Efetividade da irradiação por micro-ondas e da terapia fotodinâmica na inativação de micro-organismos presentes em próteses totais: estudo clínico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Glycolipid Sensing and Innate Immunity in Paracoccidioidomycosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Validation of a stability indicating capillary electrophoresis method for the determination of darunavir in tablets and comparison with the of infrared absorption spectroscopic method

Darunavir (DRV) is a protease inhibitor used in the treatment of HIV infection, which constitutes a keystone in the therapy of patients infected with this virus. There is no monograph described in official compendia. The literature provides few methods of analysis for the determination of DRV in pharmaceuticals which include TLC, IR, UPLC, HPLC, HPLC-MS, HPLC-MS/MS, but there are no reports of the use of capillary electrophoresis (CE) for the determination of this drug. Thus, this research proposed the development and validation of a CE method for the determination of DRV in tablets. The method was completely validated according to the International Conference on Harmonization guidelines, showing linearity, selectivity, precision, accuracy and robustness. The migration was achieved in less than 1 minute using fused-silica uncoated capillary with an id of 50 μm and total length of 21 cm and voltage of +20 kV. The sample injection was performed in the hydrodynamic mode. The method was linear over the concentration range of 50-200 μg mL-1 with correlation coefficient 0.9998 and limits of detection and quantification of 7.29 and 22.09 μg mL-1, respectively. The drug was subjected to acid, base, oxidation and photolysis degradation. Degradation products were found interfering with the assay of DRV, therefore the method can be regarded as stability indicating. The validated method is useful and appropriate for the routine quality control of DRV in tablets.

Performance characteristics of UV and visible spectrophotometry methods for quantitative determination norfloxacin in tablets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thermal analysis and validation of UV and visible spectrophotometric methods for the determination of new antibiotic tigecycline in pharmaceutical product

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development and validation of infrared spectroscopy method for the determination of darunavir in tabets

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Higienización de las manos: el cotidiano del profesional de la salud en una unidad de internación pediátrica

Objective. To describe behaviors related to hand cleaning in health professionals who work in the pediatric inpatient unit of a university hospital. Methodology. Descriptive study, in which the studied population was the sanitary staff who worked in a pediatric inpatient unit of a university hospital, there were a total of 43 people. Information was collected through an observation process and a survey applied on hand washing techniques, at the beginning of the study and a month later of the first one. Results. In just 7% of the observations, participants washed their hands before developing the procedure; one out of two followed the steps described in the technique. The most frequent failure in hand washing was presented in the step of rubbing the right hand palm over the left had dorsum, crossing the fingers and vice versa (18%). Conclusion. Participants of the study didn’t have the habit to wash their hands according to the recommended technique. Data suggest the necessity to promote educational actions to change staff behaviors and attitudes towards the steps and techniques of hand washing before and after performing any procedure.

Memory in children with temporal lobe epilepsy is at least partially explained by executive dysfunction

An association between memory and executive dysfunction (ED) has been demonstrated in patients with mixed neurological disorders. We aimed to investigate the impact of ED in memory tasks of children with temporal lobe epilepsy (TLE). We evaluated 36 children with TLE and 28 controls with tests for memory, learning, attention, mental flexibility, and mental tracking. Data analysis was composed of comparison between patients and controls in memory and executive function; correlation between memory and executive function tests; and comparison between patients with mild and severe ED in memory tests. Children with TLE had worse performance in focused attention, immediate and delayed recall, phonological memory, mental tracking, planning, and abstraction. Planning, abstraction, and mental tracking were correlated with visual and verbal memory. Children with severe ED had worse performance in verbal and visual memory and learning tests. This study showed that ED was related to memory performance in children with TLE. (C) 2012 Elsevier Inc. All rights reserved.

The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

Abstract Background a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. Results elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. Conclusion highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.

Study of materials and technology of ancient floor mosaics' substrate

Ancient pavements are composed of a variety of preparatory or foundation layers constituting the substrate, and of a layer of tesserae, pebbles or marble slabs forming the surface of the floor. In other cases, the surface consists of a mortar layer beaten and polished. The term mosaic is associated with the presence of tesserae or pebbles, while the more general term pavement is used in all the cases. As past and modern excavations of ancient pavements demonstrated, all pavements do not necessarily display the stratigraphy of the substrate described in the ancient literary sources. In fact, the number and thickness of the preparatory layers, as well as the nature and the properties of their constituent materials, are often varying in pavements which are placed either in different sites or in different buildings within a same site or even in a same building. For such a reason, an investigation that takes account of the whole structure of the pavement is important when studying the archaeological context of the site where it is placed, when designing materials to be used for its maintenance and restoration, when documenting it and when presenting it to public. Five case studies represented by archaeological sites containing floor mosaics and other kind of pavements, dated to the Hellenistic and the Roman period, have been investigated by means of in situ and laboratory analyses. The results indicated that the characteristics of the studied pavements, namely the number and the thickness of the preparatory layers, and the properties of the mortars constituting them, vary according to the ancient use of the room where the pavements are placed and to the type of surface upon which they were built. The study contributed to the understanding of the function and the technology of the pavements’ substrate and to the characterization of its constituent materials. Furthermore, the research underlined the importance of the investigation of the whole structure of the pavement, included the foundation surface, in the interpretation of the archaeological context where it is located. A series of practical applications of the results of the research, in the designing of repair mortars for pavements, in the documentation of ancient pavements in the conservation practice, and in the presentation to public in situ and in museums of ancient pavements, have been suggested.

An interferon regulatory factor element controls the major immune modulator of murine cytomegalovirus

Immune modulation by herpesviruses, such as cytomegalovirus, is critical for the establishment of acute and persistent infection confronting a vigorous antiviral immune response of the host. Therefore, the action of immune-modulatory proteins has long been the subject of research, with the final goal to identify new strategies for antiviral therapy.rnIn the case of murine cytomegalovirus (mCMV), the viral m152 protein has been identified to play a major role in targeting components of both the innate and the adaptive immune system in terms of infected host-cell recognition in the effector phase of the antiviral immune response. On the one hand, it inhibits cell surface expression of RAE-1 and thereby prevents ligation of the activating natural killer (NK)-cell receptor NKG2D. On the other hand, it decreases cell surface expression of peptide-loaded MHC class I molecules thereby preventing antigen presentation to CD8 T cells. Ultimately, the outcome of CMV infection is determined by the interplay between viral and cellular factors.rnIn this context, the work presented here has revealed a novel and intriguing connection between viral m152 and cellular interferon (IFN), a key cytokine of the immune system: rnthe m152 promoter region contains an interferon regulatory factor element (IRFE) perfectly matching the consensus sequence of cellular IRFEs.rnThe biological relevance of this regulatory element was first suggested by sequence comparisons revealing its evolutionary conservation among various established laboratory strains of mCMV and more recent low-passage wild-derived virus isolates. Moreover, search of the mCMV genome revealed only three IRFE sites in the complete sequence. Importantly, the functionality of the IRFE in the m152 promoter was confirmed with the use of a mutant virus, representing a functional deletion of the IRFE, and its corresponding revertant virus. In particular, m152 gene expression was found to be inhibited in an IRFE-dependent manner in infected cells. Essentially, this inhibition proved to have a severe impact on the immune-modulatory function of m152, first demonstrated by a restored direct antigen presentation on infected cells for CD8 T-cell activation. Even more importantly, this effect of IRFE-mediated IFN signaling was validated in vivo by showing that the protective antiviral capacity of adoptively-transferred, antigen-specific CD8 T cells is also significantly restored by the IRFE-dependent inhibition of m152. Somewhat curious and surprising, the decrease in m152 protein simultaneously prevented an enhanced activation of NK cells in acute-infected mice, apparently independent of the RAE-1/NKG2D ligand/receptor interaction but rather due to reduced ‘missing-self’ recognition.rnTaken together, this work presents a so far unknown mechanism of IFN signaling to control mCMV immune modulation in acute infection.rnrn

Mechanismen der Antigenpräsentation bei der Induktion der CD8-T-Zellantwort gegen das murine Cytomegalovirus

Die Kontrolle der Cytomegalovirus(CMV)-Infektion durch CD8 T-Zellen ist abhängig von der effizienten MHC-Klasse-I-Präsentation viraler Peptide auf der Zelloberfläche. Um die Erkennung infizierter Zellen zu unterdrücken, interferieren während der Early (E)-Phase der murinen CMV (mCMV)-Infektion virale Immunevasine mit dem intrazellulären Transport von Peptid-MHC-I (pMHC-I) Komplexen. Den Immunevasinen gelingt es allerdings nicht, ein Priming mCMV-spezifischer CD8 T-Zellen zu verhindern. Daher wurde angenommen, dass die Initiation der antiviralen CD8 T-Zellantwort primär auf der Cross-Präsentation viraler Peptide auf nicht-infizierten, professionellen Antigen-präsentierenden Zellen (profAPC) beruht und damit unabhängig von viralen Immunevasionsmechanismen ist.rnIm Rahmen der vorliegenden Arbeit wurde mittels BAC-Mutagenese eine mCMV-Rekombinante generiert, um die direkte Präsentation viraler Peptide durch die zusätzliche Expression des zentralen Immunevasins m152 bereits in der Immediate Early (IE)-Phase verstärkt zu unterdrücken. Wie erwartet reduzierte die verstärkte m152-Expression sowohl in der IE- als auch in der E-Phase die pMHC-I-Präsentation in vitro. Dies führte überraschenderweise nach Infektion immunkompetenter BALB/c-Mäuse (Haplotyp H-2d) zu einer verminderten CD8 T-Zellantwort und damit zur Verschlechterung der Kontrolle der Infektion im drainierenden Lymphknoten. Diese Beobachtungen weisen erstmals auf einen wichtigen Beitrag der direkten Antigenpräsentation bei der Initiation der mCMV-spezifischen CD8 T-Zellantwort im immunkompetenten Wirt hin. Zusätzlich konnte auch nach mCMV-Infektion von Cross-Präsentations-defizienten Mäusen (Haplotyp H-2b) eine antivirale CD8 T-Zellantwort initiiert werden. Diese Beobachtung bestätigt, dass durch direkte Antigenpräsentation auf infizierten profAPC trotz viraler Immunevasionsmechanismen eine CD8 T-Zellantwort induziert werden kann. Allerdings wurde weder die antivirale CD8 T-Zellantwort noch die Kontrolle der Infektion im Haplotyp H-2b durch die verstärkte m152-Expression moduliert.rnIn einem weiteren Teil der Arbeit konnte im klinisch relevanten Modellsystem der mCMV-Infektion von Knochenmarktransplantations (KMT)-Rezipienten (Haplotyp H-2d) gezeigt werden, dass die verstärkte m152-Expression die Rekrutierung IE1-spezifischer CD8 T-Zellen in die infizierte Lunge unterdrückt. Dies konnte sowohl früh nach Infektion, als auch während der viralen Latenz nachgewiesen werden. Zusätzlich war die Rekrutierung IE1-spezifischer CD8 T-Zellen in die Lunge deutlich vermindert in Ld--Rezipienten von Ld+-hämatopoetischen Zellen, die das IE1-präsentierende MHC-I-Molekül Ld nicht auf den nicht-hämatopoetischen Gewebszellen exprimieren. Diese Beobachtungen zeigen, dass die Rekrutierung antiviraler CD8 T-Zellen in ein peripheres Organ von der direkten Antigenpräsentation auf nicht-hämatopoetischen, infizierten Gewebszellen bestimmt wird.rnIn der vorliegenden Arbeit konnte somit erstmals gezeigt werden, dass trotz viraler Immunevasionsmechanismen nach mCMV-Infektion des immunkompetenten Wirtes und des KMT-Rezipienten die antivirale CD8 T-Zellantwort von der direkten Antigenpräsentation bestimmt wird.

Impact of a national HIV voluntary counselling and testing (VCT) campaign on VCT in a rural hospital in Tanzania

To evaluate the impact of a national HIV voluntary counselling and testing (VCT) campaign on presentation to HIV care in a rural population in Tanzania.

Minimally invasive postmortem telebiopsy

For the past 10 years, medical imaging techniques have been increasingly applied to forensic investigations. To obtain histological and toxicological information, tissue and liquid samples are required. In this article, we describe the development of a low-cost, secure, and reliable approach for a telematic add-on for remotely planning biopsies on the Virtobot robotic system. Data sets are encrypted and submitted over the Internet. A plugin for the OsiriX medical image viewer allows for remote planning of needle trajectories that are used for needle placement. The application of teleradiological methods to image-guided biopsy in the forensic setting has the potential to reduce costs and, in conjunction with a mobile computer tomographic scanner, allows for tissue sampling in a mass casualty situation involving nuclear, biological, or chemical agents, in a manner that minimizes the risk to involved staff.