Novel antiplatelet role for a protein disulfide isomerase-targeted peptide: evidence of covalent binding to the C-terminal CGHC redox motif.

Essentials Inhibitors of protein disulfide isomerase (PDI) have been considered a new antithrombotic class. CxxC is a PDI-targeted peptide that has been previously shown to inhibit its reductase activity. CxxC binds to surface PDI and inhibits ADP- and thrombin-evoked platelet activation and aggregation. CxxC binds to Cys400 on CGHC redox motif of PDI a' domain, a site for PDI prothrombotic activity. SUMMARY: Background Protein disulfide isomerase (PDI) plays a major role in platelet aggregation, and its inhibitors have emerged as novel antithrombotic drugs. In previous work, we designed a peptide based on a PDI redox motif (CGHC) that inhibited both PDI reductase activity and PDI-modulated superoxide generation by neutrophil Nox2. Thus, we hypothesized that this peptide would also inhibit platelet aggregation by association with surface PDI. Methods Three peptides were used: CxxC, containing the PDI redox motif; Scr, presenting a scrambled sequence of the same residues and AxxA, with cysteines replaced by alanine. These peptides were tested under platelet aggregation and flow cytometry protocols to identify their possible antiplatelet activity. We labeled membrane free thiol and electrospray ionization liquid chromatography tandem mass spectrometry to test for an interaction. Results CxxC decreased platelet aggregation in a dose-dependent manner, being more potent at lower agonist concentrations, whereas neither AxxA nor Scr peptides exerted any effect. CxxC decreased aIIbb3 activation, but had no effect on the other markers. CxxC also decreased cell surface PDI pulldown without interfering with the total thiol protein content. Finally, we detected the addition of one CxxC molecule to reduced PDI through binding to Cys400 through mass spectrometry. Interestingly, CxxC did not react with oxidized PDI. Discussion CxxC has consistently shown its antiplatelet effects, both in PRP and washed platelets, corroborated by decreased aIIbb3 activation. The probable mechanism of action is through a mixed dissulphide bond with Cys400 of PDI, which has been shown to be essential for PDI's actions. Conclusion In summary, our data support antiplatelet activity for CxxC through binding to Cys400 in the PDI a0 domain, which can be further exploited as a model for sitedriven antithrombotic agent development.

Leukocytosis, muscle damage and increased lymphocyte proliferative response after an adventure sprint race

The effect of an adventure sprint race (ASR) on T-cell proliferation, leukocyte count and muscle damage was evaluated. Seven young male runners completed an ASR in the region of Serra do Espinhaço, Brazil. The race induced a strong leukocytosis (6.22±2.04×103 cells/mm3 before vs 14.81±3.53×103 cells/mm3 after the race), marked by a significant increase of neutrophils and monocytes (P<0.05), but not total lymphocytes, CD3+CD4+ or CD3+CD8+ cells. However, the T-cell proliferative response to mitogenic stimulation was increased (P=0.025) after the race, which contradicted our hypothesis that ASR, as a high-demand competition, would inhibit T-cell proliferation. A positive correlation (P=0.03, r=0.79) was observed between the proliferative response of lymphocytes after the race and the time to complete the race, suggesting that the proliferative response was dependent on exercise intensity. Muscle damage was evident after the race by increased serum levels of aspartate amino transferase (24.99±8.30 vs 50.61±15.76 U/L, P=0.003). The results suggest that humoral factors and substances released by damaged muscle may be responsible for lymphocyte activation, which may be involved in muscle recovery and repair.

Leukocytosis, muscle damage and increased lymphocyte proliferative response after an adventure sprint race.

The effect of an adventure sprint race (ASR) on T-cell proliferation, leukocyte count and muscle damage was evaluated. Seven young male runners completed an ASR in the region of Serra do Espinhaço, Brazil. The race induced a strong leukocytosis (6.22±2.04×10(3) cells/mm3 before vs 14.81±3.53×10(3) cells/mm3 after the race), marked by a significant increase of neutrophils and monocytes (P<0.05), but not total lymphocytes, CD3+ CD4+ or CD3+ CD8+ cells. However, the T-cell proliferative response to mitogenic stimulation was increased (P=0.025) after the race, which contradicted our hypothesis that ASR, as a high-demand competition, would inhibit T-cell proliferation. A positive correlation (P=0.03, r=0.79) was observed between the proliferative response of lymphocytes after the race and the time to complete the race, suggesting that the proliferative response was dependent on exercise intensity. Muscle damage was evident after the race by increased serum levels of aspartate amino transferase (24.99±8.30 vs 50.61±15.76 U/L, P=0.003). The results suggest that humoral factors and substances released by damaged muscle may be responsible for lymphocyte activation, which may be involved in muscle recovery and repair.

[King's theory reach to families of persons with systemic arterial hypertension]. / Alcance da Teoria de King junto a famílias de pessoas portadoras de hipertensão arterial sistêmica.

The aim was to verify the reach of the King's theory (1981) to families of persons with systemic arterial hypertension. The study was developed analyzing the reach of this theory; verification of its applicability in the family context as related by Moreira (1999); and construction of a concept of family with chronic sick persons which is compatible with the theory. The data showed that the theory is interaccionist, with vulnerable borders, and with content elements and context not well defined. In the focalized situation, a family definition with chronic sick persons was built, showing that is possible to use it as part of part of the subject of King's theory.

[Developing the care proposed by Leininger with a person in dialysis treatment]. / Desenvolvendo o cuidado proposto por Leininger com uma pessoa em terapia dialítica.

Study of a ethnographic approach, type case study. Describing a person's bearer of chronic renal inadequacy accompaniment, with adhesion deficit to the treatment. The theoretical presupposition had the model SUNRISE proposed by Leininger. It's presented the Mr. Light and the involved sceneries. Described. Influences economical, social, cultural, technological and educational in the process of taking care. After the identification of the systems of health, were decided the actions of taking care through the maintenance, accommodation and restoration. The study possibilited effective interventions for the behaviors of non adherence. The referencial in continuous and lingering processes of care, favoured by the proximity between nurse and attended person.

Transfructosylation of thiol group by beta-fructofuranosidases.

Beta-fructofuranosidase fructosylated not only the hydroxyl group but also the thiol group of 2-mercaptoethanol in a transfer reaction using sucrose as a donor substrate. The enzymes from Candida utilis and Saccharomyces cerevisiae (bakers' yeast) were effective catalysts for the thio-fructofuranosylation. The thio-fructosylation product was isolated by activated carbon chromatography and its structure was confirmed by Fab-mass spectrometry and NMR spectroscopy. The thio-fructofuranoside was synthesized effectively at around 3.0 M for the acceptor concentration. The product increased with the sucrose concentration at least up to 1.9 M. O-Fructofuranoside was simultaneously synthesized at an early stage of the reaction, although it was hydrolyzed on further incubation. On the contrary, the thio-fructofuranoside accumulated efficiently after synthesis, indicating it was very stable against the hydrolytic action of the beta-fructofranosidase.

[The relationship among the adaptation modes of Roy and NANDA taxonomy of nursing diagnoses]. / A relação entre os modos adaptativos de ROY e a taxonomia de diagnósticos de enfermagem da NANDA.

The present study is theoretical-reflexive with the purpose to establish a correlation between NANDA's taxonomy diagnoses and the adaptation modes proposed by Roy. Authors defined the relationships among the indicators of positive adaptation, the common problems of adaptation proposed by Roy and NANDA's nursing diagnoses. Results showed a strong correspondence between the existent concepts in the studied theoretical model and NANDA's taxonomy of nursing diagnoses. Authors concluded that there is a possibility of using NANDA's nursing diagnoses and the nursing process based on Roy's Adaptation Theory.

[The process if teaching-learning in blood pressure monitoring]. / O processo ensino-aprendizagem na verificação da pressão arterial.

The nurse is considered the professional that obtains more trustworthy data in the measures insinuations of arterial pressure for inducing less reactions of alert in the customer, generating of values falsely high. Even so, a lot of times, she presents spaces in the knowledge of the subject, so much in the technical aspects, as in the anátomo-physiologic ones. That prioritizes the development of teaching strategies, seeking to minimize flaws and to turn the effective learning process. Objectifying to promote the knowledge of the technique of measurement of the arterial pressure close to a research group, it took place a reciclation and avaliation questionnaire of the knowledge of the group was applied before and after the same. The effectiveness of that method was evidenced, because 100% of the sample (nine) they referred contribution for better of the fundamentation theoretical-practice, decreasing difficulties originating from of the verification of the arterial pressure. It is ended that, being the education actions in extremely valid and necessary health, the male nurse, as educator that is, needs to recycle its knowledge and its better techniques continually.

[Effect of anatomical and physiological factors on the indirect blood pressure measurement: identification of nurses' knowledge]. / Influência de fatores anátomo-fisiológicos na medida indireta da pressão arterial: identificação do conhecimento dos enfermeiros.

The study was developed by clinical nurses specialized in cardiology and had the purpose to characterize the knowledge about the conceptual aspects and the anatomical and physiological factors that interfere in the marks of blood pressure.

[Instrumentation for blood pressure measurements: historical aspects, concepts and sources of error]. / Instrumentação na medida da pressão arterial: aspectos históricos, conceituais e fontes de erro.

According to the International Council of Nurses the measurement of blood pressure is the procedure most performed by nurses in all the world. The aim of this study is to analyse the polemical aspects of instruments used in blood pressure measurement. Considering the analyses of the literature and the American Heart Association Recommendations, the main source of errors when measuring blood pressure are discussed.

[Nurses' uniforms as seen by patients, nurses and nursing faculty]. / O uniforme da enfermeira visto pelo paciente, enfermeira e docente de enfermagem.

The exact role of the way people dress up on the nonverbal communication is still unknown. Nevertheless, we know that it influences the interpersonal answers and, in some situations, they are the main determinants of those answers. The objective of this study was to determinate differences between the perception os the nurse uniform through the answers of 100 patients, 30 nurses and 15 nursing school faculty. The data were collected by showing nine photographs of hospitals of the city of São Paulo (Brazil). White trousers and blouse was the favorite one among patients, nurses and nursing school faculty regarding personal care. White skirt above knees, white blouse and blazer was the most rejected one by three groups.

[Data collection in nursing: report of a teaching experience]. / A coleta de dados em enfermagem: relato de uma experiência de ensino.

After courses of Assessment of Adults questionnaires were sent to 84 nurses in order to know if their practice of physical examination was modified by them. These nurses worked in different hospitals and graduated schools. The majority of them related that they improved their knowledge about the matter and modified their practice.

[The teaching of patient evaluation: the delineation of the content of nursing diagnosis]. / O ensino da avaliação do paciente: delineamento do conteúdo pelo diagnóstico de enfermagem.

The nursing care is based on the nursing assessment. In the nurse's professional activity there aren't clarity and consensus about the clinical entities, problems or phenomenons that nurses intended to care. Difficulties in deciding what should be collected are determined by this indefinition, that it is also present in nursing graduate courses. In this article the authors discuss that the Nursing Diagnosis can be the framework for the nursing assessment.

[The general principles of drug administration and nursing actions]. / Princípios gerais de administração de medicamentos e ações de enfermagem.

The authors analyse the responsibility of the nurse during the administration of drugs and solutions. Three aspects are approached: the ethic aspects of professional attitudes, scientific and iatrogenic.