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1.
Clin Transplant ; 37(1): e14836, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36259556

RESUMEN

OBJECTIVES: Induction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti-thymocyte globulin (ATG) versus basiliximab as induction therapy on post-transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis. RESULTS: Of the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow-up was 3.0 (IQR, 1.7-4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p = .418), CMV viremia (22% vs. 19.6%, p = .769), and CMV-positive tissue biopsy (30% vs. 22%, p = .486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p = .022) and CAV (4% vs. 23.9%, p = .006) with no difference in mortality (8% vs. 15.2%, p = .343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR, .31; 95% CI, .09-.94; p = .039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI, .54-7.89; p = .292), CAV (HR, .30; 95% CI, .04-2.58; p = .275), and mortality (HR, .39; 95% CI, .09-1.82; p = .233) compared to basiliximab induction. DISCUSSION AND CONCLUSIONS: In conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Corazón , Humanos , Niño , Adolescente , Basiliximab/uso terapéutico , Inmunosupresores/uso terapéutico , Quimioterapia de Inducción , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/epidemiología , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Suero Antilinfocítico/uso terapéutico , Antivirales/uso terapéutico , Trasplante de Corazón/efectos adversos , Receptores de Trasplantes , Estudios Retrospectivos
2.
Clin Transplant ; 37(3): e14843, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36494889

RESUMEN

AIMS: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post-heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non-CHD patients before (Era-1) and after (Era-2) pediatric heart allocation policy implementation. METHODS: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era-1 and Era-2. RESULTS: 5551 patients were listed for HT, of whom 2447(44%) were in Era-1 and 3104(56%) were in Era-2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era-2, whereas the number of non-CHD patients listed as status 1A decreased, but status 1B increased. In Era-2 compared to Era-1, both temporary (1% to 4%, p < .001) and durable VAD (13.6% to 17.8%, p < .001) utilization increased, and the transplantation rate per 100-patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p = .06), whereas for non-CHD patients it decreased from 61 to 54 days (p < .001). Adjusted 90-day WL survival increased from 84% to 88%, p = .016 in CHD, but there was no significant change in non-CHD patients (p = .57). There was no significant difference in 1-year post-HT survival in CHD and non-CHD patients between Era-1 and Era-2. CONCLUSIONS: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non-CHD cohort, and 90-day WL survival probability improved in children with CHD without significant change in 1-year post-HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post-HT survival.


Asunto(s)
Cardiopatías Congénitas , Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Humanos , Niño , Adolescente , Estudios Retrospectivos , Políticas , Listas de Espera
3.
Artif Organs ; 46(4): 697-704, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34698399

RESUMEN

OBJECTIVES: This study aimed to compare the clinical characteristics, risk factors, and overall survival outcomes in adults with congenital heart disease (ACHD) bridged to transplantation with a ventricular assist device (VAD) versus no-VAD. METHODS: The study included 894 ACHD patients aged ≥18 years listed for primary heart transplantation between 2010 and 2019 from the United Network for Organ Sharing database. Primary outcomes were waitlist and 1-year post-transplant mortality between VAD and no-VAD ACHD patients. RESULTS: Of 894 ACHD patients included in the study, 91(10.1%) had VAD support at the time of listing. Patients who needed VAD support were mostly males, heavier, and had higher pulmonary artery pressure than the no-VAD group at the listing. The overall waitlist mortality was 38% in the VAD group than 17% in the no-VAD group (p < 0.01). ECMO use was associated with significantly higher mortality than either group. There was no significant difference in 1-year post-transplant mortality between VAD versus no-VAD at the time of transplant (15% vs. 17%; p = 0.66). Multivariate regression analysis found that BMI <20 kg/m2 (hazard ratio (HR) 1.1; p = 0.01), bilirubin >2 mg/dl (HR 1.1; p = 0.03), creatinine >2 mg/dl (HR 1.3; p = 0.04) and ECMO at transplant (HR 1.4; p = 0.03) increased early post-transplant mortality. CONCLUSIONS: The one-year post-transplant mortality rate was no different for ACHD patients that received VAD versus no-VAD. These findings suggest that a VAD should be considered an option to support ACHD patients as a bridge to heart transplantation.


Asunto(s)
Cardiopatías Congénitas , Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Adolescente , Adulto , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
4.
Cardiol Young ; 32(6): 988-992, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34657643

RESUMEN

We report a case of thyroid storm precipitated by SARS-CoV-2 infection in an adolescent girl with a history of Graves disease and dilated cardiomyopathy. This case highlights that SARS-CoV-2 infection can potentially trigger a thyrotoxicosis crisis and acute decompensated heart failure in a patient with underlying thyroid disease and myocardial dysfunction even in the absence of multi-system inflammatory syndrome in children. We systematically reviewed the thyrotoxicosis cases with SARS-CoV-2 infection and described its impact on pre-existing dilated cardiomyopathy.


Asunto(s)
COVID-19 , Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Crisis Tiroidea , Tirotoxicosis , Adolescente , COVID-19/complicaciones , Niño , Femenino , Insuficiencia Cardíaca/etiología , Humanos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , Crisis Tiroidea/complicaciones , Crisis Tiroidea/diagnóstico , Tirotoxicosis/complicaciones , Tirotoxicosis/diagnóstico
5.
J Pediatr ; 238: 26-32.e1, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34339728

RESUMEN

OBJECTIVES: To characterize the clinical course and outcomes of children 12-18 years of age who developed probable myopericarditis after vaccination with the Pfizer-BioNTech (BNT162b2) coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine. STUDY DESIGN: A cross-sectional study of 25 children, aged 12-18 years, diagnosed with probable myopericarditis after COVID-19 mRNA vaccination as per the Centers for Disease Control and Prevention criteria for myopericarditis at 8 US centers between May 10, 2021, and June 20, 2021. We retrospectively collected the following data: demographics, severe acute respiratory syndrome coronavirus 2 virus detection or serologic testing, clinical manifestations, laboratory test results, imaging study results, treatment, and time to resolutions of symptoms. RESULTS: Most (88%) cases followed the second dose of vaccine, and chest pain (100%) was the most common presenting symptom. Patients came to medical attention a median of 2 days (range, <1-20 days) after receipt of Pfizer mRNA COVID-19 vaccination. All adolescents had an elevated plasma troponin concentration. Echocardiographic abnormalities were infrequent, and 92% showed normal cardiac function at presentation. However, cardiac magnetic resonance imaging, obtained in 16 patients (64%), revealed that 15 (94%) had late gadolinium enhancement consistent with myopericarditis. Most were treated with ibuprofen or an equivalent nonsteroidal anti-inflammatory drug for symptomatic relief. One patient was given a corticosteroid orally after the initial administration of ibuprofen or an nonsteroidal anti-inflammatory drug; 2 patients also received intravenous immune globulin. Symptom resolution was observed within 7 days in all patients. CONCLUSIONS: Our data suggest that symptoms owing to myopericarditis after the mRNA COVID-19 vaccination tend to be mild and transient. Approximately two-thirds of patients underwent cardiac magnetic resonance imaging, which revealed evidence of myocardial inflammation despite a lack of echocardiographic abnormalities.


Asunto(s)
Vacunas contra la COVID-19/genética , COVID-19/prevención & control , Imagen por Resonancia Cinemagnética/métodos , Miocarditis/etiología , SARS-CoV-2/inmunología , Vacunación/efectos adversos , Vacunas Sintéticas/efectos adversos , Adolescente , COVID-19/epidemiología , COVID-19/genética , Vacunas contra la COVID-19/efectos adversos , Niño , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Miocarditis/diagnóstico , Miocarditis/epidemiología , Pandemias , Estudios Retrospectivos , Estados Unidos/epidemiología , Vacunas de ARNm
6.
Cardiol Young ; 31(2): 216-223, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33208204

RESUMEN

OBJECTIVES: We evaluated the impact of peak respiratory exchange ratio on the prognostic values of cardiopulmonary exercise variables during symptoms-limited incremental exercise tests in patients with Fontan physiology. METHODS: Retrospective single-centre chart review study of Fontan patients who underwent exercise testing using the Bruce protocol between 2014 and 2018 and follow-up. RESULTS: A total of 34 patients (age > 18 years) had a Borg score of ≥7 on the Borg 10-point scale, but only 50% of patients achieved a peak respiratory exchange ratio of ≥ 1.10 (maximal test). Peak oxygen consumption, percent-predicted peak oxygen consumption, and peak oxygen consumption at the ventilatory threshold was reduced significantly in patients with a peak respiratory exchange ratio of < 1.10. Peak oxygen consumption and percent-predicted peak oxygen consumption was positively correlated with peak respiratory exchange ratio values (r = 0.356, p = 0.039). After a median follow-up of 21 months, cardiac-related events occurred in 16 (47%) patients, with no proportional differences in patients due to their respiratory exchange ratio (odds ratio, 0.62; 95% CI: 0.18-2.58; p = 0.492). Multivariate Cox proportional hazard analysis showed percent-predicted peak oxygen consumption, peak heart rate, and the oxygen uptake efficient slope were highly related to the occurrence of events in patients only with a peak respiratory exchange ratio of ≥ 1.10. CONCLUSIONS: The value of peak cardiopulmonary exercise variables is limited for the determination of prognosis and assessment of interventions in Fontan patients with sub-maximal effort. Our findings deserve further research and clinical application.


Asunto(s)
Prueba de Esfuerzo , Insuficiencia Cardíaca , Adulto , Humanos , Persona de Mediana Edad , Consumo de Oxígeno , Pronóstico , Pruebas de Función Respiratoria , Estudios Retrospectivos
7.
Cardiol Young ; 31(1): 91-96, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33070792

RESUMEN

Peak respiratory exchange ratio is an objective marker of patient effort during cardiopulmonary exercise testing. We evaluated exercise variables in 175 adult congenital heart disease patients and the impact of respiratory exchange ratio on the prognostic value of exercise variables for short-term cardiac-related events. Of 175 patients, 110 completed the exercise test with a peak respiratory exchange ratio of ≥1.10 and the remaining 65 had a peak respiratory exchange ratio of <1.10. Peak oxygen consumption, the percentage of oxygen consumption at the ventilatory threshold, peak heart rate, percentage predicted peak heart rate, double product, oxygen uptake efficiency slope, and the number of patients with exercise oscillatory ventilation were reduced significantly in patients with a respiratory exchange ratio of <1.10 compared to those with a respiratory exchange ratio of ≥1.10. After a median follow-up of 21 months, total cardiac-related events occurred in 37 (21%) patients. Multivariate Cox proportional hazard analysis showed that the percentage predicted peak oxygen consumption, and oxygen uptake efficiency slope were independent predictors of cardiac-related events only in patients with a peak respiratory exchange ratio of ≥1.10. Sub-maximal exercise performance can be preserved in adult congenital heart disease patients. The percentage predicted oxygen consumption and the oxygen uptake efficiency slope are two independent predictors for short-term cardiac-related events in adult congenital heart disease patients.


Asunto(s)
Cardiopatías Congénitas , Insuficiencia Cardíaca , Adulto , Prueba de Esfuerzo , Tolerancia al Ejercicio , Frecuencia Cardíaca , Humanos , Consumo de Oxígeno , Pronóstico
8.
Pediatr Transplant ; 24(8): e13750, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32573886

RESUMEN

CMV infection remains a significant cause of morbidity among pediatric HTx recipients We explored the implications of CMV infection on post-transplant outcomes among CMV risk-stratified pediatric HTx recipients receiving VGC prophylaxis. Children who underwent HTx between January 2010 and October 2016 were stratified according to CMV risk at time of transplant and evaluated for evidence of post-transplant CMV infection, rejection, CAV, and graft loss. Among 97 children, 41 (42%) were considered HR or IR risk for CMV infection and received VGC prophylaxis. CMV DNAemia was observed in 34% of children, including 71% HR, 40% IR, and 18% LR individuals. Median time to CMV DNAemia following VGC prophylaxis was 32D among HR vs 277D in IR subjects (P = .042). No difference in overall graft loss was noted among groups, but CMV HR children had decreased rejection-free survival (3.5 years) compared to IR (6 years, P = .015) and LR children (8 years, P = .0003). CMV was noted on EMB in 13% of children but was not associated with increased CAV, rejection or graft loss. High-risk CMV status was associated with decreased time to CMV infection despite VGC prophylaxis, compared to IR, and decreased rejection-free survival times compared to both IR and LR recipients. Detection of CMV on EMB was not associated with increased rejection, CAV or graft loss. Additional studies are needed to explore the impact of CMV infection on rejection-free survival in HTx recipients.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Rechazo de Injerto/virología , Valganciclovir/uso terapéutico , Profilaxis Antibiótica , Niño , Preescolar , Femenino , Trasplante de Corazón , Humanos , Lactante , Masculino , Estudios Retrospectivos
9.
Pediatr Transplant ; 24(3): e13673, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32067334

RESUMEN

OBJECTIVES: To correlate gene expression profiling scores obtained by AlloMap® with cardiac hemodynamics, cardiac allograft vasculopathy (CAV), and echocardiographic parameters in asymptomatic, rejection-free pediatric heart transplant (HT) recipients. METHODS: Single-institution retrospective study of 210 AlloMap scores obtained concomitantly with cardiac catheterization and echocardiogram from 55 children during follow-up after cardiac transplantation. RESULTS: The median age at HT was 5.1 years (range, 0.9-14.1), with 29 males and 26 females. AlloMap scores were high in <2 years vs ≥2 years of age at the time of HT (P = .001), and trending higher with time after HT (R2  = .04, P = .004). There was no significant difference in scores between ACR grades 0 and 1R or CAV. There was mild to modest correlation of AlloMap scores with the mean right atrial pressure (P = .002), and pulmonary capillary wedge pressure (P = .02), but no correlation was found with LV SF% (P = .3), LV EF% (P = .5), or RV FAC % (P = .8). CONCLUSIONS: Our study provides preliminary data that the AlloMap score must be studied carefully before it can be used in children, particularly in those under 2 years of age. Monitoring of serial scores for each patient could potentially reflect changes in allograft performance that may determine indications for catheterization and biopsy which needs to be validated in future studies.


Asunto(s)
Ecocardiografía , Rechazo de Injerto/diagnóstico , Cardiopatías/diagnóstico , Trasplante de Corazón , Hemodinámica/genética , Complicaciones Posoperatorias/diagnóstico , Transcriptoma , Adolescente , Cateterismo Cardíaco , Niño , Preescolar , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Rechazo de Injerto/genética , Rechazo de Injerto/fisiopatología , Cardiopatías/etiología , Cardiopatías/fisiopatología , Cardiopatías/cirugía , Humanos , Lactante , Masculino , Complicaciones Posoperatorias/genética , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos
10.
Medicina (Kaunas) ; 56(12)2020 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-33352654

RESUMEN

The interplay between coronavirus disease 2019 (COVID-19) and pulmonary hypertension (PH) in children is unknown. Adults with PH are at potential risk for severe complications and high mortality due to associated comorbidities. It is difficult to extrapolate the outcomes of COVID-19 in adults to pediatric PH patients. Overall, a small number of COVID-19 cases is reported in patients with preexisting PH. Several factors may be responsible for the low incidence of COVID-19 in children with PH. Pulmonary hypertension is a rare disease, testing is not universal, and patients may have followed more rigorously the Center for Disease Control's guidelines recommended for personal protection with mask-wearing, social distancing, and hand sanitization through ongoing health education. The small number of COVID-19 cases in patients with preexisting PH does not support that PH is protective for COVID-19. However, medications used to treat PH may have some protection against COVID-19. This review discusses the pathophysiology of PH occurring with COVID-19, differences between children and adults with COVID-19, strategies for management of preexisting PH in children during the ongoing pandemic, and its impact within the field of PH.


Asunto(s)
COVID-19/complicaciones , COVID-19/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/fisiopatología , COVID-19/epidemiología , COVID-19/terapia , Niño , Humanos , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/terapia , Incidencia , Pandemias , SARS-CoV-2
11.
Medicina (Kaunas) ; 56(10)2020 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-32987636

RESUMEN

Segmental pulmonary hypertension is a complex condition in children that encompasses many congenital heart diseases including pulmonary atresia with ventricular septal defect, hemitruncus/truncus arteriosus with branch pulmonary artery stenosis, unilateral absent pulmonary artery, and several post-tricuspid shunt lesions. Multimodality imaging is required to confirm and assess pulmonary vascular disease in subjects with major aorto-pulmonary collaterals. We describe 3 children with complex congenital heart defects who have a variable degree of segmental pulmonary hypertension and discuss management strategies and the role of interventional and/or pulmonary hypertension targeted therapies.


Asunto(s)
Cardiopatías Congénitas , Hipertensión Pulmonar , Atresia Pulmonar , Niño , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico por imagen , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/diagnóstico por imagen , Atresia Pulmonar/diagnóstico , Atresia Pulmonar/diagnóstico por imagen
12.
Medicina (Kaunas) ; 56(12)2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33255307

RESUMEN

The interventional cardiac magnetic resonance imaging (iCMR) catheterization procedure is feasible and safe for children and adults with pulmonary hypertension and congenital heart defects (CHD). With iCMR, the calculation of pulmonary vascular resistance (PVR) in children with complex CHD with multilevel shunt lesions is accurate. In this paper, we describe the role of the MRI-guided right-sided cardiac catheterization procedure to accurately estimate PVR in the setting of multiple shunt lesions (ventricular septal defect and patent ductus arteriosus) and to address the clinical question of operability in an adolescent with trisomy 21 and severe pulmonary hypertension.


Asunto(s)
Conducto Arterioso Permeable , Cardiopatías Congénitas , Hipertensión Pulmonar , Adolescente , Adulto , Niño , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico por imagen , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Imagen por Resonancia Magnética , Resistencia Vascular
13.
Medicina (Kaunas) ; 55(7)2019 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-31324065

RESUMEN

Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD). The underlying pathophysiology of BPD-associated PH is complex and poorly understood. Echocardiogram may underestimate the severity of pulmonary hypertensive vascular disease in severe BPD. Digital subtraction pulmonary angiography (DSPA) is a potentially useful imaging modality for evaluating changes in the pulmonary vasculature of BPD-associated PH. In this study, we objectively quantified the pulmonary hypertensive vascular changes demonstrated by DSPA using a novel pulmonary vascular underperfusion score (PVUS) and correlated the scoring system with echocardiography parameters and cardiac hemodynamics by right heart catheterization.


Asunto(s)
Displasia Broncopulmonar/clasificación , Hipertensión Pulmonar/clasificación , Recien Nacido Prematuro/fisiología , Angiografía de Substracción Digital/métodos , Displasia Broncopulmonar/complicaciones , Estudios Transversales , Ecocardiografía/métodos , Humanos , Hipertensión Pulmonar/complicaciones , Recién Nacido , Recien Nacido Prematuro/crecimiento & desarrollo , Puntaje de Gravedad del Traumatismo , Pulmón/anomalías , Pulmón/fisiopatología
15.
Nature ; 491(7426): 779-83, 2012 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-23086146

RESUMEN

CXCR1 is one of two high-affinity receptors for the CXC chemokine interleukin-8 (IL-8), a major mediator of immune and inflammatory responses implicated in many disorders, including tumour growth. IL-8, released in response to inflammatory stimuli, binds to the extracellular side of CXCR1. The ligand-activated intracellular signalling pathways result in neutrophil migration to the site of inflammation. CXCR1 is a class A, rhodopsin-like G-protein-coupled receptor (GPCR), the largest class of integral membrane proteins responsible for cellular signal transduction and targeted as drug receptors. Despite its importance, the molecular mechanism of CXCR1 signal transduction is poorly understood owing to the limited structural information available. Recent structural determination of GPCRs has advanced by modifying the receptors with stabilizing mutations, insertion of the protein T4 lysozyme and truncations of their amino acid sequences, as well as addition of stabilizing antibodies and small molecules that facilitate crystallization in cubic phase monoolein mixtures. The intracellular loops of GPCRs are crucial for G-protein interactions, and activation of CXCR1 involves both amino-terminal residues and extracellular loops. Our previous nuclear magnetic resonance studies indicate that IL-8 binding to the N-terminal residues is mediated by the membrane, underscoring the importance of the phospholipid bilayer for physiological activity. Here we report the three-dimensional structure of human CXCR1 determined by NMR spectroscopy. The receptor is in liquid crystalline phospholipid bilayers, without modification of its amino acid sequence and under physiological conditions. Features important for intracellular G-protein activation and signal transduction are revealed. The structure of human CXCR1 in a lipid bilayer should help to facilitate the discovery of new compounds that interact with GPCRs and combat diseases such as breast cancer.


Asunto(s)
Membrana Dobles de Lípidos/metabolismo , Fosfolípidos/metabolismo , Receptores de Interleucina-8A/química , Receptores de Interleucina-8A/metabolismo , Disulfuros/química , Disulfuros/metabolismo , Activación Enzimática , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Humanos , Interleucina-8/química , Interleucina-8/metabolismo , Membrana Dobles de Lípidos/química , Modelos Moleculares , Conformación Molecular , Resonancia Magnética Nuclear Biomolecular , Fosfolípidos/química , Transducción de Señal
16.
Cardiol Young ; 28(9): 1077-1081, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29979147

RESUMEN

The Prospective comparison of angiotensin receptor antagonist Valsartan and neprilysin inhibitor Sacubitril with angiotensin-converting enzyme inhibitor (enalapril) to determine impact on Global Mortality and Morbidity in Heart Failure trial has demonstrated that Sacubitril/Valsartan is superior to Enalapril in reducing the risks of both sudden cardiac death and death from worsening heart failure. This novel combination, Sacubitril/Valsartan, is also shown to reduce the risk of hospitalisation and progression of heart failure in adults. However, the benefit of Sacubitril/Valsartan in paediatric heart failure patients is unknown. In this review, we discuss the similarities and differences in pathophysiology of heart failure in children versus adults, and the potential role of Sacubitril/Valsartan in paediatric heart failure patients.


Asunto(s)
Aminobutiratos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Tetrazoles/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo , Niño , Combinación de Medicamentos , Insuficiencia Cardíaca/fisiopatología , Humanos , Neprilisina , Valsartán
17.
Biochim Biophys Acta ; 1848(1 Pt B): 229-45, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24747039

RESUMEN

The motional averaging of powder pattern line shapes is one of the most fundamental aspects of sold-state NMR. Since membrane proteins in liquid crystalline phospholipid bilayers undergo fast rotational diffusion, all of the signals reflect the angles of the principal axes of their dipole-dipole and chemical shift tensors with respect to the axis defined by the bilayer normal. The frequency span and sign of the axially symmetric powder patterns that result from motional averaging about a common axis provide sufficient structural restraints for the calculation of the three-dimensional structure of a membrane protein in a phospholipid bilayer environment. The method is referred to as rotationally aligned (RA) solid-state NMR and demonstrated with results on full-length, unmodified membrane proteins with one, two, and seven trans-membrane helices. RA solid-state NMR is complementary to other solid-state NMR methods, in particular oriented sample (OS) solid-state NMR of stationary, aligned samples. Structural distortions of membrane proteins from the truncations of terminal residues and other sequence modifications, and the use of detergent micelles instead of phospholipid bilayers have also been demonstrated. Thus, it is highly advantageous to determine the structures of unmodified membrane proteins in liquid crystalline phospholipid bilayers under physiological conditions. RA solid-state NMR provides a general method for obtaining accurate and precise structures of membrane proteins under near-native conditions.


Asunto(s)
Proteínas de la Membrana/química , Secuencia de Aminoácidos , Difusión , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Pliegue de Proteína , Proteolípidos/química , Rotación
18.
Biochim Biophys Acta ; 1848(11 Pt A): 3007-3018, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26362058

RESUMEN

Virus protein U (Vpu) from HIV-1, a small membrane protein composed of a transmembrane helical domain and two α-helices in an amphipathic cytoplasmic domain, down modulates several cellular proteins, including CD4, BST-2/CD317/tetherin, NTB-A, and CCR7. The interactions of Vpu with these proteins interfere with the immune system and enhance the release of newly synthesized virus particles. It is essential to characterize the structure and dynamics of Vpu in order to understand the mechanisms of the protein-protein interactions, and potentially to discover antiviral drugs. In this article, we describe investigations of the cytoplasmic domain of Vpu as well as full-length Vpu by NMR spectroscopy. These studies are complementary to earlier analysis of the transmembrane domain of Vpu. The results suggest that the two helices in the cytoplasmic domain form a U-shape. The length of the inter-helical loop in the cytoplasmic domain and the orientation of the third helix vary with the lipid composition, which demonstrate that the C-terminal helix is relatively flexible, providing accessibility for interaction partners.


Asunto(s)
Membrana Celular/química , Proteínas del Virus de la Inmunodeficiencia Humana/química , Espectroscopía de Resonancia Magnética/métodos , Proteínas de la Membrana/química , Proteínas Reguladoras y Accesorias Virales/química , Membrana Celular/metabolismo , Membrana Celular/virología , Dicroismo Circular , Difusión , Dimiristoilfosfatidilcolina/química , VIH-1/metabolismo , VIH-1/fisiología , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismo , Humanos , Cinética , Proteínas de la Membrana/metabolismo , Micelas , Modelos Moleculares , Éteres Fosfolípidos/química , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteolípidos/química , Proteínas Reguladoras y Accesorias Virales/metabolismo
19.
Cardiol Young ; 26(4): 819-23, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26694972

RESUMEN

Although nesiritide has been used in adults with left heart failure, the experience in the paediatric population is limited. We reviewed and analysed our experience with continuous nesiritide infusion as adjunct therapy in children with biventricular dysfunction due to diverse aetiologies and suffering from oliguria despite intravenous diuretics and inotropic therapies for heart-failure management.


Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Disfunción Ventricular/tratamiento farmacológico , Adolescente , Niño , Enfermedad Crítica , Insuficiencia Cardíaca/complicaciones , Humanos , Lactante , Masculino , Oliguria/etiología , Disfunción Ventricular/etiología
20.
Pediatr Cardiol ; 36(6): 1120-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25958153

RESUMEN

The Eisenmenger syndrome (ES) is a severe form of pulmonary arterial hypertension and arises in congenital heart disease with a systemic-to-pulmonary shunt. Patients with ES have multisystem involvement as a result of chronic hypoxemia with hematologic, skeletal, renal, and neurologic systems, causing significant morbidity and mortality. In contrast to pulmonary arterial hypertension, survival prospects are far superior in patients with ES and a growing number of ES patients are surviving into adulthood. As a result, many face the prospect of incidental surgery. To date, there is no guideline for the perioperative care of ES patients in children and limited data available for adult patients. This review provides an overview of appropriate measures for the safe perioperative care of patients, based on an understanding of the pathophysiological changes that occur in ES.


Asunto(s)
Complejo de Eisenmenger/fisiopatología , Hipertensión Pulmonar/fisiopatología , Atención Perioperativa/métodos , Atención Perioperativa/normas , Guías de Práctica Clínica como Asunto , Adolescente , Adulto , Niño , Humanos
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