RESUMO
OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.
RESUMO
OBJECTIVES: The aim of this case-control study was to carry out an oral health assessment on a group of Alzheimer's patients and to establish a hypothesis regarding the implication of the characteristics of the disease and the treatment of oral health. MATERIALS AND METHODS: A total of 70 Alzheimer's patients, residents at the Alzheimer Center Reina Sofia Foundation (Madrid, Spain) and at the Alzheimer State Reference Center (Salamanca, Spain), and 36 controls (companions/acquaintances), were studied by oral examination and saliva sampling. The oral health indices DMFT/DMFS, CPI, the prosthetic condition, oral hygiene, saliva volume, and pH, as well as the specific microbiological parameters governing the risk of developing caries were assessed. RESULTS: Alzheimer's patients exhibited, as compared to the control group, (1) fewer teeth (10.9 ± 10.5 vs 23.7 ± 6.5), (2) fewer obturations (2.2 ± 3.4 vs 6.6 ± 5.6), (3) fewer periodontally healthy sextants (0.1 ± 0.4 vs 1.4 ± 2.2), (4) worse oral hygiene (43.1 vs 72.2% brushed), (5) greater use of removable prostheses (47.8 vs 8.4%), (6) higher incidence of candida infection (11.8 vs 0.0%) and cheilitis (15.9 vs 0.0%), (7) lower salivary flow (0.6 ± 0.6 vs 1.1 ± 0.6), and (8) lower buffering capacity (46 vs 80%). CONCLUSIONS: After taking into account the influence of age, Alzheimer's patients had worse oral health (caries and periodontal disease), more mucosal lesions (cheilitis and candidiasis), and worse saliva quantity and quality. CLINICAL RELEVANCE: Clinicians should be aware of the implications of Alzheimer's disease in oral health, in order to stablish the effective preventive measures and the optimal treatment plan.
Assuntos
Doença de Alzheimer/complicações , Avaliação Geriátrica , Saúde Bucal , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/patologia , Recidiva , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Adulto Jovem , GencitabinaRESUMO
Current frontline therapies have improved overall survival in acute promyelocytic leukemia (APL) patients to exceptional rates; however, relapse is still a problem among high-risk and old patients. Therefore, the development of better and safer therapies continues to be a goal in the treatment of this disease. In the present work, we examined three different pathways that hinder cell death in the APL cell line NB4, shedding light on the mechanisms that underlie resistance to apoptosis in these cells and that might help provide them with a proliferative advantage. We found that the proteasome inhibitor MG-132 specifically induces in NB4 cells an Nrf2-mediated antioxidant response which counteracts mitochondria-dependent apoptosis induced by the lipophilic cation dequalinium. More importantly, we also demonstrated that high basal autophagy levels and the gain-of-function of mutant p53 are intrinsic mechanisms of resistance to apoptosis in this cell line. According to our results, the pharmacological inhibition of autophagy and p53 mutants are useful tools to explore resistance to apoptosis in APL and other types of cancer and could be the bases of new therapeutic approaches that improve the efficiency and allow dose reduction of the current treatments.
Assuntos
Apoptose/genética , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Dequalínio/administração & dosagem , Dequalínio/farmacologia , Relação Dose-Resposta a Droga , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leupeptinas/administração & dosagem , Leupeptinas/farmacologia , Transporte Proteico/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismoRESUMO
Mitochondria play central roles in diverse physiological and pathological conditions associated with cell survival and death. Delocalized lipophilic cations, such as dequalinium (DQA), are accumulated in cancer cells attracted by the highly negative mitochondrial transmembrane potential of these cells. DQA showed a potent anticancer activity in cells from different malignancies. Here, we report the effect of DQA on PC-3 prostate cancer cells. Incubation with DQA at concentrations between 1.5 and 100 microM from 24 to 48 h decreases cell viability. The decrease in cell viability together with a loss of mitochondrial transmembrane potential induced an increase in reactive oxygen species production and cell death via caspase-3 dependent apoptotic pathway. QA was shown to cause moderate to strong cell death in a time and concentration dependent manner, causing a most advantageous effect at a concentration of 10 microM applied for a long 48 h time period, which might be a consequence of the kinetics of intracellular DQA accumulation in mitochondria, but also of the mechanisms of DQA-induced cell death. This data shows DQA as a promising agent against the human prostate cancer PC-3 cell line, activating the caspase-3 dependent apoptotic pathway. This fact might be beneficial for possible future applications in cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Dequalínio/farmacologia , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Estresse Oxidativo , Neoplasias da Próstata/metabolismo , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Relação Dose-Resposta a Droga , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Satisfaction with life is of particular interest in the study of old age well-being because it has arisen as an important component of old age. A considerable amount of research has been done to explain life satisfaction in the elderly, and there is growing empirical evidence on best predictors of life satisfaction. This research evaluates the predictive power of some aging process variables, on Angolan elderly people's life satisfaction, while including perceived health into the model. Data for this research come from a cross-sectional survey of elderly people living in the capital of Angola, Luanda. A total of 1003 Angolan elderly were surveyed on socio-demographic information, perceived health, active engagement, generativity, and life satisfaction. A Multiple Indicators Multiple Causes model was built to test variables' predictive power on life satisfaction. The estimated theoretical model fitted the data well. The main predictors were those related to active engagement with others. Perceived health also had a significant and positive effect on life satisfaction. Several processes together may predict life satisfaction in the elderly population of Angola, and the variance accounted for it is large enough to be considered relevant. The key factor associated to life satisfaction seems to be active engagement with others.
Assuntos
Envelhecimento/psicologia , População Negra/psicologia , Satisfação Pessoal , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Angola , Estudos Transversais , Análise Fatorial , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Percepção , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3⯱â¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8⯱â¯14.2 years vs 54.5⯱â¯13.9 years, pâ¯<â¯.001). Familial PCCs were more frequently associated with MEN2A (nâ¯=â¯8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3â¯cm (3-6â¯cm); 27.7% of the patients had tumors ≥6â¯cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4â¯cm [2.4-5.0â¯cm] vs 5.6â¯cm [4.0-7.0â¯cm], pâ¯<â¯.001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.
Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , 3-Iodobenzilguanidina , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/terapia , Antagonistas Adrenérgicos alfa/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Catecolaminas/urina , Conversão para Cirurgia Aberta/estatística & dados numéricos , Doxazossina/uso terapêutico , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Metanefrina/urina , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/complicações , Neoplasias Pancreáticas/genética , Fenoxibenzamina/uso terapêutico , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/genética , Feocromocitoma/patologia , Feocromocitoma/terapia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Carga Tumoral , Adulto JovemRESUMO
OBJECTIVE: Nowadays, the algorithms for the study of hydronephrosis in children include voiding cystourethrogram (VCUG) and diuretic renogram (DR) in all patients. Both are invasive, distressing, and associated with radiation risk. However, basic renal function tests (bRFTs) are not included. This study was designed to determine whether bRFTs may help avoid VCUG and/or DR in some children. METHODS: Retrospective review of hydronephrosis (≥20 mm renal pelvis) patient records over one year (n = 38) (pyeloureteral stenosis (PUS) n = 12; high-grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. Data from the three protocolized bRFTs (maximum urine osmolality after DDAVP (UOsm), albumin/creatinine ratio (Alb/Cr), and NAG/creatinine ratio (NAG/Cr), together with VCUG and DR, were analyzed. RESULTS: 38 hydronephrosis patients (pyeloureteral stenosis (PUS) n = 12; high grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. UOsm was decreased in 100% of VUR patients, 75% of PUS patients, and 16.7% of NOH patients. Alb/Cr ratio was increased in 62.5% of VUR patients, 8.3% of PUS patients, and 11.1% of NOH patients. NAG/Cr ratio was increased in 42.8% of VUR patients, 25% of PUS patients, and 6.7% of NOH patients. UOsm was decreased in most patients who required surgery (100% of VUR patients and 74% of PUS patients), but only in 11.1% of patients who did not (NOH group). CONCLUSIONS: These results suggest that bRFTs may be useful in delaying or avoiding VCUG in some hydronephrosis cases. UOsm is the most sensitive test. No child with (high grade) VUR had a normal UOsm. VCUG could have been avoided in 43% of our patients -with a normal UOsm- without missing any high grade VUR.
OBJETIVO: Actualmente, los algoritmos para estudiar hidronefrosis en niños, incluyen realizar cistografía miccional (CUMS) y renograma diurético (RD) a todos. Ambos son invasivos, molestos, y con riesgo de radiación. Contrariamente, las pruebas básicas de función renal (PFRb), no están incluidas. Este estudio se realizó para saber si las PFRb, pueden ayudarnos a evitar alguna CUMS y/o RD. METODOS: Análisis retrospectivo de todas las historias de niños con hidronefrosis (pelvis renal ≥20 mm) atendidos durante un año (n=38), [estenosis pieloureteral (EPU) n = 12; reflujo vesicoureteral (RVU) de alto grado n = 8; hidronefrosis no obstructiva (HNO) n = 18]. Analizamos las tres PFRb protocolizadas [osmolalidad urinaria máxima tras DDAVP (UOsm), albúmina/creatinina (Alb/Cr) y NAG/creatinina (NAG/Cr)], junto con CUMS y RD. RESULTADOS: UOsm estaba disminuida en 100% RVU, 75% EPU, 16,7% HNO. Alb/Cr estaba aumentado en 62,5% RVU, 8,3% EPU, 11,1% HNO. NAG/Cr estaba aumentado en 42,8% RVU, 25% EPU, 6,7% HNO. En relación a la necesidad de cirugía, UOsm estaba disminuida en la mayoría de pacientes intervenidos (100% con RVU y 74% con EPU), mientras solo en el 11% de pacientes sin cirugía (HNO). CONCLUSION: Estos resultados sugieren que las PFRb pueden ser útiles para retrasar o evitar CUMS en algunos niños con hidronefrosis. La UOsm es la PFRb más sensible. Ningún niño con RVU (de alto grado) mostró una UOsm normal. Se podrían haber evitado CUMS en el 43% de nuestros pacientes, con UOsm normal, sin haber perdido ningún diagnóstico de VUR (de alto grado).
Assuntos
Hidronefrose/diagnóstico , Testes de Função Renal/métodos , Obstrução Ureteral/complicações , Refluxo Vesicoureteral/complicações , Adolescente , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Hidronefrose/etiologia , Hidronefrose/terapia , Lactente , Recém-Nascido , Masculino , Renografia por Radioisótopo , Estudos Retrospectivos , Urografia , Adulto JovemRESUMO
BACKGROUND: Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature. PATIENTS AND METHODS: Patients with CSI GCTC were screened between January 2012 and December 2016. Patients had previously undergone inguinal orchidectomy as the primary treatment and chosen AS as their preferred management strategy after receiving information about all available strategies. RESULTS: Out of 91 patients screened, 82 patients selected AS as their preferred management strategy. Relapse rate in the overall population was 20% (95% CI 12-30) and median time to relapse was 11.5 months (range 1.0-35.0). In patients with seminomatous tumors, relapse rate decreased to 13% and median time to relapse was 13 months; whereas in patients with non-seminomatous tumors, relapse rate was 33% (IA) or 29% (IB) and median time to relapse was 12 months in stage IA and 4.5 months in stage IB patients. All relapses were rescued with three or four cycles of chemotherapy and two also required a retroperitoneal lymphadenectomy. All patients are currently alive and free of disease. CONCLUSIONS: The clinical outcomes of patients with CSI GCTC managed by AS in this series were excellent. This strategy limited the administration of active treatments specifically to the minority of patients who relapsed without compromising performance.
Assuntos
Imagem Multimodal/métodos , Neoplasias Embrionárias de Células Germinativas/prevenção & controle , Orquiectomia/mortalidade , Vigilância da População , Neoplasias Testiculares/prevenção & controle , Conduta Expectante/estatística & dados numéricos , Adolescente , Adulto , Idoso , Gerenciamento Clínico , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/cirurgia , Conduta Expectante/normas , Adulto JovemRESUMO
The effectiveness of different drying systems used for the dehydration of certain fractions of biodegradable municipal solid wastes with a high moisture content (fruit and vegetable remains) was analyzed. Some tests using small amounts of the material were carried out in natural and forced convection ovens. For larger quantities of wastes, a discontinuous cabinet dryer and a continuous rotary dryer were used. With these dryers, the moisture content was reduced from 800 to 100 g kg(-1). It was verified that the continuous rotary dryer was the most efficient type of equipment studied, since it allowed a dried waste to be obtained with better nutritional and microbiological qualities and in accordance to the specifications of the products for animal feeding.
Assuntos
Ração Animal , Dessecação/métodos , Resíduos de Alimentos , Biodegradação Ambiental , Conservação dos Recursos Naturais , Dessecação/instrumentação , Frutas , Valor Nutritivo , Eliminação de Resíduos/métodos , VerdurasRESUMO
The impact of amyotrophic lateral sclerosis and consequent disability on everyday life can be assessed with generic or specific and/or functional quality of life scales. Generic scales SF36, SIP (Sickness Impact Profiles) and SIP/ALS 19, SEIQoL have been validated for the assessment of quality of life in SLA. A specific scale has also been worked out and validated in this disease, the ALSAQ-40 scale. The ALSFRS (ALS Functional Rating Scale) is a tool validated to evaluate the patient's functional capacities. However, the patient's quality of life felt does not depend only on the disease course but also the patient's previous psychological profile, the environmental, social conditions and spiritual aspirations. The absence of a cognitive deficit makes the patient particularly lucid about the progressive degradation of health status. Evaluation must be carried out with individually for each patient, taking into account the social and familial environments, to appreciate real living conditions, and the impact of this degenerative disease.
Assuntos
Esclerose Lateral Amiotrófica , Avaliação da Deficiência , Qualidade de Vida , Esclerose Lateral Amiotrófica/diagnóstico , Humanos , Inquéritos e QuestionáriosRESUMO
Amyotrophic lateral sclerosis is a neurodegenerative disease, without any curative treatment. Clinical expression is variable and related to loss of motor neurons in the cortex, brain stem and spinal cord. There is little scientific evidence demonstrating the usefulness of physical therapy in this disease. Only stretching exercises, proprioceptive neuromuscular facilitation techniques and functional mobility training seem to have a real benefit in terms of spasticity, quality-of-life and pain. The main objective of physical therapy appears to be the preservation of optimal quality-of-life throughout the course of this incurable degenerative disease.
Assuntos
Esclerose Lateral Amiotrófica/reabilitação , Modalidades de Fisioterapia , HumanosRESUMO
Amyotrophic lateral sclerosis involves deterioration of speech and swallowing. The objectives of rehabilitation are to maintain a comprehensible speech, using exercises on airflow-phonic coordination and breath, lingual and labial movements. Rehabilitation exercises also focus on the different times of swallowing to improve management of the food bolus in the mouth, to learn facilitating techniques and to adopt postures favoring passage of the food bolus. No studies have addressed the question of the effectiveness of rehabilitation in amyotrophic lateral sclerosis, in term of quality of life, maintenance of comprehensible speech or reduction of respiratory risks. Rehabilitation programs are established on an individual basis according to the clinical presentation and course.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Distúrbios da Fala/etiologia , Distúrbios da Fala/terapia , Fonoterapia , HumanosRESUMO
Treatment with 0.2 mM hydrogen peroxide (H(2)O(2)) or with 0.5 mM cisplatin caused caspase-9 and caspase-3 activation and death by apoptosis in U-937 human promonocytic cells. However, treatment with 2 mM H(2)O(2), or incubation with the glutathione suppressor DL-buthionine-(S,R)-sulfoximine (BSO) prior to treatment with cisplatin, suppressed caspase activation and changed the mode of death to necrosis. Treatment with 2 mM H(2)O(2) caused a great decrease in the intracellular ATP level, which was partially prevented by 3-aminobenzamide (3-ABA). Correspondingly, 3-ABA restored the activation of caspases and the execution of apoptosis. By contrast, BSO plus cisplatin did not decrease the ATP levels, and the generation of necrosis by this treatment was not affected by 3-ABA. On the other hand, while all apoptosis-inducing treatments and treatment with 2 mM H(2)O(2) caused Bax translocation from the cytosol to mitochondria as well as cytochrome c release from mitochondria to the cytosol, treatment with BSO plus cisplatin did not. Treatment with cisplatin alone caused Bid cleavage, while BSO plus cisplatin as well as 0.2 and 2 mM H(2)O(2) did not. Bcl-2 overexpression reduced the generation of necrosis by H(2)O(2), but not by BSO plus cisplatin. These results indicate the existence of different apoptosis/necrosis regulatory mechanisms in promonocytic cells subjected to different forms of oxidative stress.
Assuntos
Apoptose/efeitos dos fármacos , Glutationa/deficiência , Peróxido de Hidrogênio/farmacologia , Monócitos/efeitos dos fármacos , Necrose , Trifosfato de Adenosina/metabolismo , Benzamidas/farmacologia , Western Blotting , Butionina Sulfoximina/farmacologia , Caspase 3 , Caspase 9 , Caspases/efeitos dos fármacos , Caspases/metabolismo , Cisplatino/farmacologia , Citocromos c/efeitos dos fármacos , Citocromos c/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Citometria de Fluxo , Humanos , Microscopia de Fluorescência , Monócitos/citologia , Monócitos/metabolismo , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transfecção , Células U937 , Proteína X Associada a bcl-2 , Proteína bcl-XAssuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Posicionamento do Paciente , Pneumonia Viral/terapia , Decúbito Ventral/fisiologia , Terapia Respiratória/métodos , Vibração/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Estado Terminal , Humanos , Oxigenoterapia/métodos , Pandemias , Pressão Parcial , Pneumonia Viral/complicações , Respiração Artificial , Terapia Respiratória/instrumentação , SARS-CoV-2 , Escarro , Decúbito Dorsal/fisiologiaRESUMO
OBJETIVO: Actualmente, los algoritmos para estudiar hidronefrosis en niños incluyen realizar cistografía miccional (CUMS) y renograma diurético (RD) a todos. Ambos son invasivos, molestos y con riesgo de radiación. Contrariamente, las pruebas básicas de función renal (PFRb) no están incluidas. Este estudio se realizó para saber si las PFRb pueden ayudarnos a evitar alguna CUMS y/o RD. MÉTODOS: Análisis retrospectivo de todas las historias de niños con hidronefrosis (pelvis renal ≥ 20 mm) atendidos durante un año (n = 38), [estenosis pieloureteral (EPU) n = 12; reflujo vesicoureteral (RVU) de alto grado n = 8; hidronefrosis no obstructiva (HNO) n = 18]. Analizamos las tres PFRb protocolizadas [osmolalidad urinaria máxima tras DDAVP (UOsm), albúmina/creatinina (Alb/Cr) y NAG/creatinina (NAG/Cr)], junto con CUMS y RD. RESULTADOS: UOsm estaba disminuida en 100% RVU, 75% EPU, 16,7% HNO. Alb/Cr estaba aumentado en 62,5% RVU, 8,3% EPU, 11,1% HNO. NAG/Cr estaba aumentado en 42,8% RVU, 25% EPU, 6,7% HNO. En relación a la necesidad de cirugía, UOsm estaba disminuida en la mayoría de pacientes intervenidos (100% con RVU y 74% con EPU), mientras solo en el 11% de pacientes sin cirugía (HNO). CONCLUSIÓN: Estos resultados sugieren que las PFRb pueden ser útiles para retrasar o evitar CUMS en algunos niños con hidronefrosis. La UOsm es la PFRb más sensible. Ningún niño con RVU (de alto grado) mostró una UOsm normal. Se podrían haber evitado CUMS en el 43% de nuestros pacientes, con UOsm normal, sin haber perdido ningún diagnóstico de VUR (de alto grado)
OBJECTIVE: Nowadays, the algorithms for the study of hydronephrosis in children include voiding cystourethrogram (VCUG) and diuretic renogram (DR) in all patients. Both are invasive, distressing, and associated with radiation risk. However, basic renal function tests (bRFTs) are not included. This study was designed to determine whether bRFTs may help avoid VCUG and/or DR in some children. METHODS: Retrospective review of hydronephrosis (≥ 20 mm renal pelvis) patient records over one year (n = 38) (pyeloureteral stenosis (PUS) n = 12; high-grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. Data from the three protocolized bRFTs (maximum urine osmolality after DDAVP (UOsm), albumin/creatinine ratio (Alb/Cr), and NAG/creatinine ratio (NAG/Cr), together with VCUG and DR, were analyzed. RESULTS: 38 hydronephrosis patients (pyeloureteral stenosis (PUS) n = 12; high grade vesicoureteral reflux (VUR) n = 8; non-obstructive hydronephrosis (NOH) n = 18. UOsm was decreased in 100% of VUR patients, 75% of PUS patients, and 16.7% of NOH patients. Alb/Cr ratio was increased in 62.5% of VUR patients, 8.3% of PUS patients, and 11.1% of NOH patients. NAG/Cr ratio was increased in 42.8% of VUR patients, 25% of PUS patients, and 6.7% of NOH patients. UOsm was decreased in most patients who required surgery (100% of VUR patients and 74% of PUS patients), but only in 11.1% of patients who did not (NOH group). CONCLUSIONS: These results suggest that bRFTs may be useful in delaying or avoiding VCUG in some hydronephrosis cases. UOsm is the most sensitive test. No child with (high grade) VUR had a normal UOsm. VCUG could have been avoided in 43% of our patients with a normal UOsm-without missing any high grade VUR
Assuntos
Humanos , Masculino , Feminino , Lactente , Hidronefrose/diagnóstico por imagem , Hidronefrose/cirurgia , Algoritmos , Cistografia , Renografia por Radioisótopo , Estudos Retrospectivos , Pelve Renal/diagnóstico por imagem , Pelve Renal/patologia , Albuminúria/diagnóstico , Refluxo Vesicoureteral/diagnóstico , Razão de Chances , Técnicas de Laboratório ClínicoRESUMO
In order to explore possibilities of using erythrocytes as carrier systems for delivery of pharmacological agents, we have studied the in vivo survival of murine carrier red blood cell populations enriched in young or old cells. Hypotonic-isotonic dialysis has been used to modify the cells as carrier systems and Percoll/albumin density gradients or counter-current distribution in aqueous polymer two-phase systems to separate them according to age. Hypotonic-isotonic dialysis produces a decrease in the red blood cell populations in vivo survival rate (from 9.5 to 7.8 days). Among the cells modified as carriers, the enriched young red blood cell populations show a higher in vivo survival (half-life 6.5-7.4 days) than populations made up of predominantly old red blood cells (half-life 4.7-6.2 days). Half-life of young or old circulating red blood cells was approximately one day longer when these cells were separated by counter-current distribution rather than by Percoll density gradients. Based on these results, hypotonic-isotonic dialysis of whole and enriched young or old red blood cell populations, with higher or lower survival rates, can be considered as a useful tool for modification of these cells as carriers. The final outcome of such changes can be translated into better control of plasma drug delivery during therapy.
Assuntos
Portadores de Fármacos , Envelhecimento Eritrocítico , Eritrócitos/citologia , Animais , Separação Celular/métodos , Centrifugação com Gradiente de Concentração , Distribuição Contracorrente , Diálise , Eritrócitos/metabolismo , Meia-Vida , Soluções Hipotônicas , Soluções Isotônicas , Masculino , Camundongos , Povidona , Dióxido de SilícioRESUMO
Rat erythrocytes subjected to hypotonic-isotonic dialysis, or crosslinking with bifunctional reagents (glutaraldehyde and dimethyl suberimidate hydrochloride) show a high percentage of methemoglobin and decreased oxyhemoglobin content which implies a low oxygen carrying capacity. Such modified cells maintain reversible oxygen binding properties although, they present a high hemoglobin oxygen affinity (low P50) and a diminished cooperativity in binding oxygen to hemoglobin (low n). These results suggest a reduced capacity of liberating oxygen to tissues under low PO2. Changes produced in erythrocytes can not be restored even in the presence of energy (ATP), reduced glutathione and 2,3-bisphosphoglyceric acid during the dialysis process or after crosslinking/permeabilizing treatment.
Assuntos
Eritrócitos/metabolismo , Oxigênio/sangue , Oxiemoglobinas/metabolismo , 2,3-Difosfoglicerato , Trifosfato de Adenosina/farmacologia , Animais , Reagentes de Ligações Cruzadas , Diálise , Dimetil Suberimidato , Ácidos Difosfoglicéricos/farmacologia , Glutaral , Glutationa/farmacologia , Hemoglobina H/metabolismo , Soluções Hipotônicas , Masculino , Metemoglobina/metabolismo , Fragilidade Osmótica , Ratos , Ratos WistarRESUMO
The fractionation of normal human erythrocytes by counter-current distribution (CCD) in charge-sensitive dextran-polyethylene glycol two-phase systems was confirmed and extended to red blood cells from heterozygous beta-thalassaemic patients. The differences between the distribution profiles of normal (homogeneous) and abnormal (heterogeneous) red blood cells reflect their different surface-charge properties. As suggested by the decline of membrane sialic acid released after neuraminidase treatment and the specific activities of two age-dependent enzymes (membrane acetylcholinesterase and intracellular pyruvate kinase) in the distribution profiles (from the left- to the right-hand side fractions), the fractionation seems to be according to red blood cell age. A constancy of the 2,3-bisphosphoglycerate level was observed in ageing red blood cells.