RESUMEN
BACKGROUND: Recently, the use of short tibial stems in the obese population undergoing total knee arthroplasty (TKA) has been proposed. Thus, we designed a study to assess tibial component survivorship after primary TKA using a single implant both with and without a fully cemented stem extension performed by a single surgeon. METHODS: A search of our institutional research database was performed. A minimum 2-year follow-up was selected. Cohorts were created according to patient body mass index (BMI; >40 kg/m2 and <40 kg/m2) and the presence (stemmed tibia [ST]) or absence (non-stemmed tibia [NST]) of a short tibial stem extension. Kaplan-Meier survival analyses for aseptic loosening and log-rank tests were performed. RESULTS: A total of 236 patients were identified (ST = 162, NST = 74). Baseline patient characteristics were statistically similar between cohorts with the exception of BMI which was greater in the ST cohort (32.9 kg/m2, 30.6 kg/m2; P = .01). Kaplan-Meier survival analysis at 5 years was superior for the BMI < 40 kg/m2 cohort (98.9%, 93.1%; P = .045), the ST cohort (100%, 94.5%; P = .006), and the BMI > 40 kg/m2 with ST cohort at 4 years (71.4%, 100%; P = .008). CONCLUSION: Morbid obesity and a short native tibial stem design appear to be associated with aseptic loosening in primary TKA. This appears to be mitigated through the use of an ST. As such, the use of ST may be considered in at-risk patients. Alternatively, implants with longer native stem designs can be employed. Modern short-stemmed tibial components may need to be redesigned.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Humanos , Articulación de la Rodilla/cirugía , Diseño de Prótesis , Falla de Prótesis , Tibia/cirugíaRESUMEN
We have previously demonstrated that protein kinase CK2 is a potent suppressor of apoptosis in cells subjected to diverse mediators of apoptosis. The process of apoptosis involves a complex series of molecules localized in various cellular compartments. Among the various proteins that modulate apoptotic activity are inhibitors of apoptosis proteins (IAPs) which are elevated in cancers and have been proposed to block caspase activity. We have examined the impact of CK2 signal on these proteins in prostate cancer cells. Cellular IAPs demonstrate distinct localization and responsiveness to altered CK2 expression or activity in the cytoplasmic and nuclear matrix fractions. Modulation of cellular CK2 by various approaches impacts on cellular IAPs such that inhibition or downregulation of CK2 results in reduction in these proteins. Further, IAPs are also reduced when cells are treated with sub-optimal concentrations of chemical inhibitors of CK2 combined with low or sub-optimal levels of apoptosis-inducing agents (such as etoposide) suggesting that downregulation of CK2 sensitizes cells to induction of apoptosis which may be related to attenuation of IAPs. Decreased IAP protein levels in response to apoptotic agents such as TNFalpha or TRAIL were potently blocked upon forced overexpression of CK2 in cells. Together, our results suggest that one of the modes of CK2-mediated modulation of apoptotic activity is via its impact on cellular IAPs.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Quinasa de la Caseína II/metabolismo , Neoplasias de la Próstata/enzimología , Apigenina/farmacología , Apoptosis/efectos de los fármacos , Quinasa de la Caseína II/antagonistas & inhibidores , Caspasas/metabolismo , Línea Celular Tumoral , Humanos , Masculino , Neoplasias de la Próstata/patología , Inhibidores de Proteínas Quinasas/farmacología , Fracciones Subcelulares/metabolismo , Triazoles/farmacologíaRESUMEN
Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.
Asunto(s)
Extremidades/irrigación sanguínea , Isquemia/terapia , Células Madre Multipotentes/trasplante , Animales , Vasos Sanguíneos/citología , Trasplante de Médula Ósea , Diferenciación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Células Madre Multipotentes/citología , Células Musculares/citologíaRESUMEN
Resveratrol and epigallocatechin-3-gallate (EGCG) are important candidates as chemopreventive agents by virtue of their ability to induce apoptosis in cancer cells. Casein kinase 2 (CK2) is a ubiquitous protein ser/thr kinase that plays diverse roles in cell proliferation and apoptosis. We have previously shown that overexpression of CK2 suppresses apoptosis induced by a variety of agents, whereas down-regulation of CK2 sensitizes cells to induction of apoptosis. We therefore investigated whether or not CK2 played a role in resveratrol and EGCG signaling in androgen-sensitive (ALVA-41) and androgen-insensitive (PC-3) prostate cancer cells. Resveratrol- and EGCG-induced apoptosis is associated with a significant down-regulation of CK2 activity and protein expression in both the ALVA-41 and PC-3 cells. Overexpression of CK2alpha protected prostatic cancer cells against resveratrol- and EGCG-induced apoptosis. Relatively low doses (10 mumol/L) of resveratrol and EGCG induced a modest proliferative response in cancer cells that could be switched to cell death by moderate inhibition of CK2. These findings characterize, for the first time, the effects of polyphenolic compounds on CK2 signaling in androgen-sensitive and androgen-insensitive prostatic carcinoma cells and suggest that resveratrol and EGCG may mediate their cellular activity, at least in part, via their targeting of CK2. Further, the data hint at the potential of using these polyphenols alongside CK2 inhibitors in combination chemotherapy.