A Modular Synthesis of the Rhazinilam Family of Alkaloids and Analogs Thereof.

A short, modular strategy for synthesizing three representative alkaloids of the (±)-rhazinilam family and 10 non-natural analogs is described. The protocol involves a radical addition/cyclization cascade reaction that assembles the tetrahydroindolizine system decorated with appropriate groups for a subsequent Pd-mediated cyclization, which generates the nine-membered lactam.

Eco-epidemiological study of an endemic Chagas disease region in northern Colombia reveals the importance of Triatoma maculata (Hemiptera: Reduviidae), dogs and Didelphis marsupialis in Trypanosoma cruzi maintenance.

BACKGROUND: In Colombia, Rhodnius prolixus and Triatoma dimidiata are the main domestic triatomine species known to transmit T. cruzi. However, there are multiple reports of T. cruzi transmission involving secondary vectors. In this work, we carried out an eco-epidemiological study on Margarita Island, located in the Caribbean region of Colombia, where Chagas disease is associated with non-domiciliated vectors. METHODS: To understand the transmission dynamics of Trypanosoma cruzi in this area, we designed a comprehensive, multi-faceted study including the following: (i) entomological evaluation through a community-based insect-surveillance campaign, blood meal source determination and T. cruzi infection rate estimation in triatomine insects; (ii) serological determination of T. cruzi prevalence in children under 15 years old, as well as in domestic dogs and synanthropic mammals; (iii) evaluation of T. cruzi transmission capacity in dogs and Didelphis marsupialis, and (iv) genetic characterization of T. cruzi isolates targeting spliced-leader intergene region (SL-IR) genotypes. RESULTS: Out of the 124 triatomines collected, 94% were Triatoma maculata, and 71.6% of them were infected with T. cruzi. Blood-meal source analysis showed that T. maculata feeds on multiple hosts, including humans and domestic dogs. Serological analysis indicated 2 of 803 children were infected, representing a prevalence of 0.25%. The prevalence in domestic dogs was 71.6% (171/224). Domestic dogs might not be competent reservoir hosts, as inferred from negative T. cruzi xenodiagnosis and haemoculture tests. However, 61.5% (8/13) of D. marsupialis, the most abundant synanthropic mammal captured, were T. cruzi-positive on xenodiagnosis and haemocultures. CONCLUSIONS: This study reveals the role of peridomestic T. maculata and dogs in T. cruzi persistence in this region and presents evidence that D. marsupialis are a reservoir mediating peridomestic-zoonotic cycles. This picture reflects the complexity of the transmission dynamics of T. cruzi in an endemic area with non-domiciliated vectors where active human infection exists. There is an ongoing need to control peridomestic T. maculata populations and to implement continuous reservoir surveillance strategies with community participation.

Biomarcadores de lesión miocárdica y edema pulmonar de las alturas / Biological markers of myocardial damage and high-altitude pulmonary edema

El edema pulmonar de las alturas es una entidad potencialmente fatal que se presenta en individuos que ascienden rápidamente por encima de 2.500 msnm. La hipoxia, el deterioro de la clase funcional y la dificultad respiratoria son el resultado de un edema pulmonar no cardiogénico. En este caso clínico de edema pulmonar de las alturas se encontró elevación de biomarcadores de lesión miocárdica y de sobrecarga de presión, sin compromiso estructural cardiaco o coronario, hallazgo que no ha sido ampliamente documentado. En observaciones recientes se ha evidenciado la elevación del péptido natriurético cerebral (BNP por su sigla en Inglés) en pacientes con enfermedad de las alturas y edema pulmonar de las alturas, con solo un caso clínico publicado que reportó elevación de la troponina asociado a edema pulmonar de las alturas.

The high-altitude pulmonary edema is a potentially fatal condition that occurs in people who rapidly ascend above 2,500 m. Hypoxia, functional class deterioration, and breathing difficulty are due to a non-carcinogenic pulmonary edema. In this case report of high-altitude pulmonary edema, we found an elevation of biomarkers of myocardial damage without myocardial or coronary compromise. This finding has not been widely documented. Recent observations have shown the elevation of brain natriuretic peptide, and even a case with positive troponin associated with high-altitude pulmonary edema has been found.

Cocaéna y dolor torácico / Cocaine and chest pain

El dolor torácico asociado al consumo de cocaína es uno de los síntomas más comunes referido por los pacientes. Usualmente, se presenta en jóvenes, sin factores de riesgo para enfermedad coronaria, y es independiente de la historia de abuso de sustancias, aunque aproximadamente la cuarta parte de éstos niega su consumo. El porcentaje de quienes presentan infarto agudo del miocardio posterior al consumo de cocaína es bajo; sin embargo el médico debe sospechar este diagnóstico y de acuerdo con el riesgo, definir la estrategia de estratificación y tratamiento adecuada.

Chest pain associated with cocaine use is one of the most common symptoms reported by patients. It usually occurs in young subjects with no risk factors for coronary disease, and is independent of the history of substance abuse, although about a quarter of them denies its consumption. The percentage of those who present acute myocardial infarction after cocaine use is low, but the doctor should suspect this diagnosis and according to the risk, define the stratification strategy and the appropriate treatment.