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1.
Nucl Med Biol ; 71: 23-31, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31128475

RESUMO

INTRODUCTION: Indium-111 when formulated as indium-111 oxine remains the gold standard for long term cell tracking, whereas radiometals for improved PET applications still have to be established. We here describe the on-cartridge formation of gallium-68, zirconium-89 and copper-64 complexes in small volumes suitable for cell labelling, including labelling of red blood cells (RBC) and white blood cells (WBC) and their biological evaluation in vivo. METHODS: Small volumes (1-2 mL) of tracers (oxine, tropolone) were directly prepared on an anion exchange cartridge (Sep-Pak QMA). Cells were radiolabelled and the labelling efficiency and efflux were evaluated. The in vivo biodistribution of copper-64-labelled WBC using [64Cu][Cu(oxinate)2] and [64Cu][Cu(tropolonate)2] was monitored in an infection and inflammation animal model using BALB/c mice. RESULTS: On-cartridge concentration of gallium-68, zirconium-89 and copper-64 enabled formation of oxine and tropolone tracers in small volumes with good yields (≥50%) and quality (extraction ≥90%). Prepared tracers radiolabelled the RBC comparable to indium-111 tracers and in vivo biodistribution of copper-64 labelled WBC showed clear accumulation of cells at the site of infection and inflammation. CONCLUSIONS: This on-cartridge preparation method enables simple formation of various PET tracers for cell radiolabelling. Zirconium-89 and copper-64 tracers radiolabelled cells with sufficient stability. Due to their longer half-life this approach could be promising for routine applications where longer evaluation periods for cell tracking are needed. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This novel approach for on-cartridge concentration and preparation of oxine and tropolone precursors with different positron emitters, in small volume and suitable pH, offers a versatile tool towards cell labelling for preclinical and clinical PET applications.


Assuntos
Radioisótopos de Cobre/química , Radioisótopos de Cobre/metabolismo , Radioisótopos de Gálio/química , Radioisótopos de Gálio/metabolismo , Radioquímica/instrumentação , Radioisótopos/química , Radioisótopos/metabolismo , Zircônio/química , Zircônio/metabolismo , Animais , Eritrócitos/metabolismo , Marcação por Isótopo , Leucócitos/metabolismo , Camundongos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
2.
Poult Sci ; 94(10): 2339-50, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26287001

RESUMO

Keel bone damage (KBD) is a critical issue facing the laying hen industry today as a result of the likely pain leading to compromised welfare and the potential for reduced productivity. Recent reports suggest that damage, while highly variable and likely dependent on a host of factors, extends to all systems (including battery cages, furnished cages, and non-cage systems), genetic lines, and management styles. Despite the extent of the problem, the research community remains uncertain as to the causes and influencing factors of KBD. Although progress has been made investigating these factors, the overall effort is hindered by several issues related to the assessment of KBD, including quality and variation in the methods used between research groups. These issues prevent effective comparison of studies, as well as difficulties in identifying the presence of damage leading to poor accuracy and reliability. The current manuscript seeks to resolve these issues by offering precise definitions for types of KBD, reviewing methods for assessment, and providing recommendations that can improve the accuracy and reliability of those assessments.


Assuntos
Criação de Animais Domésticos/métodos , Galinhas , Fraturas Ósseas/veterinária , Doenças das Aves Domésticas/diagnóstico , Animais , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/etiologia , Doenças das Aves Domésticas/etiologia , Reprodutibilidade dos Testes , Terminologia como Assunto
3.
Vet Rec ; 173(20): 500, 2013 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-24162507

RESUMO

The objective of this study was to assess the interobserver reliability (agreement) and accuracy of keel palpation for the purpose of detecting old fractures in an end-of-lay flock of commercial laying hens. The low level of invasiveness and the relative speed at which this evaluation can be carried out lends itself well to use in a welfare audit, but only if the results are reliable and accurate from various assessors. The palpation technique first described by Wilkins and others (2004) was used to manually palpate for keel fractures. The technique was modified in that only keel fractures were considered. Eight assessors with varying laying hen experience palpated 100 live ISA Brown hens that had been in lay for 49 weeks. The hens were then euthanased and examined by dissection to establish whether there had been a keel fracture present (yes/no). The accuracy for individual assessors ranged from 87.1 to 96.8 per cent, with a mean of 91.8 per cent among all eight assessors. The interobserver reliability among all eight assessors was moderate (κ=0.44). Accuracy and κ values were 84.8 per cent and 0.41 for the first 50 hens, and 99.5 per cent and 0.47 for the last 50 hens, respectively, indicating that there was increased accuracy and agreement as the assessors became more experienced at palpation. This level of agreement, and the high level of accuracy, would make this technique an acceptable measure of keel fracture prevalence in a welfare audit.


Assuntos
Galinhas/lesões , Fraturas Ósseas/veterinária , Palpação/veterinária , Bem-Estar do Animal , Animais , Feminino , Fraturas Ósseas/diagnóstico , Abrigo para Animais , Variações Dependentes do Observador , Reprodutibilidade dos Testes
4.
J Pharm Biomed Anal ; 52(4): 517-24, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-20189740

RESUMO

Three different procedures for the labeling of hyaluronan (HA) with (111)In, (125)I and (14)C radionuclides were compared, and the kinetic stability of radiolabeled HA under different conditions (saline, artificial gastric juice and plasma) was established. Modification of HA structure with bifunctional chelating agents (DTPA) or with the prosthetic group (tyramine or tyrosine) was essential prior (111)In and (125)I labeling. These chemical labeling techniques were fast, simple and inexpensive, and labeled agents with a high specific activity were obtained. The only disadvantage of these methods was the occurrence of unknown functional groups in the HA molecule requiring further characterization of the compound. Conversely, HA labeling with (14)C by biotechnological synthesis was found to be rather expensive and time-consuming process. Although, the final product (14)C-HA was identical to natural HA its low specific activity presents certain limitation for its application in biological experiments. Stability studies showed that (14)C-HA and (125)I-Tm-HA were stable in all studied mediums. In the case of (125)I-Trs-HA, stability slightly decreased in rat plasma and in artificial gastric juice with increasing time. The least stable was (111)In-DTPA-HA, which degraded completely after 48h in artificial gastric juice. Kinetic stability studies may provide primary information concerning the properties of radiolabeled HA in vitro, which is essential for the use and explanation of its behavior in biological experiments.


Assuntos
Radioisótopos de Carbono/química , Ácido Hialurônico/síntese química , Radioisótopos de Índio/química , Radioisótopos do Iodo/química , Animais , Radioisótopos de Carbono/farmacocinética , Estabilidade de Medicamentos , Ácido Hialurônico/farmacocinética , Radioisótopos de Índio/farmacocinética , Radioisótopos do Iodo/farmacocinética , Masculino , Ratos , Ratos Wistar
5.
Appl Radiat Isot ; 68(2): 297-302, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19906533

RESUMO

Here we describe a fully automated approach for the synthesis of (68)Ga-labelled DOTA-peptides based on pre-concentration and purification of the generator eluate by using a cation exchange-cartridge and its comparison with fully automated direct labelling applying fractionated elution. Pre-concentration of the eluate on a cation exchange cartridge both using a resin-based and a disposable cation-exchange cartridge efficiently removed (68)Ge as well as major metal contaminations with Fe and Zn. This resulted in a high labelling efficiency of DOTA-peptides at high specific activity (SA) with short synthesis times.


Assuntos
Resinas de Troca de Cátion/química , Cromatografia por Troca Iônica/instrumentação , Radioisótopos de Gálio/química , Radioisótopos de Gálio/isolamento & purificação , Compostos Heterocíclicos com 1 Anel/química , Marcação por Isótopo/instrumentação , Robótica/instrumentação , Cromatografia por Troca Iônica/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Peptídeos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/isolamento & purificação
6.
Physiol Meas ; 30(7): 661-77, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19525571

RESUMO

The detection of ventricular beats in the holter recording is a task of great importance since it can direct clinicians toward the parts of the electrocardiogram record that might be crucial for determining the final diagnosis. Although there already exists a fair amount of research work dealing with ventricular beat detection in holter recordings, the vast majority uses a local training approach, which is highly disputable from the point of view of any practical-real-life-application. In this paper, we compare five well-known methods: a classical decision tree approach and its variant with fuzzy rules, a self-organizing map clustering method with template matching for classification, a back-propagation neural network and a support vector machine classifier, all examined using the same global cross-database approach for training and testing. For this task two databases were used-the MIT-BIH database and the AHA database. Both databases are required for testing any newly developed algorithms for holter beat classification that is going to be deployed in the EU market. According to cross-database global training, when the classifier is trained with the beats from the records of one database then the records from the other database are used for testing. The results of all the methods are compared and evaluated using the measures of sensitivity and specificity. The support vector machine classifier is the best classifier from the five we tested, achieving an average sensitivity of 87.20% and an average specificity of 91.57%, which outperforms nearly all the published algorithms when applied in the context of a similar global training approach.


Assuntos
Arritmias Cardíacas/classificação , Eletrocardiografia Ambulatorial/métodos , Algoritmos , Bases de Dados como Assunto , Ventrículos do Coração , Humanos , Sensibilidade e Especificidade
7.
AJNR Am J Neuroradiol ; 29(10): 1902-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18784210

RESUMO

BACKGROUND AND PURPOSE: Blunt carotid and vertebral artery injury (BCVI) is rare but potentially devastating. The objective of our study was to prospectively evaluate the usefulness of a dedicated and optimized CT angiography (CTA) protocol of the craniocervical vessels as part of a whole-body CT work-up of patients with multiple trauma in a population of patients with blunt trauma. MATERIAL AND METHODS: From February 2006 to July 2007, a total of 368 consecutive patients with trauma were evaluated. All examinations were performed on a 16-row multisection CT (MSCT) scanner. CTA was performed from the level of the T2 vertebra to the roof of the lateral ventricles with 40 mL of iodinated contrast agent. Images were reconstructed with use of the angiography and bone window settings to evaluate vessels and bones. RESULTS: Of all eligible patients imaged, 100 had injuries to the head and neck including 35 skull base fractures (9.5%), 24 maxillofacial (6.5%), and 11 cervical spine fractures (3%). CTA was diagnostic in all patients. BCVI was diagnosed in 6 cases (6 lesions of the internal carotid artery, 3 lesions of the vertebral artery); among them were 2 who did not meet the screening criteria. No patient with negative results on CTA subsequently had development of neurologic deficits suspicious for BCVI. CONCLUSION: This study confirms that optimized craniocervical CTA can be easily integrated into a whole-body CT protocol for patients with multiple trauma. No additional screening technique is necessary to identify clinically relevant vascular injuries. Earlier recognition enables earlier treatment and may decrease mortality and morbidity rates of these rare but potentially devastating injuries.


Assuntos
Lesões das Artérias Carótidas/diagnóstico por imagem , Angiografia Cerebral/métodos , Traumatismo Múltiplo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/lesões , Imagem Corporal Total/estatística & dados numéricos , Adulto , Lesões das Artérias Carótidas/epidemiologia , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Traumatismo Múltiplo/epidemiologia , Reprodutibilidade dos Testes , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade
8.
AJNR Am J Neuroradiol ; 29(8): 1525-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18524974

RESUMO

BACKGROUND AND PURPOSE: Contrast-induced nephropathy (CIN) is one of the most common causes of in-hospital acute renal failure. The aim of this study was to assess the risk for CIN after repeated administration of the nonionic, dimeric, iso-osmolal contrast agent iodixanol regardless of pre-existing renal function. Changes in serum creatinine (SCr) levels were compared with those of control subjects who did not receive iodinated contrast media (CM). MATERIALS AND METHODS: Between January 2005 and March 2007, a total of 100 consecutive patients were prospectively included. Patients underwent a CT perfusion (CTP) study of the brain from clinical signs of acute cerebral infarction. CTP was performed with an intravenous bolus of 60 mL of iodixanol-270. Precontrast and postcontrast SCr levels were obtained, and the CTP study was repeated within 32 hours and postcontrast SCR was assessed. The control group consisted of 100 patients scheduled for plain cranial CT examination, who were not exposed to iodinated CM. RESULTS: Mean baseline SCr level was 0.96 +/- 0.35 mg/dL in the contrast group and 1.14 +/- 0.74 mg/dL in the control group. After repeated administration of CM, a total of 7 patients had a relative increase of greater than or equal to 25% compared with baseline. In the control group, a relative increase of 25% or more was seen in 12 patients. The difference in the incidence of the rise in SCr of >25% was not significantly different (P = .094). CONCLUSION: Multiple contrast-enhanced studies with intravenously administered iodixanol are not associated with a higher risk for CIN compared with a control group receiving no CM.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Nefropatias/induzido quimicamente , Tomografia Computadorizada por Raios X/métodos , Ácidos Tri-Iodobenzoicos/efeitos adversos , Idoso , Meios de Contraste/efeitos adversos , Feminino , Humanos , Íons , Nefropatias/diagnóstico por imagem , Masculino , Concentração Osmolar , Perfusão , Medição de Risco , Fatores de Risco
9.
Neuromolecular Med ; 9(3): 216-29, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17914180

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons and descending motor tracts of the CNS. We have evaluated the CNS of a murine model of familial ALS based on the over-expression of mutant human superoxide dismutase (mSOD; G93A) using magnetic resonance microscopy (MRM) and immunohistochemistry (IHC). Three-dimensional volumetric analysis was performed from 3D T2*-weighted images acquired at 17.6 T at isotropic resolutions of 40 mum. Compared to controls, mSOD mice had significant reductions in the volumes of total brain, substantia nigra, striatum, hippocampus, and internal capsule, with decreased cortical thickness in primary motor and somatosensory cortices. In the spinal cord, mSOD mice had significantly decreased volume of both the total grey and white matter; in the latter case, the volume change was confined to the dorsal white matter. Increased apoptosis, GFAP positive astrocytes, and/or activated microglia were observed in all those CNS regions that showed volume loss except for the hippocampus. The MRM findings in mSOD over-expressing mice are similar to data previously obtained from a model of ALS-parkinsonism dementia complex (ALS-PDC), in which neural damage occurred following a diet of washed cycad flour containing various neurotoxins. The primary difference between the two models involves a significantly greater decrease in spinal cord white matter volume in mSOD mice, perhaps reflecting variations in degeneration of the descending motor tracts. The extent to which several CNS structures are impacted in both murine models of ALS argues for a reevaluation of the nature of the pathogenesis of ALS since CNS structures involved in Parkinson's and Alzheimer's diseases appear to be affected as well.


Assuntos
Esclerose Lateral Amiotrófica/patologia , Encéfalo/patologia , Mutação , Medula Espinal/patologia , Superóxido Dismutase/metabolismo , Esclerose Lateral Amiotrófica/genética , Animais , Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Caspase 3/metabolismo , Ativação Enzimática , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos , Microscopia , Medula Espinal/metabolismo , Superóxido Dismutase/genética
10.
Rofo ; 177(9): 1242-9, 2005 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-16123870

RESUMO

PURPOSE: In suspected brain ischemia, the perfusion cerebral computed tomography (cCT) should be performed with the lowest amount of contrast media to avoid a contrast media induced nephropathy (CIN) even if the patient already is in renal failure. We were interested to find the best parameters for this examination. MATERIAL AND METHODS: From February 2000 to March 2003, 138 patients (58 females, 80 males, mean age 66.8 years) underwent cCT-perfusion immediately after the admission to our stroke unit. Of these patients, 62% (n = 86) had normal renal function and 38% (n = 52) renal failure (up to 381 micromol/l basic serum creatinine). We varied volume (20-80 ml), flow (5 vs. 7.2 ml/s) and concentration (270 vs. 320 ml/mg iodine) of a dimer, non-ionic contrast media (Visipaque) to establish 5 groups. So we got patients receiving 6 g, 12 g, 16 g, 19 g and 25 g of iodine. After generating the perfusion maps, two radiologists reviewed the quality of the maps and scored it (1-5). We measured the serum creatinine before contrast application and at follow up cCT (days 3 and 7). RESULTS: The quality of the maps increases with increasing amount of iodine. However, the diagnostic result was not significantly better using more than about 16 g of iodine (e. g., 60 ml--7.2 ml/s--270 mg/ml) in cCT-perfusion studies. Only one patient had a pathologic increase in serum creatinine (day 1: 93; day 4: 146 micromol/l) but died at day 5 because of massive co-morbidity and septic pneumonia. No CIN occurred even in the patient group with pre-existent renal failure. CONCLUSIONS: About 60 ml contrast media and a moderate flow rate of about 7 ml/s ensure good results in perfusion-cCT, even if the patients have poor blood circulation or arteriosclerosis. The use of a dimer, non-ionic contrast media (range of 6-25 g iodine) seems to minimize the risk of CIN in the daily routine.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Circulação Cerebrovascular , Meios de Contraste/administração & dosagem , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Tomografia Computadorizada por Raios X , Ácidos Tri-Iodobenzoicos/administração & dosagem , Idoso , Meios de Contraste/efeitos adversos , Creatinina/sangue , Feminino , Seguimentos , Humanos , Masculino , Insuficiência Renal/complicações , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Ácidos Tri-Iodobenzoicos/efeitos adversos
11.
Can J Physiol Pharmacol ; 83(2): 131-41, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15791286

RESUMO

Epidemiological studies have shown a positive relationship between cycad flour consumption and the development of the neurodegenerative disorder, amyotrophic lateral sclerosis - parkinsonism - dementia complex (ALS-PDC). Apolipoprotein E (apo E) allele variations have been associated with genetic susceptibility in neurodegenerative diseases, including ALS-PDC. We have studied cycad toxicity in a mouse model of ALS-PDC with a particular interest in its impact on the central nervous system (CNS) in both apo E knock-out (KO) mice and their wild-type (WT) counterparts. Behavioral motor tests, motor neuron counts, and immunohistochemical staining in brain and spinal cord, as well as routine histological examinations on internal organs, were performed to evaluate cycad toxicity. Plasma cholesterol levels were also measured before and during the study. Cycad treatment was associated with higher levels of plasma cholesterol only in apo E KO mice; increased levels of plasma cholesterol did not result in increased athero genesis. Cycad-fed wild-type mice developed progressive behavioral deficits including ALS-PDC-like pathological outcomes, while cycad-fed apo E KO mice were not significantly affected. Cycad-fed wild-type mice had shorter gait length measurements along with higher active caspase-3 levels in the striatum, substantia nigra, primary motor cortex, and spinal cord as compared with corresponding controls. These changes were associated with decreased labeling for glutamate transporter 1B and tyrosine hydroxylase activity levels. No evidence of cycad toxicity was observed in internal organs of either wild-type or apo E KO mice. Our data demonstrate that apo E KO mice are less susceptible to cycad toxicity, suggesting a role for apo E as a possible genetic susceptibility factor for some forms of toxin-induced neurodegeneration.


Assuntos
Esclerose Lateral Amiotrófica/etiologia , Apolipoproteínas E/genética , Cycas/efeitos adversos , Demência/etiologia , Transtornos Parkinsonianos/etiologia , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Animais , Apoptose , Comportamento Animal , Encéfalo/patologia , Caspase 3 , Caspases/metabolismo , Contagem de Células , Colesterol/sangue , Demência/metabolismo , Demência/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/patologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Medula Espinal/patologia , Tirosina 3-Mono-Oxigenase/metabolismo
12.
Neuroimage ; 23(1): 336-43, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15325381

RESUMO

Exposure to cycad (Cycas micronesica K.D. Hill) toxins via diet has been shown to induce neurodegeneration in vivo that mimics the progressive neurological disease, amyotrophic lateral sclerosis--parkinsonism dementia complex (ALS--PDC). In previous studies, specific cortical and subcortical cell loss was measured with conventional stained sections. In the present study, magnetic resonance (MR) microscopy was used to examine neurodegeneration in three dimensions (3D) in isolated intact brains and spinal cords. Mice were fed washed cycad for 2 months and showed progressive motor deficits resembling human ALS--PDC. CNS tissue was imaged at 17.6 T. T2* scans were acquired on both spinal cord and brain samples with an isotropic resolution of 41 microm. Through MR volumetrics, cycad-fed mice showed significantly decreased volumes in lumbar spinal cord gray matter, substantia nigra, striatum, basal nucleus/internal capsule, and olfactory bulb. Cortical measurements of conventionally stained sections revealed that cycad-fed mice also showed decreased cortical thickness. These results show that MR microscopy (MRM) is sensitive enough to measure degeneration in this early stage model of a progressive neurological disease with strong correlations to behavioral deficits and histological results and may be applicable in vivo to the same model. Similar analysis may be used in the future as a diagnostic aid in tracking the early progression of neurological disorders in preclinical human subjects.


Assuntos
Encéfalo/patologia , Modelos Animais de Doenças , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Microscopia , Doença dos Neurônios Motores/patologia , Degeneração Neural/patologia , Transtornos Parkinsonianos/patologia , Medula Espinal/patologia , Animais , Atrofia , Cycas , Masculino , Camundongos , Camundongos Endogâmicos , Neurônios/patologia , Neurotoxinas
14.
ALTEX ; 17(1): 3-10, 2000.
Artigo em Alemão | MEDLINE | ID: mdl-11103107

RESUMO

An important consideration for the utilisation of in vitro culture models for studies on drug metabolism as an alternative to animal testing is the maintenance of a defined degree of cell differentiation. Thus, in vitro conditions reflecting as near as possible the in vivo situation of the cells within the whole organ are required. A bioreactor was developed for the cultivation of liver cells which allows the reorganisation of hepatocytes and non-parenchymal cells of the liver in coculture to form three-dimensional, tissue-like structures including extracellular matrix components produced by the cells. In this study, the vitality and metabolic activity of isolated rat hepatocytes was investigated over a two week culture period in bioreactors. The results show that after a reorganisation phase, the cells preserve specific functions, such as protein and urea synthesis capacity and specific cytochrome P450 activities during the culture period, with maximal values during the first week. Possible applications of the model in pharmaceutical industry are studies on metabolite patterns, enzyme induction, drug-drug-interactions, first pass effects and long-term toxicity of drugs.


Assuntos
Alternativas aos Testes com Animais , Reatores Biológicos , Fígado/citologia , Fígado/metabolismo , Animais , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Cumarínicos/farmacocinética , Hepatócitos/citologia , Masculino , Oxazinas/farmacocinética , Ratos , Ratos Wistar
15.
J Nutr ; 130(10): 2434-43, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11015469

RESUMO

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.


Assuntos
Gorduras na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/uso terapêutico , Neoplasias Intestinais/prevenção & controle , Ácido Linoleico/uso terapêutico , Ácido alfa-Linolênico/uso terapêutico , Ácido gama-Linolênico/uso terapêutico , 6-Cetoprostaglandina F1 alfa/análise , Animais , Peso Corporal , Dinoprostona/análise , Ácidos Docosa-Hexaenoicos/análise , Ingestão de Alimentos , Ácidos Graxos/análise , Ácidos Graxos Ômega-3/administração & dosagem , Genes APC , Neoplasias Intestinais/genética , Neoplasias Intestinais/metabolismo , Intestinos/química , Ácido Linoleico/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , Fosfolipídeos/análise , Ácido alfa-Linolênico/administração & dosagem , Ácido gama-Linolênico/administração & dosagem
16.
J Nutr ; 130(5): 1153-8, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10801912

RESUMO

The multiple intestinal neoplasia (Apc(Min/+)) mouse possesses a germline mutation at codon 850 of the adenomatous polyposis coli (Apc) gene resulting in the formation of a nonfunctional truncated gene product. Following a somatic mutation of the remaining wild-type allele, mice spontaneously develop approximately 40-50 tumors throughout the intestinal tract. This mouse model has been used to study intestinal tumorigenesis because this mutation is analogous to the inherited APC mutation in humans with familial adenomatous polyposis (FAP). These individuals characteristically develop numerous adenomas throughout their intestinal tracts. Only a few studies have evaluated the effects of dietary fatty acids on tumorigenesis in this animal model with varying results, and none have linked these effects to alterations in arachidonic acid (AA) metabolism. This study was designed to evaluate the antitumorigenic effect of dietary (n-3) polyunsaturated fatty acids (PUFA) in the Apc(Min/+) mouse model and to determine whether these effects are related to inhibition of AA metabolism. Male Apc(Min/+)mice were fed diets supplemented with eicosapentaenoic acid (EPA), AA or a combination of AA + EPA. Mean tumor number in the EPA group was 68% lower (P<0.05) compared with the control group, whereas AA supplementation did not significantly alter tumor load. The reduction in tumor load coincided with significant reductions in intestinal AA content and levels of prostaglandins. However, supplementing AA to the EPA diet (AA + EPA) abolished the antitumorigenic effect of EPA, increased tissue AA content fourfold and prostaglandin production two- to fourfold. These results indicate that AA is involved in tumorigenesis and suggest that EPA's ability to reduce tumor load in Apc(Min/+) mice is related to reductions in tissue AA content or its metabolism.


Assuntos
Anticarcinógenos/farmacologia , Ácido Araquidônico/antagonistas & inibidores , Dieta , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Insaturados/farmacologia , Intestinos/efeitos dos fármacos , Prostaglandinas/biossíntese , Análise de Variância , Animais , Anticarcinógenos/administração & dosagem , Ácido Araquidônico/administração & dosagem , Ácido Araquidônico/metabolismo , Peso Corporal/efeitos dos fármacos , Interações Medicamentosas , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Mutação em Linhagem Germinativa , Mucosa Intestinal/metabolismo , Neoplasias Intestinais/genética , Neoplasias Intestinais/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes
17.
J Trauma ; 46(6): 1049-54, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10372623

RESUMO

BACKGROUND: The purpose of this study was to determine whether immediate primary closure of open fracture wounds can be performed without increasing the incidence of infections and delayed unions/nonunions. Although the traditional management of these injuries has been open treatment, a trend toward immediate primary closure has evolved on our service. METHODS: All open fractures presenting to an urban Level I trauma center during a 42-month period were reviewed. Of the 127 patients with open fractures, 90 patients (119 open fractures) were initially treated at the above institution within 24 hours of injury, had fractures proximal to the carpus or tarsals, and were followed-up until fracture union. All patients underwent emergent wound irrigation and debridement. The method of fracture immobilization and timing of wound closure was left to the discretion of the attending orthopedic surgeon. Immediate primary closure was used in 22 of 25 Grade I open fractures (88%), 37 of 43 Grade II fractures (86%), 24 of 32 Grade IIIa fractures (75%), 4 of 12 Grade IIIb fractures (33%), and 0 of 7 Grade IIIc fractures (0%). RESULTS: Eight fractures (7%) were complicated by a deep wound infection/osteomyelitis, and 19 fractures (16%) developed a delayed union/nonunion. Statistical analysis revealed no significant difference in delayed/nonunion and infection rates between immediate and delayed closures. CONCLUSION: Immediate primary closure of open fracture wounds after a thorough debridement by an experienced fracture surgeon appears to cause no significant increase in infections or delayed union/nonunions. In addition, early closure may decrease the requirement for subsequent debridements and soft-tissue procedures, thereby minimizing surgical morbidity, shortening hospital stays, and reducing costs. We feel that a randomized, prospective study of this aggressive approach to open fracture care is warranted.


Assuntos
Fraturas Expostas/cirurgia , Osteomielite/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Infecção dos Ferimentos/epidemiologia , Feminino , Fraturas Expostas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
18.
Z Kardiol ; 78(2): 101-8, 1989 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-2718555

RESUMO

Flow patterns in the right heart are often difficult to visualize by color-coded Doppler flow imaging. The echogenicity of blood was increased in 48 patients by intravenous injection of 10 ml echovist (200 mg/ml), a saccharide solution with defined size and concentration of microbubbles. Its effect on improving color-coding was compared with the effect of agitated gelifundol (10 ml) in 21 patients with tricuspid valve regurgitation. The non-controlled size and concentration of microbubbles resulted in weaker or uncontrollably exaggerated color-coding in half of the patients. In eight normals biphasic atrial flow was visible only after injection of echovist. In 25 patients with tricuspid regurgitation the blue coded area of reflux was 25 +/- 21% of the atrial area from the parasternal approach and 10 +/- 9% from the apical approach without correlation of these results. After echovist the area of reflux was 57 +/- 31% (p less than 0.001) in the parasternal and 53 +/- 26% (p less than 0.001) in the apical approach (r = 0.83). This was paralleled by an increase of the severity of tricuspid regurgitation as defined by the length or area of reflux (p less than 0.01-0.001). The qualitative diagnosis was safely established in the five patients with VSD in the control color Doppler flow imaging, but only in three out of 10 patients with ASD, and in nine of 10 after injection of echovist. The intravenous injection of echovist, when using color-coded Doppler flow imaging for evaluation of right heart disease, facilitates the qualitative diagnosis of ASD and also of tricuspid regurgitation, particularly in the apical approach.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Meios de Contraste , Ecocardiografia Doppler/métodos , Gelatina/análogos & derivados , Comunicação Interatrial/diagnóstico , Comunicação Interventricular/diagnóstico , Polissacarídeos , Insuficiência da Valva Tricúspide/diagnóstico , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Cor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
J Bone Joint Surg Am ; 71(2): 228-36, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2783931

RESUMO

Castrated male Sprague Dawley rats were subjected to various capacitively coupled electrical fields for six and eight weeks at two and 4.5 months after castration, respectively, with pairs of electrodes that were located paraspinally on the surface of the skin dorsally at the eleventh thoracic and fourth lumbar levels. When the animals were killed, dry and ash weights per unit of volume (apparent density), elastic modulus, ultimate stress, work to failure, trabecular area fraction, and mean trabecular width were determined for selected vertebrae. The results indicated that a sixty-kilohertz, 100-microampere signal (a calculated current density of five microamperes root-mean-square per square centimeter and a field of twelve millivolts root-mean-square per centimeter) significantly reversed the castration-induced osteoporosis in the lumbar vertebrae and restored bone mass per unit of volume in rats that had been stimulated for eight weeks after castration.


Assuntos
Terapia por Estimulação Elétrica , Orquiectomia , Osteoporose/terapia , Animais , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Vértebras Lombares/patologia , Masculino , Tamanho do Órgão , Osteoporose/etiologia , Osteoporose/patologia , Ratos , Ratos Endogâmicos , Vértebras Torácicas/patologia , Fatores de Tempo
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