Ursolic Acid Lactone Obtained from Eucalyptus tereticornis Increases Glucose Uptake and Reduces Inflammatory Activity and Intracellular Neutral Fat: An In Vitro Study.

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.

Triterpene-enriched fractions from Eucalyptus tereticornis ameliorate metabolic alterations in a mouse model of diet-induced obesity.

ETNOPHARMACOLOGICAL RELEVANCE: Eucalyptus tereticornis Sm. (Eu) is a plant species used in traditional medicine to treat diabetes mellitus. Eu leaf extracts have been shown to regulate immuno-metabolic activities that are associated with obesity and insulin resistance. OBE100 and OBE104 are two natural Eu extracts that are rich in pentacyclic triterpenes. The major compounds identified in OBE100 are ursolic acid (UA), oleanolic acid (OA), and ursolic acid lactone (UAL), and the major compounds identified in OBE104 are UA and OA. AIM OF THE STUDY: This study aimed to investigate the effects of two extracts from Eu leaves with different triterpene composition in a nutritional animal model of prediabetes. METHODS: A mouse model of diet-induced obesity was used to analyze the effects of the OBE100 and OBE104 treatments on metabolic markers and gene expression in liver and visceral adipose tissue. RESULTS: Treating the prediabetic mouse model with OBE100 and OBE104 increased glucose tolerance. However, only the Eu extract that contained three triterpenes reduced mouse body weight, hepatic and adipose fat content, and plasma lipid levels. OBE100 treatment also led to decreased hepatic mRNA levels of PPARA, CPT1A, and SERBP1. In visceral adipose tissue, OBE100 treatment reduced expression of PPARA and ACACA and increased UCP1 expression. CONCLUSIONS: These results suggest that developing a new multitargeting bioactive compound from the natural extract from Eu may help combat obesity and diabetes. Treatment with OBE100 had better effects than OBE104 in a diet-induced obesity mouse model, suggesting that the OBE100 extract, which contains three triterpenes, may be beneficial in combating obesity.

Cumplimiento de la normatividad en droguerías con servicio de glucometría en cuatro ciudades de Santander, Colombia / Regulation Compliance in drugstores with glucometry service in four cities of Santander-Colombia

RESUMEN Objetivo Evaluar el cumplimiento normativo del servicio de glucometría en droguerías del departamento de Santander-Colombia. Métodos Estudio observacional descriptivo de corte transversal. Se usó un instrumento de evaluación basado en la norma y validado por expertos. Resultados Se aplicó una encuesta a 68 droguerías. Los resultados fueron categorizados así: recursos humanos, dotación, infraestructura, documentación-registro y procesos de vigilancia y control. En la primera categoría se identificaron falencias relacionadas con la formación académica del personal a cargo de la droguería, con un porcentaje de cumplimiento del 66,2% y en la capacitación del personal en el manejo del equipo de glucometría 35,3%. En general el conocimiento de la normatividad por parte del personal fue de 36,8%. En las categorías de dotación e infraestructura se evidencia un nivel de cumplimiento superior al 50% para todos los ítems, excepto el relacionado con la calibración del equipo. En la cuarta categoría, específicamente en documentación y registro, los niveles de cumplimiento normativo son inferiores al 50% en todos los ítems, excepto el de información, que se le ofrece al paciente durante el procedimiento. Los resultados evidencian una falla en los procesos de vigilancia y control, dado que solo el 57,4% de los establecimientos confirman visitas de inspección. Conclusiones Los resultados de este estudio revelan un desconocimiento generalizado de la normatividad en droguerías que prestan el servicio de glucometría; consecuentemente, no se cumplen todas las exigencias regulatorias. Fomentar programas de capacitación y fortalecer la cultura de la autoevaluación garantiza procesos seguros para el paciente.(AU)

ABSTRACT Objective To evaluate the compliance of the service of glucometry in drugstores in the department of Santander - Colombia. Methods Cross-sectional observational study. An assessment instrument based on the normativity and validated by experts was used. Results The poll was applied to 68 drugstores. The results were categorized as follows: human resources, equipment, infrastructure, documentation - registration, and surveillance and control processes. In the first category, shortcomings related to the academic training of the staff in charge of the drugstore were identified, with a compliance percentage of 66,2% and in the training of personnel in the management of the glucometry equipment, 35,3%. In general, the knowledge of the regulations by the staff was 36,8%. In the equipment and infrastructure categories, a level of compliance of more than 50% is evident for all items, xcept in those related to calibration equipment. In the fourth category, specifically in documentation and registration, the levels of regulatory compliance are less than 50% in all items, except in the one related with the information that is offered to the patient during the procedure. The results show a failure in the surveillance and control processes, where only 57,4% of the establishments confirm inspection visits. Conclusions The results of this study reveal widespread ignorance of the regulations in drugstores that provide the glucometry service; consequently, not all regulatory requirements are met. Promoting training programs and strengthening the culture of self-evaluation guarantees safe processes for the patient.(AU)

[Regulation Compliance in drugstores with glucometry service in four cities of Santander-Colombia]. / Cumplimiento de la normatividad en droguerías con servicio de glucometría en cuatro ciudades de Santander, Colombia.

OBJECTIVE: To evaluate the compliance of the service of glucometry in drugstores in the department of Santander - Colombia. METHODS: Cross-sectional observational study. An assessment instrument based on the normativity and validated by experts was used. RESULTS: The poll was applied to 68 drugstores. The results were categorized as follows: human resources, equipment, infrastructure, documentation - registration, and surveillance and control processes. In the first category, shortcomings related to the academic training of the staff in charge of the drugstore were identified, with a compliance percentage of 66,2% and in the training of personnel in the management of the glucometry equipment, 35,3%. In general, the knowledge of the regulations by the staff was 36,8%. In the equipment and infrastructure categories, a level of compliance of more than 50% is evident for all items, xcept in those related to calibration equipment. In the fourth category, specifically in documentation and registration, the levels of regulatory compliance are less than 50% in all items, except in the one related with the information that is offered to the patient during the procedure. The results show a failure in the surveillance and control processes, where only 57,4% of the establishments confirm inspection visits. CONCLUSIONS: The results of this study reveal widespread ignorance of the regulations in drugstores that provide the glucometry service; consequently, not all regulatory requirements are met. Promoting training programs and strengthening the culture of self-evaluation guarantees safe processes for the patient.

OBJETIVO: Evaluar el cumplimiento normativo del servicio de glucometría en droguerías del departamento de Santander-Colombia. MÉTODOS: Estudio observacional descriptivo de corte transversal. Se usó un instrumento de evaluación basado en la norma y validado por expertos. RESULTADOS: Se aplicó una encuesta a 68 droguerías. Los resultados fueron categorizados así: recursos humanos, dotación, infraestructura, documentación-registro y procesos de vigilancia y control. En la primera categoría se identificaron falencias relacionadas con la formación académica del personal a cargo de la droguería, con un porcentaje de cumplimiento del 66,2% y en la capacitación del personal en el manejo del equipo de glucometría 35,3%. En general el conocimiento de la normatividad por parte del personal fue de 36,8%. En las categorías de dotación e infraestructura se evidencia un nivel de cumplimiento superior al 50% para todos los ítems, excepto el relacionado con la calibración del equipo. En la cuarta categoría, específicamente en documentación y registro, los niveles de cumplimiento normativo son inferiores al 50% en todos los ítems, excepto el de información, que se le ofrece al paciente durante el procedimiento. Los resultados evidencian una falla en los procesos de vigilancia y control, dado que solo el 57,4% de los establecimientos confirman visitas de inspección. CONCLUSIONES: Los resultados de este estudio revelan un desconocimiento generalizado de la normatividad en droguerías que prestan el servicio de glucometría; consecuentemente, no se cumplen todas las exigencias regulatorias. Fomentar programas de capacitación y fortalecer la cultura de la autoevaluación garantiza procesos seguros para el paciente.

Immunometabolic regulation by triterpenes of Eucalyptus tereticornis in adipose tissue cell line models.

BACKGROUND: Eucalyptus tereticornis Sm (Myrtaceae) is a plant used in traditional medicine to control obesity, insulin resistance and diabetes. Chronic adipose tissue inflammation is involved in generating insulin resistance, the greatest risk factor in developing type 2 diabetes mellitus and cardiovascular disease. In the present study, a mixture of triterpenes, as obtained from the starting plant material, was evaluated in inflamed adipose tissue cells models. AIM: Our goal is to advance into the understanding, at the cellular level, of the immunometabolic effects of the triterpene mixes from Eucalyptus tereticornis in in vitro models of mouse and human adipose tissues. METHODS: Triterpene mixes were obtained from Eucalyptus tereticornis leaves by organic extraction. The major compounds of these mixes were identified by 1H NMR and 13C NMR in addition to HPLC using primary and secondary standards of ursolic acid, oleanolic acid and ursolic acid lactone. To provide an approach for evaluating the cellular and molecular mechanisms through which triterpene mixes act to modify the metabolic processes associated with obesity, mouse macrophage and adipocyte cell lines, human macrophage cell line and primary culture of human adipocytes were used as models. RESULTS: Adipocytes treated with the two natural chemically characterized triterpene mixes partially reduce lipogenesis and leptin expression. Additionally, an increase in the transcriptional expression of PPARγ, and C/EBPα is observed. In macrophages, these triterpene mixes, decrease the transcriptional and translational expression of pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin 1ß (IL-1ß) and tumoral necrosis factor α (TNFα). Conditioned medium of 3T3-L1 adipocytes treated with the triterpene mix shows a stronger anti-inflammatory response on activated J774A.1 macrophages. CONCLUSION: The mixtures of the three triterpenes in the proportions obtained from the plant material may act on different components of the cell, generating a different response, which, in some cases, is more powerful than that seen when exposure to only two triterpenes. It makes this three triterpenes mix a good phytotherapeutic prototype for pathologies as complex as those associated with obesity.

Tratamiento con radioquimioterapia del cáncer de cuello uterino: resultados a largo plazo / Radiochemotherapy treatment of cervical cancer: long-term results

Introducción: la radioquimioterapia es una opción de tratamiento curativo del carcinoma de cérvix, particularmente en pacientes de medio hospitalario uruguayo cuyo diagnóstico se realiza en estadios localmente avanzados. El objetivo de este trabajo es analizar los resultados terapéuticos y la toxicidad crónica de dicho tratamiento en el Centro Hospitalario Pereira Rossell (CHPR). Método: se incluyeron 164 pacientes portadoras de carcinoma cérvico-uterino que completaron el tratamiento de radioquimioterapia entre junio de 2006 y noviembre de 2008. La radioterapia externa (RTE) consistió en irradiación pélvica (concomitante con cisplatino semanal) y braquiterapia (BT) útero-vaginal. Se calculó la dosis biológica efectiva para tumor, para recto y para vejiga. Se analizó la tasa de control locorregional y la sobrevida a cinco años, así como las complicaciones crónicas por el método de Kaplan-Meier. Resultados: la sobrevida global obtenida fue de 67% a cinco años, mostrando diferencias significativas entre el estadio II (78%) y el estadio III (49%) (Log-rank test, p = 0,0002). La tasa de complicaciones crónicas grado 3-4, según RTOG (Radiation Therapy Oncology Group), fue de 1,8% para las urinarias y 3,7% para las digestivas. El control local inicial fue de 89% y la persistencia lesional de 10,3%; recidiva locorregional (RL) en todo el período: 19,5%; metástasis con o sin RL: 10,3%. Conclusiones: se confirma en nuestro medio la eficacia terapéutica de la radioquimioterapia en cáncer de cérvix. La mayoría de las recidivas o persistencias fueron por falta de control locorregional luego del tratamiento inicial. El tratamiento fue bien tolerado, con bajo porcentaje de complicaciones crónicas, comparable con referencias internacionales.

Abstract Introduction: radiochemotherapy may be used to cure cervical cancer, particularly for patients treated in Uruguayan hospitals, whose diagnosis is made in locally advanced stages. The study aims to analyse therapy results and chronic toxicity of such treatment at the Pereira Rossell Hospital Center (CHPR). Method: 164 carriers of cervical-uterine cancer who completed the radiochemotherapy treatment between June 2006 and November 2008 were included in the study. External radiochemotherapy consisted in pelvic irradiation (in combination with weekly cisplatin) and uterus-vaginal brachytherapy. Effective biological doses for tumor were calculated, for the rectum and the bladder. Locoregional control rate and survival after 5 years, as well as chronic complications, were analysed using the Kaplan-Meier method. Results: global five-year survival rate was 67%, there being significant differences between stage II (78%) and stage III (49%) (Log-rank test, p = 0.0002). According to RTOG (Radiation Therapy Oncology Group) Grade 3/4 chronic complications rate was 1.8% for urinary complications and 3.7% for digestive complications. Initial local control was 89% and lesion persistence was 10.3%, locoregional recurrence (LR) throughout the period was 19.5%; metastases with and without LR was 10.3% Conclusions: therapeutic effectiveness of radiochemotherapy for to treat cervical cancer is confirmed in our context. In most cases recurrence or persistence resulted from lack of locoregional follow-up after initial treatment. Treatment was well tolerated, with low percentage of chronic complications, what is comparable to international literature.

Resumo Introdução: a radio-quimioterapia é uma opção de tratamento curativo do carcinoma de cérvix, particularmente em pacientes do meio hospitalar uruguaio cujo diagnóstico é feito em estádios localmente avançados. O objetivo deste trabalho é analisar os resultados terapêuticos e a toxicidade crônica deste tratamento no Centro Hospitalario Pereira Rossell (CHPR). Método: foram incluídas 164 pacientes portadoras de carcinoma cérvico-uterino que completaram o tratamento de radio-quimioterapia no período junho de 2006 - novembro de 2008. A radioterapia externa (RTE) foi feita por irradiação pélvica (concomitante com cisplatina semanal) e braquiterapia (BT) útero-vaginal. A dose biológica efetiva para tumor, reto e bexiga foi calculada. A taxa de controle loco-regional e a sobrevida aos cinco anos foram calculadas e também as complicações crônicas utilizando o método de Kaplan-Meier. Resultados: a sobrevida global obtida foi de 67% aos cinco anos, mostrando diferenças significativas entre o estádio II (78%) e o estádio III (49%) (Log-rank test, p = 0,0002). A taxa de complicações crônicas graus 3-4, de acordo com a RTOG (Radiation Therapy Oncology Group), foi 1,8% para as urinarias e 3,7% para as digestivas. O controle local inicial foi de 89% e a persistência da lesão de 10,3%; recidiva loco-regional (RL) em todo o período: 19,5%; metástases com ou sem RL: 10,3%. Conclusões: a eficácia terapêutica da radioquimioterapia no câncer de cérvix no nosso meio foi confirmada. A maioria das recidivas ou persistências foi devida a falta de controle loco-regional depois do tratamento inicial. O tratamento foi bem tolerado, com baixa porcentagem de complicações crônicas, comparável a referências internacionais.

Infeccion en el pie diabetico / Infection in diabetic foot

Objetivo: realizar una revisión de la literatura desde los años 80 con el fin de encontrar los avances para el diagnóstico y el tratamiento de las infecciones en el pie del diabético dadas la complejidad y las dificultades en esta patología. Fuente de datos: se inició la búsqueda de esta literatura médica colombiana desde el primer trimestre de 1995, cuando se fundó la línea de profundización Pie Diabético. Se ha venido desarrollando un proceso de búsqueda retrospectiva, al revisar sistemáticamente la bibliografía de cada artículo encontrado. Luego, se procedió a buscar las publicaciones por las bases de datos de Medline, Cochrane, National Guidelines Cleringhouse, Bireme de Brasil, Guidelines.gov. Selección de datos por estudios: se estudiaron 110 publicaciones de las cuales se seleccionaron las relacionadas a la infección en el pie diabético. Extracción de datos: los artículos se clasificaron de acuerdo con los diferentes niveles de evidencia encontrados: revisiones sistemáticas, experimentos clínicos, metaanálisis, consensos, artículos de revisión, informes de series de casos, reportes de casos y presentaciones en congresos. Síntesis de datos: se inició un análisis cronológico en primer lugar, en segundo lugar comparativo y en tercer lugar de acuerdo con su aplicabilidad para identificar los esquemas de terapia antibiótica empírica o dirigida de acuerdo con los cultivos y antibiogramas. Porque, si el médico tratante logra utilizar pautas terapéuticas en forma eficaz, en colaboración del equipo de salud que coordina, podrá reducir la estancia hospitalaria, mejorar la relación costo - efectividad, agilizar la toma de decisiones todo para optimizar la calidad de atención de su paciente. Conclusiones: la comprensión de la presentación de la infección en el síndrome del pie diabético, los avances en el diagnóstico y el tratamiento y por ende en el pronóstico deben ser apropiados por los diferentes actores del equipo de salud coordinado por el médico tratante.