Publications by authors named "Jose César Milisenda"

16 Publications

  • Page 1 of 1

Clinical characteristics and outcome of patients aged over 80 years with covid-19.

Medicine (Baltimore) 2021 Feb;100(8):e24750

Department of Internal Medicine.

Abstract: To investigate the clinical characteristics and outcome of octogenarians with covid-19.This is a observational, retrospective, descriptive study.Consecutive patients aged >80 years who were admitted for covid-19 pneumonia during a 6 weeks period (March 20-April 30, 2020).Illness severity on admission was classified according to World Health Organization (WHO) criteria: mild, moderate, severe, and critical. Data collected included demographics, presenting symptoms, radiological and laboratory findings, comorbidities, functional status, treatment, and clinical outcome.There were 159 patients (52.2% women) with a median age of 85.99 (IQR: 80-98). The median Barthel index was 90 (40-100) and Charlson index was 5 (5-6). Most common presenting symptoms were fever, dyspnea, and cough. Patients had mild (8.2%), moderate (52.2%), or severe (39.6%) illness according to WHO criteria. A bilateral pulmonary involvement was seen in 86% of patients. Laboratory analysis revealed increased serum concentrations of inflammatory parameters (C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer) with an abnormal lymphocyte count [0.88 × 109/L (0.5)]. Treatments included corticosteroids in 37%, and biological therapies in 17.6%. Fifty three (33.3%) patients died during hospitalization, with a median time from admission to death of 3 (IQR 1-6) days. Mortality was higher in men (55%). Deceased patients had a significantly higher frequency of dyspnea, increased inflammatory parameters, and illness severity compared to survivors.One-third of octogenarians with covid-19 died during hospitalization and most had bilateral lung involvement. A further knowledge of the characteristics and outcome of this population may assist clinicians in the decision-making process in these patients.
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http://dx.doi.org/10.1097/MD.0000000000024750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909132PMC
February 2021

Response to: 'Correspondence on 'Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis'' by Takanashi .

Ann Rheum Dis 2021 Jan 13. Epub 2021 Jan 13.

Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA

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http://dx.doi.org/10.1136/annrheumdis-2020-219767DOI Listing
January 2021

Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis.

Ann Rheum Dis 2020 09 16;79(9):1234-1242. Epub 2020 Jun 16.

Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Insititutes of Health, Bethesda, Maryland, USA

Objectives: Myositis is a heterogeneous family of diseases that includes dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), polymyositis and overlap myositis. Additional subtypes of myositis can be defined by the presence of myositis-specific autoantibodies (MSAs). The purpose of this study was to define unique gene expression profiles in muscle biopsies from patients with MSA-positive DM, AS and IMNM as well as IBM.

Methods: RNA-seq was performed on muscle biopsies from 119 myositis patients with IBM or defined MSAs and 20 controls. Machine learning algorithms were trained on transcriptomic data and recursive feature elimination was used to determine which genes were most useful for classifying muscle biopsies into each type and MSA-defined subtype of myositis.

Results: The support vector machine learning algorithm classified the muscle biopsies with >90% accuracy. Recursive feature elimination identified genes that are most useful to the machine learning algorithm and that are only overexpressed in one type of myositis. For example, CAMK1G (calcium/calmodulin-dependent protein kinase IG), EGR4 (early growth response protein 4) and CXCL8 (interleukin 8) are highly expressed in AS but not in DM or other types of myositis. Using the same computational approach, we also identified genes that are uniquely overexpressed in different MSA-defined subtypes. These included apolipoprotein A4 (APOA4), which is only expressed in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) myopathy, and MADCAM1 (mucosal vascular addressin cell adhesion molecule 1), which is only expressed in anti-Mi2-positive DM.

Conclusions: Unique gene expression profiles in muscle biopsies from patients with MSA-defined subtypes of myositis and IBM suggest that different pathological mechanisms underly muscle damage in each of these diseases.
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http://dx.doi.org/10.1136/annrheumdis-2019-216599DOI Listing
September 2020

Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases.

J Clin Med 2020 May 13;9(5). Epub 2020 May 13.

Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain.

Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis ( = 7 dermatomyositis and = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O/min; = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (-12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. -69.55 ± 21.00; = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options.
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http://dx.doi.org/10.3390/jcm9051446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290779PMC
May 2020

Anoctamin 5 (ANO5) muscular dystrophy-three different phenotypes and a new histological pattern.

Neurol Sci 2020 Oct 12;41(10):2967-2971. Epub 2020 May 12.

Muscle Research Unit, Internal Medicine Service, Hospital Clínic de Barcelona, Universidad de Barcelona and CIBERER, C/Villarroel, 170 08036, Barcelona, Spain.

Objective: Anoctamin 5 (ANO5) is a putative intracellular calcium-activated chloride channel. Recessive mutations in ANO5 may present from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here we describe the clinical, pathological, and molecular findings of three unrelated patients with ANO5-related muscular dystrophy.

Methods: In this retrospective study, we analyzed our database which includes 1700 muscle biopsies performed for diagnostic purposes from October 2004 to February 2019. Patients were attended by two myology experts, who performed and analyzed the muscle biopsies. Muscle biopsies were frozen in cooled isopenthane, cryostat sectioned, and routinely stained and reacted (minimum 16 stainings). A custom panel, including 115 genes (Nextera Rapid Capture, Illumina) and whole-exome sequencing analysis, was used for next-generation sequencing in cases without a definite pathological diagnosis.

Results: Three patients were diagnosed with ANO5-related muscular dystrophy, with all presenting the common exon 5 mutation c.191dup plus a compound heterozygous missense mutation. They showed three different phenotypes (distal myopathy, LGMD2L, and asymptomatic hyperCKemia). Curiously, all three muscle biopsies showed different patterns, but numerous ragged-red fibers with little endomysial inflammation and partial invasion cell by T lymphocytes were observed in one.

Conclusion: ANO5-related muscular dystrophy is a heterogeneous disease with different clinical phenotypes as well as different histological patterns, which may even mimic a mitochondrial myopathy. The results of this study provide further knowledge of the clinical, histological, and pathological features related to ANO5 mutations.
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http://dx.doi.org/10.1007/s10072-020-04453-yDOI Listing
October 2020

Diffusion-weighted magnetic resonance imaging is useful for assessing inflammatory myopathies.

Muscle Nerve 2019 05 14;59(5):555-560. Epub 2019 Feb 14.

Muscle Research Unit, Radiology Department. Hospital Clínic de Barcelona, Universidad de Barcelona, Villarroel, 170, 08036, Barcelona, Spain.

Introduction: Short tau inversion recovery (STIR) sequences in whole-body MRI are usually used for detecting muscle edema (ME) in inflammatory myopathies. We evaluated b-value 800 diffusion-weighted imaging (b800 DWI).

Methods: Two radiologists independently and a consensus reader retrospectively reexamined 60 patients with inflammatory myopathies and 15 controls. For each participant, 78 muscles were analyzed with 3 sets of imaging acquisitions: T1-weighted (T1) turbo spin echo and STIR; T1 and DWI; and T1, STIR and DWI. Mean edema per patient was compared between sequences. Agreement was evaluated.

Results: Diffusion-weighted imaging detected more ME compared with STIR (P < 0.001). Agreement between readers was better with both sequences (k = 0.94) than with b800 DWI (k = 0.89) or STIR (k = 0.84) alone.

Discussion: Diffusion-weighted imaging is a valuable add-on for the study of inflammatory myopathies. Muscle Nerve 59:555-555, 2019.
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http://dx.doi.org/10.1002/mus.26438DOI Listing
May 2019

Correlation between quantitative and semiquantitative magnetic resonance imaging and histopathology findings in dermatomyositis.

Clin Exp Rheumatol 2019 Jul-Aug;37(4):633-640. Epub 2018 Dec 19.

Muscle Research Unit, Internal Medicine Service, Hospital Clínic de Barcelona, Universidad de Barcelona IDIBAPS and CIBERER, Barcelona, Spain.

Objectives: The aim of this study was to compare muscle biopsy findings, as well as clinical and analytical features, with those of magnetic resonance imaging (MRI) studies of muscle in patients with dermatomyositis.

Methods: All patients from the Longitudinal Myopathy Cohort of the Hospital Clínic de Barcelona were prospectively included in the study from 2009 to 2016. MRI images of muscle and fascial oedema were compared with muscle pathology results using both quantitative and semi-quantitative scores.

Results: We found a statistically significant association between the inflammatory infiltrate and both muscle (r2=0.54, p=0.001) and fascial oedema (r2=0.54, p<0.001). In addition, muscle oedema was significantly associated with punched-out vacuoles (p=0.04) and muscle enzymes in serum (r2=0.34, p=<0.01 for CK and r2=0.22, p<0.05 for aldolase). The number of treatment drugs received at the time of MRI was inversely associated with the number of muscle inflammatory cells in the biopsy and with both muscle and fascial oedema (all p<0.05).

Conclusions: Key MRI findings correlate with the main features of dermatomyositis muscle biopsy results, suggesting that MRI findings could be used as a surrogate marker of disease activity.
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July 2019

Whole-body MRI and pathological findings in adult patients with myopathies.

Skeletal Radiol 2019 May 30;48(5):653-676. Epub 2018 Oct 30.

Department of Internal Medicine, Hospital Clinic, Universitat de Barcelona (UB) and CIBERER, Villarroel 170, 08036, Barcelona, Spain.

Magnetic resonance imaging (MRI) is considered the most sensitive and specific imaging technique for the detection of muscle diseases related to myopathies. Since 2008, the use of whole-body MRI (WBMRI) to evaluate myopathies has improved due to technical advances such as rolling table platform and parallel imaging, which enable rapid assessment of the entire musculoskeletal system with high-quality images. WBMRI protocols should include T1-weighted and short-tau inversion recovery (STIR), which provide the basic pulse sequences for studying myopathies, in order to detect fatty infiltration/muscle atrophy and muscle edema, respectively. High signal intensity in T1-weighted images shows chronic disease with fatty infiltration, whereas high signal intensity in STIR indicates an acute stage with muscle edema. Additional sequences such as diffusion-weighted imaging (DWI) can be readily incorporated into routine WBMRI study protocols. Contrast-enhanced sequences have not been done. This article reviews WBMRI as an imaging method to evaluate different myopathies (idiopathic inflammatory, dystrophic, non-dystrophic, metabolic, and channelopathies). WBMRI provides a comprehensive estimate of the total burden with a single study, seeking specific distribution patterns, including clinically silent involvement of muscle areas. Furthermore, WBMRI may help to select the "target muscle area" for biopsy during patient follow-up. It may be also be used to detect related and non-related pathological conditions, such as tumors.
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http://dx.doi.org/10.1007/s00256-018-3107-1DOI Listing
May 2019

Classification and management of adult inflammatory myopathies.

Lancet Neurol 2018 09;17(9):816-828

Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Inflammatory myopathies, collectively known as myositis, are heterogeneous disorders characterised by muscle inflammation, and frequently accompanied by extramuscular manifestations that affect the skin, lung, and joints. Patients with inflammatory myopathies were previously classified as having dermatomyositis if characteristic rashes accompanied the muscle involvement, and as having polymyositis if no rashes were present. Five main types of inflammatory myopathies are now widely recognised: dermatomyositis, immune-mediated necrotising myopathy, sporadic inclusion-body myositis, overlap myositis (including antisynthetase syndrome), and polymyositis. The discovery of autoantibodies that are specifically associated with characteristic clinical phenotypes has been instrumental to the understanding of inflammatory myopathies. Treatment is still largely based on expert opinion, but several studies have shown effectiveness of different therapies in various subsets of inflammatory myopathies. These advances will undoubtedly improve the outcomes of patients with inflammatory myopathies.
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http://dx.doi.org/10.1016/S1474-4422(18)30254-0DOI Listing
September 2018

Exhaustion of mitochondrial and autophagic reserve may contribute to the development of LRRK2 -Parkinson's disease.

J Transl Med 2018 06 8;16(1):160. Epub 2018 Jun 8.

Laboratory of Muscle Research and Mitochondrial Function-CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Internal Medicine-Hospital Clínic of Barcelona, Faculty of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain.

Background: Mutations in leucine rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). Mitochondrial and autophagic dysfunction has been described as etiologic factors in different experimental models of PD. We aimed to study the role of mitochondria and autophagy in LRRK2 -mutation, and its relationship with the presence of PD-symptoms.

Methods: Fibroblasts from six non-manifesting LRRK2 -carriers (NM-LRRK2 ) and seven patients with LRRK2 -associated PD (PD-LRRK2 ) were compared to eight healthy controls (C). An exhaustive assessment of mitochondrial performance and autophagy was performed after 24-h exposure to standard (glucose) or mitochondrial-challenging environment (galactose), where mitochondrial and autophagy impairment may be heightened.

Results: A similar mitochondrial phenotype of NM-LRRK2 and controls, except for an early mitochondrial depolarization (54.14% increased, p = 0.04), was shown in glucose. In response to galactose, mitochondrial dynamics of NM-LRRK2 improved (- 17.54% circularity, p = 0.002 and + 42.53% form factor, p = 0.051), probably to maintain ATP levels over controls. A compromised bioenergetic function was suggested in PD-LRRK2 when compared to controls in glucose media. An inefficient response to galactose and worsened mitochondrial dynamics (- 37.7% mitochondrial elongation, p = 0.053) was shown, leading to increased oxidative stress. Autophagy initiation (SQTSM/P62) was upregulated in NM-LRRK2 when compared to controls (glucose + 118.4%, p = 0.014; galactose + 114.44%, p = 0.009,) and autophagosome formation increased in glucose media. Despite of elevated SQSTM1/P62 levels of PD-NM when compared to controls (glucose + 226.14%, p = 0.04; galactose + 78.5%, p = 0.02), autophagosome formation was deficient in PD-LRRK2 when compared to NM-LRRK2 (- 71.26%, p = 0.022).

Conclusions: Enhanced mitochondrial performance of NM-LRRK2 in mitochondrial-challenging conditions and upregulation of autophagy suggests that an exhaustion of mitochondrial bioenergetic and autophagic reserve, may contribute to the development of PD in LRRK2 mutation carriers.
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http://dx.doi.org/10.1186/s12967-018-1526-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994110PMC
June 2018

Transcriptional alterations in skin fibroblasts from Parkinson's disease patients with parkin mutations.

Neurobiol Aging 2018 05 7;65:206-216. Epub 2018 Feb 7.

Laboratory of Muscle Research and Mitochondrial Function-CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Sciences, University of Barcelona (UB), Department of Internal Medicine-Hospital Clínic of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Mutations in the parkin gene (PRKN) are the most common cause of autosomal-recessive juvenile Parkinson's disease (PD). PRKN encodes an E3 ubiquitin ligase that is involved in multiple regulatory functions including proteasomal-mediated protein turnover, mitochondrial function, mitophagy, and cell survival. However, the precise molecular events mediated by PRKN mutations in PRKN-associated PD (PRKN-PD) remain unknown. To elucidate the cellular impact of parkin mutations, we performed an RNA sequencing study in skin fibroblasts from PRKN-PD patients carrying different PRKN mutations (n = 4) and genetically unrelated healthy subjects (n = 4). We identified 343 differentially expressed genes in PRKN-PD fibroblasts. Gene ontology and canonical pathway analysis revealed enrichment of differentially expressed genes in processes such as cell adhesion, cell growth, and amino acid and folate metabolism among others. Our findings indicate that PRKN mutations are associated with large global gene expression changes as observed in fibroblasts from PRKN-PD patients and support the view of PD as a systemic disease affecting also non-neural peripheral tissues such as the skin.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.01.021DOI Listing
May 2018

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations.

Expert Rev Clin Immunol 2018 03 23;14(3):215-224. Epub 2018 Feb 23.

e Internal Medicine Department, Hospital Clinic , Universitat de Barcelona , CIBERER , Barcelona , Spain.

Introduction: Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms 'myositis', 'statin-induced autoimmune myopathy', 'immune-mediate necrotizing myopathy', 'statins', 'muscular manifestations', and 'anti-HMGCR antibodies' were used. Expert commentary: Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.
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http://dx.doi.org/10.1080/1744666X.2018.1440206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019601PMC
March 2018

Tumour TIF1 mutations and loss of heterozygosity related to cancer-associated myositis.

Rheumatology (Oxford) 2018 02;57(2):388-396

Internal Medicine Department, Vall d'Hebron University Hospital, Barcelona, Spain.

Objectives: To analyse the influence of genetic alterations and differential expression of transcription intermediary factor 1 (TIF1) genes in the pathophysiology of cancer-associated myositis (CAM).

Methods: Paired blood and tumour DNA samples from patients with anti-TIF1γ-positive CAM and from controls were analysed by whole-exome sequencing for the presence of somatic mutations and loss of heterozygosity (LOH) in their TIF1 genes. The genesis and maintenance of the autoimmune process were investigated immunohistochemically by studying TIF1γ expression in the different tissues involved in CAM (skin, muscle and tumour) based on the immunohistochemical H-score.

Results: From seven patients with anti-TIF1γ-positive CAM, we detected one somatic mutation and five cases of LOH in one or more of the four TIF1 genes compared with just one case of LOH in tumours from TIF1γ-negative myositis patients (86% vs 17%; P = 0.03). Compared with type-matched control tumours from non-myositis patients, TIF1γ staining was more intense in tumours from anti-TIF1γ-positive patients (H-score 255 vs 196; P = 0.01). Also, TIF1γ staining in muscle was slightly more intense in anti-TIF1γ-positive than in anti-TIF1γ-negative myositis (H-score 22 vs 5; P = 0.03). In contrast, intense TIF1γ staining was detected in the skin of both myositis and control patients.

Conclusion: Tumours from paraneoplastic anti-TIF1γ-positive patients showed an increased number of genetic alterations, such as mutations and LOH, in TIF1 genes. These genetic alterations, in the context of a high expression of TIF1γ in the tumour, muscle and skin of these patients may be key to understanding the genesis of paraneoplastic myositis.
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http://dx.doi.org/10.1093/rheumatology/kex413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850766PMC
February 2018

Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis.

Clin Sci (Lond) 2016 10 13;130(19):1741-51. Epub 2016 Jul 13.

Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age- and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients.
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http://dx.doi.org/10.1042/CS20160080DOI Listing
October 2016

[Enteropathy associated with chronic use of olmesartan].

Med Clin (Barc) 2015 Feb 12;144(3):139-40. Epub 2014 Jun 12.

Servicio de Medicina Interna, Institut Clínic de Medicina i Dermatologia (ICMiD), Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.medcli.2014.03.031DOI Listing
February 2015