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1.
eNeuro ; 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36257704

RESUMO

Absence of presynaptic protein MUNC18-1 (gene: Stxbp1) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immature Stxbp1 knockout (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi of Stxbp1 KO mice showed cell-type specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response. To further investigate direct, neuron-specific effects of MUNC18-1 depletion, a proteomic screen was performed on murine neuronal cultures at two developmental timepoints prior to onset of neuron degeneration. 399 proteins were differentially expressed, which were primarily involved in synaptic function (especially synaptic vesicle exocytosis) and neuron development. We further show that many of the downregulated proteins upon loss of MUNC18-1 are normally upregulated during this developmental stage. Thus, absence of MUNC18-1 extensively dysregulates the transcriptome and proteome, primarily affecting synaptic and developmental profiles. Lack of synaptic activity is unlikely to underlie these effects, as the changes were observed in immature neurons without functional synapses, and minimal overlap was found to activity-dependent proteins. We hypothesize that presence of MUNC18-1 is essential to advance neuron development, serving as a 'checkpoint' for neurons to initiate cell death in its absence.Significance StatementPresynaptic protein MUNC18-1 is essential for neuronal functioning. Pathogenic variants in its gene, STXBP1, are among the most common found in patients with developmental delay and epilepsy. To discern the pathogenesis in these patients, a thorough understanding of MUNC18-1's function in neurons is required. Here, we show that loss of MUNC18-1 results in extensive dysregulation of synaptic and developmental proteins in immature neurons before synapse formation. Many of the downregulated proteins are normally upregulated during this developmental stage. This indicates that MUNC18-1 is a critical regulator of neuronal development, which could play an important role in the pathogenesis of STXBP1 variant carriers.

2.
Cir. Esp. (Ed. impr.) ; 100(7): 422-430, jul. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-207732

RESUMO

Objetivo Conocer el coste económico a largo plazo asociado al tratamiento de la incontinencia fecal grave mediante SNS frente al tratamiento conservador sintomático y la colostomía definitiva. Métodos Estudio descriptivo pormenorizado de los costes del proceso asistencial (intervenciones, consultas, dispositivos, pruebas complementarias, hospitalización, etc.) de 3 alternativas de tratamiento de la incontinencia fecal empleando herramientas de gestión y contabilidad analítica del propio Servicio de Salud con base en datos de actividad clínica. Se estimó, en cada caso, la frecuencia de uso de recursos sanitarios o la cantidad de productos dispensados en farmacias (medicación, pañales, material de ostomía, etc.). Se incluyeron costes derivados de situaciones adversas. Se incluyeron pacientes con incontinencia fecal grave, definida por una puntación superior a 9 en la escala de severidad de Wexner, en los que han fracasado los tratamientos de primera línea. Se emplearon datos de una cohorte consecutiva de 93 pacientes a los que se realizó una SNS entre los años 2002 y 2016; de pacientes intervenidos de colostomía definitiva (n=2); hernia paraestomal (n=3) y estenosis de colostomía (n=1). Resultados El coste medio acumulado en 10 años por paciente en cada alternativa fue: 10.972,9€ para el tratamiento sintomático (62% pañales); 17.351,57€ para la SNS (95,83% intervenciones; 81,6% dispositivos), y 25.858,54€ para la colostomía definitiva (70,4% material de ostomía) Conclusiones El manejo de la incontinencia fecal grave implica un gran impacto en términos económicos. La colostomía es la alternativa que más costes directos genera, seguida de la SNS y el tratamiento sintomático (AU)


Introduction Find out the long-term economic cost associated with the treatment of severe fecal incontinence by SNS versus symptomatic conservative treatment and definitive colostomy. Methods Detailed descriptive study of the costs of the healthcare process (interventions, consultations, devices, complementary tests, hospitalization, etc.) of 3 treatment alternatives for fecal incontinence using analytical accounting tools of the Health Service based on clinical activity data. The frequency of use of health resources or the quantity of products dispensed in pharmacies (medication, diapers, ostomy material, etc.) was estimated in each case. Costs derived from adverse situations were included. Patients with severe fecal incontinence, defined by a score greater than 9 on the Wexner severity scale, in whom first-line treatments had failed, were included. Data from a consecutive cohort of 93 patients who underwent an SNS between 2002 and 2016 were used; patients who underwent definitive colostomy (n=2); parastomal hernia (n=3), and colostomy stenosis (n=1). Results The mean cumulative cost in 10 years per patient in each alternative was: € 10,972.9 symptomatic treatment (62% diapers); € 17,351.57 SNS (95.83% interventions; 81.6% devices); € 25,858.54 definitive colostomy (70.4% ostomy material and accessories). Conclusions Management of severe fecal incontinence implies a great burden in economic terms. The colostomy is the alternative that generates the most direct cost, followed by SNS and symptomatic treatment (AU)


Assuntos
Humanos , Incontinência Fecal/economia , Incontinência Fecal/terapia , Tratamento Conservador/economia , Colostomia/economia , Custos de Cuidados de Saúde , Índice de Gravidade de Doença , Análise de Impacto Orçamentário de Avanços Terapêuticos
3.
An Sist Sanit Navar ; 43(3): 347-358, 2020 Dec 22.
Artigo em Espanhol | MEDLINE | ID: mdl-33275124

RESUMO

BACKGROUND: The aim is to determine whether good functional and quality of life results of sacral nerve stimulation (SNS) in patients with severe fecal incontinence are maintained in the long-term. MATERIAL AND METHODS: Consecutive cohort of patients with severe fecal incontinence not responding to conservative (drugs and/or biofeedback) or surgical (sphincteroplasty) treatment, undergoing SNS between 2002 and 2013. Patients with a definitive implant were individually assessed in consultation throughout the follow-up, until January 2016. Defeca-tory function was assessed by Wexner score and stool diary, and perceived quality of life by FIQL and EQ-5D question-naires. RESULTS: Acute percutaneous nerve evaluation (PNE) was performed on 93 patients; a temporary electrode was implanted in 91 (79.1% women, mean age 62.5 years), obtaining a good functional response in 64. A permanent implant was per-formed in 61 patients, with a mean follow-up of 78.1 months (SD: 35.4; range 1-161); at the end of the study 42 patients remained in follow-up. A significant decrease was observed in the number of days per week with an incontinent episode, from 4.98 (SD 2.1) to 1.25 (SD 1.7), and in Wexner score from 16.88 (SD 2.74) to 6.95 (SD 3.54). Specific FIQL and generic EQ-5D questionnaires showed a significant improvement in quality of life. CONCLUSION: Long-term functional and quality of life outcomes of SNS for the treatment of severe faecal incontinence is maintained, with individual follow-ups that reach 10 years.


Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal , Incontinência Fecal/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
4.
Sci Adv ; 6(8): eaax5783, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32128395

RESUMO

Synaptic transmission is the predominant form of communication in the brain. It requires functionally specialized molecular machineries constituted by thousands of interacting synaptic proteins. Here, we made use of recent advances in cross-linking mass spectrometry (XL-MS) in combination with biochemical and computational approaches to reveal the architecture and assembly of synaptic protein complexes from mouse brain hippocampus and cerebellum. We obtained 11,999 unique lysine-lysine cross-links, comprising connections within and between 2362 proteins. This extensive collection was the basis to identify novel protein partners, to model protein conformational dynamics, and to delineate within and between protein interactions of main synaptic constituents, such as Camk2, the AMPA-type glutamate receptor, and associated proteins. Using XL-MS, we generated a protein interaction resource that we made easily accessible via a web-based platform (http://xlink.cncr.nl) to provide new entries into exploration of all protein interactions identified.


Assuntos
Proteômica , Sinapses/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/química , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteínas/química , Proteínas/metabolismo , Proteômica/métodos , Reprodutibilidade dos Testes , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem , Fluxo de Trabalho
6.
Eur J Clin Nutr ; 70(2): 170-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26603881

RESUMO

BACKGROUND/OBJECTIVES: The pathogenesis of enteritis after abdominal radiotherapy (RT) is unknown, although changes in fecal microbiota may be involved. Prebiotics stimulate the proliferation of Lactobacillus spp and Bifidobacterium spp, and this may have positive effects on the intestinal mucosa during abdominal RT. SUBJECTS/METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with gynecological cancer who received abdominal RT after surgery. Patients were randomized to receive prebiotics or placebo. The prebiotic group received a mixture of fiber (50 inulin and 50% fructo-oligosaccharide), and the placebo group received 6 g of maltodextrin twice daily from 1 week before to 3 weeks after RT. The number of bowel movements and stool consistency was recorded daily. Diarrhea was evaluated according to the Common Toxicity Criteria of the National Cancer Institute. Stool consistency was assessed using the 7-point Bristol scale. Patients' quality-of-life was evaluated at baseline and at completion of RT using the EORTC-QLQ-C30 (European Organization for Research and Treatment of Cancer quality-of-life Questionnaire C30) test. RESULTS: Thirty-eight women with a mean age of 60.3±11.8 years participated in the study. Both groups (prebiotic (n=20) and placebo (n=18)) were comparable in their baseline characteristics. The number of bowel movements per month increased in both groups during RT. The number of bowel movements per day increased in both groups. The number of days with watery stool (Bristol score 7) was lower in the prebiotic group (3.3±4.4 to 2.2±1.6) than in the placebo group (P=0.08). With respect to quality-of-life, the symptoms with the highest score in the placebo group were insomnia at baseline and diarrhea toward the end of the treatment. In the prebiotic group, insomnia was the symptom with the highest score at both assessments, although the differences were not statistically significant. CONCLUSIONS: Prebiotics can improve the consistency of stools in gynecologic cancer patients on RT. This finding could have important implications in the quality-of-life of these patients during treatment.


Assuntos
Enterite/prevenção & controle , Neoplasias dos Genitais Femininos/radioterapia , Inulina/administração & dosagem , Oligossacarídeos/administração & dosagem , Prebióticos/administração & dosagem , Lesões por Radiação/prevenção & controle , Abdome/microbiologia , Abdome/efeitos da radiação , Idoso , Defecação/efeitos dos fármacos , Defecação/efeitos da radiação , Diarreia/microbiologia , Diarreia/prevenção & controle , Diarreia/psicologia , Fibras na Dieta/administração & dosagem , Método Duplo-Cego , Enterite/microbiologia , Fezes , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Lesões por Radiação/microbiologia
7.
J Immunotoxicol ; 11(1): 19-27, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23662743

RESUMO

Research on the biological effects of vanadium in humans has shown that acute poisoning in workers can manifest itself in a number of symptoms. There are no reports in humans about reproductive and developmental effects induced by vanadium compounds in humans; however, some studies with rats and mice indicate that vanadium can cross the placental barrier and accumulate in fetal membranes rather than the fetus itself. In this case, probably most consequences of administration of vanadium to pregnant females like reabsorptions, fetal death and reduction in size can be the result of maternal toxicity. Concerning genetic and related effects in humans exposed to different vanadium compounds, data are controversial. Data on genotoxic effects in workers exposed to vanadium indicate that they can have an increased risk to develop cancer, and DNA instability can give rise to an onset of genetic syndromes, fetal malformations, and cancer. This paper presents materials presented at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology in a session titled 'Relationship between occupational and environmental exposure to vanadium compounds and the reprotoxic and genotoxic effects'.


Assuntos
Doenças Fetais/prevenção & controle , Neoplasias/prevenção & controle , Vanádio/metabolismo , Animais , Dano ao DNA , Exposição Ambiental/efeitos adversos , Feminino , Doenças Fetais/etiologia , Humanos , Exposição Materna/efeitos adversos , Camundongos , Neoplasias/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Gravidez , Ratos , Estados Unidos , Vanádio/química , Vanádio/toxicidade
8.
Strahlenther Onkol ; 190(2): 171-80, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24306064

RESUMO

PURPOSE: The goal of the present study was to analyze prognostic factors in patients treated with external-beam radiation therapy (EBRT), surgical resection and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent gynecological cancer (ORGC). PATIENTS AND METHODS: From January 1995 to December 2012, 61 patients with ORGC [uterine cervix (52 %), endometrial (30 %), ovarian (15 %), vagina (3 %)] underwent IOERT (12.5 Gy, range 10-15 Gy), and surgical resection to the pelvic (57 %) and paraaortic (43 %) recurrence tumor bed. In addition, 29 patients (48 %) also received EBRT (range 30.6-50.4 Gy). Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. RESULTS: Median follow-up time for the entire cohort of patients was 42 months (range 2-169 months). The 10-year rates for overall survival (OS) and locoregional control (LRC) were 17 and 65 %, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p = 0.03), time interval from primary tumor diagnosis to locoregional recurrence (LRR) < 24 months (HR 4.02; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.95; p = 0.02) retained significance with regard to LRR. Time interval from primary tumor to LRR < 24 months (HR 2.32; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.77; p = 0.04) showed a significant association with OS after adjustment for other covariates. CONCLUSION: External-beam radiation therapy at the time of pelvic recurrence, time interval for relapse ≥ 24 months and not multi-involved fragmented resection specimens are associated with improved LRC in patients with ORGC. As suggested from the present analysis a significant group of ORGC patients could potentially benefit from multimodality rescue treatment.


Assuntos
Neoplasias dos Genitais Femininos/radioterapia , Neoplasias dos Genitais Femininos/cirurgia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Radioterapia Adjuvante , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/patologia , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Dosagem Radioterapêutica
9.
An. sist. sanit. Navar ; 36(3): 557-561, sept.-dic. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-118951

RESUMO

El carcinoma colorrectal es un tumor que con muy poca frecuencia origina metástasis cutáneas, y cuando lo hace raramente es por vía hematógena. Presentamos el caso de un varón de 55 años diagnosticado de un adenocarcinoma de recto (tercio inferior) estadioT3N2M0. Tratado inicialmente con radioquimioterapia neoadyuvante, fue intervenido ocho semanas después realizándose una amputación abdominoperineal extendida. El resultado anatomopatológico fue de adenocarcinoma mucinoso de recto, estadio ypT3bN1. Tras un postoperatorio sin complicaciones el paciente recibió tratamiento quimioterápico con capecitabina. A los 18 meses el paciente refirió la aparición progresiva de nódulos subcutáneos en distintas localizaciones. En la tomografía computarizada de control se objetivaron múltiples imágenes sugestivas de metástasis a nivel hepático y pulmonar, así como lesiones subcutáneas. La exéresis-biopsia de uno de los nódulos subcutáneos corroboró la sospecha de metástasis de adenocarcinoma de recto. Se valoró tratamiento quimioterápico que no llegó a administrarse por el rápido deterioro del paciente que llevó al exitus (AU)


Colorectal carcinoma is a tumour that very infrequently gives rise to cutaneous metastases and when it does so, it is rarely by the haematogenous route. We present the case of a 55-year old male diagnosed with anadenocarcinoma of the rectum (lower third), clinical stageT3N2M0. Initially treated with neoadjuvant radiochemotherapy, he was operated on eight weeks later, with an extended abdominoperineal amputation. The anatomopathological result was mucinous adenocarcinoma of the rectum, clinical stage ypT3bN1. Following a postoperative period without complications, the patient received chemotherapeutic treatment with capecitabine. Eighteen months later the patient reported the progressive appearance of subcutaneous nodules in different localizations. In the computerized tomography test multiple images were objectivized suggesting metastasis at the hepatic and pulmonary levels, as well as subcutaneous lesions. The biopsy-excision of one of the subcutaneous nodules corroborated the suspicion of metastasis of the adenocarcinoma of the rectum. Chemotherapy treatment was considered for the patient, which was not administered due to the rapid deterioration of the patient leading to his death (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Cutâneas/secundário , Metástase Neoplásica/patologia , Biópsia , Endoscopia Gastrointestinal
10.
Gynecol Oncol ; 130(3): 537-44, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23707668

RESUMO

OBJECTIVE: To analyze prognostic factors in patients treated with intraoperative electrons containing resective surgical rescue of locally recurrent gynecological cancer (LRGC). METHODS: From January 1995 to December 2012, 35 patients with LRGC [uterine cervix (57%), endometrial (20%), ovarian (17%), vagina (6%)] underwent extended [multiorgan (54%), bone (9%), soft tissue (54%), vascular (14%)] surgery and intraoperative electron-beam radiation therapy [IOERT (10-15 Gy)] to the pelvic recurrence tumor bed. Sixteen (46%) patients also received external beam radiation therapy [EBRT (30.6-50.4 Gy)]. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. RESULTS: Median follow-up time for the entire cohort of patients was 46 months (range, 3-169). Ten-year rates for locoregional control (LRC) and overall survival (OS) were 58 and 16%, respectively. On multivariate analysis non-EBRT at the time of pelvic re-recurrence [HR 4.15; p = 0.02], no tumor fragmentation [HR 0.13; p=0.05] and time interval from primary tumor to LRR < 24 months [HR 5.16; p=0.01], retained significance with regard to LRR. Non-EBRT at the time of pelvic re-recurrence [HR 4.18; p=0.02] and time interval from primary tumor to LRR < 24 months [HR 6.67; p=0.02] showed a significant association with OS after adjustment for other covariates. CONCLUSIONS: EBRT treatment integrated for rescue, time interval for relapse ≥ 24 months, and not multi-involved fragmented resection specimens are associated with improved LRC in patients with LRGC in the pelvis. Present results suggest that a significant group of patients may benefit from EBRT treatment integrated with extended surgery and IOERT.


Assuntos
Adenocarcinoma/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias dos Genitais Femininos/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Cuidados Intraoperatórios , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Radioterapia Adjuvante , Taxa de Sobrevida , Fatores de Tempo
11.
An Sist Sanit Navar ; 36(3): 557-61, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-24406371

RESUMO

Colorectal carcinoma is a tumour that very infrequently gives rise to cutaneous metastases and when it does so, it is rarely via the haematogenous route. We present the case of a 55-year old male diagnosed with an adenocarcinoma of the rectum (lower third), clinical stage T3N2M0. Initially treated with neoadjuvant radiochemotherapy, he was operated on eight weeks later, with an extended abdominoperineal amputation. The anatomopathological result was mucinous adenocarcinoma of the rectum, clinical stage ypT3bN1. Following a postoperative period without complications, the patient received chemotherapeutic treatment with capecitabine. Eighteen months later the patient reported the progressive appearance of subcutaneous nodules in different localizations. In the computerized tomography test multiple images were objectivized suggesting metastasis at the hepatic and pulmonary levels, as well as subcutaneous lesions. The biopsy-excision of one of the subcutaneous nodules corroborated the suspicion of metastasis of the adenocarcinoma of the rectum. Chemotherapy treatment was considered for the patient, which was not administered due to the rapid deterioration of the patient leading to his death.


Assuntos
Adenocarcinoma Mucinoso/secundário , Neoplasias Retais/patologia , Neoplasias Cutâneas/secundário , Humanos , Masculino , Pessoa de Meia-Idade
12.
Nutr Hosp ; 27(4): 1204-12, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-23165563

RESUMO

BACKGROUND: Consumption of green tea, by its antioxidant properties, has been associated with beneficial health effects, because antioxidant may play a role in the risk and pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. On the other hand, it has been reported that metal compounds such as chromium [VI] are carcinogenic and can induce genotoxic damage through the Oxidative Stress. Therefore, it is possible that green tea has a protective effect against the genotoxic damage induced by this compounds. OBJECTIVE: To evaluate the effect of oral administration of green tea over the genotoxic damage induced by Cr [VI] by quantification of micronucleus (MN) in polychromatic erythrocytes (EPC). MATERIALS AND METHODS: We use mice of CD-1 strain that were randomly divided into the following groups: (i) control, (ii) treatment with green tea, (iii) treatment with chromium trioxide, (iv) treatment with green tea and chromium trioxide. The green tea was administrated via intragastric tube every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml) and ad libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml), while chromium trioxide was administrated via intraperitoneal (20 mg/kg). Blood samples were obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48 and 72 hours after the treatments. RESULTS: The group treated with green tea showed no significant statistical changes in the average of MN. On the other hand, the group that was dosed with the chromium trioxide showed an increase between 4 and 8 MN, which was statistically significant when compared with control group, which confirmed the genotoxic damage. When the green tea treatment was administered before the application of chromium trioxide, there was a decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and 18 and 31% at 24 hours with intragastric and ad libitum respectively, compared with the group treated only with chromium trioxide. Hence, green tea reduced the genotoxic damage induced by chromium trioxide, and the highest protection was presented at 72 hours. CONCLUSIONS: Our findings support the protective effects of green tea against the damage of genetic material, induced by metal compounds such as chromium [VI], suggesting that its antioxidant compounds are those that have a chemopreventive effect on the EOX generated by the Cr [VI] during its reduction to Cr (III). The fact that the largest decrease in the frequency of MN was observed at 72 hours and ad libitum treatment, suggests that, the protective effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of the active ingredient in green tea, so the administration of green tea for a long period of time before the exposure to Cr [VI] could have a more consistent preventive effect.


Assuntos
Antimutagênicos , Carcinógenos/toxicidade , Compostos de Cromo/toxicidade , Chá , Animais , Quimioprevenção , Feminino , Masculino , Camundongos , Testes para Micronúcleos , Mutagênese/efeitos dos fármacos
13.
Eur J Surg Oncol ; 38(10): 955-61, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22819147

RESUMO

PURPOSE: To evaluate the feasibility and long-term outcome of surgery combined with intraoperative electron radiotherapy (IOERT) as rescue treatment in patients with recurrent and/or metastatic oligotopic extrapelvic cancer. METHODS AND MATERIALS: From April 1996 to April 2010, we treated 28 patients using 34 IOERT procedures. The main histopathology findings were adenocarcinoma (39%) and squamous cell carcinoma (29%). The original cancer sites were gynecologic (67%), urologic (14%) and colorectal (14%). The location of recurrence was the para-aortic region in 53.5% of patients. RESULTS: Median follow-up was 39 months (1-84 months), during which time 14% of patients experienced local recurrence and 53.5% developed distant metastasis. Overall survival at 2 and 5 years was 57% and 35% respectively. At the time of the analysis, 13 patients were alive, 6 for more than 55 months of follow-up. Local control was not significantly affected by the following histopathologic characteristics of the resected surgical specimen: number of fragments submitted for pathology study (1 to >6), maximal tumor dimension (≤ 2 to ≥ 6 cm), rate of involved nodes (0-100%) and involved resection margin (local recurrence 23% vs 7%; p = 0.21). Local recurrence was significantly affected by microscopic cancer in more than 50% of specimen fragments (38% vs 9%, p = 0.02). CONCLUSIONS: IOERT for recurrence of oligotopic extrapelvic cancer increased long-term survival in patients with controlled cancer and appears to compensate for some adverse prognostic features in local control. Individualized treatment strategies for this heterogeneous category of patients with recurrent cancer will make it possible to optimize results.


Assuntos
Cuidados Intraoperatórios/métodos , Linfonodos/patologia , Metástase Neoplásica/radioterapia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Elétrons/uso terapêutico , Estudos de Viabilidade , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/mortalidade , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/terapia , Humanos , Período Intraoperatório , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pelve , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Espanha , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia
14.
Nutr Hosp ; 27(6): 1908-15, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23588438

RESUMO

BACKGROUND & AIMS: The pathogenesis of enteritis after abdominal radiotherapy is unknown, although changes in faecal microbiota may be involved. In several studies, Lactobacillus and Bifidobacterium have proven beneficial for the host. Prebiotics stimulate the proliferation of Lactobacillus and Bifidobacterium, and this may have positive effects on the intestinal mucosa during abdominal radiotherapy. METHODS: We performed a randomised double-blind, placebo-controlled trial including 31 patients with gynaecological cancer who received radiotherapy (29 sessions, 52.2 Gy) after surgery. Patients were randomised to two groups: prebiotic and placebo. The first group received a mixture of fibre (50% inulin and 50% fructo-oligosaccharide) and the second received 6 g of maltodextrin twice daily from one week before to three weeks after radiotherapy. Lactobacillus and Bifidobacterium counts were determined in faeces samples (day -7 before radiotherapy, day 15 of radiotherapy, at the end of treatment, and three weeks after radiotherapy) by culture in selective media and fluorescent in situ hybridization (FISH) using genus-specific probes. Bacterial counts by FISH were significantly higher than by culture method. RESULTS: There were no differences in baseline microbiota between groups. At the end of radiotherapy, we observed a statistically significant decrease in Lactobacillus and Bifidobacterium counts in both groups. By cultural analysis, we observed higher numbers of Lactobacillus and Bifidobacterium three weeks after radiotherapy in the prebiotic group (5.6 vs. 6.3, p = 0.04 and 5.5 vs. 6 log cfu/g, p = 0.03). CONCLUSIONS: Abdominal radiotherapy negatively affects Lactobacillus and Bifidobacterium counts. The prebiotic mixture of inulin and fructoligosaccharide can improve the recovery of both genera after radiotherapy. Registered under ClinicalTrials.gov Identifier no. NCT01549782.


Assuntos
Bifidobacterium/efeitos dos fármacos , Fibras na Dieta , Intestinos/microbiologia , Inulina/farmacologia , Lactobacillus/efeitos dos fármacos , Oligossacarídeos/farmacologia , Radioterapia/efeitos adversos , Adulto , Idoso , Carga Bacteriana , Método Duplo-Cego , Feminino , Frutose/farmacologia , Neoplasias dos Genitais Femininos/microbiologia , Neoplasias dos Genitais Femininos/radioterapia , Humanos , Inflamação/microbiologia , Intestinos/efeitos dos fármacos , Pessoa de Meia-Idade
15.
Bioresour Technol ; 99(9): 3850-4, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17904362

RESUMO

The survival of several genera of fungi was determined in the ensiled solid fraction of swine faeces after 0, 7, 14, 28 and 56 days of ensiling. The experiment had two treatments, un-ensiled and ensiled manure, in a split-plot design. The manure was distributed into 50 containers; samples, taken at the specified times, were cultured in agar potato dextrose medium, incubated, and colony forming units (CFU/g) were counted and log-transformed. The ensiling process decreased the number of CFU after 56 days. Five fungal genera were identified (Absidia spp., Aspergillus spp., Penicillium spp., Rhizopus spp. and non-fructiferous fungi), and their vulnerability to the ensiling conditions varied, although most of them slowed their growth or disappeared after 14 days of ensiling.


Assuntos
Fezes/microbiologia , Fungos/citologia , Viabilidade Microbiana , Suínos/microbiologia , Animais , Contagem de Colônia Microbiana , Concentração de Íons de Hidrogênio , Esterco , Temperatura
16.
Rev. esp. quimioter ; 20(1): 44-50, mar. 2007. ilus, tab
Artigo em Es | IBECS | ID: ibc-056675

RESUMO

El objetivo de nuestro estudio fue analizar el consumo de antibióticos en la provincia de Ávila y en sus diferentes Zonas Básicas de Salud (ZBS) durante el año 2005. Se trata de un estudio observacional retrospectivo, referido al consumo de antibióticos sistémicos (grupo J01 de la ATC), utilizando la información del programa Concylia de la Junta de Castilla y León. El consumo se ha referido en número de dosis diarias definidas por mil habitantes, ajustado en relación a la aportación económica del usuario en el momento de adquirir el medicamento (DHDAj). Como población de referencia se utilizó la incluida en la base de la tarjeta sanitaria en 2005, año en que se consumieron en la provincia de Ávila 26,91 DHDAj de antibióticos sistémicos, con importantes diferencias entre el medio rural (36,63) y el urbano (15,44), y una gran variabilidad entre las diferentes ZBS. Las ZBS con menor número de habitantes por núcleo de población y por médico consumen más antibióticos, lo que puede estar en relación con enfermedades más graves, ausencia de autoconsumo o falta de medios diagnósticos, entre otros factores. No hay relación entre mayor consumo y mayor presión asistencial. Se concluye que el consumo de antibióticos en la provincia de Ávila es alto, a expensas del consumo en el medio rural, y que existe una elevada variabilidad entre las diferentes ZBS relacionada con el menor número de habitantes por núcleo de población y por médico, y sin relación con la presión asistencial


This study analyzed the consumption of systemic antibiotics in the province of Avila, Spain, and its Basic Health Areas (ZBS) during 2005. It was a retrospective observational study of the consumption of systemic antibiotics (ATC class J01) during 2005 using the data collected by the Concylia program. The study population was identified from the 2005 Medical Card Register database. Consumption data was expressed in defined daily doses (DDD) per 1,000 inhabitants per day (DID), calculated in relation to the contribution of the user at the time of acquiring the prescription. It was found that antibiotic consumption in the province of Avila in 2005 was 26.91 DHDAj. There was a considerable difference between rural (36.63) and urban areas (15.44) with a large variability among the different Basic Health Areas. The areas with a smaller number of inhabitants per town or city and per doctor, used more antibiotics, which could be due to more severe pathology, absence of self-medication or lack of diagnostic resources, among other factors. There is no relation between greater consumption and workload. It was concluded that the consumption of antibiotics in the province of Avila is high due to their use in rural areas. A high variability in the consumption of antibiotics was observed between the different areas, which was related to the smaller number of inhabitants per city or town and per doctor, but had no relation to workload


Assuntos
Humanos , Prescrições de Medicamentos/estatística & dados numéricos , Antibacterianos/uso terapêutico , Farmacoepidemiologia/tendências , Uso de Medicamentos/estatística & dados numéricos , Doenças Transmissíveis/tratamento farmacológico
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