Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Quinacrine as a potential treatment for COVID-19 virus infection.

A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a current outbreak of infection termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 is currently a global pandemic that may cause close to half a billion deaths around the world. Until now, there is no effective treatment for COVID-19. Quinacrine (Qx) has been used since the 1930s as preventive antimalarial compound. It is a recognized small molecule inhibitor of RNA virus replication, with known anti-prion activity, and identified as a potent Ebola virus inhibitor both in vitro and in vivo. Recently, Qx has showed anti-SARS-CoV-2 activity. Herein, we review the potential mechanisms associated with quinacrine as an antiviral compound.

Tirotoxicosis por enfermedad trofoblástica gestacional: revisión a partir de 3 casos / Thyrotoxicosis due to gestational trophoblastic disease: clinical cases

La enfermedad trofoblástica gestacional (ETG) es una complicación del embarazo poco común. Corresponde a un espectro de lesiones proliferativas del tejido trofoblástico: Mola Hidatiforme (MH) en sus formas parcial y completa, Coriocarcinoma, Tumor Trofoblástico y Tumor Trofoblástico Epiteloide. Los distintos tipos de ETG presentan en común la hipersecreción de gonadotrofina coriónica humana (hCG). La hCG es una hormona glicoproteica con una estructura muy similar a la TSH, por lo cual puede estimular la función tiroidea en condiciones fisiológicas y en algunas condiciones patológicas. La ETG puede cursar con hipertiroidismo, el cual puede variar en intensidad, desde una presentación asintomática con alteración leve de hormonas tiroideas a un cuadro de hipertiroidismo manifiesto. Se presentan 3 casos clínicos de pacientes con ETG, específicamente MH que evolucionaron con tirotoxicosis transitoria. Los casos presentaron un cuadro leve de hipertiroidismo con pocos síntomas asociados. La taquicardia fue el único síntoma en la mayoría de los casos. En todas las pacientes las hormonas tiroideas se normalizaron después del tratamiento de la ETG. Conclusión: Se debe tener presente la posibilidad de hipertiroidismo en toda paciente con ETG. Un alto nivel de sospecha permitirá identificar a aquellas pacientes que cursen con hipertiroidismo, permitiendo así un diagnóstico y tratamiento oportuno.

Gestational trophoblastic disease (GTD) is a rare complication of pregnancy. GTD includes a group of proliferative lesions of trophoblastic tissue: partial and complete hydatidiform mole, choriocarcinoma, epithelioid trophoblastic tumor, and placental site trophoblastic tumor. The different types of GTD have in common the hypersecretion of human chorionic gonadotropin (hCG). HCG is a glycoprotein hormone with a similar structure to TSH. In physiological and pathological conditions hCG can stimulate thyroid function. GTD can present with hyperthyroidism, which can vary in intensity, from an asymptomatic presentation with mild alteration of thyroid hormones to a manifest hyperthyroidism. We present 3 clinical cases of patients with GTD thyrotoxicosis. All cases presented mild hyperthyroidism. Tachycardia was the only symptom in most cases. In all patients thyroid hormones return to normal after treatment of GTD. Conclusion: In patients with GTD the possibility of hyperthyroidism should be kept in mind. A high level of suspicion will allow to identifying patients with hyperthyroidism.

Hipertiroidismo en personas mayores de 65 años: serie de casos de un hospital universitario / Thyrotoxicosis in the elderly: case series report from a university hospital

Introducción: En Chile en las últimas décadas ha aumentado la población de personas mayores de 65 años. La tirotoxicosis en este grupo está asociada a complicaciones como fibrilación auricular (FA), insuficiencia cardiaca (ICC), osteoporosis y aumento de la mortalidad. En algunos casos puede presentarse con síntomas no específicos, cuadro conocido como hipertiroidismo apático. Objetivos: Evaluar las características clínicas de la tirotoxicosis en personas mayores. Método: Serie de casos retrospectiva. Se analizaron fichas clínicas de pacientes mayores de 65 años con el diagnóstico de tirotoxicosis controlados en nuestro centro entre enero de 2012 y mayo de 2018. Resultados: En el periodo estudiado 54 pacientes fueron diagnosticados de tirotoxicosis. Se excluyen 4 por datos incompletos. El 80% corresponden a mujeres. La mediana de edad fue 71 años (rango 65-94), sin diferencias por género (p=0,61). La etiología más frecuente fue enfermedad de Graves (EG) en 64%, seguido por bocio multinodular hiperfuncionante en 20%, adenoma tóxico en 10% y asociada a fármacos en 6%. De los pacientes con EG, 28% presentó orbitopatía distiroidea (OD) clínicamente evidente. Un 30% se diagnosticó en contexto de baja de peso, deterioro cognitivo o patología cardiovascular, sin presentar síntomas clásicos de hipertiroidismo. Un 16% presentó FA, 14% ICC y 6% fractura osteoporótica. El 28% fue diagnosticado durante una hospitalización o requirió ser hospitalizado durante los meses siguientes. Los mayores de 75 años presentan una mayor probabilidad de hipertiroidismo apático (OR 5,1, IC95% 1,15-22,7 p=0,01). Además, las complicaciones aumentan en mayores de 75 años, encontrándose en este grupo todos los casos de FA. Conclusiones: La etiología más común de tirotoxicosis fue la EG, a diferencia de lo reportado en otras poblaciones. Un número importante de pacientes debutó sin síntomas clásicos de hipertiroidismo, principalmente mayores de 75 años, por lo que se debe tener una alta sospecha en este grupo etario.

Introduction: Hyperthyroidism in the elderly can produce severe complications such as atrial fibrillation (AF), heart failure (CHF) and osteoporosis. In the elderly, thyrotoxicosis may have only nonspecific symptoms, known as apathetic hyperthyroidism. Objective: To evaluate the clinical characteristics of thyrotoxicosis in the elderly. Methods: Retrospective case series. We reviewed clinical records of patients with thyrotoxicosis older than 65 years, between January 2012 and March 2019. Results: During this period, 54 patients were diagnosed with thyrotoxicosis. Four patients were excluded due to incomplete data. 80% were women. The average age was 73 years (range 65-94), without age difference between gender (p=0,61). The most frequent etiology was Graves' disease in 64%. Hyperfunctioning multinodular goiter was confirmed in 20%, toxic adenoma in 10% and drug-associated in 6%. Twenty eight percent of Graves' disease patients had dysthyroid orbitopathy. Thirty percent presented as apathetic hyperthyroidism. Sixteen percent of the patients presented AF, 14% CHF, and 6% osteoporotic fracture. Twenty-eight percent were diagnosed during hospitalization or required hospitalization in the following months. Those older than 75 years had a greater probability of presenting apathetic hyperthyroidism (OR 5.1, 95% CI 1.15- 22.7 p=0.01). Complications increase in this age group, with all cases of AF. Conclusions: The most common etiology of thyrotoxicosis in this group was GD. This differs from other populations. A significant number of patients presented without classic symptoms of hyperthyroidism, especially in people older than 75 years. Special attention should be paid to atypical symptoms of hyperthyroidism in this group.

Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age.

Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.

Relevance of Alternative Routes of Kynurenic Acid Production in the Brain.

The catabolism of tryptophan has gained great importance in recent years due to the fact that the metabolites produced during this process, with neuroactive and redox properties, are involved in physiological and pathological events. One of these metabolites is kynurenic acid (KYNA), which is considered as a neuromodulator since it can interact with NMDA, nicotinic, and GPR35 receptors among others, modulating the release of neurotransmitters as glutamate, dopamine, and acetylcholine. Kynureninate production is attributed to kynurenine aminotransferases. However, in some physiological and pathological conditions, its high production cannot be explained just with kynurenine aminotransferases. This review focuses on the alternative mechanism whereby KYNA can be produced, either from D-amino acids or by means of other enzymes as D-amino acid oxidase or by the participation of free radicals. It is important to mention that an increase in KYNA levels in processes as brain development, aging, neurodegenerative diseases, and psychiatric disorders, which share common factors as oxidative stress, inflammation, immune response activation, and participation of gut microbiota that can also be related with the alternative routes of KYNA production, has been observed.

Paratirotoxicosis y tumor cervical palpable: caso clínico de cáncer de paratiroides / Parathyrotoxicosis and palpable neck mass: a clinical presentation of parathyroid cancer

Introducción: El cáncer de paratiroides es poco frecuente. Suele presentarse como hiperparatiroidismo primario, en ocasiones como crisis hipercalcémica, con malestar general, náuseas, vómitos, alteraciones del ánimo y pérdida de peso. En algunos casos se presenta como osteítis fibrosa quística, osteopenia difusa, osteoporosis y fracturas patológicas. El diagnóstico suele estar dado por biopsia quirúrgica que muestra invasión a estructuras adyacentes, o metástasis locales y distantes. El tratamiento es la resección quirúrgica del tumor, sin uso de terapias adyuvantes. Su tasa de recurrencia es alta, de 25 a 100%. Algunos factores de mal pronóstico son metástasis a linfonodos en la presentación inicial, metástasis distantes y carcinomas no funcionantes. Caso clínico: Paciente masculino de 64 años que consultó por compromiso del estado general, bradipsiquia, poliuria, cefalea y masa cervical. Además presentaba hipercalcemia y gran elevación de PTH. Se realizó resección quirúrgica de la masa cervical, con biopsia rápida con atipias y mitosis 1/10, y de un nódulo hiperplásico tiroideo. Tras esto, sus niveles de PTH disminuyeron, así como también descendieron sus niveles de calcio. Discusión: Los pacientes que presentan cáncer de paratiroides suelen tener valores más elevados de calcemia y PTH. Para su diagnóstico, no se recomienda usar biopsia por punción, por riesgo de diseminación y por el bajo rendimiento de esta técnica. Conclusión: Pese a ser poco frecuente, se debe pensar en cáncer de paratiroides en el contexto de un paciente con hipercalcemia, especialmente si presenta PTH muy elevada. La sospecha clínica de este diagnóstico tiene directa relación con la posibilidad de tratamiento y pronóstico de la enfermedad.

Introduction: Parathyroid cancer is rare. Usually presented as primary hyperparathyroidism, sometimes as hypercalcemic crisis, with general malaise, nausea, vomiting, mood disturbances and low weight. In some cases it occurs as osteitis fibrosa cystica, diffuse osteopenia, osteoporosis and pathological fractures. The diagnosis is usually made by surgical biopsy shows invasion of adjacent structures, or local and distant metastases. The treatment is surgical resection of the tumor, without the use of adjuvant therapies. Their recurrence rate is high, 25 to 100%. Poor prognostic factors are lymph node metastases at initial presentation, distant metastases and nonfunctional carcinomas. Case report: Male patient consulted for 64 years in general conditions, bradypsychia, polyuria, headache and neck mass. He also had hypercalcemia and high elevation of PTH. Surgical resection of the cervical mass was performed, with rapid biopsy atypia and mitosis 1/10, and hyperplastic thyroid nodule. After this, PTH decreased levels as well as levels of calcium. Discussion: Patients with parathyroid cancer tend to have higher serum calcium and PTH of values. For diagnosis, it is not recommended to use needle biopsy, risk of spread and the poor performance of this technique. Conclusion: Despite being rare, you should think parathyroid cancer in the context of a patient with hypercalcemia, especially if you have very high PTH. The clinical suspicion of this diagnosis is directly related to the possibility of treatment and prognosis of the disease.

Kynurenine pathway metabolites and enzymes involved in redox reactions.

Oxido-reduction reactions are a fundamental part of the life due to support many vital biological processes as cellular respiration and glucose oxidation. In the redox reactions, one substance transfers one or more electrons to another substance. An important electron carrier is the coenzyme NAD+, which is involved in many metabolic pathways. De novo biosynthesis of NAD+ is through the kynurenine pathway, the major route of tryptophan catabolism, which is sensitive to redox environment and produces metabolites with redox capacity, able to alter biological functions that are controlled by redox-responsive signaling pathways. Kynurenine pathway metabolites have been implicated in the physiology process and in the physiopathology of many diseases; processes that also share others factors as dysregulation of calcium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation and cell death, which impact the redox environment. This review examines in detail the available evidence in which kynurenine pathway metabolites participate in redox reactions and their effect on cellular redox homeostasis, since the knowledge of the main factors and mechanisms that lead to cell death in many neurodegenative disorders and other pathologies, such as mitochondrial dysfunction, oxidative stress and kynurenines imbalance, will allow to develop therapies using them as targets. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

Incidentalomas endocrinos, más que una imagen / Endocrine incidentalomas, more than an image

Endocrine incidentalomas are nodular lesions located in endocrine glands, diagnosed serendipitously by different image techniques requested for non-endocrine reasons. They can be located in many sites, but this review describes those that compromise pituitary, adrenal and thyroid gland. The main diagnostic challenges of endocrine incidentalomas are discrimination between benign and malignant lesions, and their functional or non-functional endocrine activity. The relevance of adequate image interpretation and associated hormonal study is discussed. (AU)

Mitochondrial dysfunction related to cell damage induced by 3-hydroxykynurenine and 3-hydroxyanthranilic acid: Non-dependent-effect of early reactive oxygen species production.

The kynurenines 3-hydroxyanthranilic acid (3-HANA) and its precursor 3-hydroxykynurenine (3-HK) are metabolites derived from tryptophan degradation. 3-HK, has been related to diverse neurodegenerative diseases including Huntington's, Alzheimer's and Parkinson's diseases that share mitochondrial metabolic dysregulation. Nevertheless, the direct effect of these kynurenines on mitochondrial function has not been investigated despite it could be regulated by their redox properties that are controversial. A body of literature has suggested a ROS mediated cell death induced by 3-HK and 3-HANA. On the other hand, some works have supported that both kynurenines have antioxidant effects. Therefore, the aim of this study was to investigate 3-HK and 3-HANA effects on mitochondrial and cellular function in rat cultured cortical astrocytes (rCCA) and in animals intrastriatally injected with these kynurenines as well as to determinate the ROS role on these effects. First, we evaluated 3-HK and 3-HANA effect on cellular function, ROS production and mitochondrial membrane potential in vivo and in vitro in rCCA. Our results show that both kynurenines decreased MTT reduction in a concentration-dependent manner together with mitochondrial membrane potential. These observations were accompanied with increased cell death in rCCA and in circling behavior and morphological changes of injected animals. Interestingly, we found that ROS production was not increased in both in vitro and in vivo experiments, and accordingly lipid peroxidation (LP) was neither increased in striatal tissue of animals injected with both kynurenines. The lack of effect on these oxidative markers is in agreement with the ·OH and ONOO(-) scavenging capacity of both kynurenines detected by chemical combinatorial assays. Altogether, these data indicate that both kynurenines exert toxic effects through mechanisms that include impairment of cellular energy metabolism which are not related to early ROS production.

Sustitutos cutáneos bioingenierizados para el tratamiento de heridas cutáneas difíciles de curar / Cutaneous substitutes for cutaneous lesions which are unresponsive to conventional treatment

Existe un aumento significativo de heridas cutáneas que no curan con terapias convencionales, situación preocupante tanto para la salud pública como para la economía mundial. Como posible solución se encuentra la ingeniería tisular cuyo fin es, mediante la generación de sustitutos cutáneos, entregar elementos capaces de reemplazar in vivo tejidos dañados, estimulando además la capacidad regenerativa intrínseca del paciente. Algunos productos han sido aprobados por la FDA (food and drug administration), los que han demostrado el cierre completo de heridas cutáneas refractarias a tratamientos habituales. De esta manera, la ingeniería tisular se considera actualmente como una alternativa terapéutica eficaz tanto para la cura de heridas cutáneas agudas como para heridas cutáneas crónicas, obteniéndose un balance costo-beneficio favorable a largo plazo para el paciente.

In recent years there has been a significant increase in skin lesions which do not heal with conventional therapies. This is a worrisome situation for both public health and global economy. One possible solution is tissue engineering which goal, is to generate substitute tissues that could be used to replace damaged ones in vivo, stimulating the patient’s intrinsic healing capacity. Some products have already been approved by the FDA (the Food and Drug Administration), and have already demonstrated complete closure of cutaneous lesions which are unresponsive to conventional treatment. Tissue engineering is considered an effective alternative therapy for acute and chronic lesions, and offer a favorable cost-benefit relationship in the long term.

Consulta dermatológica geriátrica: comparación epidemiológica entre tres centros de salud / Geriatric dermatological consultation: epidemiological comparison between three health centers

El envejecimiento de la población es un fenómeno a nivel mundial, conllevando a una merma progresiva de todas las funciones de la piel. Involucra una alta prevalencia de patologías como xerosis, prurito, infecciones y neoplasias. Este estudio busca establecer las patologías dermatológicas más frecuentes en pacientes de 65 años o más de tres centros de salud con distintas características demográficas, sociales y administrativas, y las posibles diferencias entre ellos, por medio del análisis descriptivo de sus fichas clínicas entre abril de 2010 y abril de 2011. Los resultados mostraron una mayor prevalencia de patologías dermatológicas en el centro de salud primario, presentándose con mayor frecuencia en pacientes de sexo femenino. Sin importar el centro de salud de origen, las enfermedades infecciosas de la piel son el grupo de mayor prevalencia. Estos resultados coinciden con otros estudios a nivel latinoamericano, pero difieren de estudios realizados en países desarrollados.

The aging population is a worldwide phenomenon which implies all functions including skin, with pathological prevalence of xerosis, itching, infection, and neoplasia. This study establish the dermatological pathologies most frequently seen in patients 65 years and older in three health centers with distinct demographic, social, and administrative characteristics - and the possible differences between them – through the descriptive analysis of their medical records from April 2010 to April 2011. The results showed a greater prevalence of dermatological pathologies in the first health center, with greater frequency in female patients. No matter the health center, infectious diseases of the skin are the prevalent group. The results concur with other Latin American studies, but differ from studies in developed countries.

The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis.

Oncogenic stimuli trigger the DNA damage response (DDR) and induction of the alternative reading frame (ARF) tumor suppressor, both of which can activate the p53 pathway and provide intrinsic barriers to tumor progression. However, the respective timeframes and signal thresholds for ARF induction and DDR activation during tumorigenesis remain elusive. Here, these issues were addressed by analyses of mouse models of urinary bladder, colon, pancreatic and skin premalignant and malignant lesions. Consistently, ARF expression occurred at a later stage of tumor progression than activation of the DDR or p16(INK4A), a tumor-suppressor gene overlapping with ARF. Analogous results were obtained in several human clinical settings, including early and progressive lesions of the urinary bladder, head and neck, skin and pancreas. Mechanistic analyses of epithelial and fibroblast cell models exposed to various oncogenes showed that the delayed upregulation of ARF reflected a requirement for a higher, transcriptionally based threshold of oncogenic stress, elicited by at least two oncogenic 'hits', compared with lower activation threshold for DDR. We propose that relative to DDR activation, ARF provides a complementary and delayed barrier to tumor development, responding to more robust stimuli of escalating oncogenic overload.

Perfil de la consulta dermatológica en el servicio de urgencia del hospital de Quellón / Profile of dermatologic consultation in the emergency service of hospital Quellon

Las consultas por enfermedades dermatológicas en los servicios de urgencia presentan una baja frecuencia y poseen una pobre descripción de sus características en la literatura. A raíz de lo anterior, confeccionamos un estudio descriptivo y retrospectivo de las consultas dermatológicas realizadas en el Servicio de Urgencia del Hospital de Quellón, entre Abril 2010 y Marzo 2011. Los resultados mostraron que las causas dermatológicas representan un 4.9 por ciento del total de consultas. Esta cifra varía durante el transcurso del año, evidenciándose una mayor frecuencia en los meses de verano. Además, se observó que la proporción de consultas de urgencias atribuibles a una enfermedad de la piel es mayor en pacientes pediátricos y adolescentes que en los pacientes adultos. Finalmente, del total de consultas dermatológicas, las etiologías infecciosas y alérgicas fueron las diagnosticadas con mayor frecuencia. No se evidenció una diferencia estadísticamente significativa entre los promedios de consultas pediátrico adolescentes y de población adulta, entre las distintas estaciones del año.

The dermatological consultations in the emergency services have a low frequency and a poor description of its features in the literature. Therefore, we made a descriptive and retrospective study of dermatology consultations conducted in the hospital emergency service of Quellón, between April 2010 and March 2011. The results showed that skin pathology represent 4.9 percent of all consultations. This number varies throughout the year, showing a higher frequency in the summer months. In addition, we observed that the proportion of emergency visits attributable to a skin disease is higher in pediatric and adolescent patients than in adult patients. Finally, for all dermatological consultations, infectious and allergic etiologies were the more frequently diagnosed. No statistically significant difference was showed between pediatric adolescent and adult consultations, during the different seasons.

[Cardiovascular risk factors among university students]. / Factores de riesgo cardiovascular en estudiantes de la Universidad Austral de Chile.

BACKGROUND: Cardiovascular diseases are related to particular lifestyle patterns and the presence of cardiovascular risk factors (CVRF). AIM: To evaluate the presence of CVRF in students from Universidad Austral de Chile (UACh). MATERIAL AND METHODS: CVRF were evaluated in 385 university students aged 17 to 26years (63% women). Personal background, lifestyle, anthropometry, blood pressure, serum lipids and blood glucose were evaluated. RESULTS: Eighty eight percent of evaluated students had sedentary habits, 19% had high LDL cholesterol levels, 40% had high blood pressure, 28% smoked, 29% were overweight or obese and 20% had some stress level. CONCLUSIONS: There is a high frequency of non-healthy lifestyles and cardiovascular risk factors in this sample of university students.

Factores de riesgo cardiovascular en estudiantes de la Universidad Austral de Chile / Cardiovascular risk factors among university students

Background: Cardiovascular diseases are related to particular lifestyle patterns and the presence of cardiovascular risk factors (CVRF). Aim: To evaluate the presence of CVRF in students from Universidad Austral de Chile (UACh). Material and Methods: CVRF were evaluated in 385 university students aged 17 to 26years (63% women). Personal background, lifestyle, anthropometry, blood pressure, serum lipids and blood glucose were evaluated. Results: Eighty eight percent of evaluated students had sedentary habits, 19% had high LDL cholesterol levels, 40% had high blood pressure, 28% smoked, 29% were overweight or obese and 20% had some stress level. Conclusions: There is a high frequency of non-healthy lifestyles and cardiovascular risk factors in this sample of university students.

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer.

OBJECTIVE: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). METHODS: Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regeneration-related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)-α and RAR-ß expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m(2)/d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. RESULTS: The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-ß expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades ≥2. CONCLUSIONS: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-ß expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy.

On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress.

Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 µM) were tested in cerebellum and forebrain homogenates exposed to 5 µM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 µM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 µM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 µM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 µM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA, in addition to be a well-known antagonist acting on nicotinic and NMDA receptors, can be considered as a potential endogenous antioxidant.