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61.
A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo
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VMC Quent AV Taubenberger JC Reichert LC Martine JA Clements DW Hutmacher D Loessner 《Journal of tissue engineering and regenerative medicine》2018,12(2):494-504
Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients. 相似文献
62.
James R Bell Antonia JA Raaijmakers Johannes V Janssens Lea MD Delbridge 《Clinical and experimental pharmacology & physiology》2015,42(12):1327-1332
Control of cardiomyocyte cytosolic Ca2+ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca2+, Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca2+ channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca2+ levels promote the binding of a Ca2+/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca2+ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδB in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδC. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδB, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca2+ uptake and maintain cytosolic Ca2+ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart. 相似文献
63.
Acute myocardial infarction after simultaneous thrombosis in normal right and left coronary arteries
A 32-year-old male patient with clinical and electrocardiographic evidence of acute myocardial infarction underwent coronary angiographic study. We observed nonocclusive thrombosis simultaneously in right and left anterior descending coronary arteries, without confirmation of spasm or obstructive artery disease in other coronary branches. Documentation of coronary thrombosis in more than one artery is rare, and its pathophysiology is still unknown. With the advent of thrombolytic therapy and immediate coronary angiographic studies in patients with evolving myocardial infarction, it has been possible to confirm the presence of thrombus and the type of coronary disease. In this case, we observed total lysis of both thrombi and the final aspect of "normal" angiographically reperfused coronary arteries. 相似文献
64.
A M Caixeta F S Brito M Rati M A Perin P L da Luz J A Ramires J A Ambrose E E Martinez 《Catheterization and cardiovascular interventions》2000,50(4):398-401
We compared the impact of low and high-pressure balloon inflation on acute and late angiographic results of Multilink stent. Low-pressure balloon inflation (9.5 +/- 1.9 atm) was used in 43 stents and high pressure (17.1 +/- 1.5 atm) in 44. A larger immediate luminal gain was achieved in stents with high-pressure balloon inflation (1.80 +/- 0.26 vs. 1.47 +/- 0.62; P = 0.002), resulting in a larger mean diameter in this group (2.71 +/- 0.37 vs. 2.48 +/- 0.47; P = 0.017). At follow-up, a larger luminal diameter was achieved in the high pressure group (1.93 +/- 0.72 vs. 1.45 +/- 0.66; P = 0.002) and a trend to a lower rate of angiographic restenosis (15% vs. 38%, P = 0.08). 相似文献
65.
Sposito AC Santos RD Hueb W Ventura LI Vinagre CC Ramires JA Maranhão RC 《Atherosclerosis》2002,161(2):447-453
In animal model studies, the uptake of chylomicron remnants after entering in the space of Disse occurs mainly by low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP). In subjects, the relative importance of each one of these receptors for the clearance of chylomicron remnants is not fully understood. In our study, LDL cholesterol and apolipoprotein (apo) B were correlated to the plasma kinetics of a chylomicron-like emulsion in 77 subjects (11 women, mean age 58 +/- 12 years) with coronary artery disease (CAD). Their total cholesterol was 227 +/- 25 mg/dl, triglyceride 159 +/- 25 mg/dl, LDL cholesterol 148 +/- 27 mg/dl, HDL cholesterol 40 +/- 9 mg/dl, apo A1 1.80 +/- 0.53 g/l and apo B 1.65 +/- 0.48 g/l. The emulsion was double-labeled with 3H-triolein and 14C-cholesteryl oleate and injected intravenously after 12-h fasting. The decay curves of the radioisotopes were determined from blood samples collected at predetermined intervals during 60 min. A negative correlation between FCR of the emulsion cholesterol esters and LDL cholesterol and apo B plasma concentrations was found (r=-0.4, P=0.005 and r=-0.3, P=0.01, respectively) whereas FCR of the emulsion triglycerides did not correlate with any of the plasma lipids or apolipoprotein parameters. Concluding, in patients with CAD, LDL catabolic pathway significantly influences the removal from plasma of chylomicron remnants. 相似文献
66.
Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging. 总被引:3,自引:0,他引:3
Jo?o C Silva Carlos E Rochitte José S Júnior Jeanne Tsutsui Joalbo Andrade Eulógio E Martinez Paulo J Moffa José C Menegheti Roberto Kalil-Filho José F Ramires José C Nicolau 《European heart journal》2005,26(1):36-43
AIMS: To assess the recanalization effects of post-myocardial infarction (MI) on left ventricular (LV) remodelling and contractility in relation to conservative therapy. METHODS AND RESULTS: Thirty-six patients with occluded infarct-related artery between 12 h and 14 days post-anterior MI were randomized to percutaneous coronary intervention (PCI group) or conservative therapy (no-PCI group). Magnetic resonance imaging was performed at enrollment and after 6 months. The left ventricle was divided into infarct, adjacent, and remote segments. There was no difference in relation to LV volume between groups at the 6 month follow-up. Change in LV ejection fraction was favourable to the PCI group: 5.00% vs. -0.76%, P=0.012. Change in circumferential shortening (Ecc) of the remote segments in the PCI group was significantly better than in the no-PCI group: -1.67+/-6.30% vs. 0.29+/-6.02%, P<0.001. Infarct size and LV mass were similar between groups. CONCLUSIONS: Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up, but did not change the ventricular volumes. Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infarct-related artery. 相似文献
67.
Mannucci PM; Lombardi R; Castaman G; Dent JA; Lattuada A; Rodeghiero F; Zimmerman TS 《Blood》1988,71(1):65-70
When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure. 相似文献
68.
Alves PM de Freitas EJ Mathias HA da Motta AE Silva Rde C Müller M Almeida SF Stapleton E Timerman S Ramires JA 《Arquivos brasileiros de cardiologia》2001,76(4):310-314
After the incorporation of automated external defibrillators by other airlines and the support of the Brazilian Society of Cardiology, Varig Airlines began the onboard defibrillation program with the initial purpose of equipping wide-body aircrafts frequently used in international flights and that airplanes use in the Rio - S?o Paulo route. With all flight attendants trained, the automated external defibrillation devices were incorporated to 34 airplanes of a total fleet of 80 aircrafts. The devices were installed in the baggage compartments secured with velcro straps and 2 pairs of electrodes, one or which pre-connected to the device to minimize application time. Later, a portable monitor was address to the resuscitation kit in the long flights. The expansion of the knowledge of the basic life support fundamentors and the corrected implantation of the survival chain and of the automated external defibrillators will increase the extense of recovery of cardiorespiratory arrest victims in aircrafts. 相似文献
69.
Nemandra Sandiford SK Muirhead-Allwood JA Skinner 《Indian Journal of Orthopaedics》2015,49(6):595-601
Background:
Hip resurfacing arthroplasty (HRA) is primarily indicated for young, active patients with disabling coxarthrosis who wish to remain active and return to sports after surgery. Relatively few prospective studies have assessed return to sporting activity and impact of gender and age on this.Materials and Methods:
Seventy-nine consecutive patients treated with HRA were included. Patients were reviewed clinically and radiologically. Function was assessed using the modified University of California Los Angeles (UCLA) activity score. The Oxford, Harris and WOMAC hip scores were calculated.Results:
Average age at the time of surgery was 54.9 years (range 34.5–73.6 years). Average preoperative and postoperative UCLA scores were 4 and 7.6 respectively. Patients were involved in 2 (0–4) sporting activities preoperatively and 2 (0–5) postoperatively. Preoperative and postoperative Oxford Hip Scores, Harris Hip Score and WOMAC scores were 40, 46 and 51 and 16, 94 and 3 respectively (P < 0.0001). Patients returned to sports at an average of 3 months postoperatively.Conclusion:
Patients were able to return to sports by 3 months and perform the same number of activities at preoperative intensity. Activity levels are maintained up to the medium term with few complications. 相似文献70.
EH Gemmill DJ Humes JA Catton 《Annals of the Royal College of Surgeons of England》2015,97(3):173-179