Synthesis, Optical Properties, and Antiproliferative Evaluation of NBD-Triterpene Fluorescent Probes.

A fluorescent labeling protocol for hydroxylated natural compounds with promising antitumor properties has been used to synthesize, in yields of 72-86%, 12 derivatives having fluorescent properties and biological activity. The reagent used for the synthesis of these fluorescent derivatives was 7-nitrobenzo-2-oxa-1,3-diazole chloride (NBD-Cl). The linkers employed to bind the NBD-Cl reagent to the natural compounds were ω-amino acids (Aa) of different chain lengths. The natural triterpene compounds chosen were oleanolic and maslinic acid, as their corresponding 28-benzylated derivatives. Thus, 12 NBD-Aa-triterpene conjugates have been studied for their optical fluorescence properties and their biological activities against cell proliferation in three cancer cell lines (B16-F10, HT-29, and HepG2), compared with three nontumor cell lines (HPF, IEC-18, and WRL68) from different tissues. The results of the fluorescence study have shown that the best fluorescent labels are those in which the ω-amino acid chain is shorter, and the carboxylic group is not benzylated. Analysis by confocal microscopy showed that these compounds were rapidly incorporated into cells in all three cancer cell lines, with these same derivatives showing the highest toxicity against the cancer cell lines tested. Then, the fluorescent labeling of these NBD-Aa-triterpene conjugates enabled their uptake and subcellular distribution to be followed in order to probe in detail their biological properties at the cellular and molecular level.

Hyaluronic acid and human/bovine serum albumin shelled nanocapsules: Interaction with mucins and in vitro digestibility of interfacial films.

Liquid lipid nanocapsules are oil droplets surrounded by a protective shell, which enable high load and allow controlled delivery of lipophilic compounds. However, their use in food formulations requires analysing their digestibility and interaction with mucin. Here, serum albumins and hyaluronic acid shelled olive oil nanocapsules are analysed to discern differences between human and bovine variants, the latter usually used as model system. Interfacial interaction of albumins and hyaluronic acid reveals that human albumin presents limited conformational changes upon adsorption, which increase by complexation with the polysaccharide present at the interface. The latter also promotes hydrophobic interactions with mucin, especially at pH 3 and protects albumin interfacial layer under in vitro gastric digestion. The interfacial unfolding induced in human albumin by hyaluronic acid facilitates in vitro lipolysis while its limited conformational changes provide the largest protection against in vitro lipolysis.

Applications of serum albumins in delivery systems: Differences in interfacial behaviour and interacting abilities with polysaccharides.

One of the major applications of Serum Albumins is their use as delivery systems for lipophilic compounds in biomedicine. Their biomedical application is based on the similarity with Human Serum Albumin (HSA), as a fully biocompatible protein. In general, Bovine Serum Albumin (BSA) is treated as comparable to its human homologue and used as a model protein for fundamental studies since it is available in high amounts and well understood. This protein can act as a carrier for lipophilic compounds or as protective shell in an emulsion-based vehicle. Polysaccharides are generally included in these formulations in order to increase the stability and/or applicability of the carrier. In this review, the main biomedical applications of Albumins as drug delivery systems are first presented. Secondly, the differences between BSA and HSA are highlighted, exploring the similarities and differences between these proteins and their interaction with polysaccharides, both in solution and adsorbed at interfaces. Finally, the use of Albumins as emulsifiers for emulsion-based delivery systems, concretely as Liquid Lipid Nanocapsules (LLNs), is revised and discussed in terms of the differences encountered in the molecular structure and in the interfacial properties. The specific case of Hyaluronic Acid is considered as a promising additive with important applications in biomedicine. The literature works are thoroughly discussed highlighting similarities and differences between BSA and HSA and their interaction with polysaccharides encountered at different structural levels, hence providing routes to control the optimal design of delivery systems.

Pharmaceutical care practice in patients with chronic kidney disease / Seguimiento farmacoterapéutico en pacientes con insuficiencia renal crónica

Introduction: The impact of chronic kidney disease in health is no longer just a patient-physician issue, not only in terms of the increase in the number of patients diagnosed, but also regarding the human and economic cost for health systems. That is why Pharmaceutical Care should include SOPs structured by criteria reached by consensus to conduct Pharmaceutical Care Practice, which will enable to prevent, identify and solve any negative outcomes in patients that are associated with medication. Objectives: To learn about the types of problems related to medications and negative outcomes associated with drugs that can be detected, prevented and solved in patients with chronic kidney disease, through pharmaceutical care practice. Method: A quasi-experimental study was conducted, with a descriptive and retrospective design, in 47 hospitalized patients diagnosed with chronic kidney disease in a high-complexity clinic. Using the DADER methodology, their pharmacological treatments were analyzed, and it was verified whether they were necessary, effective and safe, taking into account variables such as the negative outcomes associated with medication, medication-related problems, pharmaceutical interventions, and kidney failure stages. Results: Fifty-one (51) negative outcomes associated with medication were detected during the study; of these, 13.72% were for Necessity, 45.1% for Effectiveness and 41.18% for Safety. A total of 41 pharmaceutical interventions were conducted, 35 were accepted and 6 were not accepted. Of these 6 non-accepted interventions, 3 health problems were not solved, 12 dose re-adjustments were conducted, with cefepime as the drug with the highest number of dose adjustments; most patients were in Stage III and V of CKD, and its main cause was hypertension and Diabetes Mellitus II. Conclusion: The most prevalent NOMs were those for Non-Quantitative Insecurity, therefore these are a highly prevalent problem. This highlights the importance of this public health problem and its major clinical, social and economic impact, associated with Chronic Kidney Disease; therefore, it is necessary to involve all health professionals and patients, to obtain as a result a better use of medications, the prevention of NOMs and a reduction in morbidity associated with pharmacotherapy (AU)

Introducción: El impacto de la insuficiencia renal crónica en la salud ya dejó de ser solo un problema paciente-médico, no solo por el aumento del número de pacientes diagnosticados, sino por el costo humano y económico que ocasiona en los sistemas de salud. Es por ello que la Atención Farmacéutica debe incluir procedimientos normalizados de trabajo que se encuentren estructurados por criterios consensuados para realizar el Seguimiento Farmacoterapéutico, que permitirá la prevención, identificación y resolución de resultados negativos asociados a la medicación en los pacientes. Objetivos: Conocer los tipos de problemas relacionados con los medicamentos y los resultados negativos asociados a los medicamentos que se pueden detectar, prevenir y resolver en pacientes con insuficiencia renal crónica mediante el seguimiento farmacoterapéutico. Método: Se realizó un estudio de tipo cuasi experimental, con diseño descriptivo y retrospectivo, en 47 pacientes hospitalizados, diagnosticados de Insuficiencia Renal Crónica, en una clínica de alta complejidad, empleando la metodología DADER. Se analizaron sus tratamientos farmacológicos y se verificaron si estos fueron necesarios, efectivos y seguros, teniendo en cuenta variables como los resultados negativos asociados a la medicación, los problemas relacionados con la medicación, las intervenciones farmacéuticas y los estadios de la insuficiencia renal. Resultados: Se detectaron 51 resultados negativos asociados a la medicación durante el estudio, el 13,72% fueron de necesidad, el 45,1% de efectividad y el 41,18% de seguridad. Se realizaron un total de 41 intervenciones farmacéuticas, 35 fueron aceptadas y 6 no fueron aceptadas; de estas 6 intervenciones no aceptadas, 3 problemas de salud no se solucionaron, se realizaron 12 reajustes de dosis, siendo el cefepime el medicamento con mayor número de reajustes. El mayor número de pacientes se encontraban en el estadio III y V de la IRC y su causa principal era la HTA y la DM II. Conclusión: Los RNM de mayor prevalencia fueron los de inseguridad no cuantitativa, por tanto son un problema de elevada prevalencia, lo que pone de manifiesto la trascendencia de este problema de salud pública y de sus importantes repercusiones clínicas, sociales y económicas. Estas están asociadas a la insuficiencia renal crónica, por lo que es necesario involucrar a todos los profesionales sanitarios y los pacientes, para obtener como resultado una mejor utilización de los medicamentos, una prevención de los RNM y una reducción de la morbilidad asociada a la farmacoterapia (AU)

Pharmaceutical care practice in patients with chronic kidney disease.

INTRODUCTION: The impact of chronic kidney disease in health is no longer just a patient-physician issue, not only in terms of the increase in the number of patients diagnosed, but also regarding the human and economic cost for health systems. That is why Pharmaceutical Care should include SOPs structured by criteria reached by consensus to conduct Pharmaceutical Care Practice, which will enable to prevent, identify and solve any negative outcomes in patients that are associated with medication. Objectives: To learn about the types of problems related to medications and negative outcomes associated with drugs that can be detected, prevented and solved in patients with chronic kidney disease, through pharmaceutical care practice. METHOD: A quasi-experimental study was conducted, with a descriptive and retrospective design, in 47 hospitalized patients diagnosed with chronic kidney disease in a high-complexity clinic. Using the DADER methodology, their pharmacological treatments were analyzed, and it was verified whetherthey were necessary, effective and safe, taking into account variables such as the negative outcomes associated with medication, medication-related problems, pharmaceutical interventions, and kidney failure stages. Results: Fifty-one (51) negative outcomes associated with medication were detected during the study; of these, 13.72% were for Necessity, 45.1% for Effectiveness and 41.18% for Safety. A total of 41 pharmaceutical interventions were conducted, 35 were accepted and 6 were not accepted. Of these 6 non-accepted interventions, 3 health problems were not solved, 12 dose re-adjustments were conducted, with cefepime as the drug with the highest number of dose adjustments; most patients were in Stage III and V of CKD, and its main cause was hypertension and Diabetes Mellitus II. CONCLUSION: The most prevalent NOMs were those for Non-Quantitative Insecurity, therefore these are a highly prevalent problem. This highlights the importance of this public health problem and its major clinical, social and economic impact, associated with Chronic Kidney Disease; therefore, it is necessary to involve all health professionals and patients, to obtain as a result a better use of medications, the prevention of NOMs and a reduction in morbidity associated with pharmacotherapy.

Introducción: El impacto de la insuficiencia renal crónica en la salud ya dejó de ser solo un problema paciente-médico, no solo por el aumento del número de pacientes diagnosticados, sino por el costo humano y económico que ocasiona en los sistemas de salud. Es por ello que la Atención Farmacéutica debe incluir procedimientos normalizados de trabajo que se encuentren estructurados por criterios consensuados para realizar el Seguimiento Farmacoterapéutico, que permitirá la prevención, identificación y resolución de resultados negativos asociados a la medicación en los pacientes.Objetivos: Conocer los tipos de problemas relacionados con los medicamentos y los resultados negativos asociados a los medicamentos que se pueden detectar, prevenir y resolver en pacientes con insuficiencia renal crónica mediante el seguimiento farmacoterapéutico. Método: Se realizó un estudio de tipo cuasi experimental, con diseño descriptivo y retrospectivo, en 47 pacientes hospitalizados, diagnosticados de Insuficiencia Renal Crónica, en una clínica de alta complejidad, empleando la metodología DADER. Se analizaron sus tratamientos farmacológicos y se verificaron si estos fueron necesarios, efectivos y seguros, teniendo en cuenta variables como los resultados negativos asociados a la medicación, los problemas relacionados con la medicación, las intervenciones farmacéuticas y los estadios de la insuficiencia renal.Resultados: Se detectaron 51 resultados negativos asociados a la medicación durante el estudio, el 13,72% fueron de necesidad, el 45,1% de efectividad y el 41,18% de seguridad. Se realizaron un total de 41 intervenciones farmacéuticas, 35 fueron aceptadas y 6 no fueron aceptadas; de estas 6 intervenciones no aceptadas, 3 problemas de salud no se solucionaron, se realizaron 12 reajustes de dosis, siendo el cefepime el medicamento con mayor número de reajustes. El mayor número de pacientes se encontraban en el estadio III y V de la IRC y su causa principal era la HTA y la DM II.Conclusión: Los RNM de mayor prevalencia fueron los de inseguridad no cuantitativa, por tanto son un problema de elevada prevalencia, lo que pone de manifiesto la trascendencia de este problema de salud pública y de sus importantes repercusiones clínicas, sociales y económicas. Estas están asociadas a la insuficiencia renal crónica, por lo que es necesario involucrar a todos los profesionales sanitarios y los pacientes, para obtener como resultado una mejor utilización de los medicamentos, una prevención de los RNM y una reducción de la morbilidad asociada a la farmacoterapia.

Effect of cross-linker glutaraldehyde on gastric digestion of emulsified albumin.

Human serum albumin (HSA) has been shown to be an ideal protein for nanoparticle preparation. These are usually prepared by using cross linker agents such as glutaraldehyde (GAD). Liquid lipid nanocapsules (LLN) constitute a new generation of nanoparticles more biocompatible and versatile for oral delivery of lipophylic drugs. The first barrier that an orally administered formulation must cross is the gastrointestinal tract. Hence, it is crucial to address the impact of gastrointestinal digestion on these structures in order to achieve an optimal formulation. This study evaluates the effect of gastric digestion on HSA emulsions structured with GAD as a model substrate for the preparation of LLN. This is done by SDS-PAGE, emulsion microstructure, and interfacial tension techniques. Our results demonstrate that the cross- linking procedure with GAD strongly inhibits pepsin digestion by formation of inter- and/or intramolecular covalent bonds between substrate amino acids. Emulsification of HSA also protects from gastric digestion probably by the orientation of the HSA molecule, which exposes the majority of pepsin cleaving sites preferably to the hydrophobic part of the oil-water interface. In this emulsified HSA, cross-linking with GAD at the interface promotes structural modifications on the HSA interfacial layer, restricting the access of pepsin to cleavage sites. We identify interfacial aspects underlying enzymatic hydrolysis of the protein. Assuring that HSA-GAD structures resist passage through the gastric compartment is crucial is important towards the rational design of oral delivery systems and the first step to get the complete digestion profile.

Empleo de antibióticos en situaciones sin diagnóstico de enfermedad infecciosa por los residentes de posgrado del Hospital Vargas de Caracas

Objetivo: Conocer las razones para el empleo de antibióticos en situaciones sin diagnóstico de enfermedad infecciosa, por parte de los residentes de posgrado del Hospital Vargas de Caracas. Material y métodos: Estudio analítico y comparativo mediante la aplicación de un cuestionario anónimo para la evaluación de conocimientos de médicos residentes, tanto del área médica como del área quirúrgica, con cinco preguntas cerradas para indagar en el conocimiento de los residentes sobre algunos motivos que justifican un uso racional de antibióticos y para detallar las razones que motivan el empleo de antibióticos en situaciones sin indicación formal. Resultados y Conclusiones: Fueron evaluados 73 residentes, donde un porcentaje no despreciable considera que la mayoría de las infecciones requieren tratamiento antibiótico y que a su vez lo indican en enfermedades con diagnóstico no establecido con el objeto de prevenir complicaciones de enfermedades infecciosas no tratadas a tiempo o de prevenir sobreinfecciones. La mayoría conoce el concepto de daño colateral antibiótico, sin embargo, esto no parece ser una limitante al momento del empleo indiscriminado de los mismos sin indicación formal o diagnóstico etiológico establecido. No hubo diferencia estadística significativa en los motivos de indicación antibiótica entre los grupos investigados: residentes del área médica vs residentes del área quirúrgica.

Objective: To determine the reasons for the use of antibiotics in situations without diagnosis of infectious disease by Caracas Vargas Hospital residents. Methods: Analytical and comparative study by the application of an anonymous questionnaire to assess knowledge of medical residents, in the medical field and surgical areas, with five closed questions to ascertain the knowledge of residents about some reasons for the rational use of antibiotics and to detail the reasons for the use of antibiotics in situations without formal indication. Results and Conclusions: A total of 73 residents were evaluated, and a significant percentage considered that most infections require antibiotic treatment and they prescribe them in diseases with diagnosis not established in order to prevent complications of infectious diseases not treated at time or to prevent secondary infections. Most of them know the concept of antibiotic collateral damage, however, this does not appear to be a limitation upon the indiscriminate use of them without formal indication or etiologic diagnosis established. There were no statistically significant differences in the reasons for antibiotic prescription between the investigated groups: medical versus surgical resident areas.

Analysis of the Photophysical Behavior and Rotational-Relaxation Dynamics of Coumarin 6 in Nonionic Micellar Environments: The Effect of Temperature.

The photodynamics of Coumarin 6 have been investigated in three nonionic micellar assemblies, i.e., n-dodecyl-ß-D-maltoside (ß-C12G2), p-tert-octyl-phenoxy polyethylene (9.5) ether (Triton X-100 or TX100) and n-dodecyl-hexaethylene-glycol (C12E6), to assess their potential use as encapsulation vehicles for hydrophobic drugs. To evaluate the effect of the micellar size and hydration, the study used a broad temperature range (293.15-323.15 K). The data presented here include steady-state absorption and emission spectra of the probe, dynamic light scattering, together with fluorescence lifetimes and both steady-state, as well as time-resolved fluorescence anisotropies. The time-resolved fluorescence anisotropy data were analyzed on the basis of the well-established two-step model. Our data reveal that the molecular probe in all of the cases is solubilized in the hydration layer of micelles, where it would sense a relatively polar environment. However, the probe was found to undergo a slower rotational reorientation when solubilized in the alkylpolyglycoside surfactant, as a result of a more compact microenvironment around the probe. The behavior of the parameters of the reorientation dynamics with temperature was analyzed on the basis of both micellar hydration and the head-group flexibility of the surfactants.

Self-assembly, surface activity and structure of n-octyl-ß-D-thioglucopyranoside in ethylene glycol-water mixtures.

The effect of the addition of ethylene glycol (EG) on the interfacial adsorption and micellar properties of the alkylglucoside surfactant n-octyl-ß-D-thioglucopyranoside (OTG) has been investigated. Critical micelle concentrations (cmc) upon EG addition were obtained by both surface tension measurements and the pyrene 1:3 ratio method. A systematic increase in the cmc induced by the presence of the co-solvent was observed. This behavior was attributed to a reduction in the cohesive energy of the mixed solvent with respect to pure water, which favors an increase in the solubility of the surfactant with EG content. Static light scattering measurements revealed a decrease in the mean aggregation number of the OTG micelles with EG addition. Moreover, dynamic light scattering data showed that the effect of the surfactant concentration on micellar size is also controlled by the content of the co-solvent in the system. Finally, the effect of EG addition on the microstructure of OTG micelles was investigated using the hydrophobic probe Coumarin 153 (C153). Time-resolved fluorescence anisotropy decay curves of the probe solubilized in micelles were analyzed using the two-step model. The results indicate a slight reduction of the average reorientation time of the probe molecule with increasing EG in the mixed solvent system, thereby suggesting a lesser compactness induced by the presence of the co-solvent.

Infecciones maláricas en individuos asintomáticos en la población indígena Jivi, Amazonas, Venezuela / Asymptomatic malaria infection in the indigenous Jivi population, Amazonas state, Venezuela

Se evaluó la presencia de infecciones maláricas en individuos asintomáticos en la población Jivi de Puente Parhueña. El estudio fue de tipo prospectivo en tres momentos. El diagnóstico parasitológico se realizó mediante el examen convencional de gota gruesa y extendido (GGE) y la reacción en cadena de la polimerasa (PCR). El diagnóstico por microscopia indicó 2% (5/261) de láminas positivas en Abril, 1% (3/274) en Septiembre y 4% (5/135) en Diciembre. La PCR para Plasmodium spp., fue 46% (26/57) en abril, 49% (28/57) en Septiembre y 35% (20/57) en Diciembre. En los tres momentos predominó la presencia de P. vivax. La prueba de ELISA demostró 72% (41/57) seroreactivos en Abril, 53% (30/57) en Septiembre y 60% (34/57) en Diciembre. En Puente Parhueña habitan individuos con infecciones maláricas asintomáticos, con persistencia de anticuerpos antimalaricos, que probablemente representan un reservorio de gametocitos dentro de la comunidad.

The study was carried out to determine the present malaria infection in the asymptomatic Jivi people of Puente Parhueña. The study was prospective over three periods of time. The parasitological diagnoses were from thick and thin blood smears (GGE) and polymerase chain reaction (PCR). The antibody search was performed by ELISA. Microscopy of the slides detected the following positive results: 2% (2/261) April, 1% (3/274) September and 4% (5/135) December. Detection of Plasmodium by PCR was 46% (26/57) in April, 49% (28/57) in September y 35% (20/57) in December. Plasmodium vivax infected individuals predominated during these 3 times. Positives for ELISA were 72% (41/57) in April, 53% (30/57) September and 60% (34/57) December. The study demonstrated that people living in Puente Parhueña presented asymptomatic malaria infection with malaria antibodies persistence which likely represents a gametocyte potential reservoir for infection among the population.

Infeccion por Toxoplasma Gondii en amerindios de la Selva Amazonica de Venezuela / Toxoplama gondii infection in Amerindians of Venezuelan Amazon

Se hizo una encuesta serológica para Toxoplasma gondii en un grupo de Amerindios de la etnia Guajiba, residentes en el estado Amazonas, en el bosque húmedo de Venezuela. Se estudiaron 121 individuos con edades comprendidas entre 4 y 45 años. El 88 por ciento de la población mostró evidencia serológica de exposición a T. gondii. El perfil de prevalencia y títulos de anticuerpo, para los distintos grupos de edad, es compatible con una exposición frecuente. Las tasas de prevalencia resultaron similares para ambos sexos, pero los títulos de anticuerpos fueron significativamente más elevados entre las mujeres. El estudio sugiere que estas comunidades Amerindias enfrentan factores de riesgo que favorecen la infección con T. gondii desde la niñez. (AU)

Infeccion por Toxoplasma Gondii en amerindios de la Selva Amazonica de Venezuela / Toxoplama gondii infection in Amerindians of Venezuelan Amazon

Se hizo una encuesta serológica para Toxoplasma gondii en un grupo de Amerindios de la etnia Guajiba, residentes en el estado Amazonas, en el bosque húmedo de Venezuela. Se estudiaron 121 individuos con edades comprendidas entre 4 y 45 años. El 88 por ciento de la población mostró evidencia serológica de exposición a T. gondii. El perfil de prevalencia y títulos de anticuerpo, para los distintos grupos de edad, es compatible con una exposición frecuente. Las tasas de prevalencia resultaron similares para ambos sexos, pero los títulos de anticuerpos fueron significativamente más elevados entre las mujeres. El estudio sugiere que estas comunidades Amerindias enfrentan factores de riesgo que favorecen la infección con T. gondii desde la niñez.

Epitopos B de plasmodium vivax: un estudio de pacientes infectados en el área endémica venezolana / Epitopes B of

Hemos investigado la respuesta de anticuerpos a la proteína que circunda el esporozoíto (CSP), y a la principal de la superficie de los merozoítos de Plasmodium vivax (MSP-1Pv), en individuos infectados naturalmente en el área malárica meridional de Venezuela. Peptidos sintéticos que representan la subunidad repetida de las variantes VK210 y VK247 de la CSP o fragmentos de la región N y C-terminal de la MSP-1Pv,

Suppressed induction and expression of delayed hypersensitivity responses in BALB/c mice infected with trypanosoma venezuelense

Following inoculation with 1x10E4 trypomastigotes of Trypanosome venezuelense BALB/c mice showed a progressive, fatal parasitemia and an impaired capability to develop delayed hypersensitivity responses (DHR) as induced by IV immunization with sheep red blood cells (SRBC). Depressed DHR were seen in mice immunized at the time of inoculation and challenged 4 days later. A local cell transfer of immune cells at the site of challenge in the footpad showed that T cells obtained from infected mice immunized with an optimal dose of SRBC on the day of inoculation failed to transfer DHR to naive recipients. However, significant DHR were transfered by T cells from infected mice immunized with a sub-optimal dose of SRBC. By the other hand, 4 days-infected- mice receiving a local transfer of immune T cells taken from non-infected donors failed to express DHR ascompared to controls. It is suggested that in BALB/c mice infected with T. venezuelense both the induction and expression of DHR are impared

La respuesta inmunológica a Trypanosoma venezuelense (T evansi) en ratas curadas / The immune response to Trypanosoma venezuelense (T evansi),in cured rats

Se estudió la respuesta de ratas albinas a la infección con Trypanosoma venezuelense (T. evansi). Los animales inoculados con 1x10 7 tripomastigotos, mostraron una o más ondas de una parasitemia que fue siempre fatal, pero aquellos que recibieron una dosis curativa de babenil eliminaron la parasitemia y en sus sueros encontramos anticuerpos protectores muy eficientes contra los parásitos homólogos, y más aún contra otros heterólogos

Lymph node cell responsiveness in BALB/C mice infected with Leishmania mexicana

No presente trabalho medimos a resposta blastogênica de células de nódulos linfáticos de camundongos BALB/c inoculados com Leishmania mexicana, no decurso da infecçäo. Os resultados mostraram que os animais infectados exibem respostas blastogênicas normais nos nódulos linfáticos até vinte semanas depois da infecçäo. Daí por diante houve uma supressäo gradual. A comparaçäo da capacidade de resposta imunitária no baço e nos nódulos linfáticos mostrou respostas normais nesses nódulos várias semanas depois da ocorrência da supressäo no baço. A supressäo das respostas blastogênicas nos nódulos linfáticos estava relacionada a uma célula aderente de tipo macrófago, que suprimia ativamente as respostas proliferativas normais aos agentes mitogênicos

Depressed mixed lymphocyte responses in chronic experimental cutaneous leishmaniasis

Los ratones BALB/c infectados con Leishmania mexicana presentan lesiones crónicas y progresivas. El estudio de las células esplénicas durante la fase avanzada de la enfermedad reveló una depresión acentuada de la linfoblastogénesis estimulada por los mitógenos concanavalina A y fitohemaglutinina, y de aquella provocada por células alogénicas provenientes de ratones incompatibles a nivel del locus H-2. La remoción de las células esplénicas adherentes a plástico condujo a una reversión de los índices de estimulación provocados por concanavalina A y fitohemaglutinina, hacia valores normales. Sin embargo, el mismo procedimiento tuvo poco o ningún efecto sobre las reducidas respuestas de las células esplénicas de animales infectados en cultivos mixtos. Dichas células resultaron además, defectuosas en cuanto a su capacidad para estimular respuestas alogénicas en cultivos mixtos