Combination therapy with daclatasvir and asunaprevir for dialysis patients infected with hepatitis C virus

The standard antiviral therapy for dialysis patients infected with hepatitis C virus(HCV) is(pegylated) interferon monotherapy, but its efficacy is insufficient. Oral direct-acting antiviral agents(DAAs) have recently been developed for chronic hepatitis C patients. However, some DAAs have contraindications for chronic renal failure(CRF). Daclatasvir and asunaprevir are metabolized largely in the liver and are not contraindicated in CRF. Combination therapy with daclatasvir and asunaprevir was used for 4 dialysis patients infected with genotype 1b HCV. One patient had viral breakthrough, and the 3 others had sustained virological response 12. One patient was admitted for heart failure and percutaneous coronary intervention due to concomitant ischemic disease. Heart failure was unlikely to be caused by the combination therapy, as it was probably due to water overload. The patient continued to receive the combination therapy after the remission of the heart failure. The combination therapy was well tolerated in the other patients.

Sofosbuvir/Ribavirin therapy for patients experiencing failure of ombitasvir/paritaprevir/ritonavir + ribavirin therapy: Two cases report and review of literature

BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown.CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia.CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.

Observation of the esophagus, pharynx and lingual root by gastrointestinal endoscopy with a percutaneous retrograde approach

AIM:To evaluate the efficacy of retrograde observation of the esophagus, pharynx, larynx and lingual root. METHODS:With the beagle dog under anesthesia, the anterior wall of the stomach was fixed on the abdominal wall in a similar way to percutaneous endoscopic gastrostomy. The gastrointestinal scope was inserted via a 12 mm laparoscopic port for subsequent retrograde observation from stomach to the oral cavity. RESULTS:With this technique, direct observation of gastric cardia was possible without restriction. The cervical esophagus was dilated well, also allowing clear observation of the hypopharyngo-esophageal junction. If the tongue was manually pulled out forward, observation of the lingual root was possible.CONCLUSION: This procedure is easy and effective for pre-treatment evaluation of the feasibility of endoscopic resection in cases of superficial carcinoma of head and neck.

Ipragliflozin-induced improvement of liver steatosis in obese mice may involve sirtuin signaling

BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal glomeruli.SGLT2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose excretion.The SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical studies.However,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully understood.AIM To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese mice.METHODS We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 wk.We also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were performed.RESULTSHepatic lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob mice.CONCLUSIONOur study suggests that the liver steatosis-ameliorating effects of ipragliflozin inob/ob mice may be mediated partly by hepatic SIRT1 signaling, possibly throughthe PGC-1α/PPARα-FGF21 pathway.

Conjugation of Magnetite Nanoparticles with Melanogenesis Substrate, NPrCAP Provides Melanoma Targeted, <i>in Situ</i>Peptide Vaccine Immunotherapy through HSP Production by Chemo-Thermotherapy

In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.

Rapid Disappearance of Testicular Plasmacytoma after Treatment with Lenalidomide plus Dexamethasone

We describe a rare case of testicular plasmacytoma first manifesting as a relapse. The patient was initially diagnosed with IgG-λ-type multiple myeloma and treated with melphalan and prednisolone plus bortezomib, achieving a complete remission. Four months later, his left scrotum began to swell and pathological investigation of a needle biopsy specimen revealed proliferation of plasma cells expressing IgG-λ, confirming myeloma recurrence. However, bone marrow aspiration samples showed no significant increase in myeloma cells and there was no skewed deviation of the K/λ ratio on flow-cytometric analysis. The extramedullary tumors disappeared completely soon after treatment with lenalidomide plus dexamethasone, and the patient was judged to be in very good partial remission based on negative M-protein results by serum immunoelectrophoresis. This is the first report, to our knowledge, describing complete disappearance of a testicular plasmacytoma after treatment with lenalidomide as the key-drug.

Development of a smart city planning support tool using the cooperative method

A reduction of environmental burdens is currently required. In particular, proposing a new approach for the construction of a smart city using renewable energy is important. The technological development of a smart city is founded building equipment and infrastructure. However, planning methods and their techniques using the collaboration approach with residents are only just developing. This study aimed to develop a support tool for the construction of a smart city using renewable energy while facilitating consensus-building efforts among residents using the method for a cooperative housing development. We organized the supporting methods for the construction of residential area using the cooperative method. Then, we developed supporting toots that interface the computer with these methods. We examined the support techniques for the construction of a residential area using renewable energy technology by analyzing Japanese cases of a smart city. Moreover, we developed a support toot for the construction of a smart city on a trial basis. We integrated the smart city construction toots and the cooperative housing construction support tool. This tool has a 3D modeling system that helps residents to easily understand the space image as a result of the examination. We also developed a professional supporting toot that residents can consider for cost-effectiveness in renewable energy and its environmental toad reduction rate for the planning of a smart city.

Occurrence factors of large vacant lots in central districts and their utilization by local governments in Japan

In Japan, focal cities experience a number of probtems retated to deterioration of residentiat environment, quality of public service, and vitalization of commercial rand. SpecificaLLy, the presence of Large vacant tots behind sizable stores, office buildings, hospitals, and factories devitatize urban activity and its Landscape. Many local cities are seeking to actuatize a sustainable compact city with an integrated poputation, commerce, traffic and other pubLic services in ways that promote a tow carbon and energy-conserving society. Against the backdrop of these issues, this study examines the occurrence of large vacant lots and their utilization by tocat governments in Japan based on a questionnaire and fietd survey. It highlights severat cases in which a Large vacant tot is used to forward the development of a compact city by a tocat government.

Method for the proposal and evaluation of urban structures for compact cities using an expert system

The world population is continually increasing, but the Japanese population is decreasing. By 2050, the Japanese population is calculated to be close to 100 million people, and by 2060, 40% of the Japanese are estimated to be aged 65 years or more. Data show an increase in the declining birth and aging rates of the population. The development of high-concentration urban structures will be needed to solve such problems. However, a detailed vision of the future is yet to be clarified and in the process of consideration. In this study, we developed an instrument called ＂Population Migration Tool,＂ which is based on plural planning and policy, after we formed a future population distribution model. In addition, We also established a high- concentration urban structure model with this tool with the aim of considering the kind of urban structure local cities should target in the future.