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2.
Clin Park Relat Disord ; 10: 100246, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444738

RESUMO

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare neurological emergency that shares clinical features with neuroleptic malignant syndrome. It is usually due to sudden deprivation of dopaminergic treatment, although there are cases related to failure of the deep brain stimulation system.

4.
Int J Infect Dis ; 138: 97-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38008352

RESUMO

OBJECTIVES: We aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants' peripheral blood is associated with bronchiolitis progression. METHODS: We conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room. RESULTS: Infants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007). CONCLUSIONS: An inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis.


Assuntos
Bronquiolite , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Feminino , Humanos , Lactente , Masculino , Bronquiolite/genética , Bronquiolite/complicações , Bronquiolite/metabolismo , Quimiocinas , Expressão Gênica , Ligantes , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/genética , Vírus Sincicial Respiratório Humano/genética , Fator de Necrose Tumoral alfa/genética
5.
Nat Commun ; 14(1): 7689, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001107

RESUMO

Multimorbidity -understood as the occurrence of chronic diseases together- represents a major challenge for healthcare systems due to its impact on disability, quality of life, increased use of services and mortality. However, despite the global need to address this health problem, evidence is still needed to advance our understanding of its clinical and social implications. Our study aims to characterise multimorbidity patterns in a dataset of 1,375,068 patients residing in southern Spain. Combining LCA techniques and geographic information, together with service use, mortality, and socioeconomic data, 25 chronicity profiles were identified and subsequently characterised by sex and age. The present study has led us to several findings that take a step forward in this field of knowledge. Specifically, we contribute to the identification of an extensive range of at-risk groups. Moreover, our study reveals that the complexity of multimorbidity patterns escalates at a faster rate and is associated with a poorer prognosis in local areas characterised by lower socioeconomic status. These results emphasize the persistence of social inequalities in multimorbidity, highlighting the need for targeted interventions to mitigate the impact on patients' quality of life, healthcare utilisation, and mortality rates.


Assuntos
Multimorbidade , Qualidade de Vida , Humanos , Espanha/epidemiologia , Classe Social , Aceitação pelo Paciente de Cuidados de Saúde , Doença Crônica
6.
Semin Oncol ; 50(6): 149-154, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37914616

RESUMO

PURPOSE: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. We aim to identify the main barriers hindering clinical recommendations implementation and propose consensus solutions to improve OIC control in cancer patients. METHODS: Following collaborative and prioritization techniques, a scientific committee generated statements addressing possible barriers to optimal OIC management (related to patients, health providers and health care system), and potential interventions to overcome these barriers. An expert panel of 36 oncologists assessed the statements to reach a consensus. RESULTS: The survey consisted of 70 statements. Consensus was reached on 12/45 items related to barriers (26.6%) and on 19/25 items about corrective interventions (76%). The panel considered that patients are unaware of the existence of a specific OIC treatment, and their information sources are highly variable and unreliable. Regarding health providers, the panel considered that the oncologists prioritize symptoms such as diarrhea, pain, anxiety, or other treatment toxicities, over constipation. Work overload and bureaucratic requirements were the main barriers related to health care system. Regarding potential interventions, best-rated proposals included specific training programs development for primary care physicians and nurses, and multiplatform informative resources development for patients and caregivers, including precisely written instructions about OIC recognition and management. Oncologists assessed positively measures aiming to improve coordination between primary care physicians and oncologists, and nursing consultations implementation. The panel considered useful the OIC treatment algorithms simplification. CONCLUSIONS: The expert panel identified the main barriers to optimal OIC management and suggested some feasible approaches to overcome these barriers.


Assuntos
Neoplasias , Constipação Induzida por Opioides , Humanos , Constipação Induzida por Opioides/tratamento farmacológico , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/terapia , Constipação Intestinal/diagnóstico , Analgésicos Opioides/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Inquéritos e Questionários
7.
J Oncol Pharm Pract ; : 10781552231194077, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563932

RESUMO

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy. METHODS: Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ2 test. RESULTS: Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, p = 0.0115) and delayed phase (97.6% vs 90.7%, p = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, p = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, p = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, p = 0.70). CONCLUSIONS: TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session.

8.
Healthcare (Basel) ; 11(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37372868

RESUMO

We are interested in observing how temperature differences between the wound bed and perilesional skin are related to the healing process in primary care patients with wounds. Multisite prospective cohort study with one-year follow-up in the Metropolitan North area of Barcelona. Recruitment of patients over 18 years with an open wound will take place from January 2023 to September 2023. Temperature checks will be conducted on a weekly basis at control visits and wound care. The following variables will be measured: Percentage reduction of wound area over time, thermal index, the Kundin Wound Gauge, and the Resvech 2.0 Scale. The temperature will be measured weekly using a handheld thermometer and mesh grid to frame the temperature points. The healing trajectory will also be monitored on a monthly basis via photographic imaging, the Resvech Scale, calculation of wound size, percentage reduction of wound area over time, and thermal index for one year of follow-up or until the wound is cured. This study may represent a turning point for its introduction into primary care. Early diagnosis of wound complications would facilitate treatment decision-making for healthcare professionals, thus improving the management of resources related to chronic wounds.

9.
Transfus Apher Sci ; 62(3): 103722, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37169697

RESUMO

PURPOSE: Caplacizumab was licensed for acquired thrombotic thrombocytopenic purpura (aTTP) based on prospective controlled trials. Real-world evidence is crucial in rare diseases. We aim to describe a patient population with aTTP, receiving caplacizumab in a real-world setting, reporting their outcomes, including safety and tolerability, and contrasting them with a historical cohort from our center. METHODS: We describe data collected retrospectively from 2012 to 2022 for 16 patients with aTTP (8 received caplacizumab and 8 the historical standard-of-care). Patients' characteristics and outcomes were compared between groups. RESULTS: Patients' demographic and baseline characteristics were similar in both groups. Caplacizumab led to a rapid normalization of the platelet count of 3.5 (IQR, 2-6) versus 16 (IQR, 9.5-23.5) days in the historical cohort: (p = .002). The median number of plasma exchanges and the length of days requiring them, between the caplacizumab group versus the historical cohort, was 6 (IQR, 6-10) versus 19.5 (IQR, 12.5-29.5) plasma exchanges (p = .006); and 9 (IQR, 8.5-13.5) versus 22 (15-31) days (p = .049), respectively. There were no refractory cases in the caplacizumab group in comparison with 37.5 % in the historical cohort. None of patients treated with caplacizumab experienced a recurrence after 1081 (IQR, 511-3125) days of follow-up. Safety was in line with data reported in clinical trials, with mild adverse events (mostly grade≤2). CONCLUSION: We provided real-world evidence in the treatment of aTTP, confirming the results obtained in clinical trials. Caplacizumab reduced the time to platelet count recovery and the number and length of plasma exchanges.


Assuntos
Púrpura Trombocitopênica Trombótica , Humanos , Troca Plasmática , Estudos Prospectivos , Púrpura Trombocitopênica Trombótica/terapia , Estudos Retrospectivos
10.
Front Public Health ; 11: 1081518, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37050950

RESUMO

Social determinants of multimorbidity are poorly understood in clinical practice. This review aims to characterize the different multimorbidity patterns described in the literature while identifying the social and behavioral determinants that may affect their emergence and subsequent evolution. We searched PubMed, Embase, Scopus, Web of Science, Ovid MEDLINE, CINAHL Complete, PsycINFO and Google Scholar. In total, 97 studies were chosen from the 48,044 identified. Cardiometabolic, musculoskeletal, mental, and respiratory patterns were the most prevalent. Cardiometabolic multimorbidity profiles were common among men with low socioeconomic status, while musculoskeletal, mental and complex patterns were found to be more prevalent among women. Alcohol consumption and smoking increased the risk of multimorbidity, especially in men. While the association of multimorbidity with lower socioeconomic status is evident, patterns of mild multimorbidity, mental and respiratory related to middle and high socioeconomic status are also observed. The findings of the present review point to the need for further studies addressing the impact of multimorbidity and its social determinants in population groups where this problem remains invisible (e.g., women, children, adolescents and young adults, ethnic groups, disabled population, older people living alone and/or with few social relations), as well as further work with more heterogeneous samples (i.e., not only focusing on older people) and using more robust methodologies for better classification and subsequent understanding of multimorbidity patterns. Besides, more studies focusing on the social determinants of multimorbidity and its inequalities are urgently needed in low- and middle-income countries, where this problem is currently understudied.


Assuntos
Doenças Cardiovasculares , Multimorbidade , Masculino , Adolescente , Adulto Jovem , Criança , Humanos , Feminino , Idoso , Fatores Socioeconômicos , Determinantes Sociais da Saúde , Classe Social
11.
BMC Public Health ; 22(1): 2367, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36527103

RESUMO

BACKGROUND: Childhood obesity poses a global health challenge. In recent years, there has been an increase in interventions that begin in pregnancy, putting the concept of early programming and early risk factors into practice. The present study aims to update the findings regarding interventions in the first 1000 days of life. METHODS: A systematic review based on the PRISMA guidelines was carried out in PubMed, WoS, Scopus and CINAHL to obtain the articles to be analysed. We included those studies published between 2016 and 2021. Human interventions that started within the first 1000 days of life and acted on at least one programming factor were included. Once selected, coding and quantitative content analysis was carried out to obtain a profile of the interventions during the first 1000 days. RESULTS: From all screened articles, 51 unique interventions, which met the selection criteria, were included. The majority of interventions (81%) took place in high-income areas. Almost all (86%) were targeted at the general population. The majority (54%) started in the second trimester of pregnancy. A clear majority (61%) ended at the time of birth. 44% of the interventions included all pregnant women. Only 48% of these interventions were focused on improving the nutritional status of the offspring in the short term. Most interventions collected the baby's weight at birth (68%). CONCLUSIONS: It can be concluded that current interventions are not covering as many aspects as they should. Future research should be conducted more frequently in developing countries and target disadvantaged groups. These interventions should include all pregnant women, regardless of their nutritional status, aiming to cover as many programming factors as possible and extending through the first 1000 days of life, with body mass index or skinfolds as measures of effectiveness during this period.


Assuntos
Obesidade Infantil , Recém-Nascido , Criança , Humanos , Gravidez , Feminino , Obesidade Infantil/prevenção & controle , Índice de Massa Corporal , Fatores de Risco , Gestantes
12.
Artigo em Inglês | MEDLINE | ID: mdl-36554719

RESUMO

BACKGROUND: The challenge posed by multimorbidity makes it necessary to look at new forms of prevention, a fact that has become heightened in the context of the pandemic. We designed a questionnaire to detect multimorbidity patterns in people over 50 and to associate these patterns with mental and physical health, COVID-19, and possible social inequalities. METHODS: This was an observational study conducted through a telephone interview. The sample size was 1592 individuals with multimorbidity. We use Latent Class Analysis to detect patterns and SF-12 scale to measure mental and physical quality-of-life health. We introduced the two dimensions of health and other social determinants in a multinomial regression model. RESULTS: We obtained a model with five patterns (entropy = 0.727): 'Relative Healthy', 'Cardiometabolic', 'Musculoskeletal', 'Musculoskeletal and Mental', and 'Complex Multimorbidity'. We found some differences in mental and physical health among patterns and COVID-19 diagnoses, and some social determinants were significant in the multinomial regression. CONCLUSIONS: We identified that prevention requires the location of certain inequalities associated with the multimorbidity patterns and how physical and mental health have been affected not only by the patterns but also by COVID-19. These findings may be critical in future interventions by health services and governments.


Assuntos
COVID-19 , Multimorbidade , Humanos , Pandemias , Determinantes Sociais da Saúde , COVID-19/epidemiologia , Fatores Socioeconômicos
13.
SSM Popul Health ; 20: 101268, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36353098

RESUMO

Multimorbidity is associated with lower quality of life, greater disability and higher use of health services and is one of the main challenges facing governments in Europe. There is a need to identify and characterize patterns of chronic conditions and analyse their association with social determinants not only from an individual point of view but also from a collective point of view. This paper aims to respond to this knowledge gap by detecting patterns of chronic conditions and their social determinants in 19 European countries from a multilevel perspective. We used data from the ESS round 7. The final sample consisted of 18,933 individuals over 18 years of age, and patterns of multimorbidity from 14 chronic conditions were detected through Multilevel Latent Class Analysis, which also allows detecting similarities between countries. Gender, Age, Housing Location, Income Level and Educational Level were used as individual covariates to determine possible associations with social inequalities. The goodness-of-fit indices derived in a model with six multimorbidity patterns and five countries clusters. The six patterns were "Back, Digestive and Headaches", "Allergies and Respiratory", "Complex Multimorbidity", "Cancer and Cardiovascular", "Musculoskeletal" and "Cardiovascular"; the five clusters could be associated with some geographical areas or welfare states. Patterns showed significant differences in the covariates of interest, with differences in education and income being of particular interest. Some significant differences were found among patterns and the country groupings. Our findings show that chronic diseases tend to appear in a combined and interactive way, and socioeconomic differences in the occurrence of patterns are not only of the individual but also of group importance, emphasising how the welfare states in each country can influence in the health of their inhabitants.

14.
Nat Chem ; 14(7): 754-765, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35764792

RESUMO

Natural products that contain ortho-quinones show great potential as anticancer agents but have been largely discarded from clinical development because their redox-cycling behaviour results in general systemic toxicity. Here we report conjugation of ortho-quinones to a carrier, which simultaneously masks their underlying redox activity. C-benzylation at a quinone carbonyl forms a redox-inactive benzyl ketol. Upon a specific enzymatic trigger, an acid-promoted, self-immolative C-C bond-cleaving 1,6-elimination mechanism releases the redox-active hydroquinone inside cells. By using a 5-lipoxygenase modulator, ß-lapachone, we created cathepsin-B-cleavable quinone prodrugs. We applied the strategy for intracellular release of ß-lapachone upon antibody-mediated delivery. Conjugation of protected ß-lapachone to Gem-IgG1 antibodies, which contain the variable region of gemtuzumab, results in homogeneous, systemically non-toxic and conditionally stable CD33+-specific antibody-drug conjugates with in vivo efficacy against a xenograft murine model of acute myeloid leukaemia. This protection strategy could allow the use of previously overlooked natural products as anticancer agents, thus extending the range of drugs available for next-generation targeted therapeutics.


Assuntos
Antineoplásicos , Produtos Biológicos , Pró-Fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Camundongos , Oxirredução , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Quinonas
15.
J Oncol Pharm Pract ; 28(2): 362-372, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33573462

RESUMO

INTRODUCTION: The aim of this study is to compare productivity of the KIRO Oncology compounding robot in three hospital pharmacy departments and identify the key factors to predict and optimize automatic compounding time. METHODS: The study was conducted in three hospitals. Each hospital compounding workload and workflow were analyzed. Data from the robotic compounding cycles from August 2017 to July 2018 were retrospectively obtained. Nine cycle specific parameters and five productivity indicators were analysed in each site. One-to-one differences between hospitals were evaluated. Next, a correlation analysis between cycle specific factors and productivity indicators was conducted; the factors presenting a highest correlation to automatic compounding time were used to develop a multiple regression model (afterwards validated) to predict the automatic compounding time. RESULTS: A total of 2795 cycles (16367 preparations) were analysed. Automatic compounding time showed a relevant positive correlation (ǀrs|>0.40) with the number of preparations, number of vials and total volume per cycle. Therefore, these cycle specific parameters were chosen as independent variables for the mathematical model. Considering cycles lasting 40 minutes or less, predictability of the model was high for all three hospitals (R2:0.81; 0.79; 0.72). CONCLUSION: Workflow differences have a remarkable incidence in the global productivity of the automated process. Total volume dosed for all preparations in a cycle is one of the variables with greater influence in automatic compounding time. Algorithms to predict automatic compounding time can be useful to help users in order to plan the cycles launched in KIRO Oncology.


Assuntos
Antineoplásicos , Serviço de Farmácia Hospitalar , Procedimentos Cirúrgicos Robóticos , Robótica , Composição de Medicamentos , Humanos , Estudos Retrospectivos
16.
Angew Chem Int Ed Engl ; 60(44): 23750-23755, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34472678

RESUMO

We describe maleic-acid derivatives as robust cysteine-selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide and amido-ester derivatives proved to be efficient protein-labelling species with a common mechanism in which a spontaneous cyclization occurs upon addition to cysteine. Introduction of chlorine atoms in their structures triggers ring hydrolysis or further conjugation with adjacent residues, which results in conjugates that are completely resistant to retro-Michael reactions in the presence of biological thiols and human plasma. By controlling the microenvironment of the reactive site, we can control selectivity towards the hydrolytic pathway, forming homogeneous conjugates. The method is applicable to several scaffolds and enables conjugation of different payloads. The synthetic accessibility of these reagents and the mild conditions required for fast and complete conjugation together with the superior stability of the conjugates make this strategy an important alternative to maleimides in bioconjugation.


Assuntos
Diamida/química , Proteínas/química , Humanos , Modelos Moleculares , Estrutura Molecular
17.
Theranostics ; 11(14): 6983-7004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093866

RESUMO

Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce reactive astrogliosis in an attempt to preserve the neuronal network and re-establish glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote reactive astrogliosis and increase susceptibility of neurons to stress-induced apoptosis. Such effects could be reversed by ORY1001 treatment both in vitro and in vivo, paving the way for a new therapeutic approach for Type 2 Diabetes Mellitus.


Assuntos
Astrócitos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Gliose/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adulto , Animais , Sobrevivência Celular/efeitos dos fármacos , Proteínas Correpressoras/antagonistas & inibidores , Dieta Hiperlipídica , Proteína Glial Fibrilar Ácida/metabolismo , Glucose/metabolismo , Proteínas de Grupo de Alta Mobilidade/antagonistas & inibidores , Proteínas de Grupo de Alta Mobilidade/genética , Histona Desmetilases/antagonistas & inibidores , Humanos , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , RNA Interferente Pequeno , RNA-Seq
18.
J Neurol Sci ; 425: 117452, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33892278

RESUMO

BACKGROUND: Intermediate Alleles (IAs) are expansions of CAG repeats in the HTT gene between 27 and 35 repeats which pathogenic meaning remains controversial. They are present in the general population but there is an increasing number of cases with Huntington-like phenotype reported. METHODS: We reviewed the medical records of cases in our centre where the neurologist suspected Huntington's disease (HD) as one of the feasible diagnoses and genetic testing showed the number of CAG repeats was in the "intermediate range". We gathered the type of symptoms in all cases and the main neuroimaging findings when available. RESULTS: We found 14 cases, 8 males and 6 females, with average age at onset at 64 years old. Most cases exhibited some type of extrapyramidal symptoms. Cognitive and/or behavioral symptoms were also present in most cases (being depression, anxiety and cognitive impairment the most frequent ones). In one case we found deposits of iron in the basal ganglia in the MRI, and in another case we found diffuse cortical hypometabolism with predominantly frontal bilateral involvement and bilateral focal deficit of both caudate and thalamus in the FDG-PET. CONCLUSION: The clinical and neuroimaging findings of some cases with IA in this series are compatible with the clinical picture of HD but also with several other alternative diagnoses. Therefore we can not establish association between IA and HD. Larger series with more comprehensive diagnostic workout and neuropathological studies are needed to confirm or rule out whether IAs in the HTT gene may cause HD.


Assuntos
Doença de Huntington , Alelos , Feminino , Testes Genéticos , Humanos , Proteína Huntingtina/genética , Doença de Huntington/diagnóstico por imagem , Doença de Huntington/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Repetições de Trinucleotídeos
19.
Blood Transfus ; 19(1): 45-53, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32530402

RESUMO

BACKGROUND: Autologous serum eye drops, produced by separation of liquid and cellular components of the patient's blood, contain biological nutrients present in natural tears. The aim of this study was to analyse changes in conjunctival impression cytology with transfer and both lachrymal stability and flow tests in patients with dry eye disease after treatment with autologous serum eye drops. MATERIALS AND METHODS: Conjunctival impression cytology and lachrymal flow and stability tests, namely Schirmer's and tear break-up time, were prospectively studied in patients with dry eye disease before and 1 month after treatment with autologous serum eye drops. RESULTS: Twenty-four patients (23 women, mean age 53.8±12.6 years) were included in the study. Ten patients (41.7%) had moderate and six (25.0%) had severe dry eye disease. Five patients had rheumatoid arthritis. After treatment, the number and density of conjunctival goblet cells, their size, the size of their nuclei and the nucleus/cytoplasm ratio increased significantly (202.3±107.5 vs 210.1±100.9 cells/mm2, p<0.01). Seven of ten patients with grade 3 or 4 metaplasia had an improvement in the degree of metaplasia. Both Schirmer's test and tear break-up time improved significantly in this subgroup of patients. In the multivariate study, the increase in conjunctival goblet cells was associated with the number of goblet cells and the size of the cytoplasm at baseline. No adverse reactions were noted. DISCUSSION: Treatment with autologous serum eye drops for 1 month was well tolerated and improved tear production, lachrymal flow and stability tests and conjunctival impression cytology with transfer, increasing the density of the goblet cells.


Assuntos
Síndromes do Olho Seco/terapia , Soluções Oftálmicas/uso terapêutico , Soro , Adulto , Idoso , Túnica Conjuntiva/citologia , Túnica Conjuntiva/metabolismo , Síndromes do Olho Seco/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/metabolismo , Soro/metabolismo , Lágrimas/metabolismo
20.
Autoimmun Rev ; 19(1): 102429, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734402

RESUMO

Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.


Assuntos
Interleucina-17/imunologia , Artrite Psoriásica , Artrite Reumatoide , Humanos , Interleucina-17/antagonistas & inibidores , Psoríase , Espondilite Anquilosante
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