Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
Sr Care Pharm ; 39(6): 212-217, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38803027

ABSTRACT

Background In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk.1 In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention. Objective To identify the role of a pharmacist-led aspirin deprescribing intervention within a safety-net health system in the outpatient setting. Methods This project included patients 70 years of age and older who had aspirin listed as an active medication without documented ASCVD. This project assessed aspirin deprescribing rates, time spent on pharmacist outreach, and reasons for patient and/or provider refusal to discontinue aspirin. Results One hundred thirty-one eligible patients were contacted. Of those, 78 (60%) patients discontinued aspirin after speaking with the pharmacist, and 8 patients discontinued aspirin after a clinical pharmacist recommendation to the patient's primary care provider (PCP). The median time spent on outreach was approximately eight minutes. Of the 6 patients who consented to the project but declined to discontinue aspirin therapy based on pharmacist intervention, 5 preferred to discuss the issue with their PCP, while 1 patient was told by an outside provider to take aspirin. Conclusion Results indicate the successful impact a clinical pharmacist may have in deprescribing aspirin in a high-risk population. These data may also suggest that an active and intentional approach to deprescribing is likely to be more effective than a written recommendation to providers.


Subject(s)
Aspirin , Deprescriptions , Pharmacists , Humans , Aspirin/therapeutic use , Aspirin/administration & dosage , Aged , Male , Female , Aged, 80 and over , Outpatients , Professional Role , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Primary Prevention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Ambulatory Care
2.
Diagn Microbiol Infect Dis ; 107(4): 116083, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37778156

ABSTRACT

Transmitted Resistance exists in a newly diagnosed person who has not yet started their treatment. Our objective was to obtain a profile of HIV-1 resistance to integrase inhibitors in newly diagnosed treatment-naïve patients. Fifty people newly diagnosed with HIV-1 infection who had never received antiretroviral treatment were recruited. The complete integrase gene was amplified by nested RTPCR and the sequences obtained were analyzed with the ReCall and HIVdb v9.0. The overall prevalence transmitted due to mutations with some impact on integrase strand transfer inhibitors (INSTI) activity during the study period was 8%. The major E138K mutation was detected in only 1 patient and the secondary G163R mutation was detected in the other 3. The transmitted resistance for the first generation INSTI was 8% and for the second generation it was 0%. In Chile the resistance transmitted to INSTI is low and it is in according values detect in other part of the world.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , HIV Integrase , Humans , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , Genotype , HIV Integrase/genetics , Drug Resistance, Viral/genetics , HIV Infections/epidemiology , Mutation
3.
Article in English | MEDLINE | ID: mdl-37444048

ABSTRACT

The population in the world is aging dramatically, and therefore, the economic and social effort required to maintain the quality of life is being increased. Assistive technologies are progressively expanding and present great opportunities; however, given the sensitivity of health issues and the vulnerability of older adults, some considerations need to be considered. This paper presents DigiHEALTH, a suite of digital solutions for long-term healthy and active aging. It is the result of a fruitful trajectory of research in healthy aging where we have understood stakeholders' needs, defined the main suite properties (that would allow scalability and interoperability with health services), and codesigned a set of digital solutions by applying a continuous reflexive cycle. At the current stage of development, the digital suite presents eight digital solutions to carry out the following: (a) minimize digital barriers for older adults (authentication system based on face recognition and digital voice assistant), (b) facilitate active and healthy living (well-being assessment module, recommendation system, and personalized nutritional system), and (c) mitigate specific impairments (heart failure decompensation, mobility assessment and correction, and orofacial gesture trainer). The suite is available online and it includes specific details in terms of technology readiness level and specific conditions for usage and acquisition. This live website will be continually updated and enriched with more digital solutions and further experiences of collaboration.


Subject(s)
Quality of Life , Self-Help Devices
4.
J Oral Rehabil ; 50(10): 991-1001, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37282365

ABSTRACT

BACKGROUND: With the ageing process changes in the musculature of oro-facial structures take place, consequently there is a reduction in the strength and mobility of the lips, tongue and cheeks. OBJECTIVE: The aim of this study was to correlate oro-facial structures and chewing and swallowing functions among a group of senior citizens and young adults and check the influence of lip and tongue pressure of these functions. METHODS: This is an observational, cross-sectional and analytical study. Thirty seniors with an average age of 67.13 years and 30 young adults with an average age of 22.03 years participated in the study. The Oro-facial Myofunctional Assessment Protocol with Scores for the Elderly and the Oro-facial Myofunctional Assessment Protocol with Expanded Scores were also used. The evaluation of the force of pressure of the lips and tip and dorsum of the tongue was carried out using the Biofeedback device Pró-Fono: Lip and Tongue Pressure. RESULTS: Young adults had a higher evaluation score for the aspect/posture of the face, cheeks, lips, mentalis muscle, tongue, mobility of lips, tongue, jaw and cheeks, chewing and swallowing functions, total time and chewing strokes, and tip pressure and dorsum of tongue. According to the Structural Equation Modelling, a direct relationship was found between the tongue dorsum pressure force and the swallowing function. CONCLUSION: With healthy ageing changes occurring in the appearance, posture and mobility of the lips, tongue, jaw and cheeks, with the seniors and reduced performance of chewing and swallowing functions.


Subject(s)
Lip , Tongue , Young Adult , Humans , Aged , Adult , Tongue/physiology , Cross-Sectional Studies , Pressure , Deglutition/physiology , Mastication/physiology
6.
Int J Comput Assist Radiol Surg ; 18(7): 1151-1157, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37160582

ABSTRACT

PURPOSE: Computer-assisted surgical planning methods help to reduce the risks and costs in transpedicular fixation surgeries. However, most methods do not consider the speed and versatility of the planning as factors that improve its overall performance. In this work, we propose a method able to generate surgical plans in minimal time, within the required safety margins and accounting for the surgeon's personal preferences. METHODS: The proposed planning module takes as input a CT image of the patient, initial-guess insertion trajectories provided by the surgeon and a reduced set of parameters, delivering optimal screw sizes and trajectories in a very reduced time frame. RESULTS: The planning results were validated with quantitative metrics and feedback from surgeons. The whole planning pipeline can be executed at an estimated time of less than 1 min per vertebra. The surgeons remarked that the proposed trajectories remained in the safe area of the vertebra, and a Gertzbein-Robbins ranking of A or B was obtained for 95 % of them. CONCLUSIONS: The planning algorithm is safe and fast enough to perform in both pre-operative and intra-operative scenarios. Future steps will include the improvement of the preprocessing efficiency, as well as consideration of the spine's biomechanics and intervertebral rod constraints to improve the performance of the optimisation algorithm.


Subject(s)
Pedicle Screws , Spinal Fusion , Surgery, Computer-Assisted , Humans , Tomography, X-Ray Computed/methods , Surgery, Computer-Assisted/methods , Spine/surgery , Algorithms , Spinal Fusion/methods
7.
Int J Mol Sci ; 23(16)2022 Aug 18.
Article in English | MEDLINE | ID: mdl-36012570

ABSTRACT

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine implicated in the etiology of several autoimmune diseases, including rheumatoid arthritis (RA). TNF-α regulates diverse effector functions through the activation of TNF-α receptor (TNFR)1 and TNFR2. Although the detrimental role of this cytokine has been addressed in distinct disease settings, the effects of TNF-α on cytokine production by isolated CD4+ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that TNF-α promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-γ and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed that TNFR2 mediates the decrease in IFN-γ production, while signaling through both receptors augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T cell types is similar between patients and controls. Since TNF-α receptors levels in RA patients are not significantly changed by the therapeutic blockade of TNF-α, we propose that targeting TNFR2 may represent an alternative strategy to normalize the levels of key cytokines that contribute to RA pathogenesis.


Subject(s)
Arthritis, Rheumatoid , Receptors, Tumor Necrosis Factor, Type II , Receptors, Tumor Necrosis Factor, Type I , Th1 Cells , Th17 Cells , Arthritis, Rheumatoid/metabolism , Cytokines/metabolism , Humans , Interleukin-17 , Receptors, Tumor Necrosis Factor, Type I/metabolism , Receptors, Tumor Necrosis Factor, Type II/metabolism , Tumor Necrosis Factor-alpha/metabolism
8.
CoDAS ; 34(1): e20200364, 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1345834

ABSTRACT

ABSTRACT Purpose To characterize the masticatory function of the elderly and to compare total amount of time, masticatory strokes and total mastication score among the elderly and young adults. Methods It is an observational, cross-sectional and analytical study. A total of 50 individuals participated, 25 elderly (mean age 66 years) and 25 young adults (mean age 22 years). The evaluation of mastication was performed by standardized filming of the usual mastication of a wheat flour biscuit. The masticatory type (alternated bilateral, simultaneous bilateral, preferential unilateral, chronic and anterior), masticatory score, total masticatory time and the total number of masticatory strokes were verified and compared between the elderly and young adults. Results The predominant masticatory pattern in the young adults was the alternated bilateral mastication (52%), while, in the elderly, the simultaneous bilateral mastication predominated (48%). The use of dental prostheses had a significant influence on the total mastication score; elderly presented greater masticatory time and greater amount of masticatory strokes; however, the total masticatory score was lower for this group. Conclusion The use of dental prosthesis has a significant influence on masticatory function. When compared to young adults, the elderly had a greater amount of time and masticatory strokes and a lower total mastication score.


RESUMO Objetivo Caracterizar a função mastigatória de idosos e comparar o total de tempo e golpes mastigatórios e o escore mastigatório total entre idosos e adultos jovens. Método Trata-se de um estudo observacional, transversal e analítico. Um total de 50 indivíduos participaram do estudo, 25 idosos (idade média de 66 anos) e 25 adultos jovens (idade média de 22 anos). A avaliação da função mastigatória foi realizada por meio da filmagem padronizada da mastigação habitual de um biscoito maisena. O tipo mastigatório (bilateral alternado, bilateral simultâneo, unilateral preferencial, crônica e anterior), o escore mastigatório, o total do tempo mastigatório e o número total de golpes mastigatórios foram verificados e comparados entre os idosos e os adultos jovens. Resultados O padrão mastigatório predominante nos adultos jovens foi a mastigação bilateral alternada (52%), enquanto que nos idosos predominou a mastigação bilateral simultânea (48%). O uso de prótese dentária apresentou influência significativa no escore total da mastigação; os idosos apresentaram maior tempo mastigatório e maior quantidade de golpes mastigatórios; contudo, o escore total da mastigação foi menor para este grupo. Conclusão O uso de prótese dentária apresenta influência significativa na função mastigatória. Quando comparados aos jovens, idosos apresentam maior quantidade de tempo e golpes mastigatórios e menor escore total da mastigação.

9.
Codas ; 34(1): e20200364, 2021.
Article in English | MEDLINE | ID: mdl-34705926

ABSTRACT

PURPOSE: To characterize the masticatory function of the elderly and to compare total amount of time, masticatory strokes and total mastication score among the elderly and young adults. METHODS: It is an observational, cross-sectional and analytical study. A total of 50 individuals participated, 25 elderly (mean age 66 years) and 25 young adults (mean age 22 years). The evaluation of mastication was performed by standardized filming of the usual mastication of a wheat flour biscuit. The masticatory type (alternated bilateral, simultaneous bilateral, preferential unilateral, chronic and anterior), masticatory score, total masticatory time and the total number of masticatory strokes were verified and compared between the elderly and young adults. RESULTS: The predominant masticatory pattern in the young adults was the alternated bilateral mastication (52%), while, in the elderly, the simultaneous bilateral mastication predominated (48%). The use of dental prostheses had a significant influence on the total mastication score; elderly presented greater masticatory time and greater amount of masticatory strokes; however, the total masticatory score was lower for this group. CONCLUSION: The use of dental prosthesis has a significant influence on masticatory function. When compared to young adults, the elderly had a greater amount of time and masticatory strokes and a lower total mastication score.


Subject(s)
Flour , Triticum , Adult , Aged , Cross-Sectional Studies , Humans , Mastication , Young Adult
10.
ASAIO J ; 67(9): 1018-1025, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34225279

ABSTRACT

Logfiles from the HeartWare HVAD System provide operational pump trend data to aid in patient management. Pump thrombosis is commonly associated with increases in the logfile power that may precede the clinical presentation. A Power Tracking algorithm was developed to detect significant deviations in pump power that may be associated with pump thrombus (PT). The Power Tracking algorithm was applied retrospectively to logfiles captured in the ENDURANCE, ENDURANCE Supplemental, and LATERAL clinical trials. From a combined dataset of 896 patients, available logfiles with suspected PT (n = 70 events in 60 patients) and available logfiles from patients without adverse events (AEs) (n = 106 patients, consisting of 27.4 patient-years of monitoring) were organized into two cohorts. The Power Tracking algorithm detected PT cases on or before the recorded AE date with a sensitivity of 85.7%, with detection occurring an average of 3.9 days before clinical presentation. The algorithm averaged one false alarm for every 6.85 patient-years of monitoring from logfiles without AEs. The favorable performance of the Power Tracking algorithm may enable earlier detection of pump thrombosis and allow early medical management versus surgical intervention.


Subject(s)
Heart Failure , Heart-Assist Devices , Thrombosis , Algorithms , Early Diagnosis , Heart-Assist Devices/adverse effects , Humans , Retrospective Studies , Thrombosis/diagnosis , Thrombosis/etiology
12.
J Virus Erad ; 6(3): 100002, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33251020

ABSTRACT

In this viewpoint we would like to describe our results in terms of resistance pattern in Chilean patients with virological failure (VF) on raltegravir (RAL)-containing-regimens and highlight the need for the concomitant availability of genotypic resistance testing to integrase strand transfer inhibitors (INSTIs) introduction in antiretroviral regimens, particularly in countries in South America. Indeed we found in our study the presence of two or more primary mutations in some of the participants which is associated with cross-resistance to all INSTIs. By using timely genotyping, we could optimally manage these patients, early after detection of VF.

13.
BMJ Case Rep ; 13(11)2020 Nov 02.
Article in English | MEDLINE | ID: mdl-33139364

ABSTRACT

We report a case of a 1-year and 2-month-old girl with clinical features consistent with congenital hemidysplasia with ichthyosis and limb defects syndrome. Sterol analysis from skin flakes revealed increased levels of a mono 4-alpha methyl sterol also seen in plasma as well as the presence of 4-alpha-carboxy-4-methyl-cholest-8(9)-en-3beta-ol and several keto-sterols, which are usually below the limit of detection. This sterol pattern is consistent with abnormal function of the 4-alpha-methylsterol-4-demethylase complex. NSDHL gene testing revealed the presence of a variant of uncertain significance, c.130G>A (p.Gly44Ser). This missense mutation currently is not included in population databases (ExAC no frequency) and has not been reported in individuals with an NSDHL-related condition. Parental studies showed that neither parent carries the NSDHL variant. On this basis, this variant has been reclassified as likely pathogenic. Symptomatic treatment with keratolytic agents, emollients and ketoconazole was initiated.


Subject(s)
3-Hydroxysteroid Dehydrogenases/genetics , Abnormalities, Multiple/genetics , DNA/genetics , Genetic Diseases, X-Linked/genetics , Ichthyosiform Erythroderma, Congenital/genetics , Limb Deformities, Congenital/genetics , Mutation, Missense , 3-Hydroxysteroid Dehydrogenases/metabolism , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/metabolism , DNA Mutational Analysis , Diagnosis, Differential , Female , Genetic Diseases, X-Linked/diagnosis , Genetic Diseases, X-Linked/metabolism , Genetic Variation , Humans , Ichthyosiform Erythroderma, Congenital/diagnosis , Ichthyosiform Erythroderma, Congenital/metabolism , Infant , Limb Deformities, Congenital/diagnosis , Limb Deformities, Congenital/metabolism , Radiography
14.
World Allergy Organ J ; 13(9): 100457, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32922624

ABSTRACT

BACKGROUND: Diamine Oxidase (DAO) has an essential role for degradation of exogenous histamine in the intestine; thus, histamine intolerance (HI) mainly has been correlated to a low concentration and/or activity of this enzyme. The objective of the study was to standardize a colorimetric technique to measure the enzymatic activity (function) of hDAO to then apply it to a series of 22 patients with a clinical diagnosis of HI. METHODS: For the standardization variables such as volume and type of sample, incubation time, wavelength of maximum absorption, types of substrates, and concentration of oxidized ascorbate were evaluated. Then the activity and concentration of DAO was determined in 22 patients diagnosed with HI and 22 healthy subjects. RESULTS: The mean of serum DAO concentration in the 22 patients was of 9.268 ± 1.124 U/mL. The mean of serum DAO concentration in the 22 controls was of 20.710 ± 2.509 U/mL, being significantly higher (P value 0.0002) the mean of the samples. The mean of serum DAO activity of the patients was of 1.143 ± 0.085 U/L and the controls was 1.533 ± 0.119 U/L, significantly greater than the patients (P value 0.011). In addition, the sensitivity of both techniques was 0.63. In the measuring of DAO concentration the specificity was 0.9, constituting a good diagnostic test, especially to rule out the true negatives. The determination of DAO activity had a specificity of 0.68. CONCLUSIONS: Although we used a small number of patients and controls and the absorbance values were lower than expected, statistically significant differences were found in the levels of concentration and DAO activity between the patients with histamine intolerance and the controls. Therefore, the measuring of DAO concentration and DAO activity is a good diagnostic strategy for study suspect cases of HI. The simultaneous use of both assays allows to reduce positive and negative false results, for example, patients with normal DAO levels that could present a dysfunction in the activity of this enzyme.

15.
Artif Organs ; 44(9): 935-938, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32437585

ABSTRACT

The Medtronic Autologs System allows real-time clinician review of HeartWare HVAD System logfiles, providing supplemental pump data to aid in patient management. In its first year of availability, Autologs generated a 70% increase in logfile submissions, with 73% of all logfile requests being sent to Autologs. Within a month of its launch, Autologs submissions outnumbered the amount of logfiles submitted for manual review. Following the v1.1 release, there was a 20% increase in logfile submissions, with 77% of all logfile requests being Autologs. With the introduction of v1.2, there was another 35% increase in logfile submissions, with nearly 90% of all logfile requests being Autologs. The widespread adoption and utility of the Autologs System highlights the need for clinician access to real-time data analysis in the field of Mechanical Circulatory Support.


Subject(s)
Heart Failure/surgery , Heart-Assist Devices , Monitoring, Ambulatory/instrumentation , Heart Failure/diagnosis , Heart-Assist Devices/history , History, 21st Century , Humans , Monitoring, Ambulatory/history
16.
Clin Rehabil ; 34(2): 263-275, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31795759

ABSTRACT

OBJECTIVES: The aim of this study is to design a questionnaire, the Versailles Metacognitive Strategies Evaluation Questionnaire, for assessing the use of metacognitive and help-seeking strategies in three key-domains of impaired daily functioning in schizophrenia. To evaluate its psychometric properties (internal consistency, factor structure, convergent and divergent validity, and stability). DESIGN: Development of a questionnaire and psychometric validation procedure in patients with schizophrenia compared with healthy controls. Stability over one year was assessed in the patient group. SETTING: Schizophrenia Centers of Expertise (French FondaMental Network). SUBJECTS: A total of 141 patients with schizophrenia, among whom 77 participated in the second evaluation; 97 healthy subjects. MAIN MEASURES: The Versailles Metacognitive Strategies Evaluation Questionnaire, Positive and Negative Symptoms Scale, Personal and Social Performance Scale, Evaluation of Cognitive Processes involved in Disability in Schizophrenia Scale, Schizophrenia Quality of Life Questionnaire, and Stages of Recovery Instrument. RESULTS: From the 36-items version, stepwise exploratory factor analysis (oblimin) produced a 25-items scale which had a 3-factors structure (hygiene concern, social relationships, and hygiene help-seeking). Cronbach's were respectively equal to 0.91, 0.82, and 0.78. One-year stability was good (intra-class correlation coefficient = 0.7). The three factors showed good convergent validity with measures of quality of life (rho = 0.34, P ⩽ 0.001). The first two factors correlated with recovery (N = 34, rho = 0.53, P ⩽ 0.001). On the contrary, the factors exhibited divergent validity, with no significant correlation, with symptoms and cognitive and psychosocial functioning (P > 0.05). Factor structure in healthy controls did not match with that of patients, all items but one were found significantly different among groups. CONCLUSION: The Versailles Metacognitive Strategies Evaluation Questionnaire provides a simple and valid means to assess metacognitive strategies in individuals with schizophrenia.


Subject(s)
Help-Seeking Behavior , Metacognition , Schizophrenic Psychology , Surveys and Questionnaires , Adult , Aged , Case-Control Studies , Factor Analysis, Statistical , Female , France , Humans , Longitudinal Studies , Male , Middle Aged , Psychometrics , Reproducibility of Results , Young Adult
17.
Apuntes psicol ; 36(3): 167-172, 2018.
Article in Spanish | IBECS | ID: ibc-181187

ABSTRACT

En el desarrollo de las redes atencionales interaccionan factores genéticos y ambientales. Además, dentro del modelo de redes atencionales se postula la existencia de tres redes atencionales diferentes como son la red de alerta, red de orientación y red ejecutiva donde cada una tiene una función específica pero relacionadas entre sí. Siguiendo esta línea, en la actualidad existe una línea innovadora que se centra en el desarrollo de las redes atencionales en la infancia y cómo el entrenamiento de las mismas influye a nivel cerebral y comportamental. Los resultados de estas investigaciones en entrenamiento atencional, y en concreto de la atención ejecutiva, confirman la capacidad plástica del cerebro para responder a los estímulos del medio mediante ajustes y modificaciones en su arquitectura funcional y estructural. Asimismo, apoya la necesidad de realizar programas de intervención donde se lleven a cabo un entrenamiento atencional en el niño debido a la influencia positiva en el desarrollo integral del mismo


In the development of the attention networks, genetic and environmental factors interact. In addition, within the model of attentional networks, the existence of three different attentional networks is proposed, such as the alert network, orientation network and executive network; where each one has a specific function but are related to each other. In addition, there is currently an innovative line that focuses on the development of attentional networks in childhood and how their training influences brain and behavioral levels. The results of these investigations in attentional training, and in particular of executive attention, confirm the plastic capacity of the brain to respond to stimuli in the environment through adjustments and modifications in its functional and structural architecture. It also supports the need to carry out intervention programs where attentional training is carried out on the child due to the positive influence on the child’s integral development


Subject(s)
Attention/physiology , Child Development/physiology , Executive Function/physiology , Arousal/physiology , Orientation/physiology , Cognitive Remediation/methods
18.
Front Immunol ; 6: 496, 2015.
Article in English | MEDLINE | ID: mdl-26483788

ABSTRACT

The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10(+) B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.

19.
J Transl Med ; 11: 128, 2013 May 24.
Article in English | MEDLINE | ID: mdl-23706017

ABSTRACT

BACKGROUND: Generation of tolerogenic dendritic cells (TolDCs) for therapy is challenging due to its implications for the design of protocols suitable for clinical applications, which means not only using safe products, but also working at defining specific biomarkers for TolDCs identification, developing shorter DCs differentiation methods and obtaining TolDCs with a stable phenotype. We describe here, a short-term protocol for TolDCs generation, which are characterized in terms of phenotypic markers, cytokines secretion profile, CD4+ T cell-stimulatory ability and migratory capacity. METHODS: TolDCs from healthy donors were generated by modulation with dexamethasone plus monophosphoryl lipid A (MPLA-tDCs). We performed an analysis of MPLA-tDCs in terms of yield, viability, morphology, phenotypic markers, cytokines secretion profile, stability, allogeneic and antigen-specific CD4+ T-cell stimulatory ability and migration capacity. RESULTS: After a 5-day culture, MPLA-tDCs displayed reduced expression of costimulatory and maturation molecules together to an anti-inflammatory cytokines secretion profile, being able to maintain these tolerogenic features even after the engagement of CD40 by its cognate ligand. In addition, MPLA-tDCs exhibited reduced capabilities to stimulate allogeneic and antigen-specific CD4+ T cell proliferation, and induced an anti-inflammatory cytokine secretion pattern. Among potential tolerogenic markers studied, only TLR-2 was highly expressed in MPLA-tDCs when compared to mature and immature DCs. Remarkable, like mature DCs, MPLA-tDCs displayed a high CCR7 and CXCR4 expression, both chemokine receptors involved in migration to secondary lymphoid organs, and even more, in an in vitro assay they exhibited a high migration response towards CCL19 and CXCL12. CONCLUSION: We describe a short-term protocol for TolDC generation, which confers them a stable phenotype and migratory capacity to lymphoid chemokines, essential features for TolDCs to be used as therapeutics for autoimmunity and prevention of graft rejection.


Subject(s)
Cell Movement , Chemokines/metabolism , Dendritic Cells/drug effects , Dexamethasone/pharmacology , Lipid A/analogs & derivatives , Autoimmunity , Biomarkers/metabolism , CD4-Positive T-Lymphocytes/cytology , Cell Differentiation , Cytokines/metabolism , Dendritic Cells/cytology , Flow Cytometry , Humans , Lipid A/pharmacology , Phenotype , Receptors, CCR7/metabolism , Receptors, CXCR4/metabolism
20.
Stem Cells ; 29(2): 251-62, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21732483

ABSTRACT

Human ESCs provide access to the earliest stages of human development and may serve as an unlimited source of functional cells for future cell therapies. The optimization of methods directing the differentiation of human embryonic stem cells (hESCs) into tissue-specific precursors becomes crucial. We report an efficient enrichment of mesenchymal stem cells (MSCs) from hESCs through specific inhibition of SMAD-2/3 signaling. Human ESC-derived MSCs (hESC-MSCs) emerged as a population of fibroblastoid cells expressing a MSC phenotype: CD73+ CD90+ CD105+ CD44+ CD166+ CD45- CD34- CD14- CD19- human leucocyte antigen-DR (HLA-DR)-. After 28 days of SMAD-2/3 inhibition, hESC cultures were enriched (>42%) in multipotent MSCs. CD73+CD90+ hESC-MSCs were fluorescence activated cell sorting (FACS)-isolated and long-term cultures were established and maintained for many passages displaying a faster growth than somatic tissue-derived MSCs while maintaining MSC morphology and phenotype. They displayed osteogenic, adipogenic, and chondrocytic differentiation potential and exhibited potent immunosuppressive and anti-inflammatory properties in vitro and in vivo, where hESC-MSCs were capable of protecting against an experimental model of inflammatory bowel disease. Interestingly, the efficient enrichment of hESCs into MSCs through inhibition of SMAD-2/3 signaling was not reproducible with distinct induced pluripotent stem cell lines. Our findings provide mechanistic insights into the differentiation of hESCs into immunosuppressive and anti-inflammatory multipotent MSCs with potential future clinical applications.


Subject(s)
Embryonic Stem Cells/immunology , Embryonic Stem Cells/metabolism , Inflammatory Bowel Diseases/prevention & control , Multipotent Stem Cells/immunology , Multipotent Stem Cells/metabolism , Smad2 Protein/antagonists & inhibitors , Smad3 Protein/antagonists & inhibitors , Antigens, CD , Benzamides/pharmacology , Cell Differentiation/physiology , Cell Line , Cell- and Tissue-Based Therapy , Dioxoles/pharmacology , Embryonic Stem Cells/cytology , Flow Cytometry , Humans , Immunosuppression Therapy , Inflammatory Bowel Diseases/immunology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Multipotent Stem Cells/cytology , Signal Transduction
SELECTION OF CITATIONS
SEARCH DETAIL
...