Monitoreo de la actividad depigmentantede la idebenona / Screening of depigmenting activity of idebenone

Introducción: Existen numerosos compuestos que presentan capacidad depigmentante, pero su uso presenta ciertos riesgos de toxicidad local y eventualmentesistémica, por lo que se hace necesario buscar nuevas alternativas terapéuticas para desórdenes de la pigmentación o nuevos agentes blanqueadores.Una de estas alternativas puede ser la idebenona, una análogo sintético de la coenzima Q10.Con el objeto de evaluar la capacidad de la idebenona de inhibir específicamente la síntesis de melanina, se realizó el siguiente experimento:Materiales y método: Se utilizó una línea celular continua obtenida de melanoma humano (SK-MEL28) con capacidad de síntesis de melanina, la quese expuso a diferentes concentraciones de idebenona durante 5 días. Al cabo de este tiempo se midieron las densidades ópticas de los sobrenadantescon un espectrofotómetro, determinándose así la concentración de melanina y la viabilidad celular, expresándose los resultados como un porcentajede cultivos controles sin tratar. Como control comparativo se corrieron experimentos en paralelo utilizando hidroquinona.Resultados: La idebenona inhibe la síntesis de melanina en células SK-MEL28 en forma dosis-dependiente, siendo esta inhibición mayor que la producidapor la hidroquinona, pero con menos efectos citotóxicos.Comentario: La idebenona presenta cierta analogía estructural con compuestos inhibidores de la melanogénesis. Esta analogía podría interferir con laactividad de tirosinasa necesaria para la producción de melanina. La alta seguridad de la droga y la eficacia demostrada aquí podrían poner a la idebenonaentre las moléculas de primera línea para el tratamiento de los desórdenes de la pigmentación como también como agente blanqueador (AU)

Introduction: Various agents exhibit a depigmenting activity, but their usage presents some risk of local and eventually systemic toxicity; thus, newalternatives for pigmentation disorders and bleaching agents are continuously searching. One of these alternatives could be idebenone, a syntheticanalogue to coenzyme Q10.In order to test idebenone capability to specifically inhibit melanin synthesis, the following experiment was performed:Material and methods: A continuous cell line of human origin (SK-MEL28) with melanin synthesis capability was exposed for 5 days to different concentrationsof idebenone. After 5 days, optical densities in supernatants were measured by means of an spectrophotometer in order to evaluate melanincontent and cell viability. Results were expressed as a percentage of non-treated cell cultures. As a comparative control, similar experiments wereperformed using hydroquinone.Results: Idebenone inhibits melanin synthesis in SK-MEL28 cells in a dose-dependent manner, being this inhibition stronger than that produced byhydroquinone, but with lesser cytotoxic effects.Comment: Idebenone shows structural analogies with other melanogenesis inhibitor compounds. This analogy could, in some way, interfere withtyrosinase activity to produce melanin. The high safety of the drug and the efficacy demonstrated herein could put idebenone in the first choice lineeither for the treatment of pigmentation disorders as well as a bleaching agent (AU)

Effect of prone positioning on the survival of patients with acute respiratory failure.

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.

Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 Trial.

Aspirin (ASA) and angiotensin-converting enzyme inhibitor (ACEi) therapy reduce mortality when administered early after the onset of myocardial infarction. ASA can antagonize some effects of ACEi therapy by inhibiting the synthesis of vasodilating prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive lisinopril or not to receive lisinopril within 24 hours of the onset of symptoms of myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi lisinopril in the postacute phase of acute myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum creatinine levels at 42 days were significantly higher in lisinopril group than in the control group. Systolic and diastolic blood pressures in lisinopril group were significantly lower than controls at 42 days. The effect of lisinopril on creatinine and blood pressure did not differ between the ASA and no-ASA groups. ASA does not decrease the mortality benefit of early lisinopril after myocardial infarction, nor does it increase the risk of major adverse events. Lisinopril is safe and effective when given early after the onset of myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.

Prevalence of circulating antibodies against a streptokinase C-terminal peptide in normal blood donors.

Streptokinase (SK) is a streptococcal protein widely used as a thrombolytic agent. Anti-SK antibodies (Abs) are found in most individuals due to common streptococcal infections. The presence of these Abs increases the possibility of allergic reactions and may reduce the thrombolytic efficacy of SK upon a first therapy. Previous studies report on the immunodominance of the SK C-terminus and the role of this region in plasminogen (Plg) activation. The aim of this study was to assess the prevalence of circulating Abs to the SK C-terminus in normal blood donors. Sera from 1008 subjects aged 30 to 60 years were tested by Ultra-Micro-ELISA using a synthetic peptide resembling the SKC-2 C-terminus. An overall prevalence of 30. 4% was found. Prevalence was significantly higher among male than among female donors (RR = 1.70, 1.13 < CI < 2.55). No age effect was observed. This is the first extensive study about Abs directed against a particular region of SK in normal subjects.

Simulation of control strategies for the cattle tick Boophilus microplus employing vaccination with a recombinant Bm86 antigen preparation.

Current strategies for the control of the cattle tick Boophilus microplus include the use of chemicals as the principal control method. These methods, however, have met with partially successful results. The recent development of immunological methods for the control of the cattle tick has opened new possibilities for the design of control strategies. Employing the results obtained by us in experiments testing the effect of vaccination with the recombinant vaccine, Gavac (Heber Biotec S.A.), on tick populations, we have developed a model to evaluate, through a computer program, the efficacy of the vaccine as a control method. The action of the vaccine on the control of tick populations was simulated and the specific serum antibody titers required to decrease the tick population in the field were calculated. The specific serum antibody titer required to decrease the tick population in the field after the first vaccination scheme was found to be > or = 57,200 and the antibody titer required to maintain this effect when the vaccine is already acting and after successive revaccinations was found to be > or = 27,500. Considerations about revaccination schemes and combination between vaccination and acaricide treatments as possible control strategies are discussed.

Effect of vaccination with a recombinant Bm86 antigen preparation on natural infestations of Boophilus microplus in grazing dairy and beef pure and cross-bred cattle in Brazil.

Current methods for the control of the cattle tick Boophilus microplus infestations are not effective and the parasite remains a serious problem for the cattle industry in tropical and sub-tropical areas. Recent advances have introduced the possibility for the immunological control of the parasite through the use of recombinant vaccines. Recently, it was shown that the recombinant vaccine Gavac (Heber Biotec S.A.) is able to control B. microplus populations in artificially infected grazing dairy cattle in Cuba. To assay the effect of the vaccine on a different B. microplus strain and under different ecological conditions, we conducted a trial in Brazil on grazing dairy and beef pure and cross-bred cattle under natural infestation conditions. A farm in the northeast of the state of Sao Paulo was selected and two groups of animals per breed were included in the experiment and were maintained grazing on separate but similar pastures. For each breed, one group was vaccinated with the vaccine Gavac and the second group was not vaccinated and was employed as a control. In vaccinated cattle, during 36 weeks of experiment, the average infestation rate was maintained below 78 ticks per animal while average infestation peaks (mean +/- S.E.) of 144 +/- 44 ticks per animal (for dairy cross-bred cattle) and 195 +/- 42 ticks per animal (for beef cross-bred cattle) were recorded in the control groups. Tick infestation rates showed statistical significant differences (p = 0.04) between both experimental groups throughout the experiment. These results clearly showed, as in the Cuban study, that the vaccine controlled tick numbers in successive generations in the field.

Control of Boophilus microplus populations in grazing cattle vaccinated with a recombinant Bm86 antigen preparation.

Current methods for the control of cattle tick Boophilus microplus infestations are not effective and the parasite remains a serious problem for the cattle industry in tropical and subtropical areas. Recently, we developed a vaccine against B. microplus employing a recombinant Bm86 (rBm86) antigen preparation (Gavac, Heber Biotec) and it was shown to induce a protective response in vaccinated animals under controlled conditions. Here we show that, under field conditions in grazing cattle, the vaccine is able to control B. microplus populations. Two parasite-free farms were employed for the study. In the first farm, animals were vaccinated with the recombinant vaccine, while, in the second, animals received a saline injection in adjuvant. After immunization, animals were artificially infected and the infestation rate was recorded. Over the 33 weeks of the experiment, the infestation rate was lower in the vaccinated group compared with the control group. At the end of the experiment it was necessary to use chemicals in the control farm after serious losses in production and animals.