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1.
Nature ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658751

RESUMO

WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms1-5. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a region of the helicase domain subject to interdomain movement during DNA unwinding. VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), but not in microsatellite-stable, cells. The compound was well tolerated in mice and led to robust tumour regression in multiple MSI-H colorectal cancer cell lines and patient-derived xenograft models. Our work shows an allosteric approach for inhibition of WRN function that circumvents competition from an endogenous ATP cofactor in cancer cells, and designates VVD-133214 as a promising drug candidate for patients with MSI-H cancers.

2.
Front Cell Infect Microbiol ; 14: 1297099, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495650

RESUMO

Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.


Assuntos
Doença de Chagas , Doenças Transmissíveis , Trypanosoma cruzi , Feminino , Animais , Camundongos , Humanos , Trypanosoma cruzi/metabolismo , Pepsina A/metabolismo , Parasitemia , Modelos Animais de Doenças , Cromatografia Líquida , Espectrometria de Massas em Tandem , Doença de Chagas/parasitologia , Mucinas
3.
Ultrasonics ; 138: 107230, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176289

RESUMO

Airborne acoustic trapping by ultrasonic phased arrays has seen great advances in recent years, and yet the manipulation of objects with different shapes and sizes or heavy particles remains challenging. Here, we demonstrate that the manipulation capabilities of a standing-wave acoustic levitator can be extended by introducing intracavity high-order transverse (HOT) modes in the azimuthal direction, enabling the simultaneous trapping of several objects within a wide range of shapes and sizes with positional and rotational stability, including objects with sizes larger than one wavelength and weights in the scale of millinewtons. The conditions to generate different HOT modes are theoretically analyzed and experimentally implemented. We numerically calculate the pressure distributions, exhibiting good qualitative agreement with the experimental pressure distributions obtained with schlieren images. In addition, we calculate the acoustic force field for several examples of HOT modes and different particle sizes, which leads to a qualitative understanding of the experimental observations.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36293581

RESUMO

Mini handball is among the sports included as part of school physical education in Chile to improve children's motor skills and to motivate their adherence to a healthy and active lifestyle in response to concerns about this country's high level of childhood obesity. To this end, non-linear pedagogy (NLP) has been used to develop motor skills through mini handball in the school context. However, socioeconomic differences that influence the development of children's motor skills have not been considered to determine whether the methodology applies to everyone. The aim of the present observational study is to describe and compare the effectiveness of the previously applied NLP methodology in two contrasting socioeconomic contexts to determine whether it helps to develop motor skills through mini handball in both school contexts. The Levine test was used to determine the homogeneity of the variances (p < 0.05), as the distribution of the data was not normal. The Kruskal-Wallis H statistical test was used to analyse within-group data. Additionally, the Mann-Whitney U test was applied for comparisons between groups. The results show significant improvements in the acquisition of the expected motor skills specific to mini handball. Additionally, a shortening of the gap was evidenced between the groups during the training process, with no significant differences at the end of the progression. Therefore, the investigated NLP is equally as effective for schoolchildren in two opposite socioeconomic contexts.


Assuntos
Obesidade Infantil , Esportes , Criança , Humanos , Projetos Piloto , Esportes/fisiologia , Educação Física e Treinamento , Fatores Socioeconômicos
7.
Rev. Univ. Ind. Santander, Salud ; 54(1): e600, Enero 2, 2022. tab
Artigo em Espanhol | LILACS | ID: biblio-1407042

RESUMO

Resumen Introducción: La musculatura del core involucra a todos los grupos musculares ubicados en la zona media del cuerpo. La metodología clínica de elección para el registro y análisis de su actividad bioeléctrica es la electromiografía superficial (sEMG), metodología clínica para el registro y posterior análisis de las actividades bioeléctricas del músculo esquelético. Objetivo: El objetivo de esta investigación es determinar si existen diferencias de actividad electromiográfica en la musculatura del recto abdominal y oblicuo externo entre practicantes de musculación y practicantes de calistenia. Metodología: El estudio es de tipo comparativo, de diseño no experimental, transversal de enfoque cuantitativo en una muestra de 20 sujetos; 10 practicantes de calistenia y 10 que entrenan con ejercicios de musculación clásicos. Resultados: Los ejercicios que tuvieron mayor respuesta electromiográfica fueron abdominal en suspensión y abdominal inclinado. Conclusiones: La calistenia es una alternativa viable para la activación muscular a nivel del Core.


Abstract Introduction: The Core musculature involves all the muscle groups located in the middle area of the body whose activity can be measured using superficial electromyography (sEMG), a clinical methodology for recording and subsequent analysis of skeletal muscle bioelectric activities. Objectives: The objective of this research is to determine if there are differences in electromyographic activity in the muscles of the rectus abdominis and external oblique between bodybuilding practitioners and calisthenics practitioners. Methodology: A comparative study, non-experimental design, cross-sectional with a quantitative approach in a sample of 20 subjects; 10 calisthenics practitioners and 10 who train with classic bodybuilding exercises. Results: The exercises with the greatest electromyographic response were abdominal in suspension and abdominal incline. Conclusions: Calisthenics is a viable alternative for muscle activation at the Core level.


Assuntos
Humanos , Masculino , Feminino , Adulto , Eletromiografia , Treinamento Resistido , Centro Abdominal , Exercício Físico , Tutoria , Ginástica
9.
Rev Sci Instrum ; 92(1): 015107, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33514194

RESUMO

Acoustic levitation uses focused high-intensity airborne ultrasound to hold particles in mid-air. It is becoming an important tool for experiments in spectrometry, lab-on-a-droplet, and display technologies. Nowadays, arrays of multiple small transducers can be used to build acoustic levitators; however, their performance depends on the optimal alignment. This work describes a simple method capable of visualizing a 2D projection of the acoustic field in real time using rainbow schlieren deflectometry. Good agreement was found between the images obtained with this technique and simulations of the acoustic pressure. It was also found that the maximum amplitudes of the field were obtained with the levitator aligned so that the power consumption was minimum, showing another simple and affordable way to adjust the levitators. As a result of the alignment optimization, it was possible for the first time to levitate steel and mercury in a levitator constructed with off-the-shelf components. The schlieren technique was applied to the TinyLev acoustic levitation system, but it can be applied to visualize the acoustic potential produced by different types of levitation systems.

10.
Rev. Asoc. Argent. Ortop. Traumatol ; 85(4): 349-356, dic. 2020.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1351410

RESUMO

NiResumen Objetivo: Evaluar los resultados de la retinaculotomía endoscópica para tratar el síndrome del túnel carpiano mediante la técnica de doble portal de Chow, entre enero de 2006 y diciembre de 2015. Materiales y Métodos: Estudio de 179 pacientes (edad promedio 48.2 años [rango 32-68]), con 217 casos de síndrome del túnel carpiano idiopático y un seguimiento promedio de 97.9 meses. Los pacientes eran 145 mujeres (81%) (31 bilaterales) y 34 hombres (19%) (7 bilaterales) y fueron evaluados con la Symptom Severity Scale (SSS) y la Functional Status Scale (FSS) del Boston Carpal Tunnel Questionnaire (BCTQ). Resultados: El puntaje medio de la SSS-BCTQ fue de 3,20 + 0,26 antes de la cirugía, mejoró a 1,30 + 0,12 a los 6 meses y se mantuvo en 1,25 + 0,11 a largo plazo. El puntaje medio de la FSS-BCTQ fue de 2,57 + 0,29 antes de la cirugía, mejoró a 1,28 + 0,18 a los 6 meses y se mantuvo en 1,20 + 0,09 a largo plazo. Hubo 7 casos (3,2%) de neuropraxia posquirúrgica transitoria. No hubo conversiones a técnica abierta. Conclusión: La liberación endoscópica del túnel carpiano con la técnica de Chow es un método quirúrgico eficaz y seguro para tratar el síndrome del túnel carpiano idiopático. Nivel de Evidencia; III


Objective: To evaluate the outcomes of endoscopic release of the transverse carpal ligament (TCL) in carpal tunnel syndrome (CTS) using the Chow dual-portal technique between January 2006 and December 2015. Materials and Methods: Study population consisted of 217 cases of idiopathic CTS, in 179 patients, 145 females (81%) (31 bilateral cases) and 34 males (19%) (7 bilateral cases), with an average age of 48.2 years (range, 32-68) and an average follow-up of 97.9 months. The symptom severity and functional evaluations were performed using the Boston Carpal Tunnel Questionnaire Symptoms Severity Scale (BCTQ-SSS) and the Functional Status Scale (BCTQ-FSS). Results: The average BCTQ-SSS was 3.20±0.26 in the preoperative period, which improved to 1.30±0.12 at the 6-month postoperative follow-up and remained at 1.25±0.11 in the long-term. The average BCTQ-FSS was 2.57±0.29 in the preoperative period, which improved to 1.28±0.12 at the 6-month postoperative follow-up and remained at 1.20±0.09 in the long-term. There were 7 cases (3.2%) of transient postoperative neurapraxia. No patient required to be converted to open technique. Conclusion: The endoscopic carpal tunnel release with Chow technique is an effective and safe surgical method for the treatment of idiopathic CTS. Level of Evidence; III


Assuntos
Adulto , Pessoa de Meia-Idade , Síndrome do Túnel Carpal , Nervo Mediano , Compressão Nervosa
11.
Dolor ; 30(72): 20-24, nov. 2020.
Artigo em Espanhol | LILACS | ID: biblio-1362442

RESUMO

El síndrome de dolor crónico postmastectomía es frecuente en pacientes sometidas a cirugía por cáncer de mamas, llegando a ser invalidante en casos severos. Existen distintos factores de riesgo para que éste se presente, siendo el dolor agudo postoperatorio el único en el cual podemos intervenir. La importancia de implementar estrategias de prevención en el periodo perioperatorio es fundamental. En la mantención de la anestesia general, la utilización de propofol se asocia con menor incidencia de dolor agudo postoperatorio. El uso de anestésicos locales, ya sea por vía tópica, subcutánea y sistémica, ha demostrado su beneficio para disminuir el dolor agudo. No obstante, solo el uso tópico y endovenoso ha sido útil para reducir el dolor hasta 3 meses postcirugía. Técnicas de analgesia regional, como el bloqueo PEC I y II, bloqueo paravertebral y bloqueo del erector de la espina han demostrado ser útiles para reducir el dolor agudo; pero solo el bloqueo paravertebral ha demostrado su utilidad en reducir el dolor hasta 1 año postcirugía. El uso de gabapentina, pregabalina y ketamina desde el periodo preoperatorio disminuyen la incidencia de dolor agudo postoperatorio. En tanto, la venlafaxina y dexmedetomidina demostraron su utilidad para reducir el dolor crónico.


Postmastectomy chronic pain syndrome is common in patients undergoing surgery for breast cancer, becoming invalidating in severe cases. There are different risk factors for this to occur, with acute post-operative pain being the only one in which we can intervene. The importance of implementing prevention strategies in the perioperative period is essential. In the maintenance of general anesthesia, the use of propofol is associated with a lower incidence of acute post-operative pain. The use of local anesthetics, whether topically, subcutaneously and systemically, has shown its benefit in reducing acute pain. However, only topical and endovenous use has been useful to reduce pain up to 3 months after surgery. Regional analgesia techniques, such as PEC I and II block, paravertebral block, and spinal erector block have been shown to reduce acute pain; but only the paravertebral block has shown its usefulness in reducing pain up to 1 year after surgery. The use of gabapentin, pregabalin and ketamine from the preoperative period reduce the incidence of acute postoperative pain. Meanwhile, venlafaxine and dexmedetomidine proved useful in reducing chronic pain.


Assuntos
Humanos , Feminino , Dor Pós-Operatória/prevenção & controle , Dor Crônica/prevenção & controle , Analgésicos/uso terapêutico , Mastectomia/efeitos adversos , Dor Pós-Operatória/etiologia , Neoplasias da Mama/cirurgia , Propofol/uso terapêutico , Dexmedetomidina/uso terapêutico , Dor Crônica/etiologia , Pregabalina/uso terapêutico , Gabapentina/uso terapêutico , Ketamina/uso terapêutico , Anestésicos Locais
12.
Acta Sci Pol Technol Aliment ; 19(3): 347-357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32978916

RESUMO

BACKGROUND: le tree (Sideroxylon palmeri) belongs to family Sapotaceae, and its fruits contain hydrophilic and hydrophobic gums. Aim of this study was to develop an extraction method for pectin, a hydrophilic gum, from green and ripe tempesquistle fruit. The extraction method was gentle to minimize potential structural changes in pectin, a maceration was used, and then pectin precipitation was induced with acetone at room temperature. Pectin characterization was carried out in two steps. The first step consisted of qualitative tests of Molisch, Fehling and Lugol. The second step consisted of quantitative tests to determine esterification degree (ED) by ATR-FTIR and D-galacturonic acid (D-GalA) content with a colorimetric assay. ATR-FTIR spectroscopic method revealed that green and ripe tempesquistle fruit have an ED of 0% and 30.4%, respectively. Both fruit have a low ED pectin. The content of D-GalA in green and ripe pectins was 18.8 ±2.7% and 20.2 ±0.6%, respectively. The yield obtained in green and ripe fruit samples was 1.6 ±0.2% and 3.0 ±0.1%, respectively. The extraction method allowed two types of pectins obtained in function of maturity stage of tempesquistle fruit distinguishable by. METHODS: istle tree (Sideroxylon palmeri) belongs to family Sapotaceae, and its fruits contain hydrophilic and hydrophobic gums. Aim of this study was to develop an extraction method for pectin, a hydrophilic gum, from green and ripe tempesquistle fruit. The extraction method was gentle to minimize potential structural changes in pectin, a maceration was used, and then pectin precipitation was induced with acetone at room temperature. Pectin characterization was carried out in two steps. The first step consisted of qualitative tests of Molisch, Fehling and Lugol. The second step consisted of quantitative tests to determine esterification degree (ED) by ATR-FTIR and D-galacturonic acid (D-GalA) content with a colorimetric assay. ATR-FTIR spectroscopic method revealed that green and ripe tempesquistle fruit have an ED of 0% and 30.4%, respectively. Both fruit have a low ED pectin. The content of D-GalA in green and ripe pectins was 18.8 ±2.7% and 20.2 ±0.6%, respectively. The yield obtained in green and ripe fruit samples was 1.6 ±0.2% and 3.0 ±0.1%, respectively. The extraction method allowed two types of pectins obtained in function of maturity stage of tempesquistle fruit distinguishable by ATR. RESULTS: istle tree (Sideroxylon palmeri) belongs to family Sapotaceae, and its fruits contain hydrophilic and hydrophobic gums. Aim of this study was to develop an extraction method for pectin, a hydrophilic gum, from green and ripe tempesquistle fruit. The extraction method was gentle to minimize potential structural changes in pectin, a maceration was used, and then pectin precipitation was induced with acetone at room temperature. Pectin characterization was carried out in two steps. The first step consisted of qualitative tests of Molisch, Fehling and Lugol. The second step consisted of quantitative tests to determine esterification degree (ED) by ATR-FTIR and D-galacturonic acid (D-GalA) content with a colorimetric assay. ATR-FTIR spectroscopic method revealed that green and ripe tempesquistle fruit have an ED of 0% and 30.4%, respectively. Both fruit have a low ED pectin. The content of D-GalA in green and ripe pectins was 18.8 ±2.7% and 20.2 ±0.6%, respectively. The yield obtained in green and ripe fruit samples was 1.6 ±0.2% and 3.0 ±0.1%, respectively. The extraction method allowed two types of pectins obtained in function of maturity stage of tempesquistle fruit distinguishable by ATR-FTIR.


Assuntos
Frutas/química , Pectinas/análise , Extratos Vegetais/análise , Sapotaceae/química , Esterificação , Ácidos Hexurônicos , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Sensors (Basel) ; 20(2)2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31963656

RESUMO

Industrial chemical processes are struggling with adverse effects, such as corrosion and deposition, caused by gaseous alkali and heavy metal species. Mitigation of these problems requires novel monitoring concepts that provide information on gas-phase chemistry. However, selective optical online monitoring of the most problematic diatomic and triatomic species is challenging due to overlapping spectral features. In this work, a selective, all-optical, in situ gas-phase monitoring technique for triatomic molecules containing metallic atoms was developed and demonstrated with detection of PbCl2. Sequential collinear photofragmentation and atomic absorption spectroscopy (CPFAAS) enables determination of the triatomic PbCl2 concentration through detection of released Pb atoms after two consecutive photofragmentation processes. Absorption cross-sections of PbCl2, PbCl, and Pb were determined experimentally in a laboratory-scale reactor to enable calibration-free quantitative determination of the precursor molecule concentration in an arbitrary environment. Limit of detection for PbCl2 in the laboratory reactor was determined to be 0.25 ppm. Furthermore, the method was introduced for in situ monitoring of PbCl2 concentration in a 120 MWth power plant using demolition wood as its main fuel. In addition to industrial applications, the method can provide information on chemical reaction kinetics of the intermediate species that can be utilized in reaction simulations.

14.
Dolor ; 29(71): 36-40, jul. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1118184

RESUMO

El dolor crónico postoperatorio de cirugía de columna lumbar tiene una incidencia entre un 10-50 por ciento de los pacientes postoperados, siendo de difícil manejo. Se ha denominado síndrome de fracaso de cirugía espinal lumbar (FBSS) a aquellos pacientes que han sido beneficiarios de una cirugía del raquis lumbosacro y en quienes no se logra una mejoría de manera satisfactoria, presentando dolor crónico lumbar, siendo su incidencia de alrededor de un 20 por ciento, y debido a una mala evolución del proceso de recuperación que puede ocasionar fibrosis en el canal medular. Existen diversas alternativas terapéuticas para afrontar este problema, donde destacan el tratamiento farmacológico, medicina física y el abordaje intervencionista no quirúrgico y quirúrgico implementados últimamente, con el fin de disminuir de manera efectiva el dolor en este grupo de pacientes. Sin embargo, a pesar de las terapias combinadas, existe un grupo de pacientes que debe ser sometido a una nueva intervención quirúrgica con resultados poco promisorios.


Chronic postoperative pain of lumbar spine surgery has an incidence between 10-50 percent of postoperative patients, being difficult to manage. The Failed Back Surgery Syndrome (FBSS) has been referred to those patients who have been beneficiaries of lumbosacral spinal surgery and who do not achieve a satisfactory improvement, presenting chronic lumbar pain with an incidence around 20 percent and due to a poor evolution of the recovery process that can cause fibrosis in the medullary canal. There are several therapeutic alternatives to address this problem, which highlights the pharmacological treatment, physical medicine and the non-surgical and surgical intervention approach recently implemented, in order to effectively reduce pain in this group of patients. However, despite the combination therapies, there is a group of patients that must undergo a new surgical intervention with little promising results.


Assuntos
Humanos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/terapia , Dor Lombar/etiologia , Dor Lombar/terapia , Síndrome Pós-Laminectomia/complicações , Síndrome Pós-Laminectomia/terapia , Procedimentos Neurocirúrgicos/efeitos adversos , Dor Crônica , Vértebras Lombares/cirurgia
15.
Fam Med ; 51(4): 348-352, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30973624

RESUMO

BACKGROUND AND OBJECTIVES: Many primary care clinics rely on providers and staff to generate quality improvement (QI) ideas without explicitly including patients. However, without understanding patient perspectives, clinics may miss areas for improvement. We identified practice improvement opportunities using a medical student-driven pilot of QI design that incorporates the patient voice and explored provider/staff perceptions of patient perspectives. METHODS: One medical student interviewed eight patients for their perspectives on QI opportunities at a university-based primary care practice. Two trainees independently coded interview transcripts using directed content analysis (final codebook: 11 themes) and determined frequency of mentions for each theme. We surveyed 11 providers/staff by asking them to select 5 of the 11 themes and place them in rank order based on their perceptions of patient concerns; their surveys were aggregated into one ranked list. RESULTS: Patients most frequently identified the following themes as QI opportunities: relationship (ie, feeling of personal connection with providers/staff), specialty care, convenience, sustainability, and goal follow-up. While patients frequently identified relationship (rank=1) and goal follow-up (rank=3) as QI opportunities, the provider/staff top five list did not include relationship (rank=10) or goal follow-up (rank=7). CONCLUSIONS: Our study demonstrates two things: (1) there are areas of discordance between provider/staff perceptions and patient perspectives regarding practice improvement opportunities; and (2) medical students can participate meaningfully in the QI process. By harnessing patient perspectives with the help of medical trainees, clinics may better understand patient concerns and avoid potential QI blind spots.


Assuntos
Participação do Paciente/métodos , Atenção Primária à Saúde/normas , Melhoria de Qualidade , Estudantes de Medicina , California , Educação Médica , Objetivos , Humanos , Relações Médico-Paciente , Pesquisa Qualitativa , Inquéritos e Questionários
16.
Paediatr Anaesth ; 28(12): 1078-1086, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30307663

RESUMO

BACKGROUND: Propofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharmacokinetic and pharmacodynamic propofol model, containing remifentanil pharmacodynamic interaction information, enables propofol effect-site target-controlled infusion in children with a better prediction of its hypnotic effect when both drugs are combined. AIMS: We designed this study to derive an integrated propofol pharmacokinetic-pharmacodynamic model in children and to describe the pharmacodynamic interaction between propofol and remifentanil on the electroencephalographic bispectral index effect. METHODS: Thirty children (mean age: 5.45 years, range 1.3-11.9; mean weight: 23.5 kg, range 8.5-61) scheduled for elective surgery with general anesthesia were studied. After sevoflurane induction, maintenance of anesthesia was based on propofol and remifentanil. Blood samples to measure propofol concentration were collected during anesthesia maintenance and up to 6 hours in the postoperative period. Bispectral index data were continuously recorded throughout the study. A pharmacokinetic-pharmacodynamic model was developed using population modeling. The Greco model was used to examine the pharmacokinetic-pharmacodynamic interaction between propofol and remifentanil for BIS response RESULTS: Propofol pharmacokinetic data from a previous study in 53 children were pooled with current data and simultaneously analyzed. Propofol pharmacokinetics were adequately described by a three-compartment distribution model with first-order elimination. Theory-based allometric relationships based on TBW improved the model fit. The Greco model supported an additive interaction between propofol and remifentanil. Remifentanil showed only a minor effect in BIS response. CONCLUSION: We have developed an integrated propofol pharmacokinetic-pharmacodynamic model that can describe the pharmacodynamic interaction between propofol and remifentanil for BIS response. An additive interaction was supported by our modeling analysis.


Assuntos
Eletroencefalografia/efeitos dos fármacos , Propofol/farmacologia , Propofol/farmacocinética , Remifentanil/farmacologia , Analgésicos Opioides/farmacologia , Anestésicos Intravenosos/sangue , Anestésicos Intravenosos/farmacocinética , Anestésicos Intravenosos/farmacologia , Criança , Pré-Escolar , Interações Medicamentosas , Feminino , Humanos , Lactente , Masculino , Propofol/sangue
17.
Dolor ; 28(69): 10-14, jul. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1117320

RESUMO

INTRODUCCIÓN: la anestesia espinal unilateral (AEU) es una alternativa para el desarrollo de la cirugía ortopédica ambulatoria (COA). el OBJETIVO de este ensayo clínico fue el evaluar una dosis baja de bupivacaína hiperbara (BHB), asociada a fentanilo intratecal (FI) para obtención de AEU en COA. MATERIALES Y MÉTODOS: ensayo clínico, prospectivo, controlado en pacientes ASA I a II. la AEU se efectuó con el paciente en decúbito lateral (DL), con el lado operatorio hacia abajo, a nivel de L3-L4. se inyectó 5 mg de BHB 0,75% asociado a 20 µg de FI. se evaluó el bloqueo sensitivo (BS) y motor (BM) cada 3 minutos, los primeros 20 minutos y luego cada 15 minutos. Se midió el nivel máximo alcanzado, el tiempo de regresión a T12 y el tiempo de regresión de dos segmentos. se registró la incidencia de complicaciones. RESULTADOS: 50 pacientes fueron incluidos, 66% de sexo masculino. Se obtuvo anestesia unilateral en el 84% y BM total unilateral en el 86%. La altura del BS osciló entre T9 y T11. la duración del BS fue 116 min. (SD± 23). la regresión a T12 fue de 47 min (SD±19). No se encontró correlación entre talla, dosis y duración de bloqueo. ningún paciente necesitó anestesia general. 1 paciente presentó bradicardia. DISCUSIÓN: la AEU con dosis bajas de BHB asociado a FI es eficiente en COA. se obtuvo adecuados BS y BM en la mayoría de los pacientes. la AEU mostró ser confiable, permitiendo una alta precoz y segura.


INTRODUCTION: The unilateral spinal anesthesia (USA) is an alternative for orthopedic ambulatory surgery (OAS). The AIM of this study was to evaluate a low dose of hyperbaric bupivacaine (HB) associated with intrathecal fentanyl (ITF) to produce USA. MATERIALS AND METHODS: Prospective, controlled clinical trial in ASA I ­II patients. The USA was developed in lateral position with the operating side downwards between L3-L4 space with 5 mg of HB + 20 µg ITF. We evaluated sensitive level block (SB), motor level block (MB), maximum level obtained, discharge time (DT) and collateral effects incidence. RESULTS: 50 patients were included, 66% male. The USA was obtained in 84% and total BM was present in 86% of cases. The level obtained of SB was between T9-T11 and the duration was 116 min (SD± 23). No correlation was obtained between patients height, BH dose and block duration. 1 patient presented bradycardia. No general anesthesia was necessary. DISCUSSION: The USA with a low dose of HB and ITF it's safe to developed OAS. Only 11 min were necessary to obtain a good SB and MB.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Bupivacaína/administração & dosagem , Procedimentos Ortopédicos/métodos , Procedimentos Cirúrgicos Ambulatórios/métodos , Raquianestesia/métodos , Fentanila/administração & dosagem , Estudos Prospectivos , Anestesia Local
18.
Opt Lett ; 43(10): 2260-2263, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29762567

RESUMO

Laser-induced breakdown spectroscopy is presented for trace element detection of liquid samples by analyzing a single droplet levitated by ultrasonic waves. A single liquid droplet is placed in the node of a standing acoustic wave produced by a uniaxial levitator for further chemical analysis. The acoustic levitator consists of a commercial Langevin-type transducer, attached to a concave mechanical amplifier, and a concave reflector. A micro-syringe was used to manually place individual liquid droplet samples in the acoustic levitation system. For chemical analysis, a laser-induced plasma is produced by focusing a single laser pulse on the levitated water droplet after it partially dries. The performance of the acoustic levitator on micron-sized droplets is discussed, and the detection of Ba, Cd, Hg, and Pb at parts per million (milligrams/liter) and sub-parts per million levels is reported. The process, starting from placing the sample in the acoustic levitator and ending on the chemical identification of the traces, takes a few minutes. The approach is particularly interesting in applications demanding limited volumes of liquid samples and relative simple and inexpensive techniques.

19.
Neurocirugia (Astur : Engl Ed) ; 29(1): 18-24, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-29191646

RESUMO

OBJECTIVE: The protocol for optimal antiplatelet therapy to prevent thrombotic complications following brain aneurysm embolisation is not clear. Our objective is to describe the characteristics of patients presenting with thrombotic or haemorrhagic complications secondary to endovascular treatment. METHODS: A cross sectional descriptive study was performed, which included all patients that required endovascular treatment for brain aneurysm at San Ignacio University Hospital from November 2007 to January 2016. Thrombotic and haemorrhagic complications over six months of follow-up were assessed, considering the premedication regimen with antiplatelet agents, location, size of the aneurysm and embolisation technique performed. RESULTS: 122 patients were evaluated, on whom 130 procedures were performed for endovascular treatment of brain aneurysms. Thrombotic complications were more frequent in patients who did not receive premedication (25%) compared to those who did receive an antiplatelet treatment regimen (standard dose 3.87% or loading dose 8.70%), and this difference was statistically significant (P=.043). CONCLUSIONS: Thromboembolic events are the most common complication of brain aneurysm embolisation. Both our study and the literature suggest that the use of dual antiplatelet therapy with aspirin and clopidogrel lowers the rate of symptomatic thromboembolic complications, regardless of the administration protocol.


Assuntos
Embolização Terapêutica , Hemorragia/etiologia , Aneurisma Intracraniano/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Pré-Medicação , Trombose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/complicações , Aneurisma Roto/terapia , Criança , Estudos Transversais , Embolização Terapêutica/instrumentação , Feminino , Hemorragia/induzido quimicamente , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombose/prevenção & controle , Adulto Jovem
20.
Biochimie ; 142: 31-40, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28803999

RESUMO

Emodin is an anthraquinone obtained from Rheum palmatum rootstocks. Here we tested the cytotoxic effects of emodin on Trypanosoma cruzi epimastigotes, as well as the morphological changes that were induced by this compound in the parasite. Emodin was permeable and blocked in vitro cell division of T. cruzi epimastigotes in axenic medium, causing growth arrest in a dose-dependent but reversible manner. Emodin-exposed epimastigotes underwent duplication of organelles, such as the nucleus, kinetoplast and flagellum, but were incapable of completing cytokinesis. Neither elongation of the parasite body nor appearance of the regular longitudinal cleavage furrow was displayed, suggesting that emodin is most likely affecting components of the parasite cytoskeleton. Moreover, drug-treated parasites acquired alterations such as protuberances, folds and indentations on their membrane surface. Since emodin has been shown to be a potent protein kinase CK2 inhibitor, and we have previously described an association between tubulin and CK2 in T. cruzi epimastigotes (De Lima et al. Parasitology132, 511-523, 2006), we also measured the indirect effect of the drug on tubulin. Incubation of epimastigotes with axenic medium containing emodin hindered the endogenous phosphorylation of tubulin in whole-cell parasite extracts. All our results suggested that the parasite CK2 may be important for the maintenance of the morphology and for the regulation of mitosis-cytokinesis transition in T. cruzi epimastigotes.


Assuntos
Meios de Cultura/química , Emodina/farmacologia , Trypanosoma cruzi/citologia , Trypanosoma cruzi/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Trypanosoma cruzi/crescimento & desenvolvimento
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