Seraprevir and sofosbuvir for treatment of chronic hepatitis C virus infection: A single-arm, open-label, phase 3 trial.

BACKGROUND AND AIM: This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. METHODS: Treatment-naive or interferon-experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). RESULTS: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post-treatment course and 3 discontinued follow-up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. CONCLUSIONS: The all-oral, ribavirin-free regimen of seraprevir and sofosbuvir is an effective and well-tolerated treatment option for Chinese patients mono-infected with HCV, including those with a history of interferon treatment.

A Multi-Hop Energy Neutral Clustering Algorithm for Maximizing Network Information Gathering in Energy Harvesting Wireless Sensor Networks.

Energy resource limitation is a severe problem in traditional wireless sensor networks (WSNs) because it restricts the lifetime of network. Recently, the emergence of energy harvesting techniques has brought with them the expectation to overcome this problem. In particular, it is possible for a sensor node with energy harvesting abilities to work perpetually in an Energy Neutral state. In this paper, a Multi-hop Energy Neutral Clustering (MENC) algorithm is proposed to construct the optimal multi-hop clustering architecture in energy harvesting WSNs, with the goal of achieving perpetual network operation. All cluster heads (CHs) in the network act as routers to transmit data to base station (BS) cooperatively by a multi-hop communication method. In addition, by analyzing the energy consumption of intra- and inter-cluster data transmission, we give the energy neutrality constraints. Under these constraints, every sensor node can work in an energy neutral state, which in turn provides perpetual network operation. Furthermore, the minimum network data transmission cycle is mathematically derived using convex optimization techniques while the network information gathering is maximal. Simulation results show that our protocol can achieve perpetual network operation, so that the consistent data delivery is guaranteed. In addition, substantial improvements on the performance of network throughput are also achieved as compared to the famous traditional clustering protocol LEACH and recent energy harvesting aware clustering protocols.

Analysis of 777 cases with obstruction of the ureter or extrahepatic bile duct by ultrasonography after normal saline retention enema.

BACKGROUND: Conventional transabdominal ultrasound usually fails to visualize parts of the ureter or extrahepatic bile duct covered by bowel gas. In this study, we propose a new method for gaining acoustic access to the ureters and extrahepatic bile duct to help determine the nature of obstruction to these structures when conventional transabdominal ultrasound fails. METHODS: The normal saline retention enema method, that is, using normal saline-filled colons to gain acoustic access to the bilateral ureters and extrahepatic bile duct and detecting the lesions with transabdominal ultrasonic diagnostic apparatus, was applied to 777 patients with obstructive lesions, including 603 with hydroureter and 174 with dilated common bile duct, which were not visualized by conventional ultrasonography. The follow-up data of all the patients were collected to verify the results obtained by this method. RESULTS: Of the 755 patients who successfully finished the examination after normal saline retention enema (the success rate of the enema is about 98%), the nature of obstruction in 718 patients was determined (the visualizing rate is approximately 95%), including 533 with ureteral calculus, 23 with ureteral stricture, 129 with extrahepatic bile duct calculus, and 33 with common bile duct tumor. CONCLUSIONS: Colons filled fully with normal saline can surely give acoustic access to the bilateral ureters and extrahepatic bile duct so as to determine the nature of obstruction of these structures when conventional transabdominal ultrasound fails.

Effects of high-AGE beverage on RAGE and VEGF expressions in the liver and kidneys.

BACKGROUND: The formation and accumulation of advanced glycation end products (AGEs) increase in some lifestyle-related diseases as well as in aging; however, little is known about the relationship between food-derived AGEs and the pathology of such diseases. AIM OF THE STUDY AND METHODS: To explore whether food items containing high levels of AGEs are involved in the development of lifestyle-related diseases, rats were orally administered a commercial high-AGE beverage [Lactobacillus beverage-A (LB-A)]. With a particular focus on angiogenesis-associated diseases, the gene expressions of vascular endothelial growth factor (VEGF) and the receptor for AGEs (RAGE) were examined in the liver and kidneys using real-time reverse transcription-polymerase chain reaction. Moreover, AGE deposition was immunohistochemically investigated in these tissues. RESULTS AND CONCLUSIONS: Hepatic VEGF expression was significantly increased in rats administered LB-A (P < 0.01 vs. control). Furthermore, immunohistochemical analysis detected glucose-derived AGE-positive cells in the liver from the LB-A group. These results suggest that AGE-rich beverages increase hepatic VEGF expression and AGE accumulation, bringing about early events associated with lifestyle-related diseases.

Toxic advanced glycation end products (TAGE) theory in Alzheimer's disease.

Several epidemiological studies have reported moderately increased risks of Alzheimer's disease (AD) in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress more rapidly. Recent understanding of this process has confirmed that interactions between AGEs and their receptor (RAGE) may play a role in the pathogenesis of diabetic complications and AD. The authors have recently found that glyceraldehyde-derived AGEs (AGE-2), which is predominantly the structure of toxic AGEs (TAGE), show significant toxicity on cortical neuronal cells and that the neurotoxic effect of diabetic serum is completely blocked by neutralizing antibody against the AGE-2 epitope. Moreover, in human AD brains, AGE-2 is distributed in the cytosol of neurons in the hippocampus and parahippocampal gyrus. These results suggest that TAGE is involved in the pathogenesis of AD as well as other age-related diseases. In this review, the authors discuss the molecular mechanisms of AD, especially focusing on TAGE-RAGE system.

TAGE (toxic AGEs) theory in diabetic complications.

Diabetic complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis. Chronic hyperglycemia is initially involved in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic derangements. High glucose increased production of various types of advanced glycation end-products (AGEs). Recently, we found that glyceraldehyde-derived AGEs (AGE-2) play an important role in the pathogenesis of angiopathy in diabetic patients. There is considerable interest in receptor for AGEs (RAGE) found on many cell types, particularly those affected in diabetes. Recent studies suggest that interaction of AGE-2 (predominantly structure of toxic AGEs; TAGE) with RAGE alters intracellular signaling, gene expression, release of pro-inflamatory molecules and production of reactive oxygen species (ROS) that contribute towards the pathology of diabetic complications. We propose three pathways for the in vivo formation of AGE-2 precursor, glyceraldehyde, such as i) glycolytic pathway, ii) polyol pathway, and iii) fructose metabolic pathway. Glyceraldehyde can be transported or can leak passively across the plasma membrane. It can react non-enzymatically with proteins to lead to accelerated formation of TAGE at both intracellularly and extracellularly. In this review, we discuss the molecular mechanisms of diabetic complications, especially focusing on toxic AGEs (TAGE) and their receptor (RAGE) system.