Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 103
Filtrar
1.
Neural Regen Res ; 20(8): 2395-2407, 2025 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39359096

RESUMO

JOURNAL/nrgr/04.03/01300535-202508000-00029/figure1/v/2024-09-30T120553Z/r/image-tiff Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system, including retinal ganglion cell axonal growth through the injured optic nerve. Still, it is unknown whether olfactory ensheathing glia also have neuroprotective properties. Olfactory ensheathing glia express brain-derived neurotrophic factor, one of the best neuroprotectants for axotomized retinal ganglion cells. Therefore, we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush. Olfactory ensheathing glia cells from an established rat immortalized clonal cell line, TEG3, were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments. Anatomical and gene expression analyses were performed. Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex class II molecules. Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days, forming an epimembrane. In axotomized retinas, only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days. In these retinas, microglial anatomical activation was higher than after optic nerve crush alone. In intact retinas, both transplants activated microglial cells and caused retinal ganglion cell death at 21 days, a loss that was higher after allotransplantation, triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression. However, neuroprotection of axotomized retinal ganglion cells did not improve with these treatments. The different neuroprotective properties, different toxic effects, and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

2.
J Biomater Appl ; 39(3): 207-220, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38820599

RESUMO

This study addresses the morphological and chemical characterization of PGS scaffolds after (6, 12, 18, 24, and 30 min) residence in undoped pyrrole plasma (PGS-PPy) and the evaluation of cell viability with human dental pulp stem cells (hDPSCs). The results were compared with a previous study that used iodine-doped pyrrole (PGS-PPy/I). Analyses through SEM and AFM revealed alterations in the topography and quantity of deposited PPy particles. FTIR spectra of PGS-PPy scaffolds confirmed the presence of characteristic absorption peaks of PPy, with higher intensities observed in the nitrile and -C≡C- groups compared to PGS-PPy/I scaffolds, while raman spectra indicated a lower presence of polaron N+ groups. On the other hand, PGS scaffolds modified with PPy exhibited lower cytotoxicity compared to PGS-PPy/I scaffolds, as evidenced by the Live/Dead assay. Furthermore, the PGS-PPy scaffolds at 6 and 12 min, and particularly the PGS-PPy/I scaffold at 6 min, showed the best results in terms of cell viability by the fifth day of culture. The findings of this study suggest that undoped pyrrole plasma modification for short durations could also be a viable option to enhance the interaction with hDPSCs, especially when the treatment times range between 6 min and 12 min.


Assuntos
Sobrevivência Celular , Decanoatos , Polpa Dentária , Iodo , Polímeros , Pirróis , Células-Tronco , Alicerces Teciduais , Humanos , Polpa Dentária/citologia , Pirróis/química , Células-Tronco/citologia , Iodo/química , Alicerces Teciduais/química , Polímeros/química , Sobrevivência Celular/efeitos dos fármacos , Decanoatos/química , Glicerol/química , Glicerol/análogos & derivados , Células Cultivadas , Materiais Biocompatíveis/química , Teste de Materiais , Gases em Plasma/química , Engenharia Tecidual
3.
Aging Dis ; 15(5): 2241-2254, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502581

RESUMO

This study aims to investigate two key aspects in a mouse model of ocular hypertension (OHT): first, the time course of retinal ganglion cell (RGC) death and the parallel activation of caspase-3 (a-Casp3+ cells) to narrow the therapeutic window; and second, the effect of caspase-3 and microglia inhibition by minocycline on RGC rescue in this model. RGC loss after OHT induction was significant at day 7 and progressed to 30 days. However, anatomical RGC death was preceded by significant Casp3 activation on day 3. Microglial inhibition by minocycline did not alter the course of OHT or rescue RGCs but resulted in a decrease in a-Casp3+ cells and phagocytic and total microglia. Therefore, RGC death commitment occurs earlier than their loss of Brn3a expression, microglial cells do not exacerbate RGC loss, and while this death is primarily apoptotic, apoptosis inhibition does not rescue RGCs, suggesting that alternative death pathways play a role in glaucomatous injury.


Assuntos
Sobrevivência Celular , Modelos Animais de Doenças , Minociclina , Hipertensão Ocular , Células Ganglionares da Retina , Animais , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Minociclina/farmacologia , Minociclina/uso terapêutico , Minociclina/administração & dosagem , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/patologia , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Caspase 3/metabolismo , Apoptose/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Camundongos Endogâmicos C57BL
4.
Rev Esp Enferm Dig ; 116(8): 423-437, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38305682

RESUMO

Acute pancreatitis is associated with significant morbidity and mortality. It can develop complications such as fluid collections and necrosis. Infection of necrosis occurs in about 20-40 % of patients with severe acute pancreatitis, and is associated with organ failure and worse prognosis. In the past few years the treatment of pancreatic collections has shifted from open surgery to minimally invasive techniques such as endoscopic ultrasound-guided drainage. These guidelines from a selection of experts among the Endoscopic Ultrasound Group, Spanish Society of Gastrointestinal Endoscopy (GSEED-USE) are intended to provide advice on the management of pancreatic collections based on a thorough review of the available scientific evidence. It also reflects the experience and clinical practice of the authors, who are advanced endoscopists or clinical pancreatologists with extensive experience in managing patients with acute pancreatitis.


Assuntos
Endossonografia , Pancreatite , Humanos , Endossonografia/métodos , Pancreatite/diagnóstico por imagem , Pancreatite/terapia , Drenagem/métodos , Endoscopia do Sistema Digestório/métodos , Espanha
5.
Front Neuroanat ; 18: 1335176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415017

RESUMO

Purpose: The aim of this study was to investigate, the neuroprotective effects of a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity induced by intravitreal injection of NMDA. Methods: Adult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left eye and were treated daily with subcutaneous injections of ITH12657 or vehicle. The best dose-response, therapeutic window study, and optimal treatment duration of ITH12657 were studied. Based on the best survival of Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography), and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs. Results: Administration of 10 mg/kg ITH12657, starting 12 h before NMDA injection and dispensed for 3 days, resulted in the best significant protection of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functional protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed that ITH12657 afforded a significant protection against NMDA-induced excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but not for the population of αOFF-RGC, while the population of α-ONtRGC was fully resistant to NMDA-induced excitotoxicity. Conclusion: Subcutaneous administration of ITH12657 at 10 mg/kg, initiated 12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitive while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity.

6.
Front Immunol ; 15: 1340013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384465

RESUMO

Background: Neurological dysfunction and glial activation are common in severe infections such as sepsis. There is a sexual dimorphism in the response to systemic inflammation in both patients and animal models, but there are few comparative studies. Here, we investigate the effect of systemic inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) on the retina of male and female mice and determine whether antagonism of the NLRP3 inflammasome and the extrinsic pathway of apoptosis have protective effects on the retina. Methods: A single intraperitoneal injection of LPS (5 mg/kg) was administered to two months old C57BL/6J male and female mice. Retinas were examined longitudinally in vivo using electroretinography and spectral domain optical coherence tomography. Retinal ganglion cell (RGC) survival and microglial activation were analysed in flat-mounts. Retinal extracts were used for flow cytometric analysis of CD45 and CD11b positive cells. Matched plasma and retinal levels of proinflammatory cytokines were measured by ELISA. Retinal function and RGC survival were assessed in animals treated with P2X7R and TNFR1 antagonists alone or in combination. Results: In LPS-treated animals of both sexes, there was transient retinal dysfunction, loss of vision-forming but not non-vision forming RGCs, retinal swelling, microglial activation, cell infiltration, and increases in TNF and IL-1ß. Compared to females, males showed higher vision-forming RGC death, slower functional recovery, and overexpression of lymphotoxin alpha in their retinas. P2X7R and TNFR1 antagonism, alone or in combination, rescued vision-forming RGCs. P2X7R antagonism also rescued retinal function. Response to treatment was better in females than in males. Conclusions: Systemic LPS has neuronal and sex-specific adverse effects in the mouse retina, which are counteracted by targeting the NLRP3 inflammasome and the extrinsic pathway of apoptosis. Our results highlight the need to analyse males and females in preclinical studies of inflammatory diseases affecting the central nervous system.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Camundongos , Masculino , Feminino , Animais , Lactente , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Retina , Células Ganglionares da Retina/metabolismo , Inflamação/metabolismo
8.
Viruses ; 15(9)2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37766248

RESUMO

(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07-1.09), cancer (OR: 1.99, 1.53-2.60), dementia (OR: 1.82, 1.20-2.75), the Charlson index (1.38, 1.31-1.47), the need for high-flow oxygen (OR: 6.10, 4.94-7.52), mechanical ventilation (OR: 11.554, 6.996-19.080), and CRP (OR: 1.04, 1.03-1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach.


Assuntos
COVID-19 , Epidemias , Humanos , Idoso , COVID-19/epidemiologia , Estudos Retrospectivos , Hospitais , Hospitalização
9.
Eur Spine J ; 32(12): 4428-4436, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37715790

RESUMO

PURPOSE: The aim of this study was to determine whether MRI texture analysis could predict the prognosis of patients with non-specific chronic low back pain. METHODS: A prospective observational study was conducted on 100 patients with non-specific chronic low back pain, who underwent a conventional MRI, followed by rehabilitation treatment, and revisited after 6 months. Sociodemographic variables, numeric pain scale (NPS) value, and the degree of disability as measured by the Roland-Morris disability questionnaire (RMDQ), were collected. The MRI analysis included segmentation of regions of interest (vertebral endplates and intervertebral disks from L3-L4 to L5-S1, paravertebral musculature at the L4-L5 space) to extract texture variables (PyRadiomics software). The classification random forest algorithm was applied to identify individuals who would improve less than 30% in the NPS or would score more than 4 in the RMDQ at the end of the follow-up. Sensitivity, specificity, and the area under the ROC curve were calculated. RESULTS: The final series included 94 patients. The predictive model for classifying patients whose pain did not improve by 30% or more offered a sensitivity of 0.86, specificity 0.57, and area under the ROC curve 0.71. The predictive model for classifying patients with a RMDQ score 4 or more offered a sensitivity of 0.83, specificity of 0.20, and area under the ROC curve of 0.52. CONCLUSION: The texture analysis of lumbar MRI could help identify patients who are more likely to improve their non-specific chronic low back pain through rehabilitation programs, allowing a personalized therapeutic plan to be established.


Assuntos
Dor Lombar , Humanos , Dor Lombar/diagnóstico por imagem , Dor Lombar/reabilitação , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , Imageamento por Ressonância Magnética , Prognóstico , Curva ROC , Estudos Prospectivos
10.
Discov Med ; 35(177): 553-564, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553309

RESUMO

PURPOSE: To evaluate the effects of various retinal neurotransmitters on temporal resolution, particularly, on the Critical Flicker Fusion Frequency (CFF), which has been previously applied in ophthalmic pathophysiologic research. METHODS: A binocular physiologic electroretinogram was performed on adult mice. Animals in the control group were injected in the right eye with 1 µL of phosphate-buffered saline (PBS). Animals in the experimental group were injected in the left eye with 1 µL of PBS and in the right eye with 1 µL of PBS to which different molecules were added: 2-amino-4-phosphonobutyric acid (APB), Glutamate, γ-aminobutyric acid (GABA), 6,7-dinitroquinoxaline-2,3-dione (DNQX), Bicuculline, Glycine, and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). Initially, rod response was recorded and later the cone response. RESULTS: APB suppressed the rod-driven, but not the cone-driven flicker response. The other agents severely affected the lower flickering frequency response amplitude, in particular, at 3 Hz. The threshold of CFF was lowered from 50 Hz to 40 Hz after applying APB, Glycine, and HEPES. GABA remarkably enhanced rod-driven and cone-driven flicker response at 3 Hz, whereas Glutamate and GABA/Glutamate only did in rod-driven flicker response. CONCLUSIONS: Both ON and OFF visual pathways were implied in cone-driven response, but only the ON visual pathway appears to play a relevant role in rod-driven flicker response. Flicker response seems to be enhanced by horizontal cells both in rod-driven and cone-driven response. In addition, due to the greater sensitivity of the flicker at low frequencies, it is suggested that pathophysiological studies should be carried out at said frequencies.


Assuntos
Eletrorretinografia , Vias Visuais , Camundongos , Animais , HEPES , Estimulação Luminosa , Ácido gama-Aminobutírico , Glutamatos
11.
Cancers (Basel) ; 15(16)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37627062

RESUMO

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

12.
Methods Mol Biol ; 2708: 175-194, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37558971

RESUMO

The identification of distinct retinal ganglion cell (RGC) populations in flat-mounted retinas is key to investigating pathological or pharmacological effects in these cells. In this chapter, we review the main techniques for detecting the total population of RGCs and various of their subtypes in whole-mounted retinas of pigmented and albino rats and mice, four of the animal strains most studied by the scientific community in the retina field. These methods are based on the studies published by the Vidal-Sanz's laboratory.


Assuntos
Retina , Células Ganglionares da Retina , Ratos , Camundongos , Animais , Células Ganglionares da Retina/patologia , Retina/patologia
13.
J Clin Med ; 12(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37445561

RESUMO

The effectiveness of in virtuo exposure-based treatment of performance-only social anxiety disorder (SAD) has been demonstrated in several studies. However, few studies have validated virtual environments with participants suffering from generalized SAD. The goal of this study is to confirm the potential of a virtual environment in inducing anxiety in adults suffering from generalized SAD, compared to adults without SAD, when engaged in awkward social interactions. Differences between participants from two different countries were also explored. The sample consisted of 15 participants with SAD from Canada, 17 participants without SAD from Canada, 16 participants with SAD from Spain, and 21 participants without SAD from Spain. All participants were immersed in a control virtual environment and in an experimental virtual environment considered potentially anxiety-inducing for individuals with generalized SAD. As hypothesized, results showed that the experimental virtual environment induced a higher level of anxiety than the control environment among participants with SAD compared to those without SAD. The impact on anxiety of each socially threatening task performed during the experimental immersion was statistically significant. In terms of anxiety responses, no significant differences were found between participants from Canada and Spain. However, spatial presence and ecological validity were higher in Canadians than in Spaniards. Unwanted negative side effects induced by immersions in virtual reality were higher in the SAD group. This study highlights the importance for therapists to engage people with SAD in clinically relevant tasks while immersed in VR psychotherapeutic applications.

14.
Int J Cancer ; 153(6): 1151-1161, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37260300

RESUMO

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.


Assuntos
Neoplasias da Vesícula Biliar , Cálculos Biliares , Idoso , Humanos , Estudos de Casos e Controles , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/genética , Cálculos Biliares/epidemiologia , Cálculos Biliares/genética , Cálculos Biliares/complicações , Incidência , Estudos Retrospectivos , Fatores de Risco , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
15.
J Fungi (Basel) ; 9(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36836256

RESUMO

Candida albicans is an opportunistic fungal pathogen that may cause invasive infections in immunocompromised patients, disseminating through the bloodstream to other organs. In the heart, the initial step prior to invasion is the adhesion of the fungus to endothelial cells. Being the fungal cell wall's outermost structure and the first to come in contact with host cells, it greatly modulates the interplay that later will derive in the colonization of the host tissue. In this work, we studied the functional contribution of N-linked and O-linked mannans of the cell wall of C. albicans to the interaction with the coronary endothelium. An isolated rat heart model was used to assess cardiac parameters related to vascular and inotropic effects in response to phenylephrine (Phe), acetylcholine (aCh) and angiotensin II (Ang II) when treatments consisting of: (1) live and heat-killed (HK) C. albicans wild-type yeasts; (2) live C. albicans pmr1Δ yeasts (displaying shorter N-linked and O-linked mannans); (3) live C. albicans without N-linked and O-linked mannans; and (4) isolated N-linked and O-linked mannans were administered to the heart. Our results showed that C. albicans WT alters heart coronary perfusion pressure (vascular effect) and left ventricular pressure (inotropic effect) parameters in response to Phe and Ang II but not aCh, and these effects can be reversed by mannose. Similar results were observed when isolated cell walls, live C. albicans without N-linked mannans or isolated O-linked mannans were perfused into the heart. In contrast, C. albicans HK, C. albicans pmr1Δ, C. albicans without O-linked mannans or isolated N-linked mannans were not able to alter the CPP and LVP in response to the same agonists. Taken together, our data suggest that C. albicans interaction occurs with specific receptors on coronary endothelium and that O-linked mannan contributes to a greater extent to this interaction. Further studies are necessary to elucidate why specific receptors preferentially interact with this fungal cell wall structure.

16.
J Med Virol ; 95(2): e28495, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36639911

RESUMO

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.


Assuntos
COVID-19 , Adulto , Humanos , Mesilato de Imatinib , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento
17.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1441479

RESUMO

Introducción: El surgimiento de fármacos anestésicos de corta duración estimularon a los anestesiólogos a plantearse un nuevo enfoque para la cirugía videolaparoscópica en el adulto mayor. Analgesia intensa, menor consumo de opioides, rápida recuperación de la conciencia y ventilación espontánea; extubación precoz, disminución de complicaciones y reducción de la estancia hospitalaria. Objetivo: Evaluar en los pacientes geriátricos programados para colecistectomía videolaparoscópica electiva, el efecto de la anestesia intravenosa total con la asociación ketamina/propofol en comparación con fentanil/propofol. Métodos: Se realizó un estudio cuasiexperimental en 40 pacientes con 60 años y más, estado físico II-III según la clasificación de ASA, en el Hospital Universitario "Faustino Pérez Hernández" de Matanzas, programados para cirugía videolaparoscópica electiva. Resultados: La edad promedio osciló entre 63 y 78 años, con una superioridad del sexo femenino y la raza blanca, la clasificación ASA II fue la más representativa en ambos grupos. Imperaron los antecedentes cardiovasculares, hubo ligera disminución de valores espirados de CO2 respecto a los basales, sin diferencias significativas. Hubo variación de la TAM indistintamente en ambos grupos. En el grupo 1 la frecuencia cardiaca posterior a la inducción disminuyó (70 ± 5 lat/min) y se mantuvieron valores inferiores a los basales durante los primeros 20 min, el tiempo medio de recuperación fue significativamente menor en el grupo 2. Conclusiones: La asociación ketamina/propofol proporciona resultados positivos finales.


Introduction: The emergence of short-acting anesthetic drugs stimulated the anesthesiologist to consider a new approach for videolaparoscopic surgery in the elderly. Intense analgesia, decreased opioid consumption, rapid recovery of consciousness, and spontaneous ventilation; early extubation, reduction of complications and reduction of hospital stay. Objective: To evaluate in geriatric patients scheduled for elective videolaparoscopic cholecystectomy the effects of total intravenous anesthesia with the combination of ketamine / propofol, comparing it with fentanyl / propofol. Materials and methods: a descriptive, prospective, longitudinal study was carried out in 40 patients aged 60 years and over, ASA II-III at the "Faustino Pérez Hernández" University Hospital in Matanzas in 2018, scheduled for elective videolaparoscopic surgery. Results: The average age ranged between 63 and 78 years, with a superiority of the female sex and the white race. The ASA II classification was the most representative in both groups. Cardiovascular antecedents prevailed, there was a slight decrease in expired CO2 values compared to baseline, without significant differences. There was variation of the TAM indistately in both groups. In group 1, the heart rate after induction decreased (70 ± 5 beats/min) and values lower than baseline were maintained during the first 20 min. The mean recovery time was significantly shorter in group 2. Conclusions: The association ketamine / propofol provides final positive results.


Assuntos
Humanos , Pessoa de Meia-Idade
18.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1512339

RESUMO

Introducción: Debido a la inestabilidad rotatoria de las fracturas basicervicales, en estudios recientes, se sugiere el uso de una hoja espiral, doble tornillo o tornillos de compresión en lugar del tornillo cefálico único. Objetivo: Analizar los resultados de las fracturas basicervicales tratadas con tornillo cefálico único en nuestro centro. Materiales y Métodos: Estudio retrospectivo de una serie de casos formada a partir de la revisión de todas las fracturas extracapsulares de fémur proximal tratadas con clavo intramedular con tornillo cefálico único entre 2016 y 2020. Se revisaron las historias clínicas y las radiografías de 269 pacientes, y solo 12 (6,4%) de ellos cumplieron los criterios de inclusión (fracturas en dos fragmentos no patológicas y con seguimiento mínimo de 9 meses). Se evaluaron diferentes factores, como distancia punta-ápex, posición del tornillo cefálico, calidad de la reducción, tiempo quirúrgico, complicaciones y reintervención, y se analizaron las posibles diferencias entre los pacientes que sufrieron complicaciones y los que no. Resultados: Cuatro de los 12 pacientes tuvieron una falla de la fijación que evolucionó a cut-out (única complicación identificada en la muestra). No hubo diferencias estadísticamente significativas entre pacientes con cut-outo sin cut-out respecto al resto de las variables analizadas. Conclusiones: La elevada proporción de pacientes que desarrollaroncut-out sugiere considerar la hipótesis de que debería evitarse fijar las fracturas basicervicales con tornillo cefálico único. Dada su alta tasa de inestabilidad rotatoria, podría ser más apropiado el uso de implantes que la contrarresten. Nivel de Evidencia: IV


Background: Given the rotational instability of basicervical fractures, recent studies suggest using a spiral blade, a second screw or compression screws instead of single-screw cephalomedullary nail fixation. Objective: The aim of our study is to analyze the outcomes of basicervical fractures treated with single-screw cephalomedullary nails. Materials and Methods: This is a retrospective study based on a case series identified from all extracapsular femoral fractures treated with single-screw cephalomedullary nails in our hospital from 2016 to 2020. Clinical records and radiographs from 269 patients were reviewed; only 12 (6.4%) subjects met inclusion criteria (two-part non-pathologic fractures with at least a 9-month follow-up). Different factors were evaluated, including: tip-apex distance, cephalic screw position, reduction quality, surgical time, complications and re-operations; differences between patients who experienced complications and those who did not were also assessed. Results: Four subjects out of the 12 included patients experienced fixation failure and implant cut-out. There were no statistically significant differences between subjects with and without cut-out regarding the analyzed variables. Conclusions: The high cut-out rate observed in our sample suggests considering the hypothesis that single-screw cephalomedullary nail fixation should not be used in basicervical fractures. Alternative fixation devices capable of controlling the high rotational instability of these fractures may be preferable. Level of Evidence: IV


Assuntos
Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Resultado do Tratamento , Fixação Intramedular de Fraturas , Fraturas do Quadril
19.
Pharmaceutics ; 14(12)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36559164

RESUMO

In this paper, a controlled-release system of caffeine as a corrosion inhibitor was obtained by encapsulating it in MCM-41 silica nanoparticles coated with a poly(ß-amino ester) (PbAE), a pH-sensible polymer. Encapsulation was verified using Fourier transform infrared spectroscopy (FTIR) and thermogravimetry (TGA). The release of caffeine from the nanocontainers was analyzed in electrolytes with pH values of 4, 5, and 7 using UV-Vis, showing a 21% higher release in acidic electrolytes than in neutral electrolytes, corroborating its pH sensitivity. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization were used to determine the inhibition mode and efficiency of the encapsulated and free caffeine. The caffeine released from the nanocontainers showed the highest efficiency, which was 85.19%. These results indicate that these nanocontainers could have potential use in smart anticorrosion coating applications.

20.
Front Neuroanat ; 16: 1054849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530520

RESUMO

Purpose: To identify and characterize numerically and topographically the population of alpha retinal ganglion cells (αRGCs) and their subtypes, the sustained-response ON-center αRGCs (ONs-αRGCs), which correspond to the type 4 intrinsically photosensitive RGCs (M4-ipRGCs), the transient-response ON-center αRGCs (ONt-αRGCs), the sustained-response OFF-center αRGCs (OFFs-αRGCs), and the transient-response OFF-center αRGCs (OFFt-αRGCs) in the adult pigmented mouse retina. Methods: The αRGC population and its subtypes were studied in flat-mounted retinas and radial sections immunodetected against non-phosphorylated high molecular weight neurofilament subunit (SMI-32) or osteopontin (OPN), two αRGCs pan-markers; Calbindin, expressed in ONs-αRGCs, and amacrines; T-box transcription factor T-brain 2 (Tbr2), a key transcriptional regulator for ipRGC development and maintenance, expressed in ipRGCs and GABA-displaced amacrine cells; OPN4, an anti-melanopsin antibody; or Brn3a and Brn3c, markers of RGCs. The total population of RGCs was counted automatically and αRGCs and its subtypes were counted manually, and color-coded neighborhood maps were used for their topographical representation. Results: The total mean number of αRGCs per retina is 2,252 ± 306 SMI32+αRGCs and 2,315 ± 175 OPN+αRGCs (n = 10), representing 5.08% and 5.22% of the total number of RGCs traced from the optic nerve, respectively. αRGCs are distributed throughout the retina, showing a higher density in the temporal hemiretina. ONs-αRGCs represent ≈36% [841 ± 110 cells (n = 10)] of all αRGCs and are located throughout the retina, with the highest density in the temporal region. ONt-αRGCs represent ≈34% [797 ± 146 cells (n = 10)] of all αRGCs and are mainly located in the central retinal region. OFF-αRGCs represent the remaining 32% of total αRGCs and are divided equally between OFFs-αRGCs and OFFt-αRGCs [363 ± 50 cells (n = 10) and 376 ± 36 cells (n = 10), respectively]. OFFs-αRGCs are mainly located in the supero-temporal peripheral region of the retina and OFFt-αRGCs in the mid-peripheral region of the retina, especially in the infero-temporal region. Conclusions: The combination of specific antibodies is a useful tool to identify and study αRGCs and their subtypes. αRGCs are distributed throughout the retina presenting higher density in the temporal area. The sustained ON and OFF response subtypes are mainly located in the periphery while the transient ON and OFF response subtypes are found in the central regions of the retina.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA