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1.
Hum Mol Genet ; 32(4): 659-676, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36130212

RESUMO

The large DMD gene encodes a group of dystrophin proteins in brain and retina, produced from multiple promoters and alternative splicing events. Dystrophins are core components of different scaffolding complexes in distinct cell types. Their absence may thus alter several cellular pathways, which might explain the heterogeneous genotype-phenotype relationships underlying central comorbidities in Duchenne muscular dystrophy (DMD). However, the cell-specific expression of dystrophins and associated proteins (DAPs) is still largely unknown. The present study provides a first RNA-Seq-based reference showing tissue- and cell-specific differential expression of dystrophins, splice variants and DAPs in mouse brain and retina. We report that a cell type may express several dystrophin complexes, perhaps due to expression in separate cell subdomains and/or subpopulations, some of which with differential expression at different maturation stages. We also identified new splicing events in addition to the common exon-skipping events. These include a new exon within intron 51 (E51b) in frame with the flanking exons in retina, as well as inclusions of intronic sequences with stop codons leading to the presence of transcripts with elongated exons 40 and/or 41 (E40e, E41e) in both retina and brain. PCR validations revealed that the new exons may affect several dystrophins. Moreover, immunoblot experiments using a combination of specific antibodies and dystrophin-deficient mice unveiled that the transcripts with stop codons are translated into truncated proteins lacking their C-terminus, which we called N-Dp427 and N-Dp260. This study thus uncovers a range of new findings underlying the complex neurobiology of DMD.


Assuntos
Distrofina , Distrofia Muscular de Duchenne , Camundongos , Animais , Distrofina/genética , Distrofina/metabolismo , Transcriptoma/genética , Códon de Terminação/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Retina/metabolismo , Encéfalo/metabolismo
2.
J Clin Immunol ; 44(8): 171, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102004

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.


Assuntos
Vacina BCG , Doença Granulomatosa Crônica , NADPH Oxidase 2 , Tuberculose , Humanos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/complicações , Vacina BCG/efeitos adversos , Masculino , Feminino , Criança , Tuberculose/epidemiologia , Tuberculose/imunologia , Pré-Escolar , Lactente , Adolescente , NADPH Oxidase 2/genética , Estudos de Coortes , Mycobacterium bovis , México/epidemiologia , Antituberculosos/uso terapêutico , NADPH Oxidases/genética
3.
Arch Microbiol ; 206(6): 245, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702537

RESUMO

Production of carotenoids by yeast fermentation is an advantaged technology due to its easy scaling and safety. Nevertheless, carotenoid production needs an economic culture medium and other efficient yeast stains. The study aims to isolate and identify a yeast strain capable of producing carotenoids using a cost-effective substrate. A new strain was identified as Rhodotorula toruloides L/24-26-1, which can produce carotenoids at different pretreated and unpretreated sugarcane molasses concentrations (40 and 80 g/L). The highest biomass concentration (18.6 ± 0.6 g/L) was reached in the culture using 80 g/L of hydrolyzed molasses. On the other hand, the carotenoid accumulation reached the maximum value using pretreated molasses at 40 g/L (715.4 ± 15.1 µg/g d.w). In this case, the ß-carotene was 1.5 times higher than that on the control medium. The yeast growth in molasses was not correlated with carotenoid production. The most outstanding production of The DPPH, ABTS, and FRAP tests demonstrated the antioxidant activity of the obtained carotenogenic extracts. This research demonstrated the R. toruloides L/24-26-1 strain biotechnological potential for carotenoid compounds. The yeast produces carotenoids with antioxidant activity in an inexpensive medium, such as sulfuric acid pretreated and unpretreated molasses.


Assuntos
Fermentação , Melaço , Rhodotorula , Saccharum , beta Caroteno , Rhodotorula/metabolismo , Rhodotorula/genética , Rhodotorula/crescimento & desenvolvimento , Rhodotorula/isolamento & purificação , Rhodotorula/classificação , Saccharum/metabolismo , beta Caroteno/metabolismo , beta Caroteno/biossíntese , Carotenoides/metabolismo , Antioxidantes/metabolismo , Biomassa , Meios de Cultura/química , Filogenia
4.
Int J Mol Sci ; 25(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39273262

RESUMO

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.


Assuntos
Antioxidantes , Catalase , Epilepsia do Lobo Temporal , Glutationa Peroxidase , Levetiracetam , Estresse Oxidativo , Superóxido Dismutase , Animais , Levetiracetam/farmacologia , Levetiracetam/uso terapêutico , Ratos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/metabolismo , Masculino , Superóxido Dismutase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Catalase/metabolismo , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Oxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Modelos Animais de Doenças , Peróxido de Hidrogênio/metabolismo , Ratos Wistar
5.
J Immunol ; 207(9): 2374-2384, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34588222

RESUMO

Deficiency of lymphocyte activation gene-3 (LAG3) is significantly associated with increased cardiovascular disease risk with in vitro results demonstrating increased TNF-α and decreased IL-10 secretion from LAG3-deficient human B lymphoblasts. The hypothesis tested in this study was that Lag3 deficiency in dendritic cells (DCs) would significantly affect cytokine expression, alter cellular metabolism, and prime naive T cells to greater effector differentiation. Experimental approaches used included differentiation of murine bone marrow-derived DCs (BMDCs) to measure secreted cytokines, cellular metabolism, RNA sequencing, whole cell proteomics, adoptive OT-II CD4+Lag3 +/+ donor cells into wild-type (WT) C57BL/6 and Lag3 -/- recipient mice, and ex vivo measurements of IFN-γ from cultured splenocytes. Results showed that Lag3 -/- BMDCs secreted more TNF-α, were more glycolytic, used fewer fatty acids for mitochondrial respiration, and glycolysis was significantly reduced by exogenous IL-10 treatment. Under basal conditions, RNA sequencing revealed increased expression of CD40 and CD86 and other cytokine-signaling targets as compared with WT. Whole cell proteomics identified a significant number of proteins up- and downregulated in Lag3 -/- BMDCs, with significant differences noted in exogenous IL-10 responsiveness compared with WT cells. Ex vivo, IFN-γ expression was significantly higher in Lag3 -/- mice as compared with WT. With in vivo adoptive T cell and in vitro BMDC:T coculture experiments, Lag3 -/- BMDCs showed greater T cell effector differentiation and proliferation, respectively, compared with WT BMDCs. In conclusion, Lag3 deficiency in DCs is associated with an inflammatory phenotype that provides a plausible mechanism for increased cardiovascular disease risk in humans with LAG3 deficiency.


Assuntos
Antígenos CD/metabolismo , Doenças Cardiovasculares/genética , Células Dendríticas/imunologia , Inflamação/imunologia , Linfócitos T/imunologia , Animais , Antígenos CD/genética , Doenças Cardiovasculares/epidemiologia , Células Cultivadas , Reprogramação Celular , Humanos , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Risco , Proteína do Gene 3 de Ativação de Linfócitos
6.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 1109-1114, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36331602

RESUMO

PURPOSE: Myotonic dystrophy type 1 is the most common muscular dystrophy in adulthood, caused by a triplet repeat in chromosome 19q13.3. The present study investigates the frequency of the different ocular alterations in Spanish patients with DM1 and its relationship with the severity of the genetic alteration. METHODS: Cross-sectional and multicenter study was conducted on patients with genetically confirmed DM1. Ophthalmologic examinations included visual acuity assessment, manifest refraction, slit-lamp biomicroscopy, tonometry, ocular motility, corneal tomography, and macular and optic nerve optical coherence tomography. RESULTS: A total of 42 patients (84 eyes) were included. Mean age was 46.9 ± 13.4 (SD) years, and 57.1% were women. Fifteen patients had undergone cataract surgery in at least one eye (35.7%), and 13 (30.9%) had significant cataract. Mean intraocular pressure (IOP) was 10.5 ± 2.9 mmHg, and mean central corneal thickness (CCT) was 580.04 ± 48.61 µm. Half of the patients had significant ptosis, and 8 patients (9.75%) had undergone eyelid surgery. Macular abnormalities included retinal pigment epithelium alterations in 8 eyes of 6 patients, epiretinal membrane in 3 eyes, and lamellar hole in 2 eyes. A moderate correlation was found between IOP and ptosis with the number of triplet repeats. CONCLUSION: Early cataract onset, low IOP, thicker CCT, and ptosis were the most significant manifestations of DM in our sample. Correlation found between IOP and ptosis with CTG repeat could be interesting in order to improve diagnosis and medical care of these patients but should be confirmed in further studies.


Assuntos
Blefaroptose , Catarata , Distrofia Miotônica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Distrofia Miotônica/complicações , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/genética , Estudos Transversais , Pressão Intraocular , Tonometria Ocular , Transtornos da Visão , Catarata/diagnóstico
7.
BMC Pulm Med ; 23(1): 430, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932768

RESUMO

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) due tocoronavirus disease (COVID-19) infection has a unique phenotype generating a growing need to determine the existing differences that can alter existing evidence-based management strategies for ARDS. RESEARCH QUESTION: What differences does the clinical profile of patients with ARDS due to COVID 19 and Non-COVID 19 have? STUDY DESIGN AND METHODS: We conducted a comparative, observational, retrospective study in the Intensive Care Unit (ICU)of a third-level hospital in Mexico City, from March 2020 through March 2022. Clinical, echocardiographic, and laboratory variables were compared between patients with ARDS due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and those due to other etiologies. RESULTS: We enrolled 140 patients with a diagnosis of ARDS. The study group of COVID-19 etiology were younger males, higher body mass index, progressed to organ dysfunction, required more frequently renal replacement therapy, and higher SOFA score. There was no difference in rates of right ventricular dysfunction. INTERPRETATION: COVID-19 ARDS exhibit much greater severity that led to higher admission and mortality rates, whilst being younger and less comorbid.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Masculino , México , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , SARS-CoV-2 , Atenção Terciária à Saúde , Feminino
8.
Echocardiography ; 40(11): 1216-1226, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37742087

RESUMO

BACKGROUND: Evaluation of the venous system has long been underestimated as an important component of the circulatory system. As systemic venous pressure increases, the perfusion pressure to the tissues is compromised. During initial resuscitation in cardiac surgery, excessive fluid administration is associated with increased morbidity and mortality. METHODS: We conducted a cross-sectional study of 60 consecutive adult patients who underwent cardiac surgery and in whom it was possible to obtain the venous excess ultrasound (VExUS) grading system and mean systemic filling pressure (Pmsf) in the postoperative period upon admission, at 24 and 48 h. We then determined the correlation between VExUS grading and Pmsf. RESULTS: On admission, patients with VExUS grading 0 predominated, with a progressive increase in venous congestion and an increase in Pmsf over the course of the first 48 h. There was a strong positive correlation between VExUS grading and the invasive measurement of Pmsf at 24 and 48 h after arrival. The presence of grade 2 or grade 3 venous congestion in the postoperative period poses an increased risk of developing acute kidney injury. CONCLUSION: The VExUS grading system indicates a high degree of systemic venous congestion in the first 48 h of the postoperative period after cardiac surgery and correlates with the Pmsf, which is the best surrogate of stressed circulatory volume.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Sistema Cardiovascular , Hiperemia , Humanos , Estudos Transversais
9.
Echocardiography ; 40(9): 1016-1020, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37498200

RESUMO

Congenitally corrected transposition of the great arteries is a rare clinical entity, which usually presents during adulthood with associated defects; atrioventricular block, heart failure, systemic valve failure, and arrhythmias usually complicate the clinical course. Even rarer is associated hypertrophic cardiomyopathy, which complicates the disease course and clinical decision-making. Herein, we present a patient with this condition who underwent heart transplantation, with adequate clinical resolution.


Assuntos
Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Transposição dos Grandes Vasos , Humanos , Adulto , Transposição das Grandes Artérias Corrigida Congenitamente/complicações , Transposição dos Grandes Vasos/complicações , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Insuficiência Cardíaca/complicações , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem
10.
Nanomedicine ; 52: 102691, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37329939

RESUMO

Gene therapy is a promising approach for treating genetic disorders by delivering therapeutic genes to replace or correct malfunctioning genes. However, the introduced gene therapy vector can trigger an immune response, leading to reduced efficacy and potential harm to the patient. To improve the efficiency and safety of gene therapy, preventing the immune response to the vector is crucial. This can be achieved through the use of immunosuppressive drugs, vector engineering to evade the immune system, or delivery methods that bypass the immune system altogether. By reducing the immune response, gene therapy can deliver therapeutic genes more effectively and potentially cure genetic diseases. In this study, a novel molecular imprinting technique, combined with mass-spectrometry and bioinformatics, was used to identify four antigen-binding fragments (Fab) sequences of Adeno-Associated Virus (AAV) - neutralising antibodies capable of binding to AAV. The identified Fab peptides were shown to prevent AAV8's binding to antibodies, demonstrating their potential to improve gene therapy efficiency by preventing the immune response.


Assuntos
Anticorpos Neutralizantes , Impressão Molecular , Humanos , Mapeamento de Epitopos , Dependovirus/genética , Sorogrupo , Vetores Genéticos , Peptídeos/genética
11.
Molecules ; 28(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37630269

RESUMO

Structure-activity relationship (SAR) studies allow the evaluation of the relationship between structural chemical changes and biological activity. Fluoroquinolones have chemical characteristics that allow their structure to be modified and new analogs with different therapeutic properties to be generated. The objective of this research is to identify and select the C-7 heterocycle fluoroquinolone analog (FQH 1-5) with antibacterial activity similar to the reference fluoroquinolone through in vitro, in silico, and in vivo evaluations. First, SAR analysis was conducted on the FQH 1-5, using an in vitro antimicrobial sensibility model in order to select the best compound. Then, an in silico model mechanism of action analysis was carried out by molecular docking. The non-bacterial cell cytotoxicity was evaluated, and finally, the antimicrobial potential was determined by an in vivo model of topical infection in mice. The results showed antimicrobial differences between the FQH 1-5 and Gram-positive and Gram-negative bacteria, identifying the 7-benzimidazol-1-yl-fluoroquinolone (FQH-2) as the most active against S. aureus. Suggesting the same mechanism of action as the other fluoroquinolones; no cytotoxic effects on non-bacterial cells were found. FQH-2 was demonstrated to decrease the amount of bacteria in infected wound tissue.


Assuntos
Antibacterianos , Anti-Infecciosos , Animais , Camundongos , Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Simulação de Acoplamento Molecular , Staphylococcus aureus , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Relação Estrutura-Atividade
12.
Echocardiography ; 39(8): 1138-1141, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35819108

RESUMO

A 34-year-old male was admitted with presumed acute, severe aortic regurgitation. Multimodal imaging was performed and showed a ruptured right coronary sinus of Valsalva aneurysm into the right atrium. He underwent a percutaneous closure of the ruptured sinus of Valsalva aneurysm. The patient had major clinical improvement.


Assuntos
Aneurisma Aórtico , Ruptura Aórtica , Insuficiência da Valva Aórtica , Seio Aórtico , Adulto , Coração , Humanos , Masculino
13.
Bull Environ Contam Toxicol ; 108(1): 107-113, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34160637

RESUMO

This study describes the optimization of the biodegradation of total aliphatic (tAHCs), total aromatic (tPAHs), and unresolved complex mixture (UCM) hydrocarbons from light crude oil in marine sediment. The response surface methodology (RSM), with a Box-Behnken design, was used to optimize the hydrocarbon fraction degradation, reported as degradation efficiency (E (%)), using four independent variables (inoculum, dispersant, light oil concentration, and carbon/nitrogen ratio), all at three levels. Analysis of variance (ANOVA) showed R2 values of 0.976, 0.974, and 0.975 for tAHCs, tPAHs, and UCM, respectively. All fractions exhibited a statistically significant effect (P < 0.05) in the second-order quadratic regression model for degradation. According to the models, the optimal degradation prediction was: 81.03% for tAHCs, 85.96% for tPAHs, and 92.86% for UCM. This work highlights the possibility of carrying out efficient biodegradation, of more than 80%, through an optimization process using different light oil concentrations, opening up possibilities of multiple response optimization.


Assuntos
Poluição por Petróleo , Petróleo , Biodegradação Ambiental , Sedimentos Geológicos , Hidrocarbonetos , Poluição por Petróleo/análise
14.
Bull Environ Contam Toxicol ; 108(1): 93-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33954861

RESUMO

Degradation efficiency of a heavy crude oil by a marine microbial consortium was evaluated in this study, with and without the addition of a chemical dispersant (Nokomis 3-F4). 15.50% of total petroleum hydrocarbons (TPH) were removed after 15 days of incubation without dispersant, with a degradation rate of 2.39 ± 0.22 mg L-1 day-1. In contrast, the addition of Nokomis 3-F4 increased TPH degradation up to 30.81% with a degradation rate of 5.07 ± 0.37 mg L-1 day-1. 16S rRNA gene sequencing indicated a dominance of the consortium by Achromobacter and Alcanivorax. Nonetheless, significant increases in the relative abundance of Martelella and Ochrobactrum were observed with the addition of Nokomis 3-F4. These results will contribute to further environmental studies of the Gulf of Mexico, where Nokomis 3-F4 can be used as chemical dispersant.


Assuntos
Poluição por Petróleo , Petróleo , Poluentes Químicos da Água , Biodegradação Ambiental , Consórcios Microbianos , Poluição por Petróleo/análise , RNA Ribossômico 16S/genética , Água , Poluentes Químicos da Água/análise
15.
Actas Esp Psiquiatr ; 50(1): 58-62, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35103298

RESUMO

Spinocerebellar ataxia type 10 (SCA10) is characteri- zed by ataxia, psychiatric disorders convulsions, and locus at 22q13.311. It is caused by expansions between 800-4500 pentanucleotide ATTCT repeats in intron 9 of the ATXN10 gene1-2. The ATXN10 gene encodes ataxin-10 protein (known as E46L) involved in neuritogenesis 1. SCA10 has a founder origin in Mexican, Brazilian, Argentine populattons but is rare in others.


Assuntos
Ataxias Espinocerebelares , Ideação Suicida , Ataxina-10 , Expansão das Repetições de DNA , Feminino , Humanos , México , Ataxias Espinocerebelares/genética
16.
Echocardiography ; 38(8): 1345-1351, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34286870

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) frequently involves cardiovascular manifestations such as right ventricular (RV) dysfunction and alterations in pulmonary hemodynamics. We evaluated the application of the critical care ultrasonography ORACLE protocol to identify the most frequent alterations and their influence on adverse outcomes, especially those involving the RV (dilatation and dysfunction). METHODS: This cross-sectional study included 204 adult patients with confirmed COVID-19 admitted at three centers. Echocardiography and lung ultrasound images were acquired on admission using the ORACLE ultrasonography algorithm. RESULTS: Two-hundred and four consecutive patients were evaluated: 22 (11.9%) demonstrated a fractional shortening of < 35%; 33 (17.1%) a tricuspid annular plane systolic excursion (TAPSE) of < 17 mm; 26 (13.5%) a tricuspid peak systolic S wave tissue Doppler velocity of < 9.5 cm/sec; 69 (37.5%) a RV basal diameter of > 41 mm; 119 (58.3%) a pulmonary artery systolic pressure (PASP) of > 35 mm Hg; and 14 (11%) a TAPSE/PASP ratio of < .31. The in-hospital mortality rate was 37.6% (n = 71). Multiple logistic regression modeling showed that PASP > 35 mm Hg, RV FS of < 35%, TAPSE < 17 mm, RV S wave < 9.5, and TAPSE/PASP ratio < .31 mm/mm Hg were associated with this outcome. PASP and the TAPSE/PASP ratio had the lowest feasibility of being obtained among the investigators (62.2%). CONCLUSION: The presence of RV dysfunction, pulmonary hypertension, and alteration of the RV-arterial coupling conveys an increased risk of in-hospital mortality in patients presenting with COVID-19 upon admission; therefore, searching for these alterations should be routine. These parameters can be obtained quickly and safely with the ORACLE protocol.


Assuntos
COVID-19 , Disfunção Ventricular Direita , Adulto , Estudos Transversais , Ecocardiografia Doppler , Mortalidade Hospitalar , Humanos , Artéria Pulmonar/diagnóstico por imagem , SARS-CoV-2 , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita
17.
Ophthalmic Plast Reconstr Surg ; 37(4): 377-380, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33237671

RESUMO

PURPOSE: To analyze functional results and complications of the use of autologous fascia lata in frontalis suspension in children under 3 years old and to confirm its technical viability. METHODS: A retrospective review of 8 patients (12 eyes) who underwent frontalis suspension using autologous fascia lata sling. RESULTS: Twelve eyes of 8 patients were analyzed, with an average age of 1.8 ± 0.6 years. Preoperatively, the mean margin-to-reflex distance 1 was -0.17 ± 0.577 mm. Postoperatively the mean margin-to-reflex distance 1 was 2.66 ± 0.492 mm without any graft donor site or corneal complications. No recurrence was recorded in the follow-up period (mean follow-up period 28.5 ± 32.33 months). CONCLUSIONS: Autologous fascia lata is an eligible material in frontalis suspension in children under 3 years old, despite the traditional oculoplastic dogma that advises against.


Assuntos
Blefaroptose , Fascia Lata , Blefaroptose/cirurgia , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Recidiva , Estudos Retrospectivos , Transplante Autólogo
18.
Int J Food Sci Nutr ; 72(1): 26-36, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32314935

RESUMO

Epidemiological data suggest protective effects of oestrogen and phytoestrogen on lung tissue. This study aimed to elucidate the role of 17-ß-oestradiol and phytoestrogen in age-related inhibition of surfactant synthesis and oxidative stress in rat type II pneumocytes. Forty male and 66 female Wistar rats were used. Female rats were randomly kept intact or ovariectomized at age 12 months. At age 22 months, ovariectomized rats received 17-ß-oestradiol, soy extract, or no treatment. Oxidative stress markers CO, NO, cGMP and lipid peroxide (LPO), antioxidant enzymes and phosphatidylcholine (PC) were measured in cultured type II pneumocytes isolated at ages 2, 14, 18, 22 and 24 months. Old, male and ovariectomized rats showed significantly higher CO, NO, cGMP and LPO and lower PC content and antioxidant enzymes. 17-ß-oestradiol and phytoestrogen significantly reversed these effects. In conclusion, aging and oestrogen deprivation decreased PC synthesis and altered the redox status in type II pneumocytes, which were partially restored by 17-ß-oestradiol or soy supplementation.


Assuntos
Envelhecimento/fisiologia , Células Epiteliais Alveolares/efeitos dos fármacos , Estradiol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fitoestrógenos/farmacologia , Células Epiteliais Alveolares/metabolismo , Animais , Catalase/metabolismo , Feminino , Guanosina Monofosfato/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fosfatidilcolinas/metabolismo , Ratos , Ratos Wistar , Tensoativos/farmacologia
19.
J Tissue Viability ; 30(1): 51-58, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33139157

RESUMO

The aim of the present work was to evaluate MTX treatment (0.1, 1 and 10 µg mL-1) in vitro in order to characterize its effects on cell proliferation alterations in cell cycle of HaCaT keratinocytes and wound healing in a Skh1 mice treated with MTX (low doses 30 mg kg-1, high doses 200 mg kg-1 and repeated doses at 1.5 mg kg-1). We analyzed the cytotoxic effect of methotrexate by a resazurin assay. The effects in the proliferation, cell cycle and apoptosis of HaCaT cells were analyzed by flow cytometry. The effects of MTX on wound healing in vivo were also analyzed. A trend toward reduction in the resazurin assay was found (p > 0.05). Reduced proliferation was also identified in a clonogenic assay and a CFSE assay (p < 0.05) due to the MTX treatment. A reduction in the G2/M and S phases was observed accompanied by apoptosis induction with increased sub G0 phase and annexin V FITC staining. Effect of MTX was evidenced in vivo on the wound closure process after day 10 (p < 0.05) with alterations in tissue architecture and remodeling. There is a marked effect of MTX on wound healing in vivo in Skh1 mice with implications for long-term therapy and surgical interventions.


Assuntos
Proliferação de Células/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Metotrexato/farmacologia , Cicatrização/efeitos dos fármacos , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Estatísticas não Paramétricas
20.
Gac Med Mex ; 157(3): 251-256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667326

RESUMO

INTRODUCTION: Lung ultrasound (LUS) implementation in patients with COVID-19 can help to establish the degree of pulmonary involvement, evaluate treatment response and estimate in-hospital outcome. OBJECTIVE: To evaluate the application of a LUS protocol in patients with COVID-19 infection to predict in-hospital mortality. METHODS: The study was carried out from April 1 to August 1, 2020 in patients with COVID-19 infection admitted to the Intensive Care Unit. Lung evaluation was carried out by physicians trained in critical care ultrasonography. RESULTS: Most patients were males, median age was 56 years, and 59 % required mechanical ventilation. In-hospital mortality was 39.4 %, and in those with a LUS score ≥ 19, mortality was higher (50 %). The multiple logistic regression model showed that a LUS score ≥ 19 was significantly associated with mortality (hazard ratio = 2.55, p = 0.01). CONCLUSIONS: LUS is a safe and fast clinical tool that can be applied at bedside in patients with COVID-19 infection to establish the degree of parenchymal involvement and predict mortality.


INTRODUCCIÓN: La implementación del ultrasonido pulmonar (LUS) en los pacientes con COVID-19 puede ayudar a establecer el grado de afectación pulmonar, evaluar la respuesta al tratamiento y estimar el desenlace intrahospitalario. OBJETIVO: Evaluar la aplicación de un protocolo LUS en pacientes con infección por COVID-19 para predecir mortalidad intrahospitalaria. MÉTODOS: El estudio se realizó del 1 de abril al 1 de agosto de 2020 en pacientes con infección por COVID-19, ingresados en la Unidad de Terapia Intensiva. Se realizó evaluación pulmonar por médicos entrenados en ultrasonografía crítica. RESULTADOS: La mayoría de los pacientes fue del sexo masculino, la edad mediana fue de 56 años y 59 % requirió ventilación mecánica. La mortalidad intrahospitalaria fue de 39.4 % y en aquellos con puntuación de LUS ≥ 19, de 50 %. El modelo de regresión logística múltiple mostró que la puntuación de LUS ≥ 19 se asoció significativamente a mortalidad (cociente de riesgo = 2.55, p = 0.01). CONCLUSIONES: El LUS es una herramienta clínica segura y rápida que puede realizarse al lado de la cama de los pacientes con infección por COVID-19, para establecer el grado de afectación parenquimatosa y predecir la mortalidad.


Assuntos
COVID-19/complicações , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Pulmão/diagnóstico por imagem , Ultrassonografia , Idoso , COVID-19/mortalidade , Cuidados Críticos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Respiração Artificial/estatística & dados numéricos
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