Surface Reformation of Medical Devices with DLC Coating

We evaluated the adhesion, friction characteristics, durability against bodily acids, sterilization, cleaning, and anti-reflection performance of diamond-like carbon (DLC) coatings formed as a surface treatment of intracorporeal medical devices. The major coefficients of friction during intubation in a living body in all environments were lower with DLC coatings than with black chrome plating. DLC demonstrated an adhesion of approximately 24 N, which is eight times stronger than that of black chrome plating. DLC-coated samples also showed significant stability without being damaged during acid immersion and high-pressure steam sterilization, as suggested by the results of durability tests. In addition, the coatings remained unpeeled in a usage environment, and there was no change in the anti-reflection performance of the DLC coatings. In summary, DLC coatings are useful for improving intracorporeal device surfaces and extending the lives of medical devices.     

Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients

AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis. METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV) infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade Fl-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed: normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios. RESULTS: In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC. CONCLUSION: We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.     

Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells

BACKGROUND: and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation. METHODS: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry. RESULTS: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related. CONCLUSIONS: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.     

Cryopreservation of mobilized blood stem cells at a higher cell concentration without the use of a programmed freezer

Cryopreservation of peripheral blood stem cells (PBSC) mobilized by chemotherapy combined with or without granulocyte colony-stimulating factor (G-CSF) is an essential part of procedure for anti-cancer strategies. We evaluated whether a higher cell concentration (2×10⁸/ml) without the use of a programmed freezer was acceptable for the storage of mobilized PBSC in an autologous setting. Mobilized PBSC were enriched to mononuclear cells (MNC) by Percoll separation and then frozen at cell concentrations of 2–5×10⁷/ml (group I, n=20) or 2×10⁸/ml (group II, n=44) without the use of a programmed freezer using 5% DMSO, 6% hydroxy ethyl starch, and 4% autologous serum or human albumin. CD34+ cells purified by ISOLEX300 were frozen at 2×10⁷/ml (group III, n=22) using the same method. The median recovery rates of CD34+ cells and CFU-GM were, respectively, n.d. (not determined) and 88% in group I, 103 and 64% in group II, and 98 and 53% in group III. There was a statistical significance between the recovery rate of CFU-GM in group III and that in group I (p=0.02). The median percentage of cell viability after thawing in each group was 89, 87, and 75%, respectively. The median numbers of days after PBSCT to achieve a WBC of >1.0×10⁹/l, an absolute neutrophil count of >0.5×10⁹/l, and a platelet count of >50×10⁹/l were, respectively, 11, 11 and 15 in group I; 12, 12 and 16 in group II; and 12, 12 and 27 in group III. These results suggest that enriched MNC from mobilized PBSC could be frozen at a higher cell concentration (2×10⁸/ml) without the use of a programmed freezer, leading to reduction of the toxicities associated with infusion of thawed cells and of costly space required for cell storage.     

Impact of renal insufficiency on clinical and angiographic outcomes following percutaneous coronary intervention with sirolimus-eluting stents.

BACKGROUND: Sirolimus-eluting stents (SES) have been demonstrated to reduce restenosis. However, there have been few studies evaluating the impact of renal insufficiency on the angiographic as well as clinical outcomes after SES implantation. METHODS: This study was composed of 304 consecutive patients having 361 lesions who underwent percutaneous coronary intervention with SES. The patients were divided into 3 groups according to renal function (group 1 [n = 204]; creatinine clearance (Ccr) > or = 60 ml/min, group 2 [n = 69]; Ccr < 60 ml/min, group 3 [n = 31]; hemodialysis). Clinical and angiographic follow-up were evaluated at 8 months. RESULTS: Clinical follow-up was obtained in all patients and angiographic follow-up was obtained in 283 patients (93.1%). Patients in group 3 showed a higher incidence of previous coronary artery bypass graft surgery, and there were more female gender, hypertensive, and less hyperlipidemia in this group. Late lumen loss at 8 months was significantly different among the 3 groups (group 1; 0.16 +/- 0.46 mm, group 2; 0.44 +/- 0.62 mm, group 3; 0.81 +/- 0.88 mm, P < 0.0001). Major adverse cardiac events (MACE) were documented in 22 patients (10.8%) in group 1, 13 patients (18.8%) in group 2, and 12 patients (38.7%) in group 3, respectively (P = 0.0002). CONCLUSION: Neointimal growth following SES implantation is more pronounced in patients with renal insufficiency, especially those undergoing dialysis, compared with patients with normal renal function. Regardless of the beneficial effect of SES, the increased risk of MACE mainly due to high incidence of target vessel revascularization in the subgroup of patients with renal insufficiency should be taken into account.     

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes

BACKGROUND: Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. RESULTS: Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. CONCLUSION: The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.     

Extended resection of T4 lung cancer with invasion of the aorta: is it justified?

BACKGROUND: We report our 10-year experience of performing surgical resection of T4 lung cancer invading the thoracic aorta. PATIENTS AND METHODS: From 1994 to 2004, sixteen patients with T4 primary lung cancer with local invasion of the thoracic aorta underwent tumor resection. Surgical resection included 8 pneumonectomies and 8 lobectomies. The histologic type was squamous cell carcinoma in 7 patients, adenocarcinoma in 7, large cell carcinoma in 1, and small cell carcinoma in 1. Complete resection of the tumor with mediastinal lymph node dissection was achieved in 8 patients (50 %), while the resection was incomplete in the other 8 cases. RESULTS: The overall cumulative survival of the 16 patients at 3 and 5 years was 34.7 % and 17.4 %, respectively. The survival of the patients in the complete resection group was found to be 36.5 % at 5 years, with 2 patients surviving more than 5 years without a recurrence, which was significantly better than that of the incomplete resection group ( p = 0.005). CONCLUSIONS: Extended aortic resection with primary lung cancer is complex and possibly high risk, but can achieve long-term survival in selected patients. Surgical resection should be considered as a treatment option for T4 lung cancer for this T4 subcategory.