RESUMO
Variation on chromosome 9p21 is associated with risk of coronary artery disease (CAD). This genomic region contains the CDKN2A and CDKN2B genes which encode the cell cycle regulators p16(INK4a), p14(ARF) and p15(INK4b) and the ANRIL gene which encodes a non-coding RNA. Vascular smooth muscle cell (VSMC) proliferation plays an important role in the pathogenesis of atherosclerosis which causes CAD. We ascertained whether 9p21 genotype had an influence on CDKN2A/CDKN2B/ANRIL expression levels in VSMCs, VSMC proliferation and VSMC content in atherosclerotic plaques. Immunohistochemical examination showed that VSMCs in atherosclerotic lesions expressed p16(INK4a), p14(ARF) and p15(INK4b). Analyses of primary cultures of VSMCs showed that the 9p21 risk genotype was associated with reduced expression of p16(INK4a), p15(INK4b) and ANRIL (P = 1.2 × 10(-5), 1.4 × 10(-2) and 3.1 × 10(-9)) and with increased VSMC proliferation (P = 1.6 × 10(-2)). Immunohistochemical analyses of atherosclerotic plaques revealed an association of the risk genotype with reduced p15(INK4b) levels in VSMCs (P = 3.7 × 10(-2)) and higher VSMC content (P = 5.6 × 10(-4)) in plaques. The results of this study indicate that the 9p21 variation has an impact on CDKN2A and CDKN2B expression in VSMCs and influences VMSC proliferation, which likely represents an important mechanism for the association between this genetic locus and susceptibility to CAD.
Assuntos
Aterosclerose/genética , Cromossomos Humanos Par 9/genética , Doença da Artéria Coronariana/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Miócitos de Músculo Liso/metabolismo , RNA Longo não Codificante/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Proliferação de Células , Células Cultivadas , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Expressão Gênica , Estudos de Associação Genética , Genótipo , Humanos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/fisiologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , RNA Longo não Codificante/metabolismoRESUMO
AIM: An ageing population is at significant risk of developing of renal cell carcinoma (RCC). We evaluate our units experience in managing RCC in octogenarians using either laparoscopic or open radical nephrectomy, highlighting the postoperative complication rates and survival outcomes. MATERIALS AND METHODS: From June 2001 to June 2008, 65 octogenarians underwent a radical nephrectomy for suspected renal cell carcinoma. The procedure was performed laparoscopically (group 1) in 29 patients (44%) and via an open nephrectomy (group 2) in 36 patients (56%). The presenting age, sex distribution, ASA score, preoperative co-morbidities and indications for nephrectomy were statically comparable in both groups. Postoperative complications were recorded using the Clavien-Dindo classification. RESULTS: Both groups were similar preoperatively with respect to age of presentation, ASA score and co-morbidities such as hypertension, ischemic heart disease, and chronic respiratory disease. Group 1 showed better statistically significant operative parameters (operative time and blood loss), mean length of hospital stay and most importantly postoperative complications. Postoperative complication rates were lower in group 1 (48.3%) when compared with group 2 (80.5%) (p<0.05). CONCLUSION: Surgery for renal cancer in patient over the age of 80 should only be considered after a thorough work up. Chronological age itself should not be the only determining factor. If such a surgery was to be undertaken, then in our experience, patients who underwent laparoscopic radial nephrectomy had fewer complications than those had open radical nephrectomy.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Fatores Etários , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
Several million gastropods are collected each year for the marine ornamental trade to graze on algae detrimental to aquarium species, however, little is known about popular species' suitability to perform this clean-up crew role. Three commonly traded gastropods, Turbo bruneus, Tectus fenestratus, and Tegula eiseni were assessed on their performance. Their survival was quantified as was their movement, and positioning with respect to water level and growth rates were calculated from the start and end weights. Nitrocellulose-coated slides were impregnated with an algal extract and the amount of grazing by each species was also compared. After 53 days final mortality levels of species were significantly different with all T. bruneus individuals surviving, whilst all T. fenestratus individuals apart from two and 35% of the T. eiseni had died by the end of the experiment. T. bruneus grazed significantly more than individuals of T. eiseni, and T. fenestratus. Both T. bruneus and T. eiseni were heavier after one month with T. bruneus gaining significantly more weight than T. eiseni. Greater percentages of algae were grazed by T. bruneus of increasing weight, although this relationship was not found for T. eiseni and T. fenestratus. All three species were generally active and remained within the water for the vast majority of time, although a small, but significant amount of time was spent out of the water for T. eiseni. T. fenestratus were significantly less active than T. bruneus, although the mean activity of T. eiseni was not significantly different from either species. T. bruneus out performs the other two species as a cleaning organism especially in the context of fluctuating water quality, thus highlighting the varying suitability of organisms for this task. Preference in the ornamental trade should be given to T. bruneus over the other topshells, but accurate species identification is critical.