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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 Orais , Humanos , Mucosa Bucal/patologia , PigmentaçãoRESUMO
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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Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular , Lactonas/farmacologia , Mitose/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células 3T3-L1 , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Histona Metiltransferases , Histona-Lisina N-Metiltransferase/metabolismo , Camundongos , PPAR gama/metabolismo , Ativação TranscricionalRESUMO
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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Glucose/metabolismo , Hiperglicemia/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação/fisiologia , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Fosforilação/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RatosRESUMO
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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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 , Animais , Bovinos , Metronidazol/farmacologia , Citometria de Fluxo/veterináriaRESUMO
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 , Oftalmopatias , Humanos , Masculino , Feminino , Lactente , COVID-19/complicações , SARS-CoV-2 , Estudos Retrospectivos , México/epidemiologiaRESUMO
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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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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Corpos Estranhos , Criança , Pré-Escolar , Estudos Transversais , Ingestão de Alimentos , Endoscopia Gastrointestinal , Feminino , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
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.
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Poluentes Atmosféricos/toxicidade , Manganês/toxicidade , Prolactina/sangue , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/sangue , Criança , Feminino , Cabelo/química , Humanos , Masculino , Manganês/análise , Manganês/sangue , MéxicoRESUMO
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.
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Genitália Masculina/efeitos dos fármacos , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Animais , Cricetinae , Estradiol/sangue , Feminino , Genitália Masculina/enzimologia , Hidrólise , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Motilidade dos Espermatozoides , Testosterona/sangueRESUMO
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/epidemiologia , Continuidade da Assistência ao Paciente , Transtornos Neurocognitivos/diagnóstico , Encaminhamento e Consulta , Idoso , Doença de Alzheimer/diagnóstico , Argentina/epidemiologia , Sobrecarga do Cuidador/psicologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Dehydroleucodine (DhL), a sesquiterpenic lactone, was isolated and purified from aerial parts of Artemisia douglasiana Besser, a medicinal herb used in Argentina. DhL is an alpha-methylene butyro-gamma-lactone ring connected to a seven-membered ring fused to an exocyclic alpha,beta-unsaturated cyclopentenone ring. It has been previously shown that DhL selectively induces a dose-dependent transient arrest in G2 of both meristematic cells and vascular smooth muscle cells. Treatment with DhL induces an inhibition of spontaneous and progesterone-induced maturation in a dose-dependent manner in Bufo arenarum fully grown oocytes arrested at G2, at the beginning of meiosis I. However, the nature of the mechanisms involved in the process is still unknown. The aim of this work was to analyse whether DhL's alpha-methylene-gamma-lactone function is responsible for the inhibition effect on meiosis reinitiation of Bufo arenarum oocytes as well as some of the transduction pathways that could be involved in this effect using a derivative of DhL inactivated for alpha-methylenelactone, the 11,13-dihydro-dehydroleucodine (2H-DhL). The use of 2H-DhL in the maturation promoting factor (MPF) amplification experiments by injection of both cytoplasm with active MPF and of germinal vesicle content showed results similar to the ones obtained with DhL, suggesting that the hydrogenated derivative would act in a similar way to DhL. Pretreatment with DhL or 2H-DhL did not affect the percentage of germinal vesicle breakdown (GVBD) induced by H89, a protein kinase A (PKA) inhibitor, which suggests that these lactones would act on another step of the signalling pathway that induces MPF activation. The fact that both DhL and 2H-Dhl inhibit GVBD induced by okadaic acid microinjection suggests that they could act on the activity of the Myt1 kinase. This idea is supported by the experiments of injection of GV contents in which an inhibitory effect of these lactones on GVBD was also observed. Our results indicate that the inhibitory effect on meiosis progression of DhL does not depend only on the activity of the alpha-methylenelactone function, as its hydrogenated derivative, 2H-DhL, in which this function has been inactivated, causes similar effects on amphibian oocytes. However, 2H-DhL was less active than DhL as higher doses were required to obtain a significant inhibition. On the other hand, the analysis of the participation of certain mediators in some of the signalling pathways leading to MPF activation suggests that the Myt1 kinase could be a target of these lactones, while cdc25 phosphatase would not be affected. Besides, the PKA inhibition assays indicate that these lactones would act earlier in the signalling pathways.
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Lactonas/farmacologia , Oócitos/citologia , Oócitos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Bufo arenarum , Diferenciação Celular , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Isoquinolinas/farmacologia , Lactonas/química , Fator Promotor de Maturação/metabolismo , Estrutura Molecular , Oócitos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteína Fosfatase 2/metabolismo , Sesquiterpenos/química , Sulfonamidas/farmacologiaRESUMO
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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Colo Sigmoide/cirurgia , Protectomia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Endoglin is a homodimeric membrane glycoprotein which can bind the beta 1 and beta 3 isoforms of transforming growth factor-beta (TGF-beta). We reported previously that endoglin is upregulated during monocyte differentiation. We have now observed that TGF-beta itself can stimulate the expression of endoglin in cultured human monocytes and in the U-937 monocytic line. To study the functional role of endoglin, stable transfectants of U-937 cells were generated which overexpress L- or S- endoglin isoforms, differing in their cytoplasmic domain. Inhibition of cellular proliferation and downregulation of c-myc mRNA which are normally induced by TGF-beta 1 in U-937 cells were totally abrogated in L-endoglin transfectants and much reduced in the S-endoglin transfectants. Inhibition of proliferation by TGF-beta 2 was not altered in the transfectants, in agreement with the isoform specificity of endoglin. Additional responses of U-937 cells to TGF-beta 1, including stimulation of fibronectin synthesis, cellular adhesion, platelet/endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation, and homotypic aggregation were also inhibited in the endoglin transfectants. However, modulation of integrin and PECAM-1 levels and stimulation of mRNA levels for TGF-beta 1 and its receptors R-I, R-II, and betaglycan occurred normally in the endoglin transfectants. No changes in total ligand binding were observed in L-endoglin transfectants relative to mock, while a 1.5-fold increase was seen in S-endoglin transfectants. The degradation rate of the ligand was the same in all transfectants. Elucidating the mechanism by which endoglin modulates several cellular responses to TGF-beta 1 without interfering with ligand binding or degradation should increase our understanding of the complex pathways which mediate the effects of this factor.
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Fator de Crescimento Transformador beta/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Antígenos CD , Antígenos de Diferenciação Mielomonocítica/metabolismo , Sequência de Bases , Moléculas de Adesão Celular/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Primers do DNA/genética , DNA Complementar/genética , Endoglina , Fibronectinas/biossíntese , Genes myc/efeitos dos fármacos , Humanos , Integrinas/metabolismo , Dados de Sequência Molecular , Fosforilação , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Receptores de Superfície Celular , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transfecção , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
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 terapêutico , Rim , Transplantes , Refluxo Vesicoureteral/terapia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pielonefrite/epidemiologia , Risco , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto JovemRESUMO
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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Transtornos do Desenvolvimento da Linguagem/induzido quimicamente , Desenvolvimento da Linguagem , Aprendizagem/efeitos dos fármacos , Manganês/efeitos adversos , Memória/efeitos dos fármacos , Criança , Estudos Transversais , Feminino , Humanos , Masculino , México , Testes Neuropsicológicos , Reconhecimento Psicológico/efeitos dos fármacos , VocabulárioRESUMO
Automatic text classification is an important task for many natural language processing applications. This paper presents a neural approach to develop a text classifier based on the Learning Vector Quantization (LVQ) algorithm. The LVQ model is a classification method that uses a competitive supervised learning algorithm. The proposed method has been applied to two specific tasks: text categorization and word sense disambiguation. Experiments were carried out using the Reuters-21578 text collection (for text categorization) and the Senseval-3 corpus (for word sense disambiguation). The results obtained are very promising and show that our neural approach based on the LVQ algorithm is an alternative to other classification systems.