Alostasis y carga alostática de las enfermedades / Allostasis and allostatic load of diseases

Introducción: La homeostasis es la propiedad fundamental de los sistemas biológicos de preservar el medio interno. La presión arterial, el pH, las concentraciones plasmáticas de sodio y glucosa son ejemplos de variables homeostáticos, donde el propósito de la regulación fisiológica es fijar cada parámetro interno en un punto de ajuste, detecta errores y los corrige con realimentación negativa. Los fisiólogos han evidenciado que muchos errores no son constantes sino adaptativos. Objetivo: Exponer los conceptos novedosos acerca de la influencia de un ambiente de estrés sobre nuestra fisiología y sus efectos deletéreos a largo plazo. Métodos: Se realizó una revisión bibliográfica, en el motor de búsqueda Google académico, los descriptores: homeostasis, alostasis y carga alostática. Conclusiones: Se expuso los conceptos novedosos acerca de la influencia de un ambiente de estrés sobre nuestra fisiología y sus efectos deletéreos a largo plazo. La alostasis es el precio que el cuerpo paga por verse obligado a adaptarse a situaciones psicosociales o físicas adversas. La obesidad, la diabetes, la insulinoresistencia, la hipertensión arterial, son variables alostáticas, no homeostáticas, no son parámetros constantes, sino adaptativos, el organismo cambiará su medio interno para enfrentar el desafío o perturbación que le llega desde el exterior. Pensar en muchas de estas patologías bajo un modelo alostático puede enriquecer los recursos conceptuales del médico y modificar el abordaje de enfermedades prevalentes(AU)

Introduction: Homeostasis is the fundamental property of biological systems to preserve the internal environment. Blood pressure, pH, plasma sodium and glucose concentrations are examples of homeostatic variables, where the purpose of physiological regulation is to fix each internal parameter at a set point, detect errors and correct them with negative feedback. Physiologists have shown that many errors are not constant but adaptive. Objective: To expose novel concepts about the influence of a stressful environment on our physiology and its deleterious long-term effects. Methods: A literature review was performed, in the academic Google search engine, the descriptors: homeostasis, allostasis and allostatic load. Conclusions: Novel concepts about the influence of a stressful environment on our physiology and its deleterious long-term effects were exposed. Allostasis is the price the body pays for being forced to adapt to adverse psychosocial or physical situations. Obesity, diabetes, insulin resistance, arterial hypertension, are allostatic variables, not homeostatic, they are not constant parameters, but adaptive, the organism will change its internal environment to face the challenge or perturbation that comes from the outside. Thinking about many of these pathologies under an allostatic model can enrich the conceptual resources of the physician and modify the approach to prevalent diseases(AU)

Factores predictores de muerte en pacientes con infarto cerebral isquémico / Predictive factors of death in patients with ischemic cerebral infarction

Introducción: La enfermedad cerebrovascular es la tercera causa de muerte a nivel mundial. Objetivo: Determinar los factores predictores de muerte que influyen en pacientes con ictus isquémico. Métodos: Se realizó un estudio analítico, retrospectivo, de corte transversal, en el período comprendido entre el 1 de enero de 2014 al 31 de diciembre de 2016 en el municipio de Güines. Para la selección de la muestra se realizó un muestreo probabilístico por estratos para separar los pacientes con diagnóstico de ictus isquémico en dos grupos: vivos y fallecidos. Posteriormente se realizó un muestreo aleatorio simple, la muestra quedó constituida por 89 pacientes con diagnóstico de ictus y vivos al egreso hospitalario, y 89 pacientes fallecidos por ictus isquémico durante el ingreso hospitalario. Resultados: El mayor número de pacientes vivos y fallecidos con ictus isquémico fue el grupo de 70 a 79 años, con 80 en total, predominaron los hipertensos y la hiperlipemia tanto en vivo como fallecido, dentro de los complementarios se encontró la hiperuricemia y la hiperglucemia en ambos grupos. En el electrocardiograma el intervalo QT prolongado, mostró un mayor valor porcentual superior en los pacientes fallecidos respecto a los vivos (49 por ciento y 17 por ciento respectivamente). Conclusiones: El grupo etario de 70 a 79 años, la hipertensión arterial, el hábito de fumar, la hiperlipidemia y el intervalo QT corregido en el electrocardiograma, son factores que influyen en la muerte por ictus isquémico(AU)

Introduction: Cerebrovascular disease is the third cause of death worldwide. Objective: To determine the predictive factors of death that influence patients with ischemic stroke. Methods: A retrospective, cross-sectional, analytical study was conducted from January 1, 2014 to December 31, 2016 in Güines municipality. the sample was selected using a probabilistic sampling by strata to separate the patients diagnosed with ischemic stroke in two groups: living and deceased. Subsequently, a simple random sampling was carried out. The sample consisted of 89 patients with a diagnosis of stroke and alive at hospital discharge and 89 patients who died of ischemic stroke during hospital admission. Results: The largest number of patients alive and deceased with ischemic stroke was the age group 70-79 years, 80 in total. Hypertension and hyperlipemia predominated in both groups. Hyperuricemia and hyperglycemia were found in the complementary tests for both groups. In the electrocardiogram, the prolonged QT interval showed a higher percentage value in the deceased patients than in those alive (49 percent and 17 percent respectively). Conclusions: We found factors influencing death due to ischemic stroke as the age group 70-79 years, hypertension, smoking habit, hyperlipidemia and corrected QT interval in the electrocardiogram(AU)

High-risk surgical stage 1 endometrial cancer: analysis of treatment outcome.

PURPOSE: To report the relapse and survival rates associated to treatment for patients with stage IC, grade 2 or grade 3 and IB grade 3 diseases considered high risk patients group for relapse. MATERIALS AND METHODS: From January 1993 to December 2003, 106 patients with endometrial cancer stage I were managed surgically in our institution. Based on data from the medical records, 106 patients with epithelial endometrial cancer met the following inclusion criteria: stage IC grade 2 or 3 and IB grade 3 with or without lymphovascular invasion. Staging was defined according to the FIGO surgical staging system. Postoperative adjuvant radiotherapy consisted of external beam pelvic radiation, vaginal brachytherapy alone or both. The median age was 65 years (range, 32-83 years), lymph node dissection was performed in 45 patients (42.5%) and 14 patients (13.2%) received vaginal brachytherapy only, and 92 (86.8%) received combined vaginal brachytherapy and external beam radiotherapy. The median dose of external beam radiotherapy administered to the pelvis was 4500 cGy (range 4000-5040). The median dose to vaginal surface was 2400 cGy (range 2000-3000). Predominant pathological stage and histological grade were IC (73.6%) and grade 3 (51.9%). The lymphovascular invasion was present in 33 patients (31.1%) and pathological stage IC grade 2 was most common (48. 1%) combination of risk factors in this group. RESULTS: With a follow up median of 58.3 months (range 12.8-154), five year overall survival and event free survival were 78.5% and 72.4%, respectively. Locoregional control in five year was 92.4%. Prognostic factors related with survival in univariate analyses were: lymphadenectomy (p = 0.045), lymphovascular invasion (p = 0.047) and initial failure site (p < 0.0001). In multivariate analyses the initial failure in distant sites (p < 0.0001) was the only factor associated with poor survival. Acute and chronic gastrointestinal and genitourinary toxicity grades 3 were not observed. CONCLUSION: In conclusion, our results showed that the stage IC, grade 2, 3 and IB grade 3 endometrial cancer was associated with significantly increased risk of distant relapse and endometrial carcinoma-related death independently of salvage treatment modality.

Cancer vaccines: an update with special focus on ganglioside antigens.

Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by the (CIM) from La Havana, Cuba, to developed new strategies for specific active immunotherapy. The project included two ganglioside based vaccines and one anti-idiotypic vaccine. We focused on two antigens: first GM3, an ubiquitous antigen which is over-expressed in several epithelial tumor types; and a second one, N-Glycolyl-GM3 a more molecule, not being expressed in normal tissues and recently found in several neoplastic cells, in particular breast, melanoma and neuroectodermal cancer cells. We developed two vaccines, one with each antigen, both using proteins derived from the outer membrane proteins (OMP) of Neisseria Meningitidis B, as carriers. We developed also the 1E10 vaccine; an anti-idiotype vaccine designed to mimic the N-Glycolyl-GM3 gangliosides. This monoclonal antibody is an Ab2-type-antibody which recognizes the Ab1 antibody called P3, the latter is a monoclonal antibody that specifically recognizes gangliosides as antigens. Since 1998 we initiated a clinical development program for these three compounds. Results of the phase I clinical trials proved that the three vaccines were safe and able to elicit specific antibody responses. In addition we were able to demonstrate the activation of the cellular arm of the immune response in patients treated with the GM3 vaccine. Although phase I trials are not designed to evaluate antitumor efficacy, it was encouraging to observe tumor shrinkage in some patients treated both with the GM3 and N-Glycolyl-GM3 vaccines. We have already begun a phase II program in several neoplastic diseases, with all three vaccines.