Synthesis and theoretic calculations of benzoxazoles and docking studies of their interactions with triosephosphate isomerase

One-pot synthesis was carried out for Z or E stereoisomer derivates of 3-(benzoxazoyl)-2-propenoic acid following kinetic or thermodynamic control. All compounds were characterized by ¹H and ¹³C NMR, and the single crystal X-ray structure of (2Z)-3-(6-methyl-1,3-benzoxazol-2-yl)prop-2-enoic acid (3) was obtained. Furthermore, a theoretic study was done for all the synthesized compounds at the B3LYP/6-31G(d,p) level. The target compounds were docked on triosephosphate isomerase and trypanocidal activity was explored for the 4 and 6 compounds. The Z isomers showed an intramolecular hydrogen bond O–H···N according to the X-ray structure of 3. The docking studies indicate that the test compounds insert themselves between the monomers of triosephosphate isomerase, reaching the known binding site located at interdimeric shapes of triosephosphate isomerase by means of π–π interactions and electrostatic interactions, and in this way interrupt interactions between these monomers. Thus, could explain the biologic effects of the E isomer on triosephosphate isomerase. Finally, compounds 4 and 6 showed trypanocidal activity, which could be mediated by triosephosphate isomerase inhibition.     

The clinical significance of coagulation and the inflammatory response in autoimmunity

Maintenance of normal blood flow requires equilibrium between procoagulant and anticoagulant factors; occasionally, procoagulant activity predominates, leading to clot formation; frequently, tissue damage is the triggering factor. Hereditary factors, primary or acquired, play a role in the development of thrombosis. Primary thrombophilia is associated with hereditary factors, which promote hypercoagulability because natural anticoagulants are not exerting their activity. On the other hand, acquired thrombophilia may occur associated to autoimmune diseases, cancer, surgical procedures, pregnancy, postpartum period, and obesity. Activation of the coagulation system is characterized by the co-participation of inflammatory response components, factors related to the subjacent disease, and other procoagulant factors. The study of patients with thrombosis should include both inflammatory and autoimmune response markers.     

Strengthening preventive care programs: a permanent challenge for healthcare systems; lessons from PREVENIMSS México

Background  

In 2001, the Instituto Mexicano del Seguro Social (IMSS) carried out a major reorganization to provide comprehensive preventive care to reinforce primary care services through the PREVENIMSS program. This program divides the population into programmatic age groups that receive specific preventive services: children (0-9 years), adolescents (10-19 years), men (20-59 years), women (20-59 years) and older adults (> = 60 years). The objective of this paper is to describe the improvement of the PREVENIMSS program in terms of the increase of coverage of preventive actions and the identification of unmet needs of unsolved and emergent health problems.     

Determinants of health in seasonal migrants: coffee harvesters in Los Santos, Costa Rica

In the agroexport zone of Los Santos Zone in Costa Rica, coffee is harvested by migrant labor. Most migrants are from Panama and Nicaragua. We describe migrants' housing- and service-related health determinants, with analyses of ethnicity, nationality and geography. We used interviews, observation-based assessments, and the Geographic Information System to assess a population of 8,783 seasonal migrants and 1,099 temporary dwellings at a total of 520 farms during 2004-2005. We identified determinants of poor health including widespread deficiencies in the quality of grower-provided dwellings, geographical isolation, crowding, lack of radio and television, and deficient toilets and cooking facilities. The indigenous and non-Costa Ricans shared the poorest conditions. Reluctance to use mainstream public health services was widespread, especially among foreign and indigenous migrants and the geographically isolated. Post-study, researchers organized workshops for audiences including workers, coffee producers, public officials and service providers. Topics have included migration, preventive health and hygiene, and child labor. This work was successful in convincing Costa Rican social security authorities to implement reforms that improve access to and quality of health care for the migrants. Special projects on ergonomics, psychosocial health hazards, and water quality, as well as a literacy program, are ongoing.     

Coexistence of D3R typical and atypical signaling in striatonigral neurons during dopaminergic denervation. Correlation with D3nf expression changes

Dopamine D₃R are widely expressed in basal ganglia where interact with D₁R. D₃R potentiate cAMP accumulation and GABA release stimulated by D₁R in striatonigral neurons through “atypical” signaling. During dopaminergic denervation, D₃R signaling changes to a “typical” in which antagonizes the effects of D₁R, the mechanisms of this switching are unknown. D₃nf splice variant regulates membrane anchorage and function of D₃R and decreases in denervation; thus, it is possible that D₃R signaling switching correlates with changes in D₃nf expression and increases of membranal D₃R that mask D₃R atypical effects. We performed experiments in unilaterally 6-hydroxydopamine lesioned rats and found a decrease in mRNA and protein of D₃nf, but not of D₃R in the denervated striatum. Proximity ligation assay showed that D₃R-D₃nf interaction decreased after denervation, whereas binding revealed an increased B_max in D₃R. The new D₃R antagonized cAMP accumulation and GABA release stimulated by D₁R; however, in the presence of N-Ethylmaleimide (NEM), to block G_i protein signaling, activation of D₃R produced its atypical signaling stimulating D₁R effects. Finally, we investigated if the typical and atypical effects of D₃R modulating GABA release are capable of influencing motor behavior. Injections of D₃R agonist into denervated nigra decreased D₁R agonist-induced turning behavior but potentiated it in the presence of NEM. Our data indicate the coexistence of D₃R typical and atypical signaling in striatonigral neurons during denervation that correlated with changes in the ratio of expression of D₃nf and D₃R isoforms. The coexistence of both atypical and typical signaling during denervation influences motor behavior.