Estrogens as a Possible Therapeutic Strategy for the Management of Neuroinflammation and Neuroprotection in COVID-19.

The Coronavirus disease 2019 (COVID-19) affects several tissues, including the central and peripheral nervous system. It has also been related to signs and symptoms that suggest neuroinflammation with possible effects in the short, medium, and long term. Estrogens could have a positive impact on the management of the disease, not only due to its already known immunomodulator effect, but also activating other pathways that may be important in the pathophysiology of COVID-19, such as the regulation of the virus receptor and its metabolites. In addition, they can have a positive effect on neuroinflammation secondary to pathologies other than COVID-19. The aim of this study is to analyze the molecular mechanisms that link estrogens with their possible therapeutic effect for neuroinflammation related to COVID-19. Advanced searches were performed in scientific databases as Pub- Med, ProQuest, EBSCO, the Science Citation index, and clinical trials. Estrogens have been shown to participate in the immune modulation of the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to this mechanism, we propose that estrogens can regulate the expression and activity of the Angiotensin-converting enzyme 2 (ACE2), reestablishing its cytoprotective function, which may be limited by its interaction with SARS-CoV-2. In this proposal, estrogens and estrogenic compounds could increase the synthesis of Angiotensin-(1-7) (Ang-(1-7)) that acts through the Mas receptor (MasR) in cells that are being attacked by the virus. Estrogens can be a promising, accessible, and low-cost treatment for neuroprotection and neuroinflammation in patients with COVID-19, due to its direct immunomodulatory capacity in decreasing cytokine storm and increasing cytoprotective capacity of the axis ACE2/Ang (1-7)/MasR.

Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies.

Dopamine (DA), its derivatives, and dopaminergic drugs are compounds widely used in the management of diseases related to the nervous system. However, DA receptors have been identified in nonneuronal tissues, which has been related to their therapeutic potential in pathologies such as sepsis or septic shock, blood pressure, renal failure, diabetes, and obesity, among others. In addition, DA and dopaminergic drugs have shown anti-inflammatory and antioxidant properties in different kinds of cells. AIM: To compile the mechanism of action of DA and the main dopaminergic drugs and show the findings that support the therapeutic potential of these molecules for the treatment of neurological and non-neurological diseases considering their antioxidant and anti-inflammatory actions. METHOD: We performed a review article. An exhaustive search for information was carried out in specialized databases such as PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, Bookshelf, DrugBank, Livertox, and Clinical Trials. RESULTS: We showed that DA and dopaminergic drugs have emerged for the management of neuronal and nonneuronal diseases with important therapeutic potential as anti-inflammatories and antioxidants. CONCLUSIONS: DA and DA derivatives can be an attractive treatment strategy and a promising approach to slowing the progression of disorders through repositioning.

Comparative treatment with hyperbaric oxygen therapy in a model of systemic loxoscelism in rats.

Objectives: Spiders of the Loxosceles genus, known as violin spiders, produce venom with dermonecrotic and systemic effects, as it is a species widely distributed in the world, its study represents a high medical relevance. Systemic loxoscelism, which occurs in 1 in 5 cases and is the most frequent in children, can be fatal, so the study of effective therapy is of great relevance. In the present study, we compared different therapeutic options to mitigate the systemic effects of Loxosceles boneti venom in a model in which prepubertal rats were used. Materials and Methods: A model of systemic intoxication by L. boneti venom was provoked in male Wistar rats. Study groups were formed: healthy control, with venom and untreated control, treatment with N-acetylcysteine, and/or hyperbaric oxygenation therapy. Subsequently, pathological analysis of the kidney and lung was performed. The oxidant-antioxidant response was evaluated, and molecular analysis of the COX-1 and COX-2 enzymes was performed. Results: Regenerative changes were observed at the cellular level in both treatments, being more noticeable in the hyperbaric oxygen therapy (HBO) group. The anti-oxidant response was outstanding in the same group. Conclusion: Both treatments offer considerable benefits, however; further studies are needed to provide adequate therapeutics.

Trends in Gliosis in Obesity, and the Role of Antioxidants as a Therapeutic Alternative.

Obesity remains a global health problem. Chronic low-grade inflammation in this pathology has been related to comorbidities such as cognitive alterations that, in the long term, can lead to neurodegenerative diseases. Neuroinflammation or gliosis in patients with obesity and type 2 diabetes mellitus has been related to the effect of adipokines, high lipid levels and glucose, which increase the production of free radicals. Cerebral gliosis can be a risk factor for developing neurodegenerative diseases, and antioxidants could be an alternative for the prevention and treatment of neural comorbidities in obese patients. AIM: Identify the immunological and oxidative stress mechanisms that produce gliosis in patients with obesity and propose antioxidants as an alternative to reducing neuroinflammation. METHOD: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index for research on the physiopathology of gliosis in obese patients and for the possible role of antioxidants in its management. CONCLUSION: Patients with obesity can develop neuroinflammation, conditioned by various adipokines, excess lipids and glucose, which results in an increase in free radicals that must be neutralized with antioxidants to reduce gliosis and the risk of long-term neurodegeneration.

Putative mechanism of neurological damage in COVID-19 infection.

The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS- CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS- CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.

Anorectic interaction and safety of 5-hydroxytryptophan/carbidopa plus phentermine or diethylpropion in rat.

Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to determine the anorectic interaction and safety profile of 5-hydroxytryptophan (5-HTP)/carbidopa + diethylpropion and 5-HTP/carbidopa + phentermine combinations in rats. The anorectic effect of individual drugs or in combination was evaluated by the sweetened milk test. Isobologram and interaction index were employed to determine the anorectic interaction between 5-HTP/carbidopa and diethylpropion or phentermine. Plasma serotonin (5-HT) was measured by ELISA. Safety of repeated doses of both combinations in rats was evaluated using the tail sphygmomanometer, cardiac ultrasound, hematic biometry and blood chemistry. A single oral 5-HTP, diethylpropion or phentermine dose increased the anorectic effect, in a dose-dependent fashion, in 12 h-fasted rats. A dose of carbidopa at 30 mg/kg reduced the 5-HTP-induced plasmatic serotonin concentration and augmented the 5-HTP-induced anorectic effect. Isobologram and interaction index indicated a potentiation interaction between 5-HTP/30 mg/kg carbidopa + diethylpropion and 5-HTP/30 mg/kg carbidopa + phentermine. Chronic administration of experimental ED40 of 5-HTP/30 mg/kg carbidopa + phentermine, but not 5-HTP/30 mg/kg carbidopa + diethylpropion, increased the mitral valve leaflets area. Moreover, there were no other significant changes in cardiovascular, hematic or blood parameters. Both combinations induced around 20% body weight loss after 3 months of oral administration. Results suggest that 5-HTP/30 mg/kg carbidopa potentiates the anorectic effect of diethylpropion and phentermine with an acceptable safety profile, but further clinical studies are necessary to establish their therapeutic potential in the obesity treatment.

OX40 agonists for cancer treatment: a patent review.

INTRODUCTION: OX40 is an immune checkpoint in cancer and its presence in cancer is a good prognosis, making it a highly relevant target for the development of new immunotherapies. AREAS COVERED: The patent literature reveals vital information on new trends in cancer therapies. The authors used the patent databases of the six major patent offices in the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Office of Intellectual Property of China and Korean Intellectual Property Office, to generate a panorama of patents related to OX40 agonists. Specific patents have been grouped into innovative patents and adoption patents. EXPERT OPINION: An increasing trend in the development of OX40 agonists in cancer, particularly in the years 2018 and 2019. United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986,178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists.

Catecholamine levels and gene expression of their receptors in tissues of adults with osteosarcoma.

AIM: The purpose of this work was to identify and measure catecholamines, their metabolites, and the gene expression of catecholamine receptors in osteosarcoma tissue. MATERIALS AND METHODS: The levels of 3,4-dihydroxyphenylacetic acid, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in cancer tissue and in adjacent and non-oncological bone tissue were analysed by high-performance liquid chromatography, and the gene expression of catecholamine receptors and of dopamine ß-hydroxylase, monoaminoxidase, ki67, and Runx2 in the osteosarcoma tissue, tissue adjacent to the tumour, non-oncological bone, and human brain tissue was analysed by RT-PCR. RESULTS: We found significantly higher levels of 3,4-dihydroxyphenylacetic acid and norepinephrine in the cancer sample than in adjacent and non-oncological bone. We found that ß-adrenergic receptors and dopaminergic receptors, dopamine ß-hydroxylase, ki67, Runx2, and serotonergic receptor gene expression were significantly higher in tumour tissue than in adjacent and non-oncological bone. CONCLUSION: Catecholamines and their receptors could be potential molecular markers for osteosarcoma progression.

The Mechanisms of Action of Botulinum Toxin Type A in Nociceptive and Neuropathic Pathways in Cancer Pain.

BACKGROUND: Botulinum toxin type A (BoNT-A) is widely employed for cosmetic purposes and in the treatment of certain diseases such as strabismus, hemifacial spasm and focal dystonia among others. BoNT-A effect mainly acts at the muscular level by inhibiting the release of acetylcholine at presynaptic levels consequently blocking the action potential in the neuromuscular junction. Despite the great progress in approval and pharmaceutical usage, improvement in displacing BoNT-A to other pathologies has remained very limited. Patients under diagnosis of several types of cancer experience pain in a myriad of ways; it can be experienced as hyperalgesia or allodynia, and the severity of the pain depends, to some degree, on the place where the tumor is located. Pain relief in patients diagnosed with cancer is not always optimal, and as the disease progresses, transition to more aggressive drugs, like opioids is sometimes unavoidable. In recent years BoNT-A employment in cancer has been explored, as well as an antinociceptive drug; experiments in neuropathic, inflammatory and acute pain have been carried out in animal models and humans. Although its mechanism has not been fully known, evidence has shown that BoNT-A inhibits the secretion of pain mediators (substance P, Glutamate, and calcitonin gene related protein) from the nerve endings and dorsal root ganglion, impacting directly on the nociceptive transmission through the anterolateral and trigeminothalamic systems. AIM: The study aimed to collect available literature regarding molecular, physiological and neurobiological evidence of BoNT-A in cancer patients suffering from acute, neuropathic and inflammatory pain in order to identify possible mechanisms of action in which the BoNT-A could impact positively in pain treatment. CONCLUSION: BoNT-A could be an important neo-adjuvant and coadjuvant in the treatment of several types of cancer, to diminish pro-tumor activity and secondary pain.

Protective Role of Glutathione and Nitric Oxide Production in the Pathogenesis of Pterygium.

OBJECTIVE: In the pathogenesis of pterygium, the protective role of glutathione and nitric oxide production is unclear. These are important factors for homeostasis in the redox state of cells. The aim of this study was to determine the levels of these and related parameters in pterygium tissue. Patients and Methods. The study sample consisted of 120 patients diagnosed with primary or recurrent pterygium. Five groups of tissue samples were examined: control, primary pterygium, recurrent pterygium, and two groups of primary pterygium given a one-month NAC presurgery treatment (topical or systemic). The levels of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), 3-nitrotyrosine (3NT), reduced and oxidized glutathione (GSH and GSSG), and catalase (CAT) were evaluated in tissue homogenates. RESULTS: Compared with the control, decreased levels of eNOS, NO, and 3-nitrotyrosine as well as the degree of oxidation of GSH (GSSG%) were observed in primary and recurrent pterygium. 3-Nitrotyrosine and GSSG% were reduced in the other pterygium groups. GSH and CAT were enhanced in recurrent pterygium and systemic-treated primary pterygium but were unchanged for topical-treated primary pterygium. There was a strong positive correlation of eNOS with NO and 3NT, GSSG% with NO and 3NT, and GSH with GSSG and CAT. Women showed a higher level of GSH and catalase in primary pterygium, whereas a lower level of GSH and a higher level of NO in recurrent pterygium. CONCLUSION: The results are congruent with the following proposed sequence of events leading to a protective response of the organism during the pathogenesis of primary pterygium: a decreased level of eNOS provokes a decline in the level of NO in pterygium tissue, which then leads to reduced S-nitrosylation of GSH or other thiols and possibly to the modulation of the intracellular level of GSH through synthesis and/or mobilization from other tissues.

Alterations in glutathione, nitric oxide and 3-nitrotyrosine levels following exercise and/or hyperbaric oxygen treatment in mice with diet-induced diabetes.

Oxidative stress is involved in the development of diabetes. Nitric oxide (NO) contributes to oxidative stress, affects the synthesis of glutathione (GSH) in tissues and also regulates important physiological processes. The levels of nitrosative stress, assessed by measuring the levels of 3-nitrotirosina (3NT) as well as the bioavailability of NO are modulated by exercise and hyperbaric oxygenation (HBO). The aim of the present study was to evaluate the effects of exercise and HBO on the levels of NO, 3NT and GSH in tissues of various organs obtained from diabetic mice. Female mice were fed a high-fat/high-fructose diet to induce diabetes. Mice with diabetes were subjected to exercise and/or HBO. Initial and final concentrations of NO, 3NT and GSH were assessed in the muscle, liver, kidney, heart, spleen, lung, brain, visceral adipose, thoracic aorta and small intestine. Diabetes did not affect initial values of NO, although it significantly increased the levels of 3NT. The basal level of GSH in the diabetic group was lower than or comparable to that of the control group in the majority of the organs assessed. A negative correlation was observed between 3NT and GSH levels in the initial values of all tissues of the control group only, whereas all pathological tissues showed a positive correlation between NO and GSH. There was an increase or a stabilization of GSH levels in the majority of the organs in all treated mice despite the increase in nitrosative stress.

Biosensor of Inflammation Biomarkers Based on Electrical Bioimpedance Analysis on Immobilized DNA Without Chemical Modification.

The development of biosensors to identify molecular markers or specific genes is fundamental for the implementation of new techniques that allow the detection of specific Deoxyribonucleic acid (DNA) sequences in a fast, economic and simple way. Different detection techniques have been proposed in the development of biosensors. Electrical Bioimpedance Spectroscopy (EBiS) has been used for diagnosis and monitoring of human pathologies, and is recognized as a safe, fast, reusable, easy and inexpensive technique. This study proves the development of a complementary DNA (cDNA) biosensor based on measurements of EBiS and DNA's immobilization with no chemical modifications. The evaluation of its potential utility in the detection of the gene expression of three inflammation characteristic biomarkers (NLRP3, IL-1ß and Caspase 1) is presented. The obtained results demonstrate that EBiS can be used to identify different gene expression patterns, measurements that were validated by Quantitative Polymerase Chain Reaction (qPCR). These results indicate the technical feasibility for a biosensor of specific genes through bioimpedance measurements on the immobilization of cDNA.

Efficacy of Cognitive Behavioral Therapy for Habit Modification and Drug Adherence in Obesity / Eficacia de la Terapia Cognitivo Conductual para Modificación de Hábitos y Adherencia Farmacológica en Obesidad

Abstract The obesity is a global health problem, also it is increasing in adults and pediatric population, reducing life quality. Treatment must be interdisciplinary with elements of behavior modification on self-control, habit modifications, support networks and highlighting to adherence. Cognitive behavioral therapy, specifically on problem solving model, is efficient in treatment of anthropometric control, metabolic and behavioral indicators. Methods: Quasi-experimental, comparative, clinical and randomized study, n=100 adults of both sexes with an exogenous obesity diagnostic. The intervention was performed with an interdisciplinary treatment of cognitive behavioral therapy on problem solving model and 3mg. (0-0-1) of melatonin (50 subjects), comparing it with a group that only received the treatment by melatonin 3mg. (0-0-1) (50 subjects) per 8 months; the anthropometry and blood biochemical values (glucose, triglycerides, HDL and LDL) was evaluated after and before; dropout rate and adherence to the drug was evaluated every month. A bioimpedance machine was used. Results: The analysis demonstrated in eight months that the problem solving model with melatonin group got an adherence average of 80% (p= .05); in comparison with melatonin group that showed an average of 48% (p= .05). Relating to anthropometry and blood biochemical values, problem solving model and melatonin group got better effectiveness (p= .05). Conclusions Cognitive behavioral therapy combined with melatonin, was more effective in anthropometric indicators, blood chemistry and mainly in adherence, confirming the importance of the incursion of effective psychological techniques that contribute to the management of obesity.

Resumen La obesidad es un problema de salud que aumenta en la población, reduciendo la calidad de vida. El tratamiento debe de ser interdisciplinario, que incluya autocontrol de ingesta alimentaria, modificación de hábitos, redes de apoyo y manejo de adherencia. La terapia cognitiva conductual específicamente el modelo en solución de problemas es eficaz en el manejo de antropometría, indicadores metabólicos y conductuales, sin embargo no hay evidencia de su impacto en adherencia farmacológica. Método: estudio cuasiexperimental, comparativo, aleatorio simple y clínico. Participaron 100 adultos de ambos sexos con diagnóstico de obesidad exógena. Se aplicó intervención basada en el modelo en solución de problemas combinado con 3 mg. (0-0-1) de melatonina (50 sujetos), comparándola con un grupo que solo recibió melatonina 3 mg. (0-0-1) (50 sujetos) durante 8 meses; se evaluó antropometría (IMC y porcentaje de grasa), química sanguínea (glucosa, triglicéridos, HDL y LDL), tasa de abandono y adherencia al fármaco mensualmente. Se utilizó báscula de bioimpedancia. Resultados. El grupo de terapia y melatonina obtuvo un promedio de adherencia del 80% (p = .05); en comparación con el grupo de melatonina que mostró un promedio de 48% (p = .05). En la antropometría y química sanguínea, este grupo mostró mayor eficacia (p = .05). Conclusiones. La terapia cognitivo conductual combinada con melatonina, fue más efectiva en indicadores antropométricos, de química sanguínea y principalmente en adherencia, lo que confirma la importancia de la incursión de técnicas psicológicas efectivas que coadyuven en el manejo de obesidad.

Sensitivity and Specificity of Computed Tomography in the Evaluation of Bone Mineral Density in Mexican Patients with Breast Cancer.

Introduction Breast cancer (BC) is the most frequently reported cancer among women - reported in 2012 as 25% of all cancers. BC has been related to the increased life and activity of osteoclasts, conferring a higher risk for osteoporosis/osteopenia. This study aimed to determine a cut-off point in Hounsfield units (HU) as well as the sensitivity and specificity of computed axial tomography (CT) in the diagnosis of osteoporosis/osteopenia in Mexican women with BC. Material and methods We included 108 patients with a histopathological diagnosis of BC treated at the ABC Medical Center in Mexico City. All patients were subjected to both dual X-ray densitometry and CT. The receiver operating characteristic (ROC) curve was used to identify the cutoff point and sensitivity and specificity were calculated, as were confidence intervals for the diagnoses of osteoporosis/osteopenia. Results The mean age was 58.49 ± 11.01 years. The cutoff point with the highest sensitivity (82%) and specificity (68%) was <157 HU for osteoporosis/osteopenia in patients with BC. Conclusions Women with BC are exposed to several risk factors for osteoporosis/osteopenia. The CT obtained for the general evaluation of these patients can also be used to evaluate bone mineral density, avoiding additional examinations and exposure to radiation, as well as the cost it confers, offering an earlier diagnosis of osteoporosis/osteopenia for its control.

[General characteristics of medical education in Mexico. A look from medical schools]. / Características generales de la educación médica en México. Una mirada desde las escuelas de medicina.

OBJECTIVE: To know the characteristics of medical education and identify its strengths and weaknesses. MATERIALS AND METHODS: A transversal and quantitative study of the characteristics of medical education in 29 medical schools in Mexico was carried out, between April and September 2017. Questionnaire with Likert scale was applied to explore context, regulation, structure, process, results and impact of medical education. Bivariate analysis was performed with a Chi square test and the significance level was equal to or less than 0.05. RESULTS: The political context obtained 64%, economical context 10% and mechanisms of regulation 31%. The educational structure was 61% and the social impact was 93%. CONCLUSIONS: Public policies, regulatory mechanisms and public investment must be strengthened to improve the quality of medical education.

OBJETIVO: Conocer las características de la educación médica e identificar sus fortalezas y debilidades. MATERIAL Y MÉTODOS: Se realizó un estudio transversal y cuantitativo para conocer las características de la educación médica en 29 escuelas de medicina en México, entre abril y septiembre de 2017. Se utilizó un cuestionario con escala tipo Likert para explorar el contexto, la regulación, la estructura, el proceso, los resultados y el impacto de la educación médica. Se realizó un análisis bivariado con ji cuadrada y una significancia estadística de p igual o menor a 0.05. RESULTADOS: El contexto político obtuvo 64%, el contexto económico 10%, los mecanismos de regulación 31%, la estructura educativa 61% y el impacto social 93%. CONCLUSIONES: Se requiere fortalecer las políticas públicas, la regulación y la inversión pública, para mejorar la calidad de la educación médica.

[Educating general practitioners in Latin America: a challenge for universal healthFormação de clínicos gerais na América Latina: um desafio para a saúde universal]. / Formación de médicos generales en América Latina: un reto para la salud universal.

OBJECTIVE: To gather opinions from medical schools regarding the existence of public policies on the health workforce (human resources for health) and whether sufficient public financing and regulatory mechanisms are in place for undergraduate medical education; and to identify areas of opportunity to improve the availability of general practitioners in the Region of the Americas. METHODS: Cross-sectional, descriptive study conducted with 105 medical schools (51 public and 54 private) in 17 countries. A questionnaire with a Likert scale was used to explore three dimensions (political, economic, and regulatory contexts) composed of 4, 2, and 4 variables each, respectively, and validated with the Delphi method. Frequencies of responses to the questions were estimated. A frequency analysis was performed, as well as a bivariate analysis to identify differences between public and private schools, applying the Chi-square test to compare percentages. RESULTS: The political context was considered favorable by 64% of the schools; the economic context, by 37%; and the regulatory context, by 23%. The only significant differences between public and private schools were in the financial resources they administer. CONCLUSIONS: It is necessary to strengthen public policies, public investment, and the regulation of medical education in order to improve the education and availability of general practitioners in the countries of the Region.

OBJETIVO: Conhecer a opinião das faculdades de medicina sobre o volume de políticas públicas e financiamento público e mecanismos reguladores para graduação médica e identificar áreas que possibilitem aumentar o número de clínicos gerais na Região das Américas. MÉTODOS: Estudo transversal descritivo realizado com 105 faculdades de medicina (51 públicas e 54 particulares) em 17 países. Um questionário com uma escala tipo Likert foi usado para explorar três dimensões (contexto político, contexto econômico e regulamentação), contendo 4, 2 e 4 variáveis cada, e foi validado com o método Delphi. As frequências de respostas às perguntas do questionário foram calculadas e analisadas. A fim de identificar diferenças entre as faculdades públicas e particulares, uma análise bivariada com teste qui-quadrado foi realizada para comparar porcentagens. RESULTADOS: O contexto político foi considerado favorável por 64% das faculdades; o contexto econômico por 37%; e a regulamentação por 23%. Apenas foi observada diferença significativa entre as faculdades públicas e particulares na variável recursos financeiros geridos. CONCLUSÕES: É necessário fortalecer as políticas públicas, o investimento público e a regulamentação da educação médica para melhorar a formação e aumentar o número de clínicos gerais nos países da Região.

Formación de médicos generales en América Latina: un reto para la salud universal

[RESUMEN]. Objetivo. Conocer la opinión de las escuelas de medicina sobre la existencia de políticas públicas y la suficiencia de financiamiento público y mecanismos regulatorios para la formación médica de pregrado e identificar áreas que permitan mejorar la disponibilidad de médicos generales en la Región de las Américas. Métodos. Estudio transversal, descriptivo realizado con 105 escuelas de medicina, 51 públicas y 54 privadas, de 17 países. Se utilizó un cuestionario con una escala tipo Likert para explorar tres dimensiones (contextos político, económico y regulatorio) integradas por 4, 2 y 4 variables cada una, respectivamente, y validado con el método Delphi. Se estimaron frecuencias de respuestas a las preguntas del cuestionario. Se realizó un análisis de frecuencias, y para identificar diferencias entre escuelas públicas y privadas se efectuó un análisis bivariante aplicando la prueba de Chi cuadrado para comparar porcentajes. Resultados. El contexto político fue favorable para 64% de las escuelas, el contexto económico, para 37% y la regulación, para 23%. Sólo hubo diferencias significativas entre escuelas públicas y privadas en la variable recursos financieros que ellas administran. Conclusiones. Es necesario fortalecer las políticas públicas, la inversión pública y la regulación de la educación médica, para mejorar la formación y disponibilidad de médicos generales en los países de la Región.

[ABSTRACT]. Objective. To gather opinions from medical schools regarding the existence of public policies on the health workforce (human resources for health) and whether sufficient public financing and regulatory mechanisms are in place for undergraduate medical education; and to identify areas of opportunity to improve the availability of general practitioners in the Region of the Americas. Methods. Cross-sectional, descriptive study conducted with 105 medical schools (51 public and 54 private) in 17 countries. A questionnaire with a Likert scale was used to explore three dimensions (political, economic, and regulatory contexts) composed of 4, 2, and 4 variables each, respectively, and validated with the Delphi method. Frequencies of responses to the questions were estimated. A frequency analysis was performed, as well as a bivariate analysis to identify differences between public and private schools, applying the Chi-square test to compare percentages. Results. The political context was considered favorable by 64% of the schools; the economic context, by 37%; and the regulatory context, by 23%. The only significant differences between public and private schools were in the financial resources they administer. Conclusions. It is necessary to strengthen public policies, public investment, and the regulation of medical education in order to improve the education and availability of general practitioners in the countries of the Region.

[RESUMO]. Objetivo. Conhecer a opinião das faculdades de medicina sobre o volume de políticas públicas e financiamento público e mecanismos reguladores para graduação médica e identificar áreas que possibilitem aumentar o número de clínicos gerais na Região das Américas. Métodos. Estudo transversal descritivo realizado com 105 faculdades de medicina (51 públicas e 54 particulares) em 17 países. Um questionário com uma escala tipo Likert foi usado para explorar três dimensões (contexto político, contexto econômico e regulamentação), contendo 4, 2 e 4 variáveis cada, e foi validado com o método Delphi. As frequências de respostas às perguntas do questionário foram calculadas e analisadas. A fim de identificar diferenças entre as faculdades públicas e particulares, uma análise bivariada com teste qui-quadrado foi realizada para comparar porcentagens. Resultados. O contexto político foi considerado favorável por 64% das faculdades; o contexto econômico por 37%; e a regulamentação por 23%. Apenas foi observada diferença significativa entre as faculdades públicas e particulares na variável recursos financeiros geridos. Conclusões. É necessário fortalecer as políticas públicas, o investimento público e a regulamentação da educação médica para melhorar a formação e aumentar o número de clínicos gerais nos países da Região.

Características generales de la educación médica en México. Una mirada desde las escuelas de medicina / General characteristics of medical education in Mexico. A look from medical schools

Resumen: Objetivo: Conocer las características de la educación médica e identificar sus fortalezas y debilidades. Material y métodos: Se realizó un estudio transversal y cuantitativo para conocer las características de la educación médica en 29 escuelas de medicina en México, entre abril y septiembre de 2017. Se utilizó un cuestionario con escala tipo Likert para explorar el contexto, la regulación, la estructura, el proceso, los resultados y el impacto de la educación médica. Se realizó un análisis bivariado con ji cuadrada y una significancia estadística depigual o menor a 0.05. Resultados: El contexto político obtuvo 64%, el contexto económico 10%, los mecanismos de regulación 31%, la estructura educativa 61% y el impacto social 93%. Conclusiones: Se requiere fortalecer las políticas públicas, la regulación y la inversión pública, para mejorar la calidad de la educación médica.

Abstract: Objective: To know the characteristics of medical education and identify its strengths and weaknesses. Materials and methods: A transversal and quantitative study of the characteristics of medical education in 29 medical schools in Mexico was carried out, between April and September 2017. Questionnaire with Likert scale was applied to explore context, regulation, structure, process, results and impact of medical education. Bivariate analysis was performed with a Chi square test and the significance level was equal to or less than 0.05. Results: The political context obtained 64%, economical context 10% and mechanisms of regulation 31%. The educational structure was 61% and the social impact was 93%. Conclusions: Public policies, regulatory mechanisms and public investment must be strengthened to improve the quality of medical education.

Anorectic efficacy and safety of the diethylpropion-topiramate combination in rats.

Preclinical Research & Development Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose-dependent fashion in either nondeprived or 12 hr food-deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials.

Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City.

Extracellular matrix metalloproteases and the fibrinolytic system are important protease systems interacting with each other in charge of remodeling and recycling of tissues. Their role in tumor invasion and metastasis is often discussed. In this study several metalloproteases such as MMP-1, MMP-3, MMP-9, and TIMP-1 together with molecules from the fibrinolytic system like uPA, its receptor uPAR, and its inhibitor, PAI-1, were studied by immune-histochemistry to establish a comparison with and without metastasis. From the (118) primary tumors of Mexican patients with ductal breast cancer studied, 56% were grade II and 69% were size T2; the group with metastatic ganglia included 64 samples (54.3%). In patients with metastasis the estimated expression of MMP-3 and uPA (resp., 28% and 45%) was higher than that from no metastatic tumors; it means there is higher expression of both markers in metastatic tumors (p < 0.05). At the same time, metastatic tumors showed statistically significant lower signal of PAI-1 (24%) than tumors without metastasis (p < 0.05). We concluded that overexpression of MMP-3 and uPA, altogether with diminished expression of PAI-1 from metastatic tumors, might be a crucial step towards metastasis in ductal breast cancer. Nevertheless, additional studies in different populations are necessary to establish a pattern.