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1.
Heliyon ; 9(11): e22377, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38058636

ABSTRACT

In the Chilean salmon farming industry, infection by Piscirickettsia salmonis is the primary cause of the main bacterial disease known as Piscirickettsiosis, which has an overwhelming economic impact. Although it has been demonstrated that Piscirickettsiosis modifies the expression of numerous salmonids genes, it is yet unknown how alternative splicing (AS) contributes to salmonids bacterial infection. AS, has the potential to create heterogeneity at the protein and RNA levels and has been associated as a relevant molecular mechanism in the immune response of eukaryotes to several diseases. In this study, we used RNA data to survey P. salmonis-induced modifications in the AS of Atlantic salmon and found that P. salmonis infection promoted a substantial number (158,668) of AS events. Differentially spliced genes (DSG) sensitive to Piscirickettsiosis were predominantly enriched in genes involved in RNA processing, splicing and spliceosome processes (e.g., hnRNPm, hnRPc, SRSF7, SRSF45), whereas among the DSG of resistant and susceptible to Piscirickettsiosis, several metabolic and immune processes were found, most notably associated to the regulation of GTPase, lysosome and telomere organization-maintenance. Furthermore, we found that DSG were mostly not differentially expressed (5-7 %) and were implicated in distinct biological pathways. Therefore, our results underpin AS achieving a significant regulatory performance in the response of salmonids to Piscirickettsiosis.

2.
Mar Biotechnol (NY) ; 25(2): 223-234, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36629943

ABSTRACT

Sea lice are pathogenic marine ectoparasite copepods that represent a severe risk to the worldwide salmon industry. Several transcriptomic investigations have characterized the regulation of gene expression response of Atlantic salmon to sea lice infestation. These studies have focused on the levels of transcript, overlooking the potentially relevant role of alternative splicing (AS), which corresponds to an essential control mechanism of gene expression through RNA processing. In the present study, we performed a genome-wide bioinformatics characterization of differential AS event dynamics in control and infested C. rogercresseyi Atlantic salmon and in resistant and susceptible phenotypes. We identified a significant rise of alternative splicing events and AS genes after infestation and 176 differential alternative splicing events (DASE) from 133 genes. In addition, a higher number of DASE and AS genes were observed among resistant and susceptible phenotypes. Functional annotation of AS genes shows several terms and pathways associated with behavior, RNA splicing, immune response, and RNA binding. Furthermore, three protein-coding genes were identified undergoing differential transcript usage events, among resistant and susceptible phenotypes. Our findings support AS performing a relevant regulatory role in the response of salmonids to sea lice infestation.


Subject(s)
Copepoda , Ectoparasitic Infestations , Fish Diseases , Lice Infestations , Salmo salar , Animals , Copepoda/genetics , Salmo salar/genetics , Ectoparasitic Infestations/genetics , Ectoparasitic Infestations/veterinary , Alternative Splicing
3.
Sensors (Basel) ; 24(1)2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38202893

ABSTRACT

This paper proposes a new system based on the Industrial Internet of Things (IIoT) for the monitoring of Mobile Health (m-Health) of workers in the underground mining industry. The proposed architecture uses a hybrid model in data transmission. Visible Light Communication (VLC) is used for downlink because of its narrow coverage, which aids in worker positioning. Radio frequency (RF) communication technology is used to send data for primary vital signs in the uplink, which is more efficient in transmission and is a viable solution according to the problem raised. The results obtained in terms of coverage and transmission for the downlink and uplink links show the feasibility of implementing the proposed system.

4.
Mar Biotechnol (NY) ; 23(4): 602-614, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34390423

ABSTRACT

Piscirickettsiosis is the most important bacterial disease in the Chilean salmon industry, which has borne major economic losses due to failure to control it. Cells use extracellular vesicles (EVs) as an inter-cellular communicators to deliver several factors (e.g., microRNAs) that may regulate the responses of other cells. However, there is limited knowledge about the identification and characterization of EV-miRNAs in salmonids or the effect of infections on these. In this study, Illumina sequencing technology was used to identify Coho salmon plasma EV-miRNAs upon Piscirickettsia salmonis infection at four different time points. A total of 118 novels and 188 known EV-miRNAs, including key immune teleost miRNAs families (e.g., miR-146, miR-122), were identified. A total of 245 EV-miRNAs were detected as differentially expressed (FDR < 5%) in terms of control, with a clear down-regulation pattern throughout the disease. KEGG enrichment results of EV-miRNAs target genes showed that they were grouped mainly in cellular, stress, inflammation and immune responses. Therefore, it is hypothesized that P. salmonis could potentially benefit from unbalanced modulation response of Coho salmon EV-miRNAs in order to promote a hyper-inflammatory and compromised immune response through the suppression of different key immune host miRNAs during the course of the infection, as indicated by the results of this study.


Subject(s)
Fish Diseases/microbiology , MicroRNAs/metabolism , Oncorhynchus kisutch/metabolism , Piscirickettsiaceae Infections/immunology , Animals , Extracellular Vesicles/metabolism , Fish Diseases/immunology , Gene Expression Regulation , Inflammation , Oncorhynchus kisutch/genetics , Oncorhynchus kisutch/immunology , Piscirickettsia/physiology
5.
Nutrients ; 13(8)2021 Jul 31.
Article in English | MEDLINE | ID: mdl-34444829

ABSTRACT

Our group tested the effects of Lactobacillus fermentum CECT5716 (LC40) and/or Bifidobacterium breve CECT7263 (BFM) in the prevention of gut dysbiosis, hypertension and endothelial dysfunction in a pharmacologically-induced model of systemic lupus erythematosus (SLE). We treated eight-week-old BALB/cByJRj mice without (Ctrl) or with the agonist of TLR-7 Imiquimod (IMQ) for 8 weeks. Concomitantly, LC40 (109 CFU/mL) and BFM (109 CFU/mL) were administered through oral gavage once a day. IMQ induced intestinal dysbiosis consisting of a decrease in the α-diversity measured with Chao-richness and numbers of species. LC40 and BFM did not restore these parameters. The three-dimensional principal component analysis of bacterial taxa in stool samples presented perfect clustering between Ctrl and IMQ groups. Clusters corresponding to LC40 and BFM were more akin to IMQ. BFM and LC40 were detected colonizing the gut microbiota of mice treated respectively. LC40 and BFM decreased plasma double-stranded DNA autoantibodies, and B cells in spleen, which were increased in the IMQ group. Also, LC40 and BFM treatments activated TLR9, reduced T cells activation, and Th17 polarization in mesenteric lymph nodes. Aortae from IMQ mice displayed a decreased endothelium-dependent vasodilator response to acetylcholine linked to pro-inflammatory and pro-oxidative status, which were normalized by both BFM and LC40. In conclusion, we demonstrate for the first time that the chronic treatment with LC40 or BFM prevented hypertension and endothelial dysfunction in a mouse lupus model induced by TLR-7 activation.


Subject(s)
Hypertension/prevention & control , Lupus Erythematosus, Systemic/complications , Probiotics/therapeutic use , Toll-Like Receptor 7/agonists , Animals , Bifidobacterium breve , Blood Pressure/drug effects , Disease Models, Animal , Dysbiosis/microbiology , Female , Gastrointestinal Microbiome , Immunity , Limosilactobacillus fermentum , Lupus Erythematosus, Systemic/immunology , Membrane Glycoproteins , Mice , Mice, Inbred BALB C , NADPH Oxidases/metabolism , Oxidative Stress/drug effects , RNA, Ribosomal, 16S , Reactive Oxygen Species
6.
Molecules ; 26(3)2021 Jan 22.
Article in English | MEDLINE | ID: mdl-33499286

ABSTRACT

To improve the thermochemical energy storage (TCS) behavior of Mn2O3, several Mn-Mo oxides with varying amounts of MoO3 (0-30 wt%) were prepared by a precipitation method. The physico-chemical properties of the solids were studied by N2 adsorption-desorption, X-ray diffraction (XRD), scanning electron microscopy (SEM), and H2-temperature-programmed reduction (TPR), while their TCS behavior was determined by thermogravimetric analysis coupled with differential scanning calorimetry (TGA-DSC). Apart from Mn2O3 and MoO3 phases, XRD revealed a mixed MnMoO4 phase for MoO3 loadings equal or higher than 1.5 wt%. All samples showed a well-formed coral-like surface morphology, particularly those solids with low MoO3 contents. This coral morphology was progressively decorated with compact and Mo-enriched MnMoO4 particles as the MoO3 content increased. TPR revealed that the redox behavior of Mn2O3 was significantly altered upon addition of Mo. The TCS behavior of Mn2O3 (mostly oxidation kinetics and redox cyclability) was enhanced by addition of low amounts of Mo (0.6 and 1.5% MoO3) without significantly increasing the reduction temperature of the solids. The coral morphology (which facilitated oxygen diffusion) and a smoother transition from the reduced to oxidized phase were suggested to be responsible for this improved TCS behavior. The samples containing 0.6 and 1.5 wt% of MoO3 showed outstanding cyclability after 45 consecutive reduction-oxidation cycles at high temperatures (600-1000 °C). These materials could potentially reach absorption efficiencies higher than 90% at concentration capacity values typical of concentrated solar power plants.


Subject(s)
Manganese Compounds/chemistry , Molybdenum/chemistry , Oxides/chemistry , Power Plants , Renewable Energy , Adsorption , Calorimetry, Differential Scanning , Catalysis , Microscopy, Electron, Scanning , Oxidation-Reduction , Solar Energy , Temperature , Thermogravimetry , X-Ray Diffraction
7.
Epigenetics ; 16(12): 1335-1346, 2021 12.
Article in English | MEDLINE | ID: mdl-33319647

ABSTRACT

Piscirickettsiosis is the most important bacterial disease in the Chilean salmon industry, which has sorted several efforts to its control, generating enormous economic losses. Epigenetic alterations, such as DNA methylation, can play a relevant role in the modulation of the metazoans response to pathogens. Bacterial disease may activate global and local immune responses generating intricate responses with significant biological impact in the host. However, it is scarcely understood how bacterial infections influence fish epigenetic alterations. In the present study, we utilized Pacific salmon and Piscirickettsiosis as model, to gain understanding into the dynamics of DNA methylation among fish-bacterial infection interactions. A genome-wide analysis of DNA methylation patterns in female spleen tissue of Pacific salmon was achieved by reduced representation bisulphite sequencing from a time course design. We determined 2,251, 1,918, and 2,516 differentially methylated regions DMRs among infected and control Pacific salmon in 1 dpi, 5 dpi, and 15 dpi, respectively. The mean methylation difference per DMR among control and infected groups was of ~35%, with an oscillatory pattern of hypo, hyper, and hypomethylation across the disease. DMCs, among the control and infected group, showed that they were statistically enriched in intergenic regions and depleted in exons. Functional annotation of the DMR genes demonstrated three KEGG principal categories, associated directly with the host response to pathogens infections. Our results provide the first evidence of epigenetic variation in fish provoked by bacterial infection and demonstrate that this variation can be modulated across the disease.


Subject(s)
Fish Diseases , Piscirickettsia , Animals , DNA Methylation , Female , Salmon
8.
Genomics ; 112(1): 45-54, 2020 01.
Article in English | MEDLINE | ID: mdl-31376527

ABSTRACT

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two relevant non-coding RNAs (ncRNAs) class. Oncorhynchus kisutch (coho salmon) is an important aquaculture pacific salmon species without report of miRNAs and a very limited register of lncRNAs. To gain knowledge about the interaction and discovery of miRNAs and lncRNAs in coho salmon we used high-throughput sequencing technology to sequence small and transcriptome libraries from three immune organs. A total of 163 mature miRNAs and 4,975 lncRNAs were discovered. The profiles of expression of both ncRNAs indicated that liver and head-kidney share relatively similar expression patterns. We identified 814 and 181 putative target sequences for 1048 lncRNAs and 47 miRNAs, respectively. The results obtained provide new information and enlarge our understanding of the diversities of ncRNAs in coho salmon.


Subject(s)
MicroRNAs/metabolism , Oncorhynchus kisutch/genetics , RNA, Long Noncoding/metabolism , Animals , Female , Gene Expression Profiling , Kidney/metabolism , Liver/metabolism , Male , MicroRNAs/genetics , Oncorhynchus kisutch/immunology , Oncorhynchus kisutch/metabolism , RNA, Long Noncoding/genetics , Spleen/metabolism
9.
Ind Eng Chem Res ; 57(45): 15268-15279, 2018 Nov 14.
Article in English | MEDLINE | ID: mdl-30487661

ABSTRACT

A series of Cu catalysts supported on SiO2, Al2O3-SiO2, TiO2 rutile, and Cu/TiO2 anatase metal oxides has been studied for methanol reforming in the vapor phase. The highest activity was obtained on Cu/SiO2 catalysts (5493 µmol H2 min-1·gcat -1) followed by Cu/TiO2 rutile, Cu/Al2O3-SiO2, and anatase. XRD and HRTEM characterization after reaction revealed that on Cu/SiO2 significant sintering occurred during reaction. In contrast, the particle size growth on Cu/TiO2 rutile and anatase was less pronounced, which could be associated with the interaction between Cu clusters and TiO2. Characterization by TGA showed that on Cu/Al2O3-SiO2 the main cause of deactivation was coke deposition.

10.
Minerva Cardioangiol ; 64(5): 501-6, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26006216

ABSTRACT

BACKGROUND: A National Spanish Registry to compile all patients treated with high intensity focused ultrasound (HIFU) energy for atrial fibrillation (AF) was created to evaluate the safety and efficacy of AF surgical ablation. METHODS: A national Spanish registry was created, and ten hospitals using HIFU to ablate AF joined it. A total of 412 patients undergoing cardiac surgery between 2006 and February 2013 were included. AF was divided between paroxysmal AF (33%) and persistent AF (67%) with a mean AF duration of 29.3±108.2 months. Mean left atrial diameter was 51.2±6.5 mm. Mean underlying heart disease were aortic valve disease (49.3%), ischemic disease (25.2%) and mitral disease (33.2%) Clinical follow-up of patients and a 6 months postoperative echocardiogram were performed in all patients. RESULTS: A pacemaker implantation was needed in 4.9% of patients with a perioperative stroke in 2.5%. Rhythm at discharge from hospital was sinus rhythm in 58%, AF in 35.9% and atrial flutter in 0.8% of patients. Sinus rhythm restoration at 6, 12, 24 and 36 months follow-up was achieved in 66.1%, 63.8%, 63.9% and 45.9% of patients respectively. Multivariate analysis showed paroxysmal AF and sinus rhythm restoration in the operating theatre as factors related to sinus rhythm long term restoration. CONCLUSIONS: The Spanish national registry showed an efficacy of AF ablation with the HIFU Epicor system of 66.1%, 63.8%, 63.9% and 45.9% at 6, 12, 24 and 36 months follow-up. There were no device-related complications.


Subject(s)
Atrial Fibrillation/epidemiology , Atrial Fibrillation/therapy , Cardiac Surgical Procedures/statistics & numerical data , High-Intensity Focused Ultrasound Ablation/statistics & numerical data , Aged , Atrial Fibrillation/diagnostic imaging , Cardiac Surgical Procedures/adverse effects , Echocardiography , Female , High-Intensity Focused Ultrasound Ablation/adverse effects , Humans , Male , Middle Aged , Pacemaker, Artificial , Registries , Spain/epidemiology , Treatment Outcome
11.
Comput Methods Programs Biomed ; 121(2): 66-76, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26094858

ABSTRACT

BACKGROUND AND OBJECTIVE: Meaningful targeting of brain structures is required in a number of experimental designs in neuroscience. Current technological developments as high density electrode arrays for parallel electrophysiological recordings and optogenetic tools that allow fine control of activity in specific cell populations provide powerful tools to investigate brain physio-pathology. However, to extract the maximum yield from these fine developments, increased precision, reproducibility and cost-efficiency in experimental procedures is also required. METHODS: We introduce here a framework based on magnetic resonance imaging (MRI) and digitized brain atlases to produce customizable 3D-environments for brain navigation. It allows the use of individualized anatomical and/or functional information from multiple MRI modalities to assist experimental neurosurgery planning and in vivo tissue processing. RESULTS: As a proof of concept we show three examples of experimental designs facilitated by the presented framework, with extraordinary applicability in neuroscience. CONCLUSIONS: The obtained results illustrate its feasibility for identifying and selecting functionally and/or anatomically connected neuronal population in vivo and directing electrode implantations to targeted nodes in the intricate system of brain networks.


Subject(s)
Brain/surgery , Deep Brain Stimulation/methods , Magnetic Resonance Imaging/methods , Nerve Net/physiology , Nerve Net/surgery , Surgery, Computer-Assisted/methods , Animals , Brain/anatomy & histology , Brain Mapping/methods , Deep Brain Stimulation/instrumentation , Electrodes, Implanted , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Nerve Net/anatomy & histology , Neuroimaging/methods , Neurosurgical Procedures/instrumentation , Neurosurgical Procedures/methods , Preoperative Care/methods , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity
12.
J Neurosci ; 35(15): 5926-34, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25878265

ABSTRACT

Much of our understanding of the neuronal mechanisms of spatial navigation is derived from chronic recordings in rodents in which head-direction, place, and grid cells have all been described. However, despite the proposed importance of self-reference information to these internal representations of space, their congruence with vestibular signaling remains unclear. Here we have undertaken brain-wide functional mapping using both fMRI and electrophysiological methods to directly determine the spatial extent, strength, and time course of vestibular signaling across the rat forebrain. We find distributed activity throughout thalamic, limbic, and particularly primary sensory cortical areas in addition to known head-direction pathways. We also observe activation of frontal regions, including infralimbic and cingulate cortices, indicating integration of vestibular information throughout functionally diverse cortical regions. These whole-brain activity maps therefore suggest a widespread contribution of vestibular signaling to a self-centered framework for multimodal sensorimotor integration in support of movement planning, execution, spatial navigation, and autonomic responses to gravito-inertial changes.


Subject(s)
Action Potentials/physiology , Afferent Pathways/physiology , Brain Mapping , Cerebral Cortex/physiology , Vestibule, Labyrinth/physiology , Afferent Pathways/blood supply , Animals , Cerebral Cortex/blood supply , Cerebral Cortex/cytology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Neurons/physiology , Oxygen/blood , Physical Stimulation , Rats , Rats, Wistar
13.
Appl Environ Microbiol ; 79(3): 1018-23, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23160137

ABSTRACT

Hydroxyectoine overproduction by the natural producer Chromohalobacter salexigens is presented in this study. Genetically engineered strains were constructed that at low salinity coexpressed, in a vector derived from a native plasmid, the ectoine (ectABC) and hydroxyectoine (ectD) genes under the control of the ectA promoter, in a temperature-independent manner. Hydroxyectoine production was further improved by increasing the copies of ectD and using a C. salexigens genetic background unable to synthesize ectoines.


Subject(s)
Amino Acids, Diamino/metabolism , Chromohalobacter/metabolism , Metabolic Engineering , Metabolic Networks and Pathways/genetics , Chromohalobacter/drug effects , Chromohalobacter/radiation effects , Gene Dosage , Plasmids , Salinity , Temperature
14.
PLoS One ; 7(3): e33587, 2012.
Article in English | MEDLINE | ID: mdl-22448254

ABSTRACT

The disaccharide trehalose is considered as a universal stress molecule, protecting cells and biomolecules from injuries imposed by high osmolarity, heat, oxidation, desiccation and freezing. Chromohalobacter salexigens is a halophilic and extremely halotolerant γ-proteobacterium of the family Halomonadaceae. In this work, we have investigated the role of trehalose as a protectant against salinity, temperature and desiccation in C. salexigens. A mutant deficient in the trehalose-6-phosphate synthase gene (otsA::Ω) was not affected in its salt or heat tolerance, but double mutants ectoine- and trehalose-deficient, or hydroxyectoine-reduced and trehalose-deficient, displayed an osmo- and thermosensitive phenotype, respectively. This suggests a role of trehalose as a secondary solute involved in osmo- (at least at low salinity) and thermoprotection of C. salexigens. Interestingly, trehalose synthesis was osmoregulated at the transcriptional level, and thermoregulated at the post-transcriptional level, suggesting that C. salexigens cells need to be pre-conditioned by osmotic stress, in order to be able to quickly synthesize trehalose in response to heat stress. C. salexigens was more sensitive to desiccation than E. coli and desiccation tolerance was slightly improved when cells were grown at high temperature. Under these conditions, single mutants affected in the synthesis of trehalose or hydroxyectoine were more sensitive to desiccation than the wild-type strain. However, given the low survival rates of the wild type, the involvement of trehalose and hydroxyectoine in C. salexigens response to desiccation could not be firmly established.


Subject(s)
Chromohalobacter/metabolism , Desiccation , Hot Temperature , Salinity , Trehalose/metabolism , Carbon Radioisotopes , Cells, Cultured , Chromohalobacter/genetics , Chromohalobacter/growth & development , Escherichia coli/genetics , Escherichia coli/metabolism , Glucosyltransferases/genetics , Glucosyltransferases/metabolism , Magnetic Resonance Spectroscopy , Mutation/genetics , Osmolar Concentration , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
15.
Methods Mol Biol ; 824: 167-201, 2012.
Article in English | MEDLINE | ID: mdl-22160899

ABSTRACT

Halophilic gammaproteobacteria of the family Halomonadaceae (including the genera Aidingimonas, Carnimonas, Chromohalobacter, Cobetia, Halomonas, Halotalea, Kushneria, Modicisalibacter, Salinicola, and Zymobacter) have current and promising applications in biotechnology mainly as a source of compatible solutes (powerful stabilizers of biomolecules and cells, with exciting potentialities in biomedicine), salt-tolerant enzymes, biosurfactants, and extracellular polysaccharides, among other products. In addition, they display a number of advantages to be used as cell factories, alternative to conventional prokaryotic hosts like Escherichia coli or Bacillus, for the production of recombinant proteins: (1) their high salt tolerance decreases to a minimum the necessity for aseptic conditions, resulting in cost-reducing conditions, (2) they are very easy to grow and maintain in the laboratory, and their nutritional requirements are simple, and (3) the majority can use a large range of compounds as a sole carbon and energy source. In the last 15 years, the efforts of our group and others have made possible the genetic manipulation of this bacterial group. In this review, the most relevant and recent tools for their genetic manipulation are described, with emphasis on nucleic acid isolation procedures, cloning and expression vectors, genetic exchange mechanisms, mutagenesis approaches, reporter genes, and genetic expression analyses. Complementary sections describing the influence of salinity on the susceptibility of these bacteria to antimicrobials, as well as the growth media most routinely used and culture conditions, for these microorganisms, are also included.


Subject(s)
Biotechnology/methods , Cell Culture Techniques/methods , Halomonadaceae/genetics , Halomonadaceae/metabolism , Salt Tolerance/physiology , Anti-Infective Agents/pharmacology , Blotting, Northern/methods , Cloning, Molecular , Culture Media/chemistry , Drug Resistance, Microbial/physiology , Gene Expression Profiling/methods , Gene Transfer Techniques , Genetic Vectors/genetics , Halomonadaceae/drug effects , Halomonadaceae/growth & development , Mutagenesis/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Species Specificity
16.
HIV Clin Trials ; 12(5): 235-43, 2011.
Article in English | MEDLINE | ID: mdl-22180521

ABSTRACT

PURPOSE: There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease. METHOD: Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C. RESULTS: Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9). CONCLUSION: The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability.


Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/pharmacokinetics , Hepatitis C/drug therapy , Liver Cirrhosis/drug therapy , Lopinavir/adverse effects , Lopinavir/pharmacokinetics , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , Drug Therapy, Combination , Female , HIV Infections/complications , HIV Infections/virology , HIV Protease Inhibitors/administration & dosage , Hepatitis C/complications , Hepatitis C/virology , Humans , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Lopinavir/administration & dosage , Male , Prospective Studies , Treatment Outcome
17.
BMC Microbiol ; 10: 256, 2010 Oct 13.
Article in English | MEDLINE | ID: mdl-20942908

ABSTRACT

BACKGROUND: Osmosensing and associated signal transduction pathways have not yet been described in obligately halophilic bacteria. Chromohalobacter salexigens is a halophilic bacterium with a broad range of salt tolerance. In response to osmotic stress, it synthesizes and accumulates large amounts of the compatible solutes ectoine and hydroxyectoine. In a previous work, we showed that ectoines can be also accumulated upon transport from the external medium, and that they can be used as carbon sources at optimal, but not at low salinity. This was related to an insufficient ectoine(s) transport under these conditions. RESULTS: A C. salexigens Tn1732-induced mutant (CHR95) showed a delayed growth with glucose at low and optimal salinities, could not grow at high salinity, and was able to use ectoines as carbon sources at low salinity. CHR95 was affected in the transport and/or metabolism of glucose, and showed a deregulated ectoine uptake at any salinity, but it was not affected in ectoine metabolism. Transposon insertion in CHR95 caused deletion of three genes, Csal0865-Csal0867: acs, encoding an acetyl-CoA synthase, mntR, encoding a transcriptional regulator of the DtxR/MntR family, and eupR, encoding a putative two-component response regulator with a LuxR_C-like DNA-binding helix-turn-helix domain. A single mntR mutant was sensitive to manganese, suggesting that mntR encodes a manganese-dependent transcriptional regulator. Deletion of eupR led to salt-sensitivity and enabled the mutant strain to use ectoines as carbon source at low salinity. Domain analysis included EupR as a member of the NarL/FixJ family of two component response regulators. Finally, the protein encoded by Csal869, located three genes downstream of eupR was suggested to be the cognate histidine kinase of EupR. This protein was predicted to be a hybrid histidine kinase with one transmembrane and one cytoplasmic sensor domain. CONCLUSIONS: This work represents the first example of the involvement of a two-component response regulator in the osmoadaptation of a true halophilic bacterium. Our results pave the way to the elucidation of the signal transduction pathway involved in the control of ectoine transport in C. salexigens.


Subject(s)
Amino Acids, Diamino/metabolism , Bacterial Proteins/metabolism , Chromohalobacter/genetics , Chromohalobacter/physiology , Gene Expression Regulation, Bacterial , Salinity , Bacterial Proteins/genetics , Biological Transport , Carbon/metabolism , Chromohalobacter/growth & development , DNA Transposable Elements , DNA, Bacterial/genetics , Frameshift Mutation , Genes, Bacterial , Glucose/metabolism , Membrane Transport Modulators , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Mutagenesis, Insertional , Osmolar Concentration , Osmotic Pressure , Promoter Regions, Genetic , Signal Transduction , Sodium Chloride/metabolism
18.
Saline Syst ; 4: 14, 2008 Sep 15.
Article in English | MEDLINE | ID: mdl-18793408

ABSTRACT

Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for growth. Osmoprotection is achieved by the accumulation of compatible solutes either by transport (betaine, choline) or synthesis (mainly ectoine and hydroxyectoine). Ectoines can play additional roles as nutrients and, in the case of hydroxyectoine, in thermotolerance. A supplementary solute, trehalose, not present in cells grown at 37 degrees C, is accumulated at higher temperatures, suggesting its involvement in the response to heat stress. Trehalose is also accumulated at 37 degrees C in ectoine-deficient mutants, indicating that ectoines suppress trehalose synthesis in the wild-type strain. The genes for ectoine (ectABC) and hydroxyectoine (ectD, ectE) production are arranged in three different clusters within the C. salexigens chromosome. In order to cope with changing environment, C. salexigens regulates its cytoplasmic pool of ectoines by a number of mechanisms that we have started to elucidate. This is a highly complex process because (i) hydroxyectoine can be synthesized by other enzymes different to EctD (ii) ectoines can be catabolized to serve as nutrients, (iii) the involvement of several transcriptional regulators (sigmaS, sigma32, Fur, EctR) and hence different signal transduction pathways, and (iv) the existence of post-trancriptional control mechanisms. In this review we summarize our present knowledge on the physiology and genetics of the processes allowing C. salexigens to cope with osmotic stress and high temperature, with emphasis on the transcriptional regulation.

19.
Int J Cardiol ; 117(2): e71-2, 2007 Apr 25.
Article in English | MEDLINE | ID: mdl-17320220

ABSTRACT

Prosthetic heart valve thrombosis is a serious complication with a high mortality. We report the case of a thrombosed St Jude Medical valve placed in the pulmonary position, in a patient who had undergone repair of tetralogy of Fallot, which was successfully treated with intravenous thrombolytic therapy with streptokinase.


Subject(s)
Coronary Thrombosis/drug therapy , Coronary Thrombosis/etiology , Fibrinolytic Agents/administration & dosage , Heart Valve Prosthesis/adverse effects , Streptokinase/administration & dosage , Adolescent , Humans , Male , Pulmonary Valve
20.
Qual Life Res ; 15(5): 767-75, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16721637

ABSTRACT

OBJECTIVE: To validate a questionnaire to identify psychosocial repercussions of the lipodystrophy syndrome (LD) in HIV-infected patients. METHODS: A questionnaire containing 35 items in 6 subscales [body image, anxiety, depression, social support, social distress, quality of life (QoL)] was consecutively administered to 128 patients with LD, 25 naive patients or on therapy without LD, and to 15 HIV negative patients from January to July '04. Reliability was assessed using Cronbach's alpha and the intraclass correlation coefficient (ICC). The area under the curve (AUC) was used for discrimination between patients and control groups, and the scores were compared according to the severity of the LD. RESULTS: In all the subscales, the relationship between higher scores and LD severity was statistically significant (0.37-0.64, p<0.01), whereas the control groups had significantly lower scores. The internal consistency showed Cronbach's alpha coefficients ranging from 0.64 to 0.93. Test-retest reliability after 15 days in 30 patients showed ICC values of 0.8-0.94. AUC values for the different subscales were higher than 0.7 with the exception of QoL score, and construct validity showed a significant correlation with the Beck Depression Inventory and the MOS-HIV scores (0.49 and 0.51, respectively, p<0.01). CONCLUSIONS: Our questionnaire shows satisfactory psychometric properties for identifying psychosocial repercussions of the LD in HIV-infected patients.


Subject(s)
HIV Infections , HIV-Associated Lipodystrophy Syndrome/psychology , Social Adjustment , Adult , Female , Humans , Male , Middle Aged , Quality of Life , Spain , Surveys and Questionnaires
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