Publications by authors named "Álvaro Casanova"

20 Publications

  • Page 1 of 1

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.

EMBO Mol Med 2021 Sep 11;13(9):e13929. Epub 2021 Aug 11.

Experimental Nephrology, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.

Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.
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http://dx.doi.org/10.15252/emmm.202113929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422079PMC
September 2021

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue.

Mol Cancer Res 2021 Jul 26. Epub 2021 Jul 26.

ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.

Lymphangioleiomyomatosis (LAM) is a rare, low-grade metastasizing disease characterized by cystic lung destruction. LAM can exhibit extensive heterogeneity at the molecular, cellular, and tissue levels. However, the molecular similarities and differences among LAM cells and tissue, and their connection to cancer features are not fully understood. By integrating complementary gene and protein LAM signatures, and single-cell and bulk tissue transcriptome profiles, we show sources of disease heterogeneity, and how they correspond to cancer molecular portraits. Subsets of LAM diseased cells differ with respect to gene expression profiles related to hormones, metabolism, proliferation, and stemness. Phenotypic diseased cell differences are identified by evaluating lumican (LUM) proteoglycan and YB1 transcription factor expression in LAM lung lesions. The RUNX1 and IRF1 transcription factors are predicted to regulate LAM cell signatures, and both regulators are expressed in LAM lung lesions, with differences between spindle-like and epithelioid LAM cells. The cancer single-cell transcriptome profiles most similar to those of LAM cells include a breast cancer mesenchymal cell model and lines derived from pleural mesotheliomas. Heterogeneity is also found in LAM lung tissue, where it is mainly determined by immune system factors. Variable expression of the multifunctional innate immunity protein LCN2 is linked to disease heterogeneity. This protein is found to be more abundant in blood plasma from LAM patients than from healthy women. IMPLICATIONS: This study identifies LAM molecular and cellular features, master regulators, cancer similarities, and potential causes of disease heterogeneity.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0220DOI Listing
July 2021

Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays.

Pharmaceutics 2020 Nov 7;12(11). Epub 2020 Nov 7.

Instituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, Spain.

The use of nanocarriers has been revealed as a valid strategy to facilitate drug bioavailability, and this allows for expanding the drug libraries for the treatment of certain diseases such as viral diseases. In the case of Hepatitis C, the compounds iopanoic acid and 3,3',5-triiodothyroacetic acid (or tiratricol) were identified in a primary screening as bioactive allosteric inhibitors of viral NS3 protease, but they did not exhibit accurate activity inhibiting viral replication in cell-based assays. In this work, dendritic nanocarriers are proposed due to their unique properties as drug delivery systems to rescue the bioactivity of these two drugs. Specifically, four different amphiphilic Janus dendrimers synthesized by combining 2,2'-(hydroxymethyl)propionic acid (-MPA) and 2,2'-(glyciloxy)propionic acid (-GMPA) functionalized with either hydrophilic or lipophilic moieties at their periphery were used to entrap iopanoic acid and tiratricol. Interestingly, differences were found in the loading efficiencies depending on the dendrimer design, which also led to morphological changes of the resulting dendrimer aggregates. The most remarkable results consist of the increased water solubility of the bioactive compounds within the dendrimers and the improved antiviral activity of some of the dendrimer/drug aggregates, considerably improving antiviral activity in comparison to the free drugs. Moreover, imaging studies have been developed in order to elucidate the mechanism of cellular internalization.
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http://dx.doi.org/10.3390/pharmaceutics12111062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695217PMC
November 2020

Effects of allergen-specific immunotherapy on peripheral blood regulatory T cells and serum concentrations of cytokines and immunoglobulins in horses with allergic dermatitis.

Int Immunopharmacol 2019 Sep 10;74:105674. Epub 2019 Jun 10.

Animal Pathology Department, Veterinary Faculty, Zaragoza University, 50013 Zaragoza, Spain; Clinical Immunology Laboratory, Veterinary Faculty, Zaragoza University, 50013 Zaragoza, Spain. Electronic address:

The aim of this study was to assess the effect of allergen-specific immunotherapy (ASIT) on the immunological responses of horses. Blood samples were taken from thirty-two horses with allergic dermatitis treated with ASIT and 10 healthy control horses at 0, 3, 6, 9 and 12 months to investigate the evolution of the percentage of regulatory T cells (Treg) in the peripheral blood and the serum levels of cytokines and immunoglobulins. Clinical improvement was appreciated by the majority of the horses' owners (56.6%). No effect of ASIT on CD4CD25 Treg cells was found during the one year treatment period. No differences in the percentage of CD4 T cells were observed between the groups, and no effects of ASIT over time were observed. The percentage of CD25 T cells was always higher in the ASIT group (17.9 ± 11.3%) than in the control group (7.3 ± 4.4%, p < 0.001). We did not detect any effect of ASIT on the serum levels of TGF-β, IL-10 and IFN-γ or on the serum concentrations of IgA and IgG4. A reduction in the serum levels of total IgE in the horses with allergic dermatitis was observed at the 6th month (p < 0.05), but increased again at the end of the study. The results indicate that immunotherapy was insufficient to induce significant changes that could indicate T cell tolerance, a shift in cytokine production to more protective Th1 cells. More studies are needed with new vaccine compositions and administration protocols to improve the immunological responses of the horses with allergic dermatitis.
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http://dx.doi.org/10.1016/j.intimp.2019.105674DOI Listing
September 2019

Upconverting Carbon Nanodots from Ethylenediaminetetraacetic Acid (EDTA) as Near-Infrared Activated Phototheranostic Agents.

Chemistry 2019 Apr 20;25(21):5539-5546. Epub 2019 Mar 20.

Department of Chemical and Environmental Engineering and Institute of Nanoscience of Aragon (INA), University of Zaragoza, Campus Rio Ebro, R+D Building, C/Mariano Esquillor s/n, 50018, Zaragoza, Spain.

This work describes the synthesis of nitrogen-doped carbon nanodots (CNDs) synthesized from ethylenediaminetetraacetic acid (EDTA) as a precursor and their application as luminescent agents with a dual-mode theranostic role as near-infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized by tumor cells and exhibit very limited cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for phototheranostic purposes, for example, simultaneous imaging and therapy can be carried out on cancer cells by using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs, NIR remote activation induces the in vitro killing of U251MG cells. Through the use of flow imaging cytometry, we have been able to successfully map and quantify the different types of cell deaths induced by the presence of intracellular superoxide anions ( O ) and hydrogen peroxide (H O ) ROS generated in situ upon NIR irradiation.
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http://dx.doi.org/10.1002/chem.201806307DOI Listing
April 2019

In-vitro toxicity of carbon nanotube/polylysine colloids to colon cancer cells.

IET Nanobiotechnol 2016 Dec;10(6):374-381

Instituto de Carboquímica, ICB-CSIC, Miguel Luesma Castán 4, 50018 Zaragoza, Spain.

Single-walled carbon nanotubes (SWCNTs) are thoroughly purified and dispersed in an aqueous solution of high molecular weight poly-L-lysine (pLlys). Human intestinal epithelial Caco-2/TC7 cells are incubated with the SWCNT dispersions in pLlys, and their effects on cell viability are studied by image flow cytometry. No significant changes are observed in the cell culture wells up to pLlys concentrations of 10 μg ml. However, high mortality is detected at pLlys concentrations of 100 μg ml. The presence of oxygen-free SWCNTs does not modify the effects of pLlys on cell cultures at any of the tested concentrations (≤1 μg ml). In addition, SWCNTs having an 8 wt.% of surface oxygen are tested with identical results. Thus, purified SWCNTs, even bearing oxygen functional groups, act as inert particles in the cell culture medium. This result supports the applicability of SWCNTs as carriers in pharmacological formulations against digestive tract diseases.
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http://dx.doi.org/10.1049/iet-nbt.2015.0088DOI Listing
December 2016

Understanding the priorities for women diagnosed with lymphangioleiomyomatosis: a patient perspective.

ERJ Open Res 2016 Apr 21;2(2). Epub 2016 Apr 21.

European Lung Foundation, Sheffield, UK.

Lymphangioleiomyomatosis (LAM) is a rare lung disease that almost exclusively affects women and develops in about one in 400 000 adult females. The European Lung Foundation worked closely with one of the patient organisations within its network, the European LAM Federation, to raise awareness of LAM at the 2014 European Respiratory Society International Congress in Munich, Germany. In addition, an invitation-only workshop with 45 individuals from 13 countries was held to discuss the priorities for women in Europe living with the disease. The need for ongoing collaboration to improve knowledge of this rare lung condition with healthcare professionals across Europe was highlighted.
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http://dx.doi.org/10.1183/23120541.00102-2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005183PMC
April 2016

Study of breast cancer incidence in patients of lymphangioleiomyomatosis.

Breast Cancer Res Treat 2016 Feb 7;156(1):195-201. Epub 2016 Mar 7.

Consortium for Biomedical Research in Respiratory Diseases (CIBERES), 28029, Madrid, Spain.

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.
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http://dx.doi.org/10.1007/s10549-016-3737-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788694PMC
February 2016

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.

PLoS One 2015 13;10(7):e0132546. Epub 2015 Jul 13.

Department of Medical Oncology, Breast Cancer Unit, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Catalonia, Spain.

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132546PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500593PMC
April 2016

Mitochondrial complex enzyme activities and cytochrome C expression changes in multiple sclerosis.

Mol Neurobiol 2014 Feb 13;49(1):1-9. Epub 2013 Jun 13.

Department of Biochemistry, Molecular and Cellular Biology, Science Faculty, University of Zaragoza, 50009, Zaragoza, Spain,

Blood platelets have been widely proposed as biomarkers in studies of mitochondrial function and aging-related and neurodegenerative diseases. Defects in mitochondrial function were found not only in the substantia nigra of Parkinson's disease patients but also in their blood platelets. Similarly, it has also been described in the blood platelet mitochondria of Alzheimer's disease patients. To study mitochondrial aerobic metabolism function and protein expression in platelets of multiple sclerosis (MS) patients and control subjects, mitochondrial aconitase, mitochondrial superoxide dismutases 1 and 2 (SOD1 and SOD2), and respiratory complex enzyme activities in platelets of MS patients and control subjects were determined. Likewise, mitochondrial lipid peroxidation and mitochondrial SOD1 and cytochrome c expressions were investigated. Mitochondrial aconitase activity was higher in MS patients than in controls (P < 0.05). A significant increase on all respiratory complex activities in MS patients was observed (P < 0.05). Mitochondrial lipid peroxidation was significantly higher in MS patients than in controls (P < 0.05). Significant changes of cytochrome c and mitochondrial SOD1 expressions were detected (P < 0.05), with a decrease of 44 ± 5 % and an increase of 46 ± 6 %, respectively. Our study reveals that significant changes in mitochondrial aerobic metabolism function and mitochondrial SOD1 and cytochrome c expressions are produced in platelets of MS patients.
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http://dx.doi.org/10.1007/s12035-013-8481-zDOI Listing
February 2014

[Lymphangioleiomyomatosis: new therapeutic approaches].

Arch Bronconeumol 2011 Dec 15;47(12):579-80. Epub 2011 Sep 15.

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http://dx.doi.org/10.1016/j.arbres.2011.06.008DOI Listing
December 2011

Lymphangioleiomyomatosis treatment with sirolimus.

Arch Bronconeumol 2011 Sep 25;47(9):470-2. Epub 2011 Mar 25.

Servicio de Neumología, Hospital del Henares, Madrid, España.

Lymphangioleiomyomatosis (LAM) is a rare lung disease, that predominantly affects young females and generally progresses to respiratory failure. There is not sufficient evidence to support the routine use of any treatment in LAM. The only treatment for severe LAM is currently lung transplantation. Activation of mammalian target of rapamycin (mTOR) signalling pathway has been observed in LAM. LAM is often associated with angiomyolipoma in the kidneys. mTOR inhibitor sirolimus reduces angymiolipoma volumes. Some reports have shown improvement in lung function with sirolimus in LAM. We report 3 women with LAM, with a rapid decline in lung function and symptoms and who were treated with sirolimus.
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http://dx.doi.org/10.1016/j.arbres.2011.01.014DOI Listing
September 2011

[Cyclooxygenase-2 polymorphisms and bronchoalveolar lavage cellularity of sarcoidosis].

Rev Invest Clin 2010 Sep-Oct;62(5):440-6

Unidad Médico-Quirúirgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocío, Sevilla, España.

Objectives: Recent studies have found cyclooxygenase-2 (COX-2) and its polymorphisms to be associated with sarcoidosis, being it significantly decreased in alveolar macrophages, with no information on the relationship between these polymorphisms and the rest of cells in bronchoalveolar layage (BAL). The present study aimed to investigate the potential association between COX-2 gene polymorphisms and the BAL cell profile including the CD4/CD8 ratio.

Material And Methods: This observational cross-sectional study involved six hospitals in Spain. Patients diagnosed with sarcoidosis with a BAL performed were included. The following variables were recorded: age, gender, initial diagnostic methods, serum angiotensin-converting enzyme levels, pulmonary function tests, radiological stage, and the cellularity and CD4/CD8 ratio from BAL. Genotyping of four COX-2 polymorphisms (COX2.5909T>G, COX2.8473T>C, COX2.926G>C, and COX2.3050G>C) was undertaken on DNA extracted from peripheral blood lymphocytes using fluorescent hybridization probes. The relationship between the polymorphisms and the cellularity was done by means of a multiple linear regression, adjusting for gender.

Results: A total of 51 sarcoid patients (23 males, mean age: 45 +/- 15 years) were studied. CD4/CD8 ratio was significantly higher among homozygote allele C carriers of the polymorphism COX2.8473T>C (CC 11.2 +/- 5.5 vs. CT+TT 4.4 +/- 3.5; p = 0.022; beta = 7.43; 95% CI 1.38 - 13.48). Although several differences were observed in other cell groups, they did not reach the statistical significance level.

Conclusions: In patients diagnosed with sarcoidosis, there seems to be a relationship between COX2.8473 polymorphism and CD4/CD8 ratio from BAL.
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April 2011

Melatonin and steroid hormones activate intermembrane Cu,Zn-superoxide dismutase by means of mitochondrial cytochrome P450.

Free Radic Biol Med 2011 Jun 10;50(11):1575-81. Epub 2011 Mar 10.

Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain.

Melatonin and steroid hormones are cytochrome P450 (CYP or P450; EC 1.14.14.1) substrates that have antioxidant properties and mitochondrial protective activities. The mitochondrial intermembrane space (IMS) Cu,Zn-superoxide dismutase (SOD1) is activated after oxidative modification of its critical thiol moieties by superoxide anion (O₂(•-)). This study was aimed at investigating the potential association between the hormonal protective antioxidant actions in mitochondria and the regulation of IMS SOD1 activity. Melatonin, testosterone, dihydrotestosterone, estradiol, and vitamin D induced a sustained activation over time of SOD1 in intact mitochondria, showing a bell-shaped enzyme activation dose response with a threshold at 50nM and a maximum effect at 1μM concentration. Enzyme activation was not affected by furafylline, but it was inhibited by omeprazole, ketoconazole, and tiron, thereby supporting the occurrence of a mitochondrial P450 activity and O₂(•-) requirements. Mitochondrial P450-dependent activation of IMS SOD1 prevented O₂(•-)-induced loss of aconitase activity in intact mitochondria respiring in State 3. Optimal protection of aconitase activity was observed at 0.1μM P450 substrate concentration, evidencing a likely oxidative effect on the mitochondrial matrix by higher substrate concentrations. Likewise, enzyme activation mediated by mitochondrial P450 activity delayed CaCl₂-induced loss of transmembrane potential and decreased cytochrome c release. Omeprazole and ketoconazole abrogated both protecting mitochondrial functions promoted by melatonin and steroid hormones.
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http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144380PMC
June 2011

[Predictive factors for survival in patients with idiopathic pulmonary fibrosis].

Med Clin (Barc) 2009 Sep 19;133(9):333-6. Epub 2009 May 19.

Servicio de Neumología, Hospital de la Princesa, Madrid, Spain.

Background And Objective: To determine the median survival and determinants of survival in patients with idiopathic pulmonary fibrosis (IPF).

Patients And Method: We retrospectively evaluated 29 IPF patients who died in the pneumology department between 2001 and 2006. Data from the time of diagnosis until death were analysed. Determinants of survival including age at diagnosis, gender, history of cigarette smoking, fibrosis-emphysema association, and lung function tests were analysed.

Results: The mean age at diagnosis was 69.7, 16 patients were men (55.2%). The median survival time, from the time of diagnosis, was 28.47 months (20.44-36.5 IC95%). There was a significant difference in survival between age groups. The median survival time in patients older than 65 years was 22.40 months and in patients younger than 65 years it was 56.37 months (p<0.001). There was no significant difference in survival when other determinants of survival. were evaluated.

Conclusion: The median survival of IPF patients is low. It is necessary to continue investigating to find more effective and selective therapeutic strategies.
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http://dx.doi.org/10.1016/j.medcli.2009.01.039DOI Listing
September 2009

[Methicillin-resistant Staphylococcus aureus in patients with cystic fibrosis].

Enferm Infecc Microbiol Clin 2009 Feb 13;27(2):85-8. Epub 2009 Feb 13.

Servicio de Neumología, Hospital Universitario de la Princesa, Madrid, España.

Objective: To determine the prevalence of chronic colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis, describe antibiotic sensitivity of the strains, and compare the patients' clinical characteristics with those of patients infected with methicillin-sensitive S. aureus (MSSA).

Patients And Methods: Patients with chronic S. aureus colonization were selected from a total of 50 patients with cystic fibrosis. Sputum samples were cultured according to standard microbiological procedures. Patients were considered to have chronic bronchial colonization if the same microorganism was isolated in 3 consecutive sputum samples, separated by an interval of at least 1 month. The following variables were compared between patients with MSSA (17) and MRSA (8): sex, body mass index, presence of pancreatic insufficiency, bacterial colonization, pulmonary function, Brasfield radiological score, Shwachman clinical score, and number of respiratory exacerbations in the previous year.

Results: The prevalence of infection by MRSA was 16%. All the MRSA strains were sensitive to vancomycin, teicoplanin, and linezolid. Patients with MRSA were older and had a larger number of respiratory exacerbations than patients with MSSA.

Conclusions: There is a high percentage of colonization by MRSA in adult cystic fibrosis patients. Although the pathogenic role of this microorganism remains unclear, patients with MRSA had more frequent exacerbations and poorer lung function. Thus, infection control is important and patients should be adequately monitored.
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http://dx.doi.org/10.1016/j.eimc.2008.02.008DOI Listing
February 2009

Cyclooxygenase-2 polymorphisms confer susceptibility to sarcoidosis but are not related to prognosis.

Respir Med 2009 Mar 29;103(3):427-33. Epub 2008 Nov 29.

Hospital Universitario Virgen del Rocío, Seville, Spain.

Background: The aim of this multicenter study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the cyclooxygenase-2 (COX2) gene and susceptibility to sarcoidosis, as well as the relation between these SNPs and the evolution of the disease.

Material And Methods: This multicenter investigation involved seven hospitals in Spain. We used a case-control design followed by a prospective follow-up study. Sarcoid patients were recruited from the participating institutions during outpatient routine visits. Age- and gender-matched control subjects were recruited mainly from among outpatients attending the participating hospitals. Four SNPs in the COX2 gene (COX2.5909 T > G, COX2.8473 T > C, COX2.926 G > C, and COX2.3050 G > C) were genotyped using fluorescent hybridization probes among 131 patients with sarcoidosis (63 males; mean age: 47 +/- 15 years) and 157 healthy controls (83 males; mean age: 50 +/- 16 years). We employed a binomial multiple logistic regression analysis to test the association between the selected SNPs and disease susceptibility. The clinical, functional and radiological prognosis of the sarcoidosis patients was determined after a mean follow-up of 37.4 +/- 30.4 months.

Results: Carriers of the homozygous CC genotype of the COX2.8473 T > C polymorphism had a higher risk of sarcoidosis compared with TT carriers (OR: 3.08; 95% CI: 1.2-7.7; p = 0.035). 84% of patients achieved improvement or complete remission at follow-up. No association between the investigated SNPs and prognosis was seen.

Conclusions: Our data suggest that the homozygous CC genotype of the COX2.8473 T > C polymorphism may be associated with sarcoidosis susceptibility. No significant association with prognosis was detected.
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http://dx.doi.org/10.1016/j.rmed.2008.09.014DOI Listing
March 2009

[Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease: data from the Spanish patient registry].

Arch Bronconeumol 2008 Sep;44(9):499-503

Servicio de Neumología, Complejo Hospitalario, Pontevedra, España.

Among the idiopathic interstitial lung diseases, respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and desquamative interstitial pneumonia (DIP) make up a subgroup of rare diseases that are clearly smoking related. Few large case series have been published. We describe 19 cases registered in Spain: 12 patients with DIP and 7 with RB-ILD. Clinical and radiologic features are described along with clinical course, treatments applied, and outcomes. With the exception of 2 patients with DIP, all were smokers or ex-smokers. Cough and dyspnea were the most common symptoms at onset in both diseases. The most frequent radiologic findings were ground-glass opacity in DIP and pulmonary nodules in BR-ILD. Most patients were treated with corticosteroids. Outcomes were good in general; only 1 patient, with DIP, died.
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September 2008

[Polymyositis and interstitial lung disease with a favorable response to corticosteroids and methotrexate].

Arch Bronconeumol 2007 Nov;43(11):636-9

Servicio de Neumología, Hospital de La Princesa, Madrid, España.

Polymyositis is a rare collagen disease that can involve the lungs. Between 5% and 30% of patients with polymyositis present interstitial lung disease at diagnosis or during the course of disease. Onset is usually insidious and involves dyspnea and nonproductive cough. Several histopathological findings are associated with polymyositis and the most common is nonspecific interstitial pneumonia. The prognosis of interstitial lung disease associated with polymyositis is better than that of idiopathic pulmonary fibrosis, since most patients respond to treatment with corticosteroids and immunosuppressants. We report the case of a 60-year-old woman with dyspnea and muscle weakness who was diagnosed with polymyositis and interstitial lung disease (radiography indicated possible nonspecific interstitial pneumonia). The patient responded well to prednisone and methotrexate.
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http://dx.doi.org/10.1016/s1579-2129(07)60142-6DOI Listing
November 2007
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