Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Ann Neurol ; 92(5): 819-833, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36082761

RESUMEN

OBJECTIVES: Previous studies have established the role of the cortico-mesolimbic and descending pain modulation systems in chronic pain prediction. Mild traumatic brain injury (mTBI) is an acute pain model where chronic pain is prevalent and complicated for prediction. In this study, we set out to study whether functional connectivity (FC) of the nucleus accumbens (NAc) and the periaqueductal gray matter (PAG) is predictive of pain chronification in early-acute mTBI. METHODS: To estimate FC, resting-state functional magnetic resonance imaging (fMRI) of 105 participants with mTBI following a motor vehicle collision was acquired within 72 hours post-accident. Participants were classified according to pain ratings provided at 12-months post-collision into chronic pain (head/neck pain ≥30/100, n = 44) and recovery (n = 61) groups, and their FC maps were compared. RESULTS: The chronic pain group exhibited reduced negative FC between NAc and a region within the primary motor cortex corresponding with the expected representation of the area of injury. A complementary pattern was also demonstrated between PAG and the primary somatosensory cortex. PAG and NAc also shared increased FC to the rostral anterior cingulate cortex (rACC) within the recovery group. Brain connectivity further shows high classification accuracy (area under the curve [AUC] = .86) for future chronic pain, when combined with an acute pain intensity report. INTERPRETATION: FC features obtained shortly after mTBI predict its transition to long-term chronic pain, and may reflect an underlying interaction of injury-related primary sensorimotor cortical areas with the mesolimbic and pain modulation systems. Our findings indicate a potential predictive biomarker and highlight targets for future early preventive interventions. ANN NEUROL 2022;92:819-833.


Asunto(s)
Conmoción Encefálica , Dolor Crónico , Humanos , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Dolor Crónico/diagnóstico por imagen , Dolor Crónico/etiología , Encéfalo/diagnóstico por imagen , Sustancia Gris Periacueductal , Mapeo Encefálico/métodos
2.
Medicina (Kaunas) ; 57(9)2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34577915

RESUMEN

Background and Objectives: Large radicular cysts of the maxilla present a clinical challenge, as they may cause recurrent infection, severe alveolar bone loss and disruption of the nasal and maxillary sinus floors. The aim of this study was to evaluate the effect of previous root canal treatment on the clinical presentation of large maxillary radicular cysts. Materials and Methods: All cases of radicular cysts treated at the Oral and Maxillofacial Surgery Department of a tertiary public hospital over a period of six years (2012-2018) were evaluated. Histologically confirmed radicular cysts of the maxilla with a maximal dimension of over 15 mm were included. Demographic data of the patients, clinical presentation and radiographic features of the lesions were analyzed. Results: A total of 211 inflammatory cysts were treated in the study period, of these 54 histologically diagnosed radicular cysts in the maxilla were found to have a maximal dimension of over 15 mm. The mean age of patients with large maxillary radicular cysts was 43.3 years, 57.6% of which were male and 42.4% female. The lateral incisor was the most common tooth affected (46.3%). The mean size of the large radicular cysts was 25 mm. Then, 83.8% of the cysts were observed in teeth with previous endodontic treatment. Teeth without endodontic treatment presented clinically with significantly fewer acute symptoms in comparison to teeth with previous endodontic treatment. Conclusions: the vast majority (83.8%) of large maxillary radicular cysts were associated with endodontically treated teeth. Previous endodontic treatment was correlated to increased frequency of clinical symptoms.


Asunto(s)
Quiste Radicular , Diente no Vital , Adulto , Femenino , Humanos , Incisivo , Masculino , Maxilar/diagnóstico por imagen , Quiste Radicular/diagnóstico por imagen , Quiste Radicular/epidemiología , Quiste Radicular/cirugía , Tratamiento del Conducto Radicular/efectos adversos , Diente no Vital/diagnóstico por imagen , Diente no Vital/epidemiología
3.
Fetal Diagn Ther ; 43(4): 250-265, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28728156

RESUMEN

BACKGROUND: LGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance. METHODS: First-trimester plasma samples (49 term and 18 intermediate) of PE cases matched with 196 controls were collected from King's College Hospital, London, repository. Cell-free DNA was extracted and the LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs was determined in BeWo trophoblast-like cells with luciferase assays. Adjusted odds ratio (OR) was calculated for the A/A genotype combined with maternal risk factors. RESULTS: The A/A, A/C, and C/C genotypes in the -98 promoter position were in Hardy-Weinberg equilibrium in the control but not in the PE group (p < 0.036). The dominant A/A genotype had higher frequency in the PE group (p < 0.001). The A/C and C/C genotypes protected from PE (p < 0.032). The ORs to develop term and all PE, calculated for the A/A genotype, previous PE, body mass index (BMI) >35, black ethnicity, and maternal age >40 were 15.6 and 11.0, respectively (p < 0.001). In luciferase assays, the "-98A" promoter variant had lower expression than the "-98C" variant in non-differentiated (-13%, p = 0.04) and differentiated (-26%, p < 0.001) BeWo cells. Forskolin-induced differentiation led to a larger expression increase in the "-98C" variant than in the "-98A" variant (4.55-fold vs. 3.85-fold, p < 0.001). CONCLUSION: Lower LGALS13 (PP13) expression with the "A" nucleotide in the -98 promoter region position (compared to "C") and high OR calculated for the A/A genotype in the -98A/C promoter region position, history of previous PE, BMI >35, advanced maternal age >40, and black ethnicity could serve to aid in PE prediction in the first trimester.


Asunto(s)
Población Negra , Galectinas/genética , Predisposición Genética a la Enfermedad , Edad Materna , Obesidad/complicaciones , Polimorfismo de Nucleótido Simple , Preeclampsia/etiología , Proteínas Gestacionales/genética , Primer Trimestre del Embarazo/genética , Adulto , Femenino , Genotipo , Humanos , Preeclampsia/genética , Embarazo , Recurrencia , Factores de Riesgo
4.
Disabil Rehabil Assist Technol ; 18(6): 783-790, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-33961532

RESUMEN

PURPOSE: Powered mobility has a positive effect on social skills, self-esteem and overall development of children with motor impairments, but almost all previous studies were conducted with pre-school children. The aim of this study was to explore change beyond mobility following a therapeutic powered mobility summer camp for school-aged children and adolescents with severe cerebral palsy, as perceived by school staff. MATERIALS AND METHODS: The participants in the therapeutic camp, which ran for 3 weeks, 5 days a week, three times over the summers 2018-2019, were children ages 7-19 (median age 11) with severe cerebral palsy who needed assistance in mobility and had limited hand function. Following the intervention, 19 semi-structured audio-recorded interviews were conducted with school staff, then transcribed and thematically analyzed using an inductive qualitative descriptive design with a phenomenological theoretical framework. RESULTS: Four overarching themes were identified: (1) "Every step you take: mastering new, sometimes unexpected, skills", (2) "Break on through to the other side: changes in behaviour", (3) "Make new friends (but keep the old): Boosting social behaviour" and (4) "I'm a believer: The journey through self-efficacy to empowerment". CONCLUSIONS: The interviews showed the immediate positive influence of powered mobility for children who previously did not have independent mobility, following an intensive intervention. Changes in initiative, empowerment, social relationships and behaviour highlight the importance of self-generated mobility, regardless of whether independence was achieved. School-aged children with severe cerebral palsy seem to benefit from an intensive powered mobility intervention in areas other than mobility skills themselves.IMPLICATIONS FOR REHABILITATIONPowered mobility intervention seems to encourage activity and initiation among children and youth with severe CP.This research adds to the understanding of the effect powered mobility can have on social interaction and communication.Powered mobility might be a means to allow development, in addition to being an important end.


Asunto(s)
Parálisis Cerebral , Silla de Ruedas , Adolescente , Humanos , Preescolar , Niño , Instituciones Académicas , Relaciones Interpersonales , Cognición , Autoeficacia
5.
PLoS One ; 16(9): e0257085, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34550986

RESUMEN

A kiosk-based survey at the American Museum of Natural History in New York City in 2016-2018 allowed us to assess public knowledge of antibiotics and public attitudes toward microbes in museum goers. Over 22,000 visitors from 172 countries and territories answered several carefully designed questions about microbes and antibiotics. These visitors also entered age, gender, and country demographic data that allowed for stratification along these demographic and geographic divisions. Because museum goers are likely to be better informed about these and other science-based topics, the results described here can set a potential upper bound for public knowledge on these topics. Surprisingly, the results of our analysis of museum goers' answers about microbes and antibiotics indicate a substantial lack of familiarity with both topics. For example, overall only about 50% of respondents can correctly identify penicillin as an antibiotic and less than 50% of museum visitors view microbes as beneficial. The results described here suggest that we are perhaps off target with our educational efforts in this area and that a major shift in approach toward more basic microbial topics is warranted in our educational efforts.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Conocimientos, Actitudes y Práctica en Salud , Museos , Historia Natural , Percepción , Encuestas y Cuestionarios , Análisis de Datos , Humanos , Lenguaje
6.
FEMS Microbiol Lett ; 273(2): 239-43, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17573937

RESUMEN

It is reported that some of the widely used laboratory strains of Saccharomyces cerevisiae (e.g. W303, BY4741) are sensitive to synthetic media containing all 20 amino acids [e.g. synthetic complete (SC) medium or supplemented minimal medium]. To determine the molecular basis for this unexpected sensitivity, a genomic library was screened and three genes were identified that, when overexpressed, rescue cells from this phenotype. Two of the 'rescuing' genes, BAP2 and TAT1, are related to transport of leucine, and one, LEU2, to synthesis of leucine, showing that sensitivity to SC medium is associated with the leu2 mutation. The sensitive strains seem incapable of transporting leucine when grown on synthetic complete media. This effect of the leu2 mutation should be taken into consideration when analyzing the results of genetic screens and other experiments performed with these strains.


Asunto(s)
Leucina/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , 3-Isopropilmalato Deshidrogenasa , Sistemas de Transporte de Aminoácidos/genética , Medios de Cultivo , Proteínas de Unión al ADN/genética , Biblioteca Genómica , Fenotipo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Transactivadores/genética
7.
Mol Cell Biol ; 22(23): 8101-13, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12417714

RESUMEN

Translation of terminal oligopyrimidine tract (TOP) mRNAs, which encode multiple components of the protein synthesis machinery, is known to be controlled by mitogenic stimuli. We now show that the ability of cells to progress through the cell cycle is not a prerequisite for this mode of regulation. TOP mRNAs can be translationally activated when PC12 or embryonic stem (ES) cells are induced to grow (increase their size) by nerve growth factor and retinoic acid, respectively, while remaining mitotically arrested. However, both growth and mitogenic signals converge via the phosphatidylinositol 3-kinase (PI3-kinase)-mediated pathway and are transduced to efficiently translate TOP mRNAs. Translational activation of TOP mRNAs can be abolished by LY294002, a PI3-kinase inhibitor, or by overexpression of PTEN as well as by dominant-negative mutants of PI3-kinase or its effectors, PDK1 and protein kinase Balpha (PKBalpha). Likewise, overexpression of constitutively active PI3-kinase or PKBalpha can relieve the translational repression of TOP mRNAs in quiescent cells. Both mitogenic and growth signals lead to phosphorylation of ribosomal protein S6 (rpS6), which precedes the translational activation of TOP mRNAs. Nevertheless, neither rpS6 phosphorylation nor its kinase, S6K1, is essential for the translational response of these mRNAs. Thus, TOP mRNAs can be translationally activated by growth or mitogenic stimuli of ES cells, whose rpS6 is constitutively unphosphorylated due to the disruption of both alleles of S6K1. Similarly, complete inhibition of mammalian target of rapamycin (mTOR) and its effector S6K by rapamycin in various cell lines has only a mild repressive effect on the translation of TOP mRNAs. It therefore appears that translation of TOP mRNAs is primarily regulated by growth and mitogenic cues through the PI3-kinase pathway, with a minor role, if any, for the mTOR pathway.


Asunto(s)
Ciclo Celular/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Biosíntesis de Proteínas , Proteínas Proto-Oncogénicas , ARN Mensajero/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Proteína S6 Ribosómica/metabolismo , Animales , División Celular , Línea Celular , Cromonas/metabolismo , Inhibidores Enzimáticos/metabolismo , Femenino , Humanos , Ratones , Ratones Noqueados , Morfolinas/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Factor 1 de Elongación Peptídica/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt , ARN Mensajero/genética , Ratas , Proteína S6 Ribosómica/genética , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Sirolimus/metabolismo , Tretinoina/metabolismo
8.
Int J Antimicrob Agents ; 19(2): 105-10, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11850162

RESUMEN

The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14 critically ill patients with sepsis. Patients with creatinine clearance (CrCl) higher than 50 ml/min received 1 g meropenem three times daily (Group I) and patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily (Group II). Meropenum concentrations in plasma were determined by high performance liquid chromatography with UV detection. The pharmacokinetic parameters differed between the two groups as follows, Group I, maximal concentration 56.3 +/- 19.1 microg/ml; trough concentration 3.3 +/- 2.5 microg/ml; elimination half life 2.5 +/- 1.2 h; clearance (Cl) 155.8 +/- 40.6 ml/min; MRT 2.2 +/- 0.4 h; steady state volume of distribution (V(ss)) 21.7 +/- 5.7 l, and AUC(-8) 119.4 +/- 32.6 microg/ml h. Group II, maximal concentration 71.1 +/- 5.1 microg/ml; trough concentration 3.4 +/- 1.8 microg/ml; elimination half life 3.9 +/- 1.6 h; Cl 77.7 +/- 15.8 ml/min; MRT 3.5 +/- 0.6 h; V(ss), 17.1 +/- 2.1 l, and AUC(0-12) 230.2 +/- 43.3 microg/ml h. The most frequently isolated bacteria from blood and wound infections were Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli; their meropenem minimal inhibitory concentrations (MICs) ranged from 0.064 to 3.0 mg/l. In most cases the pharmacodynamic parameters, measured as T>MIC index, were higher than 75%. In both groups, patients with susceptible pathogens (MIC<1 mg/l) had meropenem plasma levels which exceeded the MIC for the whole dosing interval. When pathogens were highly resistant (A. baumanii or P. aeruginosa) the T>MIC indices were lower.


Asunto(s)
Sepsis/tratamiento farmacológico , Tienamicinas/farmacocinética , Tienamicinas/uso terapéutico , Anciano , Creatinina/metabolismo , Enfermedad Crítica/terapia , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Humanos , Masculino , Meropenem , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Sepsis/metabolismo , Sepsis/microbiología , Tienamicinas/sangre
9.
Otolaryngol Head Neck Surg ; 129(4): 379-81, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14574292

RESUMEN

Ramsay Hunt syndrome is an herpetic disease with ominous prognosis regarding the facial nerve. Treatment with acyclovir, a well-known virostatic agent, has been given in a small number of patients in recent years with excellent results. We report on the administration of acyclovir intravenously for 7 days in 31 patients with Ramsay Hunt syndrome, with overall recovery rate of 82.6%. There were no side effects regarding this treatment.


Asunto(s)
Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Trastornos Parkinsonianos/diagnóstico , Adolescente , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Niño , Quimioterapia Combinada , Nervio Facial/fisiopatología , Femenino , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/virología , Humanos , Hidrocortisona/uso terapéutico , Masculino , Persona de Mediana Edad , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/virología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
10.
Cancer Res ; 74(20): 5700-10, 2014 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-25145670

RESUMEN

Tubulysins are highly toxic tubulin-targeting agents with a narrow therapeutic window that are interesting for application in antibody-drug conjugates (ADC). For full control over drug-antibody ratio (DAR) and the effect thereof on pharmacokinetics and tumor targeting, a dual-labeling approach was developed, wherein the drug, tubulysin variants, and the antibody, the anti-HER2 monoclonal antibody (mAb) trastuzumab, are radiolabeled. (131)I-radioiodination of two synthetic tubulysin A analogues, the less potent TUB-OH (IC50 > 100 nmol/L) and the potent TUB-OMOM (IC50, ~1 nmol/L), and their direct covalent conjugation to (89)Zr-trastuzumab were established. Radioiodination of tubulysins was 92% to 98% efficient and conversion to N-hydroxysuccinimide (NHS) esters more than 99%; esters were isolated in an overall yield of 68% ± 5% with radiochemical purity of more than 99.5%. Conjugation of (131)I-tubulysin-NHS esters to (89)Zr-trastuzumab was 45% to 55% efficient, resulting in ADCs with 96% to 98% radiochemical purity after size-exclusion chromatography. ADCs were evaluated for their tumor-targeting potential and antitumor effects in nude mice with tumors that were sensitive or resistant to trastuzumab, using ado-trastuzumab emtansine as a reference. ADCs appeared stable in vivo. An average DAR of 2 and 4 conferred pharmacokinetics and tumor-targeting behavior similar to parental trastuzumab. Efficacy studies using single-dose TUB-OMOM-trastuzumab (DAR 4) showed dose-dependent antitumor effects, including complete tumor eradications in trastuzumab-sensitive tumors in vivo. TUB-OMOM-trastuzumab (60 mg/kg) displayed efficacy similar to ado-trastuzumab emtansine (15 mg/kg) yet more effective than trastuzumab. Our findings illustrate the potential of synthetic tubulysins in ADCs for cancer treatment.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Antineoplásicos/farmacología , Animales , Anticuerpos Monoclonales Humanizados/química , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Estabilidad de Medicamentos , Femenino , Humanos , Dosis Máxima Tolerada , Ratones Desnudos , Oligopéptidos , Distribución Tisular , Trastuzumab , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Nat Protoc ; 8(5): 1010-8, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23619892

RESUMEN

IRDye800CW and zirconium-89 ((89)Zr) have very attractive properties for optical imaging and positron emission tomography (PET) imaging, respectively. Here we describe a procedure for dual labeling of mAbs with IRDye800CW and (89)Zr in a current good manufacturing practice (cGMP)-compliant way. IRDye800CW and (89)Zr are coupled inertly, without impairment of immunoreactivity and pharmacokinetics of the mAb. Organ and whole-body distribution of the final product can be assessed by optical and PET imaging, respectively. For this purpose, a minimal amount of the chelate N-succinyldesferrioxamine (N-sucDf) is first conjugated to the mAb. Next, N-sucDf-mAb is conjugated with IRDye800CW, after which the N-sucDf-mAb-IRDye800CW is labeled with (89)Zr. After each of these three steps, the product is purified by gel filtration. The sequence of this process avoids unnecessary radiation exposure to personnel and takes about 5 h. The process can be scaled up by the production of large batches of premodified mAbs that can be dispensed and stored until they are labeled with (89)Zr.


Asunto(s)
Anticuerpos Monoclonales/análisis , Bencenosulfonatos/química , Indoles/química , Microscopía Fluorescente/métodos , Tomografía de Emisión de Positrones/métodos , Circonio/química , Animales , Ratones , Ratones Desnudos , Coloración y Etiquetado
12.
EJNMMI Res ; 2(1): 50, 2012 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-23009555

RESUMEN

BACKGROUND: We describe a new method for biodistribution studies with IRDye800CW fluorescent antibody probes. This method allows the quantification of the IRDye800CW fluorescent tracer in percentage of injected dose per gram of tissue (% ID/g), and it is herein compared to the generally used reference method that makes use of radioactivity. METHODS: Cetuximab was conjugated to both the near-infrared fluorophore IRDye800CW and/or the positron emitter 89-zirconium, which was injected in nude mice bearing A431 human tumor xenografts. Positron emission tomography (PET) and optical imaging were performed 24 h post-injection (p.i.). For the biodistribution study, organs and tumors were collected 24 h p.i., and each of these was halved. One half was used for the determination of probe uptake by radioactivity measurement. The other half was homogenized, and the content of the fluorescent probe was determined by extrapolation from a calibration curve made with the injected probe. RESULTS: Tumors were clearly visualized with both modalities, and the calculated tumor-to-normal tissue ratios were very similar for optical and PET imaging: 3.31 ± 1.09 and 3.15 ± 0.99, respectively. Although some variations were observed in ex vivo analyses, tumor uptake was within the same range for IRDye800CW and gamma ray quantification: 15.07 ± 3.66% ID/g and 13.92 ± 2.59% ID/g, respectively. CONCLUSIONS: The novel method for quantification of the optical tracer IRDye800CW gives similar results as the reference method of gamma ray quantification. This new method is considered very useful in the context of the preclinical development of IRDye800CW fluorescent probes for optical molecular imaging, likely contributing to the selection of lead compounds that are the most promising for clinical translation.

13.
EJNMMI Res ; 1(1): 31, 2011 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-22214225

RESUMEN

BACKGROUND: Photoimmunodetection, in which monoclonal antibodies [mAbs] are labeled with fluorescent dyes, might have clinical potential for early detection and characterization of cancer. For this purpose, the dye should be coupled in an inert way to mAb. In this study, different equivalents of IRDye800CW, a near-infrared fluorescent dye, were coupled to 89Zr-labeled cetuximab and bevacizumab, and conjugates were evaluated in biodistribution studies. Radiolabeled mAbs were used to allow accurate quantification for assessment of the number of dye groups that can be coupled to mAbs without affecting their biological properties. METHODS: 89Zr-cetuximab and 89Zr-bevacizumab, containing 0.5 89Zr-desferal group per mAb molecule, were incubated with 1 to 10 eq IRDye800CW at pH 8.5 for 2 h at 35°C, and 89Zr-mAb-IRDye800CW conjugates were purified by a PD10 column using 0.9% NaCl as eluent. HPLC analysis at 780 nm was used to assess conjugation efficiency. In vitro stability measurements were performed in storage buffer (0.9% NaCl or PBS) at 4°C and 37°C and human serum at 37°C. 89Zr-mAb-IRDye800CW conjugates and 89Zr-mAb conjugates (as reference) were administered to nude mice bearing A431 (cetuximab) or FaDu (bevacizumab) xenografts, and biodistribution was assessed at 24 to 72 h after injection. RESULTS: Conjugation efficiency of IRDye800CW to 89Zr-mAbs was approximately 50%; on an average, 0.5 to 5 eq IRDye800CW was conjugated. All conjugates showed optimal immunoreactivity and were > 95% stable in storage buffer at 4°C and 37°C and human serum at 37°C for at least 96 h. In biodistribution studies with 89Zr-cetuximab-IRDye800CW, enhanced blood clearance with concomitant decreased tumor uptake and increased liver uptake was observed at 24 to 72 h post-injection when 2 or more eq of dye had been coupled to mAb. No significant alteration of biodistribution was observed 24 to 48 h after injection when 1 eq of dye had been coupled. 89Zr-bevacizumab-IRDye800CW showed a similar tendency, with an impaired biodistribution when 2 eq of dye had been coupled to mAb. CONCLUSION: Usage of 89Zr-mAbs allows accurate quantification of the biodistribution of mAbs labeled with different equivalents of IRDye800CW. Alteration of biodistribution was observed when more than 1 eq of IRDye800CW was coupled to mAbs.

15.
Estud. pesqui. psicol. (Impr.) ; 13(1): 205-214, jan.-abr.2013.
Artículo en Portugués | LILACS | ID: lil-756299

RESUMEN

Este artigo discute, a partir de uma perspectiva psicanalítica, como o brincarconstitui-se como um modo de tratamento ao real da doença, em crianças acometidas de diversos tipos de câncer. Traça considerações sobre o brincar e o simbólico, a partir das idéias freudianas para, em seguida, discutir omodo como Lacan pensa o brincar e a sua função na clínica com crianças. Apartir de um fragmento de caso clínico, este artigo tenta demonstrar o modocomo os pressupostos teóricos assumidos servem de operadores lógicos, no que se refere aos casos de crianças em tratamento no Instituto de Pediatria e Puericultura Marzagão Gesteira...


This article discusses, from a psychoanalytic perspective, as the play is as a way of treating the actual disease in children suffered from various types of cancer. Moth considerations play and symbolic, from the Freudian ideas tothen discuss how Lacan thinks the play and its role in clinical work with children. From a fragment of a clinical case, attempts to demonstrate how the theoretical assumptions made and logical operators are used to treat cases of children being treated at the Institute of Pediatrics and Child Care Marzagão Gesteira...


Asunto(s)
Humanos , Masculino , Femenino , Niño , Niño , Enfermedad/psicología , Psicoanálisis , Recreación/psicología , Estrés Psicológico
16.
Psicol. pesq ; 6(1): 61-67, jul. 2012.
Artículo en Portugués | LILACS | ID: lil-692908

RESUMEN

O presente artigo discute a relação existente entre adoção e filiação. Parte-se do pressuposto de que uma criança, antes mesmo de nascer ou de ser adotada, é gerada no desejo de seus pais ou do par parental podendo, também, ser fruto de um desejo morto. Pretende refletir sobre as questões referentes à adoção, bem como os impasses, no exercício das funções materna e paterna, fazendo de uma criança objeto a ser "doado" pela mãe biológica e de ser "recebido" por uma mãe adotiva. O nosso referencial é o da psicanálise de orientação lacaniana e com ele discutiremos questões clínicas sobre a adoção. Verificaremos, no tratamento analítico, o comparecimento dos significantes "rejeição, exclusão e abandono".


This article discusses the relationship between adoption and filiation. It is based on the assumption that a child, even before birth or adoption, is generated in the desire of his parents or the parental pair. But it may also be the result of a dead wish. Some aspects related to the act of adoption are discussed, as well as the narratives built around the impasses in performing maternal and paternal functions, as if the child were an object to be "donated" by the biological mother and to be "received" by an adoptive mother. In order to promote a debate on the related concepts, based on psychoanalysis from the Lacanian orientation, some clinical questions about adoption will be presented. The idea is to emphasize attendance to signifiers like "rejection", "exclusion" and "abandonment" in the analytical treatment.


Asunto(s)
Humanos , Niño , Adopción
17.
Psicol. rev. (Belo Horizonte) ; 17(3): 348-362, dez. 2011.
Artículo en Portugués | LILACS | ID: lil-647517

RESUMEN

Esta exposição trata de como a questão da temporalidade se apresenta no contemporâneo e como o sujeito responde a isso na singularidade de seu tempo. Para tal, abordaremos os efeitos sociais do discurso capitalista e como o tempo se constitui na clínica psicanalítica e no sujeito sob uma forma alienante ou não. Busca-se encaminhar, na constituição do sujeito, o que se processa como temporalidade lógica, tendo como suporte a teoria lacaniana sobre o tema. Supõe-se que o acesso ao consumo faz com que a relação de objeto, na atualidade, seja uma saída para o sofrimento que advém da falta, castração e da ideia de finitude. As diferenças que, por vezes, encontramos na psicose fornecem uma oposição à massificação da contemporaneidade, o que indica que o discurso capitalista seria uma solução para alguns, mas não para aqueles fora do laço social.


The present article is about how the issue of temporality in contemporary is presented as how the subject responds to the uniqueness of his/her time. We will discuss the social effects of capitalist discourse and how time constitutes itself in the psychoanalitic clinic and within the subject as form of alienation or not. The aim, supported by Lacan's theory on the subject, is routing in the constitution of the subject, which renders as temporal logic. It is assumed that access to consumption makes the object relationship, in the present, is a way of releasing suffering, which arises from want, castration and the idea of finiteness. The differences, which are sometimes found in psychosis, provide an opposition to the massification of contemporary times, which indicates that the capitalist discourse would be a solution for some, but not for those outside the social bond.


La exposición siguiente trata sobre la cuestión de cómo la temporalidad se muestra en lo contemporáneo y como el individuo responde a eso en la singularidad de su tiempo. Para esto, abordamos los efectos sociales del discurso capitalista y cómo el tiempo se constituye en la clínica psicoanalítica y en el individuo bajo una forma alienante o no. La búsqueda es la dirección, en la constitución del sujeto, lo que ocurre como la temporalidad lógica teniendo como su apoyo la teoría lacaniana sobre el tema. Se supone que el acceso al consumo hace que la relación de objeto, en las noticias, sea una salida para el dolor que proviene de la falta, castración y la finitud. Las diferencias que encontramos de vez em cuando en las psicosis nos ofrecem una oposición a la masificación de la contemporaneidad, al mismo tiempo en que nos apunta en ese discurso lo que sería una solución.


Asunto(s)
Humanos , Masculino , Femenino , Psicoanálisis , Alienación Social
18.
Rev. mal-estar subj ; 10(2): 537-554, jun. 2010.
Artículo en Portugués | LILACS | ID: lil-603400

RESUMEN

Este trabalho é uma tentativa de contextualizar a importância da cultura e do pai na constituição do sujeito. Para tal, utilizamos como pano de fundo o texto freudiano de 1913, Totem e Tabu, somado à contribuições de autores contemporâneos. Articulando a figura do pai com as polêmicas do século XXI, almejamos apresentar um recorte de seus reflexos no sujeito contemporâneo. Entendemos que os paradigmas do início do século passado justificavam a rebeldia dos jovens, mas o século XXI traz em seu cerne uma nova visão de mundo, uma mudança discursiva. Hoje, não há mais tempo para elaboração dos lutos, pois é preciso responder às exigências culturais imediatamente. O Outro que norteava o caminho até o inicio do século passado, já não é tão consistente. Segundo Lacan, o mestre antigo foi subvertido e em seu lugar encontramos o mestre contemporâneo que, ao mesmo tempo em que promete a completude, caso o sujeito consuma seus produtos, fomenta o isolamento e o sofrimento, tornando as relações humanas cada vez menos significativas; enfim, desmente a falta inerente ao homem, prometendo a felicidade total, impossível de ser atingida. Do que foi posto nos perguntamos quais serão as conseqüências de tamanhas exigências pulsionais e encontramos em Freud alguns encaminhamentos.


This production is an attempt to contextualize the importance of the culture and the father in the constitution of the subject. For this purpose, we utilized as our basis the 1913 Freudian text, Totem and Tabu, in addition to other contemporary authors' contributions. We desire to present a clipping of the father's reflection on the contemporary subject, articulating his image with the XXI century polemics. It can be understood that the patterns of the beginning of the last century justify the youth rebelliousness, however the XXI century brings a new world vision, a discourse change. Nowadays, there isn't any time for mourning elaborations, since the cultural demands require immediate responses. The Other, who guided the path until the beginning of the last century, is no longer consistent. Lacan said that the ancient master was subverted, changing places with the contemporary master, which at the same time that promisses the completeness if the subject consumes his products, incites isolation and suffering, transforming human relations into less significant ones, that is, contradicts the inherent man's absence, promising the total happiness that is impossible to achieve. With the previous words in mind, we can ask ourselves which will the consequences of this extinct demands be, and we can find at Freud some conduction.


Asunto(s)
Humanos , Masculino , Femenino , Capitalismo , Cultura , Padre
19.
Estilos clín ; 15(2): 306-325, dez. 2010.
Artículo en Portugués | LILACS | ID: lil-589783

RESUMEN

No presente artigo propomo-nos levantar alguns impasses escolares de crianças adoecidas pelo câncer. Ao constatarmos seus impedimentos à vida escolar buscamos trazer à discussão questões inerentes às barreiras impostas pelo adoecimento, laços sociais e pela própria instituição escola. Nossas intervenções, orientadas pela psicanálise, vêm indicando que a infância, quando inscrita no ambiente hospitalar, sofre mudanças que necessitam uma reorganizacão dos investimentos libidinais da criança, dos pais e dos profissionais envolvidos no processo. Mesmo que a legislação brasileira reconheça o direito de crianças e adolescentes hospitalizados ao atendimento pedagógico-educacional, que escolhas têm esses sujeitos? O que pode um psicanalista, desafiado em sua cidade, responder a esses impasses sem abrir mão de sua ética no laço estabelecido com as áreas da saúde e da educação?.


En el presente artículo nos proponemos a investigar las difíciles situaciones de niños enfermos por cáncer. Al percibimos sus obstáculos a la vida escolar, buscamos discutir cuestiones inherentes a las barreras impuestas por la enfermedad, a los lazos sociales y la propia institución escolar. Nuestras intervenciones, basadas por el psicoanálisis, vienen apuntando que la infancia, cuando inscrita en un ambiente hospitalario, sufre cambios, que necesitan una reorganización de las inversiones libidinales del niño, de los padres y de los profesionales envueltos en el proceso. Aunque la legislación brasileña reconozca los derechos de los niños y adolescentes hospitalizados al atendimiento pedagógico-educativa, en este panorama, ¿qué elecciones tienen esos niños? ¿Qué puede un psicoanalista, provocado en su ciudad, contestar a esos obstáculos sin renunciar de su ética, en el enlace establecido entre las áreas de la salud y de la educación.


In this paper we propose to raise some dilemmas of school children fell ill with cancer. When we realize their impediments to school we seek to bring into discussion issues related to barriers imposed by illness, social ties and the school institution itself. Our guided interventions by psychoanalysis have indicated that childhood, when entered in the hospital, undergoes changes that require a reorganization of libidinal investment of the child, parents and professionals involved in the process. Even though Brazilian law recognizes the right of children and adolescents admitted to the pedagogical-educational service, which choices are the subject child? What can a psychoanalyst, challenged in his city, to respond to these dilemmas without sacrificing their ethics in the bond established with the areas of health and education?.


Asunto(s)
Crianza del Niño , Hospitalización , Neoplasias/psicología , Psicoanálisis , Rendimiento Escolar Bajo , Política Pública
20.
Rev. mal-estar subj ; 10(4): 1245-1270, dez. 2010.
Artículo en Portugués | LILACS | ID: lil-603430

RESUMEN

Este texto aborda o estudo da fibromialgia, síndrome cujas dores crônicas sem causalidade orgânica constatável são fonte de sofrimento para pacientes e desafio para os clínicos. Situada na fronteira entre a reumatologia e a patologia psicossomática, com seu cortejo de transtornos, conduz a uma degradação da qualidade de vida no plano profissional, social e/ou familiar. Dados epidemiológicos apontam uma maior incidência dessa entidade clínica controversa em mulheres jovens. A falta de evidências na materialidade do corpo e a presença de fatores psicopatológicos problematizam seu diagnóstico e tratamento. Face à diversidade e dos fatores envolvidos nessa síndrome, a indicação de uma abordagem multidisciplinar para seu tratamento vem se firmando como consenso. Por outro lado, o caráter subjetivo da experiência de dor contribui para a reticência das autoridades médicas e governamentais em afirmar plenamente o estatuto de doença da síndrome. Nesse contexto, ao mesmo tempo em que buscam uma cura para suas dores, os pacientes clamam pela legitimação do reconhecimento da fibromialgia como doença. Nossa proposta é considerar a eventual função da fibromialgia na estruturação psíquica como solução subjetiva. Para tanto, o referencial teórico-clínico da psicanálise de orientação lacaniana fornece elementos para reflexões sobre a dor no corpo e seu lugar na economia psíquica. Dados da clínica sugerem algumas especificidades dos usos da dor em função da estruturação psíquica de cada sujeito. A partir do estado atual das pesquisas sobre o tema e considerando a escassez de estudos no campo da psicanálise, interessa-nos contribuir para uma abordagem da fibromialgia que sustente o particular da enunciação no relato da experiência de dor. Sem pretender reduzir a fibromialgia a qualquer quadro psicopatológico, como a histeria ou a depressão, interessa-nos sublinhar a relevância da posição subjetiva daquele que sofre em seu corpo para o diagnóstico e tratamento da fibromialgia.


This text concerns the study of fibromyalgia, syndrome whose chronic pains without detectable organic causality is source of suffering to patients and challenge to doctors. Located in the border between rheumatology and psychosomatic pathology, with its following symptoms, the syndrome leads to a degradation of quality of life in the professional, social and family's spheres. Epidemiologic data indicate a greater incidence of this controversial clinical entity in young females. The lack of evidences in body's materiality and the presence of psychopathological factors problematize its diagnosis and treatment. Considering the diversity of factors involved in this syndrome, the indication of a multidisciplinaly treatment has been established as a consensus. On the other hand, the subjective character of the experience of pain contributes to the reticence by medical and governmental authorities in determining the status of disease to this syndrome. In this context, the patients, while search for the cure to their pain, clamor for the legitimation of fibromyalgia as a disease. Our proposal is to consider the eventual function of fibromyalgia in psychic structuration as a subjective solution. Aiming this, the clinical and theoretical references of Lacanian psychoanalysis provide elements to reflections about the body's pain and its place in psychic economy. Clinical data suggest some specificity in the uses of pain in the psychic structuration of each subject. From the current status of researches in this matter and considering the scarcity of studies in psychoanalysis' field, we look forward to contributing to an approach to fibromyalgia which sustains the particularities of enunciation in the report of the experience of pain. Without intending to reduce fibromyalgia to any psychopathological profile, as hysteria or depression, we aim to underline the relevance of the subjective position of the one who suffers in body to the diagnosis and treatment of fibromyalgia.


Asunto(s)
Humanos , Femenino , Adulto Joven , Dolor , Dolor Crónico , Fibromialgia , Psicoanálisis , Reumatología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA