958 resultados para Margaret, Queen, consort of Malcolm III, King of Scotland, approximately 1045-1093.
Resumo:
The amount of waste generated by industries has increased gradually in recent years. The proper disposal of residues has been an area of study of many researchers. Several organic compounds are considered potential contaminants of natural waters due to their high toxicity, difficult natural degradation and long persistence in the environment. Ways of recovery and reutilization as well as concepts that minimize the generation of wastes have been increasing widely. Organometallic compound of pyrazine carboxylic acid has proven to be of great interest in many areas. Herein, we studied the use of pyrazine tetracarboxylic acid ligand for complex formation with iron (Fe). The binder (C 8H4N2O8) was synthetized with the addition of Fe (complex) and tested as a catalyst in oxidation reactions of the organic model compound methylene blue (MB). Tetramethyl pyrazine was used in the synthesis, which was oxidized with potassium permanganate in order to form the ligand. The ligand (C 8H4N2O8) was then characterized to validate its formation. For the complex solution, it was used (C 8H4N2O8) and Fe (NO3)3.9H2O 0,01molL-1. After preliminary tests, it was found that the best ratio of Fe and the ligand was 2: 1. Through the oxidation tests, it could be seen that the complex has great potential for the degradation of different concentrations of MB. During only 20 minutes of reaction, approximately 60% of MB 500 mgL -1 was oxidized. The use of the complex was found to be an attractive alternative for oxidation of effluents with high organic compounds levels and contributes to the minimization of organic contaminants hazards in the environment.
Resumo:
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Resumo:
Cogo K, de Andrade A, Labate CA, Bergamaschi CC, Berto LA, Franco GCN, Goncalves RB, Groppo FC. Proteomic analysis of Porphyromonas gingivalis exposed to nicotine and cotinine. J Periodont Res 2012; 47: 766775. (c) 2012 John Wiley & Sons A/S Background and Objective: Smokers are more predisposed than nonsmokers to infection with Porphyromonas gingivalis, one of the most important pathogens involved in the onset and development of periodontitis. It has also been observed that tobacco, and tobacco derivatives such as nicotine and cotinine, can induce modifications to P. gingivalis virulence. However, the effect of the major compounds derived from cigarettes on expression of protein by P.gingivalis is poorly understood. Therefore, this study aimed to evaluate and compare the effects of nicotine and cotinine on the P.gingivalis proteomic profile. Material and Methods: Total proteins of P gingivalis exposed to nicotine and cotinine were extracted and separated by two-dimensional electrophoresis. Proteins differentially expressed were successfully identified through liquid chromatography-mass spectrometry and primary sequence databases using MASCOT search engine, and gene ontology was carried out using DAVID tools. Results: Of the approximately 410 protein spots that were reproducibly detected on each gel, 23 were differentially expressed in at least one of the treatments. A particular increase was seen in proteins involved in metabolism, virulence and acquisition of peptides, protein synthesis and folding, transcription and oxidative stress. Few proteins showed significant decreases in expression; those that did are involved in cell envelope biosynthesis and proteolysis and also in metabolism. Conclusion: Our results characterized the changes in the proteome of P.gingivalis following exposure to nicotine and cotinine, suggesting that these substances may modulate, with minor changes, protein expression. The present study is, in part, a step toward understanding the potential smokepathogen interaction that may occur in smokers with periodontitis.
Resumo:
Background: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.
Resumo:
Pharmaceuticals are useful tools to prevent and treat human and animal diseases. Following administration, a significant fraction of pharmaceuticals is excreted unaltered into faeces and urine and may enter the aquatic ecosystem and agricultural soil through irrigation with recycled water, constituting a significant source of emerging contaminants into the environment. Understanding major factors influencing their environmental fate is consequently needed to value the risk, reduce contamination, and set up bioremediation technologies. The antiviral drug Tamiflu (oseltamivir carboxylate, OC) has received recent attention due to the potential use as a first line defence against H5N1 and H1N1 influenza viruses. Research has shown that OC is not removed during conventional wastewater treatments, thus having the potential to enter surface water bodies. A series of laboratory experiments investigated the fate and the removal of OC in surface water systems in Italy and Japan and in a municipal wastewater treatment plant. A preliminary laboratory study investigated the persistence of the active antiviral drug in water samples from an irrigation canal in northern Italy (Canale Emiliano Romagnolo). After an initial rapid decrease, OC concentration slowly decreased during the remaining incubation period. Approximately 65% of the initial OC amount remained in water at the end of the 36-day incubation period. A negligible amount of OC was lost both from sterilized water and from sterilized water/sediment samples, suggesting a significant role of microbial degradation. Stimulating microbial processes by the addition of sediments resulted in reduced OC persistence. Presence of OC (1.5 μg mL-1) did not significantly affect the metabolic potential of the water microbial population, that was estimated by glyphosate and metolachlor mineralization. In contrast, OC caused an initial transient decrease in the size of the indigenous microbial population of water samples. A second laboratory study focused on basic processes governing the environmental fate of OC in surface water from two contrasting aquatic ecosystems of northern Italy, the River Po and the Venice Lagoon. Results of this study confirmed the potential of OC to persist in surface water. However, the addition of 5% of sediments resulted in rapid OC degradation. The estimated half-life of OC in water/sediment of the River Po was 15 days. After three weeks of incubation at 20 °C, more than 8% of 14C-OC evolved as 14CO2 from water/sediment samples of the River Po and Venice Lagoon. OC was moderately retained onto coarse sediments from the two sites. In water/sediment samples of the River Po and Venice Lagoon treated with 14C-OC, more than 30% of the 14C-residues remained water-extractable after three weeks of incubation. The low affinity of OC to sediments suggests that the presence of sediments would not reduce its bioavailability to microbial degradation. Another series of laboratory experiments investigated the fate and the removal of OC in two surface water ecosystems of Japan and in the municipal wastewater treatment plant of the city of Bologna, in Northern Italy. The persistence of OC in surface water ranged from non-detectable degradation to a half-life of 53 days. After 40 days, less than 3% of radiolabeled OC evolved as 14CO2. The presence of sediments (5%) led to a significant increase of OC degradation and of mineralization rates. A more intense mineralization was observed in samples of the wastewater treatment plant when applying a long incubation period (40 days). More precisely, 76% and 37% of the initial radioactivity applied as 14C-OC was recovered as 14CO2 from samples of the biological tank and effluent water, respectively. Two bacterial strains growing on OC as sole carbon source were isolated and used for its removal from synthetic medium and environmental samples, including surface water and wastewater. Inoculation of water and wastewater samples with the two OC-degrading strains showed that mineralization of OC was significantly higher in both inoculated water and wastewater, than in uninoculated controls. Denaturing gradient gel electrophoresis and quantitative PCR analysis showed that OC would not affect the microbial population of surface water and wastewater. The capacity of the ligninolytic fungus Phanerochaete chrysosporium to degrade a wide variety of environmentally persistent xenobiotics has been largely reported in literature. In a series of laboratory experiments, the efficiency of a formulation using P. chrysosporium was evaluated for the removal of selected pharmaceuticals from wastewater samples. Addition of the fungus to samples of the wastewater treatment plant of Bologna significantly increased (P < 0.05) the removal of OC and three antibiotics, erythromycin, sulfamethoxazole, and ciprofloxacin. Similar effects were also observed in effluent water. OC was the most persistent of the four pharmaceuticals. After 30 days of incubation, approximately two times more OC was removed in bioremediated samples than in controls. The highest removal efficiency of the formulation was observed with the antibiotic ciprofloxacin. The studies included environmental aspects of soil contamination with two emerging veterinary contaminants, such as doramectin and oxibendazole, wich are common parasitic treatments in cattle farms.
Resumo:
The human DMD locus encodes dystrophin protein. Absence or reduced levels of dystrophin (DMD or BMD phenotype, respectively) lead to progressive muscle wasting. Little is known about the complex coordination of dystrophin expression and its transcriptional regulation is a field of intense interest. In this work we found that DMD locus harbours multiple long non coding RNAs which orchestrate and control transcription of muscle dystrophin mRNA isoforms. These lncRNAs are tissue-specific and highly expressed during myogenesis, suggesting a possible role in tissue-specific expression of DMD gene isoforms. Their forced ectopic expression in human muscle and neuronal cells leads to a specific and negative regulation of endogenous dystrophin full lenght isoforms. An intriguing aspect regarding the transcription of the DMD locus is the gene size (2.4Mb). The mechanism that ensures the complete synthesis of the primary transcript and the coordinated splicing of 79 exons is still completely unknown. By ChIP-on-chip analyses, we discovered novel regions never been involved before in the transcription regulation of the DMD locus. Specifically, we observed enrichments for Pol II, P-Ser2, P-Ser5, Ac-H3 and 2Me-H3K4 in an intronic region of 3Kb (approximately 21Kb) downstream of the end of DMD exon 52 and in a region of 4Kb spanning the DMD exon 62. Interestingly, this latter region and the TSS of Dp71 are strongly marked by 3Me-H3K36, an histone modification associated with the regulation of splicing process. Furthermore, we also observed strong presence of open chromatin marks (Ac-H3 and 2Me-H3K4) around intron 34 and the exon 45 without presence of RNA pol II. We speculate that these two regions may exert an enhancer-like function on Dp427m promoter, although further investigations are necessary. Finally, we investigated the nuclear-cytoplasmic compartmentalization of the muscular dystrophin mRNA and, specifically, we verified whether the exon skipping therapy could influence its cellular distribution.
Resumo:
Global warming and ocean acidification, due to rising atmospheric levels of CO2, represent an actual threat to terrestrial and marine environments. Since Industrial Revolution, in less of 250 years, pH of surface seawater decreased on average of 0.1 unit, and is expected to further decreases of approximately 0.3-0.4 units by the end of this century. Naturally acidified marine areas, such as CO2 vent systems at the Ischia Island, allow to study acclimatation and adaptation of individual species as well as the structure of communities, and ecosystems to OA. The main aim of this thesis was to study how hard bottom sublittoral benthic assemblages changed trough time along a pH gradient. For this purpose, the temporal dynamics of mature assemblages established on artificial substrates (volcanic tiles) over a 3 year- period were analysed. Our results revealed how composition and dynamics of the community were altered and highly simplified at different level of seawater acidification. In fact, extreme low values of pH (approximately 6.9), affected strongly the assemblages, reducing diversity both in terms of taxa and functional groups, respect to lower acidification levels (mean pH 7.8) and ambient conditions (8.1 unit). Temporal variation was observed in terms of species composition but not in functional groups. Variability was related to species belonging to the same functional group, suggesting the occurrence of functional redundancy. Therefore, the analysis of functional groups kept information on the structure, but lost information on species diversity and dynamics. Decreasing in ocean pH is only one of many future global changes that will occur at the end of this century (increase of ocean temperature, sea level rise, eutrophication etc.). The interaction between these factors and OA could exacerbate the community and ecosystem effects showed by this thesis.
Resumo:
Background Sedation prior to performance of diagnostic esophagogastroduodenoscopy (EGDE) is widespread and increases patient comfort. But 98% of all serious adverse events during EGDEs are ascribed to sedation. The S3 guideline for sedation procedures in gastrointestinal endoscopy published in 2008 in Germany increases patient safety by standardization. These new regulations increase costs because of the need for more personnel and a prolonged discharge procedure after examinations with sedation. Many patients have difficulties to meet the discharge criteria regulated by the S3 guideline, e.g. the call for a second person to escort them home, to resign from driving and working for the rest of the day, resulting in a refusal of sedation. Therefore, we would like to examine if an acupuncture during elective, diagnostic EGDEs could increase the comfort of patients refusing systemic sedation. Methods/Design A single-center, double blinded, placebo controlled superiority trial to compare the success rates of elective, diagnostic EGDEs with real and placebo acupuncture. All patients aged 18 years or older scheduled for elective, diagnostic EGDE who refuse a systemic sedation are eligible. 354 patients will be randomized. The primary endpoint is the rate of successful EGDEs with the randomized technique. Intervention: Real or placebo acupuncture before and during EGDE. Duration of study: Approximately 24 months. Discussion Organisation/Responsibility The ACUPEND - Trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The Interdisciplinary Endoscopy Center (IEZ) of the University Hospital Heidelberg is responsible for design and conduct of the trial, including randomization and documentation of patients' data. Data management and statistical analysis will be performed by the independent Institute for Medical Biometry and Informatics (IMBI) and the Center of Clinical Trials (KSC) at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg.
Resumo:
Tick-borne encephalitis virus is the causative agent of tick-borne encephalitis, a potentially fatal neurological infection. Tick-borne encephalitis virus belongs to the family of flaviviruses and is transmitted by infected ticks. Despite the availability of vaccines, approximately 2000-3000 cases of tick-borne encephalitis occur annually in Europe for which no curative therapy is available. The antiviral effects of RNA mediated interference by small interfering RNA (siRNA) was evaluated in cell culture and organotypic hippocampal cultures. Langat virus, a flavivirus highly related to Tick-borne encephalitis virus exhibits low pathogenicity for humans but retains neurovirulence for rodents. Langat virus was used for the establishment of an in vitro model of tick-borne encephalitis. We analyzed the efficacy of 19 siRNA sequences targeting different regions of the Langat genome to inhibit virus replication in the two in vitro systems. The most efficient suppression of virus replication was achieved by siRNA sequences targeting structural genes and the 3' untranslated region. When siRNA was administered to HeLa cells before the infection with Langat virus, a 96.5% reduction of viral RNA and more than 98% reduction of infectious virus particles was observed on day 6 post infection, while treatment after infection decreased the viral replication by more than 98%. In organotypic hippocampal cultures the replication of Langat virus was reduced by 99.7% by siRNA sequence D3. Organotypic hippocampal cultures represent a suitable in vitro model to investigate neuronal infection mechanisms and treatment strategies in a preserved three-dimensional tissue architecture. Our results demonstrate that siRNA is an efficient approach to limit Langat virus replication in vitro.
Resumo:
OBJECTIVE: The aim of this study was to assess the microcirculatory and metabolic consequences of reduced mesenteric blood flow. DESIGN: Prospective, controlled animal study. SETTING: The surgical research unit of a university hospital. SUBJECTS: A total of 13 anesthetized and mechanically ventilated pigs. INTERVENTIONS: Pigs were subjected to stepwise mesenteric blood flow reduction (15% in each step, n = 8) or served as controls (n = 5). Superior mesenteric arterial blood flow was measured with ultrasonic transit time flowmetry, and mucosal and muscularis microcirculatory perfusion in the small bowel were each measured with three laser Doppler flow probes. Small-bowel intramucosal Pco2 was measured by tonometry, and glucose, lactate (L), and pyruvate (P) were measured by microdialysis. MEASUREMENTS AND MAIN RESULTS: In control animals, superior mesenteric arterial blood flow, mucosal microcirculatory blood flow, intramucosal Pco2, and the lactate/pyruvate ratio remained unchanged. In both groups, mucosal blood flow was better preserved than muscularis blood flow. During stepwise mesenteric blood flow reduction, heterogeneous microcirculatory blood flow remained a prominent feature (coefficient of variation, approximately 45%). A 30% flow reduction from baseline was associated with a decrease in microdialysis glucose concentration from 2.37 (2.10-2.70) mmol/L to 0.57 (0.22-1.60) mmol/L (p < .05). After 75% flow reduction, the microdialysis lactate/pyruvate ratio increased from 8.6 (8.0-14.1) to 27.6 (15.5-37.4, p < .05), and arterial-intramucosal Pco2 gradients increased from 1.3 (0.4-3.5) kPa to 10.8 (8.0-16.0) kPa (p < .05). CONCLUSIONS: Blood flow redistribution and heterogeneous microcirculatory perfusion can explain apparently maintained regional oxidative metabolism during mesenteric hypoperfusion, despite local signs of anaerobic metabolism. Early decreasing glucose concentrations suggest that substrate supply may become crucial before oxygen consumption decreases.
Resumo:
BACKGROUND: Testicular tumours are relatively uncommon in infants and children, accounting for only 1-2% of all paediatric solid tumours. Of these approximately 1.5% are Leydig-cell tumours. Further, activating mutations of the luteinizing hormone receptor gene (LHR), as well as of the G protein genes, such as Gsalpha (gsp) and Gialpha (gip2) subunits, and cyclin-dependent kinase gene 4(CDK4) have been associated with the development of several endocrine neoplasms. AIMS/METHODS: In this report, the clinical variability of Leydig-cell tumours in four children is described. The LHR-, gsp-, gip2- and CDK4 genes were investigated to establish the possible molecular pathogenesis of the variable phenotype of the Leydig-cell tumours. RESULTS: No activating mutations in these genes were found in the four Leydig-cell tumours studied. Therefore, the absence of activating mutations in LHR, as well as in both the 'hot spot' regions for activating mutations within the G-alpha subunits and in the regulatory 'hot spot' on the CDK4 genes in these tumours indicates molecular heterogeneity among Leydig-cell tumours. CONCLUSION: Four children with a variable phenotype caused by Leydig-cell tumours are described. A molecular analysis of all the 'activating' genes and mutational regions known so far was performed, but no abnormalities were found. The lessons learnt from these clinically variable cases are: perform ultrasound early and most importantly, consider discrepancies between testicular swelling, tumour size and androgen production.
Resumo:
An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species approximately 141 thousand years ago (Kya), an exit out-of-Africa approximately 51 Kya, and a recent colonization of the Americas approximately 10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus.
Resumo:
The research reported in this dissertation investigates the impact of grain boundaries, film interface, and crystallographic orientation on the ionic conductivity of thin film Gd-doped CeO2 (GDC). Chapter 2 of this work addresses claims in the literature that submicron grain boundaries have the potential to dramatically increase the ionic conductivity of GDC films. Unambiguous testing of this claim requires directly comparing the ionic conductivity of single-crystal GDC films to films that are identical except for the presence of submicron grain boundaries. In this work techniques have been developed to grow GDC films by RF magnetron sputtering from a GDC target on single crystal r plane sapphire substrates. These techniques allow the growth of films that are single crystals or polycrystalline with 80 nm diameter grains. The ionic conductivities of these films have been measured and the data shows that the ionic conductivity of single crystal GDC is greater than that of the polycrystalline films by more than a factor of 4 over the 400-700°C temperature range. Chapter 3 of this work investigates the ionic conductivity of surface and interface regions of thin film Gd-doped CeO2. In this study, single crystal GDC films have been grown to thicknesses varying from 20 to 500 nm and their conductivities have been measured in the 500-700°C temperature range. Decreasing conductivity with decreasing film thickness was observed. Analysis of the conductivity data is consistent with the presence of an approximately 50 nm layer of less conductive material in every film. This study concludes that the surface and interface regions of thin film GDC are less conductive than the bulk single crystal regions, rather than being highly conductive paths. Chapter 4 of this work investigates the ionic conductivity of thin film Gd-doped CeO2 (GDC) as a function of crystallographic orientation. A theoretical expression has been developed for the ionic conductivity of the [100] and [110] directions in single crystal GDC. This relationship is compared to experimental data collected from a single crystal GDC film. The film was grown to a thickness of _300 nm and its conductivity measured along the [100] and [110] orientations in the 500-700°C temperature range. The experimental data shows no statistically significant difference in the conductivities of the [100] and [110] directions in single crystal GDC. This result agrees with the theoretical model which predicts no difference between the conductivities of the two directions.
Resumo:
BACKGROUND Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies. METHODS Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis.
Resumo:
We report the case of a patient in whom successful radiofrequency catheter ablation of an idiopathic ventricular tachycardia (VT) originating in the main stem of the pulmonary artery was performed. After successful ablation of the index arrhythmia, which was an idiopathic right ventricular outflow tract VT, a second VT with a different QRS morphology was reproducibly induced. Mapping of the second VT revealed the presence of myocardium approximately 2 cm above the pulmonary valve. Application of radiofrequency energy at this site resulted in termination and noninducibility of this VT. After 6-month follow-up, the patient remained free from VT recurrences.