Anti-trypanosomal Lignans Isolated from Salvadoran Peperomia pseudopereskiifolia.

A search for anti-trypanosomal natural compounds from plants collected in El Salvador, a country particularly endemic for Chagas disease, resulted in the isolation of five lignan-type compounds (1-5) from Peperomia pseudopereskiifolia. The lignan derivatives 1, 2, and 4 are new. Their absolute configuration was determined by chemical derivatization. Compounds 1, 5, 6, and 8 exhibited anti-trypanosomal activity against the amastigote form of T. cruzi comparable to that of the existing drug benznidazole.

Salvadoran Celastraceae Species as a Source of Antikinetoplastid Quinonemethide Triterpenoids.

Chagas disease and leishmaniasis are among the most widespread neglected tropical diseases, and their current therapies have limited efficacy and several toxic side effects. The present study reports the chemical and antikinetoplastid profiles of extracts from five Salvadoran Celastraceae species against the Trypanosoma cruzi epimastigotes stage and Leishmania amazonensis and Leishmania donovani promastigote forms. The phytochemical profile evinced the presence of flavonoids, tannins, sterols, and triterpenes as the main components in all plant species, whereas quinonemethide triterpenoids (QMTs) were restricted to the root bark of the studied species. Antikinetoplastid evaluation highlights the root bark extracts from Zinowewia integerrima, Maytenus segoviarum, and Quetzalia ilicina as the most promising ones, exhibiting higher potency against T. cruzi (IC50 0.71-1.58 µg/mL) and L. amazonensis (IC50 0.38-2.05 µg/mL) than the reference drugs, benznidazole (IC50 1.81 µg/mL) and miltefosine (IC50 2.64 µg/mL), respectively. This potent activity was connected with an excellent selectivity index on the murine macrophage J774A.1 cell line. These findings reinforce the potential of QMTs as antikinetoplastid agents for the development of innovative phytopharmaceuticals and the plant species under study as a source of these promising lead compounds.

In vitro antiparasitic and antibacterial evaluation of organic extracts of Salvadoran flora / Evaluación antiparasitaria y antibacterial in vitro de extractos orgánicos de la flora salvadoreña

Currently, in developing countries, parasitic and bacterial diseases as amebiasis, giardiasis, trichonomiasis, leishmaniasis, trypanosomiasis, tuberculosis, and nocardiasis are a public health problem. The pharmacological treatment for these diseases is not completely effective and causes several side effects in patients. Therefore, the search for new compounds with biological activity is very important to develop new drugs safely and more efficiently. In this study, different organic extracts obtained from thirty-seven species of the Salvadoran flora were evaluated in several in vitro models to determine their potential activity against five protozoa (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana, and Trypanosoma cruzi) and three bacteria (Acinetobacter baumanni, Mycobacterium tuberculosis, and Nocardia brasiliensis). The results showed the activity of eight extracts with IC50values of less than 100 µg/mL against L. mexicanaand five extracts with MICs values less than <50 µg/mL against M. tuberculosis. Besides, seven plant species showed MICs ≤3.125 µg/mL against N. brasiliensis. Additionally, secondary metabolites (flavonoids and monoterpene oxygenate) previously reported as active were fingerprint by UPLC-MS to establish a potential correlation with the biological activity showed.

Actualmente, en los países en vías de desarrollo, enfermedades parasitarias y bacterianas como la amebiasis, giardiasis, trichonomiasis, leishmaniasis, tripanosomiasis, tuberculosis y nocardiasis son un problema de salud pública. El tratamiento farmacológico de estas enfermedades no es del todo eficaz y provoca varios efectos secundarios en los pacientes. Por lo tanto, la búsqueda de nuevos compuestos con actividad biológica es muy importante para desarrollar nuevos fármacos, seguros y eficaces. En este estudio se evaluaron diferentes extractos orgánicos obtenidos de treinta y siete especies de la flora salvadoreña en varios modelos in vitro para determinar su actividad potencial contra cinco parásitos (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana y Trypanosoma cruzi) y tres bacterias (Acinetobacter baumanni, Mycobacterium tuberculosis y Nocardia brasiliensis). Los resultados mostraron la actividad de ocho extractos con valores de CI50 menores a 100 µg/mL contra L. mexicana y cinco extractos con valores de CIMs <50 µg/mL contra M. tuberculosis. Además, siete especies de plantas presentaron CIM ≤3,125 µg/mL frente a N. brasilienses. Finalmente, los metabolitos secundarios (flavonoides y monoterpenos oxigenados) previamente reportados como activos fueron determinados por UPLC-MS para establecer una posible correlación con la actividad biológica mostrada.

Screening of medicinal plants from El Salvador for anti-viral activity against Herpes simplex 1.

Herpes simplex virus 1 is one of the most prevalent pathogens worldwide. Resistant strains to current anti-viral treatment have been reported, requiring the search for novel anti-virals. Using a qPCR method to assess anti-herpetic activity from natural products, we analyzed 72 plant extracts from El Salvador and identified eighteen methanolic extracts with anti-viral activity of ≥ 75%. Anti-herpetic activity has not been previously reported in fourteen of the plants (Euphorbia lancifolia, Piper tuberculatum, Cordia alliodora, Tecoma stans, Taraxacum officinale, Hamelia patens, Witheringia solanacea, Emilia fosbergii, Gnaphalium viscosum, Citrus aurantium, Ambrosia peruviana, Carica papaya, Solanum hazenii and Melothria pendula). Four extracts were from species with previously reported anti-herpetic activity (Plantago major, Psidium guajava, Sida acuta and Bursera simaruba). These extracts effective anti-viral concentrations (EC50) were between 203 and 6.31 µg/mL, while the selectivity indexes (SI) were between 55.91 and 2.57. Euphorbia lancifolia showed the most effective anti-viral activity (EC50 = 6.31 µg/mL, SI = 51.82).

Anti-trypanosomal screening of Salvadoran flora.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and in Central America, it is considered one of the four most infectious diseases. This study aimed to screen the anti-trypanosomal activity of plant species from Salvadoran flora. Plants were selected through literature search for plants ethnobotanically used for antiparasitic and Chagas disease symptomatology, and reported in Museo de Historia Natural de El Salvador (MUHNES) database. T. cruzi was incubated for 72 h with 2 different concentrations of methanolic extracts of 38 species, among which four species, Piper jacquemontianum, Piper lacunosum, Trichilia havanensis, and Peperomia pseudopereskiifolia, showed the activity (≤ 52.0% viability) at 100 µg/mL. Separation of the methanolic extract of aerial parts from Piper jacquemontianum afforded a new flavanone (4) and four known compounds, 2,2-dimethyl-6-carboxymethoxychroman-4-one (1), 2,2-dimethyl-6-carboxychroman-4-one (2), cardamomin (3), and pinocembrin (5), among which cardamomin exhibited the highest anti-trypanosomal activity (IC50 = 66 µM). Detailed analyses of the spectral data revealed that the new compound 4, named as jaqueflavanone A, was a derivative of pinocembrin having a prenylated benzoate moiety at the 8-position of the A ring.

A Bivalent Live Attenuated Influenza Virus Vaccine Protects against Drifted H1N2 and H3N2 Clinical Isolates in Swine.

Influenza A viruses (IAVs) can cause a highly contagious respiratory disease for many mammalian species. In pigs, IAVs cause high morbidity and low mortality disease in susceptible populations that can have significant financial and production impacts. They can also present opportunities for mutations and gene reassortment, producing influenza strains with pandemic potential. Therefore, it is very important to prevent and control influenza infection in pigs, and the chief way to do so is through vaccination. The subtypes of IAV most prevalent in swine across the world are H1N1, H1N2, and H3N2; however, genetic diversity of these viruses can vary greatly by region. We previously developed an elastase-dependent bivalent live attenuated vaccine using two Canadian swine influenza A virus (swIAV) isolates, A/Swine/Alberta/SD0191/2016 (H1N2) [SD191] and A/Swine/Saskatchewan/SD0069/2015 (H3N2) [SD69], which provided protection against homologous strains. In this study, we demonstrate that this vaccine extends protection in pigs to more current, drifted non-homologous H1N2 and H3N2 strains, A/Swine/MB/SD0467/2019 (H1N2) [SD467] and A/Swine/AB/SD0435/2019 (H3N2) [SD435]. The vaccine elicited a robust immune response in the serum and the lung and reduced viral replication as well as lung pathology associated with these strains. Therefore, this bivalent vaccine remains a strong candidate that would be beneficial to the swine influenza vaccine market in North America.

Withanolide-Type Steroids from Physalis nicandroides Inhibit HIV Transcription.

The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 µM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.

Treatment of COVID-19 patients with the anti-CD6 antibody itolizumab.

OBJECTIVES: COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T-cell activation. Itolizumab is a humanised antibody targeting CD6. Nonclinical and clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. The primary objective of this study was to assess the impact of itolizumab in arresting the lung function deterioration of COVID-19 patients. Secondary objectives included safety, duration of ventilation, 14-day mortality and evaluation of interleukin 6 concentration. METHODS: Patients with confirmed SARS-CoV-2 received itolizumab in combination with other therapies included in the national protocol for COVID-19. RESULTS: Seventy critical, severe or moderate patients were treated with itolizumab in 10 Cuban hospitals. Median age was 68, and 94% had comorbidities. After 72 h, most patients improved the PO2/FiO2 ratio and reduced FiO2 requirements. Ventilation time was 8 days for critical and 1 day for severe cases. Ten patients had related adverse events while 3 subjects developed related serious events. In 30 patients, interleukin 6 decreased in individuals with high level and did not change in those with lower concentration. Fourteen-day lethality rate was 4% and 18% for moderate and severe patients, respectively. The proportion of moderate or severe patients with ventilation or death at day 14 was 9.8%. Time to treatment, neurological manifestations and biomarkers such as NLR were significantly associated with higher lethality. CONCLUSIONS: The opportune administration of itolizumab might interrupt the hyperinflammatory cascade and prevent COVID-19 morbidity and mortality.

Development and Validation of an HPLC-PDA Method for Biologically Active Quinonemethide Triterpenoids Isolated from Maytenus chiapensis.

Background: Quinonemethide triterpenoids, known as celastroloids, constitute a relatively small group of biologically active compounds restricted to the Celastraceae family and, therefore, they are chemotaxonomic markers for this family. Among this particular type of metabolite, pristimerin and tingenone are considered traditional medicines in Latin America. The aim of this study was the isolation of the most abundant celastroloids from the root bark of Maytenus chiapensis, and thereafter, to develop an analytical method to identify pristimerin and tingenone in the Celastraceae species. Methods: Pristimerin and tingenone were isolated from the n-hexane-Et2O extract of the root bark of M. chiapensis through chromatographic techniques, and were used as internal standards. Application of a validated RP HPLC-PDA method was developed for the simultaneous quantification of these two metabolites in three different extracts, n-hexane-Et2O, methanol, and water, to determine the best extractor solvent. Results: Concentration values showed great variation between the solvents used for extraction, with the n-hexane⁻Et2O extract being the richest in pristimerin and tingenone. Conclusions: M. chiapensis is a source of two biologically active quinonemethide triterpenoids. An analytical method was developed for the qualification and quantification of these two celastroloids in the root bark extracts of M. chiapensis. The validated method reported herein could be extended and be useful in analyzing Celastraceae species and real commercial samples.

Efecto analgésico, caracterización fitoquímica y análisis toxicológico del extracto etanólico de hojas de pereskia lychnidiflora / Analgesic effect, phytochemical characterization and toxicological analysis of ethanolic extract of pereskia lychnidiflora leaves

RESUMEN Objetivo Evaluar el efecto analgésico del extracto etanólico de las hojas de Pereskia lychnidiflora, la prospección de metabolitos secundarios y el análisis toxicológico. Materiales y métodos La actividad analgésica fue evaluada mediante la prueba del ácido acético y la formalina en ratones NIH a una concentración de 30, 50 y 100 mg/kg de peso corporal, utilizando como control Ibuprofeno a 200 mg/kg y agua destilada como blanco. La prospección de metabolitos secundarios se realizó por el método de cromatografía de capa fina y la toxicidad del extracto fue evaluada in vivo según la dosis máxima de 2000 mg/kg de peso corporal. Resultados La prospección fitoquímica determinó la presencia de alcaloides, taninos, triterpenos y esteroles como mayores constituyentes químicos. Se determinó que el extracto etanólico de Pereskia lychnidiflora posee una actividad analgésica similar al Ibuprofeno. No se observaron signos de toxicidad en los ratones de experimentación y se clasifica el extracto como no tóxico con una DL50 mayor de 2000 mg/kg. Conclusión El extracto etanólico de Pereskia lychnidiflora tiene un efecto analgésico antiinflamatorio que podría estar condicionado por la presencia de alcaloides, taninos y esteroles (terpenoides) presentes en esta especie vegetal y puede ser clasificado como no tóxico.

ABSTRACT Objective To evaluate the analgesic effect of the ethanolic extract of the leaves of Pereskia lychnidiflora, the prospection of secondary metabolites and the toxicologic analysis. Materials and Methods Analgesic activity was evaluated by testing acetic acid and formalin in NIH mice at a concentration of 30, 50 and 100 mg/kg body weight, using Ibuprofen control at 200 mg/kg and distilled water as the target. Secondary metabolites were prospected using the thin layer chromatography method and the toxicity of the extract was evaluated in vivo according to the maximum dose of 2,000 mg/kg body weight. Results Phytochemical prospecting determined the presence of alkaloids, tannins, triterpenes, and sterols as major chemical constituents. The ethanolic extract of Pereskia lychnidiflora was found to have an analgesic activity similar to ibuprofen. No signs of toxicity were observed in the experimental mice and the extract is classified as non-toxic with a DL50 greater than 2,000 mg/kg. Conclusions The ethanolic extract of Pereskia lychnidiflora has an anti- inflammatory analgesic effect that could be conditioned by the presence of alkaloids, tannins, and sterols (terpenoids) present in this species and can be classified as non-toxic.

[Analgesic effect, phytochemical characterization and toxicological analysis of ethanolic extract of pereskia lychnidiflora leaves]. / Efecto analgésico, caracterización fitoquímica y análisis toxicológico del extracto etanólico de hojas de pereskia lychnidiflora.

OBJECTIVE: To evaluate the analgesic effect of the ethanolic extract of the leaves of Pereskia lychnidiflora, the prospection of secondary metabolites and the toxicologic analysis. MATERIALS AND METHODS: Analgesic activity was evaluated by testing acetic acid and formalin in NIH mice at a concentration of 30, 50 and 100 mg/kg body weight, using Ibuprofen control at 200 mg/kg and distilled water as the target. Secondary metabolites were prospected using the thin layer chromatography method and the toxicity of the extract was evaluated in vivo according to the maximum dose of 2,000 mg/kg body weight. RESULTS: Phytochemical prospecting determined the presence of alkaloids, tannins, triterpenes, and sterols as major chemical constituents. The ethanolic extract of Pereskia lychnidiflora was found to have an analgesic activity similar to ibuprofen. No signs of toxicity were observed in the experimental mice and the extract is classified as non-toxic with a DL50 greater than 2,000 mg/kg. CONCLUSIONS: The ethanolic extract of Pereskia lychnidiflora has an anti- inflammatory analgesic effect that could be conditioned by the presence of alkaloids, tannins, and sterols (terpenoids) present in this species and can be classified as non-toxic.

OBJETIVO: Evaluar el efecto analgésico del extracto etanólico de las hojas de Pereskia lychnidiflora, la prospección de metabolitos secundarios y el análisis toxicológico. MATERIALES Y MÉTODOS: La actividad analgésica fue evaluada mediante la prueba del ácido acético y la formalina en ratones NIH a una concentración de 30, 50 y 100 mg/kg de peso corporal, utilizando como control Ibuprofeno a 200 mg/kg y agua destilada como blanco. La prospección de metabolitos secundarios se realizó por el método de cromatografía de capa fina y la toxicidad del extracto fue evaluada in vivo según la dosis máxima de 2000 mg/kg de peso corporal. RESULTADOS: La prospección fitoquímica determinó la presencia de alcaloides, taninos, triterpenos y esteroles como mayores constituyentes químicos. Se determinó que el extracto etanólico de Pereskia lychnidiflora posee una actividad analgésica similar al Ibuprofeno. No se observaron signos de toxicidad en los ratones de experimentación y se clasifica el extracto como no tóxico con una DL50 mayor de 2000 mg/kg. CONCLUSIÓN: El extracto etanólico de Pereskia lychnidiflora tiene un efecto analgésico antiinflamatorio que podría estar condicionado por la presencia de alcaloides, taninos y esteroles (terpenoides) presentes en esta especie vegetal y puede ser clasificado como no tóxico.

DFT study of zinc, cadmium, mercury, copper, silver, and gold complexes of 21,23-dioxaporphyrin and one-dimensional arrays of those complexes.

Complexes of 21,23-dioxaporphyrin with neutral Zn, Cd, Hg, Cu, Ag, and Au atoms as well as some one-dimensional arrays of those complexes containing up to ten repeat units were modeled at the PBE/def2-TZVPP level of theory with D3 empirical dispersion correction. The binding energy between the metal atom and the macrocycle was found to vary from 90 kcal/mol for Cu to -14 kcal/mol for Hg. Strong charge transfer from the metal to the macrocycle accompanied complex formation. The complexes were able to form dimers and nanoarrays that were held together mostly by dispersion forces. Different types of dimers were studied: face-to-face (F) and two types of parallel-displaced ones. F dimers were calculated to be the lowest-energy structures for Cu and Ag systems. Nanoarray formation was studied for these complexes. The band gaps (Eg) of the nanoarrays were found to be smaller than 1 eV, and decreased slightly as the number of repeat units in the nanoaggregates increased. The ionization potentials and electron affinities were greatly affected by the number of repeat units due to the delocalization of polarons over the entire nanoarray. The polaron delocalization and the related reorganization energies depended to a considerable extent on the metal present in the complex. For the studied nanoarrays, the reorganization energies for hole and electron transport decreased linearly with 1/n, where n is the number of repeat units in the nanoaggregate; for an infinitely long chain, the reorganization energy was zero for electron transport and 0.03-0.04 eV for hole transport.

Enzyme orientation for direct electron transfer in an enzymatic fuel cell with alcohol oxidase and laccase electrodes.

A new full enzymatic fuel cell was built and characterized. Both enzymatic electrodes were molecularly oriented to enhance the direct electron transfer between the enzyme active site and the electrode surface. The anode consisted in immobilized alcohol oxidase on functionalized carbon nanotubes with 4-azidoaniline, which acts as active-site ligand to orientate the enzyme molecule. The cathode consisted of immobilized laccase on functionalized graphite electrode with 4-(2-aminoethyl) benzoic acid. The enzymatic fuel cell reaches 0.5 V at open circuit voltage with both, ethanol and methanol, while in short circuit the highest current intensity of 250 µA cm(-2) was obtained with methanol. Concerning the power density, the methanol was the best substrate reaching 60 µW cm(-2), while with ethanol 40 µW cm(-2) was obtained.

Zinc-, cadmium-, and mercury-containing one-dimensional tetraphenylporphyrin arrays: a DFT study.

Metal-free, Zn-, Cd-, and Hg-containing one-dimensional tetraphenylporphyrin arrays containing up to eight repeat units were modeled at the PBE/def2-SVP level of theory with D3 empirical dispersion correction. Two different configurations--face to face (F) and parallel displaced (P)--were detected, the latter being the most stable for all types of nanoarrays. According to the calculations, the binding that occurs in nanoarrays is mostly due to dispersion, with binding energies of 33-35 kcal/mol seen for the metal-free nanoarrays and energies of 37-40 kcal/mol for the metal-containing ones. The band gaps, estimated as the S0 → S1 excitation energies and extrapolated to the infinite chain limit using the TD-CAM-B3LYP/def2-SVP model, were close to 2 eV; the band gap size was barely dependent on the nature of the metal and the number of repeat units in the nanoarray. The ionization potentials and electron affinities were greatly influenced by the number of repeat units due to delocalization of polarons across each nanoarray. Polaron delocalization and the related reorganization energies were clearly dependent on the nature of the metal. For the metal-free and Zn-containing nanoarrays, the reorganization energies for hole and electron transport decreased linearly with 1/n, where n is the number of repeat units in the nanoaggregate. The reorganization energies therefore reach zero for an infinitely long chain. These energies for Cd- and Hg-containing nanoarrays were found to be one order of magnitude higher for both hole and electron transport due to the localization of polarons in these nanoarrays.

Reactions of ketones with aromatics in acid media. The effect of trifluoromethyl groups and the acidity media. A theoretical study.

The reactions of acetone, 2,2,2-trifluoroacetone and hexafluoroacetone in methanesulfonic (MSA) and triflic acids (TFSA) with benzene have been studied at M06-2X/6-311+G(d,p) level using cluster-continuum model, where the carbonyl group is explicitly solvated by acid molecules. The introduction of a trifluoromethyl group into the ketone structure reduces the activation energy of the tetrahedral intermediates formation due to an increase of the electrophilicity of the carbonyl group and raises the activation and the reaction energies of the C-O bond cleavage in formed carbinol due to the destabilization of the corresponding carbocation. The introduction of the second trifluoromethyl group inhibits the hydroxyalkylation reaction due to a very strong increase of the reaction and activation energies of the C-O bond cleavage which becomes the rate determining step. The most important catalytic effect of TFSA compared to MSA is not the protonation of the ketone carbonyl, but the reduction of the activation and reaction energies of the carbinol C-O bond cleavage due to better protosolvation properties. Even for TFSA no complete proton transfer to carbonyl oxygen has been observed for free ketones. Therefore, the protonation energies of free ketones cannot be considered as a measure of ketone reactivity in the hydroxyalkylation reaction.

Respuesta inmunológica de linfocitos T frente a diferentes fracciones antigénicas de mycobacterium bovis en poliartritis crónica juvenil / T lymphocyte immunological response to different antigenic fractions of mycobacterium bovis in juvenile chronic polyarthritis

Background: The possible relationship of stress or heat-shock proteins (hsp) with the pathogenesis of autoimmune disease has been intensely studied recently. In adult rheumatoid arthritis, a bacterial hsp (65 kDa hsp from Mycobacterium tuberculosis or bovis) would have a cross reactivity with a hsp of ARTICULAR cartilage. Aim: To assess the cellular immune response to the 65 kA hsp from M Bovis in children. Patients and methods: The proliferative response of peripheral mononuclear cells of 20 children with juvenile chronic polyarthritis and 20 healthy controls, against the 65 kDa hsp and other antigenic fractions from M bovis, was studied. Results: Patients with juvenile chronic polyarthritis had a intense reaction against 65 kDa fraction and a second fraction located between 32.5 and 27.5 kDa. Patients with a prolonged evolution of the disease (more than five years), reacted preferentially to an antigenic segment located between 32.5 and 27.5 kDa and those with a shorter evolution did so with an antigen of 27.5-18.5 kDa. Conclusions: These results support the hypothesis that 65 kDa hsp from M bovis is involved in the pathogenesis of chronic juvenile polyarthritis and suggest that patients with short or prolonged evolutions of the disease would react to different antigenic fractions

Estudio histopatológico en ratones infectados experimentalmente con trypanosoma cruzi / Histopathological study in mice experimentally infected with tripanosoma cruzi

Se infectaron cuatro cepas de ratones, machos y hembras, con 2000 trypomastigotes sanguíneos de la cepa Tulahuen de trypanosoma cruzi. Los animales de las cepas A.Sw y HTI se comportaron como resistentes y los de las cepas A/Sn y HTG como susceptibles, independiente del sexo de los animales infectados. En los casos de las cepas A.Sw, HTG y HTI se observó niveles significativamente más altos de parasitemia en los machos. A nivel histopatológico el daño tisular no presenta inicialmente diferencias significativas entre cepas resistentes y susceptibles, sin embargo, con el tiempo se puede ver que en los animales resistentes se inducen fenómenos de reparación del daño, en cambio en los ratones susceptibles las lesiones parecen aumentar a pesar de no observarse parásitos intracelulares o circunlantes

Complejo de histocompatibilidad / Histocompatibility complex

El compleho principal de histocompatibilidda (MHC) es un complejo génico altamente polimórfico que controla la expresión de moléculas que desempeñan un rol fundamental en las interacciones celulares que se producen durante la respuesta inmune y en el procesamiento y presentación de antígenos a los linfocitos T. Los genes de clase I del MHC controlan la expresión de los clásicos antígenos de histocompatibilidad y que en realidad funcionan como moléculas de presentación de fragmentos antigénicos a los linfocitos TCD8+ (linfocitos T citotóxicos). Los genes de clase II corresponden a los antiguos genes de respuesta inmune (genes Ir) y codifican la expresión de moléculas de presentación de fragmentos peptídicos a linfocitos TCD4+ (linfocitos T helper). Los genes de clase II codifican la expresión de los factores de complemento C4, Bf y C2. El complejo incluye, además, genes que codifican la expresión de subunidades del proteasoma (LMP2 y LMP7), transportadores peptídicos (TAP1 y TAP2), factor de necrosis tumoral (TNFa y TBFb) y proteínas de shock térmico (hsp70)