N-ftaloil-glicin-hidroksamska kiselina kao kelator željeza u serumu štakora

The aim of this study was to investigate the activity of N-phthaloyl-glycine-hydroxamic acid (Phth-Gly-HA) as a new iron chelator in vivo to be used in iron overload diseases. After intraperitoneal application of Phth-Gly-HA to male rats (1 mg kg1 body mass) once a day for seven days, iron serum level decreased by 21%, whereas the iron value dropped by 32% in female rats (1.5 mg kg1 body mass). The results indicate that the tested substance has the ability to bind serum iron by complexation. Besides transferrin iron release, mobilization of ferritin iron is also possibleU cilju pronalaženja novog efikasnog kelatora koji bi mogao poslužiti u liječenju bolesti izazvanih viškom željeza, u ovom je radu ispitano djelovanje N-ftaloil-glicin-hidroksamske kiseline (Phth-Gly-HA) in vivo. Istraživan je utjecaj kelatora na razinu željeza u serumu štakora nakon intraperitonealne primjene vodene otopine Phth-Gly-HA (0,1 mg mL1) jednom dnevno tijekom 7 dana. Kontrolne su životinje primale fiziološku otopinu. Kod mužjaka injektiranje test supstancije (1 mg kg1) uzrokovalo je pad serumskog željeza za 21%. Kod ženki je nakon tretmana (1,5 mg kg1) izmjereno sniženje razine željeza za 35%. Rezultati pokazuju da ispitivana supstanca ima sposobnost kompleksiranja serumskog željeza, pretežno transferinskog, ali da postoji mogućnost mobilizacije željeza i iz feritinskih zaliha

Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease

Background: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. Methodology/Principal Findings: To this end, we conducted 18 FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucos

Review of the effects of protection in marine protected areas: current knowledge and gaps

The effectiveness of marine protected areas (MPAs) and the conservation of marine environments must be based on reliable information on the quality of the marine environment that can be obtained in a reasonable timeframe. We reviewed studies that evaluated all aspects related to the effectiveness of MPAs in order to describe how the studies were conducted and to detect fields in which research is lacking. Existing parameters used to evaluate the effectiveness of MPAs are summarised. Two-hundred and twenty-two publications were reviewed. We identified the most commonly used study subjects and methodological approaches. Most of the studies concentrated on biological parameters. Peer reviewed studies were based on control vs. impact design. BACI and mBACI designs were used in very few studies. Through this review, we have identified gaps in the objectives assigned to MPAs and the way in which they have been evaluated. We suggest some guidelines aimedat improving the assessment of the effects of protection in MPAs

Revisión de los efectos de la protección en las áreas marinas protegidas: conocimiento y deficiencias actuales

This work was carried out with financial support from the Commission of the European Community, specific RTD program 'Specific Support to Policies', SSP–2003–006539 'European Marine Protected Areas as Tools for Fisheries Management and Conservation (EMPAFISH)'.The effectiveness of marine protected areas (MPAs) and the conservation of marine environments must be based on reliable information on the quality of the marine environment that can be obtained in a reasonable timeframe. We reviewed studies that evaluated all aspects related to the effectiveness of MPAs in order to describe how the studies were conducted and to detect fields in which research is lacking. Existing parameters used to evaluate the effectiveness of MPAs are summarised. Two–hundred and twenty–two publications were reviewed. We identified the most commonly used study subjects and methodological approaches. Most of the studies concentrated on biological parameters. Peer reviewed studies were based on control vs. impact design. BACI and mBACI designs were used in very few studies. Through this review, we have identified gaps in the objectives assigned to MPAs and the way in which they have been evaluated. We suggest some guidelines aimed at improving the assessment of the effects of protection in MPAs.La efectividad de las áreas marinas protegidas (AMPs) y la conservación del medio ambiente marino debe basarse en información fiable sobre la calidad del medio marino que pueda obtenerse en un plazo de tiempo razonable. Se revisaron estudios que evalúan aspectos relacionados con la efectividad de las AMPs con el fin de describir cómo se realizaron los estudios y detectar donde existen vacíos en la investigación. En este estudio se enumeran los parámetros existentes para evaluar la efectividad de las AMPs. Se revisaron 224 publicaciones. Identificamos los objetos de estudio más utilizados y los enfoques metodológicos. La mayoría de los estudios se centran en el estudio de parámetros biológicos. Los estudios publicados se basaron en el diseño control frente a impacto. En muy pocos estudios se utilizaron diseños de muestreo BACI y mBACI. A través de esta revisión, se han identificado deficiencias en los objetivos de las AMPs y en la manera como han sido evaluados. Como conclusión sugerimos algunas pautas para mejorar la evaluación de los efectos de la protección en estas zonas

Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults

Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Review of the effects of protection in marine protected areas: current knowledge and gaps

The effectiveness of marine protected areas (MPAs) and the conservation of marine environments must be based on reliable information on the quality of the marine environment that can be obtained in a reasonable timeframe. We reviewed studies that evaluated all aspects related to the effectiveness of MPAs in order to describe how the studies were conducted and to detect fields in which research is lacking. Existing parameters used to evaluate the effectiveness of MPAs are summarised. Two–hundred and twenty–two publications were reviewed. We identified the most commonly used study subjects and methodological approaches. Most of the studies concentrated on biological parameters. Peer reviewed studies were based on control vs. impact design. BACI and mBACI designs were used in very few studies. Through this review, we have identified gaps in the objectives assigned to MPAs and the way in which they have been evaluated. We suggest some guidelines aimed at improving the assessment of the effects of protection in MPAsRevisión de los efectos de la protección en las áreas marinas protegidas: conocimiento y deficiencias actuales.— La efectividad de las áreas marinas protegidas (AMPs) y la conservación del medio ambiente marino debe basarse en información fiable sobre la calidad del medio marino que pueda obtenerse en un plazo de tiempo razonable. Se revisaron estudios que evalúan aspectos relacionados con la efectividad de las AMPs con el fin de describir cómo se realizaron los estudios y detectar donde existen vacíos en la investigación. En este estudio se enumeran los parámetros existentes para evaluar la efectividad de las AMPs. Se revisaron 224 publicaciones. Identificamos los objetos de estudio más utilizados y los enfoques metodológicos. La mayoría de los estudios se centran en el estudio de parámetros biológicos. Los estudios publicados se basaron en el diseño control frente a impacto. En muy pocos estudios se utilizaron diseños de muestreo BACI y mBACI. A través de esta revisión, se han identificado deficiencias en los objetivos de las AMPs y en la manera como han sido evaluados. Como conclusión sugerimos algunas pautas para mejorar la evaluación de los efectos de la protección en estas zonasPublicado

Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes

mpressive properties make graphene-based materials (GBMs) promising tools for nanoelectronics and biomedicine. However, safety concerns need to be cleared before mass production of GBMs starts. As skin, together with lungs, displays the highest exposure to GBMs, it is of fundamental importance to understand what happens when GBMs get in contact with skin cells. The present study was carried out on HaCaT keratinocytes, an in vitro model of skin toxicity, on which the effects of four GBMs were evaluated: A few layer graphene, prepared by ball-milling treatment (FLG), and three samples of graphene oxide (GOs, a research-grade GO1, and two commercial GOs, GO2 and GO3). Even though no significant effects were observed after 24 h, after 72 h the less oxidized compound (FLG) was the less cytotoxic, inducing mitochondrial and plasma-membrane damages with EC 50 s of 62.8 \u3bcg/mL (WST-8 assay) and 45.5 \u3bcg/mL (propidium iodide uptake), respectively. By contrast, the largest and most oxidized compound, GO3, was the most cytotoxic, inducing mitochondrial and plasma-membrane damages with EC 50 s of 5.4 and 2.9 \u3bcg/mL, respectively. These results suggest that only high concentrations and long exposure times to FLG and GOs could impair mitochondrial activity associated with plasma membrane damage, suggesting low cytotoxic effects at the skin level

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability