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1.
Cureus ; 16(1): e52088, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38344528

ABSTRACT

Cardiac sarcoidosis (CS) is a potentially life-threatening condition that can cause sudden, fatal conduction abnormalities, arrhythmias, and heart failure. The diagnosis of CS is challenging due to nonspecific symptoms and an unclear diagnostic criterion. Although biopsy is the gold standard method, the sensitivity of biopsy is low. About a portion of CS cases are detected through imaging. A unique aspect of our case is that our definitive diagnosis was made based on clinical and imaging criteria alone despite a negative biopsy. Our diagnosis was confirmed further on follow-up with improvement in cardiac function on imaging after a treatment course with corticosteroids. This case highlights the need to have a broad differential and more awareness of this rare etiology and the value of clinical criteria to make a definitive diagnosis.

2.
Hellenic J Cardiol ; 69: 24-30, 2023.
Article in English | MEDLINE | ID: mdl-36273803

ABSTRACT

BACKGROUND: High-output heart failure (HOHF) is an underdiagnosed type of heart failure (HF) characterized by low systemic vascular resistance and high cardiac output. OBJECTIVE: This study sought to characterize the causes, mortality, and readmissions related to HOHF within the United States. METHODS: Data were collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) National Readmissions Database (NRD) from January 1, 2017, to November 30, 2019. We used the International Classification of Diseases, 10th revision (ICD-10), diagnostic codes to identify encounters with HOHF and heart failure with reduced ejection fraction (HFrEF). RESULTS: Of the total 5,080,985 encounters with HF, 3,897 hospitalizations (mean age 62.5 ± 17.9 years, 56.5% females) with HOHF and 5,077,088 hospitalizations with HFrEF were recorded. The most commonly associated putative etiologies of HOHF included pulmonary disease (19.8%), morbid obesity (9.9%), sepsis (9.6%), cirrhosis (8.9%), myelodysplastic syndrome (MDS) (7.9%), hyperthyroidism (5.5%), and sickle cell disease (3.3%). There was no significant difference in mortality rates [4.3% vs. 5.2%; odds ratio (OR) 0.9, 95% confidence interval (CI) 0.7-1.2] between HOHF and HFrEF. However, the 30-day readmission rate for HOHF was significantly lower than that for HFrEF (5.7% vs. 21.2%; OR 0.39, 95% CI 0.30-0.51). Cardiovascular (39.9%) followed by hematological (20.6%) complications accounted for the majority of 30-day readmissions in the HOHF group. CONCLUSIONS: HOHF is an infrequently reported cardiovascular complication associated with noncardiovascular disorders and is encountered in 0.07% of all encounters with HF. Although comparable in-hospital mortality between studied cohorts was observed, raising awareness and timely recognition of this entity are warranted.


Subject(s)
Heart Failure , Female , Humans , United States/epidemiology , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Heart Failure/complications , Heart Failure/epidemiology , Heart Failure/diagnosis , Patient Readmission , Stroke Volume , Heart
3.
Cureus ; 13(7): e16344, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34306895

ABSTRACT

Background Underrepresented-minorities (URM) remain few in number amongst practicing cardiologists and across cardiology fellowship training programs in the U.S. Increased diversity is needed across the entire field and is particularly necessary within graduate medical education cardiology fellowship training programs. Objectives This cross-sectional study was performed to identify which strategies were supported and implemented by cardiology fellowship program directors (PDs) to increase URM representation, to determine which entities hold the responsibility to increase diversity according to program directors, and to quantify URM representation in cardiology fellowship programs. Methods A 15-item survey was submitted to all American College of Graduate Medical Education (ACGME) accredited cardiology fellowship programs via electronic mail. Results Of 250 cardiology fellowship programs, 71 responses were received (28.4%). The number of URM faculty varied from 0-1 to more than six, and URM faculty held leadership roles in most programs (62.0%). A total of 16 respondents (22.5%) were URM program directors. Most respondents agreed that diversity was important to their training program (85.9%). The majority endorsed direct recruitment of URM applicants (60.6%), opportunities for applicants to connect with (54.9%) or be recruited by URM fellows (54.9%), holistic application review (67.6%), promoting mentorship by URM faculty (69.0%), URM faculty involvement in applicant interviewing (54.9%), and increased recruitment of URM faculty members (73.2%). Program directors allocated major responsibility to increase diversity to fellowship programs (71.8%), residency programs (63.3%), and medical schools (53.5%). Conclusions This study found that most cardiology programs have URM faculty in leadership roles, and nearly a quarter of the surveyed program directors were URMs. Cardiology program directors endorsed and employed numerous strategies to increase diversity and URM representation in fellowship programs. Additionally, program directors held fellowship training programs most responsible for increasing URM representation in the field of cardiology.

4.
Cureus ; 13(2): e13539, 2021 Feb 24.
Article in English | MEDLINE | ID: mdl-33786246

ABSTRACT

Spontaneous coronary artery dissection (SCAD) is an important and rare cause of myocardial infarction (MI), particularly among young women without traditional atherosclerotic risk factors. Late pregnancy and postpartum period are associated with more risk for developing SCAD. No enough data exist regarding the ideal management of SCAD due to lack of randomized trials comparing medical therapy and revascularization strategies. We present three cases of SCAD, two of them were postpartum women while one involved an obese young woman with no identifiable risk factors. We describe the pathophysiology, types of SCAD, risk factors, clinical presentation, and management approach. This case series highlights the need to raise awareness of SCAD and to facilitate accurate diagnosis promptly.

5.
Cureus ; 12(8): e10015, 2020 Aug 25.
Article in English | MEDLINE | ID: mdl-32983711

ABSTRACT

Dobutamine stress echocardiography (DSE) is a commonly utilized method for coronary artery disease (CAD) diagnosis, and it provides important long-term prognostic information. We report a case of a 53-year-old female with multiple cardiovascular risk factors who underwent DSE for evaluation of underlying CAD. The examination was complicated by wide complex tachycardia and promoted administration of esmolol, which shortly led to ST-segment elevation myocardial infarction (STEMI). Coronary angiography showed complete absence of CAD. Coronary vasospasm was a possible suggested mechanism due to the pharmacologic interaction between beta-blockers and dobutamine on alpha- and beta-adrenergic receptors.

6.
Comput Biol Med ; 115: 103477, 2019 12.
Article in English | MEDLINE | ID: mdl-31605890

ABSTRACT

Parkinson's Disease (PD) is a clinical syndrome that affects millions of people worldwide. Although considered as a non-lethal disease, PD shortens the life expectancy of the patients. Many studies have been dedicated to evaluating methods for early-stage PD detection, which includes machine learning techniques that employ, in most cases, motor dysfunctions, such as tremor. This work explores the time dependency in tremor signals collected from handwriting exams. To learn such temporal information, we propose a model based on Bidirectional Gated Recurrent Units along with an attention mechanism. We also introduce the concept of "Bag of Samplings" that computes multiple compact representations of the signals. Experimental results have shown the proposed model is a promising technique with results comparable to some state-of-the-art approaches in the literature.


Subject(s)
Diagnosis, Computer-Assisted , Handwriting , Machine Learning , Neural Networks, Computer , Parkinson Disease/diagnosis , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Parkinson Disease/physiopathology
7.
Catheter Cardiovasc Interv ; 92(2): 222-246, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30160001

ABSTRACT

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.


Subject(s)
Cardiac Imaging Techniques/standards , Cardiovascular Diseases/diagnostic imaging , Occupational Exposure/standards , Radiation Dosage , Radiation Exposure/standards , Benchmarking/standards , Consensus , Evidence-Based Medicine/standards , Humans , Occupational Exposure/adverse effects , Occupational Exposure/prevention & control , Patient Safety/standards , Predictive Value of Tests , Radiation Exposure/adverse effects , Radiation Exposure/prevention & control , Risk Assessment , Risk Factors
8.
Catheter Cardiovasc Interv ; 92(2): 203-221, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30160013

ABSTRACT

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.


Subject(s)
Cardiac Imaging Techniques/standards , Cardiovascular Diseases/diagnostic imaging , Radiation Dosage , Radiation Exposure/standards , Benchmarking/standards , Consensus , Evidence-Based Medicine/standards , Humans , Patient Safety/standards , Predictive Value of Tests , Radiation Exposure/adverse effects , Radiation Exposure/prevention & control , Risk Assessment , Risk Factors
10.
J Am Coll Cardiol ; 70(19): 2421-2449, 2017 Nov 07.
Article in English | MEDLINE | ID: mdl-29055505

ABSTRACT

Mitral regurgitation (MR) is a complex valve lesion that can pose significant management challenges for the cardiovascular clinician. This Expert Consensus Document emphasizes that recognition of MR should prompt an assessment of its etiology, mechanism, and severity, as well as indications for treatment. A structured approach to evaluation based on clinical findings, precise echocardiographic imaging, and when necessary, adjunctive testing, can help clarify decision making. Treatment goals include timely intervention by an experienced heart team to prevent left ventricular dysfunction, heart failure, reduced quality of life, and premature death.


Subject(s)
Advisory Committees/standards , Cardiology/standards , Clinical Decision-Making , Disease Management , Mitral Valve Insufficiency/therapy , Research Report/standards , Cardiology/methods , Clinical Decision-Making/methods , Consensus , Humans , United States
11.
Am J Case Rep ; 18: 85-89, 2017 Jan 25.
Article in English | MEDLINE | ID: mdl-28119516

ABSTRACT

BACKGROUND Dual antiplatelet therapy has proven efficacy in primary and secondary prevention of coronary artery disease with a relatively good safety profile. Review of the literature revealed 8 cases of spontaneous retroperitoneal hematoma secondary to antiplatelet treatment. CASE REPORT We report the case of a 66-year-old male with a flare of acute gout secondary to uncontrolled chronic myeloid leukemia. The patient was started on dual antiplatelet treatment following a drug-eluted stent placement for symptomatic coronary artery disease. He suffered from an unexplained acute drop of five grams of hemoglobin from 10.4 to 5.8 g/dL and symptomatic anemia. The initial labs excluded occult GI bleeding, hemolysis, and bone marrow suppression. However, an abdominal CT scan showed an approximately 7.2×4.7×6.7 cm spontaneous retroperitoneal hematoma involving the left iliacus muscle. The patient was successfully treated conservatively by discontinuing antiplatelet therapy and supportive measures. CONCLUSIONS A spontaneous retroperitoneal hematoma often presents without localizing signs and symptoms and therefore should be considered in any case of unexplained blood loss in patients on antiplatelet therapy. CT without contrast is the modality of choice to diagnose retroperitoneal hematoma.


Subject(s)
Coronary Artery Disease/prevention & control , Hematoma/chemically induced , Platelet Aggregation Inhibitors/adverse effects , Retroperitoneal Space , Aged , Hematoma/diagnosis , Humans , Male , Platelet Aggregation Inhibitors/therapeutic use , Tomography, X-Ray Computed
12.
J Cardiol Cases ; 16(6): 202-204, 2017 Dec.
Article in English | MEDLINE | ID: mdl-30279835

ABSTRACT

The HELEX septal occluder (W.L. Gore & Associates, Newark, DE, USA) is a popular closure device for patent foramen ovale (PFO) and secundum atrial septal defect (ASD). Composed of a versatile polymer and a wire frame, it has been used for nearly a decade. A 50-year-old African American man with a PFO repaired 5 years previously with the HELEX was admitted to our hospital with methicillin-resistant Staphylococcus aureus bacteremia. A transesophageal echocardiogram demonstrated large mobile vegetations on the left and right atrial aspects of the occluder. Cardiothoracic surgery was consulted for removal of the vegetations and device, but hesitated owing to concurrent foot osteomyelitis and concern for re-infection of a potential replacement device. The patient was persistently bacteremic, his course complicated by septic pulmonary and cerebral emboli, but eventually cleared his infection on antibiotic therapy. Seventy days since admission, the patient was discharged to a rehabilitation facility. The case illustrates that infection is possible years after PFO/ASD closure despite a theoretical neoendothelialization within 6 months of implantation. Furthermore, it accentuates the success of timely and aggressive medical treatment, thereby averting high-risk open cardiac surgery. .

13.
Echocardiography ; 34(1): 143-144, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27550778

ABSTRACT

Infective endocarditis in patients with intravenous drug use commonly involves right-sided heart valves. Eustachian valve (EV) endocarditis is not commonly seen given the valve's infrequent presence. Involvement of the coronary sinus (CS) with endocarditis is also an unusual finding. We present a case with echocardiographic findings consistent with EV endocarditis along with CS involvement, which appropriately responded to antibiotics.


Subject(s)
Coronary Sinus/diagnostic imaging , Endocarditis, Bacterial/diagnosis , Heart Atria/diagnostic imaging , Staphylococcal Infections/diagnosis , Substance Abuse, Intravenous/complications , Adult , Echocardiography, Three-Dimensional/methods , Echocardiography, Transesophageal , Endocarditis, Bacterial/etiology , Female , Humans , Staphylococcal Infections/etiology , Tricuspid Valve , Vena Cava, Inferior/diagnostic imaging
14.
Ann Thorac Surg ; 100(5): e107-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26522574

ABSTRACT

We report the case of a pedunculated cystic mass on the aortic valve discovered in a patient presenting for a routine echocardiogram. The highly mobile nature of the mass warranted prompt surgical removal to prevent cardioembolic complications. The mass was preoperatively thought to be a papillary fibroelastoma. However, the patient's history, mass morphology, and histopathology pointed toward a simple degenerative cyst--previously unreported on the aortic valve. This report describes this rare finding, discusses relevant differential diagnoses, and underscores the importance of surgical intervention in such cases.


Subject(s)
Aortic Valve/diagnostic imaging , Cysts/diagnostic imaging , Heart Valve Diseases/diagnostic imaging , Incidental Findings , Diagnosis, Differential , Echocardiography, Transesophageal , Humans , Male , Middle Aged
15.
Clin Interv Aging ; 10: 209-15, 2015.
Article in English | MEDLINE | ID: mdl-25624753

ABSTRACT

OBJECTIVE: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ]) in response to multivariate drug directions for blood pressure (BP) control. METHODS: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention. RESULTS: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01) at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin-angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group. CONCLUSION: Our data demonstrates that a clinically guided antihypertensive treatment is effective in reversing the low-grade proinflammatory state of serum cytokines found in postmenopausal women and support extracardiac benefits from diuretics and renin-angiotensin system antagonists.


Subject(s)
Antihypertensive Agents/pharmacology , Hypertension/drug therapy , Hypertension/physiopathology , Inflammation Mediators/blood , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/pharmacology , Aged , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Brazil , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/pharmacology , Diuretics/administration & dosage , Diuretics/pharmacology , Drug Therapy, Combination , Female , Humans , Interferon-gamma/blood , Interleukin-6/blood , Middle Aged , Postmenopause , Prospective Studies , Tumor Necrosis Factor-alpha/blood
16.
Am J Med Sci ; 347(2): 112-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23470270

ABSTRACT

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare life-threatening condition of unclear etiology. Data on the use of cardiac magnetic resonance (CMR) imaging to characterize PPCM are limited. This study was done to assess the role of CMR imaging for the diagnosis and prognostication of patients with PPCM. METHODS: Medical records of a tertiary medical center were screened for PPCM patients with CMR imaging done within the past 5 years (2006-2011). Images were reviewed by 2 expert radiologists (blinded to clinical data) using cine sequences for chamber function and size, T2-weighted images for the determination of edema (T2-ratio), and late gadolinium enhancement (LGE) sequences for myocardial tissue characterization. RESULTS: Ten PPCM patients (aged 28 ± 6 years, 90% African American) had a total of 15 CMR examinations: 4 in the acute phase (within 7 days of diagnosis) and 11 during follow-up (median, 12 months; range, 1-72 months). Left ventricular ejection fraction was decreased in all 4 initial scans. Elevated T2 ratio (>2) seen in 1 patient decreased on follow-up imaging. LGE was seen in 1 of the 4 acute-phase scans and in 4 of the 11 follow-up phase scans. These 4 patients had multiple readmissions because of heart failure exacerbations and persistently low left ventricular ejection fraction on subsequent echocardiograms. CONCLUSIONS: LGE seems to be associated with a poor prognosis in the setting of PPCM. CMR imaging seems to have promising practical implications in the diagnosis and prognostication of PPCM patients.


Subject(s)
Cardiomyopathies/diagnosis , Magnetic Resonance Imaging , Peripartum Period , Adolescent , Adult , Cardiomyopathies/diagnostic imaging , Female , Humans , Pregnancy , Radiography , Retrospective Studies , Young Adult
17.
PLoS Negl Trop Dis ; 6(10): e1850, 2012.
Article in English | MEDLINE | ID: mdl-23071853

ABSTRACT

BACKGROUND: Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages. CONCLUSIONS/SIGNIFICANCE: Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis.


Subject(s)
Adenosine Triphosphatases/biosynthesis , Immune Evasion , Leishmania braziliensis/enzymology , Leishmania braziliensis/pathogenicity , Leishmaniasis, Mucocutaneous/pathology , Leishmaniasis, Mucocutaneous/parasitology , Virulence Factors/biosynthesis , Adenine Nucleotides/metabolism , Animals , Cell Line , Disease Models, Animal , Female , Hydrolysis , Macrophages/immunology , Macrophages/parasitology , Mice , Mice, Inbred C57BL , Nitric Oxide/metabolism
18.
Am J Med Sci ; 344(2): 160-2, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22627263

ABSTRACT

Although the incidence of purulent pericarditis has decreased significantly in the modern antibiotic era, a high index of clinical suspicion should be maintained to diagnose this life-threatening illness at an early stage. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global pathogen and notorious for its ability to cause infection in otherwise healthy individuals. However, it has been associated with purulent pericarditis only in some sporadic case reports. The authors describe a case of purulent pericardial effusion caused by CA-MRSA infection. To the best of our knowledge, this is only the fourth case of CA-MRSA pericarditis to be reported in English literature.


Subject(s)
Methicillin-Resistant Staphylococcus aureus/isolation & purification , Pericardial Effusion/microbiology , Staphylococcal Infections/microbiology , Community-Acquired Infections/microbiology , Female , Humans , Middle Aged
19.
Eur J Immunol ; 42(5): 1203-15, 2012 May.
Article in English | MEDLINE | ID: mdl-22311598

ABSTRACT

Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A(2B) adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A(2B) receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response.


Subject(s)
CD40 Antigens/immunology , Dendritic Cells/immunology , Leishmania/immunology , Leishmaniasis/immunology , Receptor, Adenosine A2B/immunology , Acetamides/pharmacology , Adenosine A2 Receptor Antagonists/pharmacology , Animals , B7-2 Antigen/biosynthesis , B7-2 Antigen/immunology , Bone Marrow Cells/immunology , CD40 Antigens/biosynthesis , Cells, Cultured , Histocompatibility Antigens Class II/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred C57BL , Nucleotidases/biosynthesis , Purines/pharmacology , Suramin/pharmacology , T-Lymphocytes/immunology , Trypanocidal Agents/pharmacology
20.
Vet Immunol Immunopathol ; 130(1-2): 43-52, 2009 Jul 15.
Article in English | MEDLINE | ID: mdl-19211152

ABSTRACT

When infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-gamma and TNF-alpha production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-gamma and TNF-alpha levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions.


Subject(s)
Chagas Cardiomyopathy/veterinary , Dog Diseases/parasitology , Interferon-gamma/biosynthesis , Interleukin-10/biosynthesis , Trypanosoma cruzi/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Cardiomegaly/immunology , Cardiomegaly/parasitology , Chagas Cardiomyopathy/immunology , Chagas Cardiomyopathy/parasitology , Chagas Cardiomyopathy/pathology , Disease Models, Animal , Dog Diseases/immunology , Dog Diseases/pathology , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Fibrosis/immunology , Fibrosis/parasitology , Histocytochemistry/veterinary , Interferon-gamma/blood , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-10/blood , Interleukin-10/genetics , Interleukin-10/immunology , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Splenomegaly/immunology , Splenomegaly/parasitology , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
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