Biomedical subjects
Publications and source records attributed to Ricardo Corral.
Di-p-chlorobenzyl azodicarboxylate (DCAD) is introduced as a novel, stable, solid alternative to DEAD and DIAD for a variety of Mitsunobu couplings. DCAD/Ph(3)P-mediated reactions in CH(2)Cl(2) generate a readily separable hydrazine byproduct. [reaction: see text]
OBJECTIVES: To create a virtual laboratory system in which experimental science students could learn required skills and competencies while overcoming such challenges as time limitations, high cost of resources, and lack of feedback often encountered in a traditional laboratory setting. DESIGN: A blended learning experience that combines traditional practices and e-learning was implemented to teach microbiological methods to pharmacy students. Virtual laboratory modules were used to acquire nonmanual skills such as visual and mental skills for data reading, calculations, interpretation of the results, deployment of an analytical protocol, and reporting results. ASSESSMENT: Learning achievement was evaluated by questions about microbiology case-based problems. Students' perceptions were obtained by assessment questionnaire. CONCLUSION: By combining different learning scenarios, the acquisition of the necessary but otherwise unreachable competences was achieved. Students achieved similar grades in the modules whose initiation was in the virtual laboratory to the grades they achieved with the modules whose complete or partial initiation took place in the laboratory. The knowledge acquired was satisfactory and the participants valued the experience.
We report the synthesis of thirty-six Sansalvamide A derivatives, and their biological activity against colon cancer HT-29 cell line, a microsatellite stable (MSS) colon cancer cell-line. The thirty-six compounds can be divided into three subsets, where the first subset of compounds contains L-amino acids, the second subset contains D-amino acids, and the third subset contains both D- and L-amino acids. Five compounds exhibited excellent inhibitory activity (>75% inhibition). The structure-activity relationship (SAR) of the compounds established that a single D-amino acid in position 2 or 3 gave up to a 10-fold improved cytotoxicity over Sansalvamide A peptide. This work highlights the importance of residues 2 and 3 and the role of D-amino acids in the extraordinary SAR for this compound class.
Described are the syntheses of 14 derivatives of the natural product Sansalvamide A, where two are more active against HCT 116 colon cancer cell lines than the natural product. These derivatives were synthesized using a combinatorial-type strategy that permits elucidation of the amino acid role in the cytotoxicity, and they lay the groundwork for development of new anticancer agents. [structure: see text]
In this work, the hydrophilic, low molecular weight and trypanocidal drug etanidazole (ETZ) was loaded in pH-sensitive liposomes (L-ETZ). Liposomes were made of dioleoyl-phosphatidylethanolamine: cholesteryl hemisuccinate (DOPE:CHEMS, 6:4, mol:mol), of 380 nm size at 14% ETZ/total lipid (w/w) ratio. To follow their uptake and intracellular fate by fluorescence microscopy, pH-sensitive liposomes were loaded with the fluorophore/quencher pair HPTS/DPX. A fast and massive delivery of the liposomal aqueous content into the cytosol of murine J774 macrophages was observed. L-ETZ vesicles were phagocytosed by both uninfected and Trypanosoma cruzi-infected macrophages. A 72% of anti-amastigote activity (AA) was demonstrated on L-ETZ-treated J774 cells, whereas the same dose of free ETZ rendered 0% AA. Endovenous administration of L-ETZ at 14 microg/mouse dose provoked significant decrease in parasitemia levels of T. cruzi-infected mice. Conversely, inoculation of a 180-fold higher dose of free ETZ failed in reducing the number of bloodstream trypomastigotes. Hence, these results point to develop systems, such as L-ETZ, designed for selective delivery of drugs to the cytoplasm of phagocytic cells, thus enhancing the efficacy of molecules considered poorly active.
The F2/3 antigenic fraction isolated from Trypanosoma cruzi trypomastigotes contains epitopes recognised by antibodies which are representative of active infection. The kinetics of disappearance of conventional serology (CS) and anti-F2/3 antibodies were compared in 21 patients with congenital Chagas disease after receiving benznidazole treatment. Patients were divided into 2 groups: (A) Age < 8 months at diagnosis; (B) Age > 9 months at diagnosis. Group A presented negative outcome for CS at 6.6 mo. (CI95 3.4-9.8 mo.) and for anti-F2/3 at 4 mo. (CI95 0.9-7.1 mo.), p = 0.18. Group B exhibited non-reactive CS at 63.1 mo. (CI95 42.1-84.2 mo.) whereas anti-F2/3 antibody determination became negative at 21.9 mo. (CI95 5.7-38.1 mo.), p = 0.0025. In patients belonging to group A, antibodies were undetectable by both CS and anti-F2/3 ELISA soon after receiving chemotherapy. In infants included into group B, a negative result for anti-F2/3 antibody detection significantly anticipated the disappearance of CS reactivity. Consequently, an anti-F2/3 antibody assay becoming negative should be considered as an early marker for assessment of cure, particularly in those patients with prolonged time of infection.
We investigated in vivo the effect of macrophage inflammatory protein-1alpha (MIP-1alpha) inhibition upon the cellular recruitment into tissue damage sites and spleen histology in mice acutely infected with Trypanosoma cruzi. Histopathological studies of spleen sections revealed a 68% decrease in macrophage/monocyte infiltration as a result of MIP-1alpha neutralisation. Moreover, a reduction in the number of plasma cells and immunoblasts was observed. However, antibody (Ab)-mediated blocking of MIP-1alpha failed to modify tissue parasite levels. Examination of myocardial sections showed an increase in inflammatory lesions in mice treated with anti-MIP-1alpha Ab. There was also an increasing trend in the number of amastigote nests in the myocardium of anti-MIP-1alpha-treated mice compared with controls. Administration of anti-MIP-1alpha Ab failed to affect either the extent of inflammatory infiltrates or the parasite count in liver and skeletal muscle. To the best of our knowledge, these data are the first in vivo demonstration that Cz.sbnd;C chemokine MIP-1alpha is involved in cellular recruitment during acute infection with T. cruzi, indicating that MIP-1alpha influences macrophage/monocyte influx into target organs.