RESUMO
Formaldehyde (FA) is an environmental xenobiotic, which is genotoxic and carcinogenic to humans and animals; it induces DNA damage, mutations, and clastogenicity during critical cytogenetic events. FA-mediated oxidative stress is an important mechanism that has been associated with the induction of cytotoxic and genotoxic damage. Therefore, the objective of this study was to evaluate the dispersion of sperm chromatin and reproductive parameters induced by exposure to different concentrations of FA in Wistar rats. Compared to the percentage of sperm with fragmented DNA in the control group (18.10 ± 8.62%), the percentage of sperm with fragmented DNA increased following exposure to 5, 10, and 30 mg FA/kg body weight (29.60 ± 8.44, 85.20 ± 20.94 and 96.0 ± 7.87, respectively; P = 0.0001). Histopathological alterations were evident, especially in the seminiferous tubules. In conclusion, this study provides experimental evidence concerning the genotoxicity of FA, with particular reference to the decreased sperm concentration and motility and increased dispersion of DNA chromatin in rats.
Assuntos
Cromatina/efeitos dos fármacos , Formaldeído/toxicidade , Mutagênicos/toxicidade , Túbulos Seminíferos/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Cromatina/ultraestrutura , Fragmentação do DNA/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Túbulos Seminíferos/ultraestrutura , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/ultraestrutura , Testículo/ultraestruturaRESUMO
In vitro, Imatinib inhibits the proliferation and stimulates the osteogenic and adipogenic differentiation of mesenchymal stromal cells (MSC). However, it is unknown whether Imatinib affects the biology of MSC in vivo. We asked whether MSC from long-term Imatinib-treated CML patients were affected by the in vivo treatment. MSC from untreated and Imatinib-treated patients displayed normal functional properties (i.e. proliferation, immunophenotype, differentiation and hematopoietic supportive capacity) - but a decreased frequency. In vitro, Imatinib lost its effect when discontinued; which suggest that it has a reversible effect on MSC. Therefore it might lose its effect on MSC after discontinuation in vivo.
Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Células-Tronco Mesenquimais/fisiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Diferenciação Celular , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Células-Tronco Mesenquimais/citologia , FenótipoRESUMO
OBJECTIVE: This study aims to determine the relationship between weakness and bioimpedance analysis (BIA)-derived phase angle in a population of untreated cancer patients with fatigue. METHODS: We prospectively evaluated 41 treatment-naive cancer patients of several origins that presented with performance status 1-2, weight loss >5% in the last 6 months, and Fatigue Numeral Scale score >4. Weakness was considered a physical component of the multidimensional fatigue syndrome and was evaluated through several parameters utilizing hand grip strength technique by dinamometry. The same assessment was also performed on a healthy control population (n = 20). BIA-derived phase angle was also determined by BIA. RESULTS: Compared to healthy controls, cancer patients exhibited significant differences in all the parameters: median fatigue was 6 (range 5-9), evaluated maximal strength mean was 27 ± 10.71 vs. 42 ± 10.74 kg (p < 0.0001 for patients vs. control, respectively), and muscle strength difference (max-min muscle strength) was also statistically different (p < 0.0001). We also determined parameter associations within the patient population. We found statistical significant correlations between median phase angle score and endurance muscle with percentage of weight loss (r = 0.43, p = 0.03) for head and neck cancer patients, and in non-small cell lung cancer patients, grip work correlated significantly with normal or decreased phase angle (r = 0.85), p = 0.006 (Spearman Rank Correlation). CONCLUSIONS: Weakness could be correlated with normal or decreased phase angle in a population with ambulatory advanced cancer with fatigue naive of treatment. We also found a significant relationship between median phase angle score and endurance muscle with percentage of weight loss in the subpopulation of patients with head and neck carcinoma.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma de Células Escamosas/complicações , Fadiga/diagnóstico , Fadiga/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias Pulmonares/complicações , Força Muscular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Impedância Elétrica , Fadiga/fisiopatologia , Feminino , Força da Mão/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Redução de PesoRESUMO
Physalia physalis is a marine cnidarian from which high molecular weight toxins with hemolytic and neurotoxic effects have been isolated. In the present work, two novel toxins, PpV9.4 and PpV19.3 were purified from P. physalis by bioactive guideline isolation. It involved two steps of column chromatography, gel filtration and RP-HPLC. The molecular weights were 550.7 and 4720.9 Da for PpV9.4 and PpV19.3, respectively. In the light of the Edman sequencing results, the structure of these toxins included the presence of modified amino acids. Both toxins increased the percentage of insulin secreting beta-cells and induced cytosolic Ca2+ elevation. To date, this is the first report of low molecular weight toxins increasing insulin secretion purified from cnidarians, by constituting a new approach to the study of beta-cells physiology.
Assuntos
Cálcio/metabolismo , Hidrozoários/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Toxinas Biológicas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia em Gel , Cromatografia de Fase Reversa , Hemólise/efeitos dos fármacos , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Ratos , Ratos Wistar , Toxinas Biológicas/isolamento & purificaçãoRESUMO
Introducción: La diálisis peritoneal aguda (DPA) es la modalidad dialítica preferentemente seleccionada para niños con injuria renal aguda por síndrome urémico hemolítico postdiarreico (SUH D+). Evaluamos la seguridad y eficacia de la colocación por punción percutánea del catéter de DPA con anestesia local en niños con SUH D+. Pacientes y métodos: Se revisaron las historias clínicas de todos los pacientes con SUH D+ internados entre el 1 de enero de 1998 y el 31 de diciembre de 2008 en el Hospital de Pediatría Prof. Dr. Juan P. Garrahan. La seguridad se evaluó por la presencia de eventos adversos mayores relacionados con la colocación del catéter (per foración de vísceras y/o vasos mayores abdominales, sangrado que requiera transfusión) y menores (infección del sitio de salida y peritonitis dentro de las 48 hs del procedimiento). La eficacia se evaluó a través de la colocación exitosa del catéter y su buen funcionamiento. Además se registró la necesidad de recambio luego de su uso por mal funcionamiento. Resultados: Identificamos 149 pacientes que realizaron DPA, edad de 20.2 meses (rango 2,9-111) y peso de 11,35 kg (rango 5-24.4). Recuento de plaquetas previo al procedimiento de 89000 (22000-148000) mm3. Seguridad: el único efecto adverso detectado fue el desarrollo de peritonitis en un paciente. No se registró perforación de órganos ni de vasos mayores abdominales, ni sangrado severo, ni infección del sitio de salida. Eficacia: en todos los casos el catéter fue colocado exitosamente y en 48 pacientes (32.2%) hubo que recambiarlo por mal funcionamiento. Tanto la colocación como el recambio fueron realizadas en todos los casos por el nefrólogo al pie de la cama. Conclusión: la colocación del catéter de DPA por punción es un procedimiento seguro y eficaz.
ntroduction: Acute peritoneal dialysis (DPA) is the dialytictreatment of choice for children with acute kidney injury dueto post-diarrheal hemolytic uremic syndrome (D+HUS). In thisstudy safety and efficacy of percutaneous placement of anAPD catheter under local anesthesia in children with D+HUSwas assessed. Patients and methods: We reviewed the cli-nical charts of all patients with D+HUS admitted to thePediatric Hospital Prof. Dr. Juan P. Garrahan betweenJanuary 1, 1998 and December 31, 2008. Safety was eva-luated based on the presence of major (perforation of theviscera and/or major abdominal vessels, bloody dialysaterequiring red-blood-cell transfusion) and minor (exit-siteinfection and peritonitis within 48 hs of the procedure) adverse events associated with catheter insertion. Efficacy was assessed based on successful catheter insertion and func-tioning. Additionally, the need for catheter replacement dueto malfunction was recorded. Results: We identified 149patients with a mean age of 20.2 months (range, 2.9-111)and weight of 11.35 kg (range, 5-24.4) who underwent APD.Median platelet count previous to the procedure was 89000(range, 22000-148000) mm3. Safety: The only adverse eventfound was the development of peritonitis in one patient.Organ or major vessel perforation, severe bleeds, or exit-site infection were not observed. Efficacy: In all patients the catheter was successfully inserted and in 48 patients (32.2%) the catheter had to be replaced due to malfunctioning. Both placement and replacement were performed by a nephrologist at the bedside in all cases. Conclusion: Percutaneous APD catheter insertion is a safe and efficacious procedure.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Catéteres/efeitos adversos , Cateterismo , Diarreia Infantil , Diálise Peritoneal , Punções/tendências , Punções , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/terapia , ArgentinaRESUMO
El retardo de crecimiento es un importante problema clínico aun no resuelto ni correctamente manejado en niños con insuficiencia renal crónica (IRC). La optimización de todos los parámetros metabólicos y nutricionales no siempre lleva a una mejoría del crecimiento en estos pacientes. Desde hace aproximadamente 20 años se utiliza el tratamiento con rhGH para mejorar la talla en este grupo de niños. La bibliografía internacional muestra mejoría de la velocidad de crecimiento en estos pacientes sin embargo la experiencia publicada en la talla final (TF) alcanzada por los mismos es escasa. Los objetivos de este estudio fueron:1) evaluar la talla final alcanzada por pacientes transplantados renales(TxR) que recibieron tratamiento con rhGH (GrGH) comparándolos con un grupo control (GrC) con similares características clínicas, 2) evaluar los factores predictores de la TF, y 3) la repercusión de dicho tratamiento en la función renal. La TF en el GrGH fue significativamente mayor que la TF del GrC (-1.96 ± 1.13 vs -3.48 ± 1.19 SDS respectivamente, p <0.05). La talla (SDS) al inicio del tratamiento con rhGH fue la única variable significativa para predecir la respuesta al tratamiento (p= 0.001). Se observó una disminución significativa ClCr final en ambos grupos (GrGH: 76 ± 18 vs 66 ± 14 ml/min/m2 sup p<0.05; GrC: 72 ± 19 vs 56 ± 9 ml/min/m2 sup, p<0.05) lo que sugiere una caída similar del filtrado glomerular en ambos grupos independiente del tratamiento. Conclusión: Nuestros hallazgos permiten confirmar que el tratamiento con rhGH es efectivo para mejorar la talla final en pacientes TxR sin afectar la función renal (AU)
Growth retardation is a common and significant clinical problem that is not adequately managed in children with chronic renal disease. Despite optimization of metabolic parameters the growth of this patients not always amelioreted. About 20 years ago rhGH treatment became to be used for this group of children to optimization final height.The international experience show that rhGH treatment improve growth velocity but the results about final heigth are scarse. The aims of our trial were: 1) to evaluate final height in renal transplant patients treated with rhGH (n=23) comparing with a control group not treated with rhGH (n=14) with similar characteristics, 2) to evaluate the effect of rhGH on creatinine clearance,3) to establish predictive variables for final height. Final Heigth was significantly greater in treated group vs control group (-1.9±1.1 vs -3.5±1.2, p<0.05). Initial height was the only significant variable to predict final height (p=0.001). We described a significantly decrease of creatinine clearence in both groups during follow up (GH Group 76±9 vs 66±14 ml/min/m2 sup, p<0.05 and Control Group 72.5±19 vs 56±9 ml/min/m2 sup, p= p<0.05).This suggest a similar decrese of creatinine clearence in both groups. Conclution: Our data confirm that rhGH treatment was effective in improving final height in renal transplant patients and did not decline allograft function (AU)
Assuntos
Humanos , Criança , Adolescente , Estatura/efeitos dos fármacos , Proteínas Recombinantes/uso terapêutico , Transplante de Rim , Hormônio do Crescimento Humano/uso terapêutico , Insuficiência Renal Crônica/complicações , Transtornos do Crescimento/tratamento farmacológico , Estudos de Casos e Controles , Doença Crônica , Resultado do TratamentoRESUMO
RESUMEN Mujer de 28 años con retraso menstrual de 15 días. Examen físico: dolor en ambas fosas ilíacas, escaso sangrado, fondos de saco laterales dolorosos no abombados y fondo de saco de Douglas (FSD) levemente doloroso. Se realizaron 3 ecografías diferentes. Observamos la evolución del embarazo ectópico desde la típica imagen ecográfica redondeada con saco en su interior hasta la imagen heterogénea (hemática) que resultó ser un aborto tubárico por laparoscopia y biopsia. Hubo correlación con el BHCG en descenso. La búsqueda bibliográfica no encontró descripciones de asociaciones iguales al caso descrito.
ABSTRACT We report a case of a 28 year old woman with 15 days menstrual delay, abdominal pain and small bleeding. During physical examination, we found no pain in lateral pouches and slight pain in pouch of Douglas. Three different vaginal ultrasounds were perfomed by 3 professionals. We saw ultrasonographic evolution of an ectopic pregnancy from typical image with a sac within it to heterogeneous image (blood). Laparoscopy and biopsy confirm these findings. BHCG correlates with them, showing descendent levels. Bibliographic search didnt find similar cases to our patient.
Assuntos
Criança , Desnutrição , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Insuficiência de Crescimento/etiologia , Insuficiência de Crescimento/terapia , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Transplante de RimRESUMO
Evaluación retrospectiva de 575 trasplantes (TX), 64,3 por ciento con donante cadavérico (DC), en 550 pacientes (311 varones) edad por x: 10.8 más menos 4.2 años, efectuados entre 1988 y 2008. edad por de donante: DC 22.5 más menos 14 años y DVR: 37.3 más menos 7.7 años. Principales causas de IRC: nefropatía por reflujo: 34,1 por ciento, hipo-displasia: 15.1 por ciento, SUH; 12.9 por ciento, GSF: 9.82 por ciento, glomerulonefritis varias: 16.4 por ciento. Inmunosupresion: en la mayoría de los pacientes, Cicloporina A; Azatioprina o micofenolato mofetil o ácido micofenólico y esteroides con linfo o timoglobulina secuencia en TXDC y profilaxis con gaciclovir en riesgo de infección por CMV. La sobrevida actuarial funcional renal (SA) a 1.3 a 5 años fue 96.5 por ciento, 94.4 por ciento y 86,2 por ciento TX DVR y 90,1 por ciento, 85,5 por ciento y 77.6 por ciento TX DC, p= 0.04, similar a resultados en EEUU (NAPRCTS 1999 - 2002). La GSF con 45.5 por ciento de recurrencia del síndrome nefrótico, tuvo inferior SA al 5to año, p= 0.001, comparado con otras etiologías de IRC. Los TX sin diálisis (D) previa, p= 0.003. Tuvieron trombosis 2.61 por ciento de los TX, más frecuentes con DPCA pre tx que con hemo D o sin diálisis, p= 0.01, con TXDC, p= 0.02 y con TX de donantes < de 6 años, p = 0.02. Los pacientes que requirieron diálisis post trasplante, tuvieron mayor creatinina al año D: 1.8 más menos 2.27 mg/dl.SD: 1.19 más menos 1.2, p < 0.01, e inferior SA al quinto año, p=0.001. Con tiempo de isquemia fria superior a 24 horas, 31,6 por ciento de los DC necesitaron diálisis. El rechazo celular agudo se dianosticó en el 14,8 por ciento de los pacientes. Las causas más frecuentes de fracaso del trasplante fueron: nefropatía crónica (69,8 por ciento) asociado a inadecuada adherencia en 54.7 por ciento, trombosis (12.6 por ciento), recurrencia (5.9 por ciento), ausencia de función (5 por ciento) rechazo severo (5 por ciento)Desarrollaron enfermedad. (AU)