RESUMO
Docosahexaenoic acid (DHA) is a ω-3 fatty acid typically obtained from the diet or endogenously synthesized through the action of elongases (ELOVLs) and desaturases. DHA is a key central nervous system constituent and the precursor of several molecules that regulate the resolution of inflammation. In the present study, we questioned whether the impaired synthesis of DHA affected neural plasticity and inflammatory status in the adult brain. To address this question, we investigated neural and inflammatory markers from mice deficient for ELOVL2 (Elovl2-/- ), the key enzyme in DHA synthesis. From our findings, Elovl2-/- mice showed an altered expression of markers involved in synaptic plasticity, learning, and memory formation such as Egr-1, Arc1, and BDNF specifically in the cerebral cortex, impacting behavioral functions only marginally. In parallel, we also found that DHA-deficient mice were characterized by an increased expression of pro-inflammatory molecules, namely TNF, IL-1ß, iNOS, caspase-1 as well as the activation and morphologic changes of microglia in the absence of any brain injury or disease. Reintroducing DHA in the diet of Elovl2-/- mice reversed such alterations in brain plasticity and inflammation. Hence, impairment of systemic DHA synthesis can modify the brain inflammatory and neural plasticity status, supporting the view that DHA is an essential fatty acid with an important role in keeping inflammation within its physiologic boundary and in shaping neuronal functions in the central nervous system.
Assuntos
Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/biossíntese , Regulação da Expressão Gênica , Microglia/metabolismo , Plasticidade Neuronal , Animais , Biomarcadores/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Caspase 1/biossíntese , Caspase 1/genética , Ácidos Docosa-Hexaenoicos/genética , Proteína 1 de Resposta de Crescimento Precoce/biossíntese , Proteína 1 de Resposta de Crescimento Precoce/genética , Elongases de Ácidos Graxos/deficiência , Elongases de Ácidos Graxos/metabolismo , Inflamação/genética , Inflamação/metabolismo , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Camundongos , Camundongos Knockout , Microglia/patologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
In breast cancer 1 (BRCA) gene mutation carriers, mastectomy is still the mainstay of treatment for breast cancers due to the increased risk of local recurrence. It is performed as a therapeutic, as well as prophylactic procedure. However, mastectomy with removal of nipple areolar complex (NAC) is associated with adverse cosmetic outcome. NAC sparing mastectomy (NSM), which results in better cosmetic outcome, has been performed in non-BRCA mutation carriers. While studies have shown that NSM is a oncologically safe in sporadic breast cancers, its application in BRCA mutation carriers is still controversial. Here we review the existing evidence of NSM and its application in BRCA mutation carriers.
Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/cirurgia , Mastectomia Subcutânea/métodos , Recidiva Local de Neoplasia/prevenção & controle , Mamilos/cirurgia , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Heterozigoto , Humanos , Mamoplastia , Mutação , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Mamilos/irrigação sanguínea , Mamilos/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
PURPOSE: This study aims to compare the efficacy and safety of bipolar endoscopic enucleation of prostate with transurethral resection in saline for large BPE greater than 70 g. METHODS: All patients from two urology centres who had bipolar enucleation or bipolar resection performed for large BPE greater than 70 g from December 2008 to April 2012 were prospectively assessed. The pre-operative and post-operative measures included IPSS, QOL score, uroflowmetry results, PSA and prostate volume. The perioperative measures were compared, and the post-operative complications/resumption of medical treatment for lower urinary tract symptoms were also assessed. RESULTS: There were 74 and 86 consecutive patients with bipolar enucleation and bipolar resection performed, respectively. No difference in pre-operative characteristics was observed between the two groups with mean prostate size 115 cc in each group. Comparing bipolar enucleation with bipolar resection, there was longer operative time (156 vs 87 min, p = 0.000), more haemoglobin drop (1.8 vs 1.1 g/dL, p = 0.006), but more prostate tissue resected (61.4 vs 45.7 g, p = 0.000). There was no difference in overall transfusion requirement and hospital stay. At 12 month after the procedure, patients with bipolar enucleation performed had better IPSS (6.4 vs 11.6, p = 0.032), QOL (1.7 vs 2.6, p = 0.040) and peak flow rate (19.5 vs 15.1 ml/s, p = 0.019). The post-operative complications had no significant difference between the two groups. CONCLUSIONS: For surgical treatment of big BPE, bipolar endoscopic enucleation of prostate provided superior functional outcome than bipolar resection but required longer operative time.