Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia.

Introduction: Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices. Methods: A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered. Results: Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of -1.47% (95% CI -1.76, -1.17), weight loss of -4.23 kg (95% CI -5.34, -3.12), and albumin/creatinine ratio of -18.6 mg/g (95% CI -60.2, -5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles. Conclusion: In Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2 kg and a decrease of 1.4% in HbA1c.

Posterior Reversible Encephalopathy Syndrome as an Adverse Effect of Lenvatinib in a Patient with Papillary Thyroid Carcinoma: A Case Report.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon transient neuroradiological phenomenon that develops vasogenic cerebral edema and could be caused by some pharmacological agents, such as molecular-specific target agents. Lenvatinib belongs to the tyrosine kinase inhibitors and was approved in 2015 for progressive locally advanced or metastatic thyroid cancer refractory to radioactive iodine (I-131) treatment. Herein, we present the case of a 65-year-old woman who, while receiving treatment with lenvatinib for radioiodine-refractory metastatic papillary thyroid carcinoma, developed PRES without hypertension at the initial evaluation. Her clinical and radiological findings improved after withdrawing from the mentioned therapy, and later it was possible to re-incorporate lower doses of the medication, as described in the other three case reports found in the worldwide medical literature. The recognition of this entity is essential to timely suspend the drug and avoid greater comorbidity. This is the first paper reporting this kind of adverse event using lenvatinib in a Hispanic population.

Complejo de Carney: reporte de un caso y revisión de la literatura / Carney complex: a case report and literature review

Resumen El complejo de Carney es una enfermedad caracterizada por lesiones en la piel, tumores endocrinos, cardiacos, gonadales y en otros órganos, que está asociada con mutaciones del gen PRKAR1A. Presentamos el caso clínico de una paciente con varias de las manifestaciones más características de este síndrome. Finalmente, se hace una revisión de la literatura.

Abstract Carney complex is a disease characterized by skin lesions, endocrine, cardiac, gonadal and other organ tumors, associated with mutations of the PRKAR1A gene. We present the clinical case of a patient with several of the most characteristic manifestations of this syndrome. Finally, there will be a review of the literature.

Activity of Mitragyna speciosa ("Kratom") Alkaloids at Serotonin Receptors.

Kratom alkaloids have mostly been evaluated for their opioid activity but less at other targets that could contribute to their physiological effects. Here, we investigated the in vitro and in vivo activity of kratom alkaloids at serotonin receptors (5-HTRs). Paynantheine and speciogynine exhibited high affinity for 5-HT1ARs and 5-HT2BRs, unlike the principal kratom alkaloid mitragynine. Both alkaloids produced antinociceptive properties in rats via an opioid receptor-independent mechanism, and neither activated 5-HT2BRs in vitro. Paynantheine, speciogynine, and mitragynine induced lower lip retraction and antinociception in rats, effects blocked by a selective 5-HT1AR antagonist. In vitro functional assays revealed that the in vivo 5-HT1AR agonistic effects may be due to the metabolites 9-O-desmethylspeciogynine and 9-O-desmethylpaynantheine and not the parent compounds. Both metabolites did not activate 5-HT2BR, suggesting low inherent risk of causing valvulopathy. The 5-HT1AR agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use.

Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for µ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats.

Relationships between µ-opioid receptor (MOR) efficacy and effects of mitragynine and 7-hydroxymitragynine are not fully established. We assessed in vitro binding affinity and efficacy and discriminative stimulus effects together with antinociception in rats. The binding affinities of mitragynine and 7-hydroxymitragynine at MOR (Ki values 77.9 and 709 nM, respectively) were higher than their binding affinities at κ-opioid receptor (KOR) or δ-opioid receptor (DOR). [35S]guanosine 5'-O-[γ-thio]triphosphate stimulation at MOR demonstrated that mitragynine was an antagonist, whereas 7-hydroxymitragynine was a partial agonist (Emax = 41.3%). In separate groups of rats discriminating either morphine (3.2 mg/kg) or mitragynine (32 mg/kg), mitragynine produced a maximum of 72.3% morphine-lever responding, and morphine produced a maximum of 65.4% mitragynine-lever responding. Other MOR agonists produced high percentages of drug-lever responding in the morphine and mitragynine discrimination assays: 7-hydroxymitragynine (99.7% and 98.1%, respectively), fentanyl (99.7% and 80.1%, respectively), buprenorphine (99.8% and 79.4%, respectively), and nalbuphine (99.4% and 98.3%, respectively). In the morphine and mitragynine discrimination assays, the KOR agonist U69,593 produced maximums of 72.3% and 22.3%, respectively, and the DOR agonist SNC 80 produced maximums of 34.3% and 23.0%, respectively. 7-Hydroxymitragynine produced antinociception; mitragynine did not. Naltrexone antagonized all of the effects of morphine and 7-hydroxymitragynine; naltrexone antagonized the discriminative stimulus effects of mitragynine but not its rate-decreasing effects. Mitragynine increased the potency of the morphine discrimination yet decreased morphine antinociception. Here we illustrate striking differences in MOR efficacy, with mitragynine having less than 7-hydroxymitragynine. SIGNIFICANCE STATEMENT: At human µ-opioid receptor (MOR) in vitro, mitragynine has low affinity and is an antagonist, whereas 7-hydroxymitragynine has 9-fold higher affinity than mitragynine and is an MOR partial agonist. In rats, intraperitoneal mitragynine exhibits a complex pharmacology including MOR agonism; 7-hydroxymitragynine has higher MOR potency and efficacy than mitragynine. These results are consistent with 7-hydroxymitragynine being a highly selective MOR agonist and with mitragynine having a complex pharmacology that combines low efficacy MOR agonism with activity at nonopioid receptors.

Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy.

Kratom is widely consumed in the United States for self-treatment of pain and opioid withdrawal symptoms. Mitragynine is the most abundant alkaloid in kratom and is a µ-opioid receptor agonist. 7-Hydroxymitragynine (7-HMG) is a mitragynine metabolite that is a more potent and efficacious opioid than its parent mitragynine. 7-HMG contributes to mitragynine's antinociceptive effects in mice, but evidence suggests it may also have a higher abuse potential. This in vitro study demonstrates that 7-HMG is stable in rodent and monkey plasma but is unstable in human plasma. Surprisingly, in human plasma 7-HMG is converted to mitragynine pseudoindoxyl, an opioid that is even more potent than either mitragynine or 7-HMG. This novel metabolite is formed in human plasma to a much greater extent than in the preclinical species tested (mouse, rat, dog, and cynomolgus monkey) and due to its µ-opioid potency may substantially contribute to the pharmacology of kratom in humans to a greater extent than in other tested species.

COVID-19 y tiroides. Revisión de la literatura y recomendaciones para pacientes con enfermedad tiroidea / Thyroid and COVID-19. Review and recommendations for patients with thyroid disease

Resumen Las enfermedades de la tiroides, tanto benignas como malignas, son altamente prevalentes a nivel mundial, por lo que es muy probable que durante la pandemia por SARS-CoV-2 veamos pacientes con ambas enfermedades. Esto exige el conocimiento de las implicaciones potenciales de este nuevo virus en el funcionamiento de la glándula, en los tratamientos usuales para estas enfermedades y en consideraciones especiales para este grupo poblacional. A la fecha no hay evidencia que soporte que las enfermedades tiroideas aumenten el riesgo de infección o severidad de la enfermedad; sin embargo, es posible que durante infecciones severas por SARS-CoV-2 en personas con o sin antecedente de enfermedad tiroidea puedan presentar alteración de las pruebas tiroideas, aunque transitoriamente y sin requerimiento de tratamiento específico. Es fundamental que los pacientes continúen con sus tratamientos ambulatorios y se difiera, en la medida de lo posible, los procedimientos quirúrgicos o la administración de yodo radioactivo hasta que se considere seguro realizarlos.

Abstract Both benign and malignant thyroid diseases are highly prevalent worldwide, so it is highly likely that during the COVID-19 pandemic we will see patients with this comorbidity. This requires knowledge of the potential implications of this new virus in the functioning of the gland, the usual treatments for these diseases and special recommendations in this population. To date, there is no evidence to support that thyroid diseases increase the risk of infection or the disease severity. However, it is possible that during severe SARS-CoV-2 infections in people with or without history of thyroid disease, the thyroid tests may be altered, although transitory and does not require specific treatment. It is essential for patients to continue with their outpatient treatments and defer as far as possible surgical procedures or administration of radioactive iodine until it is considered safe to perform.

COVID-19 y diabetes. Retos, Implicaciones y manejo durante la pandemia / COVID-19 and Diabetes. Challenges, Implications and treatment during the pandemic

Resumen Desde finales del año 2019 un nuevo coronavirus, SARS-CoV-2, se extendió desde China hacia el resto del mundo, causando la pandemia de una enfermedad denominada COVID-19. Una enfermedad sistémica que en algunos casos produce neumonía severa que incluso puede progresar a falla respiratoria aguda y finalmente la muerte. Entre las comorbilidades que se han asociado con un aumento en la mortalidad por SARS-CoV-2 se encuentra la diabetes. En general, se estima que tener diabetes aumenta un 18 % el riesgo de infecciones respiratorias, en parte por el impacto que genera sobre la inmunidad innata o adquirida, lo que estaría contribuyendo a una presentación clínica más severa del SARS-CoV-2 al comparar con población sin diabetes. Considerando que existe una asociación entre mal control glucémico y mayor severidad clínica de la infección por COVID-19, se deben hacer importantes consideraciones sobre el manejo farmacológico brindado a los pacientes; el perfilamiento dependerá de las condiciones de cada paciente, de la severidad de la enfermedad y del tipo de manejo instaurado ya sea ambulatorio o intrahospitalario.

Abstract Since the end of the year 2019 a new coronavirus called Severe Acute Respiratory Syndrome (SARS-CoV-2) has spread from China to the rest of the world, causing the pandemic of the disease called COVID-19. A systemic disease that in some cases produces severe pneumonia that can even progress to acute respiratory failure and eventually death. Among the comorbidities that have been associated with an increase in mortality from SARS-CoV-2, diabetes is one of them. In general, it is estimated that having diabetes increases the risk of respiratory infections by 18 %, in part, due to the impact on innate and acquired immunity, which would be contributing to a more severe clinical presentation of SARS-CoV-2 when compared with population without diabetes. Considering that there is an association between worse glycemic control and higher clinical severity of COVID-19 infection, important considerations must be made regarding the type of pharmacological management that is provided to patients; the profiling will depend on the conditions of each patient, the severity of the disease, and the type of management either as outpatient or in-hospital.

Percepción de los estudiantes de los programas de Química Farmacéutica, Tecnología en Regencia de Farmacia y Medicina de la Universidad de Antioquia frente al uso terapéutico de los cannabinoides / Perception of the students of the programs of Pharmaceutical Chemistry, Technology in Regency of Pharmacy and Medicine of the University of Antioquia about the therapeutic use of cannabinoids

Resumen Introducción: La planta Cannabis sativa (marihuana) contiene un número aproximado de 60 cannabinoides, de los cuales, el delta-9-tetrahidrocannabinol es el componente más estudiado para ser utilizado con fines medicinales. El conocimiento adecuado por parte de los ciudadanos de esta estrategia terapéutica es un proceso clave para garantizar la aceptación y la buena adherencia al tratamiento. Objetivo: Establecer la percepción que tienen los estudiantes de pregrado de Química Farmacéutica, Tecnología en Regencia de Farmacia y Medicina de la Universidad de Antioquia, en cuanto al uso de los productos de extractos de cannabis como tratamiento medicinal. Método: Estudio observacional de corte transversal, a partir de encuestas a estudiantes a través de un formulario en línea. Resultados: Se aplicaron 374 encuestas, 232 (62%) estudiantes de pregrado de Química Farmacéutica y Tecnología en Regencia de Farmacia y 142 (38%) de Medicina. De los estudiantes, 222 (59,4%) eran del sexo femenino, con una edad promedio de 22,5 años, y 348 (94%) viven en estrato socioeconómico bajo y medio. El 60,2% de los estudiantes dicen tener un conocimiento inadecuado sobre la utilización de la marihuana medicinal, la utilización de cannabinoides medicinales, la reglamentación y la seguridad. Relacionado con la opinión sobre la utilización medicinal, 356 (95,2%) de los encuestados estuvieron de acuerdo. Conclusiones: La mayoría de los estudiantes manifestaron un conocimiento inadecuado sobre la utilización de los cannabinoides terapéuticos. Además, gran parte de los estudiantes están de acuerdo con la utilización de la marihuana medicinal.

Abstract Introduction: Cannabis sativa (marijuana) contains approximately 60 cannabinoids, of which, delta-9-tetrahydrocannabinol is the most studied component to be used for medicinal purposes. Adequate knowledge by citizens of this therapeutic strategy is a key process to guarantee the acceptance and the good adherence to the treatment. Objective: To establish the perception of undergraduate students of Pharmaceutical Chemistry, Technology in Regency of pharmacy and medicine of the University of Antioquia, as regards to the use of cannabis extracts products as medicinal treatment. Method: Observational cross-sectional study, based on surveys to students through an online form. Results: 374 surveys were obtained, 232 (62%) from students of Pharmaceutical Chemistry and Technology in Regency of Pharmacy, and 142 (38%) from Medicine. 222 (59.4%) of the students that were female, with a mean age of 22.5 years, and 348 (94%) live in low and middle socioeconomic strata. 60.2% of students claim to have inadequate knowledge regarding the use of medical marijuana, the use of medicinal cannabinoids, regulation and safety. Related to the opinion of the medicinal use, 356 (95.2%) respondents agreed. Conclusions: Most of the students expressed inadequate knowledge about the use of therapeutic cannabinoids. In addition, the vast majority of students agree with the use of medical marijuana.

Experiencia clínica con infecciones causadas por Klebsiella pneumoniae productora de carbapenemasa, en una institución de enseñanza universitaria en Medellín, Colombia / Clinical experience with infections caused by carbapenemase-producing Klebsiella pneumoniae in a tertiary care teaching institution in Medellin, Colombia

Antecedentes: Las infecciones por Klebsiella pneumoniae productora de carbapenemasa (KPC) son un problema de salud pública mundial. Desde 2008 nuestra institución experimenta casos endémicos de infecciones por KPC posteriores a un brote cuyo caso índice fue un paciente de Israel admitido para trasplante hepático. Objetivo: Describir características clínicas y mortalidad en pacientes hospitalizados con infecciones nosocomiales por KPC. Métodos: Estudio observacional retrospectivo, descriptivo. Resultados: Un total de 52 pacientes fueron incluidos, la edad media fue 45,7 ± 27 años, 65,4% fueron hombres. Uso de inmunosupresores, cirugía gastrointestinal, hepatopatía crónica y trasplante de órgano sólido fueron las comorbilidades importantes. El 100% recibió antibióticos antes de la infección por KPC. Las principales infecciones fueron bacteriemia (30,7%), infección intraabdominal (23,1%) y neumonía (17,3%). El tratamiento fue dirigido por antibiograma en 50,7%. Tigeciclina fue administrada en el 51,9% y colistina en el 32,7%, ambas en terapia combinada con otros antibióticos. En el 15,4% se utilizó tigeciclina más colistina. La duración del tratamiento fue 15,7 ± 7,5 días. El 51,9% desarrolló bacteriemia y falla renal aguda y el 76,9% requirió atención en UCI. La mortalidad fue 48,1% y fue significativamente mayor en pacientes con bacteriemia vs. sin bacteriemia (74,1 vs. 20%; p = 0,01). No hubo diferencias significativas en mortalidad cuando se comparó uso de tigeciclina vs. colistina (45 vs. 52%; p = 0,609). Conclusión: La inmunosupresión, cirugía gastrointestinal, tratamiento previo con antibióticos y estancia en UCI son factores importantes para la infección por KPC. La mortalidad es alta a pesar de la terapia dirigida, especialmente en pacientes con bacteriemia.

Background: Carbapenemase-producing Klebsiella pneumoniae (KPC) infections are a worldwide public health problem. Since 2008, our institution has experienced endemic cases of KPC infection after an outbreak whose index case was a patient from Israel admitted for liver transplantation. Objective: To describe the clinical characteristics and mortality of inpatients with nosocomial KPC infections. Methods: Retrospective, descriptive observational study. Results: A total of 52 patients were included, with an average age of 45.7 ± 27 years; 65.4% were men. Use of immunosuppressants, gastrointestinal surgery, chronic liver disease and solid organ transplantation were significant comorbidities. All the patients had received antibiotics before the KPC infection. The primary infections were bacteraemia (30.7%), intra-abdominal infections (23.1%) and pneumonia (17.3%). Treatment was directed by antibiogram in 50.7% of cases. Tigecycline was administered in 51.9% of cases and colistin in 32.7%, both in combination therapy with other antibiotics. Colistin plus tigecycline was used in 15.4% of cases. The treatment duration was 15.7 ± 7.5 days, with 51.9% of patients developing bacteraemia and acute renal failure and 76.9% requiring ICU care. Mortality was 48.1% and was significantly higher in the patients with bacteraemia compared with those without (74.1 vs. 20%, respectively, p = 0.01). There were no significant differences in mortality between tigecycline and colistin use (45 vs. 52%, respectively, p = 0.609). Conclusion: Immunosuppression, gastrointestinal surgery, previous treatment with antibiotics and ICU stay are important factors for infection with KPC. Mortality is high despite targeted therapy, particularly in patients with bacteraemia.

Características clínicas, factores de riesgo y perfil de susceptibilidad de las infecciones por micobacterias documentadas por cultivo, en un hospital universitario de alta complejidad en Medellín (Colombia) / Clinical features, risk factors and susceptibility profile of mycobacterial infections documented by culture in a university hospital of high complexity in Medellin (Colombia)

Introduction: Tuberculosis (TB) remains an entity of high prevalence and mortality worldwide. The rising drug resistance is a public health problem. Besides, non-tuberculosis mycobacterial (NTM) infections are described with increasing frequency in areas of high prevalence of TB. Objectives: To determine epidemiological, clinical and microbiological characteristics of mycobacterial infections documented by culture. Materials and Methods: An observational, descriptive study in hospitalized patients. Results: M. tuberculosis complex was identified in 90,9% of 187 patients; 9,1% had NTM, 64% were male and the mean age was 40 years (range 1-88 years). The main co-morbidities were HIV / AIDS (23.5%), use of corticosteroids (13.3%) and chronic kidney disease (9.6%). Clinical forms were pulmonary (56.6%), extra-pulmonary (23.9%) and disseminated (19.2 The most common extra-pulmonary compromise was nodal (7.4%) and gastrointestinal (7%). 10.6% of M. tuberculosis were multi-drugresistant (MDR) and 2.12% had extended drug resistance (XDR). Mycobacterium avium andM. abscessus were the most frequent NTM. Overall mortality was 10%. Conclusions: In our study immune suppression is the main risk factor for extrapulmonary and disseminated disease. Resistance, MDR and XDR is higher in inpatients with TB. MNT infections are not uncommon in our country.

Introducción: Tuberculosis (TBC) es aún una entidad de alta prevalencia y mortalidad en el mundo. La resistencia ascendente a fármacos es un problema de salud pública. Además se describen con mayor frecuencia infecciones por micobacterias no tuberculosas (MNT) en áreas de alta prevalencia de TBC. Objetivos: Determinar características epidemiológicas, clínicas y microbiológicas de las infecciones por micobacterias documentadas por cultivo. Materiales y Métodos: Estudio observacional, descriptivo, en pacientes hospitalizados. Resultados: De 187 pacientes, en 90,9% se identificó complejo M. tuberculosis y en 9,1% MNT; 64% fueron hombres. Edad promedio 40 años (rango 1-88 años). Las principales co-morbilidades fueron infección por VIH/SIDA (23,5%), uso de corticoesteroides (13,3%) y enfermedad renal crónica (9,6%). Las formas clínicas fueron pulmonares (56,6%), extra-pulmonares (23,9%) y diseminadas (19,2%). El compromiso extra-pulmonar más frecuente fue ganglionar (7,4%) y gastrointestinal (7%). En M. tuberculosis 10,6% fueron multidrogoresistentes (MDR) y 2,12% con resistencia extendida (XDR). Mycobacterium avium y M. abscessus fueron las MNT más frecuentes. La mortalidad general fue 10%. Conclusiones: Inmuno-supresión es el principal factor de riesgo para enfermedad extrapulmonar y/o diseminada y la resistencia a fármacos en pacientes hospitalizados con TBC es llamativa, con mayor incidencia de MDR y XDR. Las infecciones por MNT no son infrecuentes en nuestro medio.

[Complications associated with hyperglycemia in liver transplant patients]. / Complicaciones asociadas a la hiperglucemia en pacientes trasplantados de hígado.

BACKGROUND: Hyperglycemia is a frequent phenomenon in hospitalized patients that is associated with negative outcomes. It is common in liver transplant patients as a result of stress and is related to immunosuppressant drugs. Although studies are few, a history of diabetes and the presentation of hyperglycemia during liver transplantation have been associated with a higher risk for rejection. AIMS: To analyze whether hyperglycemia during the first 48hours after liver transplantation was associated with a higher risk for infection, rejection, or longer hospital stay. METHODS: A retrospective cohort study was conducted on patients above the age of 15years that received a liver transplant. Hyperglycemia was defined as a value above 140mg/dl and it was measured in three different manners (as an isolated value, as a mean value, and as a weighted value over time). The relation of hyperglycemia to a risk for acute rejection, infection, or longer hospital stay was evaluated. RESULTS: Some form of hyperglycemia was present in 94% of the patients during the first 48 post-transplantation hours, regardless of its definition. There was no increased risk for rejection (OR: 1.49; 95%CI: 0.55-4.05), infection (OR: 0.62; 95%CI: 0.16-2.25), or longer hospital stay between the patients that presented with hyperglycemia and those that did not. CONCLUSIONS: Hyperglycemia during the first 48hours after transplantation appeared to be an expected phenomenon in the majority of patients and was not associated with a greater risk for rejection or infection and it had no impact on the duration of hospital stay.

[Clinical features, risk factors and susceptibility profile of mycobacterial infections documented by culture in a university hospital of high complexity in Medellin (Colombia)]. / Características clínicas, factores de riesgo y perfil de susceptibilidad de las infecciones por micobacterias documentadas por cultivo, en un hospital universitario de alta complejidad en Medellín (Colombia).

INTRODUCTION: Tuberculosis (TB) remains an entity of high prevalence and mortality worldwide. The rising drug resistance is a public health problem. Besides, non-tuberculosis mycobacterial (NTM) infections are described with increasing frequency in areas of high prevalence of TB. OBJECTIVES: To determine epidemiological, clinical and microbiological characteristics of mycobacterial infections documented by culture. MATERIALS AND METHODS: An observational, descriptive study in hospitalized patients. RESULTS: M. tuberculosis complex was identified in 90,9% of 187 patients; 9,1% had NTM, 64% were male and the mean age was 40 years (range 1-88 years). The main co-morbidities were HIV / AIDS (23.5%), use of corticosteroids (13.3%) and chronic kidney disease (9.6%). Clinical forms were pulmonary (56.6%), extra-pulmonary (23.9%) and disseminated (19.2 The most common extra-pulmonary compromise was nodal (7.4%) and gastrointestinal (7%). 10.6% of M. tuberculosis were multi-drug resistant (MDR) and 2.12% had extended drug resistance (XDR). Mycobacterium avium andM. abscessus were the most frequent NTM. Overall mortality was 10%. CONCLUSIONS: In our study immune suppression is the main risk factor for extrapulmonary and disseminated disease. Resistance, MDR and XDR is higher in inpatients with TB. MNT infections are not uncommon in our country.

Farmacognosia y farmacobotánica de especies pertenecientes a los géneros Esenbeckia y Raputia (Rutaceae) / Pharmacognosy and pharmacobotany of species of genera Esenbeckia and Raputia (Rutaceae)

Introducción: Esenbeckia y Raputia son géneros que pertenecen a la familia Rutaceae, que tienen información etnobotánica relevante, la cual deriva en estudios fitoquímicos que demuestran la cantidad de metabolitos secundarios que producen y su variabilidad molecular, lo cual muestra la importancia de estudios posteriores a estos géneros, que están distribuidos en Centroamérica y Suramérica, con el fín de tener información importante en la búsqueda de nuevos agentes terapéuticos para combatir enfermedades del tipo microbiano y afines. Objetivos: reunir y analizar información científica actualizada referente a los géneros Esenbeckia y Raputia como fuente natural de compuestos biológicamente activos, los cuales pueden llegar a ser utilizados en la medicina natural por su potencial farmacológico. Métodos: se incluyeron en el análisis artículos científicos y libros relacionados con los temas de composición química, usos tradicionales y evaluaciones farmacológicas, así como otros elementos de interés en la investigación de plantas medicinales. Resultados: la información analizada puede servir de base para el desarrollo de nuevas investigaciones que avalen el empleo en la terapéutica de productos fitoterápicos con elevada eficacia, seguridad y calidad. La revisión de los resultados en otros grupos de investigación permite establecer estrategias racionales de investigación científica, que contribuyan al uso de los recursos que se encuentran en universidades y centros de investigación y salud. Conclusiones: los elementos encontrados en la bibliografía consultada permiten asegurar que las especies pertenecientes a los géneros Esenbeckia y Raputia, pueden ser potencialmente empleadas en usos fitoterapéuticos, debido, entre otras cosas, al importante número de metabolitos secundarios identificados que poseen actividad farmacológica demostrada.

Introduction: Esenbeckia and Raputia are genera of the family Rutaceae about which relevant ethnobotanical information has been reported. Such data have been obtained from phytochemical studies showing the number of secondary metabolites they produce and their molecular variability. Hence the importance of later studies about these genera, which are distributed in Central and South America, with the purpose of obtaining important information useful in the search for new therapeutic agents against microbial and other related diseases. Objectives: collect and analyze updated scientific information about the genera Esenbeckia and Raputia as natural sources of biologically active compounds which may be used in natural medicine due to their pharmacological potential. Methods: the analysis included scientific papers and books dealing with the chemical composition, traditional uses and pharmacological evaluation of medicinal plants, as well as other topics of interest to natural medicine research. Results: the information analyzed may be the starting point for new research demonstrating the effectiveness, safety and quality of phytotherapy. Review of the results obtained by other research teams makes it possible to establish rational scientific research strategies, thus contributing to the use of resources from universities, research centers and health institutions. Conclusions: according to the information found in the literature consulted, species of genera Esenbeckia and Raputia may be used for phytotherapeutic purposes, due, among other reasons, to the considerable number of identified secondary metabolites with proven pharmacological activity.

Proteomic analysis of mice expressing human ApoE demonstrates no differences in global protein solubility between APOE 3 and APOE 4 young mice.

Apolipoprotein E (ApoE) is a major lipid carrier protein. In humans, ApoE is expressed in three polymorphic isoforms, which are encoded by three different alleles APOE2, APOE3, and APOE4. In the brains of Alzheimer's disease (AD) patients, each one of these three allelic isoforms is found in several "isoelectric" protein isoforms (qPI), i.e. protein isoforms resulting from PTMs altering the net charge (q) of the polypeptide. AD is a complex disease in which multiple causes and several risk factors affect the onset and disease outcome. A major risk factor for AD is ApoE4; therefore, it is important to characterize the different ApoE qPIs. We have implemented a detergent-based method for isolation and quantitation of protein isoforms, and we found differences in the solubility of protein isoforms depending on the type of solvent used. In this manuscript, we describe these methods and applied them to young human-ApoE targeted replacement mice. Our results indicate that there are no significant differences in the hippocampus proteome of these mice as a function of the APOE genotype.

Mortalin, apoptosis, and neurodegeneration.

Mortalin is a highly conserved heat-shock chaperone usually found in multiple subcellular locations. It has several binding partners and has been implicated in various functions ranging from stress response, control of cell proliferation, and inhibition/prevention of apoptosis. The activity of this protein involves different structural and functional mechanisms, and minor alterations in its expression level may lead to serious biological consequences, including neurodegeneration. In this article we review the most current data associated with mortalin's binding partners and how these protein-protein interactions may be implicated in apoptosis and neurodegeneration. A complete understanding of the molecular pathways in which mortalin is involved is important for the development of therapeutic strategies for cancer and neurodegenerative diseases.

Las conexiones de la enfermedad de Alzheimer: ¿Dónde están? Análisis desde la Proteómica cuantitativa: [revisión] / The Alzheimer’s connection: where is it? Insights from Quantitative Proteomics: [review]

En el presente artículo se presentan los conceptos básicos que definen la patología de la enfermedad de Alzheimer (EA) y los métodos fundamentales utilizados en Neuroproteómica para su estudio. De igual manera, se discuten algunos resultados en el análisis de esta enfermedad y su relación con el genotipo APOE4 de APOE, el gen que codifica la Apolipoproteína E (ApoE). Finalmente se hacen algunas consideraciones generales sobre la EA, cómo evitar su progresión y se discute brevemente el futuro de la investigación en esta área.

Cambios en la constante dieléctrica de implantes al entrar en contacto con radiocirugía / Changes on value of dielectric constant of implants after coming in contact with radiosurgery

OBJETIVO: el objetivo de este estudio descriptivo in Vitro fue medir los cambios existentes en el valor de la constante dieléctrica en implantes al entrar en contacto con radiocirugía. METODO: cinco implantes cilíndricos roscado de titanio comercialmente puro, de 13mm de longitud por 3.75mm con diámetro con superficie arenada, perteneciente a la misma casa comercial e igual lote, se pusieron en contacto con las ondas del radio del equipo de radiocirugía. Inicialmente, se midió la constante dieléctrica en cada uno de los implantes, por medio de un multimetro digital. Luego, se pusieron en contacto con el aparato de radiocirugía, tiempo después del cual se midió nueva mente el valor de la constante dieléctrica, en cada uno de los implantes con el fin de observar los posibles cambios en ella. RESULTADOS: se observó que el valor de la constante dieléctrica no varió al entrar en contacto los implantes con las ondas de radio del aparato de radiocirugía. CONCLUSIONES: con base en esto se podría deducirse que la radiocirugíano altera por lo tanto la interfase directa entre el hueso y el implante, es decir, la oseointegración, lo que se considera una característica de la misma.