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1.
Adv Exp Med Biol ; 1408: 147-162, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37093426

RESUMO

Adequate iodine nutrition is fundamental for all humans and is critical during pregnancy and lactation due to iodine forms part of the structure of thyroid hormones (THs) and it is required for THs function. Iodine is a scarce micronutrient that must be obtained from the diet. Sufficient iodine can be found in the nature from seafood and given it is not frequently consumed by Chileans, public health policies state that table salt in Chile must be iodized. Health plans must be monitored to determine if the intake of iodine is being appropriated and the population has not fallen in deficiency or excess. The aim of this work was to evaluate iodine intake in 26 women at the third trimester of pregnancy. Pregnant women are resident from El Bosque a low-income County located in Santiago de Chile. These Chilean pregnant women were recruited by nutritionist at the Centros de Salud familiar (CESFAM). A 24 h dietary recall (24 h-DR) was applied to them to evaluate iodine intake. Samples of urine and blood were taken by health professionals to analyze parameters of thyroid function and to measure urine iodine concentration (UIC). The survey analysis showed that the iodine consumption in these pregnant women derived mainly from salt, bread and milk and not from seafood. The survey analysis indicated that iodine intake was above the requirements for pregnant women. However, the average UIC indicated that iodine intake was adequate, suggesting the need to find a better parameter to determine iodine intake in pregnant women.


Assuntos
Iodo , Terceiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Iodo/sangue , Iodo/urina , Terceiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/urina , Ingestão de Alimentos , Chile , Estudos de Coortes , Pobreza , Glândula Tireoide/fisiologia
2.
Int J Mol Sci ; 24(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37240413

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/patologia , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Cálcio da Dieta , Canais de Cálcio Tipo L
3.
Crit Rev Food Sci Nutr ; 62(6): 1466-1479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33226264

RESUMO

Adequate iodine nutrition is crucial for all mammals by playing his starring role as a component of thyroid hormones, which are key regulators of cellular processes for life such as differentiation, growth, function, and metabolism. Deficiency or excess of iodine in the diet are worldwide highly frequent conditions that are responsible of health problems like hypothyroidism, hypothyroxinemia, goiter, thyroiditis, hyperthyroidism, and autoimmune thyroid diseases among others. The incorporation of iodine in salt or other nutrients resolved the consequences of severe iodine deficiency like goiter, cretinism. However, this strategy in several countries led to other ailments like Hashimoto autoimmune thyroiditis, hyperthyroidism, and hypothyroidism. The goal of this review is to analyze and discuss the different aspects of iodine nutrition for human health comprising its biological role through thyroid hormones, pathogen control, and the regulation of the intestinal microbiota.


Assuntos
Bócio , Hipertireoidismo , Hipotireoidismo , Iodo , Animais , Humanos , Micronutrientes
4.
Parasitol Res ; 121(5): 1295-1304, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35230547

RESUMO

Zoonotic larvae of the family Anisakidae found in several fish species represent a serious risk in public health since they may cause food-borne anisakidosis in humans. Chile has culinary preferences including eating raw fish in many traditional preparations. In the present study, a total of 180 fish specimens representing three different fish species, i.e., Chilean hake (Merluccius gayi), snoek (Thyrsites atun), and sea bream (Brama australis), were caught at central coast of Chile. Parasitological examination was performed on musculature and abdominal cavity for subsequent extraction and quantification of anisakid larvae. Estimation of infection parameters, such as prevalence, was performed indicating 100% (CI: 0.94-1.0) prevalence of anisakid L3 in Chilean hakes and snoeks. Moreover, sea breams reached a prevalence of 35% (CI: 0.23-0.48). Prevalence of anisakid larvae in muscle was also analyzed showing values of 18.6% (CI: 0.097-0.309) in Chilean hakes, 15% (CI: 0.07-0.26) in snoeks, and 1.7% (CI: 0-0.089) in sea breams. Meanwhile, prevalence of anisakid larvae in internal organs showed highest values for peritoneum (100% and 83.3%) for snoeks and Chilean hakes, respectively, for liver (96.7%) and gonads (86.6%) in Chilean hakes, and for intestine (98.3%) in snoeks. Molecular analysis of collected anisakid L3 unveiled presence of two potentially zoonotic nematode species, i.e., Pseudoterranova cattani and Anisakis pegreffii. P. cattani was found in Chilean hakes and snoeks being the first molecular host species report for Chilean snoeks. Besides, A. pegreffii was also identified in these species being the first molecular report on this regard. These findings are relevant for better understanding of epidemiology of anisakiasis in Chilean coasts and for public health issues considering potential risk of human population due to its culinary preferences in eating raw fish.


Assuntos
Anisaquíase , Anisakis , Ascaridoidea , Doenças dos Peixes , Gadiformes , Perciformes , Animais , Anisaquíase/epidemiologia , Anisaquíase/veterinária , Anisakis/genética , Ascaridoidea/genética , Chile/epidemiologia , Doenças dos Peixes/epidemiologia , Peixes , Humanos , Larva/genética , Prevalência
5.
Int J Mol Sci ; 23(12)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35743229

RESUMO

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood-brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (ß and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.


Assuntos
Barreira Hematoencefálica , Laminina , Biomarcadores/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Humanos , Laminina/metabolismo , Doenças Neuroinflamatórias
6.
Int J Mol Sci ; 23(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36362415

RESUMO

Alzheimer's disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate in several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress and lipid metabolism (along with a critical role in apolipoprotein E function). Current evidence shows that astrocytes have both neuroprotective and neurotoxic effects depending on the disease stage and microenvironmental factors. Furthermore, astrocytes appear to be affected by the presence of amyloid-beta (Aß), with alterations in calcium levels, gliotransmission and proinflammatory activity via RAGE-NF-κB pathway. In addition, astrocytes play an important role in the metabolism of tau and clearance of Aß through the glymphatic system. In this review, we will discuss novel pharmacological and non-pharmacological treatments focused on astrocytes as therapeutic targets for AD. These interventions include effects on anti-inflammatory/antioxidant systems, glutamate activity, lipid metabolism, neurovascular coupling and glymphatic system, calcium dysregulation, and in the release of peptides which affects glial and neuronal function. According to the AD stage, these therapies may be of benefit in either preventing or delaying the progression of the disease.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Neurônios/metabolismo
7.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946948

RESUMO

Neurodegenerative diseases are characterized by increased permeability of the blood-brain barrier (BBB) due to alterations in cellular and structural components of the neurovascular unit, particularly in association with neuroinflammation. A previous screening study of peptide ligands to identify molecular alterations of the BBB in neuroinflammation by phage-display, revealed that phage clone 88 presented specific binding affinity to endothelial cells under inflammatory conditions in vivo and in vitro. Here, we aimed to identify the possible target receptor of the peptide ligand 88 expressed under inflammatory conditions. A cross-link test between phage-peptide-88 with IL-1ß-stimulated human hCMEC cells, followed by mass spectrometry analysis, was used to identify the target of peptide-88. We modeled the epitope-receptor molecular interaction between peptide-88 and its target by using docking simulations. Three proteins were selected as potential target candidates and tested in enzyme-linked immunosorbent assays with peptide-88: fibronectin, laminin subunit α5 and laminin subunit ß-1. Among them, only laminin subunit ß-1 presented measurable interaction with peptide-88. Peptide-88 showed specific interaction with laminin subunit ß-1, highlighting its importance as a potential biomarker of the laminin changes that may occur at the BBB endothelial cells under pathological inflammation conditions.


Assuntos
Barreira Hematoencefálica , Células Endoteliais/metabolismo , Inflamação/metabolismo , Laminina/metabolismo , Animais , Bacteriófago M13 , Biomarcadores , Células Cultivadas , Reagentes de Ligações Cruzadas , Fibronectinas/metabolismo , Ontologia Genética , Humanos , Interleucina-1beta/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Biblioteca de Peptídeos , Ligação Proteica , Conformação Proteica , Mapeamento de Interação de Proteínas , Ratos
8.
Neural Plast ; 2018: 2941783, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405709

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It compromises patients' daily activities owing to progressive cognitive deterioration, which has elevated direct and indirect costs. Although AD has several risk factors, aging is considered the most important. Unfortunately, clinical diagnosis is usually performed at an advanced disease stage when dementia is established, making implementation of successful therapeutic interventions difficult. Current biomarkers tend to be expensive, insufficient, or invasive, raising the need for novel, improved tools aimed at early disease detection. AD is characterized by brain atrophy due to neuronal and synaptic loss, extracellular amyloid plaques composed of amyloid-beta peptide (Aß), and neurofibrillary tangles of hyperphosphorylated tau protein. The visual system and central nervous system share many functional components. Thus, it is plausible that damage induced by Aß, tau, and neuroinflammation may be observed in visual components such as the retina, even at an early disease stage. This underscores the importance of implementing ophthalmological examinations, less invasive and expensive than other biomarkers, as useful measures to assess disease progression and severity in individuals with or at risk of AD. Here, we review functional and morphological changes of the retina and visual pathway in AD from pathophysiological and clinical perspectives.


Assuntos
Doença de Alzheimer/fisiopatologia , Retina/fisiopatologia , Transtornos da Visão/fisiopatologia , Vias Visuais/fisiopatologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Progressão da Doença , Humanos , Placa Amiloide/metabolismo , Placa Amiloide/fisiopatologia , Retina/metabolismo , Transtornos da Visão/diagnóstico , Transtornos da Visão/metabolismo , Vias Visuais/metabolismo , Proteínas tau/metabolismo
9.
Adv Clin Chem ; 121: 1-88, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38797540

RESUMO

The blood-brain barrier (BBB) is a dynamic interface that regulates the exchange of molecules and cells between the brain parenchyma and the peripheral blood. The BBB is mainly composed of endothelial cells, astrocytes and pericytes. The integrity of this structure is essential for maintaining brain and spinal cord homeostasis and protection from injury or disease. However, in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis, the BBB can become compromised thus allowing passage of molecules and cells in and out of the central nervous system parenchyma. These agents, however, can serve as biomarkers of BBB permeability and neuronal damage, and provide valuable information for diagnosis, prognosis and treatment. Herein, we provide an overview of the BBB and changes due to aging, and summarize current knowledge on biomarkers of BBB disruption and neurodegeneration, including permeability, cellular, molecular and imaging biomarkers. We also discuss the challenges and opportunities for developing a biomarker toolkit that can reliably assess the BBB in physiologic and pathophysiologic states.


Assuntos
Biomarcadores , Barreira Hematoencefálica , Barreira Hematoencefálica/metabolismo , Humanos , Biomarcadores/metabolismo , Animais
10.
EJNMMI Phys ; 11(1): 33, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564100

RESUMO

BACKGROUND: Developments in transarterial radioembolization led to the conception of new microspheres loaded with holmium-166 (166Ho). However, due to the complexity of the scatter components in 166Ho single photon emission computed tomography (SPECT), questions about image quality and dosimetry are emerging. The aims of this work are to investigate the scatter components and correction methods to propose a suitable solution, and to evaluate the impact on image quality and dosimetry including Monte-Carlo (MC) simulations, phantom, and patient data. METHODS: Dual energy window (DEW) and triple energy window (TEW) methods were investigated for scatter correction purposes and compared using Contrast Recovery Coefficients (CRC) and Contrast to Noise Ratios (CNR). First, MC simulations were carried out to assess all the scatter components in the energy windows used, also to confirm the choice of the parameter needed for the DEW method. Then, MC simulations of acquisitions of a Jaszczak phantom were conducted with conditions mimicking an ideal scatter correction. These simulated projections can be reconstructed and compared with real acquisitions corrected by both methods and then reconstructed. Finally, both methods were applied on patient data and their impact on personalized dosimetry was evaluated. RESULTS: MC simulations confirmed the use of k = 1 for the DEW method. These simulations also confirmed the complexity of scatter components in the main energy window used with a high energy gamma rays component of about half of the total counts detected, together with a negligible X rays component and a negligible presence of fluorescence. CRC and CNR analyses, realized on simulated scatter-free projections of the phantom and on scatter corrected acquisitions of the same phantom, suggested an increased efficiency of the TEW method, even at the price of higher level of noise. Finally, these methods, applied on patient data, showed significant differences in terms of non-tumoral liver absorbed dose, non-tumoral liver fraction under 50 Gy, tumor absorbed dose, and tumor fraction above 150 Gy. CONCLUSIONS: This study demonstrated the impact of scatter correction on personalized dosimetry on patient data. The use of a TEW method is proposed for scatter correction in 166Ho SPECT imaging.

11.
Eur Thyroid J ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38320401

RESUMO

In 2022, the European Chemicals Agency (ECHA) made a statement concluding that iodine is an endocrine disruptor (ED). "We stress the fact that the ECHA opinion ECHA/BPC/357/2022 is based on their misguidedly zooming in on exclusively the biocidal products (e.g., hand disinfectants, disinfection of animals' teats/udder, embalming fluids before cremation, etc.) that contain molecular iodine (I2), entirely neglecting [see the 2013 ECHA Regulation (EU) n°528/2012 describing iodine as being of "great importance for human health". Clearly, the current sweeping and erroneous classification of "iodine" as an endocrine disruptor is ill-advised. We moreover call upon the scientific and medical community at large to use the accurate scientific nomenclature, i.e., iodide or iodate instead of "iodine" when referring to iodized salts and food prepared there with. Drugs, diagnostic agents, and synthetic chemicals containing the element iodine in the form of covalent bonds must be correctly labelled ''iodinated'', if possible, using each time their distinctive and accurate chemical or pharmacological name.

12.
PLoS One ; 19(4): e0302031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603692

RESUMO

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.


Assuntos
Barreira Hematoencefálica , Laminina , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Laminina/metabolismo , Doenças Neuroinflamatórias , Células Endoteliais/metabolismo , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Imageamento por Ressonância Magnética/métodos
13.
Neurochem Res ; 38(6): 1190-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23011205

RESUMO

A non-selective antihistamine, dimebon, has recently emerged as a potential treatment for Alzheimer's disease and Huntington's disease. Dimebon exerts several effects in addition to its anti-histaminergic effect, and of particular interest is its ability to enhance cognitive function in several models. The mechanism underlying this is unknown though it has been suggested that it may be associated with its anti-cholinergic action. Dimebon has also been reported to be neuroprotective, perhaps as a result of its ability to stabilize mitochondria. We considered that these effects might impact on the well-described age-related impairment in spatial learning and therefore examined the effect of repeated administration of dimebon on performance of young and aged animals in the Morris water maze. Whereas a clear age-related deficit was observed, dimebon failed to exert any effect on performance. Similarly, dimebon exerted no effect on the age-related increase in hippocampal expression of several markers of microglial and astroglial activation. We conclude that, despite its cognitive enhancing effects in some models, dimebon failed to modulate the deficit in spatial learning in aged rats and the evidence suggests that the drug does not possess anti-inflammatory properties.


Assuntos
Gliose/tratamento farmacológico , Indóis/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Envelhecimento , Animais , Cognição/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Indóis/uso terapêutico , Masculino , Ratos , Ratos Wistar
14.
Br J Nutr ; 109(12): 2276-84, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23084115

RESUMO

Low iodine intake during pregnancy may cause thyroid dysfunction in pregnant women and their newborn. In the present study, iodine status among a nation-wide representative sample of Belgian pregnant women in the first and third trimester of pregnancy was determined, and determinants of iodine status were assessed 1 year after the introduction of bread fortified with iodised salt. The women were selected according to a multistage proportionate-to-size sampling design. Urine samples were collected and a general questionnaire was completed face to face with the study nurse. The median urinary iodine concentration (UIC) among pregnant women (n 1311) was 124.1mg/l and 122.6 mg/g creatinine when corrected for urinary creatinine. The median UIC in the first trimester (118.3 mg/l) was significantly lower than that in the third trimester (131.0 mg/l) but significantly higher than among non-pregnant women (84.8 mg/l). Iodine-containing supplement intake was reported by 60.8% of the women and 57.4% of the women took this supplement daily. The risk of iodine deficiency was significantly higher in younger women, in women not taking iodine-containing supplements, with low consumption of milk and dairy drinks and during autumn. Women with a higher BMI had a higher risk of iodine deficiency but the risk was lower in women who reported alcohol consumption. The median UIC during pregnancy indicates iodine deficiency in Belgium and some women are at a higher risk of deficiency. The current low iodine intake in women of childbearing age precludes the correction of iodine deficiency in pregnant women supplemented with multivitamins containing 150 mg iodine as recommended.


Assuntos
Creatina/urina , Alimentos Fortificados , Iodo/deficiência , Cloreto de Sódio na Dieta , Adulto , Bélgica/epidemiologia , Estudos Transversais , Deficiências Nutricionais/epidemiologia , Inquéritos sobre Dietas , Suplementos Nutricionais , Feminino , Humanos , Iodo/administração & dosagem , Iodo/urina , Modelos Logísticos , Gravidez , Primeiro Trimestre da Gravidez/urina , Terceiro Trimestre da Gravidez/urina , Valores de Referência , Risco , Estatísticas não Paramétricas , Vitaminas/administração & dosagem
15.
Cir Esp (Engl Ed) ; 101 Suppl 4: S43-S51, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37979942

RESUMO

Sleeve gastrectomy (SG) is the most common bariatric surgery worldwide and has shown to cause de novo or worsen symptoms of gastroesophageal reflux disease (GERD). Esophageal motility and physiology studies are mandatory in bariatric and foregut centers. The predisposing factors in post-SG patients are disruption of His angle, resection of gastric fold and gastric fundus, increased gastric pressure, resection of the gastric antrum, cutting of the sling fibers and pyloric spasm. There are symptomatic complications due to sleeve morphology as torsion, incisura angularis stenosis, kinking and dilated fundus. In this article, we present recommendations, surgical technique and patient selection flow diagram for SG and avoid de novo or worsening GERD.


Assuntos
Cirurgia Bariátrica , Refluxo Gastroesofágico , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Refluxo Gastroesofágico/diagnóstico , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Estômago , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos
16.
Eur Thyroid J ; 12(6)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37992294

RESUMO

Objectives: The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients. Methods: A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 - scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis. Results: More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03-0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1-35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12). Conclusions: Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Tireotropina
17.
Eur J Hybrid Imaging ; 7(1): 12, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37414964

RESUMO

BACKGROUND: Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC). AIM: We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry. METHODS: This is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach. RESULTS: Between February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3-55) in group A and 21 months (range 4-39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p = 0.007) and at 6 months (77.8% vs. 22.2%, p = 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p = 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit90Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity. CONCLUSIONS: Our study aligns to recent literature and confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment.

18.
Clin Infect Dis ; 55(7): 1004-11, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22715179

RESUMO

BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. METHODS: Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. RESULTS: Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P ≤ .02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P ≤ .04) of ART. Vitamin D deficiency (total 25(OH)D <75 nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P = .004) of ART. Severe vitamin D deficiency (total 25(OH)D <25 nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. CONCLUSIONS: CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.


Assuntos
Corticosteroides/administração & dosagem , Citocinas/sangue , Infecções por HIV/complicações , Síndrome Inflamatória da Reconstituição Imune/patologia , Fatores Imunológicos/administração & dosagem , Tuberculose/complicações , Deficiência de Vitamina D/epidemiologia , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Masculino , Estudos Prospectivos , Tuberculose/patologia
19.
Eur J Nutr ; 51(4): 477-82, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21822925

RESUMO

PURPOSE: To explore whether there are regional differences in iodine status and in prevalence of thyroid diseases in the two main regions of Belgium. METHODS: A national survey of iodine status among children was performed in 1998. The raw data of this survey were reanalyzed to explore regional differences. The total number of thyroidectomies, carried out for multinodular goiter or solitary nodules, was obtained from the Minimal Clinical Summary hospital discharge database. Percentage of people with thyroid diseases going to the general practitioner or the specialist was assessed by means of data about the number of adults using anti-thyroid medications. Food consumption patterns were explored using national food consumption data. RESULTS: In Flanders, median urinary iodine concentration (UIC) was higher than in Wallonia, 84 µg/L (n = 1,316) and 78 µg/L (n = 1,268), respectively (p < 0.001). There were no differences in goiter prevalence and thyroid volume between the regions among children. Data from the food consumption survey showed a significant higher consumption of seafood in Flanders compared to Wallonia. Further, it was observed that the number of thyroidectomies, carried out for MNG or solitary nodules, and the use of anti-thyroid medication were significantly higher in Wallonia than in Flanders. CONCLUSION: Iodine status in children was found slightly different in both regions of the country. This finding is in agreement with a higher incidence of thyroidectomies and more extensive use of anti-thyroid medications in the adult population in the region with the lowest iodine excretion.


Assuntos
Bócio Nodular/epidemiologia , Iodo/deficiência , Estado Nutricional , Nódulo da Glândula Tireoide/epidemiologia , Adulto , Antitireóideos/uso terapêutico , Bélgica/epidemiologia , Criança , Bases de Dados Factuais , Prescrições de Medicamentos , Feminino , Bócio Nodular/tratamento farmacológico , Bócio Nodular/etiologia , Bócio Nodular/cirurgia , Inquéritos Epidemiológicos , Humanos , Incidência , Iodo/urina , Masculino , Tamanho do Órgão , Prevalência , Alimentos Marinhos , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/tratamento farmacológico , Nódulo da Glândula Tireoide/etiologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia
20.
Front Mol Neurosci ; 15: 937789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35866158

RESUMO

Taurine is considered the most abundant free amino acid in the brain. Even though there are endogenous mechanisms for taurine production in neural cells, an exogenous supply of taurine is required to meet physiological needs. Taurine is required for optimal postnatal brain development; however, its brain concentration decreases with age. Synthesis of taurine in the central nervous system (CNS) occurs predominantly in astrocytes. A metabolic coupling between astrocytes and neurons has been reported, in which astrocytes provide neurons with hypotaurine as a substrate for taurine production. Taurine has antioxidative, osmoregulatory, and anti-inflammatory functions, among other cytoprotective properties. Astrocytes release taurine as a gliotransmitter, promoting both extracellular and intracellular effects in neurons. The extracellular effects include binding to neuronal GABAA and glycine receptors, with subsequent cellular hyperpolarization, and attenuation of N-methyl-D-aspartic acid (NMDA)-mediated glutamate excitotoxicity. Taurine intracellular effects are directed toward calcium homeostatic pathway, reducing calcium overload and thus preventing excitotoxicity, mitochondrial stress, and apoptosis. However, several physiological aspects of taurine remain unclear, such as the existence or not of a specific taurine receptor. Therefore, further research is needed not only in astrocytes and neurons, but also in other glial cells in order to fully comprehend taurine metabolism and function in the brain. Nonetheless, astrocyte's role in taurine-induced neuroprotective functions should be considered as a promising therapeutic target of several neuroinflammatory, neurodegenerative and psychiatric diseases in the near future. This review provides an overview of the significant relationship between taurine and astrocytes, as well as its homeostatic and neuroprotective role in the nervous system.

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