RESUMO
The endoplasmic reticulum (ER) is the start site of the secretory pathway, where newly synthesized secreted and membrane proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Little is known about how post-translational modification events regulate packaging of cargo into COPII vesicles. The Saccharomyces cerevisiae protein Erv14, also known as cornichon, belongs to a conserved family of cargo receptors required for the selection and ER export of transmembrane proteins. In this work, we show the importance of a phosphorylation consensus site (S134) at the C-terminus of Erv14. Mimicking phosphorylation of S134 (S134D) prevents the incorporation of Erv14 into COPII vesicles, delays cell growth, exacerbates growth of sec mutants, modifies ER structure and affects localization of several plasma membrane transporters. In contrast, the dephosphorylated mimic (S134A) had less deleterious effects, but still modifies ER structure and slows cell growth. Our results suggest that a possible cycle of phosphorylation and dephosphorylation is important for the correct functioning of Erv14.
Assuntos
Proteínas de Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Transporte Biológico , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Transporte ProteicoRESUMO
There is little information on the milk coagulation process by plant proteases combined with chymosins. This work is aimed at studying the capability of protease enclosed in the ripe fruits of Solanum elaeagnifolium (commonly named trompillo) to form milk gels by itself and in combination with chymosin. For this purpose, proteases were partially purified from trompillo fruits. These proteases had a molecular weight of ~60 kDa, and results suggest cucumisin-like serine proteases, though further studies are needed to confirm this observation. Unlike chymosins, trompillo proteases had high proteolytic activity (PA = 50.23 UTyr mg protein-1) and low milk-clotting activity (MCA = 3658.86 SU mL-1). Consequently, the ratio of MCA/PA was lower in trompillo proteases (6.83) than in chymosins (187 to 223). Our result also showed that milk gels formed with trompillo proteases were softer (7.03 mPa s) and had a higher release of whey (31.08%) than the milk gels clotted with chymosin (~10 mPa s and ~4% of syneresis). However, the combination of trompillo proteases with chymosin sped up the gelling process (21 min), improved the firmness of milk gels (12 mPa s), and decreased the whey release from milk curds (3.41%). Therefore, trompillo proteases could be combined with chymosin to improve the cheese yield and change certain cheese features.
RESUMO
La hipoglucemia inadvertida (HI) es una complicación del tratamiento de la diabetes mellitus tipo 1 (DM1) y DM2 tratada con insulina o sulfonilureas, que se caracteriza por una capacidad reducida para percibir el inicio de los episodios de hipoglucemia. En general, coexiste con una insuficiente respuesta hormonal contrarreguladora a la hipoglucemia denominada falla autonómica asociada a la hipoglucemia (FAAH). El desarrollo de HI y de falla contrarreguladora a la hipoglucemia aumentan significativamente el riesgo de hipoglucemias severas. Se han desarrollado escalas de puntuación para identificar, en la consulta clínica, a este grupo de personas con elevado riesgo de hipoglucemias severas. La piedra angular del tratamiento consiste en evitar las hipoglucemias mediante una intervención multifactorial de cuidados clínicos y educación estructurada.
Hypoglycemia unawereness is a complication of type 1 diabetes treatment and of type 2 diabetes treatment treated with insulin or sulfonylureas, characterized by a reduced ability to perceive the onset of episodes of hypoglycemia. In general, it coexists with an insufficient counterregulatory hormonal response to hypoglycemia called: hypoglycemia associated autonomic failure (HAAF). The development of hypoglycemia unawereness and counterregulatory failure to hypoglycemia significantly increase the risk of severe hypoglycemia. Scoring scales have been developed to identify this group of people at high risk of severe hypoglycemia in the clinic. The cornerstone of treatment is to avoid hypoglycemia through a multifactorial intervention of clinical care and structured education.
Assuntos
Hipoglicemia , Terapêutica , Diagnóstico , Insuficiência Autonômica PuraRESUMO
We report a case of Alternaria chartarum sclerokeratouveitis with an unfavorable response to treatment. To the best of our knowledge, there are no previous reports of this fungus invading the sclera. A 68-year-old diabetic farmer male patient presented with a 3-week history of pain and redness and a decrease in visual acuity occurring 5 days before admittance in the right eye. Examination revealed severe mixed hyperemia and a scleral calcified plaque with a surrounding area of ischemia and lysis. The cornea showed diffuse infiltrates, stromal edema, and hypopyon. Initial scrapings were negative, and empiric antibiotics were started. After a fungus was reported, topical and systemic antifungals were initiated, but there was no clinical response. The eye was enucleated. A slow-growing fungus A. chartarum, resistant to voriconazole, was isolated. Fungal etiology must be kept in mind when dealing with infectious scleritis. Despite treatment, the outcome of this case was unfavorable due to the slow-growing nature of the fungus and this strain's resistance to voriconazole.
RESUMO
Introducción: la incidencia de formas leves y moderadas de trastornos neurocognitivos (TNC) en pacientes con VIH (virus de inmunodeficiencia humana) permanece en ascenso a pesar del uso de terapia antirretroviral (TARV). En la región existen escasos trabajos que estudiaron los TNC en VIH. Objetivos: describir características de pacientes con TNC, identificar posibles etiologías y si se realiza su búsqueda. Material y método: estudio transversal de recolección prospectiva. Se reclutaron en forma consecutiva pacientes de 18 a 60 años VIH positivos sin patología estructural del sistema nervioso central. Se aplicaron exámenes de laboratorio, preguntas para tamizaje de TNC, escala instrumental de actividades de la vida diaria (EIAVD) e internacional de demencia por VIH (EIDV), Adenbrooke's Cognitive Examination Revisado (ACE-R). ACE-R fue elegida como prueba de referencia de desempeño neurocognitivo. Se utilizó inventario de Beck para pesquisa de trastorno depresivo. Análisis estadístico con sistema SPSS. Resultados y discusión: se reclutaron 20 pacientes, se diagnosticó TNC en 9/20 (45%). Los médicos tratantes plantearon TNC en 2/9 pacientes. El análisis multivariado encontró asociación entre desempleo (p=0,012) y menor escolarización (p=0,035) en pacientes con TNC. Etiología de TNC en 9/9 fue multifactorial. Refirieron TNC en el tamizaje 8/9 pacientes. EIDV fue adecuada para detección de TNC severo, pero no para leve. EIAVD tampoco logró detectar algunos casos de TNC. Conclusiones: casi la mitad de pacientes presentaron TNC de causa multifactorial con asociación a desempleo y menor escolarización. Los médicos tratantes no plantearon este diagnóstico, lo que marca la importancia de la evaluación neuropsicológica sistemática en pacientes VIH.
Introduction: the incidence of mild and moderate neurocognitive disorders (NCDs) in HIV patients continues to increase in spite of antiretroviral therapy (ART). Only a few studies in the region focused on HIV associated NCDs. Objective: to describe the characteristics of NCDs patients, identify posible etiologies and decide whether to start the search. Method: transversal study with a prospective collection of data. HIV positive patients between 18 and 60 years old with no structural defects of the central nervous system (CNS) were consecutively recruited. Laboratory tests were applied as well as screening for CNS, the Instrumental activities of daily living (IADLs) scale, the International HIV Dementia Scale (IHDS), and the Adenbrooke's Cognitive Examination revised exam (ACE-R). The latter was chosen as the reference test for neurocognitive performance. The Beck Depression inventory (BDI) was used to identify drepression. Statistical analysis was conducted with the SPSS system. Results and discussion: 20 patients were recruited, NCD was diagnosed in 9 out of 20 patients (45%). Treating physicians spoke about NCD in 2 of the 9 patients. Multivariate analysis revealed an association between unemployment (p=0.012) and a lower schooling rate (p=0.035) in patients with NCDs. Etiology of NCD was multifactorial in all 9 patients. 8 out of 9 patients were referred as NCDs in the screening. IHDS was appropriate to identify severe NCDs, although it failed in mild cases. Also, IADLs failed to identify a few cases of NCDs. Conclusions: almost half of the patients presented multifactorial NCDs, associated to unemployment and a lower rate of schooling. Treating physicians did not consider this diagnosis, what reflects the importance of a systematic neuropsychological assessment in HIV patients.
Introdução: a incidência de formas leves e moderadas de transtornos neurocognitivos (TNC) em pacientes com VIH (vírus de imunodeficiência humana) continua crescendo apesar do uso da terapia antirretroviral (TARV). Poucos trabalhos estudaram TNC em pacientes VIH positivos na regiao. Objetivos: descrever as características dos pacientes com TNC, identificar possíveis etiologias e se são pesquisados no paciente. Método: estudo transversal com coleta de dados prospectiva. Foram incluídos de forma consecutiva pacientes com idades entre 18 e 60 anos VIH positivos sem patologia estrutural do sistema nervoso central (SNC). Foram realizados exames de laboratório, um questionário para triagem dos TNC, e foram aplicadas as escalas Instrumental de Atividades da Vida Diária (EIAVD), Internacional de Demência por VIH (EIDV) e Adenbrooke's Cognitive Examination Revisado (ACE-R). Esta última foi escolhida como prova de referencia de desempenho neurocognitivo. O inventário de Beck foi utilizado para pesquisa de transtorno depressivo. A análise estatística foi realizada com o pacote SPSS. Resultados e discussão: foram incluídos 20 pacientes sendo que os TNC foram diagnosticados em 9/20 (45%). Os médicos que atenderam esses pacientes diagnosticaram TNC em 2/9 pacientes. A análise multivariada mostrou uma associação entre desemprego (p=0,012) e menor escolarização (p=0,035) em pacientes com TNC. A etiologia dos TNC em 9/9 foi multifatorial. A triagem mostrou TNC em 8/9 pacientes. O teste EIDV foi adequado para a detecção dos TNC severos porém não para leves, e também não pode detectar alguns casos de TNC. Conclusões: quase a metade dos pacientes apresentou TNC de causa multifatorial associados a desemprego e menor escolarização. Os médicos que atenderam os pacientes não diagnosticaram esses transtornos o que mostra a importância da avaliação neuropsicológica sistemática em pacientes VIH.
Assuntos
Complexo AIDS Demência , HIV , Transtornos NeurocognitivosAssuntos
Amiloidose/genética , Pré-Albumina/genética , Adolescente , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Mutação/genética , Adulto JovemRESUMO
La neuropatía crónica es la complicación más prevalente de la diabetes. De las distintas formas de neuropatía diabética, la polineuropatía distal y simétrica y la neuropatía autonómica, particularmente la neuropatía autonómica cardíaca, son las más estudiadas y en ocasiones son asintomáticas. Los pacientes con prediabetes también pueden desarrollar neuropatías similares a la neuropatía diabética. La prevención es un componente clave en la atención de estas complicaciones. La neuropatía autonómica diabética afecta varios órganos y sistemas de la economía. Nuestro objetivo es describir aquellas manifestaciones clínicas poco conocidas, y en consecuencia poco tenidas en cuenta, que afectan el sistema cardiovascular, el gastrointestinal y el compromiso vesical
Chronic neuropathy is the most prevalent of the diabetic complications. Distal and symmetric sensitive polyneuropathy, and autonomic compromise, particularly cardiac autonomic neuropathy,are the most studied; occasionally they are asymptomatic. Like diabetic patients, prediabetics can also develop neuropathy. Prevention is a key component in these complications. Autonomic neuropathy affects several body´s organs and systems. Our goal is to describe those less known clinical manifestations, and because of this, less considered complications that affect cardiovascular, gastrointestinal system and bladder functioning
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Neuropatias Diabéticas , GastroenteropatiasRESUMO
La diabetes es una enfermedad crónica y progresiva que se asocia a complicaciones potencialmente discapacitantes, entre ellas, la neuropatía diabética es probablemente la afectación sintomática más frecuente con importante impacto social y económico. El tratamiento de la neuropatía somática dolorosa y del sistema nervioso autónomo ha sido un desafío durante años. Nuevas terapéuticas se encuentran disponibles, las cuales mejoran el dolor y brindan esperanza de lograr alivio a personas que padecen esta complicación
Assuntos
Neuropatias Diabéticas , HiperalgesiaRESUMO
La neuropatía diabética (ND) es la complicación microvascular más frecuente y más precoz asociada a la diabetes mellitus (DM), no obstante esta situación, es la más olvidada y la menos diagnosticada. Al mismo tiempo es de amplio conocimiento que el síndrome metabólico (SM) tiene una elevada prevalencia, y que la relación entre este estado y el compromiso macrovascular está documentada. Es de interés para el Comité de Neuropatía Diabética analizar la afectación neuropatía en el marco del SM y en el de uno de sus componentes constitutivos como es la disglucemia no diabética. El subdiagnóstico de esta entidad y el aumento del riesgo de la morbimortalidad de los pacientes que la padecen hacen importante alertar a la comunidad médica de la existencia de esta complicación microvascular que excede el marco de la DM y se presenta también en el SM y en la disglucemia tanto de ayunas como posprandial.
Assuntos
Neuropatias Diabéticas , Síndrome MetabólicaRESUMO
BACKGROUND: Gonadoblastoma (GB) is regarded as an in situ form of germ cell tumor in dysgenetic gonads, and 30% of patients with GB develop a dysgerminoma/seminoma tumor. OBJECTIVE: Determine whether OCT3/4 and ß-catenin are expressed in dysgenetic gonads before GB development and whether TSPY participates in the OCT3/4-ß-catenin pathways in the malignant invasive behavior. METHODS: dysgenetic gonads of Disorders of sex differentiation (DSD) patients with mixed gonadal dysgenesis were analyzed by immunohistochemistry and immunofluorescence for comparison with GB and dysgerminoma/seminoma. RESULTS: Our results suggest that the development of GB is secondary to the interaction of OCT3/4 and TSPY, that ß-catenin does not participate in this process. CONCLUSIONS: The use of this biological markers detects the potential high risk gonads.