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1.
Rev Esp Geriatr Gerontol ; 57(5): 269-272, 2022.
Article in Spanish | MEDLINE | ID: mdl-36123267

ABSTRACT

INTRODUCTION: Hip fracture is one of the most frequent disabling injuries, presenting serious complications during the acute and subacute phase. Rehabilitation at home, after hospital discharge, allows rapid functional recovery. The objective of this study is to evaluate the possible usefulness of a home rehabilitation program in patients with hip fracture integrated in a Hospital at Home Unit. METHODS: Retrospective study that consecutively included patients accepted for home rehabilitation treatment between September 9, 2019 and December 31, 2021 in the Hospital at Home Unit of the Hospital Universitario de la Ribera, Alzira, Valencia. Demographic, clinical, functional and quality of care variables were collected. RESULTS: Two hundred twenty-four subjects were included. The mean age was 84.6 (SD 7.7) years, with 66% women and 34% men, with 32% of patients diagnosed with dementia in one of its degrees of severity. The mean hospital stay was 8.4 (SD 4.1) days and 6.5 (5.3) days in the Hospital at Home Unit rehabilitation program. 90% of the patients included in the program reached the therapeutic goal outlined during hospital admission. CONCLUSIONS: The home rehabilitation of patients with hip fracture contributes to a functional recovery of the patient in a shorter time. Further studies are necessary to confirm the results obtained.


Subject(s)
Hip Fractures , Male , Humans , Female , Aged, 80 and over , Retrospective Studies , Hip Fractures/complications , Hospitalization , Length of Stay , Patient Discharge
2.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 57(5): 269-272, Sept.-oct. 2022. tab, graf
Article in Spanish | IBECS | ID: ibc-210505

ABSTRACT

Introducción: La fractura de cadera es una de las lesiones incapacitantes más frecuentes, presentando complicaciones graves durante la fase aguda y subaguda. La rehabilitación en el domicilio, tras el alta hospitalaria, permite una rápida recuperación funcional. El objetivo de este estudio es evaluar la posible utilidad de un programa domiciliario de rehabilitación en pacientes con fractura de cadera integrado en la una unidad de hospitalización a domicilio. Métodos: Estudio retrospectivo que incluyó consecutivamente a los pacientes aceptados para tratamiento rehabilitador domiciliario entre el 9 de septiembre del 2019 y el 31 de diciembre del 2021en la Unidad de hospitalización a domicilio del Hospital Universitario de la Ribera, Alzira, Valencia. Se recogieron variables demográficas, clínicas, funcionales y de calidad asistencial. Resultados: Se incluyeron 224 sujetos. La edad media fue de 84,6 (DT 7,7) años, con un 66% de mujeres, estando un 32% de pacientes diagnosticados de demencia en alguno de sus grados de severidad. La estancia media en el hospital fue de 8,4 (DT 4,1) días y de 6,5 (5,3) días en el programa rehabilitador de la unidad de hospitalización a domicilio. El 90% de los pacientes incluidos en el programa alcanzaron el objetivo terapéutico trazado durante el ingreso hospitalario. Conclusiones: La rehabilitación domiciliaria de pacientes con fractura de cadera contribuye a una recuperación funcional del paciente en un menor tiempo. Son necesarios más estudios para confirmar los resultados obtenidos. (AU)


Introduction: Hip fracture is one of the most frequent disabling injuries, presenting serious complications during the acute and subacute phase. Rehabilitation at home, after hospital discharge, allows rapid functional recovery. The objective of this study is to evaluate the possible usefulness of a home rehabilitation program in patients with hip fracture integrated in a Hospital at Home Unit. Methods: Retrospective study that consecutively included patients accepted for home rehabilitation treatment between September 9, 2019 and December 31, 2021 in the Hospital at Home Unit of the Hospital Universitario de la Ribera, Alzira, Valencia. Demographic, clinical, functional and quality of care variables were collected. Results: Two hundred twenty-four subjects were included. The mean age was 84.6 (SD 7.7) years, with 66% women and 34% men, with 32% of patients diagnosed with dementia in one of its degrees of severity. The mean hospital stay was 8.4 (SD 4.1) days and 6.5 (5.3) days in the Hospital at Home Unit rehabilitation program. 90% of the patients included in the program reached the therapeutic goal outlined during hospital admission. Conclusions: The home rehabilitation of patients with hip fracture contributes to a functional recovery of the patient in a shorter time. Further studies are necessary to confirm the results obtained. (AU)


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Hip Fractures/rehabilitation , House Calls , Retrospective Studies , Patient Discharge
3.
JAMA Netw Open ; 3(9): e2017337, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32926117

ABSTRACT

Importance: Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. Objectives: To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. Design, Setting, and Participants: A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Interventions: Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). Main Outcomes and Measures: The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Results: Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). Conclusions and Relevance: In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. Trial Registration: ClinicalTrials.gov Identifier: NCT02233413.


Subject(s)
Brain Injuries, Traumatic/radiotherapy , Low-Level Light Therapy/methods , Post-Concussion Syndrome/physiopathology , White Matter/diagnostic imaging , Adult , Aged , Anisotropy , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/physiopathology , Diffusion Tensor Imaging , Double-Blind Method , Feasibility Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/diagnostic imaging , Placebos , Severity of Illness Index , Surveys and Questionnaires , Treatment Outcome
4.
Sci Rep ; 8(1): 14004, 2018 09 18.
Article in English | MEDLINE | ID: mdl-30228335

ABSTRACT

Severe peripheral nerve injuries often result in partial repair and lifelong disabilities in patients. New surgical techniques and better graft tissues are being studied to accelerate regeneration and improve functional recovery. Currently, limited tools are available to provide in vivo monitoring of changes in nerve physiology such as myelination and vascularization, and this has impeded the development of new therapeutic options. We have developed a wide-field and label-free functional microscopy platform based on angiographic and vectorial birefringence methods in optical coherence tomography (OCT). By incorporating the directionality of the birefringence, which was neglected in the previously reported polarization-sensitive OCT techniques for nerve imaging, vectorial birefringence contrast reveals internal nerve microanatomy and allows for quantification of local myelination with superior sensitivity. Advanced OCT angiography is applied in parallel to image the three-dimensional vascular networks within the nerve over wide-fields. Furthermore, by combining vectorial birefringence and angiography, intraneural vessels can be discriminated from those of the surrounding tissues. The technique is used to provide longitudinal imaging of myelination and revascularization in the rodent sciatic nerve model, i.e. imaged at certain sequential time-points during regeneration. The animals were exposed to either crush or transection injuries, and in the case of transection, were repaired using an autologous nerve graft or acellular nerve allograft. Such label-free functional imaging by the platform can provide new insights into the mechanisms that limit regeneration and functional recovery, and may ultimately provide intraoperative assessment in human subjects.


Subject(s)
Neovascularization, Physiologic , Nerve Fibers, Myelinated/physiology , Nerve Regeneration , Peripheral Nerve Injuries/physiopathology , Recovery of Function , Sciatic Nerve/pathology , Animals , Microscopy , Sciatic Nerve/blood supply , Sciatic Nerve/injuries , Tomography, Optical Coherence
5.
J Burn Care Res ; 39(3): 423-432, 2018 04 20.
Article in English | MEDLINE | ID: mdl-28877131

ABSTRACT

Secondary burn necrosis is the expansion and deepening of the original burn injury several days after injury. Limiting the extent of secondary burn necrosis may improve outcomes. In this study, we examined the ability of the lipid mediator of inflammation-resolution resolvin D2 (RvD2) and chromatin-lysing enzyme (DNase) to reduce secondary burn necrosis. Male Wistar rats were injured using a brass comb with 4 prongs heated in boiling water. This method created 2 parallel rows of 4 rectangular burned areas separated by 3 unburned interspaces. Starting at 2 hours after the burn injury, rats received either 25 ng/kg RvD2 intravenously daily for 7 days or 200 U/kg DNase every 12 hours for 3 days. We documented the necrosis around the initial wounds by digital photography. We used laser Doppler to assess the total blood flux in the burn area. We evaluated the functionality of the capillary network in the interspaces by optical coherence tomography angiography. We performed histological examination of wound skin tissue samples collected at 14 days postburn. We found that the interspace areas were preserved and had higher blood flow in the RvD2-treated group, while the burn areas expanded into the interspace areas, which were confluent by 7 days postburn, in the control-untreated group. We found a larger monocyte-to-neutrophil ratio in the RvD2-treated group compared with the DNase-treated and control groups (P < .05). Overall, RvD2 suppresses secondary necrosis and starts regeneration, highlighting the role of inflammation resolution as a potential therapeutic target in burn care.


Subject(s)
Burns/drug therapy , Burns/pathology , Deoxyribonucleases/pharmacology , Docosahexaenoic Acids/pharmacology , Animals , Burns/diagnostic imaging , Disease Models, Animal , Male , Necrosis , Rats , Rats, Wistar , Skin/blood supply , Skin/drug effects
6.
Nutrients ; 10(1)2017 Dec 23.
Article in English | MEDLINE | ID: mdl-29295502

ABSTRACT

The human milk microbiota is a complex and diverse ecosystem that seems to play a relevant role in the mother-to-infant transmission of microorganisms during early life. Bacteria present in human milk may arise from different sources, and recent studies suggest that at least some of them may be originally present in the maternal digestive tract and may reach the mammary gland through an endogenous route during pregnancy and lactation. The objective of this work was to elucidate whether some lactic acid bacteria are able to translocate and colonize the mammary gland and milk. For this purpose, two lactic acid bacteria strains (Lactococcus lactis MG1614 and Lactobacillus salivarius PS2) were transformed with a plasmid containing the lux genes; subsequently, the transformed strains were orally administered to pregnant mice. The murine model allowed the visualization, isolation, and Polymerase Chain Reaction (PCR)-detection of the transformed bacteria in different body locations, including mammary tissue and milk, reinforcing the hypothesis that physiological translocation of maternal bacteria during pregnancy and lactation may contribute to the composition of the mammary and milk microbiota.


Subject(s)
Bacterial Translocation , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Lactococcus lactis/physiology , Ligilactobacillus salivarius/physiology , Mammary Glands, Animal/microbiology , Milk/microbiology , Animals , Female , Genes, Reporter , Ligilactobacillus salivarius/genetics , Lactococcus lactis/genetics , Luciferases/biosynthesis , Luciferases/genetics , Luminescent Measurements , Mice, Inbred BALB C , Pregnancy , Transformation, Bacterial
7.
J Am Soc Nephrol ; 27(5): 1566-74, 2016 05.
Article in English | MEDLINE | ID: mdl-26432902

ABSTRACT

Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/10(6) cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/10(6) cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.


Subject(s)
Benzhydryl Compounds/blood , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Membranes, Artificial , Phenols/blood , Renal Dialysis , Aged , Biocompatible Materials , Cross-Over Studies , Humans , Polymers , Prospective Studies , Sulfones
8.
Oncotarget ; 6(37): 39941-59, 2015 Nov 24.
Article in English | MEDLINE | ID: mdl-26498686

ABSTRACT

Cyclooxygenase2 (COX2) has been associated with cell growth, invasiveness, tumor progression and metastasis of colorectal carcinomas. However, the downstream prostaglandin (PG)-PG receptor pathway involved in these effects is poorly characterized.We studied the PG-pathway in gene expression databases and we found that PTGS2 (prostaglandin G/H synthase and cyclooxygenase) and PTGES (prostaglandin E synthase) are co-expressed in human colorectal tumors. Moreover, we detected that COX2 and microsomal Prostaglandin E2 synthase 1 (mPGES1) proteins are both up-regulated in colorectal human tumor biopsies.Using colon carcinoma cell cultures we found that COX2 overexpression significantly increased mPGES1 mRNA and protein. This up-regulation was due to an increase in early growth response 1 (EGR1) levels and its transcriptional activity. EGR1 was induced by COX2-generated PGF2α. A PGF2α receptor antagonist, or EGR1 silencing, inhibited the mPGES1 induction by COX2 overexpression. Moreover, using immunodeficient mice, we also demonstrated that both COX2- and mPGES1-overexpressing carcinoma cells were more efficient forming tumors.Our results describe for the first time the molecular pathway correlating PTGS2 and PTGES in colon cancer progression. We demonstrated that in this pathway mPGES1 is induced by COX2 overexpression, via autocrine PGs release, likely PGF2α, through an EGR1-dependent mechanism. This signaling provides a molecular explanation to PTGS2 and PTGES association and contribute to colon cancer advance, pointing out novel potential therapeutic targets in this oncological context.


Subject(s)
Colorectal Neoplasms/metabolism , Cyclooxygenase 2/metabolism , Intramolecular Oxidoreductases/metabolism , Prostaglandins/metabolism , Repressor Proteins/metabolism , Animals , Blotting, Western , Caco-2 Cells , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Cyclooxygenase 2/genetics , Disease Progression , Gene Expression Regulation, Neoplastic , HCT116 Cells , HT29 Cells , Humans , Intramolecular Oxidoreductases/genetics , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Microscopy, Confocal , Microsomes/enzymology , Prostaglandin-E Synthases , RNA Interference , Repressor Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, Heterologous , Up-Regulation
9.
Biomed Opt Express ; 5(11): 3822-32, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-25426313

ABSTRACT

We describe a complex differential variance (CDV) algorithm for optical coherence tomography based angiography. The algorithm exploits both the intensity and phase changes of optical coherence tomography (OCT) signals from flowing blood to achieve high vascular contrast, and also intrinsically reject undesirable phase signals originating from small displacement axial bulk tissue motion and instrument synchronization errors. We present this algorithm within a broader discussion of the properties of OCT signal dynamics. The performance of the algorithm is compared against two other existing algorithms using both phantom measurements and in vivo data. We show that the algorithm provides better contrast for a given number of measurements and equivalent spatial averaging.

10.
Biomed Opt Express ; 5(12): 4338-49, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25574442

ABSTRACT

Optical coherence tomography (OCT) provides both structural and angiographic imaging modes. Because of its unique capabilities, OCT-based angiography has been increasingly adopted into small animal and human subject imaging. To support the development of the signal and image processing algorithms on which OCT-based angiography depends, we describe here a Monte Carlo-based model of the imaging approach. The model supports arbitrary three-dimensional vascular network geometries and incorporates methods to simulate OCT signal temporal decorrelation. With this model, it will be easier to compare the performance of existing and new angiographic signal processing algorithms, and to quantify the accuracy of vascular segmentation algorithms. The quantitative analysis of key algorithms within OCT-based angiography may, in turn, simplify the selection of algorithms in instrument design and accelerate the pace of new algorithm development.

15.
Curr Chem Genomics ; 6: 48-54, 2012.
Article in English | MEDLINE | ID: mdl-23115613

ABSTRACT

Many fluorescent sensors are currently available for in vitro bio-physiological microscopic imaging. The ability to label cells in living animals with these fluorescent sensors would help translate some of these assays into in vivo applications. To achieve this goal, the first step is to establish a method for selectively labeling target cells with exogenous fluorophores. Here we tested whether the HaloTag® protein tagging system provides specific labeling of xenograft tumors in living animals. After systemic delivery of fluorophore-conjugated ligands, we performed whole animal planar fluorescent imaging to determine uptake in tag-expressing HCT116 xenografts. Our results demonstrate that HaloTag ligands containing red or near-infrared fluorophores have enhanced tumor uptake and are suitable for non-invasive in vivo imaging. Our proof-of-concept results establish feasibility for using HaloTag technology for bio-physiological imaging in living animals.

18.
Rev. estomat. salud ; 20(1): 45-49, Enero-Junio 2012.
Article in Spanish | LILACS, COLNAL | ID: biblio-875636

ABSTRACT

Behavior management of patient child in early childhood is a key component for success in dentistry, in this review of the literature found that dental anxiety is present in most of the child population, also evidence that one of the most common technique used is the tell-show-do. The communication with parents and their participation is a vital tool in the child's behavior. This bring us to that we must place greater emphasis on the explanation given to parents about the procedures performed on children and the important work and commitment of the dentist in the behavior management of pediatric patients...(AU)


El manejo de la conducta y el comportamiento del paciente niño en la niñez temprana es un componente clave para el éxito en la consulta odontológica, En esta revisión de la literatura se encontró que la ansiedad dental se presenta en la mayoría de la población infantil, también evidencia que una de las técnicas más usada es la técnica decir-mostrar-hacer. La comunicación con los padres y su participación son una herramienta vital en el comportamiento del niño. Esto nos lleva a que debemos hacer mayor énfasis en la explicación que se da a los padres acerca de los procedimientos a realizar en sus hijos y la importante labor y compromiso del odontopediatra en el manejo de la conducta del paciente pediátrico...(AU)


Subject(s)
Dental Anxiety , Dentistry , Dentists , Behavior , Diagnosis, Oral
19.
Circ Res ; 107(11): 1364-73, 2010 Nov 26.
Article in English | MEDLINE | ID: mdl-20930148

ABSTRACT

RATIONALE: Monocytes recruited to ischemic myocardium originate from a reservoir in the spleen, and the release from their splenic niche relies on angiotensin (Ang) II signaling. OBJECTIVE: Because monocytes are centrally involved in tissue repair after ischemia, we hypothesized that early angiotensin-converting enzyme (ACE) inhibitor therapy impacts healing after myocardial infarction partly via effects on monocyte traffic. METHODS AND RESULTS: In a mouse model of permanent coronary ligation, enalapril arrested the release of monocytes from the splenic reservoir and consequently reduced their recruitment into the healing infarct by 45%, as quantified by flow cytometry of digested infarcts. Time-lapse intravital microscopy revealed that enalapril reduces monocyte motility in the spleen. In vitro migration assays and Western blotting showed that this was caused by reduced signaling through the Ang II type 1 receptor. We then studied the long-term consequences of blocked splenic monocyte release in atherosclerotic apolipoprotein (apo)E(-/-) mice, in which infarct healing is impaired because of excessive inflammation in the cardiac wound. Enalapril improved histologic healing biomarkers and reduced inflammation in infarcts measured by FMT-CT (fluorescence molecular tomography in conjunction with x-ray computed tomography) of proteolytic activity. ACE inhibition improved MRI-derived ejection fraction by 14% on day 21, despite initially comparable infarct size. In apoE(-/-) mice, ischemia/reperfusion injury resulted in larger infarct size and enhanced monocyte recruitment and was reversible by enalapril treatment. Splenectomy reproduced antiinflammatory effects of enalapril. CONCLUSION: This study suggests that benefits of early ACE inhibition after myocardial infarction can partially be attributed to its potent antiinflammatory impact on the splenic monocyte reservoir.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Cell Movement/drug effects , Monocytes/enzymology , Monocytes/pathology , Myocardial Infarction/enzymology , Myocardial Infarction/pathology , Spleen/enzymology , Spleen/pathology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Cell Movement/physiology , Enalapril/pharmacology , Enalapril/therapeutic use , Female , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Monocytes/drug effects , Myocardial Infarction/drug therapy , Spleen/drug effects
20.
Circulation ; 122(14): 1396-404, 2010 Oct 05.
Article in English | MEDLINE | ID: mdl-20855659

ABSTRACT

BACKGROUND: Experimental autoimmune myocarditis (EAM), a mouse model of post-infectious cardiomyopathy, reflects mechanisms of inflammatory cardiomyopathy in humans. EAM is characterized by an infiltration of inflammatory cells into the myocardium that can be followed by myocyte fibrosis, edema, and necrosis, leading to ventricular wall dysfunction and heart failure. Different data indicate that CD69 exerts an important immunoregulatory effect in vivo. However, the possible role of CD69 in autoimmune myocarditis has not been studied. METHODS AND RESULTS: We have explored the role of the leukocyte regulatory molecule CD69 in the inflammation that leads to cardiac dysfunction after myocardial injury in EAM. We have found that after induction of EAM, the draining lymph nodes from CD69-deficient mice developed an exacerbated Th17 inflammatory response, resulting in increases in the numbers of infiltrating leukocytes in the myocardium. In the chronic phase of EAM, transthoracic echocardiography revealed a significantly reduced left ventricular fractional shortening and a decreased ejection fraction in CD69-deficient mice, indicative of an impaired cardiac contractility. This condition was accompanied by a greater extent of myocardial fibrosis, an elevated number of sinus pauses on ECG, and an enhanced ratio of heart weight to body weight in CD69-/- mice. Moreover, both bone marrow transplantation and adoptive transfer of Th17 cells isolated from immunized CD69-/- mice with EAM into naive wild-type recipients reproduced the severity of the disease, demonstrating that CD69 exerts its function within the lymphocyte compartment. CONCLUSION: Our findings indicate that CD69 negatively regulates heart-specific Th17 responses, cardiac inflammation, and heart failure progression in EAM.


Subject(s)
Autoimmune Diseases/physiopathology , Lectins, C-Type/deficiency , Myocarditis/physiopathology , Animals , Antigens, CD/genetics , Antigens, Differentiation, T-Lymphocyte/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Crosses, Genetic , Endomyocardial Fibrosis/immunology , Endomyocardial Fibrosis/physiopathology , Female , Flow Cytometry , Humans , Lectins, C-Type/genetics , Lymph Nodes/cytology , Lymph Nodes/physiology , Mice , Mice, Inbred BALB C , Mice, Knockout , Myocarditis/genetics , Myocarditis/immunology , Myosin Heavy Chains/immunology , Peptide Fragments/immunology , Severity of Illness Index , Spleen/cytology , Spleen/physiology
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