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1.
Trop Med Infect Dis ; 8(3)2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36977182

ABSTRACT

Strongyloides stercoralis infection is generally asymptomatic or mildly symptomatic, but in the immunosuppressed host, it is associated with more severe and complicated forms with a worse prognosis. S. stercoralis seroprevalence was studied in 256 patients before receiving immunosuppressive treatment (before kidney transplantation or starting biological treatments). As a control group, serum bank data of 642 individuals representative of the population of the Canary Islands were retrospectively analyzed. To avoid false positives due to cross-reactivity with other similar helminth antigens present in the study area, IgG antibodies to Toxocara spp. and Echinococcus spp. were evaluated in cases positive for Strongyloides. The data show this is a prevalent infection: 1.1% of the Canarian population, 2.38% of Canarian individuals awaiting organ transplants and 4.8% of individuals about to start biological agents. On the other hand, strongyloidiasis can remain asymptomatic (as observed in our study population). There are no indirect data, such as country of origin or eosinophilia, to help raise suspicion of the disease. In summary, our study suggests that screening for S. stercoralis infection should be performed in patients who receive immunosuppressive treatment for solid organ transplantation or biological agents, in line with previous publications.

2.
Trop Med Infect Dis ; 7(10)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36288059

ABSTRACT

BACKGROUND: The clinical and epidemiological data of the recent outbreak of monkeypox (MPX) differ from previous reports. One difference is the epidemiological profile; the disease mainly affects a subgroup of MSM (men who have sex with men) with high-risk sexual behaviors, frequently persons living with human immunodeficiency virus (PLHIV). METHODS: In this observational analysis, all patients with PCR (polymerase chain reaction)-confirmed MPX attending an Infectious Diseases and Tropical Medicine Unit in Gran Canaria (Spain) between May and July 2022 were considered. RESULTS: In total, 42 men were included; 88% were identified as MSM, with a median age of 40 years. Only 43% were born in Spain. All the patients had systemic symptoms and skin lesions. The distribution of lesions was more frequent in the genital/anal region, and the involvement of hands and feet was less common. Fever and lymphadenopathies were less frequent than in other series. Other unusual manifestations were proctitis, pharyngitis and penile-scrotal edema. Half of the patients had other associated infections (mainly STIs, sexually transmitted infections), and 60% of the monkeypox patients had PLHIV (People Living with HIV). When comparing the clinical characteristics between HIV-positive and -negative patients, we found three main differences: (i) a higher frequency of perioral lesions, (ii) a higher frequency of pharyngitis and (iii) a higher number of sexually transmitted infections in HIV-positive patients. CONCLUSIONS: The clinical findings in this outbreak of MPX had great variability in presentation. Several clinical differences were found in PLHIV-coinfected patients.

3.
Biomolecules ; 12(5)2022 05 19.
Article in English | MEDLINE | ID: mdl-35625649

ABSTRACT

The purpose of this study was to analyze the regenerative capacity of mesenchymal stem cells (MSCs) in the treatment of fractures. MSCs extracted from patients with osteoporotic hip fractures or hip osteoarthritis undergoing hip replacement surgeries were cultured and injected into mice with femoral fracture. Two experimental models were established, one for the systemic administration of MSCs (n = 29) and another one for local administration (n = 30). Fracture consolidation was assessed by micro-CT and histology. The degree of radiological consolidation and corticalization was better with MSCs from osteoporosis than from osteoarthritis, being significant after systemic administration (p = 0.0302 consolidation; p = 0.0243 corticalization). The histological degree of consolidation was also better with MSCs from osteoporosis than from osteoarthritis. Differences in histological scores after systemic infusion were as follows: Allen, p = 0.0278; Huo, p = 0.3471; and Bone Bridge, p = 0.0935. After local administration at the fracture site, differences in histological scores were as follows: Allen, p = 0.0764; Huo, p = 0.0256; and Bone Bridge, p = 0.0012. As osteoporosis and control groups were similar, those differences depended on an inhibitory influence by MSCs from patients with osteoarthritis. In conclusion, we found an unexpected impairment of consolidation induced by MSCs from patients with osteoarthritis. However, MSCs from patients with osteoporosis compared favorably with cells from patients with osteoarthritis. In other words, based on this study and previous studies, MSCs from patients with osteoporosis do not appear to have worse bone-regenerating capabilities than MSCs from non-osteoporotic individuals of similar age.


Subject(s)
Femoral Fractures , Mesenchymal Stem Cells , Osteoarthritis , Osteoporosis , Osteoporotic Fractures , Animals , Disease Models, Animal , Femoral Fractures/therapy , Fracture Healing , Humans , Mice
4.
Connect Tissue Res ; 63(3): 243-255, 2022 05.
Article in English | MEDLINE | ID: mdl-33618587

ABSTRACT

PURPOSE: Human mesenchymal stem cells (MSCs) have the ability to differentiate into bone-forming osteoblasts. The aim of this study was to elucidate if MSCs from patients with OP show a senescent phenotype and explore their bone-forming ability in vivo. MATERIALS AND METHODS: MSCs from patients with OP and controls with osteoarthritis (OA) were implanted into the subcutaneous tissue of immunodeficient mice for histological analysis and expression of human genes by RT-PCR. The expression of senescence-associated phenotype (SASP) genes, as well as p16, p21, and galactosidase, was studied in cultures of MSCs. RESULTS: In vivo bone formation was evaluated in 103 implants (47 OP, 56 OA). New bone was observed in 45% of the implants with OP cells and 46% of those with OA cells (p = 0.99). The expression of several bone-related genes (collagen, osteocalcin, alkaline phosphatase, sialoprotein) was also similar in both groups. There were no differences between groups in SASP gene expression, p16, and p21 expression, or in senescence-associated galactosidase activity. CONCLUSION: Senescence markers and the osteogenic capacity in vivo of MSCs from patients with OP are not inferior to that of cells from controls of similar age with OA. This supports the interest of future studies to evaluate the potential use of autologous MSCs from OP patients in bone regeneration procedures.


Subject(s)
Hip Fractures , Mesenchymal Stem Cells , Animals , Cell Differentiation/genetics , Cells, Cultured , Hip Fractures/metabolism , Humans , Mice , Osteoblasts/metabolism , Osteocalcin/metabolism , Osteogenesis/genetics
5.
DNA Cell Biol ; 39(9): 1691-1699, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32700968

ABSTRACT

Long noncoding RNAs (lncRNAs) contribute toward regulating gene expression and cell differentiation and may be involved in the pathogenesis of several diseases. The objective of this study was to determine the expression patterns of lncRNAs in bone marrow mesenchymal stem cells (BMSCs) derived from patients with osteoporotic fractures and their relevance to osteogenic function. The BMSCs were isolated from the femoral head of patients with hip fractures (FRX) and controls with osteoarthritis (OA). We found 74 differentially expressed genes between FRX and OA, of which 33 were of the lncRNA type. Among them, 52 genes (20 lncRNAs) were replicated in another independent dataset. The differentially expressed lncRNAs were over-represented among those correlated with differentially expressed protein-coding genes. In addition, the comparison of pre- and post-differentiated paired samples revealed 163 differentially expressed genes, of which 99 were of the lncRNA type. Among them, the overexpression of LINC00341 induced an upregulation of typical osteoblastic genes. In conclusion, the analysis of lncRNA expression in BMSCs shows specific patterns in patients with osteoporotic fractures, as well as changes associated with osteogenic differentiation. The regulation of bone genes through lncRNAs might bring new opportunities for designing bone anabolic therapies in systemic and localized bone disorders.


Subject(s)
Bone Marrow Cells/metabolism , Mesenchymal Stem Cells/metabolism , Osteoporosis/genetics , RNA, Long Noncoding/metabolism , Bone Marrow Cells/cytology , Cell Differentiation , Cells, Cultured , HEK293 Cells , Humans , Mesenchymal Stem Cells/cytology , Osteogenesis , Osteoporosis/pathology , RNA, Long Noncoding/genetics , Transcriptome
6.
J Bone Miner Res ; 34(2): 215-230, 2019 02.
Article in English | MEDLINE | ID: mdl-30715766

ABSTRACT

Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors, other than DNA sequence, that cause stable changes in gene expression and are maintained during cell divisions. They represent a link between environmental influences, genome features, and the resulting phenotype. The main epigenetic factors are DNA methylation, posttranslational changes of histones, and higher-order chromatin structure. Sometimes non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are also included in the broad term of epigenetic factors. There is rapidly expanding experimental evidence for a role of epigenetic factors in the differentiation of bone cells and the pathogenesis of skeletal disorders, such as osteoporosis and osteoarthritis. However, different from genetic factors, epigenetic signatures are cell- and tissue-specific and can change with time. Thus, elucidating their role has particular difficulties, especially in human studies. Nevertheless, epigenomewide association studies are beginning to disclose some disease-specific patterns that help to understand skeletal cell biology and may lead to development of new epigenetic-based biomarkers, as well as new drug targets useful for treating diffuse and localized disorders. Here we provide an overview and update of recent advances on the role of epigenomics in bone and cartilage diseases. © 2019 American Society for Bone and Mineral Research.


Subject(s)
Cartilage Diseases , DNA Methylation , Epigenesis, Genetic , Epigenomics , MicroRNAs , RNA, Long Noncoding , Animals , Cartilage Diseases/genetics , Cartilage Diseases/metabolism , Cartilage Diseases/pathology , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
9.
Curr Osteoporos Rep ; 16(3): 246-255, 2018 06.
Article in English | MEDLINE | ID: mdl-29574535

ABSTRACT

PURPOSE OF REVIEW: Epigenetic mechanisms modify gene activity in a stable manner without altering DNA sequence. They participate in the adaptation to the environment, as well as in the pathogenesis of common complex disorders. We provide an overview of the role of epigenetic mechanisms in bone biology and pathology. RECENT FINDINGS: Extensive evidence supports the involvement of epigenetic mechanisms (DNA methylation, post-translational modifications of histone tails, and non-coding RNAs) in the differentiation of bone cells and mechanotransduction. A variety of epigenetic abnormalities have been described in patients with osteoporosis, osteoarthritis, and skeletal cancers, but their actual pathogenetic roles are still unclear. A few drugs targeting epigenetic marks have been approved for neoplastic disorders, and many more are being actively investigated. Advances in the field of epigenetics underscore the complex interactions between genetic and environmental factors as determinants of osteoporosis and other common disorders. Likewise, they help to explain the mechanisms by which prenatal and post-natal external factors, from nutrition to psychological stress, impact our body and influence the risk of later disease.


Subject(s)
Bone Neoplasms/genetics , Cell Differentiation/genetics , Epigenesis, Genetic , Osteoarthritis/genetics , Osteoporosis/genetics , DNA Methylation , Histones/metabolism , Humans , Mechanotransduction, Cellular , Osteoblasts , Osteocytes , Osteogenesis , Protein Processing, Post-Translational , RNA, Untranslated/genetics
11.
Cardiovasc Toxicol ; 17(3): 360-367, 2017 07.
Article in English | MEDLINE | ID: mdl-27990617

ABSTRACT

Stroke, the second cause of death and the most frequent cause of severe disability among adults in developed countries, is related to a large variety of risk factors. This paper assesses the temporal patterns in stroke episodes in a city in Northern Spain during a 12-year period and analyzes the possible effects that atmospheric pollutants and meteorological variables may have on stroke on a daily scale. Our results show that there is an increase in stroke admissions (r = 0.818, p = 0.001) especially in patients over 85 years old. On a weekly scale, the number of hospital admissions due to stroke remains stable from Monday to Friday, whereas it abruptly decreases during the weekends, reaching its minimum values on Sunday (p < 0.005); however, mortality in patients admitted to the hospital is higher on Sundays than on other days of the week. Finally, a statistically significant positive correlation between the number of stroke hospital admissions and NO2 levels (p = 0.012) and an inverse correlation with relative humidity (p = 0.032) were found. The analysis of the relationship between ischemic strokes and atmospheric circulation shows a higher frequency of the former in Santander with enhanced negative air pressure anomalies over western Spain; the fact that under these conditions the region studied registers very low values of relative humidity is in line with the aforementioned inverse correlation, which has not been described elsewhere in the literature. This study could be a first step for implementing stroke alert protocols depending on air pollution levels and circulation patterns forecasts.


Subject(s)
Air Pollutants/adverse effects , Atmosphere , Environmental Exposure/adverse effects , Environmental Monitoring/methods , Seasons , Stroke/epidemiology , Adult , Aged , Aged, 80 and over , Air Pollutants/analysis , Air Pollution/adverse effects , Atmosphere/analysis , Environmental Exposure/analysis , Female , Humans , Male , Middle Aged , Patient Admission/trends , Retrospective Studies , Risk Factors , Spain/epidemiology , Stroke/diagnosis , Time Factors
14.
Expert Opin Drug Metab Toxicol ; 12(4): 389-98, 2016.
Article in English | MEDLINE | ID: mdl-26891809

ABSTRACT

INTRODUCTION: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. AREAS COVERED: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). EXPERT OPINION: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/toxicity , Osteoporosis/drug therapy , Osteoporosis/genetics , Bone Remodeling/drug effects , Diphosphonates/pharmacology , Dose-Response Relationship, Drug , Femoral Fractures/drug therapy , Femoral Fractures/genetics , Geranyltranstransferase/genetics , Geranyltranstransferase/metabolism , Humans , Jaw Diseases/drug therapy , Jaw Diseases/genetics , Osteonecrosis/drug therapy , Osteonecrosis/genetics , Wnt Signaling Pathway
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