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1.
Blood ; 144(6): 646-656, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38843478

RESUMO

ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.


Assuntos
Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopênica Idiopática , Piridinas , Pirimidinas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Idoso , Oxazinas/uso terapêutico , Oxazinas/efeitos adversos , Idoso de 80 Anos ou mais , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Quinase Syk/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Contagem de Plaquetas , Estudos Prospectivos
2.
Planta ; 260(1): 28, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878167

RESUMO

MAIN CONCLUSION: We generated transplastomic tobacco lines that stably express a human Basic Fibroblast Growth Factor (hFGFb) in their chloroplasts stroma and purified a biologically active recombinant hFGFb. MAIN: The use of plants as biofactories presents as an attractive technology with the potential to efficiently produce high-value human recombinant proteins in a cost-effective manner. Plastid genome transformation stands out for its possibility to accumulate recombinant proteins at elevated levels. Of particular interest are recombinant growth factors, given their applications in animal cell culture and regenerative medicine. In this study, we produced recombinant human Fibroblast Growth Factor (rhFGFb), a crucial protein required for animal cell culture, in tobacco chloroplasts. We successfully generated two independent transplastomic lines that are homoplasmic and accumulate rhFGFb in their leaves. Furthermore, the produced rhFGFb demonstrated its biological activity by inducing proliferation in HEK293T cell lines. These results collectively underscore plastid genome transformation as a promising plant-based bioreactor for rhFGFb production.


Assuntos
Cloroplastos , Fator 2 de Crescimento de Fibroblastos , Nicotiana , Plantas Geneticamente Modificadas , Proteínas Recombinantes , Nicotiana/genética , Nicotiana/metabolismo , Humanos , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Cloroplastos/metabolismo , Cloroplastos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Células HEK293 , Proliferação de Células , Folhas de Planta/metabolismo , Folhas de Planta/genética
3.
Glia ; 71(7): 1626-1647, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36919670

RESUMO

Hypothalamic circuits compute systemic information to control metabolism. Astrocytes residing within the hypothalamus directly sense nutrients and hormones, integrating metabolic information, and modulating neuronal responses. Nevertheless, the role of the astrocytic circadian clock on the control of energy balance remains unclear. We used mice with a targeted ablation of the core-clock gene Bmal1 within Gfap-expressing astrocytes to gain insight on the role played by this transcription factor in astrocytes. While this mutation does not substantially affect the phenotype in mice fed normo-caloric diet, under high-fat diet we unmasked a thermogenic phenotype consisting of increased energy expenditure, and catabolism in brown adipose and overall metabolic improvement consisting of better glycemia control, and body composition. Transcriptomic analysis in the ventromedial hypothalamus revealed an enhanced response to moderate cellular stress, including ER-stress response, unfolded protein response and autophagy. We identified Xbp1 and Atf1 as two key transcription factors enhancing cellular stress responses. Therefore, we unveiled a previously unknown role of the astrocytic circadian clock modulating energy balance through the regulation of cellular stress responses within the VMH.


Assuntos
Relógios Circadianos , Camundongos , Animais , Relógios Circadianos/genética , Astrócitos/metabolismo , Hipotálamo/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Metabolismo Energético/genética
4.
Proc Biol Sci ; 290(1990): 20222203, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629117

RESUMO

Abandonment of agricultural lands promotes the global expansion of secondary forests, which are critical for preserving biodiversity and ecosystem functions and services. Such roles largely depend, however, on two essential successional attributes, trajectory and recovery rate, which are expected to depend on landscape-scale forest cover in nonlinear ways. Using a multi-scale approach and a large vegetation dataset (843 plots, 3511 tree species) from 22 secondary forest chronosequences distributed across the Neotropics, we show that successional trajectories of woody plant species richness, stem density and basal area are less predictable in landscapes (4 km radius) with intermediate (40-60%) forest cover than in landscapes with high (greater than 60%) forest cover. This supports theory suggesting that high spatial and environmental heterogeneity in intermediately deforested landscapes can increase the variation of key ecological factors for forest recovery (e.g. seed dispersal and seedling recruitment), increasing the uncertainty of successional trajectories. Regarding the recovery rate, only species richness is positively related to forest cover in relatively small (1 km radius) landscapes. These findings highlight the importance of using a spatially explicit landscape approach in restoration initiatives and suggest that these initiatives can be more effective in more forested landscapes, especially if implemented across spatial extents of 1-4 km radius.


Assuntos
Ecossistema , Florestas , Biodiversidade , Árvores , Plantas
5.
Clin Endocrinol (Oxf) ; 98(5): 670-677, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36710456

RESUMO

OBJECTIVE: Idiopathic central precocious puberty (iCPP) is common in paediatric endocrinology. Gonadotropin-releasing hormone agonists (GnRHa) are safe, but the effect on final height and the ideal timing for treatment remains controversial. This study aims to assess the effectiveness of GnRHa on growth outcomes in girls with iCPP treated before and after the age of 8 years old. DESIGN AND PATIENTS: This retrospective longitudinal study evaluated data from Portuguese girls with iCPP who completed treatment between 2010 and 2021. MEASUREMENTS: Auxological and clinical characteristics were compared according to age at treatment onset. RESULTS: A cohort of 134 girls with iCPP, was divided into early treatment (ET) (<8 years, n = 48) and later treatment (LT) groups (≥8 years, n = 86). In both groups, most children presented with Tanner II and III. Tanner IV was more frequent in LT group (p = .003). At the end of treatment, predicted adult height increased in both groups (ET p = .032; LT p = .04) and bone age significantly slowed down in all participants (p = .008, p = .034). The height gain was greater in the ET group, but without significant differences (p = .065). CONCLUSIONS: Treatment with GnRHa improved final height in all girls with iCPP, even when initiated after 8 years. To achieve better outcomes, treatment should be provided promptly after diagnosis.


Assuntos
Hormônio Liberador de Gonadotropina , Puberdade Precoce , Adulto , Criança , Feminino , Humanos , Estatura , Hormônio Liberador de Gonadotropina/agonistas , Estudos Longitudinais , Portugal , Puberdade Precoce/tratamento farmacológico , Estudos Retrospectivos
6.
J Eukaryot Microbiol ; 70(5): e12978, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37195413

RESUMO

Blastocystis sp. is among the most frequent intestinal protists identified in humans globally. However, characterization of Blastocystis subtype diversity in humans is ongoing. We report here the identification of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening involving colonoscopy and fecal testing (microscopy, culture, PCR). The full-length ssu rRNA gene sequence of the protist was generated using MinION long-read sequencing technology. The validity of the novel subtype was confirmed via phylogenetic and pairwise distance analyses of the full-length ST41 sequence and all other valid subtypes. The study provides reference material essential for conducting subsequent experimental studies.


Assuntos
Infecções por Blastocystis , Blastocystis , Neoplasias Colorretais , Humanos , Blastocystis/genética , Infecções por Blastocystis/diagnóstico , Filogenia , Colômbia , Detecção Precoce de Câncer , Fezes , Neoplasias Colorretais/diagnóstico , Prevalência , Variação Genética
7.
Med Mycol ; 61(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37024274

RESUMO

Microsporidia are fungi-related eukaryotic intracellular parasites that opportunistically infect immunocompromised individuals such as those infected by the human immunodeficiency virus (HIV). Among them, Enterocytozoon bieneusi and Encephalitozoon spp. are the most clinically relevant species. We investigated the occurrence and genetic diversity of microsporidial and protist infections in mostly immunocompetent HIV-positive patients in Madrid, Spain. A structured questionnaire was used to retrieve data on factors potentially associated with an increased risk of infection, including sexual attitudes and sex-risk behaviour. Faecal samples (n = 96) from 81 HIV-positive patients were collected and analysed by molecular (PCR and Sanger sequencing) methods. Two microsporidial pathogens were detected: Ent. bieneusi (2.5%, 95% CI: 0.3-8.6) and Enc.intestinalis (4.9%, 95% CI: 1.4-12.2). The two Ent. bieneusi isolates were identified as zoonotic genotype A. Among protists, Entamoeba dispar was the species most prevalently found (33.3%, 95% CI: 23.2-44.7), followed by Blastocystis spp. (19.8%, 95% CI: 11.7-30.1), Giardia duodenalis (13.6%, 95% CI: 7.0-23.0), and Cryptosporidium spp. and Entamoeba histolytica (2.5%, 95% CI: 0.3-8.6 each). Cyclospora cayetanensis and Cystoisospora belli were not detected. Subtypes ST1 (70.6%, 12/17) and ST3 (29.4%, 5/17) were identified within Blastocystis sp., sub-assemblages AII and BIII (50%, 1/2 each) within G. duodenalis, and Cry. parvum and canine-adapted Cry. canis (50%, 1/2 each) within Cryptosporidium spp. Microsporidial and protist parasites were frequent in well-controlled, mostly immunocompetent HIV-positive patients and should be included in diagnostic algorithms when diarrhoea is present.


Opportunistic microsporidial and protist intestinal infections were relatively common in well-controlled HIV-positive patients in Madrid, Spain. These agents should be suspected and appropriately diagnosed in HIV-positive patients presenting with diarrhoea regardless of their immunological status.


Assuntos
Criptosporidiose , Encephalitozoon , Enterocytozoon , Microsporidiose , Infecções por Protozoários , Animais , Cães , Humanos , Criptosporidiose/complicações , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Cryptosporidium/genética , Encephalitozoon/genética , Enterocytozoon/genética , Fezes , Genótipo , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/veterinária , Microsporídios/genética , Prevalência , Espanha/epidemiologia , Infecções por Protozoários/complicações , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/parasitologia , Microsporidiose/complicações , Microsporidiose/epidemiologia , Microsporidiose/microbiologia
8.
Eur J Pediatr ; 182(1): 213-223, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36282323

RESUMO

Giardia duodenalis, Cryptosporidium spp., and Blastocystis sp. are common intestinal eukaryotic parasites affecting children in developed and resource-limited countries. Lack of information on the epidemiology and long-term stability in asymptomatic children complicates interpretation of transmission and pathogenesis. To assess the occurrence, genetic diversity, and temporal dynamics of intestinal eukaryotic parasites in young children, 679 stool samples from 125 toddlers attending six public day-care centres in Central Spain were collected bimonthly within a 1-year period. Detection and identification of species/genotypes were based on PCR and Sanger sequencing methods. Four eukaryotic species were identified: G. duodenalis (2.5‒31.6%), Cryptosporidium spp. (0.0‒2.4%), Blastocystis sp. (2.5‒6.4%), and Entamoeba dispar (0.0‒0.9%). Entamoeba histolytica and Enterocytozoon bieneusi were undetected. Sequence analyses identified assemblage A (63.6%) and B (36.4%) within G. duodenalis (n = 11), C. hominis (40%), C. parvum (40%), and C. wrairi (20%) within Cryptosporidium spp. (n = 5), and ST1 (3.8%), ST2 (46.2%), ST3 (15.4%), and ST4 (34.6%) within Blastocystis sp. (n = 26). Giardia duodenalis sub-assemblage AII/AIII was detected in a toddler for 10 consecutive months. Stable carriage of Blastocystis ST2 allele 9, ST3 allele 34, and ST4 allele 42 was demonstrated in five toddlers for up to 1 year.   Conclusions: Giardia duodenalis and Blastocystis sp. were common in toddlers attending day-care centres in Central Spain. Long-term infection/colonization periods by the same genetic variant were observed for G. duodenalis (up to 10 months) and Blastocystis sp. (up to 12 months). What is Known: • Asymptomatic carriage of G. duodenalis and Blastocystis sp. is frequent in toddlers. • The epidemiology and long-term stability of these eukaryotes in asymptomatic young children is poorly understood. What is New: • Long-term colonization/infection periods by the same genetic variant were described for Blastocystis sp. (up to 12 months) and G. duodenalis (up to 10 months).


Assuntos
Blastocystis , Criptosporidiose , Cryptosporidium , Giardia lamblia , Giardíase , Enteropatias Parasitárias , Humanos , Pré-Escolar , Giardia lamblia/genética , Blastocystis/genética , Giardíase/epidemiologia , Giardíase/parasitologia , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Prevalência , Espanha/epidemiologia , Estudos Longitudinais , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Cryptosporidium/genética , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Fezes/parasitologia , Genótipo
9.
J Exp Child Psychol ; 235: 105738, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37421925

RESUMO

The healthy development of cognitive functions, including executive functions, has been shown to depend mainly on the experiences and learning opportunities of people, especially during childhood. Over the past few years, researchers have been studying the impacts of diverse types of interventions on children's cognitive development in which computational thinking programs are a recent field. This pilot study evaluated the effect of computational thinking training based on the "Programming for Children" program on the executive functions of children aged 10 and 11 years: working memory, inhibition, and planning (N = 30). The results showed that children in the experimental group improved on tests of visuospatial working memory, cognitive inhibition, and sequential planning compared with the control group. However, tests of verbal working memory, memory strategy, and visual spatial planning did not show any observed changes. Although this was an exploratory study, and its findings should be interpreted cautiously due to the small sample size, the findings support the relevance and feasibility of conducting similar larger studies with larger samples.


Assuntos
Cognição , Função Executiva , Criança , Humanos , Função Executiva/fisiologia , Projetos Piloto , Cognição/fisiologia , Aprendizagem/fisiologia , Memória de Curto Prazo/fisiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-36758850

RESUMO

This study aimed to evaluate the hypothalamus fatty acid (FA)-sensing mechanisms response to different FA in European sea bass. For that purpose, fish (body weight of 90 g) were intraperitoneally (IP) injected (time 0 h) with five long-chain unsaturated fatty acids, namely, docosahexaenoic acid (DHA; C22:5n3); eicosapentaenoic acid (EPA; C20:4n3); α-linolenic (ALA; C18:3n3); linoleic acid (LA; C18:2n6) and oleic acid (OA; C18:1n9) at a dose of 300 µg kg-1, or with 0.9% saline solution (control). Feed intake (FI) was recorded at 3, 6, and 24 h after the IP injection. One week later, fish were IP injected with the same FA, and the hypothalamus was collected 3 h after the IP injection for measurement of molecules related to FI regulation and FA-sensing mechanisms. Cumulative FI (g/kg/day) was not affected by treatments. However, compared to the control, FI increased with the OA treatment at 6 h after the IP injection. FI decreased with mealtime in the DHA and LA groups. Gene expression of orexigenic (npy/agrp) and anorexigenic (cart2/pomc1) neurons was not affected by the FA treatments. Attending the enzymes involved in the FA-sensing mechanisms activation, compared to the control carnitine palmitoyltransferase I (CPT1) and ATP citrate lyase (ACLY) activity were not affected by FA treatments. Contrarily the key enzymes of lipid metabolisms, malic enzyme and hydroxyacylCoA dehydrogenase was higher in fish that received the EPA and OA treatment, than fish treated to the control. Overall, the results of the present study indicate that gene expression of orexigenic and anorexigenic neurons was not affected at 3 h after IP injection with different FA. However, the activity of key enzymes of lipid metabolism was differently affected by circulating FA, indicating that FA-sensing mechanisms respond to different FA. Further studies are required involving different sampling times to further characterize the response of FA-sensing mechanisms to FA. These findings may be of relevance to the aquaculture industry in an era where alternative lipid sources are being increasingly used.


Assuntos
Bass , Ácidos Graxos , Animais , Ácidos Graxos/metabolismo , Bass/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ingestão de Alimentos , Hipotálamo/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo
11.
J Sci Food Agric ; 103(1): 420-427, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36373791

RESUMO

BACKGROUND: Spent coffee grounds (SCGs) are a good source of chlorogenic acid (CGA), which can be hydrolyzed to quinic acid (QA) and caffeic acid (CA). These molecules have antioxidant and neuroprotective capacities, benefiting human health. The hydrolysis of CGA can be done by biotechnological processes, such as solid-state fermentation (SSF). This work evaluated the use of SSF with Aspergillus sp. for the joint release of the three molecules from SCGs. RESULTS: Hydroalcoholic extraction of the total phenolic compounds (TPCs) from SCGs was optimized, obtaining 28.9 ± 1.97 g gallic acid equivalent (GAE) kg-1 SCGs using 0.67 L ethanol per 1 L, a 1:9 solid/liquid ratio, and a 63 min extraction time. Subsequently, SSF was performed for 30 days, achieving the maximum yields for CGA, QA, and TPCs on the 16th day: 7.12 ± 0.01 g kg-1 , 4.68 ± 0.11 g kg-1 , and 54.96 ± 0.49 g GAE kg-1 respectively. CA reached its maximum value on the 23rd day, at 4.94 ± 0.04 g kg-1 . The maximum antioxidant capacity was 635.7 mmol Trolox equivalents kg-1 on the 14th day. Compared with unfermented SCGs extracts, TPCs and CGA increase their maximum values 2.3-fold, 18.6-fold for CA, 14.2 for QA, and 6.4-fold for antioxidant capacity. Additionally, different extracts' profiles were obtained throughout the SSF process, allowing us to adjust the type of enriched extract to be produced based on the SSF time. CONCLUSION: SSF represents an alternative to produce extracts with different compositions and, consequently, different antioxidant capacities, which is a potentially attractive fermentation process for different applications. © 2022 Society of Chemical Industry.


Assuntos
Antioxidantes , Café , Humanos , Café/química , Fermentação , Antioxidantes/química , Ácidos Cafeicos/química , Ácido Clorogênico/análise , Ácido Quínico/análise , Ácido Quínico/química , Fenóis , Extratos Vegetais
12.
Z Rheumatol ; 82(Suppl 1): 68-73, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34287668

RESUMO

BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. It can be associated with other connective tissue diseases, including systemic lupus erythematosus (SLE). OBJECTIVE: This study aimed to determine the incidence of secondary SS (sSS) in patients diagnosed with SLE (SLE-SS) and compare the clinical and serological features of SLE-SS to SLE only. METHODS: A retrospective observational study including patients diagnosed with SLE (SLICC criteria) seen at the Rheumatology Department between 1990 and 2020 was performed. A total of 453 SLE patients were assessed for fulfilment of the criteria for SS using the European questionnaire and Schirmer test, fluorescein staining/non-stimulated whole-salivary flow, anti-Ro/La antibodies, and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and rheumatoid factor (RF) were measured at entry and at SS assessment. SLE-SS was defined according to the American-European Consensus Criteria (AECC). SLE-SS was defined as a case that initially only fulfilled SLE classification criteria but which exhibited disease progression during follow-up and then met classification criteria for sSS. RESULTS: SLE-SS occurred in 11% of the SLE patients. In comparison to SLE-only patients, the SLE-SS group was older at inclusion and onset, and had a longer disease course. Sicca syndrome, oral ulcers, pulmonary involvement, and peripheral neuropathy were more frequent. Anti-SSA, anti-SSB, RF, and total IgG were higher in the SLE-SS group. CONCLUSION: SLE-SS appears to be a subgroup of patients with distinct clinical and serologic features. The frequency of SLE-SS increases with age. Patients with SLE-SS have a higher frequency of oral ulcers, anti-Ro and anti-La antibodies, and a lower frequency of renal disease, anti-dsDNA antibodies, anti-SM, and lower C3 and C4 hypocomplementemia.


Assuntos
Lúpus Eritematoso Sistêmico , Úlceras Orais , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Úlceras Orais/complicações , Anticorpos Antinucleares , Fator Reumatoide , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia
13.
J Clin Rheumatol ; 29(3): 132-138, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728382

RESUMO

BACKGROUND: Evaluating the efficacy and refractoriness to treatment and determining factors associated with adverse outcomes in uveitis associated with spondylarthritis (SpA) are complicated by the lack of validated outcome measures. OBJECTIVES: The aims of this study were to develop an outcome score SpA-U in patients with uveitis associated with SpA and to determine factors associated with adverse outcomes in patients with uveitis under systemic treatment. METHODS: The outcome score SpA-U was defined by best-corrected visual acuity, anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their SEs are displayed together with linear regression coefficients with 95% confidence intervals. For continuous factors, averages and SDs are reported in addition to linear regression coefficients with 95% confidence interval. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex. RESULTS: One hundred ninety-seven uveitis outbreaks were included. Sixty-two uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history ( ß = 0.34), axial and peripheral involvement ( ß = 0.43), Ankylosing Spondylitis Disease Activity Score >2.1 ( ß = 0.45), positive HLA-B27 ( ß = 0.29), female sex ( ß = 0.19), patients with C-reactive protein elevation ( ß = 0.002), and bilateral ocular involvement ( ß = 0.32). At the same time, shorter disease evolution ( ß = -0.02) was associated with less severe uveitis activity. CONCLUSION: We have determined factors associated with adverse outcomes in patients with uveitis associated with SpA by developing an outcome score SpA-U that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment.


Assuntos
Espondilartrite , Espondilite Anquilosante , Uveíte , Humanos , Feminino , Espondilartrite/complicações , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Uveíte/diagnóstico , Uveíte/epidemiologia , Uveíte/etiologia , Espondilite Anquilosante/complicações , Inflamação , Antígeno HLA-B27
14.
Parasitol Res ; 121(10): 3007-3011, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35906999

RESUMO

Cryptosporidiosis is a leading cause of childhood diarrhoea. Two species, Cryptosporidium hominis and Cryptosporidium parvum, are responsible for most confirmed cases globally. Close contact with pet animals can be an unnoticed source of children infections. We describe a case of infection by rodent-adapted Cryptosporidium wrairi in a 22-month-old immunocompetent toddler with no clinical manifestations in close contact with a pet guinea pig and poor personal hygiene practices in Majadahonda (Madrid, Spain). Attempts to determine the C. wrairi genotype family at the 60-kDa glycoprotein marker failed repeatedly. This is the first description of C. wrairi in a human host. Although a spurious infection cannot be completely ruled out, data presented here suggest that C. wrairi can be transmitted zoonotically.


Assuntos
Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Animais , Criptosporidiose/diagnóstico , Cryptosporidium/genética , Cryptosporidium parvum/genética , Fezes , Genótipo , Cobaias , Humanos , Lactente , Roedores , Espanha
15.
Mar Drugs ; 19(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34822469

RESUMO

Marine algae are recognised sources of bioactive compounds that have attracted great interest as nutritional supplements for aquaculture fish. Intensive rearing conditions often expose fish to husbandry-related stressors, rendering fish more susceptible to disease and reducing production yields. The present work evaluated the potential of two marine algae extracts (Fucus vesiculosus and Nannochloropsis gaditana) as nutritional supplements to mitigate stress effects in meagre (Argyrosomus regius) exposed to an acute handling stress (AS). A plant-based diet was used as a control, and three other diets were prepared, which were similar to the control diet but supplemented with 1% of each algal extract or a combination of the two extracts (0.5% each). The effects of supplemented diets on stress biomarkers, antioxidant enzyme activities, and immune response were analysed in fish exposed to AS after 4 weeks of feeding. Supplemented diets did not affect growth performance but the inclusion of F. vesiculosus promoted higher feed efficiency, as compared to the control group. Dietary algal extracts supplementation reduced plasma glucose levels, increased white blood cell counts, and reduced the expression of pro-inflammatory genes when compared with the control. N. gaditana supplementation led to a reduction in hepatic antioxidant enzyme activity and glutathione levels, while F. vesiculosus supplementation increased muscle glutathione reductase activity and reduced lipid peroxidation. These findings support the potential of algal extracts as nutraceuticals in aquafeeds to enhance the ability of fish to cope with husbandry-related stressful conditions and ultimately improve fish health and welfare.


Assuntos
Ração Animal , Microalgas , Perciformes , Estresse Fisiológico , Animais , Antioxidantes , Aquicultura , Organismos Aquáticos , Alimento Funcional
16.
Z Rheumatol ; 80(5): 481-486, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33709168

RESUMO

Anti-tumor necrosis factor­α (TNF-α)-induced lupus (ATIL) represents a diagnostic and treatment challenge. Most cases are caused by infliximab and in some cases by etanercept and adalimumab. Symptoms can range from cutaneous manifestations to more rare and serious conditions. Diagnosis requires a temporal relationship between symptoms and positive autoantibody determination. Arthritis and cutaneous symptoms are the most common manifestations accompanied by positive antinuclear antibody (ANA) and anti-double strand DNA (dsDNA) determinations. The etiology of ATILS remains to be definitively established. Several mechanisms have been proposed for anti-TNF-α-induced lupus, including apoptosis, immunosuppression and humoral autoimmunity. Treatment includes discontinuation of anti-TNF­α agents and in some cases corticosteroids and immunosuppressors. Questions to be answered: (1) Are soluble TNF receptor fusion proteins such as etanercept and anti-TNF chimeric antibodies equally likely to cause ATIL? (2) Can patients with ATIL switch from one anti-TNF­α antagonist to another? (3) Can the concurrent use of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) like methotrexate or hydroxychloroquine reduce the probability of ATIL?


Assuntos
Antirreumáticos , Inibidores do Fator de Necrose Tumoral , Adalimumab , Anticorpos Monoclonais , Antirreumáticos/efeitos adversos , Etanercepte/efeitos adversos , Humanos , Fator de Necrose Tumoral alfa
17.
Gynecol Endocrinol ; 36(12): 1112-1115, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32233827

RESUMO

The oral glucose tolerance test (OGTT) remains as the gold standard to diagnose gestational diabetes mellitus (GDM); however, this test may be inconvenient and costly. Hence, other easy to perform and accurate diagnostic alternatives would be valuable for maternal care. The objective of the study was to assess the diagnostic performance of the TyG index to screen for GDM at 24-28 of pregnancy. A total of 140 pregnant women who received the one-step 2 h 75 g OGTT were included. Overall GDM prevalence was 27.1% according to IADSPG criteria. The mean TyG index value in the GDM group was significantly higher than the TyG index for the no GDM group (4.88 ± 0.70 versus 4.68 ± 0.19, p<.001). A sensitivity of 89% [95% CI 0.75-0.97] and a specificity of 50% [95% CI 0.39-0.60)], accompanied by a high negative predictive value of 93% was observed. No differences were found in maternal and neonatal outcomes irrespective of the TyG cutoff value for GDM. According to our results, the TyG index may be a highly sensitive and easy to perform screening test for GDM.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Triglicerídeos/sangue , Adolescente , Adulto , Diabetes Gestacional/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal , Sensibilidade e Especificidade , Adulto Jovem
18.
Physiol Rev ; 92(1): 1-38, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22298650

RESUMO

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.


Assuntos
Comunicação Celular/fisiologia , Hipófise/citologia , Hipófise/fisiologia , Transdução de Sinais/fisiologia , Animais , Sistema Endócrino/fisiologia , Homeostase/fisiologia , Hormônios/metabolismo , Humanos , Sistemas Neurossecretores/fisiologia
19.
Amino Acids ; 51(9): 1307-1321, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31428910

RESUMO

This study aimed to evaluate the effect of taurine (tau) supplementation to low fishmeal (FM) diets on growth performance, oxidative status, and immune response of European seabass juveniles. Four isoproteic (46% crude protein) and isolipidic (19% crude lipid) diets were formulated to contain either 25 or 12.5% FM and a mixture of plant feedstuffs, supplemented or not with 1% tau. Twelve groups of 20 fish (IBW = 9.4 g) were fed each diet for 9 weeks. Reduction of dietary FM from 25 to 12.5% impaired growth performance, feed efficiency, and protein efficiency ratio but had no effect on nitrogen retention (% N intake). Independently of FM level, dietary tau supplementation improved growth performance and nitrogen retention without affecting feed efficiency. Dietary FM level reduction increased liver G6PDH activity, but did not affect lipid peroxidation or activities of redox key enzymes. Contrarily, dietary tau supplementation decreased hepatic G6PDH and GPX activities and lipid peroxidation. Gene expression COX-2 was not affected either by FM or tau levels but TNF-α increased with the reduction of FM level but not with the tau level. Dietary tau supplementation decreased Casp3 and Casp9 expression regardless of dietary FM level. Overall, this study evidenced that dietary tau supplementation improved growth performance and antioxidant response and reduced intestine inflammatory and apoptosis processes.


Assuntos
Ração Animal , Bass/metabolismo , Fígado/enzimologia , Taurina/administração & dosagem , Animais , Antioxidantes/metabolismo , Apoptose , Bass/imunologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Dieta/veterinária , Glucosefosfato Desidrogenase/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação , Intestinos/imunologia , Intestinos/fisiologia , Peroxidação de Lipídeos/fisiologia , Fígado/metabolismo , Nitrogênio/metabolismo , Oxirredução , Prostaglandina-Endoperóxido Sintases/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Fish Physiol Biochem ; 45(2): 681-695, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30367427

RESUMO

For an increased incorporation of plant ingredients in aquafeeds at the expense of fish meal (FM) and fish oil (FO), more knowledge is needed on the effects at the intestine level of dietary vegetable oils (VO) and carbohydrates (CH), and of possible interactions. For that purpose, in this study, the activities of digestive pancreatic enzymes (amylase, lipase, total alkaline proteases), gut microbiota, and histomorphology were assessed in gilthead sea bream (IBW 71.0 ± 1.5 g) fed four diets differing in lipid source (FO or a blend of VO) and carbohydrate content (0% or 20% gelatinized starch) for 81 days. No major changes in digestive enzyme activities were noticed in fish fed the experimental diets. Dietary VO, but not CH content, modified intestinal microbial profile, by increasing the similarity of bacterial communities. Especially when combined with CH, dietary VO promoted abnormal enterocyte architecture. Liver histology was also accessed, and an increased cytoplasmic vacuolization of hepatocytes was related with dietary CH inclusion, being only significantly different in fish fed FO-based diets. Overall, nutritional interactions between dietary lipid source and carbohydrate content were not observed on digestive enzyme activities and microbial profile. However, the intestine histological modifications observed in fish fed the VOCH+ diet suggest a negative interaction between dietary VO and CH. This requires a more in depth assessment in future studies as it can have negative consequences at a functional level.


Assuntos
Carboidratos da Dieta/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Óleos de Plantas/farmacologia , Dourada/crescimento & desenvolvimento , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Dieta/veterinária , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Intestinos/enzimologia , Óleos de Plantas/administração & dosagem , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Distribuição Aleatória
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