Complexo Hospitalario Universitario Of runa Chuac

A Coruña, Spain

Complexo Hospitalario Universitario Of runa Chuac

A Coruña, Spain
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Fernandez-Cuenca F.,University of Seville | Tomas M.,Complexo Hospitalario Universitario Of runa Chuac | Caballero-Moyano F.-J.,University of Seville | Bou G.,Complexo Hospitalario Universitario Of runa Chuac | And 6 more authors.
The Journal of antimicrobial chemotherapy | Year: 2015

OBJECTIVES: The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.METHODS: Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT-PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.RESULTS: Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan(®) was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan(®) was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan(®).CONCLUSIONS: Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan(®) may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression). © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Ribeiro M.,Complexo Hospitalario Universitario Of runa Chuac | Ribeiro M.,University of Coimbra | Lopez de Figueroa P.,Complexo Hospitalario Universitario Of runa Chuac | Nogueira-Recalde U.,Complexo Hospitalario Universitario Of runa Chuac | And 3 more authors.
Osteoarthritis and Cartilage | Year: 2016

Objective: Type 2 Diabetes (T2D) is a risk factor for osteoarthritis (OA). Autophagy, an essential homeostasis mechanism in articular cartilage, is defective in T2D and OA. However, how T2D may influence OA progression is still unknown. We aimed to determine how diabetes affects cartilage integrity and whether pharmacological activation of autophagy has efficacy in diabetic mice (db/db mice) with OA. Design: Experimental OA was performed in the right knee of 9 weeks-old C57Bl/6J male mice (Lean group, . N = 8) and of 9 weeks-old B6.BKS (D)-Leprdb male mice (db/db group, . N = 16) by transection of medial meniscotibial and medial collateral ligaments. Left knee was employed as control knee. Rapamycin (2 mg/kg weight/day) or Vehicle (dimethyl sulfoxide) were administered intraperitoneally three times a week for 10 weeks. Histopathology of articular cartilage and synovium was evaluated by using semiquantitative scoring and synovitis grading systems, respectively. Immunohistochemistry was employed to evaluate the effect of diabetes and Rapamycin on cartilage integrity and OA biomarkers. Results: Cartilage damage was increased in db/db mice compared to Lean mice after experimental OA, while no differences are observed in the control knee. Cartilage damage and synovium inflammation were reduced by Rapamycin treatment of OA-db/db mice. This protection was accompanied with a decrease in MMP-13 expression and decreased interleukin 12 (IL-12) levels. Furthermore, autophagy was increased and cartilage cellularity was maintained, suggesting that mammalian target of rapamycin (mTOR) targeting prevents joint physical harm. Conclusion: Our findings indicate that diabetic mice exhibit increased joint damage after experimental OA, and that autophagy activation might be an effective therapy for diabetes-accelerated OA. © 2016 Osteoarthritis Research Society International.


PubMed | University of Cantabria, University of Barcelona, Complexo Hospitalario Universitario Of runa Chuac and University of Seville
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2015

The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT-PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan() was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P<0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by 2 dilutions. Reduced susceptibility to Orsan() was more frequent among prevalent clones than non-prevalent clones (P<0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P=0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan().Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan() may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).


Nunez L.,University of La Coruña | Gimeno-Blanes J.R.,Hospital Universitario Virgen Of La Arrixaca | Rodriguez-Garcia M.I.,University of La Coruña | Monserrat L.,University of La Coruña | And 6 more authors.
Circulation Journal | Year: 2013

Background: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening. Elucidation of the genetic basis of HCM lead to the identification of several genes encoding sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric genes are mutated in approximately 40% of HCM patients and a possible explanation for the incomplete yield of mutation-positive HCM may be somatic mutations.Methods and Results: We studied 104 unrelated patients with non-familial HCM. Patients underwent clinical evaluation and mutation screening of 5 genes implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as several patients carried the same mutations, the total amount of different mutations was 37; 20 of these mutations have been previously described, and pathogenicity has been assessed. To determine the effect of the 17 new mutations an in silico assay was performed and it predicted that 4 variants were damaging mutations. All identified variants were also seen in the DNA isolated from the corresponding blood, which demonstrated the absence of somatic mutations. Conclusions: Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not represent an important etiologic pathway in HCM.


Sangiao-Alvarellos S.,University of La Coruña | Sangiao-Alvarellos S.,Institute Investigacion Biomedica Of A Coruna | Pena-Bello L.,University of La Coruña | Pena-Bello L.,Institute Investigacion Biomedica Of A Coruna | And 6 more authors.
Endocrinology | Year: 2014

The hypothalamus plays a crucial role in body weight homeostasis through an intricate network of neuronal circuits that are under the precise regulation of peripheral hormones and central transmitters. Although deregulated function of such circuits might be a major contributing factor in obesity, the molecular mechanisms responsible for the hypothalamic control of energy balance remain partially unknown. MicroRNAs (miRNAs) have been recognized as key regulators of different biological processes, including insulin sensitivity and glucose metabolism. However, the roles of miRNA pathways in the control of metabolism have been mostly addressed in peripheral tissues, whereas the potential deregulation ofmiRNAexpression in the hypothalamus in conditions of metabolic distress remains as yet unexplored. In this work, we used high-throughput screening to define to what extent the hypothalamic profiles of miRNA expression are perturbed in two extreme conditions of nutritional stress in male rats, namely chronic caloric restriction and high-fat diet-induced obesity. Our analyses allowed the identification of sets of miRNAs, including let-7a, mir-9, mir-30e, mir-132, mir-145, mir-200a, and mir-218, whose expression patterns in the hypothalamus were jointly altered by caloric restriction and/or a high-fat diet. The predicted targets of these miRNAs include several elements of key inflammatory and metabolic pathways, including insulin and leptin. Our study is the first to disclose the impact of nutritional challenges on the hypothalamicmiRNAexpression profiles. These data will help to characterize the molecularmiRNA signature of the hypothalamus in extreme metabolic conditions and pave the way for targeted mechanistic analyses of the involvement of deregulated central miRNAs pathways in the pathogenesis of obesity and related disorders. © 2014 by the Endocrine Society.


Ribeiro M.,Complexo Hospitalario Universitario Of runa Chuac | Ribeiro M.,University of Coimbra | Lopez de Figueroa P.,Complexo Hospitalario Universitario Of runa Chuac | Blanco F.J.,Complexo Hospitalario Universitario Of runa Chuac | And 2 more authors.
Osteoarthritis and Cartilage | Year: 2016

Objective: Autophagy, a key homeostasis mechanism, is defective in Osteoarthritis (OA) and Type 2 Diabetes (T2D). T2D has been proposed as a risk factor for OA. We hypothesized that diabetes impairs articular cartilage integrity by decreasing autophagy. Our objective was to investigate the effects of high glucose and insulin, characteristics of T2D, on cartilage homeostasis. Methods: Immortalized human chondrocytes (TC28a2) and primary human chondrocytes (HC) were cultured in 25 mM or 0 mM glucose and treated with insulin (10, 100, 500 nM) for 2, 6 or 24 h. Activity of LC3-II, Akt and rpS6 was evaluated by Western blotting (WB). Human cartilage explants were cultivated with 25 mM glucose and insulin (100,1000 nM) for 24 h to evaluate histopathology. MMP-13 and IL-1β expression was determined by immunohistochemistry and WB. Effects of Rapamycin (10 μM) were analyzed by WB. LC3 and rpS6 expression was determined by WB in chondrocytes from Healthy, Non Diabetic-OA and Diabetic-OA patients. Results: Insulin downregulates autophagy by reducing LC3 II expression and increasing Akt and rpS6 phosphorylation. Loss of proteoglycans and increased MMP-13 and IL-1β expression was observed after insulin treatment. Autophagy activation by rapamycin reversed insulin effects. Importantly, chondrocytes from diabetic-OA patients showed decreased LC3 and increased p-rpS6 expression compared to Healthy and Non-Diabetic OA patients. Conclusions: These results suggest that decreased autophagy might be a mechanism by which diabetes influences cartilage degradation. Pharmacological activation of autophagy may be an effective therapeutic approach to prevent T2D-induced cartilage damage. © 2015 Osteoarthritis Research Society International.


Poveda E.,Complexo Hospitalario Universitario Of runa Chuac | Wyles D.L.,University of California at San Diego | Mena A.,Complexo Hospitalario Universitario Of runa Chuac | Pedreira J.D.,Complexo Hospitalario Universitario Of runa Chuac | And 2 more authors.
Antiviral Research | Year: 2014

Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) infection is driven by the selection of mutations at different positions in the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance, with significant cross-resistance between compounds belonging to the same family. However, a specific mutation profile is associated with each agent or drug class and varies depending on the genotype/subtype (e.g.; genotype 1b showed higher rates of sustained virological response (SVR) and a higher genetic barrier for resistance than genotype 1a). Moreover, some resistance mutations exist as natural polymorphisms in certain genotypes/subtypes at frequencies that require baseline drug resistance testing before recommending certain antivirals. For example, the polymorphism Q80K is frequently found among genotype 1a (19-48%) and is associated with resistance to simeprevir. Similarly, L31M and Y93H, key resistance mutations to NS5A inhibitors, are frequently found (6-12%) among NS5A genotype 1 sequences. In particular, the presence of these polymorphisms may be of relevance in poorly interferon-responsive patients (i.e.; null responders and non-CC IL28B) under DAA-based therapies in combination with pegylated interferon-α plus ribavirin. The relevance of pre-existing resistance mutations for responses to interferon-free DAA therapies is unclear for most regimens and requires further study. © 2014 Elsevier B.V. All rights reserved.


PubMed | Complexo Hospitalario Universitario Of runa Chuac and University of Coimbra
Type: Journal Article | Journal: Osteoarthritis and cartilage | Year: 2016

Autophagy, a key homeostasis mechanism, is defective in Osteoarthritis (OA) and Type 2 Diabetes (T2D). T2D has been proposed as a risk factor for OA. We hypothesized that diabetes impairs articular cartilage integrity by decreasing autophagy. Our objective was to investigate the effects of high glucose and insulin, characteristics of T2D, on cartilage homeostasis.Immortalized human chondrocytes (TC28a2) and primary human chondrocytes (HC) were cultured in 25mM or 0mM glucose and treated with insulin (10, 100, 500nM) for 2, 6 or 24h. Activity of LC3-II, Akt and rpS6 was evaluated by Western blotting (WB). Human cartilage explants were cultivated with 25mM glucose and insulin (100,1000nM) for 24h to evaluate histopathology. MMP-13 and IL-1 expression was determined by immunohistochemistry and WB. Effects of Rapamycin (10M) were analyzed by WB. LC3 and rpS6 expression was determined by WB in chondrocytes from Healthy, Non Diabetic-OA and Diabetic-OA patients.Insulin downregulates autophagy by reducing LC3 II expression and increasing Akt and rpS6 phosphorylation. Loss of proteoglycans and increased MMP-13 and IL-1 expression was observed after insulin treatment. Autophagy activation by rapamycin reversed insulin effects. Importantly, chondrocytes from diabetic-OA patients showed decreased LC3 and increased p-rpS6 expression compared to Healthy and Non-Diabetic OA patients.These results suggest that decreased autophagy might be a mechanism by which diabetes influences cartilage degradation. Pharmacological activation of autophagy may be an effective therapeutic approach to prevent T2D-induced cartilage damage.


PubMed | University of California at San Diego and Complexo Hospitalario Universitario Of runa Chuac
Type: | Journal: Antiviral research | Year: 2014

Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) infection is driven by the selection of mutations at different positions in the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance, with significant cross-resistance between compounds belonging to the same family. However, a specific mutation profile is associated with each agent or drug class and varies depending on the genotype/subtype (e.g., genotype 1b showed higher rates of sustained virological response (SVR) and a higher genetic barrier for resistance than genotype 1a). Moreover, some resistance mutations exist as natural polymorphisms in certain genotypes/subtypes at frequencies that require baseline drug resistance testing before recommending certain antivirals. For example, the polymorphism Q80K is frequently found among genotype 1a (19-48%) and is associated with resistance to simeprevir. Similarly, L31M and Y93H, key resistance mutations to NS5A inhibitors, are frequently found (6-12%) among NS5A genotype 1 sequences. In particular, the presence of these polymorphisms may be of relevance in poorly interferon-responsive patients (i.e., null responders and non-CC IL28B) under DAA-based therapies in combination with pegylated interferon- plus ribavirin. The relevance of pre-existing resistance mutations for responses to interferon-free DAA therapies is unclear for most regimens and requires further study.


PubMed | Complexo Hospitalario Universitario Of runa Chuac
Type: | Journal: Anales de pediatria (Barcelona, Spain : 2003) | Year: 2016

Surgical closure of patent ductus arteriosus in premature neonates is an aggressive technique and is not free of complications. A study was designed with the aim of describing our experience with a less invasive technique, the extra-pleural approach via a posterior minithoracotomy, and to compare the results with the classic transpleural approach.A retrospective cohort study was conducted on premature neonates on whom surgical closure of the ductus was performed during a ten-year period (March 2005 to March 2015). A comparison was made of the acute complications, the outcomes on discharge, and follow-up, between the extra-pleural approach and the classic transpleural approach. The study included 48 patients, 30 in the classical approach and 18 in the extra-pleural group.The demographic and pre-operative characteristics were similar in both groups. No differences were found between the 2 groups in the incidence of acute post-operative complications (56.6 vs. 44.4%), on the dependence on oxygen at 36 weeks (33.3 vs. 55.5%), or in hospital mortality (10 vs. 16.6%). As regards the short-term progress, the extra-pleural group required fewer days until the withdrawal of supplementary oxygen (36.3 vs. 28.9) and until hospital discharge (67.5 vs. 53.2), although only the time until extubation achieved a statistically significant difference (11.5 vs. 2.7, P=.03).The extra-plural approach by posterior minithoracotomy for the surgical closure of ductus in the premature infant is viable and could bring some clinical benefits in the short-term.

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