RESUMO
BACKGROUND/AIMS: Phosphate homeostasis is controlled by the renal reabsorption of Pi by the type IIa sodium phosphate cotransporter, Npt2a, which is localized in the proximal tubule brush border membrane. Regulation of Npt2a expression is a key control point to maintain phosphate homeostasis with most studies focused on regulating protein levels in the brush border membrane. Molecular mechanisms that control Npt2a mRNA, however, remain to be defined. We have reported that Npt2a mRNA and protein levels correlate directly with the expression of the Na+/H+ exchanger regulatory factor 1 (NHERF-1) using opossum kidney (OK) cells and the NHERF-1-deficient OK-H cells. The goal of this study was to determine whether NHERF-1 contributes to transcriptional and/or post-transcriptional mechanisms controlling Npt2a mRNA levels. METHODS: Npt2a mRNA half-life was compared between OK and NHERF-1 deficient OK-H cell lines. oNpt2a promoter-reporter gene assays and electrophoretic mobility shift assays (EMSA) were used identify a NHERF-1 responsive region within the oNpt2a proximal promoter. RESULTS: Npt2a mRNA half-life is the same in OK and OK-H cells. The NHERF-1 responsive region lies within the proximal promoter in a region that contains a highly conserved CAATT box and G-rich element. Specific protein-DNA complex formation with the CAATT element is altered by the absence of NHERF-1 (OK v OK-H EMSA) although NHERF-1 does not directly contribute to complex formation. CONCLUSION: NHERF-1 helps maintain steady-state Npt2a mRNA levels in OK cells through indirect mechanisms that help promote protein-DNA interactions at the Npt2a proximal promoter.
Assuntos
DNA/genética , Fosfoproteínas/genética , Regiões Promotoras Genéticas/genética , Trocadores de Sódio-Hidrogênio/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética , Animais , Sequência de Bases , Sítios de Ligação/genética , Linhagem Celular , DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Gambás , Fosfatos/metabolismo , Fosfatos/farmacologia , Fosfoproteínas/metabolismo , Ligação Proteica , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trocadores de Sódio-Hidrogênio/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismoRESUMO
Carotid blowout syndrome is a life-threatening complication for patients with head and neck cancer. Temporizing stent graft procedures improve short-term survival and can be the definitive treatment for various reasons, including a poor oncologic prognosis, unsuitability for definitive reconstruction, or a lack of operative options. A second carotid blowout will often be fatal. Preventing such events requires multidisciplinary strategic planning because of a hostile reoperative field. We have described a case of a 44-year-old man with a history of laryngeal cancer who had experienced a carotid blowout. Treated with a stent graft, the patient had experienced a second event 6 weeks later. Treatment involved excision and suture ligation with rotational muscle flap coverage.
RESUMO
BACKGROUND AND OBJECTIVE: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. METHODS AND RESULTS: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); n = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; n = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (n = 5/group) or fludrocortisone (n = 15/group) into male ApoE -/- mice fed a normal laboratory diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR -/- mice fed Western diet reached statistical significance, compared to their vehicle. CONCLUSION: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies.
Assuntos
Angiotensina II , Aorta Abdominal , Fludrocortisona , Angiotensina II/farmacologia , Animais , Aorta Abdominal/patologia , Dimetil Sulfóxido , Modelos Animais de Doenças , Fludrocortisona/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Receptores de LDLRESUMO
We present a patient with the initial misdiagnosis of a metallic foreign body in the abdominal aorta. Computed tomographic angiography utilizing microanatomical reconstruction technique revealed the structure to instead be a partially calcified abdominal aortic congenital fibrous band. Most congenital fibrous bands spanning the aortic lumen are proximal within the aorta and are thought to be supportive structures of the aortic valve leaflets. Congenital fibrous bands distal to the sinotubular junction are quite rare.