RESUMO
It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.
Assuntos
Estresse Oxidativo , Ratos Sprague-Dawley , Vitamina E , Animais , Ratos , Vitamina E/farmacologia , Vitamina E/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , DipeptídeosRESUMO
Cardiovascular (CV) disease is the main cause of death in nonalcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Thus, we investigated the effects of ornithine aspartate (LOLA) and/or Vitamin E (VitE) on CV parameters in a steatohepatitis experimental model. Adult Sprague Dawley rats were randomly assigned (10 animals each) and treated from 16 to 28 weeks with gavage as follows: controls (standard diet plus distilled water (DW)), NAFLD (high-fat choline-deficient diet (HFCD) plus DW), NAFLD+LOLA (HFCD plus LOLA (200 mg/kg/day)), NAFLD+VitE (HFCD plus VitE (150 mg twice a week)) or NAFLD+LOLA+VitE in the same doses. Atherogenic ratios were higher in NAFLD when compared with NAFLD+LOLA+VitE and controls (p < 0.05). Serum concentration of IL-1ß, IL-6, TNF-α, MCP-1, e-selectin, ICAM-1, and PAI-1 were not different in intervention groups and controls (p > 0.05). NAFLD+LOLA decreased miR-122, miR-33a, and miR-186 (p < 0.05, for all) in relation to NAFLD. NAFLD+LOLA+VitE decreased miR-122, miR-33a and miR-186, and increased miR-126 (p < 0.05, for all) in comparison to NAFLD and NAFLD+VitE. NAFLD+LOLA and NAFLD+LOLA+VitE prevented liver collagen deposition (p = 0.006) in comparison to NAFLD. Normal cardiac fibers (size and shape) were lower in NAFLD in relation to the others; and the inverse was reported for the percentage of regular hypertrophic cardiomyocytes. NAFLD+LOLA+VitE promoted a significant improvement in atherogenic dyslipidemia, liver fibrosis, and paracrine signaling of lipid metabolism and endothelial dysfunction. This association should be further explored in the treatment of NAFLD-associated CV risk factors.
Assuntos
Doenças Cardiovasculares , Dipeptídeos , Hepatopatia Gordurosa não Alcoólica , Vitamina E , Animais , Ratos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Ratos Sprague-Dawley , Fatores de Risco , Vitamina E/uso terapêutico , Modelos Animais de Doenças , Dipeptídeos/uso terapêutico , Quimioterapia CombinadaRESUMO
INTRODUCTION: Malignant triton tumor (MTT) is an extremely rare variant of the malignant peripheral nerve sheath tumors (MPNSTs) with rhabdomyosarcomatous differentiation, which was first described in 1932 by Mason. MTT affects, in most cases, patients under 35 years of age, and it is usually manifested as a mass that may or not be painful. However, the incidence in pediatric patients is atypical. This tumor presents an aggressive course and limited survival rate, and the prognosis is different between individuals with or without a concomitant diagnosis of neurofibromatosis type 1 (NF1). Currently, the recommended treatment is surgical resection, and adjuvant chemotherapy and radiotherapy, but its efficacy is not yet clear. PRESENTATION OF THE CASE: A 13-year-old female patient was referred to the pediatric oncology service due to the presence of an abdominal mass and weight loss, initially diagnosed with Wilms' tumor. After extensive investigation, surgical resection, and immunohistopathological evaluation, the diagnosis of malignant triton tumor was confirmed. The patient also underwent cycles of chemotherapy after resection, and is currently awaiting immunotherapy. DISCUSSION AND CONCLUSION: Malignant triton tumor is extremely rare and difficult to diagnose, especially in children or young people, age groups in which the incidence of the disease is even lower. This may be the reason it is rarely suspected, and it was a great challenge for the clinical care team. It is essential to consider and investigate this possibility of differential diagnosis, as patients diagnosed with this malignant tumor have a low survival rate and poor prognosis.
RESUMO
INTRODUCTION: Cholecystectomy has been the subject of several clinical and cost comparison studies. OBJECTIVE: The results of open or laparoscopy cholecystectomy were compared in terms of cost and effectiveness from the perspective of health care institutions and from that of the patients. MATERIALS AND METHODS: The cost-effectiveness study was undertaken at two university hospitals in Bogotá, Colombia. The approach was to select the type of cholecystectomy retrospectively and then assess the result prospectively. The cost analysis used the combined approach of micro-costs and daily average cost. Patient resource consumption was gathered from the time of surgery room entry to time of discharge. A sample of 376 patients with cholelithiasis/cystitis (May 2005-June 2006) was selected--156 underwent open cholecystectomy and 220 underwent laparoscopic cholecystectomy. The following data were tabulated: (1) frequency of complications and mortality, post-surgical hospital stay, (2) reincorporation to daily activities, (3) surgery duration, (4) direct medical costs, (5) costs to the patient, and (6) mean and incremental cost-effectiveness ratios. RESULTS: Frequency of complications was 13.5% for open cholecystectomy and 6.4% for laparoscopic cholecystectomy (p=0.02); hospital stay was longer in open cholecystectomy than in laparoscopic cholecystectomy (p=0.003) as well as the reincorporation to daily activities reported by the patients (p<0.001). The duration of open cholecystectomy was 22 min longer than laparoscopic cholecystectomy (p<0.001). The average cost of laparoscopic cholecystectomy was lower than open cholecystectomy and laparoscopic cholecystectomy was more cost-effective than open cholecystectomy (US$ 995 vs. US$ 1,048, respectively). The patient out-of-pocket expenses were greater in open cholecystectomy compared to laparoscopic cholecystectomy (p=0.015). Mortality was zero. CONCLUSIONS: The open laparoscopy procedure was associated with longer hospital stays, where as the cholecystectomy procedure required a longer surgical duration. The direct cost of the latter was lower for both for the health care institution and patients. The cost-effectiveness for both procedures was comparable.
Assuntos
Colecistectomia/economia , Colecistectomia Laparoscópica/economia , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Introducción. La colecistectomía ha sido objeto de varios estudios clínicos y de costos a nivelmundial. Objetivo. Evaluar el costo-efectividad de la colecistectomía abierta y de la laparoscópica desde laperspectiva del tercer pagador. Materiales y métodos. Se llevó a cabo un estudio de costo-efectividad en dos hospitales de Bogotá. Se obtuvieron los datos de efectividad de las cirugías a partir de un estudio de cohortes, y se obtuvo enforma retrospectiva el tipo de colecistectomía y en forma prospectiva, el resultado. Se incluyeron 376 pacientes intervenidos por colecistitis o litiasis de mayo de 2005 a junio de 2006; 156 pacientes fueron intervenidos por colecistectomía abierta y 220 por laparoscopia. Los resultados que se analizaron fueron los siguientes: frecuencia de complicaciones, estancia hospitalaria, reincorporación a las labores cotidianas y duración de la cirugía. Los costos se recolectaron según el tipo de estudio económico y sólo se incluyeron los costos directos. Posteriormente, se planteó un estudio de costo-efectividad a un año desde la perspectiva del tercer pagador; se propuso un modelo de árbol de decisiones y se calcularon las razones de incremento de costo-efectividad para cada uno de los desenlaces propuestos. Resultados. Los resultados de la colecistectomía abierta frente a la laparoscópica fueron: OR ajustado de complicaciones: 2,02 (IC95% 0,94-4,37); conversión quirúrgica (tasa): 3,2%; estancia: 2,2 Vs. 1,6,p=0,003; reincorporación a cotidianidad: 32,5 Vs. 9,6, p<0,001; duración quirúrgica: 22 minutos (p<0,001) menor en la colecistectomía abierta; desde la perspectiva del tercer pagador, costo promedio: US$995 Vs. US$ 1.048; incremento del costo-efectividad: US$ 7,4 favoreciendo la laparoscópica; desde la perspectiva paciente, costo promedio: US$ 53.2 Vs. US$ 104,8; incremento del costo-efectividad: US$-7.3 favoreciendo la laparoscópica; cero mortalidad. La variable que más impactó tiene en la toma de decisiones en términos de costos es el costo del procedimiento quirúrgico. Conclusiones. Hubo mayor estancia hospitalaria en la colecistectomía abierta frente a la mayor duración quirúrgica en la laparoscópica; en el costo directo de la laparoscópica: menor para IPS y pacientes; y en costo-efectividad equiparable para ambos procedimientos.
Introduction. Cholecystectomy has been the subject of several clinical and cost comparison studies. Objective. The results of open or laparoscopy cholecystectomy were compared in terms of cost and effectiveness from the perspective of health care institutions and from that of the patients. Materials and methods. The cost-effectiveness study was undertaken at two university hospitals in Bogotá, Colombia. The approach was to select the type of cholecystectomy retrospectively and then assess the result prospectively. The cost analysis used the combined approach of micro-costs and daily average cost. Patient resource consumption was gathered from the time of surgery room entry to time of discharge. A sample of 376 patients with cholelithiasis/cystitis (May 2005-June 2006) was selected--156 underwent open cholecystectomy and 220 underwent laparoscopic cholecystectomy. The following data were tabulated: (1) frequency of complications and mortality, post-surgical hospital stay, (2) reincorporation to daily activities, (3) surgery duration, (4) direct medical costs, (5) costs to the patient, and (6) mean and incremental cost-effectiveness ratios. Results. Frequency of complications was 13.5% for open cholecystectomy and 6.4% for laparoscopic cholecystectomy (p=0.02); hospital stay was longer in open cholecystectomy than in laparoscopic cholecystectomy (p=0.003) as well as the reincorporation to daily activities reported by the patients (p<0.001). The duration of open cholecystectomy was 22 min longer than laparoscopic cholecystectomy (p<0.001). The average cost of laparoscopic cholecystectomy was lower than open cholecystectomyand laparoscopic cholecystectomy was more cost-effective than open cholecystectomy (US$ 995 vs. US$ 1,048, respectively). The patient out-of-pocket expenses were greater in open cholecystectomy compared to laparoscopic cholecystectomy (p=0.015). Mortality was zero. Conclusions: The open laparoscopy procedure was associated with longer hospital stays, where asthe cholecystectomy procedure required a longer surgical duration. The direct cost of the latter was lower for both for the health care institution and patients. The cost-effectiveness for both procedures was comparable.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colecistectomia/economia , Análise Custo-Benefício , Colecistectomia Laparoscópica/economia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
La vía de señalización de la fosfatidilinositol- 3-kinasa (PI3K) es crucial en numerosos aspectos del crecimiento y la supervivencia celular. Esta vía es estimulada fisiológicamente como consecuencia de muchos factores de crecimiento y factores reguladores. Varias alteraciones genéticas como amplificación, mutación y rearreglos cromosómicos pueden comprometer la vía PI3K, generando su activación permanente. En diferentes tipos de cáncer se han encontrado evidencias de estas modificaciones genéticas deletéreas. La activación anormal de la vía PI3K resulta en alteración de los mecanismos de control del crecimiento y la supervivencia celular, lo que favorece el crecimiento competitivo, la capacidad metastasica y, frecuentemente, una mayor resistencia a los tratamientos. El objetivo de este articulo es revisar los aspectos relacionados con el funcionamiento de la vía de señalización PI3K/ Akt y su rol dentro del proceso de carcinogénesis en los seres humanos.
The signaling pathway of phosphatidylinositol 3-kinase (PI3K) is critical in many aspects of growth and cell survival. The path of PI3K is stimulated physiologically as a result of many growth factors and regulatory factors. Several genetic alterations such as amplification, mutation and chromosomal arrangements may compromise the PI3K pathway, generating permanent activation in different cancer types have found evidence of these deleterious genetic modifications. Abnormal activation of the PI3K pathway results in alteration of the control mechanisms of growth and cell survival, which favors the competitive growth, and frequently metastatic capacity, greater resistance to treatment. The aim of this paper is to review matters relating to the operation of the PI3K/Akt signaling pathway and its role in the process of carcinogenesis in humans.
Assuntos
Humanos , Fosfatidilinositol 3-Quinase , Fosfatidilinositóis , Peptídeos e Proteínas de Sinalização Intercelular , NeoplasiasRESUMO
La educación médica ha sido y será un tema de preocupación para todas las generaciones en cualquier parte del mundo ya que de ello depende en parte el progreso de las sociedades y de nuestra profesión, necesaria en el Estado. En este artículo trataré de realizar un recuento histórico de los procesos que se han llevado a cabo en la educación médica en el mundo y en especial en los países de América Latina, tomando como puntos de referencia los dos paradigmas más importantes hasta el momento como son el paradigma "flexneriano" y el paradigma "crítico". También enuncio los inconvenientes y algunas reformas educacionales que ha tenido que pasar la mayoría de las naciones frente a la adversidad del contexto socioeconómico que los rodea. Además de ello hago un esbozo de un tercer paradigma en gestación generado por la introducción de un nuevo personaje en la educación médica: la tecnología.
The medical education has been and will continue to be a subject of concern to all generations anywhere in the world because it depends in part on the progress of societies and our profession; so necessary in the state. The objective of this article is to try to conduct a historical review of the processes that have taken place in medical education in the world and especially in Latin America; taking as a benchmark the two paradigms most important so far as the "Flexner" paradigm and the "critical" paradigm. Ill also try to show the disadvantages and some educational reforms that most of the nations have faced, related to adversity in the socio-economic context that surrounds them. Besides that, I make an outline of a third emerging paradigm generated by the introduction of a new character in medical education: Technology.