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Ceratocystis fimbriata is a destructive fungal pathogen of sweetpotato (Ipomoea batatas) that leads to losses at all stages of sweetpotato production. Accurate detection of C. fimbriata would allow for more efficient deployment of management tactics in sweetpotato production. To develop a diagnostic assay, a hybrid genome assembly of C. fimbriata isolate AS236 was generated. The resulting 31.7-MB assembly was near-chromosome level, with 18 contigs, 6,481 predicted genes, and a BUSCO completion score of 98.4% when compared with the fungus-specific lineage database. Additional Illumina DNA reads from C. manginecans, C. platani, and a second C. fimbriata isolate (C1421) were then mapped to the assembled genome using BOWTIE2 and counted using HTSeq, which identified 148 genes present only within C. fimbriata as molecular diagnostic candidates; 6 single-copy and 35 highly multi-copy (>40 BLAST hits), as determined through a self-BLAST-P alignment. Primers for PCR were designed in the 200-bp flanking region of the first exon for each candidate, and the candidates were validated against a diverse DNA panel containing Ceratocystis species, sweetpotato pathogens, and plants. After validation, two diagnostic candidates amplified only C. fimbriata DNA and were considered to be highly specific to the species. These genetic markers will serve as valuable diagnostic tools with multiple applications including the detection of C. fimbriata in seed, soil, and wash water in sweetpotato production.
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Ascomicetos , Genoma Fúngico , Ipomoea batatas , Enfermedades de las Plantas , Ipomoea batatas/microbiología , Enfermedades de las Plantas/microbiología , Ascomicetos/genética , Ascomicetos/aislamiento & purificación , Genoma Fúngico/genética , Análisis de Secuencia de ADN , ADN de Hongos/genéticaRESUMEN
Although fibromyalgia is a widespread chronic pain condition where 90 percent of patients are women, they are underrepresented in Randomized Clinical Trials (RCTs). We aim to describe the willingness to participate, assess different factors, and explore the impact of sociodemographic and clinical characteristics on perceived barriers to trial participation. This is a cross-sectional survey targeting women with fibromyalgia. Univariate and multivariate logistic regression were performed. Of the 436 women with fibromyalgia, 56 percent were very likely to participate in RCTs. Minorities expressed less interest than non-minorities, while higher pain scores, previous participation, and younger patients reported a higher interest. Barriers significantly associated with a reduced willingness were: the participant's perception (side effects, distance, potential negative impact), the center (reputation), the trial protocol (number of visits, placebo), and trial awareness by their physician. In a multivariate analysis, older age, low education, lower income, and higher pain scores were associated with perceived barriers to RCT participation. Despite the high interest to participate, factors such as side effects, the center's distance, number of visits, placebo treatments, and the institution's reputation must be considered in clinical trials for women with fibromyalgia.
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Fibromialgia , Participación del Paciente , Humanos , Fibromialgia/psicología , Fibromialgia/terapia , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Estados Unidos , Encuestas y Cuestionarios , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores Socioeconómicos , Anciano , Selección de PacienteRESUMEN
The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.
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In the Yucatan Peninsula, tropical preserved forests harbor a high diversity of phlebotomine sand fly species, potential vectors of Leishmania. As a result, a significant risk of contracting localized cutaneous leishmaniasis (LCL) is associated with entry into these forest ecosystems. However, with the current trajectory of land use in the region, communities now live within modified landscapes which could increase their risk of contact with vectors. In this study, we characterized the sand fly fauna and its relationship with the characteristics of peridomestic habitats in two rural communities in Yucatan characterized by contrasting records of leishmaniasis. Five human dwellings in each community were randomly selected and the peridomestic landscape was characterized (i.e., type and percentage of land use). For the collection of sand flies, CDC traps were deployed in both the intra and peridomicile. Differences in alpha and beta diversity between communities and ecotopes were estimated considering three separate groups, all species together, zoophilic species, and anthropophilic species. In total, 1, 241 sand flies represented by eight species were collected from November 2021-March 2022. Both communities registered the presence of sand flies in the intra and peridomicile, and females were more abundant than males. However, the greatest diversity of species was recorded in the peridomicile of the community with the highest composition of land uses. Our study demonstrates that the transformation of the forest around the communities favors the abundance and richness of sand flies in the peridomestic environment. We discuss the limitations and implications of our findings regarding the potential risk of the emergence of perirural cycles of leishmaniasis in the region.
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Leishmaniasis Cutánea , Phlebotomus , Psychodidae , Humanos , Masculino , Animales , Femenino , Ecosistema , México/epidemiología , Población Rural , Insectos Vectores , Leishmaniasis Cutánea/epidemiologíaRESUMEN
Could tropical forest conversion shape sand fly (Diptera: Phlebotominae) biting rhythms and Leishmania infection rates? Using a Shannon trap, we estimated the bite rate and infection prevalence among anthropophilic sand flies at sites with different land use in southern Mexico. We estimated the expected monthly infection rate of the Leishmania parasite along the gradient and generated information on the biting rhythm of sand flies in a poorly characterized cutaneous leishmaniasis endemic region. We used generalized mixed linear and mixed additives models to evaluate differences in the biting rate, nocturnal activity, and inoculation rate of female sand flies, as well as their relationship with the loss of forest cover and environmental disparities recorded throughout the study area. Our results show that the loss of forest cover influences the biting rhythm of sand fly species and the potential number of infectious bites with Leishmania, but the greatest entomological and potential epidemiological risk continues to be associated with sylvatic areas (amplification events). Despite this, we detected that the effect of forest cover (%) on the entomological exposure seems to be also dependent on the sand fly species, and that, albeit to a lesser extent, Leishmania parasite is circulating in disturbed landscapes through generalist and competent sand fly vector species. We also found that land use change did not affect the nocturnal activity, however we detected that important vector species were active most of the time. Contrary to our expectation, temperature and humidity did not shape the biting rhythm of sand fly species. We discuss the limitations and epidemiological implications of our findings regarding the risk of contracting leishmaniasis in southern Mexico.
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Mordeduras y Picaduras , Leishmania , Leishmaniasis Cutánea , Phlebotomus , Psychodidae , Animales , Femenino , Psychodidae/parasitología , México/epidemiología , Insectos Vectores/parasitología , Leishmaniasis Cutánea/epidemiologíaRESUMEN
Rickettsial diseases have seen a re-emergence in the Americas in the last few decades, with concerning morbidity, mortality and economic implications that result from loss of productivity, income, curbs in liberal trade agreements, and reduction in agricultural practices. The aim of this study is to determine the socioecological determinants and seroprevalence for Rickettsia typhi and Rickettsia rickettsii among residents of Teabo, a rural community of Yucatán, Mexico. Sociodemographic data and serum samples were obtained from 180 consenting participants. Antibody titers for R. typhi and R. rickettsii were determined by indirect immunofluorescence assay (IFA). Participants also submitted tick samples collected from their residential area. We conducted logistic regression models to evaluate the association between exposure variables and seroprevalence. Rhipicephalus sanguineus s.l. (37%; n = 65), and Amblyomma cajennense Fabricius (17%; n = 29) were the predominant tick species in peri-domestic areas. Out of the 180 participants, there was significantly higher seroprevalence of R. typhi (n = 77; 46%) compared to R. rickettsii [n = 27, 15%, (p < 0.05)]. Pearson's chi-square test of independence revealed significant differences in R. rickettsii seroprevalence by gender (X2 [n = 175, df = 4, (p < 0.001)] = 180.26), level of education, (X2 [n = 180, df = 4, (p < 0.001)] = 44.0), and by tick species found in residential area, (X2 [n = 180, df = 4, (p = 0.050)] = 9.48). After adjusting for other variables in a logistic regression model, for each unit increase in the number of dogs present in the residential area, there was a 27% increase in the odds of human seroprevalence for R. typhi IgG (AOR = 1.27, 95% CI: 1.01-1.63). Compared to study participants living in residential areas with a 'low' height of vegetation, those living in residential areas with a 'medium' height of vegetation had 2.5 times greater odds of human seroprevalence for R. typhi IgG (AOR = 2.51, 95% CI: 1.19-5.40). Potentially modifiable existing factors in the peri-domestic area may constitute a high-risk source of seroprevalence for rickettsial antibodies among residents of the rural community of Teabo, Yucatán, Mexico.
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Enfermedades de los Perros , Rhipicephalus sanguineus , Rickettsia , Animales , Enfermedades de los Perros/microbiología , Perros , Humanos , Inmunoglobulina G , México/epidemiología , Rhipicephalus sanguineus/microbiología , Población Rural , Estudios SeroepidemiológicosRESUMEN
As land use intensifies in tropical forests, it is expected that species assemblages will be modified and that key functions of these ecosystems will be affected. The latter scenario is important from a public health perspective, because the land use change has been linked the outbreaks of vector-borne diseases. In this study, we evaluated the response of Phlebotominae (Diptera: Psychodidae) assemblages and their pattern of co-occurrence in four sites with different land use in an emerging cutaneous leishmaniasis focus in Yucatan, Mexico. Our hypothesis is that the conservation status (as forest cover) will positively influence the structure and composition of sand flies' assemblages. Using three different traps over a period of five months, a sampling effort of 1, 440 night-traps was performed. A total of 7, 897 sand fly specimens belonging to six genera and 10 species were collected. Our hypothesis was partially achieved since sand fly diversity increased as forest cover increased and vice versa, however random patterns of co-occurrence in assemblages were detected among sites. Even though the high abundance of sand flies in the forest fragment suggests an amplification effect, our results show that different vector species directly dominate in each site. We discuss the potential implications of the nestedness of species dominance. We suggest that in this emerging focus and under the land use gradient, Lutzomyia cruciata and Psathyromyia cratifer could play a pivotal role in maintaining the transmission cycles of Leishmania. The apparent generalist or colonialist profile of Lu. cruciata in disturbed areas deserves attention, due to the potential risk of leishmaniasis "domiciliation". This information is essential to understand the eco-epidemiology of leishmaniasis and the factors associated with its emergence in Yucatan, Mexico.
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Leishmaniasis Cutánea , Phlebotomus , Psychodidae , Animales , Ecosistema , Insectos Vectores , Leishmaniasis Cutánea/epidemiología , México/epidemiologíaRESUMEN
The origin of deterministic macroscopic properties often lies in microscopic stochastic motion. Magnetic fluctuations that manifest as domain avalanches and chaotic magnetization jumps exemplify such stochastic motion and have been studied in great detail. Here we report Fourier space studies of avalanches in a system exhibiting competing magnetic stripe and skyrmion phase using a soft X-ray speckle metrology technique. We demonstrate the existence of phase boundaries and underlying critical points in the stripe and skyrmion phases. We found that distinct scaling and universality classes are associated with these domain topologies. The magnitude and frequency of abrupt magnetic domain jumps observed in the stripe phase are dramatically reduced in the skyrmion phase. Our results provide an incisive way to probe and understand phase stability in systems exhibiting complex spin topologies.
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The original version of this Article contained an error in Fig. 4d, in which the label of the region to the left of the white dashed lines incorrectly read 'Order stripes'. The correct version states 'Disorder stripes'. This has been corrected in both the PDF and HTML versions of the Article.
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The strong coupling constant α s is determined from inclusive jet and dijet cross sections in neutral-current deep-inelastic ep scattering (DIS) measured at HERA by the H1 collaboration using next-to-next-to-leading order (NNLO) QCD predictions. The dependence of the NNLO predictions and of the resulting value of α s ( m Z ) at the Z-boson mass m Z are studied as a function of the choice of the renormalisation and factorisation scales. Using inclusive jet and dijet data together, the strong coupling constant is determined to be α s ( m Z ) = 0.1157 ( 20 ) exp ( 29 ) th . Complementary, α s ( m Z ) is determined together with parton distribution functions of the proton (PDFs) from jet and inclusive DIS data measured by the H1 experiment. The value α s ( m Z ) = 0.1142 ( 28 ) tot obtained is consistent with the determination from jet data alone. The impact of the jet data on the PDFs is studied. The running of the strong coupling is tested at different values of the renormalisation scale and the results are found to be in agreement with expectations.
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Several studies have demonstrated an increase in peripheral resistance to insulin associated with hypertension. To assess the hemodynamic and metabolic effects of exercise training, normotensive and N(omega)-nitro-L-arginine methyl ester (L-NAME)-hypertensive male Wistar rats were submitted to low-intensity treadmill exercise training for 10 weeks and compared with their sedentary controls. Blood pressure signals were obtained and processed with a data acquisition system (CODAS, 1 kHz) to evaluate mean arterial pressure, heart rate, autonomic control of heart rate, and baroreflex sensitivity. Exercise training induced a nonsignificant 6.5-mm Hg decrease in mean arterial pressure in trained hypertensive rats (163+/-9 mm Hg) compared with sedentary hypertensive rats (169.5+/-5. 5 mm Hg). The hypertensive groups showed impairment of baroreflex function in response to changes in arterial pressure compared with sedentary controls. Furthermore, exercise training improved the tachycardic response to decreasing arterial pressure and reduced intrinsic heart rate in trained control rats compared with all other groups. Sedentary hypertensive rats presented a decrease in body weight compared with normotensive animals. Basal evaluation of the glucose/insulin ratio showed increased insulin resistance in sedentary (28.4+/-3) and trained (23.5+/-2.7) hypertensive rats compared with sedentary control rats (40.5+/-3). However, the glucose/insulin ratio evaluated during the exercise session in trained rats showed an improvement in insulin resistance (54.5+/-5 for control rats and 44+/-9 for hypertensive rats). In conclusion, L-NAME-induced hypertension is accompanied by an increase in insulin resistance in rats. The improvement in peripheral insulin sensitivity during exercise and the body weight gain observed in trained hypertensive rats may support the positive role of physical activity in the management of hypertension.
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Hipertensión/metabolismo , Hipertensión/fisiopatología , Resistencia a la Insulina , NG-Nitroarginina Metil Éster , Sistema Nervioso Simpático/fisiopatología , Animales , Hipertensión/inducido químicamente , Masculino , Condicionamiento Físico Animal , Presorreceptores/fisiopatología , Ratas , Ratas WistarRESUMEN
The usefulness of pulmonary carcinogenicity data from rats exposed to high concentrations of particles for quantitatively predicting lung cancer risk in humans exposed to much lower environmental or occupational concentrations has been questioned. The results of several chronic inhalation bioassays of poorly soluble, nonfibrous particles have suggested that rats may be more prone than other rodent species to develop persistent pulmonary epithelial hyperplasia, metaplasia, and tumors in response to the accumulation of inhaled particles. In addition, rats and primates differ in their pulmonary anatomy and rate of particle clearance from the lung. This paper reviews results of recent Lovelace Respiratory Research Institute (Albuquerque, NM) investigations that directly compared the anatomical patterns of particle retention and the lung tissue responses of rats and monkeys exposed chronically to high occupational concentrations of poorly soluble particles. Lung sections from male cynomolgus monkeys and F344 rats exposed 7 hr/day, 5 days/week for 24 months to filtered ambient air, diesel exhaust (2 mg soot/m3), coal dust (2 mg respirable particulate material/m3), or diesel exhaust and coal dust combined (1 mg soot and 1 mg respirable coal dust/m3) were obtained from a study conducted at the U.S. National Institute for Occupational Safety and Health and examined histopathologically and morphometrically. Within each species, the sites of particle retention and lung tissue responses were the same for diesel soot, coal dust, and combined material. Rats retained a significantly greater portion of the particulate material in the lumens of alveolar ducts and alveoli than monkeys. Conversely, monkeys retained a significantly greater portion of the particulate material in the interstitium than rats. Rats, but not monkeys, had significant alveolar epithelial hyperplastic, inflammatory, and septal fibrotic responses to the retained particles. These results suggest that anatomic patterns of particle retention and lung tissue reactions in rats may not be predictive of retention patterns and tissue responses in primates that inhale poorly soluble particles at concentrations representing high occupational exposures.
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Contaminantes Ocupacionales del Aire/efectos adversos , Contaminantes Ocupacionales del Aire/metabolismo , Carbón Mineral , Polvo/efectos adversos , Gasolina , Pulmón/patología , Emisiones de Vehículos/efectos adversos , Animales , Pulmón/metabolismo , Macaca fascicularis , Masculino , Pleura/metabolismo , Pleura/patología , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Ratas , Ratas Endogámicas F344RESUMEN
The cortisol suppression index (CSI) is a ratio of pre- to postdexamethasone plasma cortisol concentrations. In a sample of 24 psychiatric inpatients, an 8 a.m. CSI detected 66% of patients with major depression. Further studies with larger samples and additional controls, including normal subjects, are suggested to validate these prospective findings. This index may serve as a useful and more practical way of detecting major depression in outpatients.
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Trastorno Depresivo/diagnóstico , Dexametasona , Hidrocortisona/sangre , Adulto , Anciano , Atención Ambulatoria , Trastorno Bipolar/sangre , Trastorno Bipolar/diagnóstico , Trastorno Depresivo/sangre , Humanos , Trastornos Mentales/sangre , Trastornos Mentales/diagnóstico , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The abundance and activity of three subgroups of mitogen-activated protein (MAP) kinases, the extracellular signal regulated kinase 1 (ERK1), stress-activated protein kinase 1/ Jun N-terminal kinase (SAPK1), and stress-activated protein kinase 2/ p38 (SAPK2), were measured in gill epithelium of the euryhaline teleost Fundulus heteroclitus exposed for 1 h to 4 weeks to hyper- and hyposmotic stress. The abundance of ERK1, SAPK1 and SAPK2 was analyzed by standard Western immunodetection. MAP kinase activity is a function of phosphorylation and was measured using phospho-specific and MAP kinase subgroup-specific antibodies. The abundance of the 63 kDa fish isoform of SAPK2 increases significantly during hyper- but not hyposmotic stress while ERK1 and SAPK1 protein levels remain unchanged during both types of osmotic stress. In contrast to this small effect of osmotic stress on MAP kinase abundance, the activity of all MAP kinases decreases significantly in response to hyperosmotic stress and increases significantly during hyposmotic stress. These results demonstrate for the first time that the activity of all major MAP kinases is osmoregulated in gill epithelium of euryhaline fish. Based on these results we conclude that MAP kinases are important components of salinity adaptation and participate in osmosensory signaling pathways in gill epithelium of euryhaline fishes.
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Sistema de Señalización de MAP Quinasas , Transducción de Señal , Animales , Western Blotting , Electroforesis en Gel de Poliacrilamida , Peces , Branquias/fisiología , Proteína Quinasa 3 Activada por Mitógenos , Proteína Quinasa 8 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Presión Osmótica , Isoformas de Proteínas , Sales (Química)/metabolismo , Transducción Genética , Agua/metabolismo , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
PURPOSE: Mucoceles are cystic lesions, resulting from an obstruction in the paranasal sinuses and an accumulation of mucus, causing enlargement of the affected paranasal sinus. The signs and symptoms depend on the affected sinus. Treatment consists of surgical resection. The purpose of this study was to describe the clinical presentation of patients with mucocele, and also to describe the surgical results with our mucocele resection in patients treated in our institution over the last 10 years. METHODS: All patients with a diagnosis of mucocele over the last 10 years and treated in our institution were included. An analysis was performed on the symptoms, surgical technique, and results. RESULTS: Frontoethmoidal sinus mucoceles were the most common. Both eyes were affected but with no significant statistical differences. The median age at presentation was 52 years old, with no difference between both genders. The time to seek medical attention was shorter in frontal mucoceles. Proptosis was the most common symptom. Complications during surgery were reported in just one patient. Recurrence was reported in 12% of patients. DISCUSSION: Our results correlate with those in the literature. We reported satisfying results with our technique, avoiding sinus obliterations, with a recurrence of 12% versus 6% reported in previous studies. We believe that our technique is safe and accessible for ophthalmologists in mucoceles treatment.
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Mucocele/diagnóstico , Mucocele/cirugía , Enfermedades de los Senos Paranasales/diagnóstico , Enfermedades de los Senos Paranasales/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Instituciones de Salud , Humanos , Masculino , Persona de Mediana Edad , Oftalmología , Adulto JovenRESUMEN
The introduction of high-frequency oscillatory ventilation (HFOV) to the intensive care nursery has stimulated us to develop infant care protocols for babies so treated. We identified specific areas unique to the SensorMedics HFOV and initiated nursing techniques to address each of the following areas: assessment, airway care, feedings, positioning, and safety. In summary, while on HFOV, an infant's assessment and care need not be minimized.
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Ventilación de Alta Frecuencia/enfermería , Enfermería Neonatal/métodos , Planificación de Atención al Paciente , Protocolos Clínicos , Ventilación de Alta Frecuencia/efectos adversos , Ventilación de Alta Frecuencia/instrumentación , Ventilación de Alta Frecuencia/métodos , Humanos , Recién NacidoRESUMEN
Several chronic inhalation bioassays of poorly soluble, nonfibrous particles have resulted in an increased incidence of lung tumors in rats, no increase in lung tumors in Syrian hamsters, and inconsistent results in mice. These results have raised concerns that rats may be more prone than other species to develop persistent pulmonary epithelial hyperplasia, metaplasia, and tumors in response to the accumulation of inhaled particles. In addition, particle deposition and the rate of particle clearance from the lung differ between rats and primates, as does the anatomy of the centriacinar region. For these reasons, the usefulness of pulmonary carcinogenicity data from rats exposed to high concentrations of particles for quantitatively predicting lung cancer risk in humans exposed to much lower environmental or occupational concentrations has been questioned. The purpose of this investigation was to directly compare the anatomical patterns of particle retention and the lung tissue responses of rats and monkeys exposed chronically to high occupational concentrations of poorly soluble particles. Lung sections from male cynomolgus monkeys and F344 rats exposed 7 hr/day, 5 days/week for 24 months to filtered ambient air, diesel exhaust (2 mg soot/m3), coal dust (2 mg respirable particulate material/m3), or diesel exhaust and coal dust combined (1 mg soot and 1 mg respirable coal dust/m3) were examined histopathologically. The relative volume density of particulate material and the volume percentage of the total particulate material in defined pulmonary compartments were determined morphometrically to assess the relative amount and the anatomic distribution of retained particulate material. In all groups, relatively more particulate material was retained in monkey than in rat lungs. After adjustment for differences between rat and monkey controls, the coal dust- and the combined diesel exhaust and coal dust-exposed monkeys retained more particulate material than the coal dust- and the combined diesel exhaust and coal dust-exposed rats, respectively. There was no significant difference in the relative amount of retained particulate material between diesel exhaust-exposed monkeys and rats. Within each species, the sites of particle retention and lung tissue responses were the same for diesel soot, coal dust, and the combined material. Rats retained a greater portion of the particulate material in lumens of alveolar ducts and alveoli than monkeys. Conversely, monkeys retained a greater portion of the particulate material in the interstitium than rats. Rats, but not monkeys, had significant alveolar epithelial hyperplastic, inflammatory, and septal fibrotic responses to the retained particles. These results suggest that intrapulmonary particle retention patterns and tissue reactions in rats may not be predictive of retention patterns and tissue responses in primates exposed to poorly soluble particles at concentrations representing high occupational exposures.
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Carbón Mineral/efectos adversos , Polvo/efectos adversos , Pulmón/efectos de los fármacos , Emisiones de Vehículos/efectos adversos , Animales , Femenino , Pulmón/patología , Macaca fascicularis , Masculino , Tamaño de la Partícula , Ratas , Ratas Endogámicas F344RESUMEN
Two members of the cytochrome P450 2A subfamily, CYP2A10 and 2A11, are abundant nasal enzymes previously characterized in rabbit olfactory microsomes. Rabbit CYP2A is active toward a number of nasal toxicants, including the rat nasal procarcinogen hexamethylphosphoramide (HMPA). While P450s immunochemically related to the rabbit CYP2As have been detected in rat and human nasal mucosa, confirmation of these enzymes as members of the CYP2A subfamily and efforts to characterize their ability to bioactivate toxicants have been limited. In the present study, the regional distribution and cell-specific expression of CYP2A in the rat nasal cavity were examined using an antibody to rabbit CYP2A10/11. In sections of the anterior nose, immunoreactive CYP2A was present in ciliated cells of the nasal respiratory epithelium and cuboidal epithelial cells of the nasal transitional epithelium, but was absent in squamous epithelial cells. The most intense immunostaining was observed in the posterior nose. Olfactory sustentacular cells and Bowman's gland cells in sections posterior to the nasal papilla stained most intensely. Western blot analysis revealed that anti-CYP2A10/11 recognized a sharp band of approximately 50 kDa in nasal respiratory and olfactory microsomes, supporting the premise that the antibody is reacting with a cytochrome P450 enzyme. The nasal expression of CYP2A6 mRNA--a member of the human CYP2A subfamily having a high degree of homology to rabbit 2A10 and 2A11--was examined in human surgical patients. Middle turbinectomy tissues--largely composed of nasal respiratory epithelia--from 11 patients were analyzed for the presence of CYP2A6 using reverse transcription-polymerase chain reaction (RT-PCR). Identification of CYP2A6 was confirmed by DNA sequencing of RT-PCR products. CYP2A6 mRNA was detected in all of the human samples analyzed. In additional experiments, human CYP2A6 metabolized HMPA to formaldehyde, suggesting that this compound might cause nasal toxicity in humans. The identification of CYP2A cytochromes in rat and human nasal tissues may have important implications for risk assessment of inhaled xenobiotics.
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Hidrocarburo de Aril Hidroxilasas , Carcinógenos/farmacocinética , Sistema Enzimático del Citocromo P-450/metabolismo , Hempa/farmacocinética , Oxigenasas de Función Mixta/metabolismo , Mucosa Nasal/enzimología , Animales , Biotransformación , Citocromo P-450 CYP2A6 , Sistema Enzimático del Citocromo P-450/genética , Familia 2 del Citocromo P450 , Humanos , Pulmón/metabolismo , Masculino , Microsomas/metabolismo , Microsomas Hepáticos/metabolismo , Oxigenasas de Función Mixta/genética , Mucosa Nasal/ultraestructura , Mucosa Olfatoria/enzimología , Mucosa Olfatoria/ultraestructura , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , Profármacos/farmacocinética , ARN Mensajero/análisis , Conejos , Ratas , Ratas Endogámicas F344 , Especificidad de la EspecieRESUMEN
Colorectal cancer (CRC) is the second leading cause of cancer death in Argentina. The cumulative lifetime risk of developing CRC for both men and women is 4-6%. Despite advances in the management of this disease, the 5-year survival rate is about 60% because only 35% of patients are diagnosed when the disease is localized. Risk factors for CRC include age, diet and life style factors, personal or family history of adenomas or CRC and personal history of inflammatory bowel disease. Scientific evidence shows that primary and secondary prevention, through screening programs, permit to reduce incidence and mortality significantly. Chemopreventive agents, including nonsteroidal antiinflammatory drugs, folate, and calcium, have been shown to have some preventive effect. Physical inactivity and excess body weight are consistent risk factors for CRC. Tobacco exposure, diet high in red meat and low in vegetables and alcohol consumption, probably in combination with a diet low in folate, appear to increase risk. The dietary fiber and risk of CRC has been studied but the results are still inconclusive. Screening for CRC is cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. The advantages and disadvantages or limitations of screening modalities for CRC are analyzed. The literature and clinical practice guidelines are reviewed, with an emphasis on advances and evolving screening methods and recommendations for patients with average, moderate and high-risk CRC.
El cáncer colorrectal (CCR) ocupa el segundo lugar en mortalidad por tumores malignos en Argentina. Elriesgo de padecer un CCR a través de toda la vida es de 4-6%. A pesar de los avances en el tratamiento, la sobrevidaa 5 años del CCR se ubica en el 60% debido a que sólo el 35% de los pacientes tienen enfermedadlocalizada en el momento del diagnóstico. Los factores de riesgo incluyen la edad, dieta y estilo de vida, historia personal o familiar de adenomas o CCR y antecedentes de enfermedad inflamatoria intestinal. La evidenciacientífica permite señalar que la prevención primaria y secundaria a través de programas de pesquisapermitiría reducir la incidencia y la mortalidad significativamente. Agentes quimiopreventivos, como los antiinflamatorios no esteroideos, ácido fólico y calcio han mostrado algún efecto preventivo. El sedentarismoy el exceso de peso son convincentes factores de riesgo de CCR. El tabaco, una dieta rica en carnes rojas,pobre en vegetales y el consumo de alcohol, probablemente en combinación con una reducción de la ingestade ácido fólico, parecen incrementar el riesgo de CCR. La relación entre la ingesta de fibra y el riesgo deCCR ha sido largamente estudiada pero los resultados no son aún concluyentes. La pesquisa del CCR es costoefectivacomparada con su no realización. Se analizan las ventajas y desventajas o limitaciones de las diferentes estrategias. La literatura y las distintas normativas fueron revisadas evaluando los avances, nuevos métodosy recomendaciones para personas con riesgo promedio, moderado y alto.