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1.
J Cell Biochem ; 124(8): 1173-1185, 2023 08.
Article in English | MEDLINE | ID: mdl-37357420

ABSTRACT

Sialyl Lewis X (sLex ) antigen is a fucosylated cell-surface glycan that is normally involved in cell-cell interactions. The enhanced expression of sLex on cell surface glycans, which is attributed to the upregulation of fucosyltransferase 6 (FUT6), has been implicated in facilitating metastasis in human colorectal, lung, prostate, and oral cancers. The role that the upregulated FUT6 plays in the progression of tumor to malignancy, with reduced survival rates, makes it a potential target for anticancer drugs. Unfortunately, the lack of experimental structures for FUT6 has hampered the design and development of its inhibitors. In this study, we used in silico techniques to identify potential FUT6 inhibitors. We first modeled the three-dimensional structure of human FUT6 using AlphaFold. Then, we screened the natural compound libraries from the COCONUT database to sort out potential natural products (NPs) with best affinity toward the FUT6 model. As a result of these simulations, we identified three NPs for which we predicted binding affinities and interaction patterns quite similar to those we calculated for two experimentally tested FUT6 inhibitors, that is, fucose mimetic-1 and a GDP-triazole derived compound. We also performed molecular dynamics (MD) simulations for the FUT6 complexes with identified NPs, to investigate their stability. Analysis of the MD simulations showed that the identified NPs establish stable contacts with FUT6 under dynamics conditions. On these grounds, the three screened compounds appear as promising natural alternatives to experimentally tested FUT6 synthetic inhibitors, with expected comparable binding affinity. This envisages good prospects for future experimental validation toward FUT6 inhibition.


Subject(s)
Fucosyltransferases , Neoplasms , Humans , Male , Drug Discovery , Fucosyltransferases/antagonists & inhibitors , Fucosyltransferases/metabolism , Glycosylation , Sialyl Lewis X Antigen/metabolism
2.
Vaccines (Basel) ; 11(2)2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36851241

ABSTRACT

Candida dubliniensis is an opportunistic pathogen associated with oral and invasive fungal infections in immune-compromised individuals. Furthermore, the emergence of C. dubliniensis antifungal drug resistance could exacerbate its treatment. Hence, in this study a multi-epitope vaccine candidate has been designed using an immunoinformatics approach by targeting C. dubliniensis secreted aspartyl proteinases (SAP) proteins. In silico tools have been utilized to predict epitopes and determine their allergic potential, antigenic potential, toxicity, and potential to elicit interleukin-2 (IL2), interleukin-4 (IL4), and IFN-γ. Using the computational tools, eight epitopes have been predicted that were then linked with adjuvants for final vaccine candidate development. Computational immune simulation has depicted that the immunogen designed emerges as a strong immunogenic candidate for a vaccine. Further, molecular docking and molecular dynamics simulation analyses revealed stable interactions between the vaccine candidate and the human toll-like receptor 5 (TLR5). Finally, immune simulations corroborated the promising candidature of the designed vaccine, thus calling for further in vivo investigation.

3.
Front Vet Sci ; 10: 1280273, 2023.
Article in English | MEDLINE | ID: mdl-38192725

ABSTRACT

Feline infectious peritonitis (FIP) is a grave and frequently lethal ailment instigated by feline coronavirus (FCoV) in wild and domestic feline species. The spike (S) protein of FCoV assumes a critical function in viral ingress and infection, thereby presenting a promising avenue for the development of a vaccine. In this investigation, an immunoinformatics approach was employed to ascertain immunogenic epitopes within the S-protein of FIP and formulate an innovative vaccine candidate. By subjecting the amino acid sequence of the FIP S-protein to computational scrutiny, MHC-I binding T-cell epitopes were predicted, which were subsequently evaluated for their antigenicity, toxicity, and allergenicity through in silico tools. Our analyses yielded the identification of 11 potential epitopes capable of provoking a robust immune response against FIPV. Additionally, molecular docking analysis demonstrated the ability of these epitopes to bind with feline MHC class I molecules. Through the utilization of suitable linkers, these epitopes, along with adjuvants, were integrated to design a multi-epitope vaccine candidate. Furthermore, the stability of the interaction between the vaccine candidate and feline Toll-like receptor 4 (TLR4) was established via molecular docking and molecular dynamics simulation analyses. This suggests good prospects for future experimental validation to ascertain the efficacy of our vaccine candidate in inducing a protective immune response against FIP.

4.
Med. crít. (Col. Mex. Med. Crít.) ; 36(4): 210-214, Jul.-Aug. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1430750

ABSTRACT

Resumen: Introducción: Las fuerzas mecánicas generadas durante la ventilación mecánica por la interacción entre el ventilador y el sistema respiratorio pueden dañar al pulmón en un proceso que se ha denominado lesión inducida por el ventilador. El grado de lesión se ha relacionado con la cantidad de energía transferida desde el ventilador mecánico al sistema respiratorio dentro de un periodo de tiempo determinado, denominado poder mecánico; datos experimentales basados en tomografías sugieren que el poder mecánico mayor de 12 J/min podría generar lesión. Se proyecta como otra de las variables a controlar dentro de las estrategias de protección pulmonar, determinado en estudios experimentales como un umbral de energía a partir del cual inician los cambios mecánicos en el pulmón que pueden conducir a lesión inducida por el ventilador. Material y métodos: Se realizó un estudio retrospectivo, analítico, comparativo, se incluyeron todos los pacientes con diagnóstico de neumonía por SARS-CoV-2 que requieren ventilación mecánica invasiva; en un periodo de tiempo comprendido de marzo-agosto de 2021 que ingresaron a la Unidad de Cuidados Intensivos y utilizaron el poder mecánico como variable para predecir la mortalidad. Resultados: La población estudiada se compuso de 67 pacientes; se evaluó la asociación entre el poder mecánico alto a las 48 horas y la mortalidad, se documentó que 49.25% (n = 33) de los casos que mantuvieron el poder mecánico alto en 48 horas murieron, 28.35% (n = 19) con poder mecánico alto no se asoció con mortalidad, 8.95% (n = 6) que no mantuvieron cálculo de poder mecánico alto murieron y 13.43% (n = 9) de los pacientes con poder mecánico menor a 12 J/min no murieron. Se realizó una prueba de asociación con χ2 de Pearson en la que se obtiene un valor de p = 0.105, por lo que no existe diferencia estadísticamente significativa y no se corrobora la asociación entre la mortalidad de los pacientes con poder mecánico alto (> 12 J/min) a las 48 horas. Conclusión: El poder mecánico puede considerarse como otra variable a controlar como estrategia de protección pulmonar del paciente con infección por SARS-CoV-2, basado en que la energía transmitida al pulmón tiene mayor impacto en los pacientes que reciben ventilación mecánica por un intervalo de tiempo mayor de siete días, con un promedio de estancia en la Unidad de Cuidados Intensivos 12.3 + 6.2 días y el promedio de días de ventilación mecánica invasiva 9.2 + 5.6.


Abstract: Introduction: The mechanical forces generated during mechanical ventilation by the interaction between the ventilator and the respiratory system can damage the lung in a process that has been called ventilator induced injury. The degree of injury has been related to the amount of energy transferred from the mechanical ventilator to the respiratory system within a given period of time, called mechanical power, experimental data based on tomographies suggest that mechanical power greater than 12 J/min could generate injury. It is projected as another variables to control within lung protection strategies, determining in experimental studies as an energy threshold from which mechanical changes in the lung begin that can lead to ventilator induced injury. Material and methods: A retrospective, analytical, comparative study was carried out. All patients with a diagnosis of SARS-CoV-2 pneumonia who required invasive mechanical ventilation were admitted; In a period of time between March-August 2021, they were admitted to the intensive care unit and used mechanical power as a variable to predict mortality. Results: The studied population consisted of 67 patients; the association between high mechanical power at 48 hours and mortality was evaluated, it was documented that 49.25% (n = 33) of the patients who maintained high mechanical power in 48 hours died, 28.35% (n = 19) with power high mechanical was not associated with mortality, 8.95% (n = 6) who did not have high mechanical power calculation died and 13.43% (n = 9) of patients with mechanical power less than 12 J/min survived. An association test was performed with Pearson's χ2 in which a p value of 0.105 was obtained, so there is no statistically significant difference and the association between the mortality of the patients is not corroborated. with high mechanical power (> 12 J/min) at 48 hours. Conclusion: Mechanical power can be considered as another variable to control as a lung protection strategy for patients with SARS-CoV-2 infection, based on the fact that the energy transmitted to the lung has a greater impact on patients who receive mechanical ventilation for an interval time greater than seven days, with an average stay in the intensive care unit 12.3 + 6.2 days and the average days of invasive mechanical ventilation 9.2 + 5.6.


Resumo: Introdução: As forças mecânicas geradas durante a ventilação mecânica pela interação entre o ventilador e o sistema respiratório podem lesar o pulmão em um processo que tem sido chamado de lesão induzida pelo ventilador. O grau de lesão tem sido relacionado à quantidade de energia transferida do ventilador mecânico para o sistema respiratório em um determinado período de tempo, denominado potência mecânica. Dados experimentais baseados em tomografia sugerem que potência mecânica superior a 12 J/min pode gerar lesão. Ele é projetado como mais uma das variáveis a serem controladas dentro das estratégias de proteção pulmonar, determinando em estudos experimentais como um limiar de energia a partir do qual se iniciam as alterações mecânicas no pulmão que podem levar à lesão induzida pelo ventilador. Material e métodos: Realizou-se um estudo retrospectivo, analítico e comparativo, foram admitidos todos os pacientes com diagnóstico de pneumonia por SARS-CoV-2 que necessitaram de ventilação mecânica invasiva; em um período de março a agosto de 2021 que foram internados na unidade de terapia intensiva e utilizaram a potência mecânica como variável para predizer mortalidade. Resultados: A população do estudo foi composta por 67 pacientes; Foi avaliada a associação entre alta potência mecânica em 48 horas e mortalidade, foi documentado que 49.25% (n = 33) dos pacientes que mantiveram potência mecânica alta em 48 horas morreram, 28.35% (n = 19) com potência mecânica alta não foi associado à mortalidade, 8.95% (n = 6) que ñao mantiveran o calculo de alta potencia mecanoca morreram e 13.4% (n = 9) dos pacientes com potencia mecanica menor que 12 J/min nao morreram. Realizou-se um teste de associação com o χ2 de Pearson, no qual se obtém um valor de p de 0.105, portanto não há diferença estatisticamente significante e a associação entre mortalidade do paciente não é corroborada com alta potência mecânica (> 12 Joul/min) em 48 horas. Conclusão: A potência mecânica pode ser considerada mais uma variável a ser controlada como estratégia de proteção pulmonar para pacientes com infecção por SARS-CoV-2, tendo em vista que a energia transmitida ao pulmão tem maior impacto em pacientes que recebem ventilação mecânica por um intervalo de tempo superior a 7 dias, com média de permanência na unidade de terapia intensiva 12.3 + 6.2 dias e média de dias de ventilação mecânica invasiva 9.2 + 5.6.

5.
Med. crít. (Col. Mex. Med. Crít.) ; 36(3): 132-137, May.-Jun. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1430736

ABSTRACT

Resumen Introducción: El porcentaje de pacientes gravemente enfermos por COVID-19 que toleran el retiro de la ventilación mecánica es mínimo, por lo cual es fundamental determinar cuáles son los predictores de éxito en el retiro de la ventilación mecánica. Objetivos: Determinar si los índices de oxigenación, tiempo en presión soporte e índice de choque diastólico son predictores de éxito en el retiro de la ventilación mecánica en pacientes críticamente enfermos por COVID-19. Material y métodos: Estudio de cohorte prospectivo en pacientes con COVID-19 que ingresaron a la Unidad de Cuidados Intensivos y fueron sometidos a pruebas de ventilación espontánea, siendo posteriormente liberados del ventilador mecánico. Se recolectaron datos demográficos, resultados de laboratorio y parámetros ventilatorios con la finalidad de analizar y determinar predictores de éxito en el retiro de la ventilación mecánica. Resultados: Se observó una diferencia significativa entre los pacientes que toleraron y los que no toleraron el retiro de la ventilación mecánica en las siguientes variables: índice de respiración rápida superficial 47 ± 17.9 vs 90 ± 20.2 (p = 0.08), días de ventilación mecánica 5.8 vs 9.3 (p = 0.03), sesiones de prono 1.36 vs 2.33 (p = 0.058) y presión arterial diastólica 57 ± 3.6 (p = 0.027). Conclusión: En los pacientes críticamente enfermos por COVID-19 que son candidatos a retiro de la ventilación mecánica sugerimos usar como predictores de éxito: el índice de respiraciones rápidas superficiales < 64, días de ventilación mecánica < 8, presión arterial diastólica > 57 mmHg y haber tenido máximo dos sesiones de prono como predictores de éxito en el retiro de la ventilación mecánica.


Abstract Introduction: The percentage of critically ill patients due to COVID-19 who tolerate the withdrawal of mechanical ventilation is minimal. It is essential to determine which are the predictors of success in weaning. Objectives: To determine if the oxygenation indices, time in pressure support, and diastolic shock index are predictors of success in the withdrawal of mechanical ventilation in critically ill patients due to COVID-19. Material and methods: Prospective cohort study in patients with COVID-19 who were admitted to the ICU and underwent tests of spontaneous ventilation, being later released from the mechanical ventilator. Demographic data, laboratory results, ventilatory parameters were collected in order to analyze and determine predictors of success in weaning. Results: A significant difference was found between those who tolerated and those who did not tolerate the withdrawal of mechanical ventilation in the following variables: rapid shallow breathing index 47 ± 17.9 vs 90 ± 20.2 (p = 0.08), days of mechanical ventilation 5.8 vs 9.3 (p = 0.03), prone sessions 1.36 vs 2.33 (p = 0.058), diastolic blood pressure 57 ± 3.6 (p = 0.027). Conclusion: In critically ill patients due to COVID-19 who are candidates for withdrawal from mechanical ventilation, we suggest using as predictors of success: Index of rapid shallow breaths < 64, days of mechanical ventilation < 8, diastolic blood pressure > 57 mmHg and having had a maximum two prone sessions as predictors of success in the withdrawal of mechanical ventilation.


Resumo Introdução: A porcentagem de pacientes graves com COVID-19 que toleram a retirada da ventilação mecânica é mínima, por isso é essencial determinar os preditores de sucesso na retirada da ventilação mecânica. Objetivos: Determinar se os índices de oxigenação, tempo em pressão suporte, índice de choque diastólico são preditores de sucesso no desmame da ventilação mecânica em pacientes críticos com COVID-19. Material e métodos: Estudo de coorte prospectivo em pacientes com COVID-19 admitidos na unidade de terapia intensiva e submetidos a testes de ventilação espontânea e posteriormente liberados do ventilador mecânico. Foram coletados dados demográficos, resultados laboratoriais e parâmetros ventilatórios para analisar e determinar os preditores de sucesso no desmame da ventilação mecânica. Resultados: Observou-se uma diferença significativa entre os pacientes que toleraram e os que não toleraram a retirada da ventilação mecânica nas seguintes variáveis: índice de respiração rápida e superficial 47 ±17.9 vs 90 ± 20.2 (p = 0.08), dias de ventilação mecânica 5.8 vs 9.3 (p = 0.03), sessões de prona 1.36 vs 2.33 (p = 0.058) e pressão arterial diastólica 57 ± 3.6 (p = 0.027). Conclusão: Em pacientes em estado crítico com COVID-19 candidatos à retirada da ventilação mecânica, sugerimos usar como preditores de sucesso: índice de respirações rápidas e superficiais < 64, dias de ventilação mecânica < 8, pressão arterial diastólica > 57 mmHg e ter realizado no máximo 2 sessões em decúbito ventral como preditores de sucesso no desmame da ventilação mecânica.

6.
Ann Vasc Surg ; 66: 385-389, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31918038

ABSTRACT

BACKGROUND: Carotid endarterectomy (CEA) represents a standard procedure in case of symptomatic carotid stenosis of 50-99% within 2 weeks from onset of stroke or transient ischemic attack (TIA) symptoms. The optimal time to perform CEA after intravenous thrombolysis (IVT) is still unclear. The aim of this study was to analyze the safety of CEA performed within 2 weeks from IVT. MATERIALS AND METHODS: A consecutive series of 70 patients affected by symptomatic carotid stenosis have been treated as per the international guidelines during 3 years. Eleven (15.7%) patients have been treated with IVT before CEA for ischemic stroke; remaining 59 (84.3%) patients received only CEA. CEA was performed in median 8 days (range: 2-13) after IVT. We examined the grade of disability before and after surgery as well as at 3 months follow-up, using the modified Ranking Scale (mRS). RESULTS: Among the patients who underwent CEA + IVT, CEA was performed in median 8 days (range: 2-13) after IVT. One patient received CEA within 48 hours from IVT, 3 patients within 72 hours, and 7 patients within 2 weeks. The complications within 90 days from surgery, in CEA + IVT group, were 3 cases of intracerebral hemorrhage (ICH) without symptoms. In patients who received only CEA, the complications were 1 case of stroke and 2 cases of ICH. The mortality registered was 0% in both groups. Among CEA + IVT group at 90 days after surgery, 9 patients had a mRS grade of 0-2, 2 patients had mRS of 3-5. CONCLUSIONS: In our series, IVT before CEA did not seem to increase the rate of complications. However, the study has several limitations, and further studies must be performed before solid evidence is available for recommendations regarding the timing of CEA after IVT.


Subject(s)
Brain Ischemia/drug therapy , Carotid Stenosis/surgery , Endarterectomy, Carotid , Fibrinolytic Agents/administration & dosage , Stroke/drug therapy , Thrombolytic Therapy , Time-to-Treatment , Administration, Intravenous , Aged , Aged, 80 and over , Brain Ischemia/diagnosis , Brain Ischemia/etiology , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Disability Evaluation , Endarterectomy, Carotid/adverse effects , Female , Fibrinolytic Agents/adverse effects , Humans , Male , Middle Aged , Postoperative Complications/etiology , Recovery of Function , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/diagnosis , Stroke/etiology , Thrombolytic Therapy/adverse effects , Time Factors , Treatment Outcome
7.
Med. crít. (Col. Mex. Med. Crít.) ; 32(3): 156-159, may.-jun. 2018. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1091040

ABSTRACT

Resumen: Son múltiples las formas de interpretar una gasometría, aunque ninguna mejor que la otra. Una correcta interpretación de la gasometría es una habilidad que todo médico debe dominar. Intentar interpretar «todo a la vez¼ y de forma poco organizada es el error más común. Entonces el secreto para desarrollar dicha habilidad radica en el «orden¼, por lo que te sugerimos utilizar sólo 3 pasos, sólo 3 fórmulas. El abordaje diagnóstico de los trastornos ácido-base con el método tradicional de Henderson-Hasselbalch no permite explicar todos los trastornos, pero en combinación con el exceso de base descrito por Siggaard-Andersen, facilita el diagnóstico, además que esta combinación es sencilla, rigurosa y práctica.


Abstract: There are multiple ways of interpreting gasometry, although no better than the other. A correct interpretation of gasometry is a skill that every doctor must dominate. Try to interpret «all at once¼ and little organized is the most common error. Then the secret to developing that skill lies in the «order¼, so we suggest you use only 3 steps, just 3 formulas. The diagnostic approach of acid-base disorders with the method. Traditional of Henderson-Hasselbalch does not allow to explain all disorders, but in combination with the excess of base described by Siggaard-Andersen, facilitates the diagnosis, besides that this combination is simple, rigorous and practical.


Resumo: Há muitas maneiras de interpretar uma gasometria, embora nenhuma melhor que a outra. Uma interpretação correta da gasometria é uma habilidade que todo médico deve dominar. Tentar interpretar «tudo de uma vez¼ e de maneira mal organizada é o erro mais comum. Então o segredo para desenvolver essa habilidade está na «ordem¼, por isso sugerimos que você use apenas 3 passos, somente 3 fórmulas. A abordagem diagnóstica de distúrbios ácido-base com o método tradicional de Henderson-Hasselbalch não explica todas as desordens, mas em combinação com o excesso de base descrito por Siggaard-Andersen, facilita o diagnóstico, além de que esta combinação é simples, rigorosa e prática.

8.
Rev. colomb. anestesiol ; 45(4): 353-359, Oct.-Dec. 2017. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-900382

ABSTRACT

Abstract Lactic acidosis is defined as the presence of pH <7.35, blood lactate >2.0 mmol/L and PaCO2 <42 mmHg. However, the definition of severe lactic acidosis is controversial. The primary cause of severe lactic acidosis is shock. Although rare, metformin-related lactic acidosis is associated with a mortality as high as 50%. The treatment for metabolic acidosis, including lactic acidosis, may be specific or general, using sodium bicarbonate, trihydroxyaminomethane, carbicarb or continuous haemodiafiltration. The successful treatment of lactic acidosis depends on the control of the aetiological source. Intermittent or continuous renal replacement therapy is perfectly justified, shock being the argument for deciding which modality to use. We report a case of a male patient presenting with metformin poisoning as a result of attempted suicide, who developed lactic acidosis and multiple organ failure. The critical success factor was treatment with continuous haemodiafiltration.


Resumen Definimos acidosis láctica en presencia de pH<7,35, lactato en sangre >2,0 mmol/ly PaCO2 <42 mmHg. Por otro lado, la definición de acidosis láctica grave es controvertida. La causa principal de acidosis láctica grave es el estado de choque. La acidosis láctica pormetformina es rara, pero alcanza una mortalidad del 50%. La acidosis metabólica, incluyendo a la acidosis láctica, puede recibir tratamiento específico o tratamiento general con bicarbonato de sodio, trihidroxiaminometano, carbicarb o hemodiafiltracion continua. El éxito del tratamiento de la acidosis láctica yace en el control de la fuente etiológica; la terapia de reemplazo renal intermitente o continua está perfectamente justificada, y el argumento para decidir cuál utilizar es el estado de choque. Presentamos el informe de un caso de un paciente masculino con intoxicación por metformina como intento suicida, quien desarrolló acidosis láctica y falla orgánica múltiple; la base para el éxito del caso fue el tratamiento con hemodiafiltración continua.


Subject(s)
Humans
9.
J Control Release ; 163(1): 75-81, 2012 Oct 10.
Article in English | MEDLINE | ID: mdl-22580225

ABSTRACT

Microbubbles (MB) are routinely used contrast agents for functional and molecular ultrasound (US) imaging. In addition, they have been attracting more and more attention for drug delivery purposes, enabling e.g. US-mediated drug delivery across biological barriers and US-induced triggered drug release from the MB shell. The vast majority of efforts in this regard have thus far focused on phospholipid-based soft-shell MB, which are suboptimal for stably incorporating large amounts of drug molecules because of their relatively thin shell. Using poly(butyl cyanoacrylate) (PBCA)-based hard-shell MB, we show here that both hydrophilic (Rhodamine-B) and hydrophobic (Coumarin-6) model drugs can be efficiently and stably entrapped within the ~50 nm shell of PBCA MB. In addition, we demonstrate that model drug loading does not negatively affect the acoustic properties of the MB, and that functionalizing the surface of fluorophore-loaded MB with anti-VEGFR2 antibodies enables image-guided and targeted model drug delivery to tumor blood vessels. Finally, we show both in vitro and in vivo that disintegrating VEGFR2-targeted MB with high-mechanical index US pulses leads to high levels of model drug release. Consequently, these findings indicate that polymer-based MB are highly suitable systems for image-guided, targeted and triggered drug delivery to tumors and tumor blood vessels.


Subject(s)
Cyanoacrylates/chemistry , Drug Delivery Systems , Microbubbles , Neoplasms/metabolism , Acoustics , Animals , Cell Line, Tumor , Coumarins/administration & dosage , Coumarins/chemistry , Enbucrilate , Fluorescent Dyes/administration & dosage , Fluorescent Dyes/chemistry , Mice , Microscopy, Fluorescence , Rhodamines/administration & dosage , Rhodamines/chemistry , Thiazoles/administration & dosage , Thiazoles/chemistry , Vascular Endothelial Growth Factor Receptor-2/metabolism
10.
Drug Deliv Transl Res ; 2(1): 56-64, 2012 Feb.
Article in English | MEDLINE | ID: mdl-25786599

ABSTRACT

Microbubbles (MB) are routinely used as contrast agents for functional and molecular ultrasound (US) imaging. For molecular US imaging, MB are functionalized with antibodies or peptides, in order to visualize receptor expression by angiogenic or inflamed endothelium. In general, initial in vitro binding studies with targeted MB are performed using phase contrast microscopy. Difficulties in the identification of MB in standard phase contrast microscopy, however, generally result in high variability, high observer dependency, and low reproducibility. To overcome these shortcomings, we here describe a simple post-loading strategy for labeling polymer-based MB with fluorophores, and we show that the use of rhodamine-loaded MB in combination with fluorescence microscopy substantially reduces the variability and the observer dependency of in vitro binding studies. In addition, we demonstrate that rhodamine-loaded MB can also be used for in vivo and ex vivo experimental setups, e.g., for analyzing MB binding to inflamed carotids using two-photon laser scanning microscopy, and for validating the binding of VEGFR2-targeted MB to tumor endothelium. These findings demonstrate that fluorescently labeled MB substantially facilitate translational molecular US studies, and they suggest that a similar synthetic strategy can be exploited for preparing drug-loaded MB, to enable image-guided, targeted, and triggered drug delivery to tumors and to sites of inflammation.

11.
Med. reabil ; (57): 7-11, 2001. tab, graf
Article in Portuguese | LILACS | ID: lil-300557

ABSTRACT

No presente estudo, valores da latência de conduçäo motora foram avaliados em vinte e três pacientes em um total de vinte e nove nervos, usando diferentes calibraçöes (1mV/2ms por divisäo e 5mV/2ms por divisäo) em um ponto distal e outro proximal de um mesmo nervo.O objetivo do trabalho foi comparar os valores de latências obtidos com as duas calibraçöes distintas e estabelecer a possibilidade de um erro diagnóstico induzido pela escolha do parâmetro usado. Os resultados mostram diferenças significativas entre os valores obtidos com as calibraçöes de 1mV e5mV por divisäo, acima de 12 por cento. Uma alternativa de cálculo foi a velocidade de conduçäo motora feita com duas calibraçöes diferentes


Subject(s)
Humans , Diagnostic Errors , Neurologic Examination , Calibration
12.
Med. reabil ; (51): 11-6, 1999. ilus, tab
Article in Portuguese | LILACS | ID: lil-283463

ABSTRACT

Os autores avaliaram quarenta pacientes diabéticos de uma Clínica multidisciplinar especializada na conduçäo dos pés. Todos foram submetidos à avaliaçäo clínica e à determinaçäo da velocidade de conduçäo neural e da pressäo plantar.O objetivo foi verificar a incidência de alteraçöes nos aspectos citados e obter informaçöes que possam ser úteis na prediçäo e prevençäo de complicaçöes terciárias mais graves tais como úlceras plantares e amputaçöes.Os resultados revelaram uma alta prevalência de arreflexia osteotendínea (sessenta e sete por cento), alteraçäo clínica mais frequente.A incidência de neuropatia periférica(oitenta por cento)e de hiperpressäo plantar(quarenta e sete por cento)foi também bastante alta.A avaliaçäo clínica revelou-se importante na identificaçäo de pacientes com neuropatia e aumento da pressäo plantar.Porém, o faz de forma menos acurada que os exames de eletroneurografia e baropodometria. A observaçäo de tais alteraçöes com esses testes, definem grupo de risco para ulceraçäo plantar que deve ser mantido sob cuidados preventivos


Subject(s)
Humans , Diabetic Foot/complications , Diabetic Foot/diagnosis
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