Kant e o problema da origem das representações elementares: apontamentos

Il s'agit d'examiner l'origine des représentations fondamentales (formes de la réceptivité et formes intelectuelles )face à la critique faite par Kant des idées innées et abstraites.Trata-se de considerara origem das representações fundamentais (formas de receptividade e formas intelectuais), face à crítica de Kant às idéias inatas e abstratas.UNESP Faculdade de Filosofia e Ciências Departamento de FilosofiaUNESP Faculdade de Filosofia e Ciências Departamento de Filosofi

Atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly for 5 weeks in patients with acute coronary syndromes

Background - The antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins. We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes (ACS) could affect the antiplatelet potency of clopidogrel. Methods and Results - Forty-five hypercholesterolemic patients with the first episode of an ACS were included in the study. Patients were randomized to receive daily either 10 mg of atorvastatin (n = 21) or 40 mg of pravastatin ( n = 24). Thirty patients who underwent percutaneous coronary intervention ( PCI) received a loading dose of 375 mg of clopidogrel, followed by 75 mg/d for at least 3 months. In the remaining 15 patients who refused to undergo PCI, clopidogrel therapy was not administered. Eight normolipidemic patients with the first episode of an ACS were also included and received only clopidogrel. The serum levels of soluble CD40L and the adenosine 5'-diphosphate - or thrombin receptor activating peptide-14- induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline ( within 30 minutes after admission) and 5 weeks later. Neither atorvastatin nor pravastatin significantly influenced the clopidogrel-induced inhibition of platelet activation, nor did clopidogrel influence the therapeutic efficacy of atorvastatin. Conclusions - Atorvastatin does not affect the antiplatelet potency of clopidogrel when coadministered for 5 weeks in ACS patients.Circulatio

Structure-activity relationships of alpha(IIb) 313-320 derived peptide inhibitors of human platelet aggregation

The alpha(IIb)beta(3) receptor, which is the most abundant receptor on the surface of platelets, can interact with a variety of adhesive proteins including fibrinogen, fibronectin and the von Willebrand factor. Fibrinogen binding on alpha(IIb)beta(3) is an event essential for platelet aggregation and thrombus formation. Mapping of the fibrinogen-binding domains on alpha(IIb) subunit suggested the sequence 313-332 as a possible binding site. This region was restricted to sequence alpha(IIb) 313-320 (Y(313)MESRADR(320)) using synthetic octapeptides overlapping by six residues. The YMESRADR octapeptide inhibits ADP-stimulated human platelets aggregation and binds to immobilized fibrinogen. In this study, we used the Ala scanning methodology within the sequence 313-320 aiming to evaluate the contribution of each amino acid in inhibiting platelet aggregation. It was found that the substitution of Y-313, M-314, E-315 or S-316 by A does not affect the activity of the parent, octapeptide. The-RADR-motif seems to be the most essential for the biological activity of the all,, 313-320 site. The conformational analysis of the YAESRADR, YMESAADR and YMESRAAR analogs by using NMR spectroscopy and distance geometry calculations revealed significant differences in their conformational states. in DMSO-d(6). Copyright (C) 2008 European Peptide Society and John Wiley & Sons, Ltd.Journal of Peptide Scienc

Experiences of Parents and Teachers of Sinugbuanong Binisaya as a Medium of Instruction in Math Subject for Grade 2 Learners

This study delved into the experiences of parents and teachers in the use of mother tongue as a medium of instruction in mathematics for the Grade 2 learners in three identified public elementary schools during the school year 2020-2021. The findings were the basis for implication for practice. It utilized a qualitative-phenomenological method through interview to 15 teachers and 30 parents from the three schools. An interpretative phenomenological analysis with the use of interview guide was performed in finding out the experiences of both the participants the parents and teachers. The result revealed that parents were more comfortable with using the local dialect and translating Sinugbuanong Binisaya terms to English while teaching their children at home since the learners can understand English more due to their exposure of the language on the internet. The advantages include familiarization of its own dialect while the disadvantages include lacks practicality. On the other hand, participants encountered challenges like unfamiliar words and various lengths of difficulties in understanding. Furthermore, the coping mechanism was to intensify home teaching using fitting strategy effect comprehension in math. It is concluded that teaching Sinugbuanong Bisaya as a medium of instruction in math subject greatly affects the learners. It is recommended that educational stakeholders, particularly curriculum developers and school administrators, consider a more flexible and context-sensitive approach in implementing the Mother Tongue-Based Multilingual Education (MTB-MLE) policy in mathematics instruction

Investigation of the role of adjacent amino acids to the 313-320 sequence of the alpha(IIb) subunit on platelet activation and fibrinogen binding to alpha(IIb)beta(3)

The platelet integrin receptor alpha(IIb)beta(3) plays a critical role in thrombosis and haemostasis by mediating interactions between platelets and several ligands, primarily fibrinogen. We have previously shown that the synthetic peptide YMESRADRKLAEVGRVYLFL corresponding to residues 313-332 of alpha(IIb), is a potent inhibitor of platelet aggregation and fibrinogen binding to alpha(IIb)beta(3), interacting with fibrinogen rather than the receptor. Furthermore, we have demonstrated that the biological activities of the above peptide are due to the sequence YMESRADR, which corresponds to residues 313-320. By using new synthetic peptide analogues we investigated the structural characteristics responsible for the biological activity of YMESRADR as well the possible influence of the adjacent amino acids on the peptide's biological potency. According to our results, the synthetic octapeptide YMESRADR, is a potent inhibitor of platelet aggregation and P-selectin expression. Furthermore, YMESRADR inhibits fibrinogen binding but it does not significantly influence the binding of PAC-1 to ADP-activated platelets. The inhibitory potency of YMESRADR was gradually diminished by deleting the YMES sequence from the amino terminus and prolonging the carboxyl terminus of this peptide with the KLAE sequence. Extension of YMESRADR towards the amino terminus with the GAPL sequence (GAPLYMESRADR) does not modify the biological activity of YMESRADR. Furthermore, extension of GAPLYMESRADR at its carboxy terminus with the KLAE sequence (GAPLYMESRADRKLAE) significantly diminished its biological potency. Substitution of E 315 with D significantly enhances antiaggregatory potency and completely abolishes the inhibitory effect on P-selectin expression. Importantly, the D-315-containing peptides inhibit to a similar extent both fibrinogen and PAC-1 binding to activated alpha(IIb)beta(3) in contrast to the E-315-containing peptide which only inhibits fibrinogen binding. In conclusion, the present study suggests that the YMESRADR sequence 313-320 of alpha(IIb), is an important functional region of the insert connecting the beta(2) and beta(3) antiparallel beta-strands of the W5 blade of the alpha(IIb) subunit. Structural changes significantly modify the biological properties of this region.Platelet