ABSTRACT
Maternal malnutrition can alter developmental biology, programming health and disease in offspring. The increase in sugar consumption during the peripubertal period, a worldwide concern, also affects health through adulthood. Studies have shown that maternal exposure to a low protein diet (LPD) is associated with an increase in prostate disease with aging. However, the combined effects of maternal LPD and early postnatal sugar consumption on offspring prostate disorders were not investigated. The effects on aging were evaluated using a maternal gestational model with lactational LPD (6% protein) and sugar consumption (10%) from postnatal day (PND) 21-90, associating the consequences on ventral prostate (VP) rats morphophysiology on PND540. An increase was shown in mast cells and in the VP of the CTR + SUG and Gestational and Lactational Low Protein (GLLP) groups. In GLLP + SUG, a significant increase was shown in TGF-ß1 expression in both the systemic and intra-prostatic forms, and SMAD2/3p had increased. The study identified maternal LPD and sugar consumption as risk factors for prostatic homeostasis in senility, activating the TGFß1-SMAD2/3 pathway, a signaling pathway with potential markers for prostatic disorders.
Subject(s)
Malnutrition , Maternal Nutritional Physiological Phenomena , Prenatal Exposure Delayed Effects , Prostate , Prostatic Diseases , Animals , Male , Female , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Prostatic Diseases/pathology , Prostatic Diseases/etiology , Prostatic Diseases/metabolism , Malnutrition/complications , Prostate/metabolism , Prostate/pathology , Rats , Inflammation/pathology , Inflammation/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Diet, Protein-Restricted/adverse effects , Smad2 Protein/metabolism , Rats, Wistar , Smad3 Protein/metabolism , Smad3 Protein/genetics , Signal Transduction , Animals, Newborn , Mast Cells/metabolismABSTRACT
The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.
Subject(s)
MicroRNAs , Prostatic Neoplasms , Animals , Male , Rats , Gene Expression Profiling , MicroRNAs/genetics , MicroRNAs/metabolism , Prostatic Neoplasms/genetics , Proteomics , TranscriptomeABSTRACT
INTRODUÇÃO: Apesar do sucesso das intervenções por cateter nos defeitos congênitos em geral, a possibilidade de se dispor de um dispositivo percutaneamente implantável e que desapareça sem deixar vestígios é altamente desejável. Neste estudo apresentamos a experiência inicial dos autores com uma nova prótese parcialmente bioabsorvível. Método: Foram selecionados pacientes portadores de forame oval patente (FOP) com pelo menos um evento embólico prévio, sem defeitos associados, passíveis de correção cirúrgica. O diagnóstico foi feito por meio de ecocardiograma transesofágico (ETE) e teste de bolhas. Durante o procedimento as próteses foram escolhidas de acordo com as medidas de comprimento e abertura do FOP, ao ETE. O seguimento foi realizado por meio de avaliação clínica e ecocardiograma transtorácico com um mês e três meses de ETE aos seis meses após o implante. Os pacientes utilizaram a associação de ácido acetilsalicilico e clopidogrel por três meses a ácido acetilsalicilico isolado nos três meses subsequentes. A profilaxia antimicrobiana...
BACKGROUND: Despite the overall high success rate of per-cutaneous intervention in congenital defects, the possibility of having a percutaneous bioabsorbable implantable device is extremely desirable. The initial experience of the authors with a new partially bioabsorbable prosthesis is reported in this study. METHOD: Patients with patent foramen ovale (PFO), with at least one previous embolic event, without additional surgical defects were selected. Diagnosis was made by transesophageal echocardiography (TEE) and the bubble test. Devices were chosen according to length and opening of PFO at the TEE. Patients were followed-up by transthoracic echocardiogram at 1 and 3 months and TEE at 6 months post implantation. Patients received a combination of acetylsalicylic acid and clopidogrel for 3 months and acetylsalicylic acid for another 3 months. Patients were maintained on antimicrobial prophylaxis for infectious endocarditis for 6 months. RESULTS: Nine patients (5 male and 4 female) were treated from February to August 2010. Mean age was 43.4 ± 13.5 years and mean weight was 71.4 ± 16.3 kg. Pulmonary arterial pressure was normal in all of the patients. PFO tunnel lengths ranged from 6-11 mm and the opening ranged from 2-3 mm. Mean range from rest to stretched PFO opening was 2.1 ± 0.8 mm. Prosthesis implantation was possible in all of the cases. Thirteen devices were used in 9 patients, and one of them required a second device for an additional orifice. No major complications or procedure-related deaths were observed. CONCLUSION: The use of the BioSTAR TM device was safe and effective. It is an excellent alternative for PFO closure.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Prostheses and Implants , Cardiac Catheterization/methods , Cardiac Catheterization , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/diagnosis , Echocardiography/methods , Echocardiography , Prospective StudiesABSTRACT
Foi realizada reavaliaçäo clínica e radiológica de 92 pacientes somando um total de 111 casos de artroplastia total do quadril com utilizaçäo da prótese cimentada de Charnley, entre 1975 e 1985, no Serviço de Quadril do Hospital de Tráumato-Ortopedia Dr. Mßrio Jorge, com seguimento mínimo de dez anos. Um total de 60 por cento das próteses cimentadas estäo estáveis, sem sinais clínicos ou radiológicos de soltura. Foram encontradas evidências de afrouxamento nos outros 40 por cento, das quais 64 por cento foram do componente acetabular, 23 por cento do femural e 23 por cento em ambos os componentes. Esse percentual está de acordo com a estatística presente nos artigos de toda a literatura mundial, permanecendo a prótese cimentada de Charnley como uma grande alternativa para as artroplastias totais do quadril.
