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OBJECTIVE: The objective of this commentary is to advocate for a holistic, ontology-based definition of bruxism. The intention is to synthesise the best aspects of current definitions into a structured ontological model, thereby refining and enhancing a comprehensive understanding of the full spectrum of bruxism. MATERIALS AND METHODS: The commentary elaborates on the process of integrating these insights into a hierarchical ontology that aligns with ontological principles. SETTINGS AND SAMPLE POPULATION: Not directly applicable as this is a commentary. RESULTS/CONCLUSION: The proposed ontology-based definition of bruxism aims to clarify communication within the medical community and advance research by enabling a comprehensive ontology-based classification of bruxism. By aligning with ontological principles, this approach aspires to act as a catalyst for further research, discussion and consensus in the field.
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Bruxismo , Semántica , Terminología como Asunto , Humanos , Ontologías Biológicas , Salud HolísticaRESUMEN
We report the first experimental demonstration of the replica symmetry breaking (RSB) phenomenon in a fiber laser system supporting standard mode-locking (SML) regime. Though theoretically predicted, this photonic glassy phase remained experimentally undisclosed so far. We employ an ytterbium-based mode-locked fiber laser with a very rich phase diagram. Two phase transitions are observed separating three different regimes: cw, quasi-mode-locking (QML), and SML. The regimes are intrinsically related to the distinct dynamics of intensity fluctuations in the laser spectra. We set the connection between the RSB glassy phase with frustrated modes and onset of L-shaped intensity distributions in the QML regime, which impact directly the replica overlap measure.
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RESUMEN El tumor sólido pseudopapilar de páncreas (TSP) es un tumor infrecuente, de bajo grado de malignidad, que representa el 1-3% de todas las neoplasias pancreáticas, con predilección por el sexo femenino, y es el tumor sólido de páncreas más frecuente en la infancia. Mujer de 13 años que consultó por dolor abdominal de 5 días de evolución, en hipocondrio derecho e irradiado a espalda, con náuseas y vómitos. TSP es diagnosticado con ecografía, tomografía computarizada (TC) y resonancia magnética (RM). Se realizó duodenopancreatectomía cefálica. La paciente fue dada de alta. El examen anatomopatológico informó un TSP de páncreas. El abordaje quirúrgico de estos tumores, abierto o laparoscópico, permite una excelente supervivencia alejada.
ABSTRACT Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm with a low malignant potential and represents 1- 3% of all pancreatic tumors. They usually occur in women and are the most common solid pancreatic tumor in children. A 13-year-old girl visited the emergency department due to abdominal pain in the right hypochondrium radiating to the back, nausea and vomiting lasting 5 days. A SPT was diagnosed by ultrasound, computed tomography (CT) scan and magnetic resonance imaging (MRI). The patient underwent cephalic pancreaticoduodenectomy and was discharged. The pathological study reported a SPT of the pancreas. The surgical approach of these tumors through open surgery or laparoscopy offers excellent long-term survival.
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BACKGROUND: Tardive Oromandibular Dystonia is an iatrogenic drug-induced movement form of extrapyramidal symptoms associated primarily with chronic consumption of dopamine receptor blocking agents. Tardive symptoms attributable to selective serotonin reuptake inhibitors antidepressants are far less prevalent. CLINICAL CASE: The authors will present a clinical case and management, from the dental specialist perspective, of a 55-year-old female patient who developed tardive oromandibular dystonia induced by Trazodone prescribed for sleep insomnia. CONCLUSIONS: Trazodone-induced oromandibular dystonia is extremely rare. Early identification and assessment of tardive symptoms are imperative for successful treatment. Trazodone should be prescribed with caution in patients taking other medications with the potential to cause tardive syndromes.
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Distonía , Trastornos Distónicos , Trazodona , Femenino , Humanos , Persona de Mediana Edad , Distonía/inducido químicamente , Distonía/diagnóstico , Distonía/tratamiento farmacológico , Trazodona/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Receptores DopaminérgicosRESUMEN
We present numerical evidence of a critical-like transition in an out-of-equilibrium mean-field description of a quantum system. By numerically solving the Gross-Pitaevskii equation we show that quantum turbulence displays an abrupt change between three-dimensional (3D) and two-dimensional (2D) behavior. The transition is observed both in quasi-2D flows in cubic domains (controlled by the amplitude of a 3D perturbation to the flow), as well as in flows in thin domains (controlled by the domain aspect ratio) in a configuration that mimics systems realized in laboratory experiments. In one regime the system displays a transfer of the energy towards smaller scales, while in the other the system displays a transfer of the energy towards larger scales and a coherent self-organization of the quantized vortices.
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OBJECTIVE: To describe the epidemiology of Guyana's road traffic injuries and perform the first geocoding of road traffic injuries in this setting. METHODS: This was a registry-based retrospective cross-sectional study investigating collisions resulting in serious and fatal injuries. Police reports from two police divisions were used to identify victim, second party (ie, non-victim) and collision characteristics of all serious and fatal collisions between January 2012 and June 2015. Collisions with available location data were geocoded using Geographic Information Systems. Distributions of characteristics were compared for urban and rural areas. Multivariable logistic regression was used to assess variables associated with fatal collisions. RESULTS: The study included 751 collisions, resulting in 1002 seriously or fatally injured victims. Fatally injured victims tended to be older, male and either pedestrians or cyclists. Fatal collisions tended to take place in rural areas, occur on weekends and involve speeding. Fifty-three per cent of fatalities occurred due to non-motorised road users being struck by motorised road users, and the most common fatal collision type was between pedestrians and motor vehicles (35%). The distribution of collisions was similar for urban (43.8%) and rural (56.2%) areas. Fatal collisions were more likely to occur in rural settings. CONCLUSIONS: Road traffic injuries pose a considerable public health burden in Guyana. These results suggest a pattern of high mortality in rural collisions and a disproportionate burden of injuries on vulnerable road users. The spatial distribution of collisions should be considered in order to target interventions and improve road traffic safety.
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Accidentes de Tránsito/estadística & datos numéricos , Ciclismo/lesiones , Sistemas de Información Geográfica , Peatones , Heridas y Lesiones/epidemiología , Accidentes de Tránsito/prevención & control , Adolescente , Adulto , Ciclismo/estadística & datos numéricos , Estudios Transversales , Femenino , Guyana/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Peatones/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Población Rural , Población Urbana , Heridas y Lesiones/prevención & control , Adulto JovenRESUMEN
We reviewed the history, volume, outcomes, uniqueness, and challenges of living donor liver transplantation (LDLT) in Latin America. We used the data from the Latin American and Caribbean Transplant Society, local transplant societies, and opinions from local transplant experts. There are more than 160 active liver transplant teams in Latin America, but only 30 centers have used LDLT in the past 2 years. In 2014, 226 LDLTs were done in the region (8.5% of liver transplant activities). Living donor liver transplantation is mainly restricted to pediatric patients. Adult-to-adult LDLT activities decreased after the implementation of the model for end-stage liver disease score and a concomitant increase on the rate of deceased donors per million population. Posttransplant outcome analysis is not mandatory, transparent or regulated in most countries. More experienced teams have outcomes comparable to international expert centers, but donor and recipient morbidity might be underreported. Latin America lags behind in terms of the number of adult LDLT and the rate of living donor utilization in comparison with other continents with similar donation rates. Local alliances and collaborations with major transplant centers in the developed world will contribute to the development of LDLT in Latin America.
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Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Donadores Vivos , Brasil , Enfermedad Hepática en Estado Terminal/etnología , Humanos , Relaciones Interinstitucionales , Cooperación Internacional , América Latina , Índice de Severidad de la Enfermedad , Obtención de Tejidos y Órganos , Resultado del TratamientoRESUMEN
In this study, we isolated, identified and characterized isolates of Tenacibaculum dicentrarchi in Atlantic salmon (Salmo salar) farmed in Chile for the first time. In 2010 and 2014, mortalities were observed in Atlantic salmon (average weight 25-30 and 480-520 g, respectively) at an aquaculture centre in Puerto Montt, Chile. Severe tail rots, frayed fins and, in some cases, damaged gills were detected. Wet smear analyses of these lesions revealed a high occurrence of Gram-negative, filamentous bacteria. Microbiological analysis of infected gill and tail tissues yielded six bacterial isolates. All were identified as T. dicentrarchi through polyphasic taxonomy, which included phenotypic characterization, 16S rRNA sequencing and multilocus sequence typing. The latter method revealed a close relationship of the Chilean genotype with the T. dicentrarchi type strain and two Norwegian Atlantic cod (Gadus morhua) isolates. The pathogenic potential of the TdChD05 isolate was assessed by challenging Atlantic salmon and rainbow trout (Oncorhynchus mykiss) for one hour, which resulted in mean cumulative mortality rates of 65% and 93%, respectively, as well as clinical signs 14 days post-challenge. However, challenged Coho salmon (Oncorhynchus kisutch) presented no mortalities or clinical signs of infection. These findings indicate that the geographical and host distribution of T. dicentrarchi is wider than previously established and that this bacterium may have negative impacts on salmonid cultures.
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Enfermedades de los Peces/epidemiología , Infecciones por Flavobacteriaceae/veterinaria , Tenacibaculum/aislamiento & purificación , Animales , Acuicultura , Chile/epidemiología , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/mortalidad , Infecciones por Flavobacteriaceae/epidemiología , Infecciones por Flavobacteriaceae/microbiología , Genotipo , Datos de Secuencia Molecular , ARN Ribosómico 16S , Salmón , Tenacibaculum/genética , VirulenciaRESUMEN
BACKGROUND: Intimate partner violence (IPV) is prevalent throughout the world and is a devastating public health problem. Healthcare workers (HCWs) are tasked with treating victims of IPV but may be victims themselves. Guyana is a lower-middle income country in South America. This study sought to determine the knowledge and attitudes of Guyanese HCWs and their perceived barriers to providing care in addition to determining the prevalence of IPV victimization and perpetration among HCWs. METHODS: HCWs at the only tertiary care hospital in the Guyana completed an anonymous survey that comprised 30 questions relating to IPV. RESULTS: The survey was completed by 87.5% of eligible HCWs. Of the respondents, 81.8% were female, 49.9% had ever experienced abuse and 21% admitted to perpetrating violence. Multivariate analysis found that the age groups 31-40 years (OR 2.3, 95% CI 1.1-4.6) and 41-50 years (OR 2.3, 95% CI 1.2-4.7) had higher odds of accepting justification for physical violence, and so did nursing staff (OR 4.3, 95% CI 1.4-13.1). Overall, 29.9% of HCWs accepted justification for physical violence in at least one of the named scenarios. CONCLUSION: This study demonstrates a high prevalence of IPV among HCWs and identifies prevailing attitudes regarding IPV. This knowledge is essential in developing effective, appropriate training programs and identifies a need to address IPV among the healthcare workforce.
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Actitud del Personal de Salud , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricos , Parejas Sexuales/psicología , Maltrato Conyugal/psicología , Maltrato Conyugal/estadística & datos numéricos , Adulto , Distribución por Edad , Víctimas de Crimen/psicología , Víctimas de Crimen/estadística & datos numéricos , Femenino , Guyana/epidemiología , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Academic departments of emergency medicine are becoming increasingly involved in assisting with the development of long-term emergency medicine training programs in low and middle-income countries. This article presents our 10-year experience working with local partners to improve emergency medical care education in Guyana. METHODS: The Vanderbilt Department of Emergency Medicine has collaborated with the Georgetown Public Hospital Corporation on the development of Emergency Medicine skills followed by the implementation of an emergency medicine residency training program. Residency development included a needs assessment, proposed curriculum, internal and external partnerships, University of Guyana and Ministry of Health approval, and funding. RESULTS: In our experience, we have found that our successful program initiation was due in large part to the pre-existing interest of several local partners and followed by long-term involvement within the country. As a newer specialty without significant local expertise, resident educational needs mandated a locally present full time EM trained attending to serve as the program director. Both external and internal funding was required to achieve this goal. Local educational efforts were best supplemented by robust distance learning. The program was developed to conform to local academic standards and to train the residents to the level of consultant physicians. Despite the best preparations, future challenges remain. CONCLUSION: While every program has unique challenges, it is likely many of the issues we have faced are generalizable to other settings and will be useful to other programs considering or currently conducting this type of collaborative project.
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Equinococosis Hepática/complicaciones , Echinococcus granulosus/aislamiento & purificación , Vena Porta/parasitología , Antagonistas Adrenérgicos beta/uso terapéutico , Albendazol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Equinococosis Hepática/diagnóstico por imagen , Equinococosis Hepática/tratamiento farmacológico , Equinococosis Hepática/parasitología , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/parasitología , Femenino , Humanos , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/parasitología , Persona de Mediana Edad , Vena Porta/diagnóstico por imagen , Propranolol/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
The mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC(50)). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p<0.0001) in KLF6 mRNA levels were observed depending on the cellular p53 status upon cell damage. KLF6 expression was significantly increased in 63% of p53-deficient cells (122/195). Conversely, KLF6 mRNA level decreased nearly 4 fold in more than 70% of p53+/+ cells. In addition, klf6 gene promoter activity was down-regulated by DNA damaging agents in cells expressing the functional p53 protein whereas it was moderately increased in the absence of functional p53. Consistent results were obtained for the endogenous KLF6 protein level. Results indicate that human klf6 gene expression is responsive to external cell damage mediated by IC(50) concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable marker for the efficiency of cell death upon cancer treatment.
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Antineoplásicos/farmacología , Expresión Génica/efectos de los fármacos , Expresión Génica/efectos de la radiación , Inhibidores de Crecimiento/farmacología , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias/genética , Estrés Oxidativo , Proteínas Proto-Oncogénicas/genética , Línea Celular Tumoral , Regulación de la Expresión Génica/efectos de los fármacos , Genes Supresores de Tumor , Genes p53 , Células Hep G2 , Humanos , Factor 6 Similar a Kruppel , Mutágenos/farmacología , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues in a microarray format representing fifteen human organs. Results indicate that while both nuclear and cytoplasmic distribution of KLF6 is detected in normal breast tissues, breast carcinomas express KLF6 mainly detected in the cytoplasm. Expression of KLF6 was further analyzed in breast cancer tissues overexpressing ERBB2 oncoprotein, which is associated with poor disease prognosis and patient's survival. The analysis of 48 ductal carcinomas revealed a significant population expressing KLF6 predominantly in the nuclear compartment (X(2)p = 0.005; Fisher p = 0.003). Moreover, this expression pattern correlates directly with early stage and small ductal breast tumors and linked to metastatic events in lymph nodes. CONCLUSIONS/SIGNIFICANCE: Data are consistent with a preferential localization of KLF6 in the nuclear compartment of early stage and small HER2-ERBB2 overexpressing ductal breast tumor cells, also presenting lymph node metastatic events. Thus, KLF6 tumor suppressor could represent a new molecular marker candidate for tumor prognosis and/or a potential target for therapy strategies.
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Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Núcleo Celular/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Proteínas Proto-Oncogénicas/genética , Receptor ErbB-2/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Inmunohistoquímica , Factor 6 Similar a Kruppel , Fracciones Subcelulares/metabolismoRESUMEN
BACKGROUND: Fabry disease is an X-linked disorder that results from the deficiency of the lysosomal enzyme alpha-galactosidase A. The defect leads to the accumulation of globotriaosylceramide (Gb3). The detection of Gb3 accumulated in different tissues may help in the diagnosis and enzyme replacement therapy monitoring. For this reason, we developed a simple method available to clinical laboratories to measure this analyte. METHODS: Gb3 excretion was determined by the incubation of urine sediment glycolipids from Fabry patients with agalsidase alpha and subsequent determination of galactose produced. RESULTS: The amount of urinary Gb3 in Fabry hemizygotes was significantly higher (p = 0.00001) than the amount in normal controls. Patients undergoing enzyme replacement therapy with agalsidase alpha showed a significantly lower content of Gb3 in urine sediment. This method showed a good recovery and comparability with a previously validated method. CONCLUSIONS: We developed an easy method for quantification of Gb3 in urine samples from Fabry patients, by the use of the specific recombinant enzyme for this glycolipid, that does not require complex infrastructure. Urinary Gb3 as measured by this enzymatic method could be useful for the diagnosis and monitoring of treatment in Fabry patients.
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Enfermedad de Fabry/orina , Trihexosilceramidas/orina , Adulto , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/terapia , Femenino , Humanos , Modelos Lineales , Masculino , Sensibilidad y EspecificidadRESUMEN
Arteriovenous malformation (AVM) of the pancreas (AVMP) is uncommon and generally asymptomatic; therefore, few cases have so far been reported. The symptoms of AVMP include gastrointestinal bleeding, pain, and portal hypertension. Definitive diagnosis is confirmed by angiographic study, and surgery is the only effective treatment. We report a case of AVMP confirmed by computed tomography, magnetic resonance imaging, and angiographic study of the abdomen, in a patient who presented to us with epigastric pain. He underwent a pancreaticoduodenectomy, following which his symptoms resolved.
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Malformaciones Arteriovenosas/diagnóstico , Arteria Gastroepiploica/anomalías , Páncreas/irrigación sanguínea , Adulto , Angiografía , Malformaciones Arteriovenosas/cirugía , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Páncreas/cirugía , Pancreaticoduodenectomía , Tomografía Computarizada por Rayos XRESUMEN
Obesity is highly prevalent in both liver transplant candidates and recipients, and can have a significant impact on perioperative morbidity and mortality and the overall cost of transplantation. Herein, we describe an obese patient who was managed sequentially with an intragastric balloon in the pre-transplant setting and a gastric sleeve following transplantation, with good long-term results. Sleeve gastrectomy is a non-malabsorptive bariatric procedure with potential benefit for liver transplant patients due to its lack of influence on the absorption of immunosuppressive agents.
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Gastrectomía/métodos , Fallo Hepático/complicaciones , Fallo Hepático/cirugía , Trasplante de Hígado , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Balón Gástrico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The Krüppel-like transcription Factor 6 (KLF6) is regulated during cell proliferation and differentiation events like mammalian development and tissue regeneration, while its aberrant expression is associated with tumor formation. To investigate KLF6 transcriptional control, the genomic organization of human KLF6 together with its cis-regulatory region was analyzed. A high sequence homology of KLF6 regulatory regions was found in mammals, which in turn predicts a high degree of evolutionary conserved transcriptional mechanisms. A transcription start site was identified at the first nucleotide downstream of a potential initiator element. Also, the role of KLF6 regulatory regions was determined by transfection experiments. A minimal promoter region lacking a TATA-box yet containing an Initiator was identified and found to be active in all cells analyzed. In addition, two strong activating sequences were located between positions -407/-344 and -307/-207, where the latter contained Sp1 and CAAT-box sites. Furthermore, ectopic expression of Sp1 increased the transcriptional activity of the KLF6 promoter. In conclusion, our data revealed that KLF6 gene transcription is under control of a TATA-box independent initiation mechanism together with an evolutionary conserved array of positive cis-acting elements.
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Regulación de la Expresión Génica , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/fisiología , Secuencias Reguladoras de Ácidos Nucleicos , Transactivadores/genética , Transactivadores/fisiología , Animales , Secuencia de Bases , Humanos , Factor 6 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel , Mamíferos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico , TATA Box , Transcripción Genética , TransfecciónRESUMEN
Kruppel-like transcription factors (KLFs) represent one of the most diverse set of regulators in vertebrate organisms. KLF family members are involved in cell proliferation and differentiation control in normal as well as in pathological situations. Here, we demonstrate that KLF6 behaves as a functional antagonist of the c-Jun proto-oncoprotein. Thus, KLF6 overexpression downregulated c-Jun-dependent transcription and a physical interaction between c-Jun and KLF6 was detected. Moreover, cell proliferation induced by c-Jun was significantly decreased by KLF6. The inhibition of c-Jun functions correlates directly with c-Jun protein degradation induced by KLF6. We also show that all KLF6 effects on c-Jun were largely dependent on phorbol ester (TPA/ionomycin) extracellular stimulation, which enhanced KLF6 nuclear translocation and transcriptional activity and modified its phosphorylation status. Our data are consistent with a novel mechanism of KLF6's role as an inhibitor of cell proliferation by counteracting the function of the c-Jun proto-oncoprotein involving enhanced c-Jun degradation by the proteasome-dependent pathway, and further reinforces KLF6 as a potential tumor suppressor gene product.
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Proteínas Proto-Oncogénicas c-jun/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/fisiología , Transactivadores/fisiología , Animales , Células COS , División Celular/fisiología , Núcleo Celular/metabolismo , Humanos , Hidrólisis , Células Jurkat , Factor 6 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel , Fosforilación , Transporte de Proteínas , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Proto-Oncogénicas c-jun/fisiología , Transactivadores/metabolismo , Transcripción Genética/fisiologíaRESUMEN
Gangliosides have been found to reside in glycosphingolipid-enriched microdomains (GEM) of the plasma membrane and to be involved in the regulation of epidermal growth factor receptor (EGFr or ErbB1) activity. To gain further insight into the mechanisms involved in EGFr modulation by gangliosides, we investigated the distribution of EGFr family members in the plasma membrane of CHO-K1 cells, which were genetically modified to express different ganglioside molecules or depleted of glycolipids. Our data demonstrate that at least four different sets of endogenously expressed gangliosides, including GD3, did not have a significant effect on EGFr distribution in the plasma membrane. In addition, using confocal microscopy analysis we clearly demonstrated that the EGFr co-localizes only to a minor extent with GD3. We also explored the endogenous expression, in wild-type CHO-K1 cells, of the orphan receptor ErbB2 (which is the preferred heteroassociation partner of all other ErbB proteins) and the effect of GD3 expression on its membrane distribution. Our results showed that CHO-K1 cells endogenously express ErbB2 and that expression of the GD3 affected, to some extent, the membrane distribution of endogenous ErbB2. Finally, our findings support the notion that most EGFr are excluded from GEM, while an important fraction of ErbB2 is found to be associated with these microdomains in membranes from CHO-K1 cells.
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Membrana Celular/metabolismo , Receptores ErbB/metabolismo , Gangliósidos/metabolismo , Animales , Células CHO , Membrana Celular/química , Cricetinae , Gangliósidos/química , Fosforilación , Receptor ErbB-2/metabolismo , Tirosina/metabolismoRESUMEN
The effect of dermaseptin (DS), a 34 amino acid residue cationic peptide isolated from Phyllomedusa sauvagii skin, has been studied on promastigotes of Leishmania mexicana growing in vitro. Within 5 min of incubation in the presence of DS, the flagellated parasites lost their motility. DS inhibited promastigote growth by 50% at a concentration of 3 microM and by 100% at 10 microM. Immunocytochemical, freeze fracture, label fracture and electron microscopic observations have shown that the amphipathic peptide generates perturbations of the lipid bilayer leading to altered permeability of the surface membrane and death of the parasite.