received amphotericin B; in four patients, it was combined with itraconazole and four with fluconazole. Clinical and mycological cure was achieved in 4/21 patients (19.04%). CONCLUSION: Zygomycosis with palatal involvement occurs in around 18% of cases, usually associated with RC modalities; it has an acute and generally lethal course.


Asunto(s)
Enfermedades de la Boca/microbiología , Hueso Paladar/microbiología , Cigomicosis/diagnóstico , Absidia/aislamiento & purificación , Adolescente , Adulto , Anciano , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Encefalopatías/microbiología , Niño , Cetoacidosis Diabética/complicaciones , Combinación de Medicamentos , Femenino , Fluconazol/administración & dosificación , Fluconazol/uso terapéutico , Humanos , Itraconazol/administración & dosificación , Itraconazol/uso terapéutico , Masculino , Enfermedades de la Boca/tratamiento farmacológico , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Enfermedades Nasales/microbiología , Infecciones Oportunistas/diagnóstico , Úlceras Bucales/microbiología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicaciones , Estudios Retrospectivos , Rhizopus/aislamiento & purificación , Resultado del Tratamiento , Cigomicosis/tratamiento farmacológico
11.
Sci Total Environ ; 590-591: 695-707, 2017 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-28291614

RESUMEN

Methane (CH4) concentrations were measured along three sections of the eastern Gulf of Cadiz (designated "Guadalquivir", "Sancti Petri" and "Trafalgar") during eight cruises in 2014 and 2015. The concentration of CH4 varied from 3.6 to 19.7nmolkg-1 (CH4 saturation percent of 122 and 916%), showing seasonal variation. The highest values were found in December 2014 and November 2015. In most of the sampling area the highest concentration of CH4 was found in subsurface waters at depths close to the thermocline, and in the bottom waters near the coast. The seawater-air flux of CH4 ranged between 0.8 and 59.7µmolm-2d-1, showing seasonal variation in function of the temperature of the surface water. In the "Guadalquivir" and "Sancti Petri" sections, the CH4 fluxes increased with proximity to the coast; this may be a result of continental inputs and CH4 emissions from sediments. The whole study area behaves as a source of CH4 to the atmosphere with mean values of 0.5 and 0.6GgCH4yr-1 in 2014 and 2015, respectively.

12.
Sci Total Environ ; 593-594: 796-808, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28366870

RESUMEN

Distribution of N2O has been determined in eight cruises along three transects (Guadalquivir, Sancti Petri and Trafalgar) in the Gulf of Cadiz, during 2014 and 2015. The mean N2O value for this area was 10.0±0.9nM, with large spatial and temporal variations. Stratification in the water column has been observed; the concentration of this gas increases with the depth, because of the presence of the Eastern North Atlantic Central Water (ENACW) and the Mediterranean Outflow Waters (MOW). The N2O production measured in this study is mainly due to nitrification. N2O yields from nitrification were estimated from the linear correlation of the excess of N2O (ΔN2O) with Apparent Oxygen Utilization (AOU) and nitrate (NO3-), with values of their slopes ranged between 0.010 and 0.021% and 0.017-0.025% respectively. There is an onshore - offshore gradient of N2O; the highest values were found at the shallower stations, indicating coastal input and benthic remineralization. The seawater-air flux of N2O is affected by several variables (temperature, AOU and NO3-), and the average flux calculated is 2.7±2.0µmolm-2d-1. The fluxes show a decrease with increasing distance from the coast, and with proximity to the Strait of Gibraltar. The study area behaves as a source of N2O to the atmosphere, with a global emission of 0.18Ggyear-1.

13.
Arch Oral Biol ; 60(2): 313-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25438100

RESUMEN

OBJECTIVE: Connexins (Cxs) are important to control growth and cell differentiation of dental tissues. The aim of the present study was to assess the impact of chronic exposure to sodium fluoride (NaF) on Cxs expression and alkaline phosphatase (ALP) activity in dental pulp, and on morphometric parameters of adult rat mandible and incisors. DESIGN: Three groups of male Wistar rats (22 days-old) were given water containing: (a) 0.3 mg/L (Control), (b) 10 mg/L and (c) 50 mg/L of NaF for eight weeks. Incisor pulp homogenates were prepared for determination of Cx32, Cx43 and Cx45 gene expression, using semi-quantitative RT-PCR, and of ALP activity. Morphometric parameters of mandible and incisors were determined on radiographs. RESULTS: Cx43 gene expression increased with exposure to NaF in a dose-dependent manner. Cx32 mRNA levels were higher than controls in the 10mg/L NaF group only; Cx45 mRNA levels were lower in groups given 10 and 50mg/L of NaF than in controls. ALP activity was higher in both high-NaF dose groups compared to the control group (p<0.05). Lower incisor diameter was lower in the 50 mg/L NaF than in the control group (p<0.01). None of the mandibular growth parameters were affected by NaF treatment. CONCLUSION: Our results showed that fluorotic alterations in rat incisor were associated with increased Cx43 expression and ALP activity, as well as with changes in the expression pattern of different Cxs in pulp tissue. The observed changes may have a stimulating effect on dentin mineralization.


Asunto(s)
Conexinas/metabolismo , Pulpa Dental/efectos de los fármacos , Pulpa Dental/metabolismo , Fluoruro de Sodio/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Conexinas/genética , Expresión Génica , Incisivo , Masculino , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
J Immunol Methods ; 256(1-2): 35-46, 2001 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11516753

RESUMEN

One method for examining cell cycle kinetics by flow cytometry uses continuous DNA labeling with bromodeoxyuridine (BrdU), a thymidine analogue. Upon incorporation into DNA, BrdU causes stoichiometric quenching of the DNA fluorochrome Hoechst 33258. After counterstaining with a secondary DNA fluorochrome (e.g., ethidium bromide), the analyst can distinguish cells in different phases of the cell cycle over a number of mitotic cycles with flow cytometry. In this report, we describe a modification of the flow cytometric BrdU-Hoechst assay that allows combined analysis of cell proliferation and immunophenotyping at the single cell level. To demonstrate an application of this method, human peripheral blood mononuclear cells were stimulated with tetanus toxoid or interleukin-2 for up to 6 days in the presence of BrdU, harvested, and immunostained for the cell surface markers CD3, CD4, CD8, CD14, CD19, and the cytokine receptor, CCR5. We used four-color flow cytometry analyses to simultaneously measure cell proliferation and surface marker expression, for the purpose of immunophenotyping and identifying specific cell subsets responding to antigen stimulation. Our successful application of this method suggests that it may be used to study immune responses at the molecular and cellular level and to identify mechanisms of immune system modulation.


Asunto(s)
Antígenos de Diferenciación de Linfocitos B/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Inmunofenotipificación/métodos , Subgrupos Linfocitarios/clasificación , Bisbenzimidazol/química , Bromodesoxiuridina/química , Ciclo Celular , Permeabilidad de la Membrana Celular , Células Cultivadas , ADN/análisis , Dactinomicina/análogos & derivados , Dactinomicina/química , Etidio/química , Fijadores/química , Citometría de Flujo , Colorantes Fluorescentes/química , Formaldehído/química , Humanos , Activación de Linfocitos , Subgrupos Linfocitarios/química , Subgrupos Linfocitarios/citología , Polímeros/química
15.
Environ Health Perspect ; 108 Suppl 1: 13-21, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10698720

RESUMEN

An important public health challenge has been the need to protect children's health. To accomplish this goal, the scientific community needs scientifically based child-specific risk assessment methods. Critical to their development is the need to understand mechanisms underlying children's sensitivity to environmental toxicants. Risk is defined as the probability of adverse outcome and when applied to environmental risk assessment is usually defined as a function of both toxicity and exposure. To adequately evaluate the potential for enhanced health risks during development, both child-specific factors affecting toxicity and exposure need to be considered. In the first section of this article, example mechanisms of susceptibility relevant for toxicity assessment are identified and discussed. In the second section, examples of exposure factors that help define children's susceptibility are presented. Examples of pesticide research from the newly funded Child Health Center at the University of Washington will be given for illustration. The final section discusses the importance of putting these considerations of children's susceptibility into an overall framework for ascertaining relevancy for human risk assessment.


Asunto(s)
Protección a la Infancia , Contaminantes Ambientales/toxicidad , Niño , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/análisis , Genética , Humanos , Medición de Riesgo
16.
Toxicol Sci ; 75(1): 124-33, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12805652

RESUMEN

5'-bromodeoxyuridine (BrdU) labeling was employed to explore the effects of methylmercury (MeHg) on cell cycle kinetics in the developing rat midbrain during gestational days (GDs) 11 to 14. Contrary to what has been previously reported in mice, no effects of MeHg on cell cycle kinetics were observed up to embryonic brain concentrations of 3-4 microg/g. The absence of an effect was confirmed using stereology and counts of midbrain cell number. Treatment with colchicine, the positive control, resulted in significant effects on cell cycle kinetics in the developing rat midbrain. The parallelogram method, borrowed from genetic toxicology, was subsequently used to place the data obtained in the present study in the context of previously collected in vitroand in vivo data on MeHg developmental neurotoxicity. This required developing a common dose metric (microg Hg/g cellular material) to allow in vitro and in vivo study comparisons. Evaluation suggested that MeHg's effects on neuronal cell proliferation show a reasonable degree of concordance across mice, rats, and humans, spanning approximately an order of magnitude. Comparisons among the in vivo data suggest that humans are at least or more sensitive than the rodent and that mice may be a slightly better model for MeHg human developmental neurotoxicity than the rat. Such comparisons can provide both a quantitative and a qualitative framework for utilizing both in vivo and in vitro data in human health risk assessment.


Asunto(s)
Desarrollo Embrionario y Fetal/efectos de los fármacos , Mesencéfalo/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Organogénesis/efectos de los fármacos , Animales , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Citometría de Flujo , Humanos , Técnicas In Vitro , Inyecciones Subcutáneas , Mesencéfalo/embriología , Compuestos de Metilmercurio/administración & dosificación , Ratones , Embarazo , Ratas , Ratas Sprague-Dawley , Medición de Riesgo , Especificidad de la Especie , Factores de Tiempo
17.
J Gastrointest Surg ; 4(5): 547-53, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11077333

RESUMEN

Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta-glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta-glucuronidase or slime production. Ninety-one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta-glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P <0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta-glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62% of patients with primary CBD stones, and 50% of patients with biliary tubes had one or more bacteria that produced beta-glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta-glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes.


Asunto(s)
Bacterias/enzimología , Sistema Biliar/microbiología , Colelitiasis/etiología , Glucuronidasa/biosíntesis , Colelitiasis/enzimología , Colelitiasis/microbiología , Colelitiasis/fisiopatología , Heces/microbiología , Femenino , Cálculos Biliares/enzimología , Cálculos Biliares/microbiología , Humanos , Masculino , Persona de Mediana Edad
18.
Neurotoxicology ; 20(5): 793-804, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10591515

RESUMEN

Previous studies indicate that the ability of cells to up-regulate levels of intracellular glutathione (GSH) synthesis may determine their sensitivity to MeHg exposure. The purpose of the current study is two-fold. First, we determined whether the vulnerability of the developing central nervous system (CNS) to MeHg lies in its intracellular GSH content. The intracellular GSH content and the activity of gamma-glutamyl cysteine synthetase (GCS) were determined with and without MeHg exposure in primary cultures of rat embryonic CNS cells. In addition, the effect of GSH modulation on MeHg-induced cytotoxicity was determined. Second, we characterized the mechanism of GCS regulation, initially by studying the GCS heavy chain subunit (GCS-HC). Primary embryonic limb bud cells were used as a reference cell type for comparing the response of CNS cells. The results indicate that constitutive intracellular GSH content, GCS activity, and GCS-HC mRNA and protein levels of CNS cells were approximately ten-, two-, five-, and ten-fold higher, respectively, than those in limb bud cells. A dose-dependent increase in GSH levels and GCS activity was observed in CNS and limb bud cells following 1 and 2 microM MeHg exposure for 20 hr. Further characterization of GCS up-regulation in CNS cells showed that the increase in GCS activity following MeHg exposure, unlike limb bud cells, was not accompanied by an elevation of GCS-HC mRNA and protein levels. Pretreatment with N-acetylcysteine led to a significant increase in intracellular GSH, while L-buthionine-(S,R)-sulfoximine (BSO) resulted in decreased GSH levels, however neither pretreatment had a significant impact on MeHg-induced cytotoxicity in either cell type. Our results suggest that although oxidative stress may mediate aspects of MeHg toxicity, disruption of GSH homeostasis alone is not responsible for the sensitivity of embryonic CNS cells to MeHg.


Asunto(s)
Sistema Nervioso Central/patología , Embrión de Mamíferos/citología , Glutatión/fisiología , Compuestos de Metilmercurio/toxicidad , Neuronas/efectos de los fármacos , Acetilcisteína/farmacología , Aminoaciltransferasas/biosíntesis , Animales , Butionina Sulfoximina/farmacología , Diferenciación Celular/efectos de los fármacos , Sistema Nervioso Central/embriología , Embrión de Mamíferos/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Extremidades/embriología , Extremidades/inervación , Citometría de Flujo , Depuradores de Radicales Libres/farmacología , Homeostasis/fisiología , Neuronas/patología , Estrés Oxidativo/fisiología , Pirazoles , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos
19.
Sci Total Environ ; 274(1-3): 79-91, 2001 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-11453307

RESUMEN

Analyses of competing risks are currently limited by the lack of empirically well-founded and generalizable quantitative methods. Specifically, quantitative methods for comparative risk analysis require the consideration of the population impacted, the duration of impact, the health endpoints at risk, and the impact on individual quality of life. Whereas risk analysis can be used to provide quantitative estimates of disease incidence, environmental health policy analyses do not often account for differences in health impact from alternative disease states. We discuss the methodological issues related to the use of quality adjusted life years (QALY) as a metric for normalizing expected disease incidence to account for health impact. Through a case study of the risks and benefits of fish consumption, we demonstrate the use of QALY weights with dose-response models for environmental health policy decision making. We suggest that, although this approach can be generalized for use in comparative risk and health policy analysis, it is informationally intensive and requires additional assumptions to those used in traditional safety/risk assessment.


Asunto(s)
Salud Ambiental , Política de Salud , Modelos Biológicos , Años de Vida Ajustados por Calidad de Vida , Adulto , Distribución por Edad , Animales , Niño , Proteínas en la Dieta , Femenino , Peces , Humanos , Tablas de Vida , Masculino , Modelos Estadísticos , Mortalidad , Medición de Riesgo , Factores de Riesgo
20.
Int J Circumpolar Health ; 57 Suppl 1: 572-5, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-10093344

RESUMEN

Persistent organic compounds and trace metals are found in the arctic food chain, generating concerns about the safety of subsistence food consumption. One approach for evaluating subsistence food safety is a process used extensively in regulating environmental clean-up and pollution standards. This process, regulatory risk assessment, is substantially different from approaches used in public health risk assessment. Limitations to the use of regulatory risk assessment in assessing public health threats from environmental exposures in the diet include a narrow scope, a lack of incorporation of the nutritional and health benefits of subsistence foods, and the overestimation of risks because of the incorporation of worst-case assumptions in the absence of scientific information. Sound public health policy recognizes that attempts to err on the side of safety for one exposure by recommending reduced consumption of a selected food may inadvertently err on the side of harm by reducing a coexisting exposure of potentially great health benefit. The following discussion should serve as a useful background for future multidisciplinary discussions on the safety of subsistence foods in the Arctic.


Asunto(s)
Dieta , Contaminación Ambiental/efectos adversos , Contaminación de Alimentos/análisis , Salud Pública/tendencias , Alaska , Regiones Árticas , Seguridad de Productos para el Consumidor , Monitoreo del Ambiente/métodos , Humanos , Medición de Riesgo , Gestión de Riesgos
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