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1.
Ann Hematol ; 102(2): 447-456, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36422672

RESUMO

The SARS-CoV-2 pandemic has favored the expansion of telemedicine. Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN) might be good candidates for virtual follow-up. In this study, we aimed to analyze the follow-up of patients with Ph-MPN in Spain during COVID-19, its effectiveness, and acceptance among patients. We present a multicenter retrospective study from 30 centers. Five hundred forty-one patients were included with a median age of 67 years (yr). With a median follow-up of 19 months, 4410 appointments were recorded. The median of visits per patient was 7 and median periodicity was 2.7 months; significantly more visits and a higher frequency of them were registered in myelofibrosis (MF) patients. 60.1% of visits were in-person, 39.5% were by telephone, and 0.3% were videocall visits, with a predominance of telephone visits for essential thrombocythemia (ET) and polycythemia vera (PV) patients over MF, as well as for younger patients (< 50 yr). The proportion of phone visits significantly decreased after the first semester of the pandemic. Pharmacological modifications were performed only in 25.7% of the visits, and, considering overall management, ET patients needed fewer global treatment changes. Telephone contact effectiveness reached 90% and only 5.4% required a complementary in-person appointment. Although 56.2% of the cohort preferred in-person visits, 90.5% of our patients claimed to be satisfied with follow-up during the pandemic, with an 83% of positive comments. In view of our results, telemedicine has proven effective and efficient, and might continue to play a complementary role in Ph-MPN patients' follow-up.


Assuntos
COVID-19 , Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Humanos , Idoso , Pandemias , Estudos Retrospectivos , Satisfação do Paciente , Espanha/epidemiologia , SARS-CoV-2 , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/terapia , Policitemia Vera/epidemiologia , Mielofibrose Primária/epidemiologia , Trombocitemia Essencial/epidemiologia
2.
Ann Hepatol ; 25: 100350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33864948

RESUMO

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.


Assuntos
COVID-19/epidemiologia , Hospitalização , Cirrose Hepática/epidemiologia , Índice de Massa Corporal , Comorbidade , Feminino , Seguimentos , Humanos , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , América do Sul/epidemiologia , Taxa de Sobrevida/tendências
3.
Ann Hepatol ; 21: 100298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33359234

RESUMO

INTRODUCTION & OBJECTIVES: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. MATERIALS & METHODS: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. RESULTS: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. CONCLUSIONS: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.


Assuntos
COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , Hepatopatias/epidemiologia , SARS-CoV-2 , Comorbidade , Feminino , Humanos , América Latina/epidemiologia , Hepatopatias/diagnóstico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
4.
J Pers ; 88(6): 1252-1267, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32557617

RESUMO

OBJECTIVES: The Dark Triad traits (i.e., narcissism, psychopathy, Machiavellianism) capture individual differences in aversive personality to complement work on other taxonomies, such as the Big Five traits. However, the literature on the Dark Triad traits relies mostly on samples from English-speaking (i.e., Westernized) countries. We broadened the scope of this literature by sampling from a wider array of countries. METHOD: We drew on data from 49 countries (N = 11,723; 65.8% female; AgeMean  = 21.53) to examine how an extensive net of country-level variables in economic status (e.g., Human Development Index), social relations (e.g., gender equality), political orientations (e.g., democracy), and cultural values (e.g., embeddedness) relate to country-level rates of the Dark Triad traits, as well as variance in the magnitude of sex differences in them. RESULTS: Narcissism was especially sensitive to country-level variables. Countries with more embedded and hierarchical cultural systems were more narcissistic. Also, sex differences in narcissism were larger in more developed societies: Women were less likely to be narcissistic in developed (vs. less developed) countries. CONCLUSIONS: We discuss the results based on evolutionary and social role models of personality and sex differences. That higher country-level narcissism was more common in less developed countries, whereas sex differences in narcissism were larger in more developed countries, is more consistent with evolutionary than social role models.


Assuntos
Maquiavelismo , Narcisismo , Afeto , Transtorno da Personalidade Antissocial , Feminino , Humanos , Masculino , Personalidade
5.
J Org Chem ; 83(4): 1779-1789, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29320179

RESUMO

Trifluoromethyl vinyl sulfide, a potential building block for pharmaceutically and agrochemically relevant products, is prepared and used for the first time in high-pressure-mediated 1,3-dipolar cycloaddition reactions with nitrones to synthesize (trifluoromethyl)sulfanyl isoxazolidines.

6.
Hemoglobin ; 39(1): 30-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25572186

RESUMO

The 3' untranslated region (3'UTR) region is well known to be associated with mRNA stability because of its associations with 3' end processing, polyadenylation and mRNA capping. Mutations located in this area cause a ß-thalassemia (ß-thal) phenotype compatible with ß(+)-thal. Two brothers, 49- and 41-years-old, were diagnosed with ß-thal intermedia (ß-TI) at 2 years of age. The ß-globin gene from the promoter region to the 3'UTR was sequenced and both brothers were diagnosed to be compound heterozygotes for the 3'UTR +1592 (A > G) (HBB: c.*+118A > G) and codon 39 (C > T) (HBB: c.118C > T) mutations. Their mother was a carrier of the nonsense codon 39 mutation and her hematological data suggested ß-thal trait; their father was a carrier of the 3'UTR +1592 mutation, though he did not have hematological parameters associated with ß-thal. The adenine at position +1592 or +118 bases downstream of the termination codon is highly conserved among primates and placental mammals, as it is located between the polyadenylation A signal (PAS) and the polyadenylation A cleavage (PAC) sites. Given its location, it is likely that this mutation would interfere with mRNA maturation; however, the clinical data of the heterozygous carriers show virtually no significant alterations. Therefore, we suggest that the impact on cleavage-stimulation factor (CstF) recognition of the mRNA sequence would be minimal and not significantly alter polyadenylation. Although the mechanism is not known, and because the carrier has no ß-thal minor, the mRNA is stable enough that the synthesis of the ß-globin chain is unaffected.


Assuntos
Mutação Puntual , Globinas beta/genética , Talassemia beta/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Talassemia beta/sangue , Talassemia beta/epidemiologia
7.
Am Surg ; 90(11): 3131-3133, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38807267

RESUMO

Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a rare tumor described as a mucosal exophytic neoplastic lesion that projects into the gallbladder lumen. In regards to the size, lesions that did not make the arbitrary 1cm cutoff are described as "incipient" ICPN. Not much is known about these incipient ICPNs, as they are often excluded in ICPN studies, given the attempted adherence to the traditional 1cm cutoff. We present the youngest reported case of incipient, non-mucinous gastric-pylorus type ICPN who underwent cholecystectomy. Resection with negative margin for ICPN appears to be sufficient treatment and post resection imaging surveillance could be of value but further studies are required.


Assuntos
Colecistectomia , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/diagnóstico , Feminino , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Carcinoma Papilar/diagnóstico , Masculino , Pessoa de Meia-Idade
8.
Rev Esp Patol ; 57(2): 151-155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599738

RESUMO

Adenocarcinoma with enteroblastic differentiation is a rare histologic subtype of adenocarcinoma of the gastrointestinal tract that shows unique histologic and immunohistochemical features that resemble fetal intestinal epithelium. This histological subtype has been widely described in the stomach, where it most frequently appears, but, in other locations, it is misdiagnosed because of the poor experience in routine diagnostic setting. Here we present a case of an 87-year-old male with an adenocarcinoma of the ampulla of Vater with enteroblastic differentiation with a literature review of the cases described of this subtype in this location to date. The anatomical peculiarity of the ampulla, joined with the infrequent nature of this histological subtype, makes this case of great interest to aid to better characterize the biological behavior of these tumors.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Masculino , Humanos , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Adenocarcinoma/patologia
9.
Am J Clin Nutr ; 120(2): 449-458, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38830408

RESUMO

BACKGROUND: Non-time-consuming and easy-to-administer dietary assessment tools specific for pregnancy are needed. OBJECTIVES: The aim of this validation study nested in the IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa) trial is to determine the concurrent validity of the 17-item pregnancy-adapted Mediterranean diet score (preg-MEDAS) and to analyze whether changes in the preg-MEDAS score were associated with maternal favorable dietary and cardiometabolic changes after 3 mo of intervention in pregnant women. METHODS: Dietary data was collected in 812 participants using the preg-MEDAS and a 151-item validated food frequency questionnaire (FFQ) at baseline (19-23 wk gestation) and final visit (31-34 wk gestation). Concurrent preg-MEDAS validity was evaluated by Pearson and intraclass correlation coefficients, κ statistic, and Bland-Altman methods. RESULTS: The preg-MEDAS had a good correlation with the FFQ (r = 0.76 and intraclass correlation coefficient 0.75). The agreement of each of the preg-MEDAS items ranged from 40.9% to 93.8% with a substantial agreement mean concordance (κ = 0.61). A 2-point increase in preg-MEDAS was associated with a decrease in maternal mean and systolic blood pressure (ß: -0.51 mmHg; 95% confidence interval [CI]: -0.97, -0.04 mmHg and -0.87 mmHg; 95% CI: -1.48, -0.26 mmHg, respectively). CONCLUSIONS: The preg-MEDAS displays good validity for assessing adherence to the Mediterranean diet, allowing detection of dietary changes over time. In addition, changes observed in preg-MEDAS are significantly associated with a decrease in maternal blood pressure. Therefore, we propose preg-MEDAS as a rapid and simple dietary assessment tool during pregnancy. This trial was registered at clinicaltrials.gov as NCT03166332.


Assuntos
Dieta Mediterrânea , Cuidado Pré-Natal , Humanos , Feminino , Gravidez , Adulto , Cuidado Pré-Natal/métodos , Cooperação do Paciente , Reprodutibilidade dos Testes , Inquéritos e Questionários , Espanha , Avaliação Nutricional
10.
Healthcare (Basel) ; 12(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38727505

RESUMO

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.

11.
Psychol Assess ; 36(1): 14-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010780

RESUMO

Coronavirus Anxiety Scale (CAS) is a widely used measure that captures somatic symptoms of coronavirus-related anxiety. In a large-scale collaboration spanning 60 countries (Ntotal = 21,513), we examined the CAS's measurement invariance and assessed the convergent validity of CAS scores in relation to the fear of COVID-19 (FCV-19S) and the satisfaction with life (SWLS-3) scales. We utilized both conventional exact invariance tests and alignment procedures, with results revealing that the single-factor model fit the data well in almost all countries. Partial scalar invariance was supported in a subset of 56 countries. To ensure the robustness of results, given the unbalanced samples, we employed resampling techniques both with and without replacement and found the results were more stable in larger samples. The alignment procedure demonstrated a high degree of measurement invariance with 9% of the parameters exhibiting noninvariance. We also conducted simulations of alignment using the parameters estimated in the current model. Findings demonstrated reliability of the means but indicated challenges in estimating the latent variances. Strong positive correlations between CAS and FCV-19S estimated with all three different approaches were found in most countries. Correlations of CAS and SWLS-3 were weak and negative but significantly differed from zero in several countries. Overall, the study provided support for the measurement invariance of the CAS and offered evidence of its convergent validity while also highlighting issues with variance estimation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Ansiedade , COVID-19 , Humanos , Reprodutibilidade dos Testes , Psicometria/métodos , Ansiedade/diagnóstico , COVID-19/diagnóstico , Medo
12.
Front Nutr ; 10: 1122289, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927499

RESUMO

Introduction: Clinical practice guidelines (CPGs) contain recommendations for specific clinical circumstances, including maternal malnutrition. This study aimed to identify the CPGs that provide recommendations for preventing, diagnosing, and treating women's malnutrition. Additionally, we sought to assess the methodological quality using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Methods: An online search for CPGs was performed, looking for those that contained lifestyle and nutritional recommendations to prevent, diagnose and treat malnutrition in women during the preconception period using PubMed and different websites. The reviewers utilized the AGREE II instrument to appraise the quality of the CPGs. We defined high-quality guidelines with a final score of > 70%. Results: The titles and abstracts from 30 guidelines were screened for inclusion, of which 20 guidelines were fully reviewed for quality assessment. The overall quality assessment of CPGs was 73%, and only 55% reached a high-quality classification. The domains in the guidelines classified as high-quality had the highest scores in "Scope and Purpose" and "Clarity of Presentation" with a median of 98.5 and 93%, respectively. Discussion: Further assessment is needed to improve the quality of the guidelines, which is an opportunity to strengthen them, especially in the domains with the lowest scores.

13.
Nutrients ; 14(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364841

RESUMO

This work aimed to identify clinical practice guidelines (CPGs) that include recommendations for the prevention, diagnosis, and treatment of women's malnutrition during pregnancy and to evaluate the quality of these guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. We conducted a literature review using PubMed and different websites from January 2009 to February 2021. The quality of the CPGs was independently assessed by reviewers using the AGREE II instrument, which defines guidelines scoring >70% in the overall assessment as "high quality". The analysis included 43 guidelines. Among the main findings, we identified that only half of the CPGs (51.1%) obtained a final "high quality" evaluation. AGREE II results varied widely across domains and categories. The two domains that obtained the highest scores were scope and purpose with 88.3% (range 39 to 100%) and clarity of presentation with 87.2% (range 25 to 100%). Among the "high quality" CPGs, the best scores were achieved by the three guidelines published by the National Institute of Health and Care Excellence (NICE) and the World Health Organization (WHO). Due to the importance of maternal nutrition in pregnancy, it is essential to join forces to improve the quality of the guidelines, especially in CPGs that do not meet the reference standards for quality.


Assuntos
Desnutrição , Guias de Prática Clínica como Assunto , Feminino , Humanos , Gravidez , Desnutrição/diagnóstico , Desnutrição/prevenção & controle
14.
Front Med (Lausanne) ; 9: 1011940, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569141

RESUMO

Introduction: Maternal and child malnutrition is a worldwide public health problem with short, medium, and long-term adverse consequences for both mother and child. In Mexico, maternal and child malnutrition represents a serious public health problem that must be urgently addressed. In this context, Primary Health Care (PHC) plays an important role in the prevention, detection, monitoring, and treatment of the different forms of maternal and child malnutrition. Assessing the quality of nutritional care offered at this level of care is necessary in order to improve it; however, there are no indicators for the evaluation of this quality. Therefore, this study aimed at developing a set of indicators to assess the quality of maternal and child nutritional care at PHC. Methods: We developed indicators for different stages of life: preconception, pregnancy, infancy, and preschool age. A systematic review of the literature on clinical guidelines for the prevention, diagnosis, and treatment of the different forms of malnutrition was carried out; the recommendations of the guidelines evaluated with good quality were extracted. Results: Based on these recommendations, 22 indicators were constructed. A pilot study was carried out to validate the indicators and 16 indicators were selected to assess the maternal and child nutritional care at PHC.

15.
Assessment ; 28(4): 1125-1135, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32484407

RESUMO

The Dark Triad (i.e., narcissism, psychopathy, Machiavellianism) has garnered intense attention over the past 15 years. We examined the structure of these traits' measure-the Dark Triad Dirty Dozen (DTDD)-in a sample of 11,488 participants from three W.E.I.R.D. (i.e., North America, Oceania, Western Europe) and five non-W.E.I.R.D. (i.e., Asia, Middle East, non-Western Europe, South America, sub-Saharan Africa) world regions. The results confirmed the measurement invariance of the DTDD across participants' sex in all world regions, with men scoring higher than women on all traits (except for psychopathy in Asia, where the difference was not significant). We found evidence for metric (and partial scalar) measurement invariance within and between W.E.I.R.D. and non-W.E.I.R.D. world regions. The results generally support the structure of the DTDD.


Assuntos
Maquiavelismo , Narcisismo , Transtorno da Personalidade Antissocial , Ásia , Europa (Continente) , Feminino , Humanos , Masculino , América do Norte
16.
Sci Total Environ ; 698: 134168, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505353

RESUMO

Arsenic and fluoride in drinking water present a significant challenge to public health worldwide. In this study, we analyze the results of one of the largest surveys of drinking water quality in Mexico: 14,058 samples from 3951 sites, collected between January and December 2017. We use these data to identify the distribution and possible origin of arsenic and fluoride in drinking water throughout the country, and to estimate the associated health burden. The highest concentrations appear in alluvial aquifers in arid northern Mexico, where high-silica volcanic rock likely releases both arsenic and fluoride to the groundwater. We find fluoride contamination to be significantly correlated with aridity (Pearson correlation = -0.45, p = 0.0105), and also find a significant difference in fluoride concentrations between arid and humid states (Welch's t-test, p = 0.004). We estimate population exposure by assigning to each town in Mexico the average concentration of any sampling sites within 5 km. Our results show that 56% of the Mexican population lives within 5 km of a sampling site, 3.05 million people are exposed to fluoride above the reference dosage of 0.06 mg/(kg ∗ day), 8.81 million people are exposed to arsenic above the limit of 10 µg/L, and an additional 13,070 lifetime cases of cancer are expected from this arsenic exposure alone. This burden of disease is concentrated in the arid states of north-central Mexico.


Assuntos
Arsênio/análise , Água Potável/química , Monitoramento Ambiental , Fluoretos/análise , Poluentes Químicos da Água/análise , Humanos , México , Medição de Risco
17.
J Neurochem ; 111(6): 1398-408, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19799708

RESUMO

Thrombin levels increase in brain during ischemia and hemorrhagic episodes, and may contribute to excitotoxic neural damage. This study examined the effect of thrombin on glutamate efflux from rat cortical cultured astrocytes using 3H-D-aspartate as radiotracer. The glutamate efflux was initiated by addition of 100 mM K+ plus 1 mM ouabain (K/O) to replicate extracellular and intracellular ionic changes that occur during cerebral ischemia. Upon exposure to K/O, astrocytes swelled slowly and progressively with no evidence of volume regulation. The K/O-induced swelling was inhibited by 65% with bumetanide and 25% with BaCl2, suggesting contribution of Na+/K+/Cl) co-transporter and Kir channels. K/O-elicited 3H-D-aspartate that consisted of two phases. The first transient component of the release corresponded to 13.5% of total 3H-D-aspartate loaded. It was markedly reduced (61%) by the glutamate transporter blocker DL-threo-b-benzyloxyaspartic acid and weakly inhibited (21%) by the volume-sensitive anion channel blocker 4-[(2-Butyl-6,7-dichloro-2-cyclopentyl-2,3-di-hydro-1oxo-1H-inden-5-yl)oxy] butanoic acid (DCPIB). During the second sustained phase of release, cells lost 45% of loaded of 3H-D-aspartate via a mechanism that was insensitive to DL-threo-b-benzyloxyaspartic acid but nearly completely suppressed by DCPIB. Thrombin (5 U/mL) had only marginal effects on the first phase but strongly potentiated(more than two-fold) 3H-D-aspartate efflux in the second phase. The effect of thrombin effect was proportional to cell swelling and completely suppressed by DCPIB. Overall our data showed that under K/O swelling conditions, thrombin potently enhance glutamate release via volume-sensitive anion channel. Similar mechanisms may contribute to brain damage in neural pathologies which are associated with cell swelling, glutamate efflux and increased thrombin levels.


Assuntos
Astrócitos/efeitos dos fármacos , Ácido D-Aspártico/metabolismo , Hemostáticos/farmacologia , Homeostase/efeitos dos fármacos , Potássio/metabolismo , Trombina/farmacologia , Animais , Animais Recém-Nascidos , Ácido Aspártico/farmacologia , Bário/farmacologia , Bumetanida/farmacologia , Cálcio/metabolismo , Células Cultivadas , Córtex Cerebral/citologia , Ciclopentanos/farmacologia , Ácido D-Aspártico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Indanos/farmacologia , Oligopeptídeos/farmacologia , Ouabaína/farmacologia , Ratos , Ratos Wistar , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Taurina/metabolismo , Fatores de Tempo , Trítio/metabolismo
18.
Mol Neurobiol ; 56(12): 8008-8017, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31161422

RESUMO

Uveitis, defined as inflammation of the uveal tract of the eye, is a leading cause of blindness and visual impairment throughout the world. The etiology of uveitis is complex, and autoimmunity plays a major role in its pathogenesis. Intermediate uveitis (IU), a subtype of ocular inflammation, has been associated with systemic autoimmune disorders, specifically with multiple sclerosis (MS). This article reports a rare three-generation family with several members affected by IU (four siblings) and comorbid MS (two siblings fulfilling MS diagnostic criteria and a third sibling presenting some neurological symptoms). Based on the clinical findings, we captured and sequenced whole exomes of seven pedigree members (affected and unaffected). Using a recessive model of transmission with full penetrance, we applied genetic linkage analysis to define minimal critical regions (MCRs) in suggestive or nominal regions of linkage. In these MCRs, we defined functional (some pathogenic), novel, and rare mutations that segregated as homozygous in affected and heterozygous in unaffected family members. The genes harboring these mutations, including DGKI, TNFRSF10A, GNGT1, CPAMD8, and BAFF, which are expressed in both eye and brain tissues and/or are related to autoimmune diseases, provide new avenues to evaluate the inherited causes of these devastating autoimmune conditions.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/genética , Mutação/genética , Uveíte/diagnóstico por imagem , Uveíte/genética , Criança , Feminino , Humanos , Masculino , Esclerose Múltipla/complicações , Linhagem , Uveíte/complicações , Sequenciamento do Exoma/métodos , Adulto Jovem
20.
Environ Sci Pollut Res Int ; 23(12): 12085-94, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26965279

RESUMO

Humic substances (HS), a broad category of organic compounds and a major constituent of soil, are responsible for serious problems during water purification processes. In particular, HS react with chlorine during disinfection processes to produce a variety of organochlorine compounds such as trihalomethanes (THMs), which are potentially carcinogenic to humans. The use of ozone as a disinfection method represents a potential solution to this problem; however, HS that are not completely oxidized may form by-products more reactive than the original molecules. The structural changes of HS during oxidation with ozone were evaluated through a replicated 2(2) design, where concentrations of 5 and 30 mg/L of two commercial HS (Aldrich and Fluka) were ozonized over different time intervals (0, 10, and 20 min). The ozone-treated HS were titrated with acid and base solutions, and the shifts of the slopes were then analyzed and finally related to the ionic alterations of the HS. The Aldrich HS (AHS) showed only protonated functional groups; the Fluka HS (FHS) showed only ionized groups; and in both cases, the amount of functional groups increased with increasing ozonation. For AHS and FHA, respectively, the maximum ozone exposure time (20 min) and the highest concentration of HS (30 mg/L) produced the greatest reductions in total organic carbon (TOC) (39 and 34 %), UV254 (50 and 60.8 %), and color (16.4 and 19.6 %). As for aromaticity, AHS showed removals of 39.6 % (from a starting concentration of 5 mg/L) and 17.2 % (from a starting concentration of 30 mg/L). FHS showed the opposite effect, with removals of 33.3 % (starting at 5 mg/L) and 40.1 % (starting at 30 mg/L). In this study, the structural changes of HS submitted to ozonation were inferred in a relatively quick and easy way by using a conductometric titration, thus demonstrating the applicability of the technique.


Assuntos
Substâncias Húmicas , Oxidantes/química , Ozônio/química , Condutometria , Desinfecção , Oxirredução , Purificação da Água
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