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1.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38612700

RESUMEN

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing.


Asunto(s)
Hipersensibilidad a las Drogas , Hipersensibilidad Inmediata , Poliquetos , Fármacos Sensibilizantes a Radiaciones , Tionas , Humanos , Animales , Prueba de Desgranulación de los Basófilos , Compuestos de Platino , Carboplatino/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Antineoplásicos Alquilantes , Inmunoglobulina E
2.
Int J Mol Sci ; 24(14)2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37511302

RESUMEN

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays for PBMCs. We included five nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT result for at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT result. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.


Asunto(s)
COVID-19 , Hipersensibilidad a las Drogas , Humanos , Azitromicina/efectos adversos , Activación de Linfocitos , SARS-CoV-2 , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Citocinas , Prueba de COVID-19
3.
Semin Cancer Biol ; 73: 101-115, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-32931953

RESUMEN

Selective estrogen receptor modulators (SERMs) are a class of compounds that bind to estrogen receptors (ERs) and possess estrogen agonist or antagonist actions in different tissues. As such, they are widely used drugs. For instance, tamoxifen, the most prescribed SERM, is used to treat ERα-positive breast cancer. Aside from their therapeutic targets, SERMs have the capacity to broadly affect cellular cholesterol metabolism and handling, mainly through ER-independent mechanisms. Cholesterol metabolism reprogramming is crucial to meet the needs of cancer cells, and different key processes involved in cholesterol homeostasis have been associated with cancer progression. Therefore, the effects of SERMs on cholesterol homeostasis may be relevant to carcinogenesis, either by contributing to the anticancer efficacy of these compounds or, conversely, by promoting resistance to treatment. Understanding these aspects of SERMs actions could help to design more efficacious therapies. Herein we review the effects of SERMs on cellular cholesterol metabolism and handling and discuss their potential in anticancer pharmacology.


Asunto(s)
Colesterol/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Neoplasias , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Animales , Humanos , Metabolismo de los Lípidos/fisiología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo
4.
Cardiovasc Diabetol ; 20(1): 72, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33766036

RESUMEN

BACKGROUND: Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. METHODS: CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. RESULTS: The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. CONCLUSIONS: Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 . Unique Identifier: NCT00924937.


Asunto(s)
Colesterol/sangre , Enfermedad Coronaria/sangre , Diabetes Mellitus Tipo 2/sangre , Macrófagos/metabolismo , Enfermedad Arterial Periférica/sangre , Adulto , Anciano , Apolipoproteína B-100/sangre , Biomarcadores/sangre , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , España/epidemiología , Células THP-1 , Adulto Joven
5.
Int J Mol Sci ; 22(8)2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33920193

RESUMEN

Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.


Asunto(s)
Ceramidas/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Trastornos Psicóticos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antipsicóticos/farmacología , Membrana Celular/genética , Membrana Celular/metabolismo , Femenino , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Metabolismo de los Lípidos/genética , Lisofosfolípidos/genética , Masculino , Olanzapina/farmacología , Trastornos Psicóticos/sangre , Trastornos Psicóticos/patología , Risperidona/farmacología , Esfingolípidos/genética
6.
Pediatr Allergy Immunol ; 31(2): 175-185, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31655013

RESUMEN

BACKGROUND: Peptide microarray technology has been proposed as a useful tool for diagnosing food allergy. However, there is considerable heterogeneity in the clinical methods and analytical procedures used to assess its diagnostic and prognostic performance. We performed a systematic review of studies that have used B-cell epitopes by peptide microarray in food allergies to identify the clinical utility of this immunologic technique. METHODS: Studies were screened in PubMed, Web of Science, and Embase according to an established keyword algorithm. Data extraction was performed, and information was collected in an Excel database. Descriptive analysis was carried out using Stata software. RESULTS: Thirty relevant studies were identified. Most articles were cross-sectional (n = 24), included epitope mapping (n = 9), and assessed diagnostic utility (n = 11). All studies recruited allergic patients, and some included additional patients (sensitized, persistent, and tolerant). The primary microarray variables studied were IgE intensity (n = 29), IgG4 intensity (n = 15), and number of peptides (n = 17). Statistical approaches differed significantly between studies, with the Wilcoxon test being the most frequently used (n = 10). CONCLUSIONS: Sensitization to particular epitopes of milk, peanut, and shrimp allergens can be used to determine clinical reactivity, persistence, severity, or response to oral immunotherapy; however, important methodological questions need to be addressed before drawing definitive conclusions. More research is needed to address the accuracy and clinical benefits of microarray-based technology. Standards are required to improve consistency and reproducibility, and to allow for better understanding of research findings.


Asunto(s)
Alérgenos/genética , Mapeo Epitopo/métodos , Epítopos de Linfocito B/genética , Hipersensibilidad a los Alimentos/diagnóstico , Péptidos/genética , Alérgenos/inmunología , Animales , Epítopos de Linfocito B/inmunología , Alimentos , Humanos , Análisis por Micromatrices , Péptidos/inmunología , Reproducibilidad de los Resultados
7.
J Thromb Thrombolysis ; 50(3): 543-547, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32519165

RESUMEN

A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients. In addition, small series of patients with coronary, cerebrovascular and peripheral arterial thrombotic events have also been reported, but their true incidence and consequences are not well described, and constitute the objective of this study. From February 1st to April 21st, 2020, 2115 COVID-19 patients were treated at Hospital Universitario Fundación Alcorcón (Madrid, Spain), and 1419 were eventually admitted. Patient characteristics and outcomes were collected by reviewing their electronic medical records. Fourteen patients had a systemic arterial thrombotic event, which represents a 1% incidence in relation to the total number of hospitalized patients. Three patients suffered an acute coronary syndrome, two with persistent ST-segment elevation, one of whom was treated invasively, and one with transient ST-segment elevation. Eight patients had a cerebrovascular event. Six suffered an acute ischemic stroke and two a transient ischemic attack, 50% of them had a Rankin score ≥ 3 at discharge. Three additional patients had a limb thrombotic event, all of them infrapopliteal, and were managed conservatively. All three cases developed necrosis of the toes, two of them with bilateral involvement. The hospitalization death rate of patients with an arterial event was 28.6%. Although COVID-19 may favor the occurrence of thrombotic events, the destabilization and thrombosis of arterial atherosclerotic plaques do not seem to be a frequent mechanism which warrants the need for specific systematic preventive measures.


Asunto(s)
Síndrome Coronario Agudo/epidemiología , Infecciones por Coronavirus/epidemiología , Enfermedad Arterial Periférica/epidemiología , Neumonía Viral/epidemiología , Accidente Cerebrovascular/epidemiología , Trombosis/epidemiología , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/virología , Anciano , Anciano de 80 o más Años , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Femenino , Interacciones Huésped-Patógeno , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pandemias , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/virología , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2 , España/epidemiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/virología , Trombosis/diagnóstico , Trombosis/virología
8.
Eur Heart J ; 39(15): 1255-1264, 2018 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-29281101

RESUMEN

Aims: We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart disease (VHD). Methods and results: The sildenafil for improving outcomes after valvular correction (SIOVAC) study was a multricentric, randomized, parallel, and placebo-controlled trial that enrolled stable adults with mean pulmonary artery pressure ≥ 30 mmHg who had undergone a successful valve replacement or repair procedure at least 1 year before inclusion. We assigned 200 patients to receive sildenafil (40 mg three times daily, n = 104) or placebo (n = 96) for 6 months. The primary endpoint was the composite clinical score combining death, hospital admission for heart failure (HF), change in functional class, and patient global self-assessment. Only 27 patients receiving sildenafil improved their composite clinical score, as compared with 44 patients receiving placebo; in contrast 33 patients in the sildenafil group worsened their composite score, as compared with 14 in the placebo group [odds ratio 0.39; 95% confidence interval (CI) 0.22-0.67; P < 0.001]. The Kaplan-Meier estimates for survival without admission due to HF were 0.76 and 0.86 in the sildenafil and placebo groups, respectively (hazard ratio 2.0, 95% CI = 1.0-4.0; log-rank P = 0.044). Changes in 6-min walk test distance, natriuretic peptides, and Doppler-derived systolic pulmonary pressure were similar in both groups. Conclusion: Treatment with sildenafil in patients with persistent PH after successfully corrected VHD is associated to worse clinical outcomes than placebo. Off-label usage of sildenafil for treating this source of left heart disease PH should be avoided. The trial is registered with ClinicalTrials.gov, number NCT00862043.


Asunto(s)
Enfermedades de las Válvulas Cardíacas/complicaciones , Hipertensión Pulmonar/tratamiento farmacológico , Citrato de Sildenafil/uso terapéutico , Anciano , Método Doble Ciego , Femenino , Insuficiencia Cardíaca/epidemiología , Enfermedades de las Válvulas Cardíacas/epidemiología , Enfermedades de las Válvulas Cardíacas/mortalidad , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Placebos/administración & dosificación , Presión Esfenoidal Pulmonar/efectos de los fármacos , Citrato de Sildenafil/administración & dosificación , Resultado del Tratamiento , Vasodilatadores/uso terapéutico
10.
Biochim Biophys Acta ; 1851(9): 1240-53, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26055626

RESUMEN

The mevalonate pathway is tightly linked to cell division. Mevalonate derived non-sterol isoprenoids and cholesterol are essential for cell cycle progression and mitosis completion respectively. In the present work, we studied the effects of fluoromevalonate, a competitive inhibitor of mevalonate diphosphate decarboxylase, on cell proliferation and cell cycle progression in both HL-60 and MOLT-4 cells. This enzyme catalyzes the synthesis of isopentenyl diphosphate, the first isoprenoid in the cholesterol biosynthesis pathway, consuming ATP at the same time. Inhibition of mevalonate diphosphate decarboxylase was followed by a rapid accumulation of mevalonate diphosphate and the reduction of ATP concentrations, while the cell content of cholesterol was barely affected. Strikingly, mevalonate diphosphate decarboxylase inhibition also resulted in the depletion of dNTP pools, which has never been reported before. These effects were accompanied by inhibition of cell proliferation and cell cycle arrest at S phase, together with the appearance of γ-H2AX foci and Chk1 activation. Inhibition of Chk1 in cells treated with fluoromevalonate resulted in premature entry into mitosis and massive cell death, indicating that the inhibition of mevalonate diphosphate decarboxylase triggered a DNA damage response. Notably, the supply of exogenously deoxyribonucleosides abolished γ-H2AX formation and prevented the effects of mevalonate diphosphate decarboxylase inhibition on DNA replication and cell growth. The results indicate that dNTP pool depletion caused by mevalonate diphosphate decarboxylase inhibition hampered DNA replication with subsequent DNA damage, which may have important consequences for replication stress and genomic instability.


Asunto(s)
Carboxiliasas/metabolismo , Desoxirribonucleósidos/metabolismo , Linfocitos/efectos de los fármacos , Ácido Mevalónico/farmacología , Adenosina Trifosfato/metabolismo , Carboxiliasas/antagonistas & inhibidores , Carboxiliasas/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Daño del ADN , Replicación del ADN/efectos de los fármacos , Desoxirribonucleósidos/farmacología , Regulación de la Expresión Génica , Células HL-60 , Halogenación , Hemiterpenos/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Linfocitos/citología , Linfocitos/metabolismo , Ácido Mevalónico/análogos & derivados , Ácido Mevalónico/metabolismo , Compuestos Organofosforados/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal
12.
J Bone Miner Metab ; 34(6): 655-661, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26438320

RESUMEN

Metabolic bone disease may appear as a complication of obesity surgery. Because an imbalance in the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system may underlie osteoporosis, we aimed to study this system in humans in the metabolic bone disease occurring after obesity surgery. In this study we included sixty women with a mean age of 47 ± 10 years studied 7 ± 2 years after bariatric surgery. The variables studied were bone mineral density, ß-isomer of C-terminal telopeptide of type I collagen cross-links (a bone resorption marker), the bone formation markers osteocalcin and N-terminal propeptide of procollagen 1, serum osteoprotegerin and receptor-activator of nuclear factor-κB ligand. Serum osteoprotegerin inversely correlated with the bone remodeling markers osteocalcin, ß-isomer of C-terminal telopeptide of type I collagen cross-links and N-terminal propeptide of procollagen 1. The osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio also correlated inversely with serum parathormone and osteocalcin. Bone mineral density at the lumbar spine was associated with age (ß = -0.235, P = 0.046), percentage of weight loss (ß = 0.421, P = 0.001) and osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio (ß = 0.259, P = 0.029) in stepwise multivariate analysis (R 2 = 0.29, F = 7.49, P < 0.001). Bone mineral density at the hip site was associated only with percentage of weight loss (ß = 0.464, P < 0.001) in stepwise multivariate regression (R 2 = 0.21, F = 15.1, P < 0.001). These data show that the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system is associated with bone markers and bone mineral density at the lumbar spine after obesity surgery.


Asunto(s)
Cirugía Bariátrica/efectos adversos , Densidad Ósea , Enfermedades Óseas Metabólicas , Obesidad , Osteoprotegerina/sangre , Complicaciones Posoperatorias/sangre , Ligando RANK/sangre , Adulto , Anciano , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/etiología , Femenino , Humanos , Persona de Mediana Edad , Obesidad/sangre , Obesidad/cirugía , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Huesos Pélvicos/metabolismo , Columna Vertebral/metabolismo
14.
Arthroscopy ; 30(9): 1131-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24951133

RESUMEN

PURPOSE: To define the variations in the expression of 5 growth factor genes in meniscal tissue after a lesion is created in the avascular zone of the medial meniscus of the rabbit. METHODS: A longitudinal lesion was created in the avascular zone of the anterior horn of the medial meniscus in 42 rabbits. Six animals were killed at 0, 1, 3, 7, 14, 21, and 120 days after lesion creation. Meniscal tissue from the avascular and vascular zones was harvested. A quantitative polymerase chain reaction analysis was performed to evaluate the expression levels of 5 different growth factors: vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1), transforming growth factor ß1 (TGF-ß1), platelet-derived growth factor ß (PDGF-ß), and interleukin 1ß. RESULTS: The basal expression levels of all the growth factors studied were similar in the avascular and vascular zones. There was an increase in VEGF-A expression in the avascular zone on the 14th day, an increase in IGF-1 expression in the vascular zone on the 14th day, a decrease in PDGF-ß expression in both zones in the first week, an increase in interleukin 1ß expression in both zones on the first day, and a decrease in TGF-ß1 expression in the vascular zone in the first week. At 120 days, the expression levels of all 5 growth factors returned to basal levels. CONCLUSIONS: There are significant variations in the expression of the growth factors studied during the first weeks after meniscal lesion creation. The preinjury expression levels are similar in the avascular and vascular zones and are not significantly different from the basal levels 4 months after injury. CLINICAL RELEVANCE: This study identifies potential therapeutic molecular targets (VEGF-A, IGF-1, TGF-ß1, and PDGF-ß) that can be used in the treatment of meniscal tears.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/metabolismo , Meniscos Tibiales/metabolismo , Lesiones de Menisco Tibial , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Traumatismos de la Rodilla , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-sis/metabolismo , Conejos , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas
15.
Surg Laparosc Endosc Percutan Tech ; 34(1): 1-8, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37963307

RESUMEN

BACKGROUND: High CO 2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes. MATERIALS AND METHODS: One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure. RESULTS: Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P =0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P =0.025, and 0.74±0.89 vs. 0.24±1.15; P =0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups. CONCLUSIONS: Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon's expertise.


Asunto(s)
Colecistectomía Laparoscópica , Insuflación , Laparoscopía , Neumoperitoneo , Humanos , Peritoneo/cirugía , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos , Neumoperitoneo/etiología , Insuflación/efectos adversos , Insuflación/métodos , Laparoscopía/métodos , Neumoperitoneo Artificial/efectos adversos , Neumoperitoneo Artificial/métodos
16.
J Am Nutr Assoc ; : 1-14, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39384179

RESUMEN

OBJECTIVE: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. METHOD: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. RESULTS: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% ± 12.54% and -6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. CONCLUSIONS: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.

17.
Int Arch Allergy Immunol ; 161(1): 11-20, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23257567

RESUMEN

BACKGROUND: Ovomucoid (Gal d 1) has been demonstrated to be the most important allergen in IgE-mediated egg allergy. Peptide microarray analysis is a novel method that can provide useful information on the nature of specific allergens. METHODS: A peptide microarray immunoassay was performed using a 15- and 20-amino acid (aa) library of overlapping peptides (3-offset) of the primary sequence of ovomucoid. Sera from 50 patients with IgE-mediated egg allergy and reactivity to ovomucoid, with more than 1 year of follow-up, and sera from 10 controls were tested. Peptides were considered major epitopes when the average weighted Z-score was greater than 3 and recognized by at least 20% of the patient's sera. Specific IgE epitopes were established on the basis of the IgE/IgG4 Z-score ratio. RESULTS: The IgE and IgG4 recognition pattern was similar in both sets of peptides, but the signal intensity was generally higher in the 20-aa set. Thirty-four percent of the patients did not recognize any IgE sequential peptide and 20% of the patients recognized more than 10 sequential peptides. We identified 3 major IgE B-cell epitopes in domains I and II of ovomucoid. IgE/IgG4 ratio analysis showed that peptides 1-2 (aa 4-20) and peptides 29-31 (aa 91-104) were specific IgE epitopes. CONCLUSION: By using peptide microarray immunoassay in egg-allergic patients, we established that 34% of the patients do not have any linear epitope recognized by IgE. Further studies are needed to determine the clinical relevance of this finding.


Asunto(s)
Hipersensibilidad al Huevo/inmunología , Epítopos/inmunología , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Ovomucina/inmunología , Adolescente , Niño , Preescolar , Hipersensibilidad al Huevo/sangre , Mapeo Epitopo/métodos , Epítopos/química , Femenino , Humanos , Inmunoglobulina E/química , Inmunoglobulina G/química , Masculino , Ovomucina/química , Análisis por Matrices de Proteínas/métodos
18.
Cardiol J ; 30(5): 696-704, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36510791

RESUMEN

BACKGROUND: Early readmission (< 30 days) after percutaneous coronary intervention (PCI) is associated with a worse prognosis, but little is known regarding the causes and consequences of late readmission. The aim of the present study was to determine the incidence, causes, and prognosis of patients readmitted > 1 < 12-months after PCI (late readmission). METHODS: Single-center retrospective cohort study of 743 consecutive post-PCI patients. Patient characteristics and follow-up data were collected by reviewing their electronic medical records and from standardized telephone interviews performed at 1 year and at the end of follow-up. RESULTS: Of the 743 patients, 224 (30.14%) were readmitted 1-12 months after PCI, 109 due to chest pain (48.66%), and 115 for other reasons (51.34%). Hospital readmission was associated with lower survival rates of 77.6% vs. 98.3% at 24 months and 73.5% vs. 97.6% at 36 months (p < 0.001). Univariate predictors for late readmission were hypertension, older age, chronic kidney disease, lower left ventricular ejection fraction, and lower baseline hemoglobin concentration. Only baseline hemoglobin concentration was an independent predictor of late readmission (odds ratio: 0.867, 95% confidence interval: 0.778-0.966, p = 0.01). Readmission for chest pain portrayed a lower mortality rate compared to other causes, with survival rates of 90.2% vs. 50% at 36 months (p < 0.001). CONCLUSIONS: Late hospital readmission after PCI is associated with a worse prognosis and is related to patient comorbidities. Readmission for chest pain is common and portrayed a more favorable prognosis, similar to patients not readmitted. A readily available parameter, baseline anemia, was the main predictor of late readmission.


Asunto(s)
Intervención Coronaria Percutánea , Humanos , Estudios Retrospectivos , Readmisión del Paciente , Incidencia , Volumen Sistólico , Función Ventricular Izquierda , Pronóstico , Dolor en el Pecho , Hemoglobinas , Factores de Riesgo , Resultado del Tratamiento
19.
Methods Mol Biol ; 2578: 219-236, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36152291

RESUMEN

Peptide microarrays are a powerful tool to identify linear epitopes of food allergens in a high-throughput manner. The main advantages of the microarray-based immunoassay are as follows: the possibility to assay thousands of targets simultaneously, the requirement of a low volume of serum, the more robust statistical analysis, and the possibility to test simultaneously several immunoglobulin subclasses. Among them, the last one has a special interest in the field of food allergy, because the development of tolerance to food allergens has been associated with a decrease in IgE and an increase in IgG4 levels against linear epitopes. However, the main limitation to the clinical use of microarray is the automated analysis of the data. Recent studies mapping the linear epitopes of food allergens with peptide microarray immunoassays have identified peptide biomarkers that can be used for early diagnosis of food allergies and to predict their severity or the self-development of tolerance. Using this approach, we have worked on epitope mapping of the two most important food allergens in the Spanish population, cow's milk, and chicken eggs. The final aim of these studies is to define subsets of peptides that could be used as biomarkers to improve the diagnosis and prognosis of food allergies. This chapter describes the protocol to produce microarrays using a library of overlapping peptides corresponding to the primary sequences of food allergens and data acquisition and analysis of IgE and IgG4 binding epitopes.


Asunto(s)
Hipersensibilidad a los Alimentos , Inmunoglobulina G , Alérgenos , Animales , Biomarcadores , Bovinos , Mapeo Epitopo/métodos , Epítopos , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Inmunoensayo/métodos , Inmunoglobulina E/metabolismo , Péptidos
20.
Artículo en Inglés | MEDLINE | ID: mdl-37059386

RESUMEN

Dihydrosphingolipids are lipids biosynthetically related to ceramides. An increase in ceramides is associated with enhanced fat storage in the liver, and inhibition of their synthesis is reported to prevent the appearance of steatosis in animal models. However, the precise association of dihydrosphingolipids with non-alcoholic fatty liver disease (NAFLD) is yet to be established. We employed a diet induced NAFLD mouse model to study the association between this class of compounds and disease progression. Mice fed a high-fat diet were sacrificed at 22, 30 and 40 weeks to reproduce the full spectrum of histological damage found in human disease, steatosis (NAFL) and steatohepatitis (NASH) with and without significant fibrosis. Blood and liver tissue samples were obtained from patients whose NAFLD severity was assessed histologically. To demonstrate the effect of dihydroceramides over NAFLD progression we treated mice with fenretinide an inhibitor of dihydroceramide desaturase-1 (DEGS1). Lipidomic analyses were performed using liquid chromatography-tandem mass spectrometry. Triglycerides, cholesteryl esters and dihydrosphingolipids were increased in the liver of model mice in association with the degree of steatosis and fibrosis. Dihydroceramides increased with the histological severity observed in liver samples of mice (0.024 ± 0.003 nmol/mg vs 0.049 ± 0.005 nmol/mg, non-NAFLD vs NASH-fibrosis, p < 0.0001) and patients (0.105 ± 0.011 nmol/mg vs 0.165 ± 0.021 nmol/mg, p = 0.0221). Inhibition of DEGS1 induce a four-fold increase in dihydroceramides improving steatosis but increasing the inflammatory activity and fibrosis. In conclusion, the degree of histological damage in NAFLD correlate with dihydroceramide and dihydrosphingolipid accumulation. LAY SUMMARY: Accumulation of triglyceride and cholesteryl ester lipids is the hallmark of non-alcoholic fatty liver disease. Using lipidomics, we examined the role of dihydrosphingolipids in NAFLD progression. Our results demonstrate that de novo dihydrosphingolipid synthesis is an early event in NAFLD and the concentrations of these lipids are correlated with histological severity in both mouse and human disease.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/patología , Fibrosis , Triglicéridos , Ceramidas
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