Kinetic study of the pyrolysis and combustion of tomato plant

A kinetic study of the thermal decomposition of tomato plant has been carried out under different conditions by TG and TG–MS. A total of 24 experiments were performed in a nitrogen atmosphere (pyrolysis runs) and also in an oxidative atmosphere with two different oxygen concentrations (10% and 20% oxygen in nitrogen). Dynamic runs and dynamic + isothermal runs have been carried out to obtain many data of decomposition under different operating conditions. A scheme of five independent reactions for pseudocomponents has been proposed for the pyrolysis process, although only three fractions have probed to be significant, comparing the weight fractions of volatiles evolved with the hemicellulose, cellulose and lignin content of the plant. For the combustion runs, four new reactions have been added: two competitive oxidation reactions for the cellulose and lignin, and two combustion reactions of the carbonaceous residue obtained from pyrolysis. The kinetic parametres have been calculated by integration of the differential equations and minimizing the differences between the experimental and calculated values. It is important to emphasize that the same set of parameters has been proposed for the pyrolysis and combustion runs, and which do not depend on either the heating rate in dynamic runs or whether the run is carried out in a dynamic or isothermal mode. The influence of the oxygen pressure has been also discussed.Support for this work was provided by Spanish MEC, research project CTQ2005-05262

The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis

Introduction: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. Methods: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. Results: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). Discussion: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine

Antioxidant therapies and oxidative stress in Friedreich's ataxia: the right path or just a diversion?

Friedreich's ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those 'antioxidant' drugs that went beyond the disease's models and were approved for its application in clinical trials. The evaluation of these trials highlights some crucial aspects of the FRDA research. On the one hand, the analysis contributes to elucidate whether oxidative stress plays a central role or whether it is only an epiphenomenon. On the other hand, it comments on some limitations in the current trials that complicate the analysis and interpretation of their outcome. We also include some suggestions that will be interesting to implement in future studies and clinical trials

Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity

Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have many advantages in the laboratory, such as a short life cycle, easy handling and inexpensive maintenance. Furthermore, they can be raised in a large number. In addition, flies are greatly appreciated because they offer a considerable number of genetic tools to address some of the unresolved questions concerning disease pathology, which in turn could contribute to our understanding of the metal metabolism and homeostasis. This review recapitulates the metabolism of the principal transition metals, namely iron, zinc and copper, in Drosophila and the utility of this organism as an experimental model to explore the role of metal dyshomeostasis in different human diseases. Finally, a summary of the contribution of Drosophila as a model for testing metal toxicity is provided

Drosophila melanogaster models of Friedreich's ataxia

Friedreich's ataxia (FRDA) is a rare inherited recessive disorder affecting the central and peripheral nervous systems and other extraneural organs such as the heart and pancreas. This incapacitating condition usually manifests in childhood or adolescence, exhibits an irreversible progression that confines the patient to a wheelchair, and leads to early death. FRDA is caused by a reduced level of the nuclear-encoded mitochondrial protein frataxin due to an abnormal GAA triplet repeat expansion in the first intron of the human FXN gene. FXN is evolutionarily conserved,with orthologs in essentially all eukaryotes and some prokaryotes, leading to the development of experimental models of this disease in different organisms.These FRDA models have contributed substantially to our current knowledge of frataxin function and the pathogenesis of the disease, as well as to explorations of suitable treatments. Drosophila melanogaster, an organism that is easy to manipulate genetically, has also become important in FRDA research. This review describes the substantial contribution of Drosophila to FRDA research since the characterization of the fly frataxin ortholog more than 15 years ago. Fly models have provided a comprehensive characterization of the defects associatedwith frataxin deficiency and have revealed genetic modifiers of disease phenotypes. In addition, these models are now being used in the search for potential therapeutic compounds for the treatment of this severe and still incurable disease

Using gene expression and systems biology to interrogate auditory hallucinations in schizophrenic patients

Schizophrenia is a severe mental disorder affecting around 1% of the opulation. This disease presents a complex aetiology that has not been completely unveiled yet. Auditory hallucinations are a very significant and disruptive symptom of schizophrenia affecting between 60% and 80% of schizophrenic patients. In this paper we have used a network-based transcriptomic analysis aiming to identify differences in gene expression between schizophrenic patients with and without auditory hallucinations. Gene expression data from blood samples drained from 30 schizophrenia patients were generated using Affymetrix Human Gene 2.0 ST Genechips. Affymetrix Expression console was used for normalization and quality control purposes. The RMA normalization method was applied for gene summarization and then a filter applied to keep only the most variably expressed probesets (4,508). These dataset was analysed using the weighted gene co-expression network analysis (WGCNA) package in R. The gene co-expression network analyses allowed us to identify eleven different gene modules based on their topological overlap. These modules were related to the relevant phenotypic information and allowing us to identify modules related with different phenotypic traits of interest. Gene co-expression network analysis is a useful tool for the analysis of gene expression analysis. Its application in the analysis of schizophrenia gene expression provides an insight on the molecular mechanisms related with this disease and the differences at the molecular level between patients presenting auditory hallucinations and those that do not. In our analysis we have been able to identify different gene modules containing genes expression profiles that can be related with clinically relevant phenotypes. These gene modules could be functionally annotated and related with different pathways and gene ontology terms that are relevant in the context of this analysis

Altered lipid metabolism in a Drosophila model of Friedreich’s ataxia

Producción CientíficaFriedreich’s ataxia (FRDA) is the most common form of autosomal recessive ataxia caused by a deficit in the mitochondrial protein frataxin. Although demyelination is a common symptom in FRDA patients, no multicellular model has yet been developed to study the involvement of glial cells in FRDA. Using the recently established RNAi lines for targeted suppression of frataxin in Drosophila, we were able to study the effects of general versus glial-specific frataxin downregulation. In particular, we wanted to study the interplay between lowered frataxin content, lipid accumulation and peroxidation and the consequences of these effects on the sensitivity to oxidative stress and fly fitness. Interestingly, ubiquitous frataxin reduction leads to an increase in fatty acids catalyzing an enhancement of lipid peroxidation levels, elevating the intracellular toxic potential. Specific loss of frataxin in glial cells triggers a similar phenotype which can be visualized by accumulating lipid droplets in glial cells. This phenotype is associated with a reduced lifespan, an increased sensitivity to oxidative insult, neurodegenerative effects and a serious impairment of locomotor activity. These symptoms fit very well with our observation of an increase in intracellular toxicity by lipid peroxides. Interestingly, co-expression of a Drosophila apolipoprotein D ortholog (glial lazarillo) has a strong protective effect in our frataxin models, mainly by controlling the level of lipid peroxidation. Our results clearly support a strong involvement of glial cells and lipid peroxidation in the generation of FRDA-like symptoms.2015-09-1

Time dependent expression of the blood biomarkers EIF2D and TOX in patients with schizophrenia

Background During last years, there has been an intensive search for blood biomarkers in schizophrenia to assist in diagnosis, prognosis and clinical management of the disease. Methods In this study, we first conducted a weighted gene coexpression network analysis to address differentially expressed genes in peripheral blood from patients with chronic schizophrenia (n?=?30) and healthy controls (n?=?15). The discriminating performance of the candidate genes was further tested in an independent cohort of patients with first-episode schizophrenia (n?=?124) and healthy controls (n?=?54), and in postmortem brain samples (cingulate and prefrontal cortices) from patients with schizophrenia (n?=?34) and healthy controls (n?=?35). Results The expression of the Eukaryotic Translation Initiation Factor 2D (EIF2D) gene, which is involved in protein synthesis regulation, was increased in the chronic patients of schizophrenia. On the contrary, the expression of the Thymocyte Selection-Associated High Mobility Group Box (TOX) gene, involved in immune function, was reduced. EIF2D expression was also altered in first-episode schizophrenia patients, but showing reduced levels. Any of the postmortem brain areas studied did not show differences of expression of both genes. Conclusions EIF2D and TOX are putative blood markers of chronic patients of schizophrenia, which expression change from the onset to the chronic disease, unraveling new biological pathways that can be used for the development of new intervention strategies in the diagnosis and prognosis of schizophrenia disease.Acknowledgments: This work was supported by Fondo de Investigación Sanitaria, Ministerio de Economía y Competitividad, Spain (PI10/01399, PI13/00447; PI17/00402, co-financed by FEDER) to J. Sanjuan and M.D. Moltó; Generalitat Valenciana PROMETEO Excellence Program, Spain (PROMETEO2016/082) to J Sanjuán. J Gilabert-Juan and N. Sebastiá-Ortega were recipients of research contracts from CIBERSAM, Spain. The RNA samples donated bythe Stanley Medical Research Institute Brain Collection were courtesy of Drs. Michael B. Knable, E. Fuller Torrey, Maree J. Webster, and Robert H. Yolken. The authors also thank the collaboration of the staff members of the hospitals

FOXP2 expression and gray matter density in the male brains of patients with schizophrenia

Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls.This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia