CYP3A5*3A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia

Background: The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on biotransformation of xenobiotics. CYP3A5 SNPs have been associated with variations on enzyme activity that can modify the metabolism of several drugs. Methods: In order to evaluate the influence of CYP3A5 variants on response to lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were selected. After a wash-out period of 4 weeks, individuals were treated with atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA sequencing. Results: >Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non-Africans (*3C: 84.9% and *1D 84.8%, p<0.01). Non-Africans carrying *3A allele (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to atorvastatin than non-*3A allele carriers (p<0.05). Conclusion: CYP3A5*3A allele is associated with reduced cholesterol-lowering response to atorvastatin in non-African individuals. (C) 2008 Elsevier B.V. All rights reserved.

Nitric oxide participation in granulomatous response induced by Paracoccidioides brasiliensis infection in mice

The role of nitric oxide (NO) in granulomas of Paracoccidioides brasiliensis-infected inducible NO synthase-deficient C57BL/6 mice (iNOS KO) and their wild-type counterparts and its association with osteopontin (OPN) and matrix metalloproteinases (MMPs) was studied. At 15 days after infection (DAI), iNOS KO mice showed compact and necrotic granulomas with OPN+ macrophages and multinucleated giant cells, whereas wild-type mice developed loose granulomas with many fungi and OPN+ cells distributed throughout the tissue. In addition, high OPN levels and fungal load were observed in iNOS KO mice. Both experimental groups had MMP-9 activity. At 120 DAI, iNOS KO had smaller granulomas with OPN+ cells, lower OPN levels, lower fungal load and decreased MMP-9 activity compared with wild-type mice. These findings suggest that NO has an important role in granuloma modulation, by controlling OPN and MMP production, as well as by inducing loose granulomas formation and fungal dissemination, resulting, at later phases, in progression of paracoccidioidomycosis.

Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response

Components of the DNA mismatch repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei. (C) 2010 Elsevier B.V. All rights reserved.

Emergency department triage scales and their components : a systematic review of the scientific evidence

Emergency department (ED) triage is used to identify patients' level of urgency and treat them based on their triage level. The global advancement of triage scales in the past two decades has generated considerable research on the validity and reliability of these scales. This systematic review aims to investigate the scientific evidence for published ED triage scales. The following questions are addressed: 1. Does assessment of individual vital signs or chief complaints affect mortality during the hospital stay or within 30 days after arrival at the ED? 2. What is the level of agreement between clinicians' triage decisions compared to each other or to a gold standard for each scale (reliability)? 3. How valid is each triage scale in predicting hospitalization and hospital mortality? A systematic search of the international literature published from 1966 through March 31, 2009 explored the British Nursing Index, Business Source Premier, CINAHL, Cochrane Library, EMBASE, and PubMed. Inclusion was limited to controlled studies of adult patients (≥15 years) visiting EDs for somatic reasons. Outcome variables were death in ED or hospital and need for hospitalization (validity). Methodological quality and clinical relevance of each study were rated as high, medium, or low. The results from the studies that met the inclusion criteria and quality standards were synthesized applying the internationally developed GRADE system. Each conclusion was then assessed as having strong, moderately strong, limited, or insufficient scientific evidence. If studies were not available, this was also noted. We found ED triage scales to be supported, at best, by limited and often insufficient evidence. The ability of the individual vital signs included in the different scales to predict outcome is seldom, if at all, studied in the ED setting. The scientific evidence to assess interrater agreement (reliability) was limited for one triage scale and insufficient or lacking for all other scales. Two of the scales yielded limited scientific evidence, and one scale yielded insufficient evidence, on which to assess the risk of early death or hospitalization in patients assigned to the two lowest triage levels on a 5-level scale (validity).

A systematic review of triage-related interventions to improve patient flow in emergency departments

Background Overcrowding in emergency departments is a worldwide problem. A systematic literature review was undertaken to scientifically explore which interventions improve patient flow in emergency departments. Methods A systematic literature search for flow processes in emergency departments was followed by assessment of relevance and methodological quality of each individual study fulfilling the inclusion criteria. Studies were excluded if they did not present data on waiting time, length of stay, patients leaving the emergency department without being seen or other flow parameters based on a nonselected material of patients. Only studies with a control group, either in a randomized controlled trial or in an observational study with historical controls, were included. For each intervention, the level of scientific evidence was rated according to the GRADE system, launched by a WHO-supported working group. Results The interventions were grouped into streaming, fast track, team triage, point-of-care testing (performing laboratory analysis in the emergency department), and nurse-requested x-ray. Thirty-three studies, including over 800,000 patients in total, were included. Scientific evidence on the effect of fast track on waiting time, length of stay, and left without being seen was moderately strong. The effect of team triage on left without being seen was relatively strong, but the evidence for all other interventions was limited or insufficient. Conclusions Introducing fast track for patients with less severe symptoms results in shorter waiting time, shorter length of stay, and fewer patients leaving without being seen. Team triage, with a physician in the team, will probably result in shorter waiting time and shorter length of stay and most likely in fewer patients leaving without being seen. There is only limited scientific evidence that streaming of patients into different tracks, performing laboratory analysis in the emergency department or having nurses to request certain x-rays results in shorter waiting time and length of stay.

A violência no contexto de um serviço de urgência: análise do processo de cuidar na visão das vítimas e profissionais de saúde em Natal/RN

Exploratory descriptive study, with a quantitative approach and prospective data, performed in Pronto Socorro Clóvis Sarinho (PSCS), in Natal/RN, aiming to analyze care given by the nursing and medical staff to victims of violence attended to in an emergency hospital in Natal/RN; to identify care given by the nursing and medical staff as viewed by the victims; to compare data observed during the process of care with the victim s view on the care given by the nursing and medical staff; to identify the existing knowledge on violence and the process of caring for victims and its relation with prejudice; to identify obstacles and perspectives for prevention during the process of caring for victims in the emergency services. The population consisted of 97 physicians, 16 nurses, 75 nursing technicians and assistants and 365 victims of violence, with data collected from April to May 2009. Out of 188 professionals, 52.1% are female; 32% were aged 41 to 50; 99.5% had given care to a victim of violence; 90.4% reported to have given care to patients under custody; among these, 17.3% felt prejudice; 55.3% stated they don t provide different care for assaulted victims and assailants, however 44.7% stated they do; 86.7% feel their workplace is unsafe; 61.7% denied the existence of any obstacle and 38.3% reported the existence of obstacles; among these, 26.1% referred to inadequate facilities; 37.8% believe reinforcing security and professional training are the main solutions. Among the 365 researched violence victims, 82.2% were assaulted; male (69.6%); aged 18 to 24 (24.9%); hailing from the Greater Natal area (89.9%); on 19.7% the event happened on Saturday; during the night (48.8%); victim of physical assault (61.4%); produced by body force (27.7%); 24.4% were injured in the head and neck. 57% had used some drug, among which alcohol was predominant (75.5%). On 621 observations performed during the victim care process, when compared to the report of assaulted victims, there was a statistical difference, at 5% significance level, regarding reception, resistance from the professionals, questioning about the violent event, providing of guidance, interaction with the patient and the understanding of receiving proper care, and care resolution. In comparisons involving the observed and the assailant victims reports, there was a statistical difference regarding the resence of resistance from the professionals, performance of necessary procedures and the nteraction with the patient and the understanding of receiving proper care and 58.1% reported the nursing team was the one that provided the best care. We conclude that professionals had lready given care to assailant patients, acknowledge the importance of knowing how the vent took place and acquired this preparation during their practice. The most often referred bstacles that hinder assistance were: inadequate facilities, material deficit and lack of rofessional preparation. As solutions for these problems, they cited the reinforcement of ecurity and professional training

Satisfação da equipe de enfermagem do serviço de atendimento móvel às urgências (SAMU) no ambiente de trabalho

Descriptive exploratory study, prospective with quantitative approach, performed on the Medical Regulation Central of SAMU/Natal, aiming to identify the level of professional satisfaction of the members of the nursing team working at SAMU/Natal; and verify the degree of importance attributed by the professionals to each of the components Professional Satisfaction: autonomy, interaction, professional status , work requirements, organizational rules and remuneration. The population was of 60 professionals, with data collected from january to february 2005. We used an instrument translated and validated by Lino (1999) to the portuguese language, the Professional Satisfaction Rate (PSR). The results demonstrate that there was a slight predominance of the female gender (54,9%); aged between 36 and 45 years old (60,8%); married (58,8%), 82,4% with children, 30,8% aged between 05 and 09. Regarding formation, we observed that 78,4% were nursing technicians and 21,6% nurses, formed for 11 to 15 years (17,5%). From the 11 nurses, 09 (81,8%) informed they have specialization, 29,4% of the team has been working for 11 to 15 years on the urgency area, 58.8% works for more than 02 years on SAMU, 72,6% of the team members have fixed work schedules. There was homogeneity on the work shifts: 41,2% on the day shift and 53% on the night shift. Regarding the reason to be working on SAMU, 64% chose to work in the service, and among these 76,3% predominantly perform direct care to the patients, 96,1% like and are satisfied to work in the service. Regarding the remuneration, 90,9% informed they receive 05 to 10 minimum wages; 70% of the technicians informed they receive -2 to 05 minumum wages, 50,1% informed they receive no additional benefit. The analysis of PSR through Cronbach s Alpha Coeficient resulted on the value of 0,94 and through Kendall s Tau Coeficient on 0,87, demonstrating to be a trustworthy instrument to measure the level of professional satisfaction of the SAMU nursing team, in our environment. As for the level of importance attributed to the components of professional satisfaction, we indentified that the nursing team considered the Autonomy component as the most important, followed by the component Remuneration, Interaction, Work Requirements, Work Requirements, Organizational Rules and Professional Status . Regarding the current level of professional satisfaction, we identified they were most satisfied with the Professional Status , Autonomy, Interaction, Remuneration, Work Requirements and Organizational Rules. The real professional satisfaction level, calculated through statistics, however, tells these professionals are more satisfied with Autonomy, Remuneration, Interaction, Work Requirements, professional Status and Organizational Rules. The PSR in our work was of 8,6, indicating the SAMU Natal nursing team has little satisfaction on their work environment

Modelo arquitetural de comunicação para monitoramento de pacientes baseado em middleware, computação móvel e ubíqua

Hospital Automation is an area that is constantly growing. The emergency of new technologies and hardware is transforming the processes more efficient. Nevertheless, some of the hospital processes are still being performed manually, such as monitoring of patients that is considered critical because it involves human lives. One of the factors that should be taken into account during a monitoring is the agility to detect any abnormality in vital signs of patients, as well as warning of this anomaly to the medical team involved. So, this master's thesis aims to develop an architecture to automate this process of monitoring and reporting of possible alert to a professional, so that emergency care can be done effectively. The computing mobile was used to improve the communication by distributing messages between a central located into the hospital and the mobile carried by the duty

IgE antibody response to the main antigenic component of Paracoccidioides brasiliensis in patients with paracoccidioidomycosis

Paracoccidioidomycosis (PCM) has two main clinical presentations, a chronic form (CF) and an acute, more severe form (AF). The AF is associated with a more marked dysfunction of the patient's immune response, and a distinct anti-Paracoccidioides brasiliensis immunoglobulin (Ig)A and IgG antibody subclass expression, compared with that seen in the CF. In this study we investigated the presence of IgE antibodies against the main P. brasiliensis antigen (a 43-kDa molecule) in the serum of PCM patients using an enzyme-linked immunosorbent assay. We found that 100% of the AF patients (n = 16) produced IgE antibodies, mostly at high levels, whereas only 9 (27%) out of 33 CF patients produced this isotype. Interestingly, these nine patients presented higher serological titers on the counter-immunoelectrophoresis assays than did those who did not produce IgE; a finding that suggests that they had a relatively more severe disease. As IgE is a characteristic feature of the AF patients, and switching to a positive IgE response is dependent on interleukin-4, our results support the notion that the relatively more severe impairment of cellular immunity in the AF is probably related to a Th-2 pattern of immune response.

Effects of mercury intoxication on the response of horizontal cells of the retina of thraira fish (Hoplias malabaricus)

Methyl mercury (MeHg) is highly neurotoxic, affecting visual function in addition to other central nervous system functions. The effect of mercury intoxication on the amplitude of horizontal cell responses to light was studied in the retina of the fish Hoplias malabaricus. Intracellular responses were recorded from horizontal cells of fish previously intoxicated with MeHg by intraperitoneal injection (IP group) or by trophic exposure (T group). Only one retina per fish was used. The doses of MeHg chloride administered to the IP group were 0.01, 0.05, 0.1, 1.0, 2.0, and 6.0 mg/kg. The amplitudes of the horizontal cell responses were lower than control in individuals exposed to 0.01 (N = 4 retinas), 0.05 (N = 2 retinas) and 0.1 mg/kg (N = 1 retina), whereas no responses were recorded in the 1.0, 2.0, and 6.0 mg/kg groups. T group individuals were fed young specimens of Astyanax sp previously injected with MeHg corresponding to 0.75 (N = 1 retina), 0.075 (N = 8 retinas) or 0.0075 (N = 4 retinas) mg/kg fish body weight. After 14 doses, one every 5 days, the amplitude of the horizontal cell response was higher than control in individuals exposed to 0.075 and 0.0075 mg/kg, and lower in individuals exposed to 0.75 mg/kg. We conclude that intoxication with MeHg affects the electrophysiological response of the horizontal cells in the retina, either reducing or increasing its amplitude compared to control, and that these effects are related to the dose and/or to the mode of administration.

Malaria at Humaita county, Amazonas state, Brazil: XVII - immune response in patients with Plasmodium falciparum according to gametocytes

Em agosto de 1983, os Autores, estudaram 36 doentes com infecção causada pelo Plasmodium falciparum e 14 indivíduos normais, nascidos na região de Humaitá, que nunca tiveram malária, sem esplenomegalia, com exame parasitológico de sangue e hemaglutinação passiva negativas. Todos eles foram submetidos à observação clínica completa, exame hematológico, exame parasitológico de sangue e tipagem de linfócitos. Os linfócitos foram isolados e congelados em nitrogênio líquido, para posterior tipagem pela formação de rosetas. Os doentes foram classificados em dois grupos de acordo com a presença (13 doentes), ou ausência (23 doentes) de gametócitos antes do tratamento. Houve predomínio de formas graves no grupo de doentes sem gametócitos. Os resultados mostraram diminuição do número de linfócitos T em ambos os grupos de doentes, com ou sem gametócitos antes do tratamento, enquanto que o número de linfócitos B foi normal apenas no grupo de doentes com gametócitos. Essas observações, assim como as que foram relatadas pelos Autores anteriormente, permitem associar a presença de gametócitos circulantes com o número normal de células B em doentes com formas leves de malária causada pelo Plasmodium falciparum.

Teaching the Rational Use of Medicines to medical students: a qualitative research

Background: Prescribing is a complex and challenging task that must be part of a logical deductive process based on accurate and objective information and not an automated action, without critical thinking or a response to commercial pressure. The objectives of this study were 1) develop and implement a discipline based on the WHO's Guide to Good Prescribing; 2) evaluate the course acceptance by students; 3) assess the impact that the Rational Use of Medicines (RUM) knowledge had on the students habits of prescribing medication in the University Hospital.Methods: In 2003, the RUM principal, based in the WHO's Guide to Good Prescribing, was included in the official curriculum of the Botucatu School of Medicine, Brazil, to be taught over a total of 24 hours to students in the 4th year. We analyzed the students' feedback forms about content and teaching methodology filled out immediately after the end of the discipline from 2003 to 2010. In 2010, the use of RUM by past students in their medical practice was assessed through a qualitative approach by a questionnaire with closed-ended rank scaling questions distributed at random and a single semistructured interview for content analysis.Results: The discipline teaches future prescribers to use a logical deductive process, based on accurate and objective information, to adopt strict criteria (efficacy, safety, convenience and cost) on selecting drugs and to write a complete prescription. At the end of it, most students considered the discipline very good due to the opportunity to reflect on different actions involved in the prescribing process and liked the teaching methodology. However, former students report that although they are aware of the RUM concepts they cannot regularly use this knowledge in their daily practice because they are not stimulated or even allowed to do so by neither older residents nor senior medical staff.Conclusions: This discipline is useful to teach RUM to medical students who become aware of the importance of this subject, but the assimilation of the RUM principles in the institution seems to be a long-term process which requires the involvement of a greater number of the academic members.

Maxillo-mandibular counter-clockwise rotation and mandibular advancement with TMJ Concepts (R) total joint prostheses Part IV - Soft tissue response

The purpose of this Study was to evaluate Soft tissue response to rnaxillo-mandibular counter-clockwise rotation, with TMJ reconstruction and mandibular advancement using TMJ Concepts (R) total joint prostheses, and maxillary osteotomies in 44 females. All patients were operated at Baylor University Medical Center, Dallas TX, USA, by one Surgeon (Wolford). Eighteen patients had genioplasties with either porous block hydroxyapatite or hard tissue replacement implants (Group 2) 26 had no genioplasty (Group 1). Surgically, the maxilla moved forward and upward by counter-clockwise maxillo-mandibular rotation with greater horizontal movement in Group 2. Vertically, both groups showed diversity of maxillo-mandibular mean movement. Group I showed a consistent 1:0.97 ratio of hard to soft tissue advancement at pogonion; Group 2 results were less consistent, with ratios between 1:0.84 and 1:1.02. Horizontal changes in upper lip morphology after maxillary advancement/impaction, VY closure, and alar base cinch sutures showed greater movement in both groups, than observed in hard tissue. Counter-clockwise rotation of the maxillo-mandibular complex using TMJ Concepts total joint prostheses resulted in similar soft tissue response as previously reported for traditional maxillo-mandibular advancement without counter-clockwise rotation of the occlusal plane. The association of chin implants, in the present sample, showed higher variability of soft tissue response.

Quantification of fibrosis and mast cells in the tissue response of endodontic sealer irradiated by low-level laser therapy

Low-level laser therapy (LLLT) accelerates tissue repair. Mast cells induce the proliferation of fibroblasts and the development of local fibrosis. The objective of this study was to quantify fibrosis rate and mast cells in connective tissue after endodontic sealer zinc oxide and eugenol (ZOE) was implanted and submitted to LLLT, immediately after implant and again 24 h later. Sixty mice were distributed into three groups: GI, GII, and GIII (n = 20). In GI, the tubes filled with Endofill were implanted in the animals and were not irradiated with LLLT. In GII, the tubes containing Endofill were implanted in the animals and then irradiated with red LLLT (InGaAIP) 685-nm wavelength, D=72 J/Cm(2), E = 2 J, T=58 s, P=35 mW, and in GIII, the tubes with Endofill were implanted and irradiated with infrared LLLT (AsGaAl) 830-nm wavelength, D=70 J/Cm(2), E = 2 J, T=40 s, P=50 mW. After 7 days and 30 days, the animals were killed. A series of 6-mu m-thick sections were obtained and stained with Toluidine Blue and Picrosirius and analyzed under a standard light microscope using a polarized light filter for the quantification of fibrosis. The statistics were qualitative and quantitative with a significance of 5%. The irradiation with LLLT did not offer improvement in the fibrosis rate, however, it provided a significant decrease in the concentration of independent mast cells for the period studied.

Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis

We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 µg DNA-HSP65. on day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.