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1.
Artículo en Inglés | MEDLINE | ID: mdl-38664124

RESUMEN

BACKGROUND AND AIMS: While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we propose its potential predictive role over a 12-month period of standard care, with the ability to complement anthropometric measures. METHODS AND RESULTS: Hierarchical clustering revealed a notable association of urinary OPN (uOPN) with MetS criteria and overcame anthropometric measures in predicting the improvement at 12 months (OR of 2.74 [95% CI 1.32 to 6.29]). uOPN significantly contributed to the homogeneity of the nodes in the random forest and ultimately enhanced the performance of anthropometric measures when assessed for accuracy and area under the curve (AUC). CONCLUSION: Our findings offer insights into potential applications in cardiometabolic medicine for uOPN, which is easily detectable in non-invasive biological samples through an affordable assay.

2.
Eur J Clin Invest ; : e14143, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38041605

RESUMEN

Despite the institution of an interdisciplinary Inflammatory Bowel Disease (IBD) centre is encouraged, how it may improve patient care is still unknown. In a 5-year period following organisation of an IBD centre, hospitalisations per patient/year decreased (0.41-0.17) and patients on biologics increased (7.7%-26.7%). Total number of hospitalisations (-18.4%) and length of hospitalisation (-29.4%) improved compared with a preceding 5-year period. These findings suggest that institution of an interdisciplinary IBD centre is associated with improved healthcare utilisation.

3.
Nutr Metab Cardiovasc Dis ; 33(1): 185-193, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36411219

RESUMEN

BACKGROUND AND AIMS: Inflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements. METHODS AND RESULTS: patients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961-0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949-0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings. CONCLUSION: Improvement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.


Asunto(s)
Síndrome Metabólico , Humanos , Síndrome Metabólico/diagnóstico , Metaloproteinasa 8 de la Matriz , Metaloproteinasa 9 de la Matriz , Neutrófilos/metabolismo , Biomarcadores , Inflamación , Curva ROC , Circunferencia de la Cintura
4.
Muscle Nerve ; 65(1): 96-104, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34687219

RESUMEN

INTRODUCTION/AIMS: Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition. METHODS: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement. All patients underwent a neurological examination and nerve conduction and electromyography studies. The first step of the investigation included a screening for Pompe disease. We then evaluated the patients for myotonic dystrophy type II-related CCTG expansion and excluded patients with copy number variations in the DMD gene. Subsequently, the undiagnosed patients were investigated using a target gene panel that included 20 genes associated with isolated hyperCKemia. RESULTS: Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings. DISCUSSION: We have described our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening, and first-line genetic investigations, followed by successive targeted sequencing panels. Both clinical signs and electromyographic abnormalities are associated with increased diagnostic yields.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II , Enfermedades Musculares , Creatina Quinasa , Variaciones en el Número de Copia de ADN , Electromiografía , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Humanos
5.
Neuropediatrics ; 53(1): 69-74, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34852372

RESUMEN

Alternating Hemiplegia of Childhood (AHC) is a rare neurological disease characterized by early-onset recurrent paroxysmal events and persistent neurological deficits. TBC1D24 gene variants have been associated with a phenotypic spectrum having epilepsy as the main clinical manifestation. Herein, we report the case of a child affected by developmental delay, polymorphic seizures, and nonepileptic episodes characterized by hemiplegia or bilateral plegia, pallor, hypotonia, and dystonic postures without loss of consciousness that resolved with sleep. Noteworthy, the patient fulfills all the diagnostic criteria for AHC. An epilepsy gene panel revealed a novel TBC1D24 mutation. This variant may be considered a PM5, according to the American College of Medical Genetics and Genomics guidelines. TBC1D24 gene variants are associated with various clinical features, and increasing data confirms the association with permanent and paroxysmal movement disorders. Our report suggests that the TBC1D24 molecular analysis could be considered in the diagnostic workup of AHC patients.


Asunto(s)
Epilepsia , Hemiplejía , Niño , Epilepsia/diagnóstico , Epilepsia/genética , Proteínas Activadoras de GTPasa/genética , Hemiplejía/diagnóstico , Hemiplejía/genética , Humanos , Mutación , Convulsiones
6.
Am J Hum Genet ; 103(3): 431-439, 2018 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-30100084

RESUMEN

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition.

7.
Eur J Clin Invest ; 51(3): e13403, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32918277

RESUMEN

Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.


Asunto(s)
Glucemia/metabolismo , Dieta Mediterránea , Intolerancia a la Glucosa/dietoterapia , Síndrome Metabólico/dietoterapia , Osteopontina/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Intolerancia a la Glucosa/metabolismo , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Proyectos Piloto , Pronóstico
8.
Neuropediatrics ; 51(6): 425-429, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32392611

RESUMEN

RTN4IP1 pathogenic variants (OPA10 syndrome) have been described in patients with early-onset recessive optic neuropathy and recently associated with a broader clinical spectrum, from isolated optic neuropathy to severe encephalopathies with epilepsy. Here we present a case of a patient with a complex clinical picture characterized by bilateral optic nerve atrophy, horizontal nystagmus, myopia, mild intellectual disability, generalized chorea, isolated small subependymal heterotopia, and asynchronous self-resolving midbrain MRI (magnetic resonance imaging) lesions. By using massive gene sequencing, we identified in this patient the c.308G > A (p.Arg103His) homozygous pathogenic variant in the RTN4IP1 gene. Complex movement disorders and relapsing-remitting neuroradiological lesions have not been previously reported in this condition. Our case expands the clinical spectrum of OPA10 syndrome and opens new opportunities for the molecular diagnosis.


Asunto(s)
Proteínas Portadoras/genética , Corea/diagnóstico , Corea/genética , Proteínas Mitocondriales/genética , Atrofia Óptica/diagnóstico , Atrofia Óptica/genética , Encéfalo/patología , Niño , Corea/complicaciones , Humanos , Masculino , Mutación , Atrofia Óptica/complicaciones
10.
Eur J Clin Invest ; 49(8): e13128, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31091356

RESUMEN

BACKGROUND: Inflammation, overweight and other cardiovascular risk factors might negatively impact on hypertension remission in metabolic syndrome (MetS), independently of the pharmacological treatment. Here, the potential influence of systemic inflammation (assessed by serum high-sensitivity C-reactive protein [hs-CRP]) on hypertension remission will be investigated in a cohort of hypertensive patients with MetS. MATERIAL AND METHODS: Hypertensive patients with MetS (n = 100) were enrolled, treated under current behavior/dietary/pharmacological recommendations and followed up for 12 months. All patients received medications and nutritional advice based on Mediterranean-like dietary pattern in addition to psychological and physical activity counselling. At baseline (T0), 6 (T1) and 12 (T2) months of follow-up, clinical data, haematological and biochemical profiles and serum hs-CRP were measured. RESULTS: As compared to T0, at T2 patients displayed improvements in anthropometric and metabolic profiles. At T2, the hypertension remission rate was 13.0%. Serum hs-CRP did not change overtime in the overall cohort. Surprisingly, patients who experienced hypertension remission were less treated with antihypertensive drugs, but developed a weak improvement in anthropometric measures during follow-up. The hypertension remission group had lower baseline levels of hs-CRP as compared to non-remission. Low baseline hs-CRP (<2 µg/mL, cut-off value identified by ROC curve) predicted hypertension remission, independently of antihypertensive treatment implementation, baseline systolic blood pressure and waist circumference improvement. CONCLUSIONS: Remission of hypertension in MetS is independently associated with baseline low CRP levels, which might suggest a critical role for inflammation in sustaining high blood pressure levels.


Asunto(s)
Proteína C-Reactiva/metabolismo , Hipertensión/sangre , Síndrome Metabólico/sangre , Adulto , Antropometría , Antihipertensivos/uso terapéutico , Estudios de Cohortes , Dieta , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/dietoterapia , Hipertensión/tratamiento farmacológico , Inflamación/dietoterapia , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/dietoterapia , Síndrome Metabólico/tratamiento farmacológico , Metaboloma , Persona de Mediana Edad , Sobrepeso/complicaciones , Curva ROC , Remisión Espontánea , Circunferencia de la Cintura , Adulto Joven
11.
Neuropediatrics ; 50(5): 327-331, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31319423

RESUMEN

The X-linked alpha thalassemia mental retardation (ATR-X) syndrome is a genetic disorder caused by X-linked recessive mutations in ATRX gene, related to a wide spectrum of clinical manifestations, such as alpha thalassemia, developmental delay, genital abnormalities, and gastrointestinal disorders. Patients with ATR-X syndrome can suffer from different types of epileptic seizures, but a severe epileptic encephalopathy pattern has not been described to date. We describe, for the first time, two brothers with genetically confirmed ATR-X syndrome who presented with drug-resistant epileptic encephalopathy, with tonic and polimorphic seizures reported in the elder brother and epileptic spasms in the younger brother. Moreover, both brothers showed a peculiar movement disorder with myoclonus-dystonia, worsened during periods of distress or pain. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe epileptic encephalopathies and movement disorders.


Asunto(s)
Trastornos Distónicos/diagnóstico , Epilepsias Mioclónicas/diagnóstico , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Pubertad Precoz/diagnóstico , Proteína Nuclear Ligada al Cromosoma X/genética , Talasemia alfa/diagnóstico , Niño , Trastornos Distónicos/complicaciones , Trastornos Distónicos/genética , Epilepsias Mioclónicas/complicaciones , Epilepsias Mioclónicas/genética , Humanos , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/complicaciones , Discapacidad Intelectual Ligada al Cromosoma X/genética , Mutación , Pubertad Precoz/complicaciones , Pubertad Precoz/genética , Hermanos , Talasemia alfa/complicaciones , Talasemia alfa/genética
12.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(9): 991-997, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29852278

RESUMEN

Proprotein convertase subtilisin/kexin 9 (PCSK9), a protein regulating the number of cell-surface LDL receptors (LDLR), circulates partially associated to plasma lipoproteins. How this interaction alters PCSK9 plasma levels is still unclear. In the present study, we took advantage of the availability of a large cohort of carriers of genetic HDL disorders to evaluate how HDL defects affect plasma PCSK9 levels and its distribution among lipoproteins. Plasma PCSK9 concentrations were determined by ELISA in carriers of mutations in LCAT, ABCA1, or APOAI genes, and lipoprotein distribution was analyzed by FPLC. Carriers of one or two mutations in the LCAT gene show plasma PCSK9 levels comparable to that of unaffected family controls (homozygotes, 159.4 ng/mL (124.9;243.3); heterozygotes, 180.3 ng/mL (127.6;251.5) and controls, 190.4 ng/mL (146.7;264.4); P for trend = 0.33). Measurement of PCSK9 in plasma of subjects carrying mutations in ABCA1 or APOAI genes confirmed normal values. When fractionated by FPLC, PCSK9 peaked in a region between LDL and HDL in control subjects. In carriers of all HDL defects, lipoprotein profile shows a strong reduction of HDL, but the distribution of PCSK9 was superimposable to that of controls. In conclusion, the present study demonstrates that in genetically determined low HDL states plasma PCSK9 concentrations and lipoprotein distribution are preserved, thus suggesting that HDL may not be involved in PCSK9 transport in plasma.


Asunto(s)
Transportador 1 de Casete de Unión a ATP/sangre , Apolipoproteína A-I/sangre , Hipolipoproteinemias/sangre , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Proproteína Convertasa 9/sangre , Transportador 1 de Casete de Unión a ATP/deficiencia , Transportador 1 de Casete de Unión a ATP/genética , Adulto , Anciano , Apolipoproteína A-I/deficiencia , Apolipoproteína A-I/genética , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Heterocigoto , Homocigoto , Humanos , Hipolipoproteinemias/genética , Hipolipoproteinemias/patología , Lipoproteínas HDL/sangre , Lipoproteínas HDL/genética , Lipoproteínas LDL/sangre , Lipoproteínas LDL/genética , Masculino , Persona de Mediana Edad , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Proproteína Convertasa 9/genética
13.
Eur J Clin Invest ; 48(3)2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29327345

RESUMEN

BACKGROUND: Different cut-off values of serum lipoprotein (a) [Lp (a)] were recently identified to better stratify cardiovascular risk categories. Both pathophysiological and prognostic values of Lp (a) remain unclear. MATERIALS AND METHODS: Here, the prognostic value of Lp (a) and its correlation with intraplaque features were assessed in patients with severe carotid artery stenosis undergoing endarterectomy (n = 180). The cut-off value of 10 mg/dL for serum Lp (a) was selected to predict 24-month follow-up acute coronary syndrome (ACS). In addition, the association between serum Lp (a) and intraplaque lipids, collagen, inflammatory and vascular cells was assessed. Serum Lp (a) levels were measured by nephelometric assay. RESULTS: Patients with high Lp (a) had similar comorbidities, medications and laboratory parameters as compared to low Lp (a) levels. At 24-month follow-up, patients with high Lp (a) had more ACS as compared to low levels. Histological parameters within plaques were comparable in the study groups. No significant correlation between Lp (a) serum levels and intraplaque parameters was found, except for a weak positive association with smooth muscle cells in upstream plaque portions. When adjusted for gender, the presence of dyslipidaemia and chronic coronary artery disease, Lp (a) ≥10 mg/dL remained predictive for ACS. CONCLUSIONS: Lp (a) determination could be a useful tool to predict ACS in patients with severe carotid stenosis.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Estenosis Carotídea/complicaciones , Lipoproteína(a)/metabolismo , Síndrome Coronario Agudo/sangre , Cuidados Posteriores , Anciano , Biomarcadores/metabolismo , Estenosis Carotídea/sangre , Femenino , Humanos , Masculino , Proyectos Piloto , Placa Aterosclerótica/sangre , Placa Aterosclerótica/diagnóstico
14.
Neuropediatrics ; 49(3): 217-221, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29631299

RESUMEN

Adams-Oliver syndrome (AOS) is characterized by a combination of congenital scalp defects (aplasia cutis congenita) and terminal transverse limb malformations of variable severity. When neurological findings are present, patients are reported as AOS variants. We describe a child with compound heterozygosity of the DOCK6 gene, aplasia cutis, terminal transverse limb defects, cardiovascular impairment, intellectual disability, and brain malformations with intracranial calcifications. He suffers from a severe refractory epileptic encephalopathy characterized by polymorphic seizures with prolonged periods of electroencephalogram (EEG), continuous epileptiform activity related to clinical inactivity, and closure of eyes with an "ON-OFF" behavior.


Asunto(s)
Displasia Ectodérmica/genética , Epilepsia/genética , Factores de Intercambio de Guanina Nucleótido/genética , Deformidades Congénitas de las Extremidades/genética , Mutación , Dermatosis del Cuero Cabelludo/congénito , Encéfalo/fisiopatología , Displasia Ectodérmica/fisiopatología , Epilepsia/fisiopatología , Humanos , Lactante , Deformidades Congénitas de las Extremidades/fisiopatología , Masculino , Fenotipo , Dermatosis del Cuero Cabelludo/genética , Dermatosis del Cuero Cabelludo/fisiopatología
15.
Cephalalgia ; 37(12): 1202-1206, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27651281

RESUMEN

Introduction Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs. Case description We report on the emergency personalized treatment protocol used in an 11 year-old girl with CACNA1A-related encephalopathy for the management of acute attacks of headache, hemiconvulsions and hemiplegia with coma. Discussion Combined corticosteroid pulses and hypertonic solution led to a reduction in severity and duration of acute attacks when administered in the early stages, characterized by migraine, seizure, fever, vomiting and impairment of consciousness associated to hemispheric slowing on the EEG.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Edema Encefálico/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Migraña con Aura/tratamiento farmacológico , Edema Encefálico/genética , Canales de Calcio/genética , Niño , Dexametasona/uso terapéutico , Erupciones por Medicamentos/etiología , Femenino , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Humanos , Lamotrigina , Migraña con Aura/genética , Mutación Missense , Topiramato , Triazinas/efectos adversos
16.
Arterioscler Thromb Vasc Biol ; 36(8): 1647-50, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27079874

RESUMEN

OBJECTIVE: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? APPROACH AND RESULTS: Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured by flow cytometry and confocal microscopy was higher in ARH than in control lymphocytes. PCSK9 significantly reduced LDL receptor expression in ARH lymphocytes albeit to a lower extent than in control lymphocytes (25% versus 76%, respectively), an effect reversed by alirocumab. Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes. PCSK9 significantly lowered LDL cellular uptake in ARH lymphocytes, on average by 18%, compared with a 46% reduction observed in control lymphocytes, an effect also reversed by alirocumab. Overall, the effects of recombinant PCSK9, and hence of alirocumab, on LDL receptor expression and function were significantly less pronounced in ARH than in control cells. CONCLUSIONS: PCSK9 inhibition with alirocumab on top of statin treatment has the potential to lower LDL cholesterol in some autosomal recessive hypercholesterolemia patients.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticolesterolemiantes/farmacología , Hipercolesterolemia/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Inhibidores de PCSK9 , Inhibidores de Serina Proteinasa/farmacología , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados , Estudios de Casos y Controles , Células Cultivadas , LDL-Colesterol/metabolismo , Quimioterapia Combinada , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/enzimología , Hipercolesterolemia/genética , Lovastatina/análogos & derivados , Lovastatina/farmacología , Linfocitos/enzimología , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Proproteína Convertasa 9/metabolismo , Receptores de LDL/metabolismo , Adulto Joven , Hiperlipoproteinemia Tipo III
18.
Genes (Basel) ; 15(6)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38927590

RESUMEN

Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder characterized by intellectual disability, facial dysmorphisms, and enlarged thumbs and halluces. Approximately 55% of RTS cases result from pathogenic variants in the CREBBP gene, with an additional 8% linked to the EP300 gene. Given the close relationship between these two genes and their involvement in epigenomic modulation, RTS is grouped into chromatinopathies. The extensive clinical heterogeneity observed in RTS, coupled with the growing number of disorders involving the epigenetic machinery, poses a challenge to a phenotype-based diagnostic approach for these conditions. Here, we describe the first case of a patient clinically diagnosed with RTS with a CREBBP truncating variant in mosaic form. We also review previously described cases of mosaicism in CREBBP and apply clinical diagnostic guidelines to these patients, confirming the good specificity of the consensus. Nonetheless, these reports raise questions about the potential underdiagnosis of milder cases of RTS. The application of a targeted phenotype-based approach, coupled with high-depth NGS, may enhance the diagnostic yield of whole-exome sequencing (WES) in mild and mosaic conditions.


Asunto(s)
Proteína de Unión a CREB , Mosaicismo , Mutación , Fenotipo , Síndrome de Rubinstein-Taybi , Femenino , Humanos , Masculino , Proteína de Unión a CREB/genética , Secuenciación del Exoma/métodos , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/diagnóstico , Síndrome de Rubinstein-Taybi/patología
19.
Nutrients ; 16(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38257158

RESUMEN

This narrative review delves into the intricate relationship between irritable bowel syndrome (IBS) and food intolerances. IBS, a chronic functional gastrointestinal disorder, is characterized by symptoms like abdominal pain and altered bowel habits. The prevalence of IBS has increased globally, especially among young adults. Food and dietary habits play a crucial role in IBS management. About 85-90% of IBS patients report symptom exacerbation linked to specific food consumption, highlighting the strong connection between food intolerances and IBS. Food intolerances often exhibit a dose-dependent pattern, posing a challenge in identifying trigger foods. This issue is further complicated by the complex nature of gastrointestinal physiology and varying food compositions. This review discusses various dietary patterns and their impact on IBS, including the low-FODMAP diet, gluten-free diet, and Mediterranean diet. It highlights the importance of a personalized approach in dietary management, considering individual symptom variability and dietary history. In conclusion, this review emphasizes the need for accurate diagnosis and holistic management of IBS, considering the complex interplay between dietary factors and gastrointestinal pathophysiology. It underlines the importance of patient education and adherence to treatment plans, acknowledging the challenges posed by the variability in dietary triggers and the psychological impact of dietary restrictions.


Asunto(s)
Hipersensibilidad a los Alimentos , Síndrome del Colon Irritable , Adulto Joven , Humanos , Intolerancia Alimentaria , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/etiología , Hipersensibilidad a los Alimentos/epidemiología , Alimentos , Dolor Abdominal
20.
Int J Cardiol ; 400: 131791, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38244890

RESUMEN

BACKGROUND: Adipokines are key mediators of inflammation in metabolic syndrome perpetuating the effect of excess nutrient intake by setting a self-maintaining vicious circle. Here, we assess levels of adiponectin and leptin in a cohort of individuals with MetS undergoing dietary and behavioral counselling. Specifically, we investigate their role as predictors of metabolic syndrome remission after 1 year. METHODS: Patients with MetS (n = 127) received behavioral and dietary recommendations and were followed-up for 1 year. Serum was available for 108 individuals, levels of adiponectin and leptin were tested at baseline, at 6 months (t1) and after 1 year (t2). Adiponectin/leptin (A/L) ratio was also calculated and tested for predictive ability. RESULT: At the end of the follow-up period, 59 patients did not show enough criteria to define MetS anymore. When considered alone, adiponectin and leptin levels did not show difference over follow-up. Their ratio instead was significantly reduced at t1 and t2 with respect to baseline. Remitters also showed lowers level of leptin and A/L ratio as compared to non-remitters at t1. At this timepoint, A/L ratio independently predicted MetS remission at 1 year [OR 9.082 95%CI (1.394-59.160), p = 0.021]. Bootstrap resampling analysis internally validated our findings. CONCLUSIONS: Preliminary results from our pilot study suggest that MetS remission after counselling associates with changes in adipokine balance. A/L ratio decreases overtime and its value at 6 months can independently predict MetS remission.


Asunto(s)
Leptina , Síndrome Metabólico , Humanos , Síndrome Metabólico/diagnóstico , Adiponectina , Proyectos Piloto , Adipoquinas
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