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1.
Sci Rep ; 12(1): 19073, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351956

RESUMO

In this paper, we investigate brain activity associated with complex visual tasks, showing that electroencephalography (EEG) data can help computer vision in reliably recognizing actions from video footage that is used to stimulate human observers. Notably, we consider not only typical "explicit" video action benchmarks, but also more complex data sequences in which action concepts are only referred to, implicitly. To this end, we consider a challenging action recognition benchmark dataset-Moments in Time-whose video sequences do not explicitly visualize actions, but only implicitly refer to them (e.g., fireworks in the sky as an extreme example of "flying"). We employ such videos as stimuli and involve a large sample of subjects to collect a high-definition, multi-modal EEG and video data, designed for understanding action concepts. We discover an agreement among brain activities of different subjects stimulated by the same video footage. We name it as subjects consensus, and we design a computational pipeline to transfer knowledge from EEG to video, sharply boosting the recognition performance.


Assuntos
Eletroencefalografia , Reconhecimento Psicológico , Humanos , Consenso , Encéfalo
2.
Neural Netw ; 155: 574-591, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36208615

RESUMO

Helmholtz Machines (HMs) are a class of generative models composed of two Sigmoid Belief Networks (SBNs), acting respectively as an encoder and a decoder. These models are commonly trained using a two-step optimization algorithm called Wake-Sleep (WS) and more recently by improved versions, such as Reweighted Wake-Sleep (RWS) and Bidirectional Helmholtz Machines (BiHM). The locality of the connections in an SBN induces sparsity in the Fisher Information Matrices associated to the probabilistic models, in the form of a finely-grained block-diagonal structure. In this paper we exploit this property to efficiently train SBNs and HMs using the natural gradient. We present a novel algorithm, called Natural Reweighted Wake-Sleep (NRWS), that corresponds to the geometric adaptation of its standard version. In a similar manner, we also introduce Natural Bidirectional Helmholtz Machine (NBiHM). Differently from previous work, we will show how for HMs the natural gradient can be efficiently computed without the need of introducing any approximation in the structure of the Fisher information matrix. The experiments performed on standard datasets from the literature show a consistent improvement of NRWS and NBiHM not only with respect to their non-geometric baselines but also with respect to state-of-the-art training algorithms for HMs. The improvement is quantified both in terms of speed of convergence as well as value of the log-likelihood reached after training.


Assuntos
Algoritmos , Sono , Modelos Estatísticos , Probabilidade
3.
Front Cardiovasc Med ; 9: 897244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35722114

RESUMO

In addition to long-term regulation of blood pressure (BP), in the kidney resides the initial trigger for hypertension development due to an altered capacity to excrete sodium and water. Betaine is one of the major organic osmolytes, and its betaine/gamma-aminobutyric acid transporter (BGT-1) expression in the renal medulla relates to interstitial tonicity and urinary osmolality and volume. This study investigated altered water and sodium balance as well as changes in antidiuretic hormone (ADH) activity in female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats from their 3-5 weeks of age (prehypertensive phase) to SHR's 28-30 weeks of age (established hypertension-organ damage). Young prehypertensive SHRs showed a reduced daily urine output, an elevated urine osmolarity, and higher immunostaining of tubule BGT-1, alpha-1-Na-K ATPase in the outer medulla vs. age-matched WKY. ADH circulating levels were not different between young prehypertensive SHR and WKY, but the urine aquaporin2 (AQP2)/creatinine ratio and labeling of AQP2 in the collecting duct were increased. At 28-30 weeks, hypertensive SHR with moderate renal failure did not show any difference in urinary osmolarity, urine AQP2/creatinine ratio, tubule BGT-1, and alpha-1-Na-K ATPase as compared with WKY. These results suggest an increased sensitivity to ADH in prehypertensive female SHR. On this basis, a second series of experiments were set to study the role of ADH V1 and V2 receptors in the development of hypertension, and a group of female prehypertensive SHRs were treated from the 25th to 49th day of age with either V1 (OPC21268) or V2 (OPC 41061) receptor antagonists to evaluate the BP time course. OPC 41061-treated SHRs had a delayed development of hypertension for 5 weeks without effect in OPC 21268-treated SHRs. In prehypertensive female SHR, an increased renal ADH sensitivity is crucial for the development of hypertension by favoring a positive water balance. Early treatment with selective V2 antagonism delays future hypertension development in young SHRs.

4.
Front Cardiovasc Med ; 8: 704281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414219

RESUMO

Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association between depression and hypotension. This phenomenon may depend, at least in part, on the use of antidepressant drugs, which may influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems. This review summarizes extant literature on the effect of antidepressant drugs on blood pressure. Selective serotonin reuptake inhibitors are characterized by limited effects on autonomic system activity and a lower impact on blood pressure. Thus, they represent the safest class-particularly among elderly and cardiovascular patients. Serotonin-norepinephrine reuptake inhibitors, particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system. The norepinephrine reuptake inhibitor reboxetine is considered a safe option because of its neutral effects on blood pressure in long-term studies, even if both hypotensive and hypertensive effects are reported. The dopamine-norepinephrine reuptake inhibitor bupropion can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension, especially in patients with cardiovascular diseases. The norepinephrine-serotonin modulators, mirtazapine and mianserin, have minimal effects on blood pressure but may rarely lead to orthostatic hypotension and falls. These adverse effects are also observed with the serotonin-reuptake modulators, nefazodone and trazodone, but seldomly with vortioxetine and vilazodone. Agomelatine, the only melatonergic antidepressant drug, may also have limited effects on blood pressure. Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine. Oral monoamine-oxidase inhibitors, less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis due to ingestion of tyramine-containing food (i.e., cheese reaction). Lastly, a hypertensive crisis may complicate antidepressant treatment as a part of the serotonin syndrome, also including neuromuscular, cognitive, and autonomic dysfunctions. Clinicians treating depressive patients should carefully consider their blood pressure status and cardiovascular comorbidities because of the effects of antidepressant drugs on blood pressure profiles and potential interactions with antihypertensive treatments.

5.
Diagnostics (Basel) ; 11(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34441429

RESUMO

(1) Background: Perivascular adipose tissue attenuation, measured with computed tomography imaging, is a marker of mean local vascular inflammation since it reflects the morphological changes of the fat tissue in direct contact with the vessel. This method is thoroughly validated in coronary arteries, but few studies have been performed in other vascular beds. The aim of the present study is to provide insight into the potential application of perivascular adipose tissue attenuation through computed tomography imaging in extra-coronary arteries. (2) Methods: A comprehensive search of the scientific literature published in the last 30 years (1990-2020) has been performed on Medline. (3) Results: A Medline databases search for titles, abstracts, and keywords returned 3251 records. After the exclusion of repetitions and the application of inclusion and exclusion criteria and abstract screening, 37 studies were selected for full-text evaluation. Three papers were finally included in the systematic review. Perivascular adipose tissue attenuation assessment was studied in the internal carotid artery, ascending thoracic aorta, and abdominal aorta. (4) Conclusions: Perivascular adipose tissue attenuation seems to be an applicable parameter in all investigated vascular beds, generally with good inter-observer reproducibility.

6.
Blood Press ; 30(5): 322-326, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34176388

RESUMO

PURPOSE: Pheochromocytoma, a catecholamine-secreting tumour leading to neurological and cardiovascular life-threatening conditions through hypertension crisis, occurs in 0.1-0.5% of hypertensive patients, but it is extremely rare in pregnancy (0.0018-0.006%). Some classes of drugs, even commonly used in pregnancy, can trigger catecholamine secretion, precipitating the clinical situation. MATERIALS AND METHODS AND RESULTS: We report a 33-year-old woman, gravida 2 para 1, with previous mild hypertension, was admitted to the emergency room, at 28 2/7 weeks of gestation due to headache, tachycardia and severe arterial hypertension (220/120 mm Hg) triggered by the antiemetic metoclopramide used for a week because of nausea. In the emergency room, a paradoxical rise in blood pressure followed intravenous labetalol infusion was observed. Both metoclopramide and labetalol-triggered hypertensive crisis raised the suspicion of an undiagnosed pheochromocytoma. Diagnostic work-up showed elevated normetanephrine urinary excretion ​​and a right adrenal pheochromocytoma by abdominal magnetic resonance imaging. Oral alpha-1 and beta-1-adrenergic antagonist and calcium-channel blocker were started. At 33-weeks of gestation, she underwent a caesarean section giving birth to a female child. Seven weeks later she underwent a video-laparoscopic right adrenalectomy which normalised her blood pressure. CONCLUSIONS: Both metoclopramide, a selective dopamine type-2 receptor antagonist and partial agonist of 5-hydroxytryptamine 4 receptor, and labetalol, a non-selective ß-adrenoreceptor-blocker with weak α1-adrenergic antagonism, exacerbated an acute hypertensive crisis revealing an unrecognised pheochromocytoma in a pregnant patient. Careful attention to potential drug-triggered catecholamine crises and especially early recognition of pheochromocytomas, are mandatory in hypertensive pregnant women. A missed or delayed diagnosis could result in catastrophic results affecting foetal and maternal outcomes.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adrenalectomia , Adulto , Cesárea , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Recém-Nascido , Metoclopramida/efeitos adversos , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Gravidez
7.
Acta Biomed ; 92(S1): e2021162, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33944843

RESUMO

Background Fibromuscolar dysplasia (FMD) is an idiopathic, non-atherosclerotic and non-inflammatory stenotic lesion of renal arteries causing renovascular hypertension up-regulating renin-angiotensin-aldosterone system. Case report: A 18-year-old man was referred to our Hypertension Center (Clinica e Terapia Medica) for the recent onset of hypertension, poorly controlled on calcium channel blockers, already associated to electrocardiographic and echocardiography signs of left ventricular hypertrophy and significant albuminuria (728 mg/24 h). An increased plasma renin activity (PRA), aldosterone level and a mild hypokalemia raised the suspicion of renovascular hypertension. Abdominal CT and MRI angiography showed mild kidneys asymmetry and a tubular stenosis of the right renal artery in its mid-distal portion close to renal hilum. Radionuclide renal scintigraphy documented a kidneys asymmetry of separated glomerular filtration rate. Renal FMD was diagnosed based on patient age and the absence of cardiovascular risk factors for atherosclerosis. Patient successfully underwent right renal angioplasty giving a rapid normalization of blood pressure levels without antihypertensive drugs. Plasma aldosterone and PRA rapidly normalized as well as serum potassium levels. Six months after angioplasty echocardiography showed a regression of left ventricular hypertrophy and the patient albumin urine excretion became normal (14 mg/24 h). Conclusions FMD can cause renovascular hypertension associated to organ damage such myocardial hypertrophy and albuminuria through mechanisms dependent but also independent from blood pressure levels. Renal angioplasty turned off renin-angiotensin-aldosterone overactivity allowing the cure the hypertension and a surprisingly rapid reverse of myocardial hypertrophy and of excess of albumin urine excretion not only dependent on blood pressure normalization.


Assuntos
Displasia Fibromuscular , Hipertensão , Adolescente , Angioplastia , Angiotensinas , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico por imagem , Displasia Fibromuscular/terapia , Humanos , Hipertensão/complicações , Hipertrofia , Rim/diagnóstico por imagem , Masculino , Renina
8.
Front Endocrinol (Lausanne) ; 12: 652045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815297

RESUMO

Background: Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP). Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus. Conclusions: A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.


Assuntos
Acidose/diagnóstico , Diarreia/diagnóstico , Hipopotassemia/diagnóstico , Feocromocitoma/fisiopatologia , Peptídeo Intestinal Vasoativo/química , Acidose/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adrenalectomia , Idoso , Células Cromafins/citologia , Diarreia/complicações , Humanos , Hipopotassemia/complicações , Masculino , Peptídeos Cíclicos/uso terapêutico , Neoplasias do Sistema Nervoso Periférico , Cintilografia , Receptores de Somatostatina/uso terapêutico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Síndrome , Tomografia Computadorizada por Raios X , Redução de Peso
9.
Entropy (Basel) ; 23(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652911

RESUMO

Word embeddings based on a conditional model are commonly used in Natural Language Processing (NLP) tasks to embed the words of a dictionary in a low dimensional linear space. Their computation is based on the maximization of the likelihood of a conditional probability distribution for each word of the dictionary. These distributions form a Riemannian statistical manifold, where word embeddings can be interpreted as vectors in the tangent space of a specific reference measure on the manifold. A novel family of word embeddings, called α-embeddings have been recently introduced as deriving from the geometrical deformation of the simplex of probabilities through a parameter α, using notions from Information Geometry. After introducing the α-embeddings, we show how the deformation of the simplex, controlled by α, provides an extra handle to increase the performances of several intrinsic and extrinsic tasks in NLP. We test the α-embeddings on different tasks with models of increasing complexity, showing that the advantages associated with the use of α-embeddings are present also for models with a large number of parameters. Finally, we show that tuning α allows for higher performances compared to the use of larger models in which additionally a transformation of the embeddings is learned during training, as experimentally verified in attention models.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33166669

RESUMO

Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males.


Assuntos
Alcoolismo/etiologia , Filho de Pais com Deficiência/estatística & dados numéricos , Interação Gene-Ambiente , Adulto , Filhos Adultos/psicologia , Filhos Adultos/estatística & dados numéricos , Alcoolismo/epidemiologia , Alcoolismo/genética , Alelos , Estudos de Casos e Controles , Filho de Pais com Deficiência/psicologia , Análise por Conglomerados , Feminino , Predisposição Genética para Doença/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Receptores de Dopamina D2/genética , Fatores de Risco , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Inquéritos e Questionários
11.
Sci Rep ; 10(1): 16549, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024225

RESUMO

The retina is a complex circuit of the central nervous system whose aim is to encode visual stimuli prior the higher order processing performed in the visual cortex. Due to the importance of its role, modeling the retina to advance in interpreting its spiking activity output is a well studied problem. In particular, it has been shown that latent variable models can be used to model the joint distribution of Retinal Ganglion Cells (RGCs). In this work, we validate the applicability of Restricted Boltzmann Machines to model the spiking activity responses of a large a population of RGCs recorded with high-resolution electrode arrays. In particular, we show that latent variables can encode modes in the RGC activity distribution that are closely related to the visual stimuli. In contrast to previous work, we further validate our findings by comparing results associated with recordings from retinas under normal and altered encoding conditions obtained by pharmacological manipulation. In these conditions, we observe that the model reflects well-known physiological behaviors of the retina. Finally, we show that we can also discover temporal patterns, associated with distinct dynamics of the stimuli.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Algoritmos , Animais , Camundongos , Estimulação Luminosa
12.
Front Oncol ; 10: 779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509580

RESUMO

The use of antineoplastic drugs has a central role in treatment of patients affected by cancer but is often associated with numerous electrolyte derangements which, in many cases, could represent life-threatening conditions. In fact, while several anti-cancer agents can interfere with kidney function leading to acute kidney injury, proteinuria, and hypertension, in many cases alterations of electrolyte tubular handling and water balance occur. This review summarizes the mechanisms underlying the disturbances of sodium, potassium, magnesium, calcium, and phosphate metabolism during anti-cancer treatment. Platinum compounds are associated with sodium, potassium, and magnesium derangements while alkylating agents and Vinca alkaloids with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Novel anti-neoplastic agents, such as targeted therapies (monoclonal antibodies, tyrosine kinase inhibitors, immunomodulators, mammalian target of rapamycin), can induce SIADH-related hyponatremia and, less frequently, urinary sodium loss. The blockade of epidermal growth factor receptor (EGFR) by anti-EGFR antibodies can result in clinically significant magnesium and potassium losses. Finally, the tumor lysis syndrome is associated with hyperphosphatemia, hypocalcemia and hyperkalemia, all of which represent serious complications of chemotherapy. Thus, clinicians should be aware of these side effects of antineoplastic drugs, in order to set out preventive measures and start appropriate treatments.

13.
Acta Biomed ; 91(2): 365-372, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32420975

RESUMO

BACKGROUND: Posterior reversible encephalopathy (PRES) is a rare syndrome characterized by headache, confusion, seizures, visual changes and white matter edema at radiological imaging. Its pathophysiology is not clarified and different causes, including uncontrolled hypertension, eclampsia, chemotherapy and hypomagnesemia have been suggested. CASE REPORT: A woman affected by stage IV breast cancer with lower extremity deep vein thrombosis treated with low-molecular-weight-heparin, currently in therapy with Palbociclib/Fulvestrant (antiCDK4 and 6/estrogen receptor antagonist) but previously treated with several other chemotherapy lines (including VEGF inhibitor bevacizumab), was admitted to our Internal Medicine department because of ascites and abdominal pain. She was treated with diuretics (and paracentesis). Recently (six-month earlier) a pan-encephalic radiotherapy was done because of brain and skull metastasis. Among blood tests, low serum levels of hypomagnesemia were observed. She developed PRES that rapidly progressed to lethargy, unresponsiveness till coma without changes in blood pressure. Magnetic Resonance Imaging study showed bilateral parieto-occipital edema and a thrombosis of left transverse and sigmoid sinuses. Anti-edema therapy, intravenous supplementation of magnesium and decoagulation were started, with complete and rapid recovery (within 18 hours) of clinical and radiologic changes. CONCLUSIONS: PRES diagnosis was based on the rapid clinical recovery after antiedema treatment and magnesium supplementation. Low magnesium level related to both diuretic and Fulvestrant/Palbociclib therapies and recent radiotherapy can represent potential mechanisms favouring PRES development. The previous bevacizumab treatment may also be involved as a PRES predisposing factor. The concomitant occurrence of cerebral thrombosis can have precipitated the clinical situation.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Deficiência de Magnésio/complicações , Síndrome da Leucoencefalopatia Posterior/etiologia , Antineoplásicos/uso terapêutico , Feminino , Humanos
14.
Eur J Prev Cardiol ; 27(8): 850-867, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31088130

RESUMO

Excessive or inappropriate use of non-steroidal anti-inflammatory drugs can affect cardiovascular and renal function. Non-steroidal anti-inflammatory drugs, both non-selective and selective cyclooxygenase 2 inhibitors, are among the most widely used drugs, especially in the elderly, with multiple comorbidities. Exposition to a polypharmacy burden represents a favourable substrate for the onset of non-steroidal anti-inflammatory drug-induced deleterious effects. Cardiovascular and renal issues concerning the occurrence of myocardial infarction, atrial fibrillation, heart failure and arterial hypertension, as well as acute or chronic kidney damage, become critical for clinicians in their daily practice. We discuss current available knowledge regarding prostanoid physiology in vascular, cardiac and renal systems, pointing out potential negative non-steroidal anti-inflammatory drug-related issues in clinical practice.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Sistema Cardiovascular/efeitos dos fármacos , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/induzido quimicamente , Animais , Cardiotoxicidade , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Humanos , Rim/metabolismo , Rim/fisiopatologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Risco
15.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269783

RESUMO

Atrial natriuretic peptide (ANP) is a cardiac hormone with pleiotropic cardiovascular and metabolic properties including vasodilation, natriuresis and suppression of the renin-angiotensin-aldosterone system. Moreover, ANP induces lipolysis, lipid oxidation, adipocyte browning and ameliorates insulin sensitivity. Studies on ANP genetic variants revealed that subjects with higher ANP plasma levels have lower cardio-metabolic risk. In vivo and in humans, augmenting the ANP pathway has been shown to exert cardiovascular therapeutic actions while ameliorating the metabolic profile. MANP is a novel designer ANP-based peptide with greater and more sustained biological actions than ANP in animal models. Recent studies also demonstrated that MANP lowers blood pressure and inhibits aldosterone in hypertensive subjects whereas cardiometabolic properties of MANP are currently tested in an on-going clinical study in hypertension and metabolic syndrome. Evidence from in vitro, in vivo and in human studies support the concept that ANP and related pathway represent an optimal target for a comprehensive approach to cardiometabolic disease.


Assuntos
Fator Natriurético Atrial/metabolismo , Fator Natriurético Atrial/uso terapêutico , Doenças Cardiovasculares/metabolismo , Doenças Metabólicas/metabolismo , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Variação Genética , Humanos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/genética , Terapia de Alvo Molecular
16.
Arthritis Rheumatol ; 71(11): 1913-1922, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31233292

RESUMO

OBJECTIVE: Chronic periaortitis (CP) is a rare disease characterized by periaortic and periiliac fibroinflammatory tissue. The pathogenic mechanisms leading to tissue accumulation and activation of fibroblasts are unclear. This study was undertaken to explore the role of fibrocytes, circulating precursors of tissue fibroblasts, in patients with CP. METHODS: We studied 44 patients with newly diagnosed CP and 30 healthy controls. Circulating fibrocytes were identified as Col1+CD45+ cells using flow cytometry. Retroperitoneal tissue biopsy samples from 9 CP patients were stained with anti-type I procollagen, anti-CXCR4, and anti-CD45 antibodies and analyzed by confocal microscopy to detect tissue-infiltrating fibrocytes. Circulating levels and tissue expression of CXCL12, a CXCR4 ligand that promotes fibrocyte homing, were investigated using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. We also characterized T helper polarization in biopsy samples from CP patients and measured serum levels of a panel of cytokines that are hallmarks of T helper responses and capable of influencing fibrocyte differentiation. RESULTS: The frequency of circulating Col1+CD45+ fibrocytes was higher in patients than in controls (P = 0.0371). CD45+proCol1+ and CXCR4+proCol1+ cells were detected in all examined biopsy samples from CP patients. Serum levels of CXCL12 were also higher in CP patients than controls (P = 0.0056), and tissue-infiltrating inflammatory cells intensely expressed CXCL12. Increased serum levels of Th2 cytokines (e.g., interleukin-13 [IL-13] and IL-10) were found in patients, and immunohistochemistry revealed a dominant infiltration of GATA-3+ cells, also indicating Th2 polarization; Th2-skewed responses are known to promote fibrocyte differentiation. CONCLUSION: Our findings indicate that fibrocytes are enriched in the peripheral blood of CP patients and infiltrate target lesions. The accumulation of fibrocytes in the pathologic tissue might be driven by CXCL12, and Th2-skewed immune responses are likely to facilitate their differentiation.


Assuntos
Fibroblastos/metabolismo , Fibrose Retroperitoneal/metabolismo , Células Th2/metabolismo , Estudos de Casos e Controles , Diferenciação Celular , Quimiocina CXCL12/metabolismo , Colágeno Tipo I/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/citologia , Fibroblastos/imunologia , Fibrose , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Inflamação , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-13/imunologia , Interleucina-13/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Receptores CXCR4/metabolismo , Fibrose Retroperitoneal/imunologia , Fibrose Retroperitoneal/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Células Th2/imunologia
17.
Gerontology ; 65(5): 485-494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31112977

RESUMO

OBJECTIVES: We investigated the clinical, electrocardiographic, and echocardiographic determinants of the cardiac status in nonagenarian patients. METHODS: We consecutively examined 654 Caucasian patients (232 males and 422 females) aged ≥90 years. All patients underwent clinical examination, ECG, and transthoracic echocardiography. RESULTS: Their average age was 92.5 ± 2.5 years. Patients were predominately female of older age (p < 0.0001 and p = 0.02, respectively). A history of cardiovascular disease was present in 78.4% of the participants. One third of the patients was hospitalized for cardiovascular causes, with females being twice as many (p < 0.0001). Females showed higher levels of serum cholesterol, triglycerides, and glycemia (p < 0.0001, p< 0.0001, and p = 0.04 respectively). Sinus rhythm was detected in 65%, and atrial fibrillation in 31% of the overall population. Heart rate, PR and corrected QT (QTc) intervals, right bundle branch block (RBBB) and RBBB associated with left anterior fascicular block (LAFB) were higher in males (p < 0.0001, p = 0.036, p = 0.009, p = 0.001, and p = 0.004, respectively). Aortic root dimension, left ventricular (LV) mass index, and indexed LV systolic-diastolic volumes were higher in males (p < 0.001, p < 0.0001, p < 0.001, and p < 0.0001, respectively). Women showed fewer LV segmental kinetic disorders (p = 0009) and higher LV ejection fraction (LVEF; p< 0.0001). Hyperuricemia was positively associated with a history of cardiovascular disease (r = 0.15), glycemia (r = 19), creatininemia (r = 0.50), uremia (r = 0.51), triglycerides (r = 0.19), PR interval (r = 0.14), and left bundle branch block (r = 0.11), and inversely associated with sinus rhythm (r = -0.14) and LVEF (r = -0.17). Diabetes was positively correlated with PR and QTc intervals (r = 0.14 and r = 0.10, respectively), and RBBB with LFAB (r = 0.10), and inversely correlated with LVEF (r = -0.10). CONCLUSIONS: We found a remarkable presence of cardiovascular risk factors, ECG, and structural alterations in hospitalized nonagenarians, which presents more commonly in males.


Assuntos
Fibrilação Atrial/epidemiologia , Bloqueio de Ramo/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hiperuricemia/epidemiologia , Volume Sistólico , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , Diabetes Mellitus/epidemiologia , Ecocardiografia , Eletrocardiografia , Feminino , Hospitalização , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Distribuição por Sexo , Triglicerídeos/sangue , Uremia/epidemiologia
18.
Acta Cardiol ; 74(6): 501-507, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30507282

RESUMO

Background: We aimed to depict the electrocardiographic and echocardiographic aspects in patients before elective major vascular surgery.Methods: We evaluated through standard 12 lead electrocardiography and transthoracic echocardiography 469 patients with asymptomatic large abdominal aortic aneurysm (AAA), 334 with critical carotid stenosis (CAS), and 238 with advanced peripheral artery disease (PAD) before surgical revascularization.Results: Patients with AAA were predominantly males (p < .001) with normal sinus rhythm (p = .026), were more affected by atrioventricular block (p = .033) and left anterior fascicular block (p < .001). They also presented larger aortic root size (p < .001) and septal hypertrophy (p = .036), in addition, atrial fibrillation was less frequent in the same group (p = .023). Patients with CAS were of older age (p < .001) with a substantial number of females (p < .001). They presented less left ventricular segmental kinetic disorders and fewer dilated ventricles (p = .004 and p < .001 respectively). Finally, those with PAD had reduced septal and posterior wall thickness (p < .01, p = .009 respectively), greater mitral and aortic annular calcification (p < .001), and were more affected by previous myocardial infarction (p < .001). The PR interval, left anterior fascicular block and aortic root size were independently associated with aneurysm, previous myocardial infarction with PAD, while smaller left ventricular end systolic volumes with carotid artery stenosis.Conclusions: Patients with AAA were mostly affected by cardiac conduction disorders, septal hypertrophy, aortic root dilation and less affected by atrial fibrillation. Patients with CAS were older with more normal sized ventricles, whereas, previous myocardial infarction was most common amongst patients with peripheral artery disease.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Estenose das Carótidas/diagnóstico , Ecocardiografia , Eletrocardiografia , Cardiopatias/diagnóstico , Doença Arterial Periférica/diagnóstico , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Procedimentos Cirúrgicos Eletivos , Feminino , Nível de Saúde , Cardiopatias/complicações , Cardiopatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Procedimentos Cirúrgicos Vasculares/efeitos adversos
19.
Viruses ; 10(9)2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30231575

RESUMO

Human cytomegalovirus (HCMV) is a highly prevalent opportunistic agent in the world population, which persists as a latent virus after a primary infection. Besides the well-established role of this agent causing severe diseases in immunocompromised individuals, more recently, HCMV has been evoked as a possible factor contributing to the pathogenesis of autoimmune diseases such as systemic sclerosis (SSc). The interplay between HCMV and immune surveillance is supposed to become unbalanced in SSc patients with expanded anti-HCMV immune responses, which are likely involved in the exacerbation of inflammatory processes. In this study, blood samples from a cohort of SSc patients vs. healthy subjects were tested for anti-HCMV immune responses (IgM, IgG antibodies, and T cells to peptide pools spanning the most immunogenic HCMV proteins). Statistically significant increase of HCMV-specific CD8+ T cell responses in SSc patients vs. healthy subjects was observed. Moreover, significantly greater HCMV-specific CD8+ T cell responses were found in SSc patients with a longer disease duration and those with higher modified Rodnan skin scores. Given the known importance of T cells in the development of SSc and that this virus may contribute to chronic inflammatory diseases, these data support a relevant role of HCMV-specific CD8+ T cell responses in SSc pathogenesis.


Assuntos
Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Adulto , Idoso , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/etiologia , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia , Pele/imunologia , Pele/metabolismo , Pele/patologia
20.
Environ Health ; 16(1): 130, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29212512

RESUMO

CORRECTION: After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

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