Efecto de Petiveria alliacea y drogas colinérgicas sobre la habituación / Effects of Petiveria alliacea and cholinergic drugs on the habituation cognitive behavior

Petiveria alliacea (PA) have anxiolytic, antidepressant and cognitive effects. In the present paper the effect of PA water infusion and cholinergic drugs on cognitive behavior were studied. For that, 40 male NMRI mice were divided in 4 groups: Control (n=10), Drug Control (n=10), PA (n=10) and PA plus Drug (n=10). PA 1% was administered orally (7.59±1.39 ml/day); while scopolamine (2 mg/Kg), galantamine (1 mg/Kg) and nicotine (0.1 mg/Kg) were administered intraperitoneally. Behavioral tests included: anxiety maze (AM), open field (OF) and marble burying (MB). Habituation cognitive behavior was evaluated in 4 sessions, one week each session. PA had anxiolytic and antidepressant effect effect in AM, combined with nicotine potentiated an anxiogenic effect in AM, galantamine favored habituation in OF. Scopolamine potentiated the habituation in LA and decreased the obsessive-compulsive behavior in OF. In conclusion; PA had an anxiolytic effect and favored deshabituation, combined with nicotine induced an anxiogenic effect, galantamine favored habituation and scopolamine decreased obsessive-compulsive behavior and favored motor habituation indicated a possible anxiolytic effect.

La Petiveria alliacea (PA) está relacionada con efectos ansiolíticos, antidepresivos y cognitivos. El presente trabajo estudió el efecto de la infusión de PA y drogas colinérgicas sobre la habituación. 40 ratones NMRI machos fueron divididos en 4 grupos: Control (n=10), Control Drogas (n=10), PA (n=10) y PA plus Drogas (n=10). La PA (1%) fue administrada vía oral (7.59±1.39 ml/día); escopolamina (2 mg/Kg), galantamina (1 mg/Kg) y nicotina (0.1 mg/Kg) fueron administrados vía intraperitoneal. Los ensayos conductuales incluyeron: laberinto de ansiedad (LA), campo abierto (CA) y enterramiento aversivo (EA). La habituación fue evaluada en 4 sesiones con duración de una semana cada una. PA mostró un efecto ansiolítico en el LA, combinada con nicotina potenció un efecto ansiogénico en el LA. Galantamina favoreció la habituación en CA, y escopolamina potenció el fenómeno de habituación en LA y disminuyó la conducta obsesivo-compulsiva en CA. En conclusión, la PA mostró un efecto ansiolítico y antidepresivo que potencia la deshabituación, combinada con nicotina indujo un efecto ansiogénico, galantamina favoreció la habituación y escopolamina disminuyó la conducta obsesivo­ compulsiva y favoreció la habituación motora indicando un posible efecto ansiolítico.

Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis.

BACKGROUND: As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy. OBJECTIVE: To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease. METHODS: NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods. FINDINGS: In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved. MAIN CONCLUSION: DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.

Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis

BACKGROUND As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy. OBJECTIVE To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease. METHODS NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods. FINDINGS In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved. MAIN CONCLUSION DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.

ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY.

Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY / Atividade da adenosina deaminase e níveis de proteina C reativa sérica como marcadores de gravidade na doença de Chagas

SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

Introdução e objetivo . A Doença de Chagas é um problema de saúde pública mundial. A disponibilidade de ferramentas diagnósticas para prever o desenvolvimento de miocardiopatia chagásica crônica é fundamental para reduzir a morbidade e a mortalidade. Aqui estudamos o valor prognóstico da atividade sérica da adenosina deaminase (ADA) e dos níveis de proteína C reativa (PCR) em indivíduos chagásicos. Métodos : 110 indivíduos: 28 saudáveis e 82 pacientes chagásicos foram divididos de acordo com a gravidade da doença em fase I (n = 35), II (n = 29) e III (n = 18). Para cada indivíduo foram feitos uma história médica, eletrocardiograma, radiografia de tórax e ecocardiografía transtorácica. O diagnóstico de Chagas foi confirmado por ELISA e MABA utilizando antígenos recombinantes, a atividade sérica da enzima ADA foi determinada por espectrofotometria, e os níveis séricos de PCR por ELISA. Resultados : os níveis de PCR e da atividade da ADA aumentaram linearmente em relação à fase da doença, sendo a PCR significativamente maior na fase III, e a ADA em todas as fases. Além disso, PCR e ADA foram correlacionados positivamente com parâmetros ecocardiográficos de remodelamento cardíaco e alterações eletrocardiográficas, e negativamente com a fração de ejeção. PCR e ADA foram mais elevadas em pacientes com índice cardiotorácico ≥ 50%, enquanto que a ADA foi maior em pacientes com alterações da repolarização ventricular. Finalmente, os níveis de PCR foram correlacionados positivamente com a atividade da ADA. Conclusão : ADA e PCR são marcadores prognósticos de disfunção e remodelamento cardíaco na Doença de Chagas, e devem ser incluídos na avaliação e acompanhamento dos pacientes.

Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE: The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS: We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS: These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

[Trypanosoma cruzi infection decreases malignant melanoma development and increases survival in C57BL/6 mice]. / La infección por Trypanosoma cruzi disminuye el desarrollo del melanoma maligno e incrementa la supervivencia en ratones C57BL/6.

Some infectious pathogens have the capacity to affect cancer progression. In the present paper we studied the effect of infection or immunization with Trypanosoma cruzi (Tc) against malignant melanoma development. We worked on 258 C57BL/6 male mice divided in five melanoma groups: control melanoma, melanoma Tc acutely infected, melanoma Tc chronically infected, melanoma Tc immunized and infected melanoma; and three control groups: healthy, Tc acutely infected and Tc chronically infected. 100.000 B16-BL6 melanoma cells were inoculated in the thigh of melanoma groups; 3 or 20 trypomastigotes/g were inoculated intraperitoneally in chronic or acute Tc groups, before the melanoma injection, respectively; melanoma Tc immunized were subcutaneously inoculated with 30.000 formaldehide-fixed epimastigotes diluted in complete Freund's adjuvant and the infected melanoma group was inoculated with melanoma cells obtained from melanoma Tc acutely infected mice. We evaluated survival, parasitemia, tumor volume and tumor histopathology. Results showed that in mice infected with Tc, the tumor development and survival were significantly lower as compared with control melanoma and melanoma Tc immunized. Histopathologically, the tumor displayed necrosis areas with melanin deposits, cytopathic degeneration and amastigotes in parasitophorous vacuoles. In conclusion, Tc inhibits the development of malignant melanoma, increasing C57BL/6 survival, a phenomena that could be related to the parasite tumoral invasive capacity, its ability to produce melanoma cell lysis and to induce a robust immune response.

La infección por Trypanosoma cruzi disminuye el desarrollo del melanoma maligno e incrementa la supervivencia en ratones C57BL/6 / Trypanosoma cruzi infection decreases malignant melanoma development and increases survival in C57BL/6 mice

Diversos agentes infecciosos interfieren en la progresión del cáncer. En esta investigación se estudió el efecto de la infección o inmunización con Trypanosoma cruzi (Tc) sobre el desarrollo del melanoma maligno. Se utilizaron 258 ratones machos C57BL/6 divididos en 5 grupos melanoma: melanoma control, melanoma Tc inmunizado, melanoma Tc agudo, melanoma Tc crónico y melanoma Tc infectado; 3 grupos controles: control sano, control Tc agudo, control Tc crónico. 100.000 células de melanoma B16-BL6 fueron inoculados vía intramuscular a los grupos melanoma; 3 ó 20 tripomastigotes/g de peso fueron inoculados vía intraperitoneal a los grupos Tc crónicos o Tc agudos previo a la inoculación del melanoma, respectivamente, el grupo melanoma Tc inmunizado fue inoculado con 30.000 epimastigotes fijados en formol y suspendidos en adyuvante completo de Freund, y el grupo melanoma Tc infectado fue inoculado con células de melanoma obtenidas de ratones melanoma Tc agudo. Se evaluó volumen tumoral, supervivencia, parasitemia e histopatología tumoral. Los grupos melanoma Tc: agudo, crónico y melanoma infectado, respectivamente, mostraron una disminución significativa del desarrollo tumoral y de la supervivencia al ser comparados con los grupos melanoma control e inmunizado. Los estudios histopatológicos mostraron áreas de necrosis asociadas con depósitos de melanina, degeneración citopática tumoral y amastigotes intracelulares contenidos en vacuolas parasitofóricas. En conclusión, Tc inhibe el desarrollo tumoral del melanoma maligno y aumenta la supervivencia de ratones C57BL/6, fenómeno que podría estar relacionado con la capacidad invasiva tumoral del parásito y a la respuesta inmune generada.

Some infectious pathogens have the capacity to affect cancer progression. In the present paper we studied the effect of infection or immunization with Trypanosoma cruzi (Tc) against malignant melanoma development. We worked on 258 C57BL/6 male mice divided in five melanoma groups: control melanoma, melanoma Tc acutely infected, melanoma Tc chronically infected, melanoma Tc immunized and infected melanoma; and three control groups: healthy, Tc acutely infected and Tc chronically infected. 100.000 B16-BL6 melanoma cells were inoculated in the thigh of melanoma groups; 3 or 20 trypomastigotes/g were inoculated intraperitoneally in chronic or acute Tc groups, before the melanoma injection, respectively; melanoma Tc immunized were subcutaneously inoculated with 30.000 formaldehide-fixed epimastigotes diluted in complete Freund´s adjuvant and the infected melanoma group was inoculated with melanoma cells obtained from melanoma Tc acutely infected mice. We evaluated survival, parasitemia, tumor volume and tumor histopathology. Results showed that in mice infected with Tc, the tumor development and survival were significantly lower as compared with control melanoma and melanoma Tc immunized. Histopathologically, the tumor displayed necrosis areas with melanin deposits, cytopathic degeneration and amastigotes in parasitophorous vacuoles. In conclusion, Tc inhibits the development of malignant melanoma, increasing C57BL/6 survival, a phenomena that could be related to the parasite tumoral invasive capacity, its ability to produce melanoma cell lysis and to induce a robust immune response.

[Risk factors associated with the diagnosis of chronic Chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela]. / Factores de riesgo asociados con el diagnóstico de miocardiopatía chagásica crónica en individuos seropositivos del estado Barinas, Venezuela.

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual. Risk factors were determined through binary logistic regression. Results showed that 81 patients (70,4%; CI 95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC 95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC 95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC 95% = 4.0-8.2) in phase III. In a one year period, two patients in phase III died of heart failure. The diagnosis of CChM was associated with hunting practice, maternal history of cardiopathies, chewing chimó, medical history of hypertension and apex beat visible; it was negatively associated with canned and preserved foods ingest. In conclusion the CChM diagnosis has high frequency in seropositive individuals in Barinas and heart failure prevention must be based on an early medical attention and educative strategies in order to control risk factors.

Factores de riesgo asociados con el diagnóstico de miocardiopatía chagásica crónica en individuos seropositivos del estado Barinas, Venezuela / Risk factors associated with the diagnosis of chronic chagasic miocardiopathy in seropositive individuals from Barinas state, Venezuela

Se determinaron los factores de riesgo asociados al diagnóstico de miocardiopatía chagásica crónica (MChC) en 115 individuos seropositivos para anticuerpos anti-Trypanosoma cruzi, en el Estado Barinas, Venezuela. La seropositividad fue determinada mediante ELISA y MABA (Multiple Antigen Blot Assay) y el diagnóstico de MChC fue establecido mediante electrocardiografía y ecocardiografía. A cada individuo se le realizó una historia clínica completa que incluyó antecedentes epidemiológicos, antecedentes patológicos personales y familiares, y hábitos psicobiológicos; además se realizó una encuesta donde se interrogó acerca de factores de riesgo socioeconómicos, psicosociales y de hábitos alimentarios. Los factores de riesgo fueron establecidos mediante una regresión logística binaria. Los resultados mostraron que 81 (70,4%; IC95% = 66,4-74,4) pacientes reunían criterios para el diagnóstico de MChC, de los cuales 74 (64,4%; IC95% = 60,2-68,6) estaban en Fase II (6,1%; IC95% = 4,0-8,2) y 7 en Fase III, mientras que 34 (29,6%; IC95% = 25,5-33,5) estaban en Fase I. En el periodo de 1 año murieron 2 individuos en Fase III. El diagnóstico de MChC estuvo asociado con la práctica de la caza de animales silvestres, el consumo de chimó, antecedentes maternos de cardiopatía, antecedentes personales de hipertensión arterial y un ápex visible, como factores de riesgo, mientras que: el consumo de alimentos preservados y enlatados constituyó un factor de protección. En conclusión, el diagnóstico de MChC tiene una alta frecuencia en individuos seropositivos del estado Barinas y la prevención del desarrollo de insuficiencia cardíaca debe basarse en la atención médica precoz y en medidas educativas para controlar los factores de riesgo.

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual. Risk factors were determined through binary logistic regression. Results showed that 81 patients (70,4%; CI95% = 66.4-74.4) had criteria for CChM, of which 74 (64.4%; IC95% = 60.2-68.6) were in phase II; while 34 (29.6%; IC95% = 25.5-33.5) were in phase I of the disease and 7 (6.1%; IC95% = 4.0-8.2) in phase III. In a one year period, two patients in phase III died of heart failure. The diagnosis of CChM was associated with hunting practice, maternal history of cardiopathies, chewing chimó, medical history of hypertension and apex beat visible; it was negatively associated with canned and preserved foods ingest. In conclusion the CChM diagnosis has high frequency in seropositive individuals in Barinas and heart failure prevention must be based on an early medical attention and educative strategies in order to control risk factors.

Factores de riesgo asociadas a la enfermedad Chagas en comunidades rurales en Lara, Venezuela / Comparative analysis of risk factors associated with Chagas disease in Lara State, Venezuela

La reinfestación por vectores secundarios es un problema emergente para la transmisión de la enfermedad de Chagas. Objetivo: Realizar un análisis comparativo para determinar los factores de riesgo asociados a la seropositividad en humanos. Materiales y Métodos: Estudio ecoentomológico y seroepidemiológico realizado en dos comunidades del Estado Lara, infestadas por Triatoma maculata o Panstrongylus geniculatus. Resultados: Guariquito (bosque húmedo tropical templado intervenido para actividad agrícola) mostró una seroprevalencia (SP) canina del 33,33 % y humana del 6,81 % asociada a: menores de 40 años, vector en vivienda anterior, comer animales de caza, migración rural, reconocimiento y contacto con el vector, siendo factores protectores conocimiento del vector y haber vivido en ranchos; infestación 20,45 %, colonización 0 % e infección 18,75 %; ninfas capturadas en cuevas de Xenarthra, los cuales se encontraron infectados (20 %), al igual que Rodentias (25 %). Cauderales (región semidesértica): SP humana del 11,56 % asociada a: mayores de 40 años, vector en vivienda anterior tipo rancho, comer animales de caza, migración rural, reconocimiento y contacto con el vector, siendo factor protector presencia de caninos en la vivienda, los cuales fueron seronegativos; infestación 5,51 %, colonización 0 % e infección-vivienda 0 %; ninfas y Chiropteras no infectadas fueron capturadas en Cactáceas. Conclusión: Panstrongylus geniculatus es responsable de la transmisión reciente en regiones intervenidas de bosque tropical húmedo y con reservorios de los géneros Xenarthra y Rodentia; Tm tiene capacidad vectorial limitada debido a bajos índices de infección producto de sus fuentes de alimento.

Reinfestation by secondary vectors is an emerging problem for h g ’ i e e smission. Objective: To make a comparative analysis and to identify risk factors associated with human seropositivity. Methods: We have done and ecoentomological and seroepidemiologic study in two communities in Lara state, infested by Triatoma maculata or Panstrongylus geniculatus. Results: Guariquito (temperate rainforest, human intervened for agricultural activity) showed 33,33 % og’ e op ev le ce (SP) 6,81 % hum SP associated with: individuals under 40 years, vector infestation of previous house, eating hunting animals, rural migration, vector recognition or contact; protective factors were: knowledge about vectors and used to live in dwellings; 20,45 % infestation, 0% colonization and 18,75 % infection; nymphs were capture in Xenarthra caves, which were found infected (20 %), as well as Rodentias (25 %). Cauderales (semi-desert region) showed 11,56 % human SP associated with: individuals older than 40 years, vector presence in dwellings, eating wild animals, rural migration, recognition and vector contact; as protective factors presence of dogs in the house, which were seronegative; 5,51 % infestation, 0 % colonization or infection indexes; non-infected Chiropteras and Tm nymphs were captured in Cactaceae. Conclusion: Panstrongylus geniculatus is the vector responsible for recent transmission of Chagas disease in tropical rain forest regions, where human intervention is in evolution and reservoirs of genera Xenarthra and Rodentia are present, while Tm has a limited vector capacity because of their low rates of infection as consequence of their food sources.

Antígenos parasitarios de O-Glicosilación incompleta: Un enfoque inmunoterapeutico contra el cáncer / Incomplete O-Glycosylation parasite antigens: An immunotherapeutic approach against cancer

Es cada vez mayor la evidencia experimental y clínica de que el sistema inmune interviene activamente en la patogénesis y el control de la progresión tumoral. Una respuesta antitumoral efectiva depende de la correcta interacción de diversos componentes del sistema inmune, como las células presentadoras de antígeno y diferentes sub-poblaciones de células T. Sin embargo, los tumores malignos desarrollan numerosos mecanismos para evadir su reconocimiento y eliminación. Diversos estudios reportan que estructuras asociadas a tumor tales como los antígenos Tn y sialil-Tn se expresan en algunos parásitos protozoarios y helmintos, planteando numerosas interrogantes a nivel de la interacción parásito-hospedador. Considerando que existe una correlación negativa entre ciertas infecciones parasitarias y el desarrollo de cáncer, los antígenos de O-glicosilación incompleta obtenidos de parásitos podrían ser potenciales estructuras miméticas para la inducción de respuestas cruzadas contra antígenos tumorales. Actualmente, el área de la glicobiología del cáncer tiene muchas expectativas para encontrar solución a uno de los grandes problemas de salud que afecta a la población tanto desde el punto de vista económico como social.

There is increasing experimental and clinical evidence that the immune system plays an active role in the pathogenesis and control of tumor progression. An effective antitumor response depends on the correct interaction of the various components of the immune system, such as antigen presenting cells and sub-populations of T cells. However, malignant tumors develop numerous mechanisms to evade recognition and elimination. Several studies report that structures associated with tumors such as Tn and sialyl-Tn antigens are expressed in some protozoan parasites and helminths, thus raising many questions regarding parasite-host interactions. The negative correlation between certain parasite infections and cancer development suggests that antigens from incomplete O-glycosylation obtained from parasites could represent potential mimetic structures for inducing cross responses against tumor antigens. Currently, cancer glycobiology is a promising area in the search for a solution to one of the major health problems affecting the population both from an economic and a social perspective.

O-glicosilación incompleta en células cancerígenas y parásitos: Importancia biomédica / Incomplete O-glycosylation in cancer cells and parasites: biomedical significance

Durante la carcinogénesis ocurren modificaciones importantes en la glicosilación, entre ellas la elongación incompleta de las cadenas sacarídicas con uniones de tipo O y la exposición de antígenos que en condiciones normales estaban ocultos, los cuales son reconocidos por componentes de la respuesta inmune que promueven o limitan el crecimiento tumoral. Diversos estudios reportan que estructuras asociadas a tumor tales como los antígenos Tn y sialil-Tn se expresan en algunos parásitos protozoarios y helmintos, planteando numerosas interrogantes a nivel de la interacción parásito-hospedador. Considerando que existe una correlación negativa entre ciertas infecciones parasitarias y el desarrollo de cáncer, los antígenos de O-glicosilación incompleta obtenidos de parásitos podrían ser potenciales blancos en la inmunoterapia del cáncer.

During carcinogenesis important modifications in glycosylation occur, among them incomplete elongation of the saccharide chains with type O bonds and the exposure of antigens that were hidden under normal conditions, which are recognized by components of the immune system which promote or limit tumor growth. Several studies report that tumor-associated structures, such as Tn and sialil-Tn, are expressed in some parasites protozoa and helminths, and pose many questions regarding parasite-host interaction. Considering the negative correlation between certain parasite infections and cancer development, antigens from incomplete O-glycosylation obtained from parasites could be potential targets in cancer immunotherapy.

Molecular epidemiologic source tracking of orally transmitted Chagas disease, Venezuela.

Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing.

Electrophysiological and pharmacological evaluation of the nicotinic cholinergic system in chagasic rats.

BACKGROUND: Two theories attempt to explain the changes observed in the nicotinic acetylcholine receptors (nAChRs) in chagasic cardiomyopathy. The neurogenic theory proposes that receptor changes are due to loss of intracardiac ganglia parasympathetic neurons. The immunogenic theory proposes that the nAChRs changes are the result of autoantibodies against these receptors. Both theories agreed that nAChRs functional expression could be impaired in Chagas disease. METHODS: We evaluated nAChRs functional integrity in 54 Sprague Dawley rats, divided in two groups: healthy and chronic chagasic rats. Rats were subjected to electrocardiographic studies in the whole animal under pentobarbital anesthesia, by isolation and stimulation of vagus nerves and in isolated beating hearts (Langendorff's preparation). RESULTS: Nicotine, 10 µM, induced a significant bradycardia in both groups. However, rats that had previously received reserpine did not respond to nicotine stimulation. ß-adrenergic stimulation, followed by nicotine treatment, induced tachycardia in chagasic rats; while inducing bradycardia in healthy rats. Bilateral vagus nerve stimulation induced a significantly higher level of bradycardia in healthy rats, compared to chagasic rats; physostigmine potentiated the bradycardic response to vagal stimulation in both experimental groups. Electric stimulation (e.g., ≥ 2 Hz), in the presence of physostigmine, produced a comparable vagal response in both groups. In isolated beating-heart preparations 1 µM nicotine induced sustained bradycardia in healthy hearts while inducing tachycardia in chagasic hearts. Higher nicotine doses (e.g.,10 - 100 uM) promoted the characteristic biphasic response (i.e., bradycardia followed by tachycardia) in both groups. 10 nM DHßE antagonized the effect of 10 µM nicotine, unmasking the cholinergic bradycardic effect in healthy rats only. 1 nM α-BGT alone induced bradycardia in healthy hearts but antagonized the 10 µM nicotine-induced tachycardia in chagasic rats. In healthy but not in chagasic hearts, 10 µM nicotine shortened PQ and PR interval, an effect counteracted by MA, DHßE and αBGT CONCLUSION: Our results suggest that cholinergic function is impaired in chronic Chagas disease in rats, a phenomena that could be related to alteration on the nAChR expression.

[Adenosine deaminase in severe combined immunodeficiency syndrome]. / Adenosin deaminasa en el síndrome de inmunodeficiencia combinada severa.

Adenosine deaminase is an enzyme of the purine metabolism whose function is to convert adenosine to inosine and deoxyadenosine to deoxyinosine. The ecto-ADA1 binding to the cell surface through CD26 contributes to the regulation of cytokines and stimulates the proliferation of T cells by activating CD45. The deficiency of this enzyme generates the severe combined immunodeficiency syndrome, characterized by the accumulation of deoxyadenosine and adenine metabolites, which have toxic effects on lymphocytes, affecting DNA synthesis and consequently, clonal expansion. Early diagnosis of this immunodeficiency is essential, as it significantly reduces morbidity and mortality associated with recurrent infections. Recent advances in molecular biology and genetics have led to the identification of genetic defects of many primary immunodeficiencies and the development of promising diagnostic tools and treatment.

Electrocardiography repolarization abnormalities are characteristic signs of acute chagasic cardiomyopathy / Los trastornos de la repolarización ventricular son signos característicos de la cardiomiopatía chagásica aguda

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi (T. cruzi), whose reemergence as oral outbreaks is currently a public health problem in Venezuela. T. cruzi infection induces myocardial damage; which according to the microvascular theory, is derived from parasite-mediated disruption of the endothelium, inducing platelet aggregation and ischemia. In order to determine whether ventricular repolarization disorders observed in human patients are characteristic signs of the disease that can be reproduced in NMRI mice; we studied 12 patients with a well documented diagnosis of acute Chagas disease, based on epidemiological, clinical, parasitological and molecular data. Also, T. cruzi isolates from the blood of human patients from other Venezuelan geographical regions were characterized and inoculated in albino NMRI mice. A standard 12-lead and bipolar electrocardiogram configuration were done in human patients during the acute phase of the disease and in mice, after three weeks of infection. Results in human showed repolarization disorders, characterized by: negative, bimodal or biphasic T waves, ST segment depression or elevation and early repolarization. In mice a significant increase in T wave amplitude, increased QT interval duration and elevation or depression of ST segment were observed. These findings were evidenced in all infected mice, suggesting that electrocardiographic repolarization abnormalities in a well documented clinical and epidemiological context are signs that increase the sensitivity for the diagnosis of acute Chagas´ disease.

La enfermedad de Chagas es una hemoparasitosis causada por Trypanosoma cruzi (T. cruzi), cuya re-emergencia como epidemias por contaminación oral es actualmente un problema de salud pública en Venezuela. La infección por T. cruzi causa miocarditis; que de acuerdo con la teoría microvascular deriva del daño del endotelio vascular, al inducir agregación plaquetaria e isquemia. Con el objetivo de demostrar que los trastornos de repolarización son signos propios de la miocarditis chagásica aguda (MChA) reproducibles en modelos animales, estudiamos 12 pacientes humanos con diagnostico bien documentado de MChA, basado en datos epidemiológicos, clínicos, parasitológicos y moleculares. A partir de la sangre de los pacientes obtuvimos los aislados de T cruzi, los caracterizamos molecularmente y los inoculamos en ratones albinos NMRI; paralelamente, aislados de T cruzi provenientes de otras regiones de Venezuela fueron también ensayados. Tanto en los pacientes humanos como en los ratones con Chagas agudo, se realizaron estudios electrocardiográficos en 12 derivaciones estándares y en configuración bipolar, respectivamente. En humanos observamos trastornos de la repolarización ventricular caracterizados por: onda T negativa, bimodal o bifásica; elevación o depresión del segmento ST y despolarizaciones tempranas. En ratones observamos incrementos en la amplitud de la onda T, aumento en la duración del intervalo QT y elevación o depresión del segmento ST. Estos hallazgos fueron evidenciados en todos los ratones infectados con los diferentes aislados, sugiriendo que los trastornos de repolarización, en un adecuado y bien documentado contexto epidemiológico y clínico, son signos que aumentan la sensibilidad para el diagnóstico de MChA.

Adenosin deaminasa en el síndrome de inmunodeficiencia combinada severa / Adenosine deaminase in severe combined immunodeficiency syndrome

La Adenosin deaminasa es una enzima del metabolismo de las purinas cuya función es transformar la adenosina en inosina y la desoxiadenosina en desoxiinosina. La unión de ecto-ADA1 a la superficie celular a través de CD26 contribuye a la regulación de citocinas y estimula la proliferación de células T mediante la activación de CD45. La deficiencia de esta enzima genera el síndrome de inmunodeficiencia combinada severa, caracterizado por la acumulación de metabolitos de adenina y desoxiadenosina, los cuales tienen efectos tóxicos sobre los linfocitos, afectando así la síntesis de ADN y en consecuencia la expansión clonal. Un diagnóstico temprano de esta inmunodeficiencia es esencial ya que reduce notablemente la morbilidad y mortalidad asociada con infecciones recurrentes. Los avances recientes en biología molecular y genética han conducido a la identificación de los defectos genéticos de muchas de las inmunodeficiencias primarias y al desarrollo de herramientas de diagnóstico y tratamiento prometedoras.

Adenosine deaminase is an enzyme of the purine metabolism whose function is to convert adenosine to inosine and deoxyadenosine to deoxyinosine. The ecto-ADA1 binding to the cell surface through CD26 contributes to the regulation of cytokines and stimulates the proliferation of T cells by activating CD45. The deficiency of this enzyme generates the severe combined immunodeficiency syndrome, characterized by the accumulation of deoxyadenosine and adenine metabolites, which have toxic effects on lymphocytes, affecting DNA synthesis and consequently, clonal expansion. Early diagnosis of this immunodeficiency is essential, as it significantly reduces morbidity and mortality associated with recurrent infections. Recent advances in molecular biology and genetics have led to the identification of genetic defects of many primary immunodeficiencies and the development of promising diagnostic tools and treatment.

Electrocardiography repolarization abnormalities are characteristic signs of acute chagasic cardiomyopathy.

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi (T. cruzi), whose reemergence as oral outbreaks is currently a public health problem in Venezuela. T. cruzi infection induces myocardial damage; which according to the microvascular theory, is derived from parasite-mediated disruption of the endothelium, inducing platelet aggregation and ischemia. In order to determine whether ventricular repolarization disorders observed in human patients are characteristic signs of the disease that can be reproduced in NMRI mice; we studied 12 patients with a well documented diagnosis of acute Chagas disease, based on epidemiological, clinical, parasitological and molecular data. Also, T. cruzi isolates from the blood of human patients from other Venezuelan geographical regions were characterized and inoculated in albino NMRI mice. A standard 12-lead and bipolar electrocardiogram configuration were done in human patients during the acute phase of the disease and in mice, after three weeks of infection. Results in human showed repolarization disorders, characterized by: negative, bimodal or biphasic T waves, ST segment depression or elevation and early repolarization. In mice a significant increase in T wave amplitude, increased QT interval duration and elevation or depression of ST segment were observed. These findings were evidenced in all infected mice, suggesting that electrocardiographic repolarization abnormalities in a well documented clinical and epidemiological context are signs that increase the sensitivity for the diagnosis of acute Chagas' disease.

[Morphometric analysis of Panstrongylus geniculatus (Heteroptera: Reduviidae) from Caracas City, Venezuela]. / Análisis morfométrico de Panstrongylus geniculatus de Caracas, Venezuela.

INTRODUCTION: In recent years, the assassin bug, Panstrongylus geniculatus, has been found infected with Trypanosoma cruzi in rural and urban areas of Caracas, Venezuela. Although historically this insect has been considered a forest species, it has become adapted to more urban artificial environments. OBJECTIVE: The presence of sexual dimorphism was determined as an indicator of adaptation to domiciles. MATERIAL AND METHODS: By Generalized Procrustes Analysis (GPA) and Elliptical Fourier Analysis (EFA), the isometric size and shape of wings, head and pronotums of P. geniculatus was assessed for actively and passively captured specimens. These were collected within domiciles in urban areas of Petare and Altagracia in Caracas City, and from rural or wild environments of Sanare in Andres Eloy Blanco in the state of Lara. RESULTS: Sexual dimorphism was observed in the Sanare specimens, with female wings consistently larger than male wings. Similarly, female wings and heads from bugs captured in Caracas were smaller than those of female bugs captured in Sanare. No significative differences in the conformation of the pronotum were found between male and female bugs. CONCLUSIONS: Based on the assumption that the sexual dimorphism of bugs is reflected by smaller size in domesticated triatomines than in wild bugs, the conclusion is that Caracas P. geniculatus has become adapted to living indoors. This represents an additional risk factor for the Chagas disease transmission in Caracas.