Intoxicación crónica con el fruto maduro de karwinskia humboldtiana en ratas wistar: daño renal / Chronic intoxication with ripe fruit of karwinskia humboldtiana in wistar rats: renal damage

Karwinskia humboldtiana (Kh) es un arbusto venenoso responsable de numerosos casos de intoxicación accidental en humanos. En la literatura se ha descrito a la intoxicación crónica con Kh como uno polineuropatía sin describir si existen o no alteraciones en órganos distintos al SNC y SNP como lo es el riñón. El objetivo de este estudio fue evaluar la morfología renal en un modelo de intoxicación crónica con Kh. Se utilizaron 32 ratas Wistar, se dividieron en cuatro grupos (n=8) en donde 5 ratas de cada grupo fueron intoxicadas y 3 fueron control no intoxicadas. A las ratas intoxicadas se les administraron por vía oral 3,5 g/kg del fruto seco y molido de Kh fraccionados en 5 dosis de 1,5; 0,5; 0,5; 0,5 y 0,5 g/kg los días 0, 3, 7, 10 y 14 respectivamente. Las ratas control solo recibieron agua. Cada grupo fue sacrificado a diferentes tiempos según la evolución de la parálisis. Se obtuvieron muestras de riñón, se procesaron hasta obtener bloques de parafina y resinas epóxicas, se obtuvieron cortes y se tiñeron y contrastaron para su observación al microscopio de luz y electrónico de transmisión (MET) respectivamente. A microscopia de luz identificamos congestión vascular, necrosis de los túbulos contorneados y fibrosis de la cápsula de renal, en la etapa de parálisis se realizo un conteo de los glomérulos afectados en las muestras tratadas con Kh, a MET además de los hallazgos previamente descritos se identificó la presencia de abundantes depósitos de matriz extracelular en la membrana basal de la cápsula renal y en la barrera de filtración de todos los grupos intoxicados, siendo más evidentes en el grupo de recuperación, lo que demuestra que la intoxicación crónica con Kh es una intoxicación sistémica y no exclusiva del SNC y SNP.

Karwinskia humboldtiana (Kh) is a poisonous shrub causing a number a accidental intoxications in humans. In previous studies, damage has been reported to Peripheral and Central Nervous System. Main intoxication sign is the presence of paralysis. However, no studies have been documented about damage to other organs like the kidney. The objective of this research is to evaluate kidney histology during chronic intoxication. Thirty two (32) Wistar rats were divided into 4 groups (n=8). For each group, 5 rats were intoxicated with Kh and 3 received water only as a control. Intoxicated rats received 3.5 g/Kg body weight of dry powder of Kh fruit, fractionated in 5 doses as follows 1.5, 0.5, 0.5, 0.5, 05 on days 0, 3, 7, 10 and 14 respectively. Control rats received water only. Each group was euthanized at different times during paralysis evolution. Samples of kidney were obtained and processed by routine technique until paraffin embedding for light microscopy studies, and in epoxy resins for transmission electron microscopy. Sections were obtained and stained with H&E, Masson's trichrome, and treated for PAS with diastase reaction to demonstrate basal membranes. At the light microscopic level we observed blood vessel congestion, tubular necrosis and fibrosis of renal capsule. Both at Light microscopy and electron microscopy, it was identified a thickening of the filtration barrier and of renal capsule, in all intoxicated animals, especially in the recovery group. These findings demonstrate that Kh causes a systemic intoxication and not only of the nervous system, as has been considered up to now.

Paradigmas de control de la malaria en Guatemala, siglos XX y XXI, de la erradicación a la eliminación / Paradigms of the malarial control in Guatemala in the 20th and 21st centuries moving from eradication to elimination

La malaria continúa siendo un problema de salud pública mundial. Durante los siglos XX y XXI el abordaje de esta enfermedad sufrió cambios paradigmáticos muy interesantes, pero principalmente estuvo influenciado por los descubrimientos relacionados con la segunda guerra mundial, la situación económica mundial, el advenimiento de nuevas estrategias de control y el abordaje de la enfermedad por medio de la participación comunitaria y el sector de la salud. El propósito de este trabajo es presentar los cambios de paradigmas desde una óptica vertical o erradicación, a una horizontal o eliminación, y desde lo positivista cuantitativo a lo mixto, en el abordaje de la malaria en Guatemala. Se realiza una reseña histórica de la malaria y se discuten los aspectos bioéticos del uso del insecticida dicloro-difenil-tricloroetano a nivel mundial. En los países desarrollados fueron justificadas las intervenciones de erradicación con el rociamiento intradomiciliar del insecticida citado y completarlas con el diagnóstico y tratamiento de la malaria; la realidad en la mayoría de los países en vías de desarrollo, fue diferente, puesto que no pudieron mantener los programas de erradicación por problemas financieros, un ejemplo claro de iniquidad global. Guatemala en esta década trabaja en la fase de preeliminación-eliminación, con buenos resultados, lo que marca un cambio de paradigma e indica que las medidas contra la malaria deben ser horizontales y favorecer el trabajo intra e intersectorial.

Malaria remains a world health problem. During the 20th and 21st centuries, the approach to this disease underwent very interesting paradigmatic changes, but they were influenced by breakthroughs derived from the Second World Wear, the international economic situations, the advent of new monitoring strategies and the approach to the disease based on the community and the health sector involvement. The objective of this paper was to present changes in paradigms form a vertical perspective or eradication to a horizontal viewpoint or elimination, and from a quantitative positivist to a combined standpoint in addressing malaria in Guatemala. A historical account of malaria was made and the bioethical aspects of the use of dichlorodiphenyltrichloroethane worldwide were discussed. The eradicating interventions by using the insecticidal spraying of houses were backed up in the developed countries. This was supplemented with the diagnosis and treatment of malaria. However, the situation was different in most of the developing countries, since their financial restrictions did not make possible to keep the eradication programs, being a clear example of the global inequality. In the present decade, Guatemala is going through the pre-elimination-elimination phase and it works with good results, which is indicative of a change in paradigm and shows that actions against malaria should be horizontal in order to encourage the intrasectorial and the intersectorial work.

Vector control intervention towards interruption of transmission of Chagas disease by Rhodnius prolixus, main vector in Guatemala

In Guatemala, the Ministry of Health (MoH) began a vector control project with Japanese cooperation in 2000 to reduce the risk of Chagas disease infection. Rhodnius prolixus is one of the principal vectors and is targeted for elimination. The control method consisted of extensive residual insecticide spraying campaigns, followed by community-based surveillance with selective respraying. Interventions in nine endemic departments identified 317 villages with R. prolixus of 4,417 villages surveyed. Two cycles of residual insecticide spraying covered over 98% of the houses in the identified villages. Fourteen villages reinfestated were all resprayed. Between 2000-2003 and 2008, the number of infested villages decreased from 317 to two and the house infestation rate reduced from 0.86% to 0.0036%. Seroprevalence rates in 2004-2005, when compared with an earlier study in 1998, showed a significant decline from 5.3% to 1.3% among schoolchildren in endemic areas. The total operational cost was US$ 921,815, where the cost ratio between preparatory, attack and surveillance phases was approximately 2:12:1. In 2008, Guatemala was certified for interruption of Chagas disease transmission by R. prolixus. What facilitated the process was existing knowledge in vector control and notable commitment by the MoH, as well as political, managerial and technical support by external stakeholders.

Evaluación del efecto del tratamiento con ácido lipoico administrado a la rata Wistar intoxicada con el fruto de Karwinskia humboldtiana / Evaluation of the effect of treatment with lipoic acid administered to the Wistar rat intoxicated with the fruit of Karwinskia humboldtiana

La ingesta accidental de fruto de Karwinskia humboldtiana ocasiona una parálisis flácida, simétrica, progresiva y ascendente, similar al síndrome de Guillain-Barré. Evoluciona en el transcurso de 3 a 12 meses hasta su recuperación total, pero los casos graves terminan en la muerte por insuficiencia respiratoria. No existe un tratamiento específico. La lesión histopatológica descrita en nervio periférico de pacientes, y animales de experimentación corresponde a una desmielinización segmentaria acompañada de degeneración Walleriana. Una de las toxinas extraídas a partir de la semilla, la T-514, ocasiona un incremento de radicales libres in vitro. Los radicales libres se han relacionado con la desmielinización que se presenta en otros tipos de neuropatías como en la diabética. Ya que la lesión ultraestructural que se presenta en los modelos animales de diabetes es similar a la que se observa en la intoxicación experimental con fruto de K. humboldtiana, se decidió administrar un potente agente antioxidante, el ácido a-lipoico en un modelo de intoxicación crónica por fruto de K. humboldtiana. Sin embargo, no se observó mejoría sobre las manifestaciones clínicas evaluadas en los animales o sobre las lesiones histopatológicas presentes en el nervio periférico. Estos resultados sugieren que los radicales libres no son el mecanismo principal de lesión sobre el nervio periférico en la polineuropatía causada por K. humboldtiana.

The accidental ingestion of Karwinskia humboldtiana causes a flaccid, symmetrical, progressive and ascending paralysis, similar to Guillain-Barre syndrome. It evolves over the course of 3 to 12 months until full recovery, but severe cases end in death due to respiratory failure. There is no specific treatment. The histopathological lesions described in peripheral nerve of patients and in experimental animals, corresponds to segmental demyelination accompanied by Wallerian degeneration. One of the toxins extracted from the seed, T-514, causes an increase of free radicals in vitro. Free radicals have been associated to demyelination that occurs in other types of neuropathy such as diabetic neuropathy. Since the ultrastructural damage that occurs in animal models of diabetes is similar to that observed in experimental poisoning with the fruit of K. humboldtiana, we decided to administer a powerful antioxidant, a-lipoic acid, in a model of chronic poisoning due of K. humboldtiana. However, no improvement was observed on the clinical manifestations evaluated in animals or in the histopathological lesions in the peripheral nerve. These results suggest that free radicals are not the primary mechanism of injury on the peripheral nerve caused by K. humboldtiana.