Resumen La verificación del cumplimiento de los principios éticos en la investigación en salud legitima su ejercicio ante la sociedad y posibilita la resolución de dilemas éticos frente a nuevos intereses y métodos de investigación. En Colombia, la Resolución 8430 de 1993 es una de las principales pautas éticas que regulan la investigación en salud. Dado que no ha sido revisada ni actualizada desde su adopción, se hace necesario valorar su vigencia y suficiencia para abordar los potenciales dilemas éticos que se plantean actualmente en la investigación en salud en el país. En este contexto, se detallan algunos vacíos y contradicciones, así como aspectos que requieren de una revisión profunda, a partir de una concepción amplia de las áreas y los métodos de investigación en salud. Tras discutir las principales falencias e imprecisiones, se proponen alternativas para que la Resolución responda a las necesidades actuales del país frente a la ética en investigación en salud con seres humanos.

Abstract Verifying the compliance with the ethical principles of health research legitimizes its exercise in the eyes of the society and allows for the resolution of ethical dilemmas that emerge from new research interests and methods. Resolution 8430 of 1993 is one of the main ethical guidelines governing health research on human beings in Colombia. Considering that the resolution has not been revised or updated since its promulgation it becomes necessary to evaluate its current validity and adequacy to address the potential ethical dilemmas in the existing country’s health research. Some gaps, contradictions, and aspects that require a deep review are detailed in this paper from a wide conception of health research areas and methods. After discussing the main weaknesses and inaccuracies, some alternatives are proposed to adjust the resolution to the present needs in health research with human beings.

Introducción. La reacción a la prueba cutánea de Montenegro (a leishmanina) y la lesión de leishmaniasis comparten características fundamentales de la reacción de hipersensibilidad de tipo retardado. Objetivos. Determinar si la respuesta cutánea a leishmanina se aproxima y podría modelar la respuesta inflamatoria e inmune temprana a la infección por Leishmania. Materiales y métodos. Este estudio comparó la respuesta inflamatoria de biopsias de lesiones agudas (tiempo de evolución £1 mes) y lesiones crónicas (tiempo de evolución ³6 meses) con su respectiva reacción a la prueba cutánea de Montenegro, y con la reacción a la prueba de Montenegro de individuos infectados asintomáticos. Resultados. La proporción de linfocitos T CD4+ y CD8+, células fagocíticas mononucleares y granulocitos fue similar entre lesiones agudas y sus reacciones a la prueba cutánea a leishmanina. En contraste, los linfocitos CD4+ (32,6%) representaron una proporción significativamente mas baja, y los linfocitos B (20%) y macrófagos (27%) una proporción significativamente más alta del infiltrado celular en lesiones crónicas que en sus correspondientes reacciones a la prueba cutánea de Montenegro (CD4+: 43,7%, linfocitos B: 0.9%; macrófagos: 17,5%). Se encontró una asociación positiva entre linfocitos T CD8+ y macrófagos ( P=0,038) en la reacción a la prueba cutánea de Montenegro de los individuos con infección asintomática, mientras que los linfocitos T CD8+ y CD4+ estuvieron asociados positivamente en las reacciones a la prueba cutánea de Montenegro de pacientes crónicos ( P=0,002). Adicionalmente, la proporción de linfocitos B en lesiones crónicas (20%) fue más alta que en lesiones agudas (5,3%) ( P=0,002). Conclusión. La reacción cutánea de Montenegro permitió diferenciar la respuesta celular inmune entre infección asintomática y enfermedad crónica, y simula la respuesta temprana a la infección.

Introduction. The Montenegro skin test reaction and leishmaniasis lesions share fundamental characteristics of a delayed type hypersensitivity reaction. Objectives. To determine whether the Montenegro skin test reaction (response to leishmanin) might approximate and thereby provide insight into the early inflammatory and immune response to Leishmania infection. Materials and methods. We compared the inflammatory response in biopsies of acute (evolution time £one month), and chronic lesions (evolution time ³6 months) with the Montenegro skin test reaction in the corresponding patients, and with the Montenegro skin test of asymptomatically infected volunteers. Results. The proportion of CD4+ and CD8+ T lymphocytes, mononuclear phagocytes and granulocytes were similar in acute lesions and in their corresponding Montenegro skin test reactions. In contrast, CD4+ lymphocytes (32.6%) represented a significantly lower, and B cells (20%) and macrophages (27%) a significantly higher proportion of the cellular infiltrate in chronic lesions as compared to reactions in the corresponding skin test site (CD4+: 43.7%, B cells: 0.9%; macrophages: 17.5%). CD8+ T lymphocytes and macrophages were positively associated ( P=0.038) in the Montenegro skin test of asymptomatically infected individuals whereas CD8+ and CD4+ T cells were positively associated in the Montenegro skin test of chronic patients ( P=0.002). Notably, B cells were markedly more frequent in chronic lesions (20%) than in acute lesions (5.3%) ( P=0.002). Conclusion. The Montenegro skin test distinguished the cellular immune response to Leishmania in asymptomatic infection and chronic disease and may provide a surrogate of the early response to infection.

Introducción. Los comités de ética de investigación en humanos que aplican los estándares internacionales en la evaluación ética de proyectos de investigación son un recurso indispensable para garantizar la integridad ética de la investigación en humanos. Objetivo. El presente trabajo se propuso conocer las características de los comités de ética de investigación en humanos y sus necesidades con miras a su fortalecimiento en Colombia. Materiales y métodos. En el 2003, se seleccionaron 280 grupos de investigación en humanos de un listado de grupos de investigación que acudieron a la convocatoria del año 2002 de la Red de Ciencia y Tecnología de Colciencias. El 80% de estos grupos pertenecía a 40 instituciones entre universidades, hospitales y centros de investigación públicos y privados. Treinta de 40 instituciones tenían comité de ética. Se les envió un cuestionario que indagaba sobre la constitución, reglamentación, composición multidisciplinaria, pluralidad, representatividad e independencia de los comités. Las respuestas se analizaron utilizando como referencia las Guías operacionales para comités de ética de investigación biomédica (TDR/PRD/ETHICS/2000). Se complementó la información obtenida mediante discusiones con miembros de estos comités en cinco ciudades del país. Resultados. Veintiséis comités respondieron la encuesta. El 47% de los miembros eran médicos, 23% de los comités tenía un miembro representante de la comunidad, 40% tenía un miembro independiente, 70% tenía manual de operaciones. Mencionaron la necesidad de mejorar la constitución de los comités, la capacitación de sus miembros, la regulación y las guías nacionales. Conclusión. Es urgente que en Colombia se elaboren guías nacionales para los comités de ética de investigación basados en estándares internacionales, se capacite a sus miembros y se promueva la integridad ética de la investigación

Introduction. Ethics committees are a necessary resource to guarantee ethical integrity in human research; they must apply international standards in their ethical evaluation of research projects involving human subjects. Objective. The ethics committees for human research of Colombia were characterized, and recommendations for strengthening them were formulated. Materials and Methods. In 2003, 280 groups with research projects involving human subjects were selected from a list of research groups which form part of the science and technology network of Colciencias. (Colciencias is the Colombian national agency that promotes and funds science and technology.) Eighty percent (224) of the projects were associated with 40 institutions, consisting of universities, hospitals, and public or private research centers. Thirty of these institutions had at least one ethics committee for evaluating use of human subjects. A questionnaire was mailed to each of these Committees, requesting information concerning its their compostition, regulations, multidisciplinarity, plurality, representativity and independence. The World Health Organization’s Operational Guidelines for Ethic Committees that Evaluate Biomedical Research (TDR/PRD/ETHICS/2000) was used as reference for the analysis. In 5 of the cities, supplemental information was obtained by direct discussions with members of the ethics committees. Results. Twenty-six committees responded to the questionnaire. The results indicated that 47% of the committee members were physicians,but only 23% of the committees had representatives from the community. In 60% of the Committees, members were not independent from the organization in which it was based. Seventy percent had established operating procedures. Lack of national regulations and limited education in research ethics were mentioned as the main drawbacks in providing effective guidance. Conclusions. These observations led to the conclusion that national guidelines must be established for ethics committees that correspond to international standards. Committee members must be trained before accepting committee responsibilities. Finally, new committees must be created along with the improvement of the currently existing committees for reinforcing and promoting the importance of ethical integrity in research.

The chitin is a natural polymer that is extracted commercially from the shells of crustaceans generated as raw material from the fishing industry. Their chemical structure is constituted by residual units of N-acetyl glucosamine linked by b (1 ® 4) and its derivatives can be obtained from alkaline chitosan. The chitin, chitosan and their derivatives present very good perspectives to be used in agriculture. These derivatives are biodegradable and they exhibit fungicides, germicides, nemacides properties and natural defensive mechanisms of the plants. The chlorophosphonic-2-acid (Ethephon®) is a commercial product employed for the early maturation of fruits. The objective of the present work is the synthesis and characterization of chitosan-O-ethyl phosphonate chitosan to obtain a controlled released system with potential plant growth regulation properties. Alkaline chitosan was obtained; and then reacted with the 2-chlorophosphonic acid. The synthesis of new chitosan derivatives and its complete characterization by FT-IR, 13C, ¹H and 31P NMR is described and gas chromatographic, the effects on field blueberries are also tested. A chitosan 99 % deacetylated and Mv = 89,000 g/mol is prepared. The O-(ethyl phosphonic) chitosan (QOEP) with a degree of substitution of 58% is obtained

Alternative, non-microscopic methods for the diagnosis of malaria have recently become available. Among these, rapid dipstick methods stand out. One such test, OptiMAL®, is based on the immunochromatographic detection of Plasmodium lactate dehydrogenase (pLDH) and has the capacity to detect and distinguish infections caused by P. falciparum and Plasmodium sp. This capacity is particularly important in countries where different species of Plasmodium co-exist. In this study we evaluated the performance of OptiMAL® in an urban referral center for malaria diagnosis. Two sets of patients were included: one (n = 112) having predetermined infections with P. falciparum or P. vivax and individuals with negative blood smears; and another consisting of all eligible consecutive patients (n = 80) consulting for diagnosis at the referral center during one month. The overall diagnostic efficiency of OptiMAL® for both sets of patients was 96.9%. Efficiency was higher for P. vivax (98.1%) than for P. falciparum (94.9%). These results corroborate the diagnostic utility of OptiMAL® in settings where P. vivax and P. falciparum co-exist and support its implementation where microscopic diagnosis is unavailable and in circumstances that exceed the capacity of the local microscopic diagnosis facility.

In order to determine the frequency of therapeutic failures to chloroquine (CQ) in patients with malaria due to either Plasmodium falciparum or P. vivax, and to explore the usefulness of a malaria-free city as a sentinel site to monitor the emergence of drug resistance, 53 patients (44 infected with P. vivax and 9 with P. falciparum) were evaluated at the Laboratory of Parasitology, Universidad del Valle in Cali, Colombia. Patients received 25 mg/kg of CQ divided in three doses over 48 h; they were followed during 28 days according to WHO/PAHO protocols. While therapeutic failures to CQ in the P. vivax group were not detected, the proportion of therapeutic failures in the P. falciparum group was high (78%) and consistent with the reports from endemic areas in Colombia. The diverse origin of cases presenting therapeutic failure confirmed that P. falciparum resistant to CQ is widespread in Colombia, and further supports the change in the national antimalarial drug scheme. Monitoring of drug resistance in malaria free areas would be useful to identify sites requiring efficacy evaluation, and in some situations could be the most appropriate alternative to collect information from endemic areas where therapeutic efficacy studies are not feasible.

The indirect immunoperoxidase method was evaluated in 265 biopsies with the purpose of increasing the sensitivity of the diagnostic histopathology of tegumentary lesions caused by subspecies of the Leishmania braziliensis complex. A diagnosis of leishmaniasis was established by parasitological methods (181) or clinical criteria (12) in 193 patients (72.8%). In the latter group of confirmed cases standard histochemstry and immunoperoxidase were compared with direct examination of tissue scraping and culture of lesion aspirates. The detection and localization of amastigotes was more efficient using the immunoperoxidase method (61.3%) than conventional histopathology with hematoxilin and eosin (34.6%) or direct examination of tissue scraping (43.9%). Howerver, culture of lesion aspirates was the most sensitive procedure (89.8%). The efficiency of the immunoperoxidase method was greater in recent lesions, being positive in 75% of cases with less than 3 months evolution, while 55.6%, 37.5% and 21.1% of cases with lesion evolution of 3-5.9, 6-11, and 12 months or greater, respectively, were positive. The combined use of the direct examination of lesion scraping and immunoperoxidase applied to histological sections of the biopsy from the lesion border allowed an etiologic diagnosis of 72% of confirmed cases. Cross-reactivity was observed with Paracoccidioides braziliensis but not with Mycobacterium leprae, Sporothrix schenckii, or Histoplasma capsulatum.

Con el objeto de aumentar la sensibilidad del diagnóstico histopatológico de lesiones cutáneas y mucocutáneas causada por subespecies del complejo Leismania braziliensis y para lograr una mejor visualización de los parásitos en las lesiones, se evaluó el método de la inmunoperoxidas indirecta para localizar en forma rápida y específica los amastigotas en biopsia de tejido afectado. Los cortes de tejido se fijaron en formol y se incluyeron en parafina; después se evaluaron por inmunohistoquímica usando un antisuero policlonal producido en conejo, como reactivo primario, Se examinaron 265 biopsias de pacientes con lesiones sospechosas de leishmaniasis de la costa Pacífica y región suroriental colombiana. a 1983 (72.8%) pacientes se les estableció el diagnóstico por métodos clínicos y/o poarasitológicos. Los resultados obtenidos por la inmunoperoxidasa en el grupo de pacientes a los cuales se les confirmó la leishmaniasis se compararn con la histopatología convencional, el examen directo de frotis y el aislamiento del parásito por cultivo del aspirado de la lesión. La localización inmunoenzimática de las amastigotas fue más efectivas (61.3%) que la histopatología com hematoxilina y eosina (34.6%), y que el frotis (43,9%). En cambio, el cultivo de aspirado fue más sensible (89.8%). La eficiencia del método de inmunoperoxidasa fue mayor en las lesiones recientes (72.5%) positivos en los casos con menos de tres meses de evolución) que en las lesiones más antiguas (55.6, 37.5 y 21.1% para 3-5.9, 6-11 meses y mayores o iguales a 12 mese, respectivamente). La combinación de frotis e inmunoperoxidasa incrementó el porcentaje de caso diagnosticados a 72.0%, lo que indica la importancia de combinar métodos para obtener una mayor eficiencia de diagnóstico. La especificidad fue de 100% en controles sanos y 92.9% en pacientes con lesiones causadas por agentes etiológicos distintos a leishmania.