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1.
Mol Imaging Biol ; 25(3): 554-559, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36369484

RESUMO

AIM/PURPOSE: 18F-labeled PSMA ligands offer various advantages as PET tracers over 68Ga-labeled PSMA counterparts. Especially, an improved spatial resolution leads to improved detection rates of smaller prostate cancer (PCa) lesions. However, physiological PSMA uptake of ganglia of the sympathetic trunk can be quickly misinterpreted as possible PSMA-positive lymph node metastases. The aim of this retrospective study is to investigate [18F]PSMA-1007 uptake and its intra-individual reproducibility in ganglia of the sympathetic trunk. METHODS: We retrospectively included 28 consecutive patients (median age 69 ± 9 with a range of 49-90) with biochemical recurrence of PCa who underwent [18F]PSMA-1007 PET/CT scan and, accordingly, a follow-up examination between August 2018 and August 2021. Cervical, coeliac, and sacral ganglia were identified on the iterative PET reconstructions and correlated with CT component. Tracer uptake of ganglia was determined by measuring SUVmax and SUVmean values. Anatomical position of the ganglia in relation to adjacent vertebral bodies were noted. Statistical analyses were conducted using two-way repeated measures ANOVA and descriptive statistics. RESULTS: The highest [18F]PSMA-1007 uptake was found in coeliac ganglia followed by cervical and sacral ganglia. The SUVmax in coeliac ganglia was 3.13 ± 0.85 (follow-up scan 3.11 ± 0.93), in cervical ganglia 2.73 ± 0.69 (follow-up scan 2.67 ± 0.74), and in sacral ganglia 1.67 ± 0.50 (follow-up scan 1.64 ± 0.52). The SUVmean in coeliac ganglia was 2.28 ± 0.64 (follow-up scan 2.28 ± 0.66), in cervical ganglia 1.62 ± 0.43 (follow-up scan 1.61 ± 0.43) and in sacral ganglia 1.15 ± 0.33 (follow-up scan 1.12 ± 0.34). In a given ganglion station, there was no statistically significant difference of SUVmax or SUVmean values between baseline and follow-up scans. CONCLUSIONS: The first systematically described physiological [18F]PSMA-1007 uptake in ganglia of the sympathetic trunk showed a low variability of SUVmax or SUVmean and a good intra-individual reproducibility of [18F]PSMA-1007 uptake in follow-up scans. These findings might improve and guide the differentiation of ganglia from possible malignant lesions.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Reprodutibilidade dos Testes , Radioisótopos de Gálio , Neoplasias da Próstata/patologia , Gânglios/patologia , Ácido Edético
2.
Ann Pharm Fr ; 80(5): 749-757, 2022 Sep.
Artigo em Francês | MEDLINE | ID: mdl-34999123

RESUMO

At the Grenoble Alpes University Hospital Center, patients with cardiovascular disease have the opportunity to participate in a therapeutic education program in the cardiac rehabilitation department. The objective of this study is to analyze the educational needs of patients with coronary stents and heart valve prostheses. Using an exploratory qualitative method, semi-structured research interviews were conducted with 22 patients and an inductive thematic analysis was performed. We found that emergency surgery does not facilitate the assimilation of information in comparison with a scheduled procedure. The image of the "repaired heart" creates a cognitive conflict with the chronicity imposed by secondary preventive monitoring, a particularity of the implantable medical device. Patients feel that the information they receive is sometimes too voluminous and not adapted to their current needs. Thus, we propose an individualized support model based on the respect of temporality and on the psycho-behavioral functioning of the patient.


Assuntos
Reabilitação Cardíaca , Procedimentos Cirúrgicos Cardíacos , Desfibriladores Implantáveis , Valvas Cardíacas , Humanos , Motivação , Stents
3.
Urologe A ; 60(12): 1561-1569, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34850260

RESUMO

BACKGROUND: Local treatment of the primary or metastatic sites in urologic malignancies is promising when compared to systemic therapy alone, leading to the definition of a potentially curative oligometastatic state. OBJECTIVES: Comparison of imaging modalities regarding local and metastatic tumor sites in urologic cancers. METHODS: Review of comparative trials addressing quality criteria of imaging modalities. RESULTS: Depending on primary tumor and metastatic site, conventional imaging modalities such as computer tomography (CT) and bone scintigraphy still represent the standard of care in Germany. Due to superior quality criteria, hybrid-imaging techniques were widely adopted for oncological staging and particular due to the new PSMA-ligand (PSMA-PET/CT) in prostate cancer imaging. The development of new radioisotopes as well as their clinical application remains a focus of current research. CONCLUSIONS: High-quality diagnostic imaging modalities lay the groundwork for a precise definition of an oligometastatic state. By enabling treatment of the entire tumor burden, a delay of systemic therapy, longer progression-free survival, or even curative treatment may become achievable.


Assuntos
Neoplasias da Próstata , Neoplasias Urológicas , Humanos , Masculino , Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Carga Tumoral , Neoplasias Urológicas/diagnóstico por imagem
5.
Strahlenther Onkol ; 197(5): 385-395, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33410959

RESUMO

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Europa (Continente) , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral/efeitos da radiação
6.
Sci Total Environ ; 743: 140487, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32653703

RESUMO

Application of phosphate fertilizers beyond plants needs favors phosphorus (P) accumulation in soils, which may alter its reactivity and chemical speciation. The objective of this study was to assess the changes in P speciation in a Brazilian oxisol that received consecutive applications of varying rates of pig slurry (PS) over 11 years. The soils were treated with PS at rates of 50, 100 and 200 m3 ha-1 year-1, whereas a control plot received P and potassium (K) to replenish the amounts removed by harvest. The soils were sampled and characterized for its P sorption capacity (PSC) as determined by Langmuir sorption isotherms, P partitioning by sequential chemical fractionation (SCF), P chemical speciation via P K-edge XANES and iron (Fe) mineralogy via Fe K-edge EXAFS spectroscopies. Increases in applied PS rates were accompanied by increases in PSC at the 0 to 2.5 and 0 to 10 cm soil layers. P accumulation was observed to be restricted up to the depth of 20 cm, regardless of the PS rate applied. The P K-edge XANES analysis indicated that P accumulation in the topmost soil layers, occurred predominantly associated with Fe-(hydr)oxide minerals. In this soil layer (0 to 2.5 cm), the organic P pool was of particular importance likely due to no-tillage. A dramatic change in Fe mineralogy in the topmost soil layer was observed across the studied soils, with the predominance of hematite in the reference soil and in the control plot, whereas the occurrence of goethite and ferrihydrite was followed by the application of PS.


Assuntos
Ferro , Fósforo/análise , Animais , Brasil , Fertilizantes , Solo , Suínos
7.
Eur J Trauma Emerg Surg ; 45(1): 91-98, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29238847

RESUMO

PURPOSE: To find ways to reduce the rate of over-triage without drastically increasing the rate of under-triage, we applied a current guideline and identified relevant pre-hospital triage predictors that indicate the need for immediate evaluation and treatment of severely injured patients in the resuscitation area. METHODS: Data for adult trauma patients admitted to our level-1 trauma centre in a one year period were collected. Outpatients were excluded. Correct triage for trauma team activation was identified for patients with an ISS or NISS ≥ 16 or the need for ICU treatment due to trauma sequelae. In this retrospective analysis, patients were assigned to trauma team activation according to the S3 guideline of the German Trauma Society. This assignment was compared to the actual need for activation as defined above. 13 potential predictors were retained. The relevance of the predictors was assessed and 14 models of interest were considered. The performance of these potential triage models to predict the need for trauma team activation was evaluated with leave-one-out cross-validated Brier and logarithmic scores. RESULTS: A total of 1934 inpatients ≥ 16 years were admitted to our trauma department (mean age 48 ± 22 years, 38% female). Sixty-nine per cent (n = 1341) were allocated to the emergency department and 31% (n = 593) were treated in the resuscitation room. The median ISS was 4 (IQR 7) points and the median NISS 4 (IQR 6) points. The mortality rate was 3.5% (n = 67) corresponding to a standardized mortality ratio of 0.73. Under-triage occurred in 1.3% (26/1934) and over-triage in 18% (349/1934). A model with eight predictors was finally selected with under-triage rate of 3.3% (63/1934) and over-triage rate of 10.8% (204/1934). CONCLUSION: The trauma team activation criteria could be reduced to eight predictors without losing its predictive performance. Non-relevant parameters such as EMS provider judgement, endotracheal intubation, suspected paralysis, the presence of burned body surface of > 20% and suspected fractures of two proximal long bones could be excluded for full trauma team activation. The fact that the emergency physicians did a better job in reducing under-triage compared to our final triage model suggests that other variables not present in the S3 guideline may be relevant for prediction.


Assuntos
Serviços Médicos de Emergência/normas , Serviço Hospitalar de Emergência/normas , Triagem/normas , Feminino , Alemanha , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Ressuscitação , Estudos Retrospectivos , Centros de Traumatologia , Índices de Gravidade do Trauma
8.
Arq. bras. med. vet. zootec ; 68(6): 1647-1654, nov.-dez. 2016. tab, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-827929

RESUMO

O objetivo deste trabalho foi avaliar o padrão de deslocamento de bovinos em pastos de capim-quicuiu submetidos a diferentes alturas de entrada (10, 15, 20 e 25cm) e mesma proporção de rebaixamento (redução em 50% da altura inicial). O padrão de exploração das estações alimentares foi avaliado com base na observação direta de dois animais (1/observador) por unidade experimental, com concomitante registro de códigos em gravadores de voz dos passos, bocados e outras atividades. As avaliações foram realizadas duas vezes por dia (10 e 15h) durante uma hora, no primeiro e no último dia do período de ocupação dos piquetes. Adicionalmente, foram realizadas avaliações em pré e pós-pastejo da massa de forragem, massa de lâminas foliares e altura do perfilho e da bainha estendida. O experimento foi conduzido de acordo com um delineamento em blocos completos ao acaso, com quatro tratamento e três repetições. Durante a fase inicial de rebaixamento, as variáveis passos por minuto, número de bocados por estação alimentar e taxa de bocados foram maiores nos pastos mais baixos, reduzindo com o aumento da altura em pré-pastejo, sem diferenças significativas durante a fase final de rebaixamento. Ocorrem variações no padrão de deslocamento dos animais em pastos de capim-quicuiu durante a fase inicial de rebaixamento, quando alturas entre 20-25cm apresentam melhores condições para o processo de forrageamento. O rebaixamento em 50% da altura inicial interfere negativamente no padrão de deslocamento dos animais, independentemente das metas de altura em pré-pastejo utilizadas.(AU)


The aim of this work was to evaluate the pattern of displacement of cattle grazing kikuyu grass swards at different pre-grazing heights of 10, 15, 20 and 25cm and submitted to grazing down to a same level of defoliation of 50% of initial pre-grazing height. Patterns of exploitation of feed stations were evaluated from direct observation of two animals (1/observer) per experimental unit with recording of codes (steps, bites, and other activities in a portable recorder device. The evaluations were performed twice a day (10 and 15h) during one hour, at the first and the last day of stocking period. Moreover, at pre and post-grazing were evaluated: herbage mass, leaf mass and sheath, and extended tiller height. The experimental design was a complete randomized block design with three replications and four treatments. The variables steps per minute, number of bites per feeding station, and bite rate were higher in lower pastures decreasing as the sward height increased in the initial phase with no difference in the final phase of grazing down. During the initial phase of the grazing down the animals presented differences in displacement patterns, where sward heights of 20 to 25cm in Kikuyu grass presented better conditions for foraging by grazing animals. Grazing down pastures to 50% of initial grazing height negatively affects displacement patterns of animals, irrespective of pre-grazing heights targets.(AU)


Assuntos
Animais , Bovinos , Comportamento Animal , Comportamento Alimentar , Pennisetum , Brachiaria , Pastagens
9.
Int J Toxicol ; 35(5): 558-67, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27358239

RESUMO

In a subchronic toxicity study, administration of ß-caryophyllene (BCP) oil by oral gavage to Wistar rats at dosages of 0, 150, 450, or 700 mg/kg/d for 90 days, including a 21-day recovery period, did not produce any significant toxicologic manifestations. The study design also included a 28-day interim sacrifice in the control and high-dose groups. The BCP oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral end points, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, and necropsy findings. The no observed adverse effect level was the highest dosage level administered of 700 mg/kg body weight/d for both male and female rats. The study was conducted as part of an investigation to examine the safety of BCP oil for its proposed use in medical food products.


Assuntos
Sesquiterpenos/toxicidade , Sesquiterpenos/uso terapêutico , Testes de Toxicidade Subcrônica , Animais , Peso Corporal , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Dose Letal Mediana , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Sesquiterpenos Policíclicos , Ratos , Ratos Wistar , Urinálise
10.
Cell Death Dis ; 6: e1742, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25950472

RESUMO

Although the role of the ErbB2/HER2 oncogene in cancers has been extensively studied, how ErbB2 is regulated remains poorly understood. A novel microRNA, mir-4728, was recently found within an intron of the ErbB2 gene. However, the function and clinical relevance of this intronic miRNA are completely unknown. Here, we demonstrate that mir-4728 is a negative regulator of MAPK signaling through directly targeting the ERK upstream kinase MST4 and exerts numerous tumor-suppressive properties in vitro and in animal models. Importantly, our patient sample study shows that mir-4728 was under-expressed in breast tumors compared with normal tissue, and loss of mir-4728 correlated with worse overall patient survival. These results strongly suggest that mir-4728 is a tumor-suppressive miRNA that controls MAPK signaling through targeting MST4, revealing mir-4728's significance as a potential prognostic factor and target for therapeutic intervention in cancer. Moreover, this study represents a conceptual advance by providing strong evidence that a tumor-suppressive miRNA can antagonize the canonical signaling of its host oncogene.


Assuntos
Neoplasias da Mama/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Receptor ErbB-2/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células HeLa , Humanos , Íntrons , MicroRNAs/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Receptor ErbB-2/metabolismo , Transdução de Sinais
11.
Phys Med Biol ; 59(22): 6797-810, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25332308

RESUMO

Electromagnetic (EM) tracking allows localization of small EM sensors in a magnetic field of known geometry without line-of-sight. However, this technique requires a cable connection to the tracked object. A wireless alternative based on magnetic fields, referred to as transponder tracking, has been proposed by several authors. Although most of the transponder tracking systems are still in an early stage of development and not ready for clinical use yet, Varian Medical Systems Inc. (Palo Alto, California, USA) presented the Calypso system for tumor tracking in radiation therapy which includes transponder technology. But it has not been used for computer-assisted interventions (CAI) in general or been assessed for accuracy in a standardized manner, so far. In this study, we apply a standardized assessment protocol presented by Hummel et al (2005 Med. Phys. 32 2371-9) to the Calypso system for the first time. The results show that transponder tracking with the Calypso system provides a precision and accuracy below 1 mm in ideal clinical environments, which is comparable with other EM tracking systems. Similar to other systems the tracking accuracy was affected by metallic distortion, which led to errors of up to 3.2 mm. The potential of the wireless transponder tracking technology for use in many future CAI applications can be regarded as extremely high.


Assuntos
Fenômenos Eletromagnéticos , Neoplasias/radioterapia , Imagens de Fantasmas , Telemetria/instrumentação , Telemetria/normas , Terapia Assistida por Computador/instrumentação , Terapia Assistida por Computador/normas , Calibragem , Humanos , Neoplasias/patologia , Terapia Assistida por Computador/métodos
12.
Int J Pediatr Otorhinolaryngol ; 78(10): 1742-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25156198

RESUMO

OBJECTIVES: Diagnostic and therapeutic processing of a thyroid nodule in children and adolescents may require lobectomy-isthmusectomy (LI) or nodule-resection (NR). Very few data in the literature report the long-term evolution of the remaining thyroid lobe in a defined pediatric population. In this study, we aimed to answer the following questions: Does a nodule recurrence occur in the remainder lobe? Is a post-operative thyroxine treatment necessary? MATERIAL AND METHODS: This retrospective study describes 28 patients under 18 who underwent LI (22 cases) or NR (6 cases) from January 2004 to March 2012. Ten of them were lost to follow up, 18 could be assessed (4 NR (22%) and 14 LI (78%) - mean follow-up 45±31 months). All patients benefited of post-operative thyroid ultrasonography, and regular endocrinologic follow-up. The following data were analysed: emergence of new thyroid nodules, evolution of pre-existing nodules, occurrence of post-operative hypothyroidism and requirement for completion thyroidectomy. RESULTS: The mean age at the time of surgery was 14.3±1.9 years. Two patients (11%) had pre-existing nodules in the remaining thyroid gland, none of which showed an increase in size after surgery. De novo nodules developed in five patients (27.8%). Three patients who underwent LI (21.4%) needed thyroxine treatment for post-operative hypothyroidism. One patient (5.5%) needed completion thyroidectomy. CONCLUSIONS: In this children and adolescents population, after performing LI or NR, remaining thyroid tissue stays free of nodules in 72.2% of the cases. A post-operative thyroxin treatment is necessary in 21.4% of cases after LI.


Assuntos
Hipotireoidismo/etiologia , Recidiva Local de Neoplasia/cirurgia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tiroxina/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
13.
Food Chem Toxicol ; 50(11): 4149-57, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22960629

RESUMO

DHA-rich algal oil ONC-T18, tested for subchronic, reproductive, and developmental toxicity in the rat, did not produce any significant toxicologic manifestations. Based on the absence of maternal or developmental toxicity at any dosage level, a dosage level of 2000 mg/kg/day was considered to be the no observed adverse-effect level (NOAEL) for maternal toxicity and embryo/fetal development when DHA-rich algal oil was administered orally by gavage to pregnant Crl:CD(SD) rats during gestation days 6-19. In a dietary combined one-generation/90-day reproductive toxicity study in rats, the NOAEL for F0 male and female and F1 male systemic toxicity was considered to be 50,000 ppm (highest concentration administered) and 25,000 ppm for F1 female systemic toxicity (higher mean body weight, body weight gain, and food consumption). F0 reproductive performance values, estrous cycle length, gestation length, or the process of parturition, and the numbers of former implantation sites and unaccounted-for sites were unaffected by algal oil exposure. Postnatal survival and developmental parameters in the F1 generation were unaffected by algal oil exposure at all dietary concentrations. There were no neurotoxic effects noted at any algal oil exposure level. The results support the safety of DHA-rich algal oil for its proposed use in food.


Assuntos
Ácidos Docosa-Hexaenoicos/toxicidade , Microalgas/química , Óleos de Plantas/toxicidade , Administração Oral , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Relação Dose-Resposta a Droga , Ciclo Estral/efeitos dos fármacos , Feminino , Masculino , Exposição Materna , Nível de Efeito Adverso não Observado , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Gravidez , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Subcrônica
14.
Food Chem Toxicol ; 50(10): 3567-76, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22898615

RESUMO

DHA-rich algal oil ONC-T18, tested in a battery of in vitro and in vivo genotoxicity tests, did not show mutagenic or genotoxic potential. The acute oral LD50 in rats has been estimated to be greater than 5000 mg/kg of body weight. In a 90-day subchronic dietary study, administration of DHA-rich algal oil at concentrations of 0, 10,000, 25,000, and 50,000 ppm in the diet for 13 weeks did not produce any significant toxicologic manifestations. The algal oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral endpoints, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The no observed adverse effect level (NOAEL) was the highest level fed of 50,000 ppm which is equivalent to 3,305 and 3,679 mg/kg bw/day, for male and female rats, respectively. The studies were conducted as part of an investigation to examine the safety of DHA-rich algal oil. The results confirm that it possesses a toxicity profile similar to other currently marketed algal oils and support the safety of DHA-rich algal oil for its proposed use in food.


Assuntos
Dano ao DNA/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/química , Óleos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Feminino , Masculino , Micronúcleos com Defeito Cromossômico , Óleos/química , Ratos , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
15.
Acta Biomater ; 8(3): 1239-47, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21925622

RESUMO

There is increasing demand for automated cell reprogramming in the fields of cell biology, biotechnology and the biomedical sciences. Microfluidic-based platforms that provide unattended manipulation of adherent cells promise to be an appropriate basis for cell manipulation. In this study we developed a magnetically driven cell carrier to serve as a vehicle within an in vitro environment. To elucidate the impact of the carrier on cells, biocompatibility was estimated using the human adenocarcinoma cell line Caco-2. Besides evaluation of the quality of the magnetic carriers by field emission scanning electron microscopy, the rate of adherence, proliferation and differentiation of Caco-2 cells grown on the carriers was quantified. Moreover, the morphology of the cells was monitored by immunofluorescent staining. Early generations of the cell carrier suffered from release of cytotoxic nickel from the magnetic cushion. Biocompatibility was achieved by complete encapsulation of the nickel bulk within galvanic gold. The insulation process had to be developed stepwise and was controlled by parallel monitoring of the cell viability. The final carrier generation proved to be a proper support for cell manipulation, allowing proliferation of Caco-2 cells equal to that on glass or polystyrene as a reference for up to 10 days. Functional differentiation was enhanced by more than 30% compared with the reference. A flat, ferromagnetic and fully biocompatible carrier for cell manipulation was developed for application in microfluidic systems. Beyond that, this study offers advice for the development of magnetic cell carriers and the estimation of their biocompatibility.


Assuntos
Ouro/química , Magnetismo , Imãs , Teste de Materiais , Técnicas Analíticas Microfluídicas , Níquel/química , Células CACO-2 , Adesão Celular , Proliferação de Células , Humanos
16.
Med Phys ; 39(6Part8): 3686, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28518909

RESUMO

PURPOSE: Evaluation of different calculation methods for dose modification due to intrafraction prostate motion using film measurements as ground truth. METHODS: We acquired intrafraction motion data with the Calypso tumor tracking system by Varian Medical Systems Inc for 4 prostate IMRT patients treated with 35 fractions each. These motion data were transferred to a phantom platform which reproduces the observed motion and has a 20 cm diameter cylindrical solid water phantom mounted. For each patient all fractions were irradiated on one radiochromic MD-V2-55 film placed in the isocentric transversal slice of this phantom. These films serve as ground truth for three calculation Methods: 1) Recalculation of the plan with shifted target point for every segment with the segment's mean Calypso position. 2)+3) Convolution of the static dose distribution with a probability density function of the observed positions. For 2) only Calypso positions with activated beam on signal were used whereas for 3) all Calypso positions between the first and the last beam on signal for all fractions were employed. The comparisons between films and calculated dose distributions were made with the verification software VeriSoft 3.2 (PTW, Freiburg, Germany) where an 8×8 cm̂2 ROI around the isocenter was selected for gamma evaluation. RESULTS: The segment shifted plans reach 3%/3mm gamma values above 90% against the films for all four patients. For both convolution methods three values are above 90%, only for the patient with the largest intrafraction motion they decrease to 89%. CONCLUSIONS: Shifting of the target point for every segment is well suited to estimate the dosimetric consequences of intrafraction prostate motion. This may facilitate the evaluation of different margin sizes or dose prescribing recipes under different motion conditions. If such a lengthy calculation is not possible, a convolution with motion data can be used for acceptable results, too. Our work was partially supported by Siemens Healthcare and Varian Medical Systems Inc.

17.
Food Chem Toxicol ; 48(10): 2663-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20600527

RESUMO

The toxicity of sodium stearoyl lactylate (SSL) was examined in Wistar rats fed diets containing 0, 1.25, 2.5, and 5% SSL for one year, equivalent to mean daily intakes of 558, 1115, and 2214 mg/kg/day in males and 670, 1339, and 2641 mg/kg/day in females, respectively. SSL was well tolerated at these dietary levels as evidenced by the absence of toxicologically significant changes in the general condition and appearance of the rats, survival, neurobehavioral endpoints, growth, feed and water intake, ophthalmoscopic examinations, hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The occurrence of uterine endometrial stromal polyps was the only finding of potential significance. Given the frequent occurrence of these benign tumors in rats, wide variability in the reported incidence of this type of polyps in rats, the lack of statistical significance and lack of biological evidence to suggest a mechanism for the slightly greater incidence in the groups fed 2.5 and 5% SSL, it was concluded that the endometrial stromal polyps observed in females fed SSL were not related to treatment. The no observed adverse effect level (NOAEL) of SSL was placed at 5%, the highest dietary level tested (equivalent to 2214 mg/kg/day for males and 2641 mg/kg/day for females).


Assuntos
Estearatos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Emulsões , Tumores do Estroma Endometrial/epidemiologia , Feminino , Contagem de Leucócitos , Masculino , Neoplasias/epidemiologia , Nível de Efeito Adverso não Observado , Ratos , Ratos Endogâmicos F344 , Caracteres Sexuais , Sobrevida , Urinálise
18.
Ger Med Sci ; 8: Doc12, 2010 Jun 15.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-20577643

RESUMO

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie, DGTHG) and the German Society for Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin, DGAI) made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess the available monitoring methods with regard to indication, procedures, predication, limits, contraindications and risks for use. The differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilatators, inodilatators and calcium sensitizers and the use of intra-aortic balloon pumps will also be addressed. The guideline has been developed following the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cuidados Críticos/normas , Monitorização Fisiológica/normas , Cuidados Pós-Operatórios/normas , Guias de Prática Clínica como Assunto , Volume Sanguíneo , Cuidados Críticos/métodos , Alemanha , Hemodinâmica , Humanos , Monitorização Fisiológica/métodos , Cuidados Pós-Operatórios/métodos , Vasoconstritores/uso terapêutico
19.
Pediatr Transplant ; 13(5): 540-4, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19210267

RESUMO

Portal vein thrombosis can occur as a result of primary anomalies, after liver transplantation, and for other reasons. It may result in severe complications secondary to portal hypertension, such as bleeding from esophageal or gastric varices, hypersplenism, or impaired somatic growth. In this retrospective study, we analyzed the outcome of 25 children who underwent a Rex shunt procedure. The following venous grafts were used as the shunt: the autologous internal or external jugular vein (n = 17) or a cryopreserved graft (n = 5); in three patients the umbilical vein was recanalized. The median follow up time was 109 months (range 18 days-146 months). The best results were achieved in patients in whom an autologous jugular vein segment was used as a vascular graft for the Rex shunt (shunt patency of 88%). In patients with a functioning shunt no further lower or upper gastrointestinal bleeding occurred. And in the entire study population hypersplenism syndrome improved after surgery. In our large cohort of pediatric patients, the Rex shunt has shown to be an effective method to eliminate portal hypertension and to revascularize the liver and thereby prevents the possible consequences of long-term portosystemic shunting.


Assuntos
Hipertensão Portal/terapia , Transplante de Fígado/métodos , Veia Porta/patologia , Trombose Venosa/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Criopreservação , Feminino , Humanos , Lactente , Masculino , Modelos Anatômicos , Derivação Portossistêmica Cirúrgica , Estudos Retrospectivos , Resultado do Tratamento , Veias Umbilicais/patologia
20.
Theriogenology ; 70(7): 1030-40, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18760463

RESUMO

The objective was to validate a high-sensitivity chemiluminescent assay of serum progesterone concentrations for pregnancy diagnosis in manatees. Assay analytical sensitivity was 0.1 ng/mL, with mean intra- and inter-assay coefficients of variation of 9.7 and 9.2%, respectively, and accuracy had a mean adjusted R(2) of 0.98. Methods comparison (relative to Siemen's Coat-A-Count RIA) demonstrated r=0.98, Deming regression slope of 0.95, and an intercept of 0.01. Based on ROC analysis, a progesterone concentration >or=0.4 ng/mL was indicative of pregnancy. Assay results were not significantly altered by two freeze-thaw cycles of samples. Characteristic progesterone concentrations during pregnancy were Months 1-4 (1.7-4.7 ng/mL), 5-8 ( approximately 1.0 ng/mL), and 10 and 11 (0.3-0.5 ng/mL), whereas two late-pregnant females with impending abortion had progesterone concentrations of 0.1 ng/mL. Among pregnant females, maximum progesterone concentrations occurred in autumn (3.9+/-1.8 ng/mL), and were greater during all seasons than concentrations in non-pregnant females (0.1-0.2 ng/mL). Progesterone concentrations were also significantly higher in pregnant females than in non-pregnant females and males. This highly sensitive, specific, and diagnostic assay will be valuable for monitoring pregnancy and abortion in manatees.


Assuntos
Imunoensaio/veterinária , Progesterona/sangue , Trichechus manatus/sangue , Aborto Animal/sangue , Distribuição por Idade , Animais , Feminino , Imunoensaio/métodos , Masculino , Gravidez , Prenhez/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Caracteres Sexuais , Manejo de Espécimes
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