Enhanced osteoconductivity of micro-structured titanium implants (XiVE S CELLplus™) by addition of surface calcium chemistry: a histomorphometric study in the rabbit femur

Objectives: This study evaluated the osseointegration in rabbit cancellous bone of titanium (Ti) implants with a micro-topographically complex surface structure produced by grit-blasting/acid-etching with or without the addition of surface calcium ion (Ca) chemistry.
Material and methods: Micro-structured Ti implants (XiVE S CELLplus^™ screw implant, Dentsply Friadent GmbH) were hydrothermally treated in an alkaline Ca-containing solution to produce a nano-structured Ca-incorporated oxide surface layer. The surface characteristics were evaluated by scanning electron microscopy and stylus profilometry before and after Ca surface treatment. Twenty implants (10 control and 10 experimental) were placed in the femoral condyles of 10 New Zealand White rabbits. Histomorphometric analysis was performed 6 weeks after implantation.
Results: Ca-incorporated and untreated control implants showed similar surface morphologies and surface roughness values at the micron scale. Untreated micro-structured Ti implants achieved a high degree of bone-to-implant contact (BIC), and Ca incorporation further increased BIC% ( P <0.05). Active new bone apposition was found on surfaces of Ca-incorporated implants in areas of loose trabeculae.
Conclusion: The nano-structured Ca-incorporated oxide surface significantly enhanced osteoconductivity of micro-structured Ti implants in rabbit cancellous bone. Results indicate that this surface produced by simple hydrothermal treatment may be effective in improving the osseointegration of implants with micro-topographically complex surface structures in areas of loose cancellous bone.     

Adoptive Transfer of Human Papillomavirus E7-specific CTL Enhances Tumor Chemoresponse Through the Perforin/Granzyme-mediated Pathway

Adoptive cytotoxic T lymphocyte (CTL) therapy has an important implication in treating cancer patients. Here, we investigate whether adoptive transfer of human papillomavirus (HPV) E7-specific CTL can enhance tumor chemoresponse using an established cervical cancer animal model. Cisplatin-based chemotherapy plus CTL therapy showed an improved therapeutic effectiveness, along with antitumor protective responses to a parental tumor cell rechallenge. Cisplatin treatment dose-dependently increased the expression of Fas, intercellular adhesion molecule (ICAM)-1, and major histocompatibility complex (MHC) class I antigens (Ags) on tumor cells in vitro. However, CTL-expressing FasL failed to improve antitumor activity in vitro and in animals, resulting from nonfunctional Fas expressed on tumor cells. In contrast, ethylene glycol tetraacetic acid (EGTA) treatment blocked increased sensitivity of cisplatin-treated tumor cells to CTL-mediated killing in vitro, suggesting an important role of the perforin/granzyme-mediated pathway for improved therapeutic effectiveness. This notion was further confirmed by perforin knockout animal studies. Thus, this study shows that (i) modulation of Ag (Fas, ICAM-1) expression by tumor cells has little effect on their increased sensitivity to CTL-mediated killing, (ii) improved therapeutic effectiveness is mediated mainly through the perforin/granzyme-mediated tumor killing pathway, and (iii) a combination of chemotherapy and adoptive E7-specific CTL transfer augments antitumor therapeutic activity in vivo. This finding may have important implications for treating HPV-associated cervical cancer.     

Exodeviated Ophthalmoplegia in a Patient with Progressive Supranuclear Palsy

We report a patient with progressive supranuclear palsy (PSP) with his serial photographs before the onset of ocular symptoms and after the onset with two year intervals. These photographs show his progressive eyeball deviations toward complete exotropia. There were no effective voluntary eyeball movements, Bell''s phenomenon, doll''s eye movements, and vestibulo-ocular reflexes. These signs indicate the involvement of the oculomotor nuclear complex by the disease. We suggest that PSP may cause not only ''supranuclear'' but also ''nuclear'' complete ophthalmoplegia with exodeviation of the eyes.     

Characteristics and reproducibility of anterior chamber angle assessment by anterior‐segment optical coherence tomography

Purpose: To evaluate the basic characteristics and reproducibility of anterior chamber angle (ACA) measurements determined by anterior‐segment optical coherence tomography (AS‐OCT) in open‐angle and primary angle closure suspect (PACS) patients. Methods: Thirty‐nine open‐angle and 18 PACS patients were imaged for ACA by AS‐OCT. Subjects underwent imaging of the nasal, temporal and inferior ACA under conditions of constant light, and darkness. For analysis, we used three ACA parameters handled by the Visante OCT software: angle opening distance at 500 μm (AOD₅₀₀), trabecular‐iris space area at 500 μm (TISA₅₀₀) and angle recess area at 500 μm (ARA₅₀₀). For determination of inter‐session reproducibility, a single well‐trained operator (D.Y.K.) scanned all patients at two different visits. For determination of inter‐operator variability, a second operator (S.B.P.) acquired another set of images independently. Three sets of images were acquired at least 24 hour apart. Results: All parameters were significantly different when measured both in light and darkness, and in the nasal and temporal quadrants. There were no significant differences between the left and right eyes in the three ACA parameters in all quadrants. The temporal angle was wider than the nasal and inferior angles. All parameters of the nasal, temporal angles had excellent inter‐session and inter‐operator reproducibility [intra‐class correlation coefficient (ICC) 0.796–0.981], but these values were slightly lower for inferior angle measurements (ICC 0.662–0.892) in both open‐angle and PACS groups. Conclusion: AS‐OCT provides quantitative and reproducible assessment of ACA. Reproducibility was lower in the inferior angle compared with the nasal and temporal angles, perhaps because of variable placement of the scleral spur.     

Additive Effect of Vitamin C to Statin in Improving the Endothelial Function in Hypercholesterolemic Patients

Lipid lowering agents and anti-oxidants are known to improve endothelial dysfunction in hypercholesterolemic patients, respectively. The objective of this study is to investigate whether vitamin C has additional benefit on endothelial function of statin-treated hypercholesterolemic patients. The endothelial function was estimated using venous occlusion plethysmography (VOP) in 13 hypercholesterolemic patients and 9 healthy volunteers. The patients in the HC group were treated with the statin, then examined again. The change of the forearm blood flow (FBF) was measured with the acetylcholine infusion through brachial artery and also with intra-arterial vitamin C. Endothelium-dependent vasodilatation was significantly impaired in the HC group compared to the control group (p < 0.01). The FBF increased significantly after statin therapy (8.4 ± 1.3 25.2 ± 3.1 ml/min/100 mg forearm tissue, p < 0.01). Vitamin C infusion in these patients results in additional improvement in FBF (25.2 ± 3.1 31.9 ± 4.9, p < 0.05). Vitamin C seems to have additional benefit on the endothelial function of statin-treated hypercholesterolemic patients.     

Characteristics of cytomegalovirus enterocolitis in patients with or without inflammatory bowel diseases

Objectives: Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients.

Methods: This was a retrospective study of 82 patients with CMV enterocolitis based on the pathologic findings at two tertiary referral hospitals from 2003 to 2013. Clinical and endoscopic characteristics and clinical course were analyzed according to the presence of IBD.

Results: Of the 82 patients, 25 (30.5%) had IBD and 57 (69.5%) did not have IBD. Hematochezia was more common in IBD patients (84.0% vs. 35.1%; p = .001), but fever and positive CMV antigenemia were more common in non-IBD patients (50.9% vs. 12.0%; p = .001; 54.4% vs. 28.0; p = .027). Endoscopic findings showed more ulcer with inflammation in IBD patients (68.0% vs. 35.2%; p = .005). Sixty-four patients were treated with antiviral agents and 12 patients who did not receive antiviral agents recovered spontaneously. All naturally healed patients were in normal immune status.

Conclusions: Hematochezia is more common in IBD patients and fever/CMV antigenemia is more common in patients without IBD. In patients without IBD, the natural resolution of CMV enterocolitis is expected at least in normal immune function.     

Ghrelin increases food intake in obese as well as lean subjects

OBJECTIVE: To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin. DESIGN: Randomised, double-blind, placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/min. SUBJECTS: In all, 12 healthy lean subjects (mean body mass index (BMI) 20.5+/-0.17 kg/m(2)) and 12 healthy overweight and obese subjects (mean BMI 31.9+/-1.02 kg/m(2)). MEASUREMENTS: Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth hormone. RESULTS: Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean increase 36.6+/-9.4%, P<0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1+/-10.6% in the lean and 70.1+/-15.5% in the obese, P<0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese group. CONCLUSION: Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.