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1.
Toxicol In Vitro ; 46: 273-283, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29032072

RESUMO

A response surface was built to predict the lipid peroxidation level, generated in an iron-ascorbate in vitro model, of any organ, which is correlated with the oxidative stress injury in biological membranes. Oxidative stress studies are numerous, usually performed on laboratory animals. However, ethical concerns require validated methods to reduce the use of laboratory animals. The response surface described here is a validated method to replace animals. Tissue samples of rabbit liver, kidney, heart, skeletal muscle and brain were oxidized with different concentrations of FeCl3 (0.1 to 8mM) and ascorbate (0.1mM), during different periods of time (0 to 90min) at 37°C. Experimental data obtained, with lipid content and antioxidant activity of each organ, allowed constructing a multidimensional surface capable of predicting, by interpolation, the lipid peroxidation level of any organ defined by its antioxidant activity and fat content, when exposed to different oxidant conditions. To check the predictive potential of the technique, two more experiments were carried out. First, in vitro oxidation data from lung tissue were collected. Second, the antioxidant capacity of kidney homogenates was modified by adding melatonin. Then, the response surface generated could predict lipid peroxidation levels produced in these new situations. The potential of this technique could be reinforced using collaborative databases to reduce the number of animals in experimental procedures.


Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo , Testes de Toxicidade/métodos , Animais , Encéfalo/efeitos dos fármacos , Cloretos/toxicidade , Compostos Férricos/toxicidade , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Músculo Esquelético/efeitos dos fármacos , Coelhos
2.
Int J Obes (Lond) ; 42(4): 618-624, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29158541

RESUMO

BACKGROUND/OBJECTIVES: We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism and dysfunction in abdominal adipose tissue from male pediatric patients with obesity. SUBJECTS/METHODS: Samples were collected from five children with obesity (percentile ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ coactivator-1α (PGC1α), nuclear respiratory factors 1 and 2 (NRF1, NRF2) and mitochondrial transcription factor A (TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by western blot. Citrate synthase (CS), complex I (CI) activity, adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) content and oxidative stress end points were also determined. RESULTS: Most MB proteins were significantly decreased in samples from children with obesity except complex I, V and superoxide dismutase-2 (SOD2). Similarly, CS and CI activity showed a significant reduction, as well as ATP levels and mtDNA content. PPARγ, PGC1α, complex I and V and SOD2 were hyperacetylated compared with lean samples. Concurrently, in samples from children with obesity, we found decreased SOD2 activity and redox state imbalance highlighted by decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and significant increases in protein carbonylation. CONCLUSIONS: Adipose tissue from children with obesity demonstrates a dysregulation of key modulators of MB and organelle structure, and displays hyperacetylation of key proteins and altered expression of upstream regulators of cell metabolism.


Assuntos
Tecido Adiposo/fisiopatologia , Mitocôndrias/fisiologia , Biogênese de Organelas , Obesidade Infantil/fisiopatologia , Acetilação , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Criança , DNA Mitocondrial/metabolismo , Humanos , Masculino , Proteínas Mitocondriais/análise , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Estresse Oxidativo/fisiologia , Obesidade Infantil/metabolismo
3.
Biomech Model Mechanobiol ; 16(2): 625-634, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27714474

RESUMO

A novel technique is proposed to predict force reduction in skeletal muscle due to fatigue under the influence of electrical stimulus parameters and muscle physiological characteristics. Twelve New Zealand white rabbits were divided in four groups ([Formula: see text]) to obtain the active force evolution of in vitro Extensor Digitorum Longus muscles for an hour of repeated contractions under different electrical stimulation patterns. Left and right muscles were tested, and a total of 24 samples were used to construct a response surface based in the proper generalized decomposition. After the response surface development, one additional rabbit was used to check the predictive potential of the technique. This multidimensional surface takes into account not only the decay of the maximum repeated peak force, but also the shape evolution of each contraction, muscle weight, electrical input signal and stimulation protocol. This new approach of the fatigue simulation challenge allows to predict, inside the multispace surface generated, the muscle response considering other stimulation patterns, different tissue weight, etc.


Assuntos
Modelos Biológicos , Contração Muscular/fisiologia , Fadiga Muscular/fisiologia , Músculo Esquelético/fisiologia , Animais , Estimulação Elétrica , Coelhos , Fatores de Tempo
4.
J Mech Behav Biomed Mater ; 61: 444-454, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27111629

RESUMO

In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction.


Assuntos
Músculos Abdominais/fisiologia , Modelos Biológicos , Contração Muscular , Parede Abdominal , Animais , Fenômenos Biomecânicos , Contração Isométrica , Masculino , Coelhos
5.
Ann Biomed Eng ; 43(10): 2444-55, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25691399

RESUMO

In the field of computational biomechanics, the experimental evaluation of the material properties is crucial for the development of computational models that closely reproduce real organ systems. When simulations of muscle tissue are concerned, stress/strain relations for both passive and active behavior are required. These experimental relations usually exhibit certain variability. In this study, a set of material parameters involved in a 3D skeletal muscle model are determined by using a system biology approach in which the parameters are randomly varied leading to a population of models. Using a set of experimental results from an animal model, a subset of the entire population of models was selected. This reduced population predicted the mechanical response within the window of experimental observations. Hence, a range of model parameters, instead of a single set of them, was determined. Rat Tibialis Anterior muscle was selected for this study. Muscles ([Formula: see text]) were activated through the sciatic nerve and during contraction the tissue pulled a weight fixed to the distal tendon (concentric contraction). Three different weights 1, 2 and 3 N were used and the time course of muscle stretch was analyzed obtaining values of (mean [Formula: see text] standard deviation): [Formula: see text], [Formula: see text] and [Formula: see text] respectively. A paired two-sided sign rank test showed significant differences between the muscle response for the three weights ([Formula: see text]). This study shows that the Monte Carlo method could be used for determine muscle characteristic parameters considering the variability of the experimental population.


Assuntos
Simulação por Computador , Modelos Biológicos , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Animais , Análise de Elementos Finitos , Masculino , Ratos , Ratos Wistar
6.
Biomech Model Mechanobiol ; 13(6): 1373-85, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24706095

RESUMO

The present study shows a new computational FEM technique to simulate the evolution of the mechanical response of 3D muscle models subjected to fatigue. In an attempt to obtain very realistic models, parameters needed to adjust the mathematical formulation were obtained from in vivo experimental tests. The fatigue contractile properties of three different rat muscles (Tibialis Anterior, Extensor Digitorium Longus and Soleus) subjected to sustained maximal isometric contraction were determined. Experiments were conducted on three groups [Formula: see text] of male Wistar rats [Formula: see text] using a protocol previously developed by the authors for short tetanic contractions. The muscles were subjected to an electrical stimulus to achieve tetanic contraction during 10 s. The parameters obtained for each muscle were incorporated into a finite strain formulation for simulating active and passive behavior of muscles with different fiber metabolisms. The results show the potential of the model to predict muscle fatigue under high-frequency stimulation and the 3D distribution of mechanical variables such as stresses and strains.


Assuntos
Simulação por Computador , Contração Isométrica/fisiologia , Modelos Biológicos , Fadiga Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Animais , Fenômenos Biomecânicos , Estimulação Elétrica , Processamento de Imagem Assistida por Computador , Masculino , Tamanho do Órgão , Ratos Wistar , Estresse Mecânico , Tíbia/fisiologia
7.
Genet Couns ; 25(4): 429-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25804023

RESUMO

In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.


Assuntos
Distrofina/genética , Distrofia Muscular de Duchenne/genética , Adolescente , Humanos , Masculino , México , Mosaicismo , Distrofia Muscular de Duchenne/fisiopatologia , Mutação , Linhagem
8.
Eur J Appl Physiol ; 111(6): 1127-33, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21116825

RESUMO

Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.


Assuntos
Membrana Eritrocítica/fisiologia , Exercício Físico/fisiologia , Indicadores Básicos de Saúde , Fluidez de Membrana/fisiologia , Estresse Oxidativo/fisiologia , Plasma/metabolismo , Adulto , Membrana Eritrocítica/metabolismo , Humanos , Masculino , Oxirredução , Esforço Físico/fisiologia , Carbonilação Proteica , Fatores de Tempo , Adulto Jovem
9.
Neurobiol Aging ; 32(11): 2045-54, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20096480

RESUMO

We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilizes membrane fluidity. Fluidity was measured by polarization changes of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate. Results showed that in untreated animals at 5 months of age, synaptosomal and mitochondrial fluidity was decreased in SAMP(8) compared to SAMR(1), as was the cathepsin D/B ratio, indicating dysfunction of the autophagy-lysosomal pathway. Moreover, we detected synaptosomal rigidity and programmed cell death capability in both groups at 10 months of age. Mitochondrial fluidity, however, did not show a significant age-dependent change but was lower in SAMP(8) than in SAMR(1) at the 5- and 10-month time points. Melatonin administration prevented rigidity in the mitochondrial membrane and seemed to decrease age-related autophagy-lysosomal alterations. These data suggest that melatonin may act to slow down the aging process because of its ability to enhance membrane fluidity and maintain structural pathways.


Assuntos
Encéfalo/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Melatonina/farmacologia , Fluidez de Membrana/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Senilidade Prematura/metabolismo , Animais , Encéfalo/metabolismo , Catepsina B/metabolismo , Catepsina D/metabolismo , Membrana Celular/metabolismo , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
12.
J Membr Biol ; 231(2-3): 93-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19847470

RESUMO

The ability of several indoleamines to scavenge free radicals is well documented. Our aim was to evaluate the ability of 0.01-3 mM tryptophan (Trp) and 0.1-5 mM 5-hydroxytryptophan (5-OH-Trp) to protect hepatic cell membranes against 0.1 mM FeCl(3) plus 0.1 mM ascorbic acid-induced lipid peroxidation and increases in membrane rigidity. Membrane fluidity was evaluated using fluorescence spectroscopy. Lipid and protein oxidation were estimated by quantifying malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations and carbonyl group content, respectively. Exposure to FeCl(3) plus ascorbic acid increased hepatic cell membrane rigidity, MDA + 4-HDA and carbonyl content. The presence of 5-OH-Trp, but not Trp, attenuated these changes. In the absence of oxidative stress, neither indoleamine modified fluidity, MDA + 4-HDA or carbonylation. These results suggest that C5 hydroxylation determines the ability of Trp to preserve membrane fluidity in the presence of oxidative stress.


Assuntos
5-Hidroxitriptofano/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Fígado/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triptofano/farmacologia , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
13.
Restor Neurol Neurosci ; 26(6): 459-65, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19096133

RESUMO

PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is a paralyzing disorder that kills individuals within three to five years of onset without any possibility for effective treatment. One proposed therapy has been the use of neurotrophic factors to inhibit the apoptosis of motorneurones. At the present, one way to deliver neurotrophic factors after intramuscular injection to the motor neurones is through the use of adenoviral vectors. An alternative strategy is the use of the atoxic C fragment of tetanus toxin (TTC) as a neurotrophic factor carrier for motorneurones. METHODS: We have produced the recombinant protein fusion Glial Derived Neurotrophic Factor and C fragment of tetanus toxin (GDNF-TTC) and we have tested its antiapoptotic activity in degeneration culture cells and in the symptomatic SOD;{G93A} transgenic animal model for ALS. RESULTS: We demonstrated that GDNF-TTC induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and~maintains its antiapoptotic neuronal activity in Neuro2A cells. Moreover, we have found that genetic fusion is able to increase survival by 9 days and improves life quality in symptomatic ALS animal models. CONCLUSION: These results suggest that recombinant GDNF-TTC fusion protein intramuscular injections provide a potential therapy for ALS treatment.


Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/microbiologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Toxina Tetânica/uso terapêutico , Esclerose Lateral Amiotrófica/genética , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Córtex Cerebral/citologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Técnicas de Transferência de Genes , Humanos , Camundongos , Camundongos Transgênicos , Neuroblastoma , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteína Oncogênica v-akt/metabolismo , Superóxido Dismutase/genética , Análise de Sobrevida , Transfecção
14.
Acta Vet Hung ; 55(2): 171-80, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17555281

RESUMO

Pluripotent stem cells (PSCs), already described in human beings, are fibroblast-like cells that exhibit a CD34 marker specific for haematopoietic stem cells. In this work we have demonstrated the presence of PSCs in the peripheral blood of pigs, a species frequently used in transplantation studies as an animal model for human diseases. Differentiation into haematopoietic colonies (granulomacrophagic colonies, erythroid colonies and mixed colonies) has been carried out with the peripheral blood of adult and newborn pigs, using solely human commercial media. Peripheral blood mononuclear cells (PBMNCs) were cultured in semisolid methylcellulose based media enriched with recombinant human cytokines, achieving granulomacrophagic-colony forming unit (GM-CFU) and mixed-colony forming unit (Mix-CFU) growth with erythroblastic lineage proliferation in the presence of erythropoietin (Epo). In all the samples CFU growth was associated with the presence of recombinant human cytokine. No evidence of proliferation in control plates without cytokines was found. From liquid medium culture, a population of macrophages and CD34+ fibroblast like cells were retrieved 21 days after sowing. These findings allow us to think about the direct application of this simple and standardised method in several work fields such as the study of pharmacological effects of many drugs over the haematopoietic line and in the study of new strategies in cellular therapy for some human diseases.


Assuntos
Células Cultivadas , Células-Tronco Hematopoéticas , Células-Tronco Pluripotentes , Suínos/sangue , Animais , Animais Recém-Nascidos , Antígenos CD34/análise , Meios de Cultura/química , Modelos Animais de Doenças
15.
Res Vet Sci ; 81(1): 87-91, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16289159

RESUMO

The aim of this work was to isolate and cultivate a subpopulation of pluripotent stem cells present in peripheral blood of different animal species, frequently used in laboratory studies (mice, rats and hamsters). Pluripotent stem cells (PSCs), already described in human beings, are fibroblast-like cells that exhibit a CD34 marker, specific for haematopoietic stem cells. Commonly used human commercial media were investigated for culturing animal PSCs. These findings suggest that this simple and standardized methodology may be applicable in several fields such as the study of the pharmacological effects of drugs on the haematopoietic line and the study of new strategies in cellular therapy for some human diseases.


Assuntos
Células Cultivadas , Células-Tronco Hematopoéticas , Células-Tronco Pluripotentes , Animais , Antígenos CD34/análise , Cricetinae/sangue , Meios de Cultura , Camundongos/sangue , Ratos/sangue
17.
Nefrologia ; 24(4): 329-32, 334, 336-7, 2004.
Artigo em Espanhol | MEDLINE | ID: mdl-15455492

RESUMO

BACKGROUND: Although the epidemiology of subjects with end-stage renal disease is well-known in Spain, the prevalence of mild to moderate chronic kidney disease (CKD) in the general population is unknown. In order to measure this, it is necessary to carry out studies in the general population including those who are not health service patients. During epidemiology studies, the method of measuring glomerular filtration rate can change significantly the measurements of the prevalence of mild to moderate CKD. METHODS: Between 1997 and 2000, we performed a multi-phase descriptive polistratified epidemiological transversal study. The section of public chosen was between the ages of 15 and 85 living in the health area of western Valladolid (Spain). We calculated creatinine clearance using four methods: serum creatinine concentration, creatinine clearance using 24-hour urine samples adjusting the volume to the expected creatinuria with the Walser formulas, using the Cockcroft-Gault (CG) equation and applying the Modification of Diet in Renal Disease (MDRD) study abbreviated formula. We classified the level of kidney function, according to the National Kidney Foundation-Dialysis Outcomes Initiative (NFK-DOQI) guidelines. RESULTS: The instances of stages 2 and 3 CKD rise with age and are more common in women than men. This tendency is apparent in middle age and persons of 65 and above. Using the CG method, almost half the old women had a stage 3 CKD as opposed to a third of the men. If the measurement is performed using the abbreviated MDRD study, there are very few differences between the sexes. The prevalence of stage 3 CKD is similar (around 8%) but the prevalence of stage 2 CKD rises to 60% as opposed to 36% calculated using the CG equation. After comparing the results obtained with those of the third National Health and Nutrition Examination Survey Study (see table VII), the measurements of stage 3 CKD using the CG formula or by means of expected creatininuria coincide relatively, although the prevalence of stage 2 CKD is higher in persons of 65 and over. If we use the abreviated MDRD study, the prevalences increase by more than 20%. CONCLUSIONS: The prevalence of stages 2 and 3 CKD is clearly influenced by the method of calculation used. The prevalence of stage 2 CKD affects at least a third of the general population while those affected by stage 3 CKD are between 3.3% and 8.5%.


Assuntos
Nefropatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Doença Crônica , Creatinina/urina , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos de Amostragem , Índice de Gravidade de Doença , Espanha/epidemiologia
18.
Arch Esp Urol ; 54(6): 493-510, 2001.
Artigo em Espanhol | MEDLINE | ID: mdl-11512394

RESUMO

OBJECTIVE: For optimum treatment planning and to establish the prognosis, the main objectives of diagnostic imaging techniques after detecting a tumor in the urinary bladder are to determine 1) its nature and histological structure, 2) depth of bladder wall invasion, 3) tumor localization and involvement of the ureter and trigone, 4) involvement of bladder wall lymphatics, and (5) to determine if there is or no regional and/or distant mestatasis. The capabilities of the diagnostic imaging techniques in regard to achieving the foregoing objectives are analyzed. METHODS: This study comprised 160 patients with a suspected or confirmed bladder tumor. The imaging methods utilized were: conventional radiology including IVP, retrograde and double contrast cystography, ultrasound, CT and MRI. RESULTS: Analysis of the images allowed assessment of 18 morphological parameters, of which the following were among the most relevant: presence of ureterohydronephrosis, filling defect(s), tumor localization, tumor base, tumor-mucosa angle, wall stiffness, total wall thickness, changes observed in the perivesical space and degree of pelvic lymph node involvement. Visualization of a bladder filling defect confirms a bladder tumor. The predictors of the biological behaviour of bladder tumors, such as wall stiffness and lumen asymmetry, characteristically express tumor invasiveness. The tumor-mucosa angles in relation to tumor base and peritumoral edema express a higher grade of infiltration for the obtuse angles and a lower grade for the acute angles. Determining tumor stage with accuracy is the essential challenge of the imaging methods in the assessment of bladder cancer. Both CT and MRI are used to analyze four basic aspects prior to treatment: 1) tumor appearance, 2) presence or absence of perivesical invasion, 3) presence or absence of invasion of the adjacent organs, and 4) presence or absence of lymphadenopathies. The accuracy of CT for tumor staging is estimated to be 88%-92% for stage D1 and 80%-85% for stages C and B2, respectively, while MRI has an accuracy of 95% for stage B2 and 85% for tumor stages that compromise adjacent organs such as the prostate, uterus or vagina. CONCLUSIONS: Conventional radiological methods, together with transabdominal or transrectal ultrasound, have a high rate of accuracy for tumor detection. Determination of the stage of tumor invasion requires analysis of wall thickness, width of tumor base, tumor-mucosa angles and perivesical space. CT and MRI provide highly reliable diagnostic information on the foregoing. CT may present some difficulty in determining the stage of bladder wall invasion. With contrast enhancement, MRI has shown a greater capability to differentiate tumor stages B2 and C and is very similar to CT in detecting pelvic or retroperitoneal lymph node involvement.


Assuntos
Neoplasias da Bexiga Urinária/diagnóstico , História do Século XIX , História do Século XX , Humanos , Imageamento por Ressonância Magnética , Ultrassonografia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Urografia/história
19.
Arch Esp Urol ; 54(6): 541-54, 2001.
Artigo em Espanhol | MEDLINE | ID: mdl-11512398

RESUMO

OBJECTIVES: This study was carried out 1) to analyze the growth and clinical manifestations of renal adenocarcinoma; 2) to determine the presence of tumor, its malignant nature, size, local extent or distant spread and route of dissemination according to the imaging methods utilized, and 3) to determine the accuracy of the different imaging procedures, such as IVP, US, CT, and MRI, in staging renal adenocarcinoma. These objectives attempted to provide answers to the following questions: a) Are there currently substantial changes in the biological behavior of renal adenocarcinoma?, b) Does the route of tumor dissemination (direct infiltration through the capsule, lymphohematogenous, cancer embolus carried by the bloodstream to a distant location) affect the rate of progression to stages III and IV?, and c) What are the most relevant findings of the imaging methods that aid in determining the extent of the renal tumor? METHODS: 106 renal masses were evaluated; of these, 93 were renal adenocarcinomas. The diagnosis, clinical evaluation and preoperative staging were based on the clinical history, physical examination, symptoms and imaging methods (IVP, US, CT, and MRI) to assess renal morphological changes, presence of calcifications, mass effect, tumor mass ultrasound characteristics, densitometry or MR signal pattern, perinephric fat involvement, venous vasculature, involvement of renal fascia, locoregional lymph nodes or metastasis and distant neoplastic changes. RESULTS: A third of the tumors had a size greater than 10 cms and practically half were 5-10 cms in size. Calcifications were found in 47%; 85% were punctiform and showed a central location. 88% of the tumors showed areas of necrosis. Due to the presence, in most of the cases, of a viable tumor, necrosis, calcification or cystic degeneration, the adenocarcinomas showed a very inhomogeneous ultrasound pattern and with varying degrees of vascularization on CT volumetric assessment. Invasion of perinephric fat and tumor fibrous septae were found in 65% on CT evaluation, although MRI was particularly sensitive in detecting fat infiltration in the early stages of perinephric involvement, venous thrombosis, involvement of adjacent and distant organs and tumor hemorrhagic changes. CONCLUSIONS: In determining the biological behaviour of renal adenocarcinoma, preoperative staging of infiltration and prognosis, US, volumetric CT and MRI are currently the diagnostic methods with the highest accuracy, specificity and sensitivity. These diagnostic methods allow early detection of tumors thereby making them potentially curable. Lymphatic drainage of the tumor may be determinant in its more or less rapid progression from Robson stage II to IIIa and IIIb, and thereafter to stage IV. CT and MRI showed a higher accuracy for tumor detection, localization, determining local extent, tumor characterization and staging. Detection of a tumor pseudocapsule comprised of reactive fibrous tissue and compact renal parenchyma by CT or MRI allows determination of the borders of the renal tumor. Lymph node involvement radically changes the prognosis and survival in renal adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Renais/diagnóstico , Idoso , Humanos , Pessoa de Meia-Idade
20.
Arch. esp. urol. (Ed. impr.) ; 54(6): 541-554, jul. 2001.
Artigo em Es | IBECS | ID: ibc-1706

RESUMO

Los OBJETIVOS generales se enmarcan en: 1) Analizar el crecimiento y manifestaciones clínicas del adenocarcinoma renal; 2) Determinar en base a los métodos radiológicos empleados, la presencia de tumor, el carácter maligno del mismo, el tamaño y extensión local o a distancia y las vías de diseminación así como precisar, 3) la fiabilidad de los distintos métodos de adquisición de imagen como la UIV, US, TC y RM respecto al estadiaje del adenocarcinoma renal. Estos objetivos básicos se encuentran diseñados en base al ejercicio de las siguientes cuestiones: a) ¿Existen actualmente variaciones sustanciales dentro del comportamiento biológico del adenocarcinoma renal? b) Las vías de diseminación marcadas por el tumor, a saber: (1) Infiltración directa a través de la cápsula; (2) Linfohematógena y (3) Hematógena por émbolos de células neoplasicas, ¿marca la velocidad de paso de los estadios III y IV? y c) ¿Cuáles son los datos radiológicos más ponderables en lo referente a los distintos métodos de imagen para determinar la extensión del tumor renal? MÉTODOS: Para la consecución de estos objetivos se evaluaron 106 masas renales, de las que 93 se correspondieron con adenocarcinomas renales. Los métodos diagnósticos, valoración clínica y estadiaje pre-quirúrgico se protocolizaron en base a Hª clínica, exploración física, sintomatología y modos radiológicos (UIV, ASD, US, TC y RM) y se valoraron como parámetros las alteraciones del contorno renal, presencia de calcificaciones, efecto masa, características ecoestructurales de la masa, comportamiento densitométrico o de señal RM, afectación de la grasa perinéfrica, estado de las redes vasculares venosas, afectación de las fascia renal, presencia de nodos linfáticos loco-regionales o metástasis y cambios neoplásicos a distancia. RESULTADOS: Un tercio de los tumores estudiados presentó un tamaño superior a 10 cms y, prácticamente la mitad entre 5 y 10 cms. La presencia de calcificaciones se detectó en un 47 por ciento de la población tumoral y en un 85 por ciento de la misma fue de topografía central y de morfología puntiforme. El 88 por ciento de los tumores presentaron áreas de necrosis. Debido a la presencia, en la mayoría de los casos, de tumor viable, necrosis, calcificación o degeneración quística, los adenocarcinomas tuvieron un comportamiento muy dishomogéneo en ultrasonografía y con variables grados de vascularización en TC volumétrica. La infiltración de la grasa perinéfrica y de los septos fibrosos de la misma se registró en un 64 por ciento en TC, aunque, la RM se mostró especialmente sensitiva para la detección de infiltración grasa en etapas tempranas de afectación perinéfrica y para la detección de trombosis venosa, afectación de órganos por contiguidad y a distancia y ante cambios hemorrágicos tumorales. CONCLUSIONES: En la determinación del comportamiento biológico de un adenocarcinoma y en la estimación del estadío infiltrativo pre-quirúrgico así como en la emisión de un pronóstico, la Ultrasonografía, la TC volumétrica y la RMI suponen, en el contexto diagnóstico actual los modos diagnósticos de más alta fiabilidad, sensitividad y especificidad. Debido a la accesibilidad actual a estos modos diagnósticos: 1) El descubrimiento temprano del tumor hace que éste sea potencialmente curable. 2) El drenaje linfático del tumor puede ser determinante de la evolución más o menos rápida desde los estadios II de Robson a los III(a) y III(b) y, desde éstos, a los IV de Robson. 3) La mayor fiabilidad en la determinación de: a) presencia de tumor, b) localización; c) extensión local, d) caracterización y e) estadiaje, pertenecen a la TC y RM. 4) La detección de una pseudocápsula tumoral, compuesta por tejido fibroso reactivo y parénquima renal comprimido, bien sea mediante TC o RM, determina los límites del tumor renal.5) El elemento evolutivo que cambia radicalmente el pronóstico y la supervivencia en el adenocarcinoma es la afectación linfátic (AU)


Assuntos
Pessoa de Meia-Idade , Idoso , Humanos , Adenocarcinoma , Neoplasias Renais
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