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1.
bioRxiv ; 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37215018

RESUMO

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, which are essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters could overcome the shortcomings of parenteral vaccines and enhance pre- existing systemic immunity. Here we present a new protein subunit nanovaccine using multiadjuvanted (e.g. RIG-I: PUUC, TLR9: CpG) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL- NPs, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lung, and showed robust systemic humoral immunity. Interestingly, as a purely intranasal vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. Our data suggest that PUUC+CpG PAL-NP subunit vaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

2.
Interv Neuroradiol ; : 15910199231153195, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36751025

RESUMO

BACKGROUND AND AIMS: Endovascular treatment for cerebrovascular disease is accepted as a first-line option with level I evidence in patients with an early and late time of window of onset symptoms, and an additional option in patients who do not respond or with contraindications to systemic thrombolysis; nevertheless the efficacy and outcomes of some groups were not clear, one of them are patients aged 80 years and older, because they were excluded of the trials, so the evidence is controversial with significant heterogeneity, for that reason in our study, we decided to analyze the age in the patients treated in our stroke center, as a predictor of prognosis, and to provide a baseline for the establishment of personalized treatment plans. METHODS: Observational, retrospective study of patients that received endovascular treatment for cerebrovascular disease in a Colombian stroke center between 2016 and 2020, continuous and categorical variables were compared using the Student's t test and Chi-Square. To determine cut-off points in the variable against death and Rankin score variable on 90th day. RESULTS: In total, 108 patients were recruited, 35 of them were of 80 or more years, and the mean age was 72.7 years, we found age as a significant variable to predict the risk in the population over 80 years of age [RR 3.37 CI (95% 1.14-103) p = 0.029]. CONCLUSIONS: Age younger than 80 is a significant predictor for results and long-term outcomes in patients suffering from stroke, and in patients older than 80 years old a Thrombolysis in Cerebral Infarction score 2b-3 is a predictor of good outcomes. Further studies are needed to evaluate the relationship between intrahospital complications and long-term outcomes.

3.
Interv Neuroradiol ; 29(1): 47-55, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34967258

RESUMO

OBJECTIVES: This study evaluated the clinical impact of the Sim&Size® simulation software on the endovascular treatment with flow-diverter stents of patients with unruptured saccular intracranial aneurysms. METHODS: This monocentric retrospective study evaluated a cohort of patients treated with flow-divert stents between June 1, 2014, and December 31, 2019, for cerebral aneurysms. Patients belonged to two groups, patients treated with and without the Sim&Size® simulation software. Univariate, bivariate, and multivariate analyses were used to evaluate the clinical impact of simulation software. RESULTS: Out of the 73 interventions involving 68 patients analyzed by the study, 76.7% were simulated using the Sim&Size® simulation software, and 23.3% were not. Patients treated with the simulation software had shorter stent lengths (16.00 mm vs. 20.00 mm p-value = 0.001) and surgical time (100.00 min vs. 118.00 min p-value = 0.496). Also, fewer of them required more than one stent (3.6% vs. 17.6% p-value = 0.079). Three patients belonging to the non-stimulated group presented hemorrhagic complications. CONCLUSIONS: Using the Sim&Size® simulation software for the endovascular treatment of intracranial aneurysms with pipeline flow-diverter stents reduces the stent length.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/terapia , Estudos Retrospectivos , Resultado do Tratamento , Embolização Terapêutica/métodos , Stents/efeitos adversos , Software , Procedimentos Endovasculares/métodos , Angiografia Cerebral
4.
Prog Community Health Partnersh ; 16(2): 155-168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662143

RESUMO

BACKGROUND: Community health assessment and improvement planning processes (CHA/CHIP) are often challenged with developing health actions that reach across a large community, city or county and that incorporate locally informed issues and place-specific strategies. In co-learning about approaches for enhancing CHA/CHIP processes through youth stakeholder input, a partnership of academic and community leaders came together to create The Youth-Led Community Health Learning Initiative (YLCHLI), a 1-year pilot initiative aimed at identifying health needs and assets in partnership with youth leaders and two central Texas communities. OBJECTIVE: To describe our approach, key findings, and lessons learned in implementing the YLCHLI in two different organizational settings: a high school-based setting and a community-based organization setting. METHODS: Guided by a community advisory board and the Mobilizing for Action through Planning and Partnerships framework, the YLCHLI incorporated a mixed methods design consisting of quantitative community health indicator analysis for topics identified in the Austin/Travis County CHA followed by a youth-led qualitative assessment of selected health issues via methods that included participatory mapping, data walks, and photovoice. RESULTS: Youth-informed findings provided rich insights and context for understanding disparities in selected health issues, including identification of social and environmental barriers to physical activity, healthy eating, health services, and mental health, and locally informed recommendations for community health improvement. CONCLUSION: High school health science tracks and community- based organizations represent promising settings for fostering community partnerships and youth engagement in identifying local health needs and opportunities that can enhance community health improvement planning and contribute to positive youth development.


Assuntos
Planejamento em Saúde Comunitária , Saúde Pública , Adolescente , Pesquisa Participativa Baseada na Comunidade/métodos , Educação em Saúde , Promoção da Saúde , Humanos
5.
J Control Release ; 347: 476-488, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35577151

RESUMO

Despite success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability remain. Molecular adjuvants targeting pattern recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulates various PRRs, including toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. We hypothesized that targeting PRRs using molecular adjuvants on nanoparticles (NPs) along with a stabilized spike protein antigen could stimulate broad and efficient immune responses. Adjuvants targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer NPs were combined with the S1 subunit of spike protein and assessed in vitro with isogeneic mixed lymphocyte reactions (isoMLRs). For in vivo studies, the adjuvant-NPs were combined with stabilized spike protein or spike-conjugated NPs and assessed using a two-dose intranasal or intramuscular vaccination model in mice. Combination adjuvant-NPs simultaneously targeting TLR and RIG-I receptors (MPLA+PUUC, CpG+PUUC, and R848+PUUC) differentially induced T cell proliferation and increased proinflammatory cytokine secretion by APCs in vitro. When delivered intranasally, MPLA+PUUC NPs enhanced CD4+CD44+ activated memory T cell responses against spike protein in the lungs while MPLA NPs increased anti-spike IgA in the bronchoalveolar (BAL) fluid and IgG in the blood. Following intramuscular delivery, PUUC NPs induced strong humoral immune responses, characterized by increases in anti-spike IgG in the blood and germinal center B cell populations (GL7+ and BCL6+ B cells) in the draining lymph nodes (dLNs). MPLA+PUUC NPs further boosted spike protein-neutralizing antibody titers and T follicular helper cell populations in the dLNs. These results suggest that protein subunit vaccines with particle-delivered molecular adjuvants targeting TLR4 and RIG-I could lead to robust and unique route-specific adaptive immune responses against SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Proteína DEAD-box 58 , Nanopartículas , Receptores Imunológicos , Receptor 4 Toll-Like , Adjuvantes Imunológicos , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Sistemas de Liberação de Medicamentos , Imunidade Humoral , Imunoglobulina G , Camundongos , Nanopartículas/química , Receptores Imunológicos/agonistas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Receptor 4 Toll-Like/agonistas
6.
bioRxiv ; 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35132413

RESUMO

Despite recent success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability, remain. Although mRNA, pDNA, and viral-vector based vaccines are being administered, no protein subunit-based SARS-CoV-2 vaccine is approved. Molecular adjuvants targeting pathogen-recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulate various PRRs, including toll-like receptors (TLRs) and retinoic-acid-inducible gene I-like receptors (RIG-I). We hypothesized that targeting the same PRRs using adjuvants on nanoparticles along with a stabilized spike (S) protein antigen could provide broad and efficient immune responses. Formulations targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer-nanoparticles (NPs) were combined with the S1 subunit of S protein and assessed in vitro with isogeneic mixed lymphocyte reactions (iso-MLRs). For in vivo studies, the adjuvanted nanoparticles were combined with stabilized S protein and assessed using intranasal and intramuscular prime-boost vaccination models in mice. Combination NP-adjuvants targeting both TLR and RIG-I (MPLA+PUUC, CpG+PUUC, or R848+PUUC) differentially increased proinflammatory cytokine secretion (IL-1ß, IL-12p70, IL-27, IFN-ß) by APCs cultured in vitro, and induced differential T cell proliferation. When delivered intranasally, MPLA+PUUC NPs enhanced local CD4+CD44+ activated memory T cell responses while MPLA NPs increased anti-S-protein-specific IgG and IgA in the lung. Following intramuscular delivery, PUUC-carrying NPs induced strong humoral immune responses, characterized by increases in anti-S-protein IgG and neutralizing antibody titers and germinal center B cell populations (GL7+ and BCL6+ B cells). MPLA+PUUC NPs further boosted S-protein-neutralizing antibody titers and T follicular helper cell populations in draining lymph nodes. These results suggest that SARS-CoV-2-mimicking adjuvants and subunit vaccines could lead to robust and unique route-specific adaptive immune responses and may provide additional tools against the pandemic.

7.
Rev. Eugenio Espejo ; 16(1): 112-121, 20220111.
Artigo em Espanhol | LILACS | ID: biblio-1353016

RESUMO

Se presenta el caso de un paciente masculino de 43 años, que ingresa con cuadro clínico caracterizado por dolor precordial de tipo opresivo con irradiación a cuello y mandíbula, cuya intensidad era de 8/10 atendiendo a la escala del dolor visual análoga (EVA). Además, manifestó diaforesis, disnea de pequeños esfuerzos, hiposmia y ageusia. El diagnóstico establecido fue de infección por coronavirus más infarto del miocardio. Las condiciones extraordinarias generadas por la pandemia de Covid-19 provocó que se decidiera una intervención mediante tratamiento fibrinolítico, obteniendo resultados positivos


The case of a 43-year-old male patient is presented, who is admitted with a clinical picture characterized by Chest pain of an oppressive type with irradiation to the neck and jaw, whose intensity was 8/10 according to the analogous visual pain scale (VAS). In addition, he manifes-ted diaphoresis, dyspnea on small efforts, hyposmia and ageusia. The determined diagnosis was coronavirus infection plus myocardial infarction. The extraordinary conditions generated by the Covid-19 pandemic led to an intervention by fibrinolytic treatment being decided, obtaining positive results.


Assuntos
Humanos , Masculino , Adulto , Diagnóstico , COVID-19 , Infarto do Miocárdio , Pacientes , Síndrome do Desconforto Respiratório do Recém-Nascido , Infecções por Coronavirus
8.
Cancers (Basel) ; 13(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638271

RESUMO

Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on-target off-tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents to treat a disease. In the context of multiple myeloma, immune therapy can be subdivided into four main categories: immune modulatory imide drugs, targeted antibodies, adoptive cell transfer therapies, and vaccines. In recent years, advances in all four of these categories have led to improved therapies with enhanced antitumor activity and specificity. In IMiDs, modified chemical structures have been developed that improve drug potency while reducing dose limiting side effects. Targeted antibody therapies have resulted from the development of new selectively expressed targets as well as the development of antibody drug conjugates and bispecific antibodies. Adoptive cell therapies, particularly CAR-T therapies, have been enhanced through improvements in the manufacturing process, as well as through the development of CAR constructs that enhance CAR-T activation and provide protection from a suppressive immune microenvironment. This review will first cover in-class breakthrough therapies for each of these categories, as well as therapies currently utilized in the clinic. Additionally, this review will explore up and coming therapeutics in the preclinical and clinical trial stage.

9.
BMC Neurosci ; 22(1): 37, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001031

RESUMO

BACKGROUND: Pathophysiological evidence from temporal lobe epilepsy models highlights the hippocampus as the most affected structure due to its high degree of neuroplasticity and control of the dynamics of limbic structures, which are necessary to encode information, conferring to it an intrinsic epileptogenicity. A loss in this control results in observable oscillatory perturbations called fast ripples, in epileptic rats those events are found in CA1, CA3, and the dentate gyrus (DG), which are the principal regions of the trisynaptic circuit of the hippocampus. The present work used Granger causality to address which relationships among these three regions of the trisynaptic circuit are needed to cause fast ripples in CA1 in an in vivo model. For these purposes, male Wistar rats (210-300 g) were injected with a single dose of pilocarpine hydrochloride (2.4 mg/2 µl) into the right lateral ventricle and video-monitored 24 h/day to detect spontaneous and recurrent seizures. Once detected, rats were implanted with microelectrodes in these regions (fixed-recording tungsten wire electrodes, 60-µm outer diameter) ipsilateral to the pilocarpine injection. A total of 336 fast ripples were recorded and probabilistically characterized, from those fast ripples we made a subset of all the fast ripple events associated with sharp-waves in CA1 region (n = 40) to analyze them with Granger Causality. RESULTS: Our results support existing evidence in vitro in which fast ripple events in CA1 are initiated by CA3 multiunit activity and describe a general synchronization in the theta band across the three regions analyzed DG, CA3, and CA1, just before the fast ripple event in CA1 have begun. CONCLUSION: This in vivo study highlights the causal participation of the CA3 back-projection to the DG, a connection commonly overlooked in the trisynaptic circuit, as a facilitator of a closed-loop among these regions that prolongs the excitatory activity of CA3. We speculate that the loss of inhibitory drive of DG and the mechanisms of ripple-related memory consolidation in which also the CA3 back-projection to DG has a fundamental role might be underlying processes of the fast ripples generation in CA1.


Assuntos
Região CA1 Hipocampal/fisiologia , Região CA3 Hipocampal/fisiologia , Giro Denteado/fisiologia , Epilepsia do Lobo Temporal/fisiopatologia , Inibição Neural/fisiologia , Animais , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/induzido quimicamente , Masculino , Vias Neurais/fisiologia , Pilocarpina/toxicidade , Ratos , Ratos Wistar
10.
Exp Brain Res ; 239(6): 2015-2024, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33909110

RESUMO

Epilepsy is a neurological disorder in which an imbalance between excitatory and inhibitory transmission is observed. Glutamate is the principal excitatory neurotransmitter that acts through ionic and metabotropic receptors; both types of receptors are involved in temporal lobe epilepsy (TLE). High frequency oscillations called fast ripples (FR, 250-600 Hz) have been observed, particularly in the hippocampus, and they are involved in epileptogenesis. The present study analyzed the immunoreactivity of the principal glutamate receptors associated with epilepsy in epileptic animals with FR activity. Male Swiss-Wistar rats (210-250 gr) were injected with pilocarpine (2.4 mg/2 µl) and were video monitored (24/7) until the appearance of spontaneous and recurrent seizures. Then, a deep microelectrode implantation surgery was performed in the DG, CA3 and CA1 regions, and FR activity was observed 1-, 2-, 3-, 7-, and 14-day postsurgery. The animals were sacrificed on day 15, and fluorescence immunohistochemistry was carried out in the hippocampus for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and mGlu-R5 glutamate receptors as well as Neuronal Nuclear Protein (NeuN) and Glial Fibrillary Acidic Protein (GFAP). An increase in the immunoreactivity for the three receptors was found. However, the AMPA receptor showed an increase in the three regions analyzed (i.e., DG, CA1 and CA3). The findings showed a decrease of NeuN in the DG and an increase of GFAP. These results suggest an important role of glutamate receptors in the hippocampus of epileptic rats with FR activity.


Assuntos
Epilepsia , Proteínas Nucleares , Animais , Epilepsia/induzido quimicamente , Proteína Glial Fibrilar Ácida , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
11.
Neuroreport ; 32(4): 306-311, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33470771

RESUMO

Fast ripples (FRs) are found in the hippocampus of epileptic brains, and this fast electrical activity has been described as a biomarker of the epileptogenic process itself. Results from our laboratory, such as the observation of decreased seizure rates and FR incidence at a specific citalopram dose, have suggested that serotonin (5-HT) may play a key role in the FR generation process. Therefore, to gather more details about the state of the serotoninergic system in the hippocampus under an epileptogenic process, we studied the immunoreactivity of three 5-HT receptors (5-HT1A, 5-HT2 and 5-HT7) as well as the extracellular levels of 5-HT in the hippocampal tissue of epileptic rats with FR. Wistar rats (210-300 g) were injected with a single dose of pilocarpine hydrochloride (2.4 mg/2 µl) in the right lateral ventricle and video-monitored 24 h/d to detect spontaneous and recurrent seizures; microelectrodes were implanted in the dentate gyrus (DG) and CA3 and CA1 regions of these rats ipsilateral to the pilocarpine injection site 1 day after the first spontaneous seizure was observed, and only rats who suffered FR events were used in this work. Thirty-three days after the first spontaneous seizure, an immunostaining procedure and high performance liquid chromatography were performed to measure the 5-HT levels. A general depletion of the 5-HT and 5-HIIA levels in hippocampal tissue from epileptic animals compared with those in controls was observed; in addition, a general decrease in immunoreactivity for the three receptors was found, especially in the DG, which may support the establishment of an excitatory/inhibitory imbalance in the trisynaptic circuit that underlies the FR generation process.


Assuntos
Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptores 5-HT2 de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA3 Hipocampal/efeitos dos fármacos , Região CA3 Hipocampal/metabolismo , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/induzido quimicamente , Hipocampo/efeitos dos fármacos , Ácido Hidroxi-Indolacético/metabolismo , Imuno-Histoquímica , Agonistas Muscarínicos/toxicidade , Pilocarpina/toxicidade , Ratos , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT2 de Serotonina/efeitos dos fármacos , Serotonina/metabolismo
12.
Nat Biomed Eng ; 5(1): 89-102, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33483713

RESUMO

Using endogenous mesenchymal stem cells for treating myocardial infarction and other cardiovascular conditions typically results in poor efficacy, in part owing to the heterogeneity of the harvested cells and of the patient responses. Here, by means of high-throughput screening of the combinatorial space of mechanical-strain level and of the presence of particular kinase inhibitors, we show that human mesenchymal stem cells can be mechanically and pharmacologically conditioned to enhance vascular regeneration in vivo. Mesenchymal stem cells conditioned to increase the activation of signalling pathways mediated by Smad2/3 (mothers against decapentaplegic homolog 2/3) and YAP (Yes-associated protein) expressed markers that are associated with pericytes and endothelial cells, displayed increased angiogenic activity in vitro, and enhanced the formation of vasculature in mice after subcutaneous implantation and after implantation in ischaemic hindlimbs. These effects were mediated by the crosstalk of endothelial-growth-factor receptors, transforming-growth-factor-beta receptor type 1 and vascular-endothelial-growth-factor receptor 2. Mechanical and pharmacological conditioning can significantly enhance the regenerative properties of mesenchymal stem cells.


Assuntos
Fenômenos Biomecânicos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica/fisiologia , Regeneração/fisiologia , Adulto , Animais , Feminino , Humanos , Isquemia , Masculino , Transplante de Células-Tronco Mesenquimais , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento/metabolismo , Regeneração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Adulto Jovem
13.
Sci Rep ; 10(1): 15469, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963285

RESUMO

Mechanical forces are important in the regulation of physiological homeostasis and the development of disease. The application of mechanical forces to cultured cells is often performed using specialized systems that lack the flexibility and throughput of other biological techniques. In this study, we developed a high throughput platform for applying complex dynamic mechanical forces to cultured cells. We validated the system for its ability to accurately apply parallel mechanical stretch in a 96 well plate format in 576 well simultaneously. Using this system, we screened for optimized conditions to stimulate increases in Oct-4 and other transcription factor expression in mouse fibroblasts. Using high throughput mechanobiological screening assays, we identified small molecules that can synergistically enhance the increase in reprograming-related gene expression in mouse fibroblasts when combined with mechanical loading. Taken together, our findings demonstrate a new powerful tool for investigating the mechanobiological mechanisms of disease and performing drug screening in the presence of applied mechanical load.


Assuntos
Reprogramação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Embrião de Mamíferos/metabolismo , Células-Tronco Embrionárias/metabolismo , Fibroblastos/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Estresse Mecânico , Animais , Embrião de Mamíferos/citologia , Embrião de Mamíferos/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/efeitos dos fármacos , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Masculino , Camundongos
14.
Behav Neurol ; 2020: 4385706, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32211080

RESUMO

Physiological behaviours such as the sleep-wake cycle and exploratory behaviours are important parameters in intact and sham-operated animals and are usually thought to be unaffected by experimental protocols in which neurosurgery is performed. However, there is insufficient evidence in the literature on the behavioural and cognitive effects observed after deep microelectrode implantation surgery in animal models of neurological diseases. Similarly, in studies that utilize animal models of neurological diseases, the impact of surgery on the pathological phenomena being studied is often minimized. Based on these considerations, we performed a temporal analysis of the effects of deep microelectrode implantation surgery in the hippocampus of rats on quiet wakefulness, sleep, and exploratory activity and the pathological behaviours such as convulsive seizures according to the Racine scale. Male Wistar rats (210-300 g) were used and grouped in sham and epileptic animals. Single doses of pilocarpine hydrochloride (2.4 mg/2 µl; i.c.v.) were administered to the animals to generate spontaneous and recurrent seizures. Deep microelectrode implantation surgeries in both groups and analysis of Fast ripples were performed. Physiological and pathological behaviours were recorded through direct video monitoring of animals (24/7). Our principal findings showed that in epileptic animals, one of the main behaviours affected by surgery is sleep; as a consequence of this behavioural change, a decrease in exploratory activity was also found as well as the mean time spent daily in seizures of scale 4 and the number of seizure events of scales 4 and 5 was increased after surgery. No significant correlations between the occurrence of FR and seizure events of scale 4 (rho 0.63, p value 0.25) or 5 (rho -0.7, p value 0.18) were observed. In conclusion, microelectrode implantation surgeries modified some physiological and pathological behaviours; therefore, it is important to consider this fact when it is working with animal models.


Assuntos
Eletrodos Implantados/efeitos adversos , Eletrodos Implantados/psicologia , Microeletrodos/efeitos adversos , Animais , Encéfalo/fisiologia , Modelos Animais de Doenças , Eletrodos Implantados/veterinária , Eletroencefalografia/métodos , Epilepsia/patologia , Comportamento Exploratório/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Pilocarpina/farmacologia , Ratos , Ratos Wistar , Convulsões/fisiopatologia , Sono/fisiologia , Vigília/fisiologia
16.
MedUNAB ; 23(3): 450-463, 26/11/2020.
Artigo em Espanhol | LILACS | ID: biblio-1141198

RESUMO

Introducción. En el proceso de envejecimiento, la mayoría de los sistemas orgánicos mantienen su funcionamiento basal, pero existe una reducción de la reserva funcional y de la capacidad para compensar el estrés fisiológico, lo que hace que los pacientes de mayor edad sean más propensos a complicaciones postoperatorias. Se realizó un estudio en instituciones de Bucaramanga para determinar la incidencia de déficit cognitivo postoperatorio y los factores de riesgo asociados. Metodología. Estudio observacional analítico de cohorte prospectivo realizado en instituciones de salud de Bucaramanga durante 2017 con pacientes mayores de 55 años intervenidos bajo anestesia regional, general balanceada o anestesia total intravenosa. Resultados. Se estudiaron 173 pacientes, 112 mujeres (64.74%) y 61 hombres (35.26%) operados. Las técnicas anestésicas más empleadas fueron: Regional (46.24%) y General balanceada (44.51%). La incidencia de Déficit Cognitivo Postoperatorio a corto plazo fue 6.36% en pacientes previamente sanos, con valor P significativo (0.001) ajustado. Se detectó deterioro cognitivo del 51.41% con alteraciones en los dominios de lenguaje, atención y memoria; con aumento en la evaluación a largo plazo. Durante el seguimiento de pacientes a largo plazo resultó en un 11.55%, determinando la incidencia de Déficit Cognitivo Postoperatorio tardío en un 17.91%. La técnica anestésica con mayor proporción de déficit a largo plazo fue la anestesia mixta, comparada con anestesia regional. Discusión. En la actualidad no existe una definición estandarizada de Déficit Cognitivo Postoperatorio, se ha observado mayor frecuencia y mayor prolongación en pacientes de edad avanzada. El estudio demostró una incidencia temprana significativamente menor, comparándolo con artículos internacionales, pero una incidencia mayor en déficit postoperatorio tardío, resultado de mayores complicaciones intraoperatorias, comparado con otros estudios. Conclusiones. El Déficit Cognitivo Postoperatorio involucra múltiples factores de riesgo; en el estudio se encontró mayor asociación con la edad, la escolaridad, la hipotensión y la anestesia general. No hubo asociación entre comorbilidades y el Déficit Cognitivo Postoperatorio. Se determinó la presencia de hipotensión para desarrollo de este déficit. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711


Introduction. Within the aging process, most organic systems maintain their basal functions. However, there is a reduction in functional reserve and the capacity to compensate physiological stress, which makes older patients more prone to postoperative complications. A study was performed in institutions in Bucaramanga to determine the incidence of postoperative cognitive dysfunction and the associated risk factors. Methodology. This was a analytical observational prospective cohort study performed in healthcare institutions in Bucaramanga in 2017 with patients older than 55 years of age under regional, balanced general or total intravenous anesthesia. Results. One hundred and seventy-three operated patients were studied, among which 112 (64.74%) were women and 61 (35.26%) were men. The most commonly used anesthetic techniques were: regional (46.24%) and balanced general (44.51%). Short-term Postoperative Cognitive Dysfunction incidence was 6.36% in previously healthy patients, with an adjusted significant P value (0.001). Cognitive deterioration was detected in 51.41% of patients, with alterations in their mastery of language, attention and memory. This increased for the long-term evaluation. During long-term patient follow-up, it resulted in 11.55%, determining the incidence of delayed Postoperative Cognitive Dysfunction at 17.91%. The anesthetic technique with the highest proportion of long- term dysfunction was mixed anesthesia, compared to regional anesthesia. Discussion. There is currently no standardized definition for Postoperative Cognitive Dysfunction. It has been observed more frequently and for longer extensions in older patients. The study demonstrated a significantly lower early incidence when compared to international articles, but a greater incidence of delayed postoperative dysfunction as a result of more intraoperative complications compared to other studies. Conclusions. Postoperative Cognitive Dysfunction involves multiple risk factors. The study observed a greater association with age, level of education, hypotension and general anesthesia. There was no association between comorbidities and Postoperative Cognitive Dysfunction. The presence of hypotension was determined for developing this dysfunction. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711


Introdução. No processo de envelhecimento, a maioria dos sistemas orgânicos mantém seu funcionamento basal, mas há uma diminuição da reserva funcional e da capacidade de compensar o estresse fisiológico que torna os pacientes idosos mais sujeitos a complicações pós-operatórias. Foi realizado um estudo em instituições da cidade de Bucaramanga para determinar a incidência de déficit cognitivo pós-operatório e os fatores de risco associados. Métodos. Estudo observacional analítico de coorte prospectivo realizado em instituições de saúde em Bucaramanga durante o ano de 2017 em pacientes com idade superior a 65 anos operados sob anestesia regional, geral balanceada ou anestesia geral intravenosa. Resultados. Foram estudados 173 pacientes, 112 mulheres (64.74%) e 61 homens (35.26%) operados. As técnicas anestésicas mais utilizadas foram: regional (46.24%) e geral balanceada (44.51%). A incidência de déficit cognitivo pós-operatório de curto prazo foi de 6.36% em pacientes previamente saudáveis, com um valor P significativo (0.001) ajustado. Detectou- se deterioração cognitiva de 51.41% com alterações nos domínios da linguagem, atenção e memória; com aumento na avaliação de longo prazo. No seguimento a longo prazo dos pacientes resultou em 11.55%, determinando a incidência de déficit cognitivo pós-operatório tardio em 17.91%. A técnica anestésica com maior proporção de déficit no longo prazo foi a anestesia mista, em comparação com a anestesia regional. Discussão. Atualmente não existe uma definição padronizada de Déficit Cognitivo Pós-operatório, a qual observa-se com maior frequência e por mais tempo em pacientes idosos. O estudo demonstrou incidência precoce significativamente menor, em comparação com resultados de artigos internacionais, mas maior incidência de déficit pós-operatório tardio, resultado de maiores complicações intraoperatórias, em comparação com outros estudos. Conclusões. O Déficit Cognitivo Pós-operatório envolve múltiplos fatores de risco; o estudo encontrou maior associação com idade, escolaridade, hipotensão e anestesia geral. Não houve associação entre comorbidades e Déficit Cognitivo Pós-operatório. Determinou-se a presença de hipotensão para o desenvolvimento desse déficit. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711


Assuntos
Complicações Cognitivas Pós-Operatórias , Incidência , Anestesia Balanceada , Disfunção Cognitiva , Anestesia Geral , Anestesia Intravenosa
17.
Rev. ecuat. med. Eugenio Espejo ; 7(11): 1-6, septiembre 2019.
Artigo em Espanhol | LILACS | ID: biblio-1022377

RESUMO

Antecedentes: La glucogenosis (GSD) hepática es una enfermedad hereditaria autosómica recesiva caracterizada por la alteración del depósito de glucógeno en los tejidos. La enfermedad se presenta con hepatomegalia, debilidad muscular y retraso del crecimiento. Esta patología usualmente se diagnostica clínicamente a partir de los 6 meses de edad cuando la ingesta de alimentos del lactante es más espaciada y puede debutar con sintomatología de hipoglicemia. Debido a la inespecificidad de la presentación clínica de la enfermedad es muy importante la sospecha diagnóstica desde los centros de primer nivel de atención y su derivación oportuna a centros de especialidad. Objetivo: Evaluar y describir el perfil nutricional y clínico en pacientes menores de 15 años con Glucogenosis Hepática. Método: Se describe una serie de casos de 14 pacientes menores de 15 años con diagnóstico clínico de GSD hepática, atendidos en la consulta de Gastroenterología y Nutrición Pediátrica del Hospital Carlos Andrade Marín entre 2016 y 2018. El diagnóstico se lo realizó de acuerdo a la clínica que presentó cada paciente como la presencia de distensión abdominal, hepatomegalia, adinamia, retraso en el crecimiento y datos laboratoriales como niveles de glicemia en sangre periférica, transaminasas, y realización de elastografía entre los principales. Se analizaron datos sociodemográficos, antropométricos, de laboratorio (transaminasas, glicemia periférica) y elastografía hepática. Para el análisis de datos se creó una base de datos en Microsoft Excel 2013 y se procesó con el programa Epi Info 7. Resultados: En este grupo de casos, los tipos específicos de GSD hepática fueron tipo IX, 57,14% (8), tipo III, 28,57% (4) y tipo Ia-b, 14,29% (2) pacientes. La prevalencia de características clínicas ante la sospecha de la GSD hepática fueron: hepatomegalia 100% (14), y retraso en el crecimiento el 64,3% (9). De acuerdo a los exámenes de sangre periférica los valores promedio de transaminasas hepáticas (AST/TGO U/L) (ALT/TGP U/L) y glucosa, fueron de 364±384, 302±255 y 61±15 mg/dL, respectivamente. La elastografía con la que se evaluó el nivel de fibrosis hepática al momento del diagnóstico arrojó los siguientes resultados: F0 (no fibrosis hepática) en el 28,57% (4), F1 con el 28,57% (4), F2-F3 con el 35,71% (5), y F4 7,14%. Conclusión: La Glucogenosis es una patología que debería ser sospechada a tiempo en centros del primer nivel de salud para luego referir oportunamente los casos a los centros de referencia. La hepatomegalia y el retardo en el crecimiento son signos cardinales de alerta para la sospecha de esta patología.


Assuntos
Humanos , Relatório de Pesquisa , Administração de Caso , Glicosúria Renal
18.
Int Ophthalmol ; 39(8): 1809-1818, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30136018

RESUMO

PURPOSE: To evaluate the results of optical biometry using the IOLMaster 500, Lenstar LS 900 and Aladdin in eyes with cataract. METHODS: In 231 eyes of 152 patients with cataract, the measurements of 3 different biometers were retrospectively compared. Paired comparisons were performed for axial length (AL), mean keratometry (mean K) and anterior chamber depth (ACD). RESULTS: In only 197 of the 231 eyes (85.3%), it was possible to obtain reliable measurements of AL with all the three devices. It was not possible to determine AL in 16 eyes (6.9%) with Lenstar LS 900; in 19 eyes (8.2%) with Aladdin; and in 20 eyes (8.6%) with IOLMaster 500 possibly related to the severity of lens opacification (the corneas had good transparency in the eyes included in the study). There was a statistically significant difference in AL between IOLMaster 500 and the remaining two biometers (P = 0.03). However, the amount of difference was considered clinically not significant (0.04 mm). The mean keratometry (mean K) was determined in 203 eyes (87.9%) with all the three devices. Differences in mean K were between - 0.1 and 0.06 Diopters (D), which were considered neither statistically (P > 0.05) nor clinically significant. The anterior chamber depth (ACD) was determined in 197 eyes (85.28%) with all the three biometers. The differences between the three devices (0.03 to 0.13 mm) were not statistically significant and considered also clinically not significant. CONCLUSIONS: There were no clinically significant differences between these 3 biometers in AL, mean K and ACD.


Assuntos
Câmara Anterior/diagnóstico por imagem , Comprimento Axial do Olho/diagnóstico por imagem , Biometria/instrumentação , Catarata/diagnóstico , Idoso , Extração de Catarata , Desenho de Equipamento , Feminino , Humanos , Cristalino/diagnóstico por imagem , Masculino , Estudos Retrospectivos
19.
MedUNAB ; 22(2): 153-161, 2019/08/01.
Artigo em Espanhol | LILACS | ID: biblio-1021539

RESUMO

Introducción. Diversas condiciones oftalmológicas son causas de consultas a los servicios de urgencias. El objetivo de este trabajo fue determinar las causas más comunes de consulta al servicio de urgencias oftalmológicas de una institución terciaria en Colombia y, así, poder explorar en el futuro la posibilidad de identificar algunas medidas preventivas dirigidas a disminuir la frecuencia de esas causas. Metodología. Estudio descriptivo retrospectivo basado en los registros de pacientes que asistieron al servicio de urgencias durante los años 2014 y 2015. Las patologías se identificaron a partir de los códigos de la Clasificación Internacional de Enfermedades, CIE-10. Resultados. Se identificaron 9,088 y 8,162 registros para los años 2014 y 2015, respectivamente. Las causas de consulta a urgencias oftalmológicas más frecuentes para el año 2014 fueron: cuerpo extraño en la córnea o en la conjuntiva con un 20.2 % de los casos, conjuntivitis aguda no especificada con 11.3 %, traumatismo de la conjuntiva y abrasión corneal con 8.3 %, hemorragia conjuntival con 5.8 % y quemaduras corneales con 4.7 %. En el año 2015, las causas fueron: cuerpo extraño en la córnea o en la conjuntiva (23.6 %), traumatismo de la conjuntiva y abrasión corneal (9.0 %), conjuntivitis aguda no especificada (8.9 %), hemorragia conjuntival (4.4 %) y quemaduras corneales (4.0 %). Discusión. Las causas más frecuentes de consulta a urgencias oftalmológicas incluyeron los traumas y las infecciones del segmento anterior del ojo. Conclusiones. Existe la posibilidad de identificar algunas medidas preventivas (elementos de protección adecuados, protocolos de conducta en situaciones de riesgo, etc.) que ayuden a disminuir la frecuencia de traumas oculares y minimicen el riesgo de infecciones. Hay, entonces, cabida para más estudios en los que se analicen los mecanismos específicos de estas lesiones. Cómo citar. Galvis V, Díaz AL, Ochoa ME, Rey JJ, Ardila LC, Olivero LP, Tello A. Principales causas de consulta de urgencias oftalmológicas en un instituto de atención terciaria en Colombia. MedUNAB 2019;22(2):153-161. doi:10.29375/01237047.3489


Introduction. Several ophthalmological conditions are causes of consultations to the emergency services. The objective of this study was to determine the most common causes of consultation to the ophthalmological emergency service of a tertiary institution in Colombia and thus be able to explore in the future the possibility of identifying some preventive measures aimed at reducing the frequency of these causes. Methodology. Retrospective descriptive study based on the records of patients attending the emergency department during 2014 and 2015, identifying the diseases based on the International Classification of Diseases (ICD-10) codes. Results. 9,088 and 8,162 records were identified for 2014 and 2015, respectively. The most frequent causes of ophthalmologic urgency consultation for the year 2014 were: corneal or conjunctive foreign body with 20.2 %, acute conjunctivitis not specified 11.3 %, conjunctival trauma and corneal abrasion 8.3 %, conjunctival haemorrh age 5.8 % and corneal burns 4.7 %. In 2015 the causes were: foreign body in the cornea or conjunctiva (23.6 %), conjunctival trauma and corneal abrasion (9.0 %), acute unspecified conjunctivitis (8.9 %), conjunctival hemorrhage (4.4 %), and corneal burns (4.0 %). Discussion. The most frequent causes of consultation with ophthalmologic emergencies included trauma and infections of the anterior segment of the eye. Conclusions. There is a possibility of identifying some preventive measures (adequate protection elements, behavior protocols in situations of risk, etc.) that help to reduce the frequency of eye traumas and minimize the risk of infections. There is room for more studies in which the specific mechanisms of these injuries are analyzed. Cómo citar: Galvis V, Díaz AL, Ochoa ME, Rey JJ, Ardila LC, Olivero LP, Tello A. Principales causas de consulta de urgencias oftalmológicas en un instituto de atención terciaria en Colombia. MedUNAB 2019;22(2):153-161. doi:10.29375/01237047.3489


Introdução. Várias condições oftalmológicas são causas de atendimento nos serviços de emergência. O objetivo deste trabalho foi determinar as causas mais comuns de atendimento oftalmológico emergencial em uma instituição terciária na Colômbia e, assim, poder explorar no futuro a possibilidade de identificar algumas medidas preventivas para reduzir a frequência dessas causas. Métodos. Estudo descritivo retrospectivo baseado nos registros de pacientes que compareceram ao serviço de emergência oftalmológica durante os anos 2014 e 2015. As patologias foram identificadas a partir dos códigos da Classificação Internacional de Doenças, CID-10. Resultados. Foram identificados 9,088 e 8,162 registros para os anos 2014 e 2015, respectivamente. As causas de atendimento oftalmológico emergencial mais frequentes em 2014 foram: corpo estranho na córnea ou na conjuntiva com 20,2 % dos casos, conjuntivite aguda não especificada com 11,3 %, trauma conjuntival e abrasão corneana com 8,3 %, hemorragia conjuntival com 5,8 % e queimaduras corneanas com 4,7 %. No ano 2015, as causas foram: corpo estranho na córnea ou na conjuntiva (23,6 %), trauma conjuntival e abrasão corneana (9,0 %), conjuntivite aguda não especificada (8,9 %), hemorragia conjuntival (4,4 %) e queimaduras corneanas (4,0 %). Discussão. As causas mais frequentes de atendimento oftalmológico emergencial incluíram traumas e infecções do segmento anterior do olho. Conclusões. Existe a possibilidade de identificar algumas medidas preventivas (elementos de proteção adequados, protocolos de conduta em situações de risco, etc.) que ajudem na redução da frequência de trauma ocular e para minimizar o risco de infecções. Há, então, espaço para mais estudos que analisem os mecanismos específicos dessas lesões Cómo citar. Galvis V, Díaz AL, Ochoa ME, Rey JJ, Ardila LC, Olivero LP, Tello A. Principales causas de consulta de urgencias oftalmológicas en un instituto de atención terciaria en Colombia. MedUNAB 2019;22(2):153-161. doi:10.29375/01237047.3489


Assuntos
Oftalmologia , Queimaduras Oculares , Corpos Estranhos no Olho , Traumatismos Oculares , Conjuntivite , Doenças da Córnea , Emergências
20.
3D Print Med ; 4(1): 4, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29782609

RESUMO

BACKGROUND: Cranial defects usually occur after trauma, neurosurgical procedures like decompressive craniotomy, tumour resections, infection and congenital defects. The purpose of cranial vault repair is to protect the underlying brain tissue, to reduce any localized pain and patient anxiety, and improve cranial aesthetics. Cranioplasty is a frequent neurosurgical procedure achieved with the aid of cranial prosthesis made from materials such as: titanium, autologous bone, ceramics and polymers. Prosthesis production is often costly and requires complex intraoperative processes. Implant customized manufacturing for craniopathies allows for a precise and anatomical reconstruction in a shorter operating time compared to other conventional techniques. We present a simple, low-cost method for prosthesis manufacturing that ensures surgical success. CASE PRESENTATION: Two patients with cranial defects are presented to describe the three-dimensional (3D) printing technique for cranial reconstruction. A digital prosthesis model is designed and manufactured with the aid of a 3D computed tomography. Both the data of large sized cranial defects and the prosthesis are transferred to a 3D printer to obtain a physical model in poly-lactic acid which is then used in a laboratory to cast the final customised prosthesis in polymethyl methacrylate (PMMA). CONCLUSIONS: A precise compliance of the prosthesis to the osseous defect was achieved. At the 6 month postoperative follow-up no complications were observed i.e. rejection, toxicity, local or systemic infection, and the aesthetic change was very significant and satisfactory. Customized 3D PMMA prosthesis offers cost advantages, a great aesthetic result, reduced operating time and good biocompatibility.

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