Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment.

BACKGROUND: Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment-induced sustained virologic response (SVR) in patients on haemodialysis. AIMS: To assess the risk of HCV reinfection among patients on haemodialysis with treatment-induced SVR. METHODS: Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct-acting antiviral (DAA)-based treatment received follow-up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12 . The low-risk general population who achieved SVR12 and who underwent the same post-SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person-years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. RESULTS: We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post-SVR12 follow-up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24 . The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09-0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10-0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44-4.38, P = 0.57). CONCLUSIONS: The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low-risk general population. HCV microelimination in this special population is feasible once universal screening and scaled-up treatment are implemented.

Hybrid vs sequential therapy for eradication of Helicobacter pylori in Taiwan: A prospective randomized trial.

AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori (H. pylori) infection. METHODS: From March 2013 to May 2014, one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before were randomized to receive either sequential therapy (rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d, followed by rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy (rabeprazole 20 mg and amoxicillin 1 g for 7 d, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy, or (13)C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: One hundred and sixty-seven patients (83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups, respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis (P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis (P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group. CONCLUSION: Due to a grade A (> 95%) success rate for H. pylori eradication by PP analysis, similar compliance and adverse events, hybrid therapy seems to be an appropriate eradication regimen in Taiwan.

Performance of Routine Helicobacter pylori Invasive Tests in Patients with Dyspepsia.

Background. This study was designed to compare the accuracy of three different invasive methods for the detection of Helicobacter pylori (H. pylori) infection in patients with dyspepsia. These tests included culture, histology, and the rapid urease test (CLO test). Methods. H. pylori infection was diagnosed prospectively in 246 untreated dyspeptic patients who underwent upper gastrointestinal endoscopy. The gold standard for H. pylori infection was based on a positive culture or both a positive histological examination and a CLO test. Results. H. pylori was diagnosed in 33.3% of the patients. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were as follows: histology from the antrum (95.12; 95.12; 90.7; 97.5; 95.12%); histology from the antrum and corpus (95.12; 95.12; 90.7; 97.5; 95.12%); histology from the corpus (76.83; 96.95; 92.65; 89.33; 90.24%); culture (91.46; 100; 100; 95.91; 97.15%); a CLO test from the antrum and corpus (85.59; 100; 100; 93.71; 95.52%); a CLO test from the antrum (64.63; 100; 100; 84.97; 88.21%); a CLO test from the corpus (69.51; 100; 100; 96.77; 89.83%), respectively. Conclusions. Antral biopsy histology and culture are the best methods for the diagnosis of H. pylori infection in our cohort of patients with dyspepsia.

Baicalein loaded in tocol nanostructured lipid carriers (tocol NLCs) for enhanced stability and brain targeting.

The objective of the present work was to investigate the specific brain targeting of baicalein by intravenous injection after incorporation into nanostructured lipid carriers (NLCs). The NLC system, composed of tripalmitin, Gelucires, vitamin E, phospholipids, and poloxamer 188 (referred to as tocol NLCs), was characterized in terms of its physicochemical properties, differential scanning calorimetry (DSC), stability, in vivo pharmacokinetics, and brain distribution. The lipid nanoparticles were spherical with an average size of ∼100 nm. The zeta potential of the nanoparticles was about -50 mV. DSC studies suggested that the majority of the inner cores of tocol NLCs had a slightly disordered crystal arrangement. The nanoparticulate dispersions demonstrated good physical stability during storage for 6 days. The incorporation of vitamin E in the formulations greatly reinforced baicalein's stability. The aqueous control and tocol NLCs were intravenously administered to rats. The plasma level of baicalein in NLCs was much higher and the half-life much longer than those in the free control. In the experiment on the brain distribution, NLCs respectively revealed 7.5- and 4.7-fold higher baicalein accumulations compared to the aqueous solution in the cerebral cortex and brain stem. Greater baicalein accumulations with NLCs were also detected in the hippocampus, striatum, thalamus, and olfactory tract. A 2-3-fold increase in baicalein amounts were achieved in these regions. Tocol NLCs improved baicalein's stability and the ability of baicalein to penetrate the brain; thus, this is a promising drug-targeting system for the treatment of central nervous system disorders.

Conversion of squid pen by Serratia ureilytica for the production of enzymes and antioxidants.

Two proteases (P1 and P2) and a chitinase (C1) were purified from the culture supernatant of Serratia ureilytica TKU013 with squid pen as the sole carbon/nitrogen source. The molecular masses of P1, P2 and C1 determined by SDS-PAGE were approximately 50 kDa, 50 kDa and 60 kDa, respectively. The optimum pH, optimum temperature, pH stability, and thermal stability of P1, P2 and C1 were (pH 10, 40 degrees C, pH 7-11, and <50 degrees C), (pH 10, 40 degrees C, pH 8-11, and <40 degrees C) and (pH 6, 50 degrees C, pH 5-8, and <50 degrees C), respectively. P1 and P2 were inhibited by Mg(2+), EDTA and C1 was inhibited completely by Cu(2+). The antioxidant activity of TKU013 culture supernatant was 72% per mL (DPPH scavenging ability). With this method, we have shown that squid pen wastes can be utilized and have revealed its hidden potential in the production of functional foods.

Portal vein pulsatility index is a more important indicator than congestion index in the clinical evaluation of right heart function.

AIM: To study the changes of portal blood flow in congestive heart failure. METHODS: We studied the congestion index (CI) and portal vein pulsatility index (PI) in patients with varied degrees of congestive heart failure using ultrasonic Doppler. Ten patients with (mean) right atrial pressure (RA) < 10 mmHg were classified as group 1 and the remaining 10 patients with RA > or = 10 mmHg as group 2. RESULTS: There were no difference on cardiac index (HI, P=0.28), aortic pressure (AO, P=0.78), left ventricular end-diastolic pressure (LVED, P=0.06), (max)imum portal blood velocity (Vmax, P=0.17), (mean) portal blood velocity (Vmean, P=0.15) and portal blood flow volume (PBF, P=0.95) between the two groups. Group 2 patients had higher pulmonary wedge pressure (PW, 29.9+/-9.3 mmHg vs 14.6+/-7.3 mmHg, P=0.002), pulmonary arterial pressure (PA, 46.3+/-13.2 mmHg vs 25.0+/-8.2 mmHg, P=0.004), RA (17.5+/-5.7 mmHg vs 4.7+/-2.4 mmHg, P<0.001), right ventricular end-diastolic pressure (RVED, 18.3+/-5.6 mmHg vs 6.4+/-2.7 mmHg, P<0.001), CI (8.7+/-2.4 vs 5.8+/-1.2, P=0.03), and PI (87.8+/-32.3% vs 27.0+/-7.4%, P<0.001) than Group 1. CI was correlated with PI (P<0.001), PW (P<0.001), PA (P<0.001), RA (P=0.043), RVED (P=0.005), HI (P<0.001), AO (P<0.001), CO (P<0.001), LVED (P<0.001), Vmax (P<0.001), Vmean (P<0.001), cross-sectional area of the main portal vein (P<0.001) and PBF (P<0.001). CI could be as high as 8.3 in patients with RA < 10 mmHg and as low as 5.9 in those with RA > or = 10 mmHg. CONCLUSION: Our data show that RI is a more significant indicator than CI in the clinical evaluation of high RA > or = 10 mmHg, whereas CI is better than PI in the assessment of left heart function.

Staurosporine-induced G2/M arrest in primary effusion lymphoma BCBL-1 cells.

Staurosporine, an inhibitor of protein kinase C, is a potential antitumor drug and its derivatives are used as anticancer drugs in clinical trials. Human herpesvirus 8 (HHV-8) is implicated in all forms of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), indicating it to be a DNA tumor virus. It is difficult to culture cell lines derived from KS patients; we therefore used a cell line derived from PEL (BCBL-1) to investigate whether staurosporine affects the HHV-8-related tumors. Our results show that staurosporine treatment reduces the cell viability of BCBL-1 cells and causes cell cycle arrest in the G2/M phase. The G2/M arrest was associated with the decrease in the expression of Cdc2 and cyclin B. Furthermore, the induction of the HHV-8 lytic cycle was not observed under the staurosporine treatment.