Transplantation of viral-positive hepatitis C-positive kidneys into uninfected recipients offers an opportunity to increase organ access

The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R−). Thirty D+/R− patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D−/R−) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R− patients was 100%. The initial median viral load was 531 copies/μL (range: 10-1 × 10⁸ copies/μL) with a median peak viral load of 3.4 × 10⁵ copies/μL (range: 804-1.0 × 10⁸ copies/μL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R− patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R− transplantation offers patients an alternative strategy to increase access.     

Greater Biosynthetic Liver Dysfunction in Primary Sclerosing Cholangitis Suggests Co-existent or Impending Cholangiocarcinoma

Background and Aim: Patients with primary sclerosing cholangitis (PSC) who develop cholangiocarcinoma (CCA) have a median survival of less than 6 months. In half of cases, PSC and CCA will be diagnosed either concurrently or within a year of one another. The aim of the present study is to demonstrate that the degree of biochemical liver dysfunction is associated with concomitant or impending CCA. Methods: We did a chart review of patients diagnosed with PSC and CCA up to 18 months from presentation (“CCA” group) as well as patients with PSC that underwent transplantation with no sign of CCA in their explanted liver (“nCCA” group). Along with demographic data and follow-up length, we recorded their presenting liver function tests, including alanine and aspartate aminotransferases (ALT, AST), total bilirubin (TBil), alkaline phosphatase (ALP), international normalization ratio (INR), and serum Ca 19-9 levels. Differences between mean values of the two groups were analyzed with a student’s t-test. Results: Twenty-four patients were included. The “CCA” group consisted of eight patients, and the “non-CCA” group had 16 patients. There was no significant difference between the two groups in their presenting values of ALT, ALP, or serum Ca 19-9. However, the “CCA” group had significantly higher levels of AST, TBil, and INR. Conclusion: Patients with PSC and concurrent or impending CCA appear to exhibit significantly greater biochemical liver dysfunction than those who do not develop CCA. Therefore, newly-diagnosed PSC patients presenting with these findings may warrant more rigorous evaluation.     

Torque expression of self-ligating brackets compared with conventional metallic, ceramic, and plastic brackets

The purpose of this research was to investigate the torque capacity of active and passive self-ligating brackets compared with metallic, ceramic, and polycarbonate edgewise brackets. Six types of orthodontic brackets were included in the study: the self-ligating Speed and Damon2, the stainless steel (SS), Ultratrimm and Discovery, the ceramic bracket, Fascination 2, and the polycarbonate bracket, Brillant. All brackets had a 0.022-inch slot size and were torqued with 0.019 x 0.025-inch SS archwires. For this purpose, the labial crown torque of an upper central incisor was measured in a simulated intraoral clinical situation using the orthodontic measurement and simulation system (OMSS). A torque of 20 degrees was applied and the correction of the misalignement was simulated experimentally with the OMSS. Each bracket/wire combination was measured five times. Maximum torquing moments and torque loss were determined. The results were analysed with one-way analysis of variance, with the bracket serving as the sole discriminating variable, and the Tukey test at the 0.05 level of significance. The ceramic bracket (Fascination 2) presented the highest torquing moment (35 Nmm) and, together with a SS bracket, the lowest torque loss (4.6 degrees). Self-ligating, polycarbonate, and selective metallic brackets demonstrated almost a 7-fold decreased moment developed during insertion of a 0.019 x 0.022-inch SS wire into a 0.022-inch slot and a 100 per cent increase in loss.     

Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls

OBJECTIVES: Superoxide dismutase (SOD) is an antioxidant enzyme that acts against superoxide, an oxygen radical, released in inflammatory pathways and causes connective tissue breakdown. In this study, SOD activities in gingiva and gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and periodontally healthy controls were compared. MATERIAL AND METHODS: Twenty-six CP patients and 18 controls were studied. In patients, teeth with moderate-to-severe periodontal breakdown and > or =5 mm pockets that required full-thickness flap surgery in the right or left maxillary quadrant, and in controls, teeth scheduled for extraction for orthodontic reasons were studied. After the clinical measurements (probing depth, clinical attachment level, gingival index, gingival bleeding index, plaque index), GCF samples were collected. Tissue samples were harvested from the same teeth, during flap operation in patients and immediately after tooth extraction in controls. SOD activities were spectrophotometrically assayed.The results were statistically analysed. RESULTS: Gingival SOD activity was significantly higher in the CP group than in controls (p<0.05). No significant difference was found in GCF SOD activity between the groups (p>0.05). Correlations between gingival and GCF SOD activities were not statistically significant in CP and control groups (p>0.05). CONCLUSION: In CP, SOD activity seems to increase in gingiva, probably as a result of a higher need for SOD activity and protection in gingiva in CP than in periodontal health, while not significantly changing in GCF, suggesting a weak SOD activity in GCF in periodontal disease state. The weak correlation between gingival and GCF SOD activities suggests distinct actions of these SODs.     

Protein carbonyl levels in serum and gingival crevicular fluid in patients with chronic periodontitis

OBJECTIVE: Evidence reveals the role of reactive oxygen species (ROS) in many pathologies including periodontitis. Protein carbonylation is the most widely used biomarker for oxidative damage to proteins, and reflects cellular damage induced by ROS. In this study protein carbonyl (PC) levels in serum and gingival crevicular fluid (GCF) in patients with chronic periodontitis (CP) was evaluated. MATERIALS AND METHODS: Thirty-three patients with CP and 24 healthy controls were included in the study. Following the clinical measurements and samplings, total protein levels in serum and GCF were determined by Bradford method, and serum and GCF PC levels were measured by modified Levine method. RESULTS: PC levels in serum and GCF were significantly higher in the CP group compared to the control group (p<0.05). In all subjects, serum and GCF PC levels showed statistically significant positive correlations with all clinical parameters (p<0.05). CONCLUSIONS: The results suggest that both systemic and local/periodontal protein carbonylation increase in CP compared to health and that elevated levels of PCs may be a sign of oxidative damage in periodontitis and correlate well with the periodontal status.     

Pretargeting vs. direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody

IntroductionWe previously demonstrated MORF/cMORF pretargeting of human islets and betalox 5 cells (a human beta cell line) transplanted subcutaneously in mice with the anti-human islet antibody, HPi1. We now compare pretargeting with direct targeting in the beta cell transplant model to evaluate the degree to which target/non-target (T/NT) ratios may be improved by pretargeting.MethodsSpecific binding of an anti-human islet antibody HPi1 to the beta cells transplanted subcutaneously in mice was examined against a negative control antibody. We then compared pretargeting by MORF-HPi1 plus ¹¹¹In-labeled cMORF to direct targeting by ¹¹¹In-labeled HPi1.ResultsHPi1 binding to betalox5 human cells in the transplant was shown by immunofluorescence. Normal organ ¹¹¹In backgrounds by pretargeting were always lower, although target accumulations were similar. More importantly, the transplant to pancreas and liver ratios was, respectively, 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting.ConclusionsPretargeting greatly improves the T/NT ratios, and based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful imaging of human islets within this organ.