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Here we reported a case of primary sclerosing epitheloid fibrosarcoma (SEF) of the kidney, an extremely rare and aggressive tumor. The patient presented a mass in the upper part of the right kidney with pulmonary metastasis at the time of diagnosis, a right radical nephrectomy was performed, it was a solid tumor of 15 cm × 9 cm affecting almost the entire kidney. Histological study revealed a neoplasm of uniform epithelioid cells with scant cytoplasm with dense and sclerotic stroma. immunohistochemistry positive for MUC-4, detection by fusion of EWSR1-CREB3L1 by FISH positive.
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Introduction and objectives: Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico. Material and methods: This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation. Results: A total of 3,081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95 ± 15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p = 0.665). Conclusions: The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings.
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Introducción y objetivos Aunque las manifestaciones oftálmicas parecen estar asociadas a la enfermedad por coronavirus 2019 (COVID-19), no hay suficiente evidencia. Por ello, el objetivo de este estudio fue determinar los distintos tipos y la frecuencia de las manifestaciones oftálmicas en pacientes recuperados de la infección con SARS-CoV-2 en México. Material y métodos Este estudio retrospectivo, observacional y descriptivo incluyó a los pacientes infectados con SARS-CoV-2 de junio de 2020 a junio de 2022. El examen oftalmológico fue realizado bajo luz de linterna por un oftalmólogo del Departamento de Oftalmología. Los datos fueron analizados estadísticamente mediante la prueba exacta de Fisher y la correlación de Spearman. Resultados Se registraron un total de 3.081 pacientes positivos de SARS-CoV-2, de los cuales 318 (10,32%) cumplían los criterios de inclusión. De ellos, 21 (6,60%) tenían manifestaciones oftálmicas y la proporción entre mujeres y hombres era de 1,6:1. La edad media (±DE) fue 47,95±15,27 años y la mediana (rango intercuartil) del tiempo transcurrido desde el diagnóstico de COVID-19, definido por la prueba RT-PCR del SARS-CoV-2 positiva, hasta la detección de la manifestación oftálmica fue de 31 (142) días. La manifestación ocular más común fue la mucormicosis orbital (23,80%). Interesantemente, la presencia de manifestaciones oftálmicas no fue asociada con COVID-19 grave (p=0,665). Conclusiones Las manifestaciones oftálmicas son infrecuentes en los pacientes recuperados de COVID-19 grave. No obstante, se necesitan más estudios con una muestra de mayor tamaño para confirmar estos hallazgos (AU)
Introduction and objectives Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico. Material and methods This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation. Results A total of 3,081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95±15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p=0.665). Conclusions The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings (AU)
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Infecciones por Coronavirus/complicaciones , Pandemias , Oftalmopatías/virología , Estudios Retrospectivos , México , Estudios TransversalesRESUMEN
INTRODUCTION AND OBJECTIVES: Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico. MATERIAL AND METHODS: This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation. RESULTS: A total of 3081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95±15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p=0.665). CONCLUSIONS: The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings.
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COVID-19 , Oftalmopatías , Humanos , Masculino , Femenino , Lactante , COVID-19/complicaciones , SARS-CoV-2 , Estudios Retrospectivos , México/epidemiologíaRESUMEN
Bovine Trichomonosis (BT), a sexually transmitted disease endemic in countries with extensive cattle farming and natural service, is one of the most common causes of reproductive failure. 5-nitroimidazoles and their derivatives are used for its treatment, mainly metronidazole. The emergence of drug resistance mechanisms and treatment failures raise the need to investigate the effectiveness of new active compounds that contribute to parasite control. In this regard, extracts of Lantana camara (Verbenacea) have shown high biocidal potential against isolates of Trypanosoma cruzi and Leishmania braziliensis in vitro assays, although their effect on Tritrichomonas foetus has not been demonstrated yet. The available information on in vitro susceptibility of trichomonicidal drugs comes from the use of a diversity of methodologies and criteria, especially the observation of parasite motility under the optical microscope to assess their viability. Recently, in our laboratory, the use of flow cytometry has been described for the first time as a rapid and efficient method to evaluate the viability of T. foetus against metronidazole. The present study aimed to evaluate the cytostatic effect of L. camara extracts against T. foetus isolates by flow cytometry. Under aerobic conditions, IC50 values of 22.60 µg/mL were obtained on average. Under anaerobic conditions, the IC50 oscilated around 29.04 µg/mL. The results obtained allowed describing the susceptibility exhibited by these protozoa, being a valuable information for the development of potential BT treatments.
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Lantana , Tritrichomonas foetus , Verbenaceae , Animales , Bovinos , Metronidazol/farmacología , Citometría de Flujo/veterinariaRESUMEN
BACKGROUND: The diagnosis of oral melanotic lesions is, more often than not, challenging in the clinical practice due to the fact that there are several reasons which may cause an increase in pigmentation on localized or generalized areas. Among these, medication stands out. MATERIAL AND METHODS: In this work, we have carried out a review in the reference pharma database: Micromedex® followed by a review of the scientific published literature to analyse coincidences and possible discrepancies. RESULTS: Our findings show that there are several prescription drugs that can cause pigmented lesions in the oral mucosa. This must be known by clinicians in order to properly diagnose pigmented lesions. We have identified a set of 21 medicaments which cause these lesions, some of which are used frequently in the clinic, such as Metronidazole, Amitriptyline, conjugated oestrogens and Chlorhexidine gluconate. We also found discrepancies with the data published in specialized literature, some of which wasn't reflected in the Summary of Product Characteristics. CONCLUSIONS: Our work highlights the importance of the proper communication of adverse drug reactions (ADR) by health professionals in order to provide thorough and accurate information and diagnosis.
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Mucosa Bucal , Úlceras Bucales , Humanos , Mucosa Bucal/patología , PigmentaciónRESUMEN
INTRODUCTION AND AIMS: Foreign body (FB) ingestion is a common problem in children under 5 years of age and is one of the main indications for endoscopy. The aim of the present study was to describe the clinical, radiographic, and endoscopic characteristics of patients with FB ingestion, as well as the factors associated with the anatomic location and the type of object ingested. MATERIALS AND METHODS: An analytic cross-sectional study was conducted on all patients with FB ingestion seen at the gastroenterology service from January 2013 to December 2018. The data were analyzed using the SPSS program, obtaining frequencies, percentages, medians, and interquartile ranges. Associations were assessed through the chi-square test. RESULTS: Eighty-five patients (52 males and 33 females) were included, with a median age of 4 years. The most common symptom was vomiting (29.4%). Two radiographic projections were carried out in 72.9% of the cases and the stomach was the site where the FB was most frequently visualized (32.9%). The objects most commonly ingested were coins (36%), with esophageal location (p<0.05), as well as objects with a diameter larger than 2cm (p<0.05). An endoscopic procedure was performed on 76 patients (89.4%) for FB extraction, with findings of erythema (28.9%), erosion (48.6%), ulcer (10.5%) and perforation (1.3%). CONCLUSIONS: Numerous factors should be taken into account in the approach to FB ingestion in pediatric patients, including type and size of the FB, time interval from ingestion to hospital arrival, and patient clinical status and age.
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Cuerpos Extraños , Niño , Preescolar , Estudios Transversales , Ingestión de Alimentos , Endoscopía Gastrointestinal , Femenino , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/epidemiología , Humanos , Masculino , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
INTRODUCTION AND AIMS: Foreign body (FB) ingestion is a common problem in children under 5 years of age and is one of the main indications for endoscopy. The aim of the present study was to describe the clinical, radiographic, and endoscopic characteristics of patients with FB ingestion, as well as the factors associated with the anatomic location and the type of object ingested. MATERIALS AND METHODS: An analytic cross-sectional study was conducted on all patients with FB ingestion seen at the gastroenterology service from January 2013 to December 2018. The data were analyzed using the SPSS program, obtaining frequencies, percentages, medians, and interquartile ranges. Associations were assessed through the chi-square test. RESULTS: Eighty-five patients (52 males and 33 females) were included, with a median age of 4 years. The most common symptom was vomiting (29.4%). Two radiographic projections were carried out in 72.9% of the cases and the stomach was the site where the FB was most frequently visualized (32.9%). The objects most commonly ingested were coins (36%), with esophageal location (p <0.05), as well as objects with a diameter larger than 2cm (p <0.05). An endoscopic procedure was performed on 76 patients (89.4%) for FB extraction, with findings of erythema (28.9%), erosion (48.6%), ulcer (10.5%) and perforation (1.3%). CONCLUSIONS: Numerous factors should be taken into account in the approach to FB ingestion in pediatric patients, including type and size of the FB, time interval from ingestion to hospital arrival, and patient clinical status and age.
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INTRODUCTION: Health systems in numerous countries around the world are suffering a serious burden as a consequence of the COVID-19 pandemic. As a result of this situation, the follow-up of such chronic diseases as dementia may be at risk. Similarly, neuropsychiatric complications related to lockdown measures may also be neglected; Argentina's lockdown has been the longest implemented in Latin America. This study aims to determine the frequency of the different types of medical consultations for neurocognitive disorders and the predictors for requiring consultation since the beginning of the lockdown. METHODS: We performed a descriptive, observational, cross-sectional study based on data collected through an online survey. RESULTS: Data were collected on 324 participants, with 165 (50.9%) having had at least one medical consultation. Consultations were held by telephone in 109 cases (33.6%), by e-mail in 62 (19.1%), by video conference in 30 (9.3%), and at the emergency department in 23 (7.1%). Predictors of requiring consultation were Clinical Dementia Rating scores ≥1 (P<.001) and diagnosis of Alzheimer disease (P=.017). Higher Neuropsychiatric Inventory scores were found in the group of respondents who did require medical consultation (P<.001), but no significant differences were found between groups for Zarit Burden Interview scores. CONCLUSION: We identified a high prevalence of behavioural disorders and caregiver burden during lockdown. Nevertheless, only 50% of respondents had sought medical consultation (by telephone or email in 52.7% of cases). Care of people with dementia must be emphasised, guaranteeing follow-up of these patients.
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COVID-19/epidemiología , Continuidad de la Atención al Paciente , Trastornos Neurocognitivos/diagnóstico , Derivación y Consulta , Anciano , Enfermedad de Alzheimer/diagnóstico , Argentina/epidemiología , Carga del Cuidador/psicología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The time that waves spend inside 1D random media with the possibility of performing Lévy walks is experimentally and theoretically studied. The dynamics of quantum and classical wave diffusion has been investigated in canonical disordered systems via the delay time. We show that a wide class of disorder-Lévy disorder-leads to strong random fluctuations of the delay time; nevertheless, some statistical properties such as the tail of the distribution and the average of the delay time are insensitive to Lévy walks. Our results reveal a universal character of wave propagation that goes beyond standard Brownian wave-diffusion.
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INTRODUCTION AND AIM: Surgery for distal rectal cancer (DRC) can be performed with or without sphincter preservation. The aim of the present study was to analyze the outcomes of two surgical techniques in the treatment of DRC patients: low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: Patients with advanced DRC that underwent surgical treatment between 2002 and 2012 were evaluated. We compared the outcomes of the type of surgery (APR vs LAR) and analyzed the associations of survival and recurrence with the following factors: age, sex, tumor location, lymph nodes obtained, lymph node involvement, and rectal wall involvement. Patients with distant metastases were excluded. RESULTS: A total of 148 patients were included, 78 of whom were females (52.7%). The mean patient age was 61.2years. Neoadjuvant chemoradiation therapy was performed in 86.5% of the patients. APR was performed on 86 (58.1%) patients, and LAR on 62 (41.9%) patients. No differences were observed between the two groups regarding clinical and oncologic characteristics. Eighty-seven (62%) patients had pT3-4 disease, and 41 patients (27.7%) had lymph node involvement. In the multivariate analysis, only poorly differentiated tumors (P=.026) and APR (P=.009) correlated with higher recurrence rates. Mean follow-up time was 32 (16-59.9) months. Overall 5-year survival was 58.1%. The 5-year survival rate was worse in patients that underwent APR (46.5%) than in the patients that underwent LAR (74.2%) (P=.009). CONCLUSIONS: Patients with locally advanced DRC that underwent APR presented with a lower survival rate and a higher local recurrence rate than patients that underwent LAR. In addition, advanced T/stage, lymph node involvement, and poor tumor differentiation were associated with recurrence and a lower survival rate, regardless of the procedure.
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Colon Sigmoide/cirugía , Proctectomía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Manganese (Mn) is an essential nutrient for cellular function, but in high concentrations, it is neurotoxic. Environmental exposure to Mn has been associated with cognitive effects in children. This study aimed to assess the effect of environmental exposure to Mn on verbal memory and learning in schoolchildren residents from two municipalities in the state of Hidalgo, Mexico. Cross-sectional studies were conducted in 2006 and 2013 with a total of 265 schoolchildren of 7 to 11 years old. Children's Auditory Verbal Learning Test-2 (CAVLT-2) was used to assess verbal memory and learning. Mn exposure tertiles were defined according to hair manganese (MnH) levels determined by atomic absorption spectrophotometry. Linear regression models were used to estimate the association between MnH levels and CAVLT-2 scores. The models were adjusted by potential confounders. The lowest and highest exposure tertiles were defined below and above MnH levels of ≤ 0.72 and ≥ 3.96 µg/g, respectively. Mn exposure was significantly associated with an average of 5- to 9-point decrease in learning curves and summary CAVLT-2 scores in the highest tertile. This study adds to the evidence of decreased verbal memory and learning in schoolchildren environmentally exposed to manganese.
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Trastornos del Desarrollo del Lenguaje/inducido químicamente , Desarrollo del Lenguaje , Aprendizaje/efectos de los fármacos , Manganeso/efectos adversos , Memoria/efectos de los fármacos , Niño , Estudios Transversales , Femenino , Humanos , Masculino , México , Pruebas Neuropsicológicas , Reconocimiento en Psicología/efectos de los fármacos , VocabularioRESUMEN
OBJECTIVE: To identify the results of polydimethylsiloxane application in the endourological management of symptomatic vesicoureteral reflux to the kidney graft and to determine the factors associated with persistent symptoms and with vesicoureteral reflux. MATERIAL AND METHODS: We included 23 patients diagnosed with symptomatic VUR in kidney graft, evaluated from January 2010 to August 2018 in the High Specialty Medical Unit # 14 in Veracruz. These patients received endourological application of polydimethylsiloxane. The descriptive analysis was carried out, and, if possible, the relative risk measures for clinical failure (CF) were determined with odds ratio (OR). RESULTS: 18 (78.3%) patients presented clinical success (CS). There was a significant difference in the mean age (CS 30.61±9.7, CF 46.0±11.46; U Mann Whitney, P=.037), and in the number of episodes of AGPN prior to the application of PDMS (CS 2.27±1.27, CF 3.6±0.89, U Mann Whitney, P=.019). The most frequently identified pathogen was E. Coli, with 45.4%. VUR resolution was observed in 47.8% of the cases. There was a decreased degree of VUR in 73.9% of cases. A lower degree of VUR was determined as a protective factor for CF (OR: 0.031, 95% CI: 0.002-0.437, with P=.008). CONCLUSIONS: The endourological application of PDMS proved to be useful in the management of patients with symptomatic VUR in kidney graft, as it decreased the VUR degree and allowed CS in most cases.
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Dimetilpolisiloxanos/uso terapéutico , Riñón , Trasplantes , Reflujo Vesicoureteral/terapia , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pielonefritis/epidemiología , Riesgo , Estadísticas no Paramétricas , Resultado del Tratamiento , Adulto JovenRESUMEN
Aberrant levels of preadipocyte differentiation, triggered by adipocyte hyperplasia and hypertrophy, results in the obesogenic phenotype. Obesity is a risk factor for several metabolic disorders. In this paper, dehydroleucodine inhibited the accumulation of lipid droplets and decreased the elevations of triglycerides, and this inhibitory effect occurred during the early stage of adipogenesis. Thus, not only did dehydroleucodine downregulate the expression of C/EBPα and PPARγ, it also strongly blocked the expression of C/EBPß, an early stage biomarker of early adipogenesis, in a concentration-dependent manner. The proliferation of preadipocytes was dramatically suppressed when dehydroleucodine was added to the medium as early as 24 hr. These results indicate that dehydroleucodine may specifically affect mitotic clonal expansion to inhibit preadipocyte differentiation. Dehydroleucodine arrested the cell cycle at the G0 /G1 phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). Additionally, dehydroleucodine decreased phosphorylation of Erk1/2 and Akt. Furthermore, dehydroleucodine downregulated expression of histone demethylase JMJD2B as well as repressed the expression of histone methyltransferase MLL4, which in turn diminished the expression of C/EBPß and PPARγ, respectively. Collectively, our results indicate that dehydroleucodine inhibits preadipocyte differentiation by blocking mitotic clonal expansion via cell cycle arrest, which may be mediated by regulation of selective histone methylation/demethylation in transcription activation during the early step of adipogenesis.
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Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Puntos de Control del Ciclo Celular , Lactonas/farmacología , Mitosis/efectos de los fármacos , Sesquiterpenos/farmacología , Células 3T3-L1 , Animales , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/metabolismo , Ratones , PPAR gamma/metabolismo , Activación TranscripcionalRESUMEN
BACKGROUND: Manganese (Mn) is an essential metal involved in multiple physiological functions. Environmental exposure to airborne Mn is associated with neurocognitive deficits in humans. Children, whose nervous system is in development, are particularly susceptible to Mn neurotoxicity. OBJECTIVE: The objective of this study was to assess the association between Mn environmental exposure, and effects on visuoperception and visual memory in schoolchildren. METHODS: We assessed schoolchildren between 7 and 11 years old, with similar socioeconomic status, from the mining district of Molango (n=148) and Agua Blanca (n=119, non-mining area) in Hidalgo state, Mexico. The Rey-Osterrieth Complex Figure (ROCF) test was used to assess visuoperception and short-term visual memory. Hair manganese (MnH) concentrations were determined. Linear regression models were constructed to estimate the associations between MnH and ROCF scores, adjusted for potential confounders. RESULTS: The geometric mean MnH was nine times higher in schoolchildren from the Mn mining area (5.25µg/g) than in schoolchildren from the non-mining area (0.55µg/g). For the ROCF Copy trial, MnH was significantly associated with an increase in distortion errors (tangency, closure), angle errors, overtracing (partial overtracing). In the Immediate Recall trial, MnH was significantly associated with increased overtracing (partial overtracing) and omissions, and negatively associated with the number of perceptual drawn units, total score and percentage immediate recall. CONCLUSIONS: MnH is associated with alterations in visuoperception and short-term visual memory in schoolchildren exposed to airborne Mn.
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Exposición a Riesgos Ambientales , Manganeso/toxicidad , Memoria a Corto Plazo/efectos de los fármacos , Percepción Visual/efectos de los fármacos , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Manganeso/sangre , México/epidemiología , Minería , Pruebas Neuropsicológicas , Desempeño Psicomotor/efectos de los fármacos , Estudios RetrospectivosRESUMEN
Increasing resistance of Pseudomonas aeruginosa (P. aeruginosa) to conventional treatments demands the search for novel therapeutic strategies. In this study, the antimicrobial activity of dehydroleucodine (DhL), a sesquiterpene lactone obtained from Artemisia (A.) douglasiana, was screened against several pathogenic virulence effectors of P. aeruginosa. In vitro, minimum inhibitory concentration of DhL was determined against P. aeruginosa strains PAO1, PA103, PA14, and multidrug resistant clinical strain, CDN118. Results showed that DhL was active against each strain where PAO1 and PA103 showed higher susceptibility (MIC 0.48 mg/mL) as compared to PA14 (MIC 0.96 mg/mL) and CDN118 (MIC 0.98 mg/mL). Also, when PAO1 strain was grown in the presence of DhL (MIC50, 0.12 mg/mL), a delay in the generation time was noticed along with significant inhibition of secretory protease and elastase activities, interruption in biofilm attachment phase in a stationary culture, and a significant decline in Type III effector ExoS. At MIC50, DhL treatment increased the sensitivity of P. aeruginosa towards potent antibiotics. Furthermore, treatment of P. aeruginosa with DhL prevented toxin-induced apoptosis in macrophages. These observations suggest that DhL activity was at the bacterial transcriptional level. Hence, antimicrobial activity of DhL may serve as leads in the development of new anti-Pseudomonas pharmaceuticals.
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Biopelículas/efectos de los fármacos , Lactonas/administración & dosificación , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Sesquiterpenos/administración & dosificación , Antibacterianos/uso terapéutico , Artemisia/química , Humanos , Lactonas/química , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/patogenicidad , Sesquiterpenos/químicaRESUMEN
The apoptosis of ß cells induced by hyperglycemia has been associated with p53 mobilization to mitochondria and p53 phosphorylation. Murine double minute 2 (Mdm2) induces the degradation of p53 and thereby protects cells from apoptosis. We studied the effect of glucose at high concentration on the ability of Mdm2 to ubiquitinate p53 and promote its degradation. RINm5F cells were grown in RPMI-1640 medium with 5 or 30 mM glucose for varying periods of time. After this treatment, the expression of Mdm2 was measured using real-time PCR. The phosphorylation of Mdm2 at Ser166, p53 at Ser15, and the kinases Akt and ATM were measured by Western blotting. The formation of the p53-Mdm2 complex and p53 ubiquitination was assessed by p53 immunoprecipitation and immunofluorescence. Our results showed that high glucose reduced Mdm2 mRNA expression and protein concentration and increased Mdm2 and Akt phosphorylation, albeit with slower kinetics for Akt. It also promoted p53-Mdm2 complex formation, whereas p53 ubiquitination was suppressed. Furthermore, phosphorylation of both p53 Ser15 and ATM was increased in the presence of 30 mM glucose. These data indicate that high concentration glucose decrease the mRNA expression and cytosolic concentration of Mdm2. However, although the increase in glucose promoted the phosphorylation of Mdm2, it also decreased p53 ubiquitination, thus avoiding p53 degradation. In hyperglycemic conditions, such as diabetes mellitus, the reduction of pancreatic ß cells mass is favored by stabilization of p53 in association with low p53 ubiquitination and reduced expression of Mdm2.
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Glucosa/metabolismo , Hiperglucemia/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitinación/fisiología , Animales , Apoptosis/fisiología , Línea Celular Tumoral , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiología , Mitocondrias/metabolismo , Mitocondrias/fisiología , Fosforilación/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , RatasRESUMEN
Early studies on manganese (Mn) exposure have shown that this transition metal affects dopamine neurotransmission. Dopamine serves as a tonic inhibitor of prolactin release in the anterior hypophysis, thus the serum prolactin levels in occupationally Mn exposed workers has been found increased. However, little is known about environmental Mn exposure effect on this hormone. In the present study we assessed serum prolactin in environmentally (mainly through air) exposed children living in the proximity of a rich Mn zone in Mexico and a control group with similar socioeconomic and ethnic characteristics. We also determined Mn levels in blood and hair, hemoglobin and anthropometric variables. Children between 7 and 11 years old were included (77 from Mn exposed and 93 from control communities). Blood Mn was higher in exposed children (median 9.5 µg/L, rank [5.5, 18]) as compared to the control group (median 8 µg/L, rank [5, 14]) (p<0.05, Mann-Whitney). Hair Mn was also increased in the exposed group (median 13.2 µg/g, rank [4.2, 48]) in comparison to the control group (median 0.6 µg/g rank [0.06, 3.6]). Prolactin was found increased in the exposed children (median 12.35 ng/ml, rank [2.90, 33.70]) versus controls (median 7.77 ng/ml, rank [2.7, 23.6]). Positive correlations were found between prolactin and both blood Mn and hair Mn (Rho=0.217 and 0.250, respectively, p<0.05). A linear regression, with prolactin as the dependent variable, showed hair Mn as the determinant variable after adjusting by age, hemoglobin and sex. After a stratification of hair and blood Mn into low, medium and high content, significant associations were also found, confirming the relationship between prolactin and hair Mn. Results suggest that children from these Mn environmentally exposed communities could be at risk of endocrine alterations.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Manganeso/toxicidad , Prolactina/sangre , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/sangre , Niño , Femenino , Cabello/química , Humanos , Masculino , Manganeso/análisis , Manganeso/sangre , MéxicoRESUMEN
The effects of a sesquiterpene lactone, dehydroleucodine, on the reproductive tract were investigated using adult male mice. Dehydroleucodine was dissolved in tap water and administered as drinking water for 30 days. All the parameters were compared with a control group that received only vehicle. Animals were killed by decapitation and the trunk blood, the testes and the epididymes were collected. Plasma concentrations of testosterone and oestradiol, and testicular weight and concentration of spermatids did not change by dehydroleucodine. Nevertheless, in epididymal cauda dehydroleucodine treatment caused a diminution in sperm number, a decrease in the amount of tubular fluid and a reduction in the activity of the hydrolytic enzyme N-acetyl-ß-d-glucosaminidase. However, the sperm motility was not altered by dehydroleucodine treatment, although sperm binding to zona-free oocytes increased significantly. These results suggest that dehydroleucodine, which has been implicated in the inhibition of aromatase P450, does not affect the plasma concentration of testosterone and oestradiol or testicular activity, whereas altering several epididymal parameters. The epididymis is thus a more sensitive target for dehydroleucodine action.