Sero-Epidemiological Study of Respiratory Syncytial Virus

Background: Respiratory syncytial virus (RSV) is one of the major viruses that cause respiratory infections in all generations, not only in neonates and infants. There is a limited number of reports on serological epidemiology of RSV subgroups A and B. Neutralizing test (NT) antibody reflects protective immunity but bothersome. Sero-epidemiological study should be performed using practical NT method. Methods: Two wild-type viruses subgroups A and B, isolated in 2013, and the Long strain was used as the challenge viruses. NT antibody with 100% inhibition of cytopathic effect (CPE) was examined. A total of 91 serum samples obtained from 0 to 12 years subjects without RSV infection who visited our hospital with some health problems and 121 sera obtained from healthy subjects in different age groups were used. Serological epidemiology of subgroups A and B was investigated in this study using new NT methods. Results: 1) A simple and practical NT method was developed. 2) The NT antibody titer was lowest in \u3c1 year of age (5 × 21.70 ± 2.03 against subgroup A and 5 × 20.85 ± 1.31 against subgroup B) and increased in 3 years of age or older, and high antibody titers were maintained during school age. 3) A slight difference was observed in the NT antibody titers against subgroups A and Bin young children \u3c3 years, but not after 3 years of age, reflecting the repeated infections. 4) Specific IgG antibody against RSV was measured. The IgG EIA values decreased with age. No association was observed between IgG EIA and NT titers. Conclusions: A simple NT assay method was developed in the present study. By the age of 3 years, high NT antibody titers were observed and maintained until 12 years. The IgG (EIA) values decreased with age. No association was observed between IgG (EIA) and NT titers

Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination

Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2-like phenotype of tumor-associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination

Effects of Physical Exercise and of Dietary Protein Levels on Nitrogen Retention in Energy-Restricted Adult Rats

たんぱく質および脂肪含量が異なる種々の実験食を自由摂取時の50〜60%量与え, 同時に1日30分のトレッドミル歩行(20m/分)または50分の遊泳を課して10〜35日間減量させた成熟ラット(約100日齢)について, 窒素出納, 体組成, 血液性状, 筋グリコーゲン量などを測定し, 以下の成績が得られた.1.食餌制限した運動負荷ラットは, たんぱく質摂取水準が等しい非運動ラットに比べて窒素保留量の増加がみられ, 体構成的にも水分とたんぱく質が多くなり脂肪が著るしく減少した.2.運動・非運動群ともに, 25%カゼイン食給与ラットは10%および40%カゼイン食ラットと比較すると, 窒素出納が正に傾き, 減食に伴う体たんぱく質の損失も著るしく軽減された.3.食餌制限下においても, 運動群ラットの血清コレステロール値は同一食の非運動群ラットよりも低下する傾向が認められた.また, 自由摂取時に血清コレステロール上昇作用をもつラードとカゼインは食餌中の添加量が増すにつれ, 減食中のラットに対しても血清コレステロール値を高めるように作用した.4.10%カゼイン食給与ラットを食餌制限と運動負荷を併用して減量させると貧血傾向が出現したが, 25%および40%カゼイン食ラットではこの傾向は認められなかった.運動群ラットの筋グリコーゲン量は非運動群ラットに比べて著明に増加した.以上の結果から, 減食時の運動は体たんぱく質さらには活性組織の損失を抑制し体脂肪の減少を促進するほかに, 血清コレステロール値を低下させ筋グリコーゲン量を高めるなど, 体力・保健上有利な作用を示すことが明らかになった.また, 減食時の体構成の変化に食餌たんぱく質量, 血清コレステロール値には食餌脂肪がそれぞれ強く影響する

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

An Overview of Pituitary Incidentalomas: Diagnosis, Clinical Features, and Management

Pituitary incidentalomas are tumors or mass lesions of the pituitary gland. These are incidentally discovered during imaging studies for symptoms that are not causally related to pituitary diseases. The most common symptom that triggers an examination is headache, and the most common type of pituitary incidentalomas are pituitary neuroendocrine tumors (PitNETs) and Rathke cleft cysts. The existing treatment strategy is controversial; however, surgical resection is recommended in cases of clinically non-functioning PitNETs with optic chiasm compression. In contrast, cystic lesions, such as Rathke cleft cysts, should be followed if the patients are asymptomatic. In this case, MRI and pituitary function tests are recommended every six months to one year; if there is no change, the follow-up period should be extended. The natural history of PitNET is partially known, and the management of pituitary incidentalomas is determined by this history. However, the pathogenesis of PitNET has significantly changed with the new World Health Organization classification, and follow-up is important based on this new classification. Therefore, a high level of evidence-based research is needed to consider treatment guidelines for pituitary incidentalomas in the future

Predictive ability of visit-to-visit blood pressure indices for adverse events in patients with non-valvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry

Background: We previously reported that standard deviation (SD) of systolic blood pressure (SBP), an index of BP variability, and SBP-time in target range (TTR), an index of BP consistency, were significantly associated with adverse events in patients with non-valvular atrial fibrillation (NVAF). Thus, this study aimed to compare predictive ability for adverse events among visit-to-visit BP variability/consistency indices using data from the J-RHYTHM Registry. Methods: Of 7406 outpatients with NVAF, 7226 (age, 69.7 ± 9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6 ± 5.0 times) during the 2-year follow-up period or until occurrence of an event, were included. As BP consistency for target SBP between 110 and 130 mmHg, SBP-TTR by the Rosendaal method and SBP-frequency in range (FIR) were calculated. Predictive ability was expressed by the area under receiver-operating-characteristic curve (AUC). AUCs of SBP-TTR and SBP-FIR for adverse events were compared with those of SBP-SD by the DeLong’s test. Results: SBP-SD, SBP-TTR, and SBP-FIR were 11.0 ± 4.2 mmHg, 49.5 ± 28.3%, and 52.3 ± 23.0%, respectively. AUCs of these indices for thromboembolism, major hemorrhage, and all-cause death were 0.62, 0.64, and 0.63 for SBP-SD; 0.56, 0.55, and 0.56 for SBP-TTR; and 0.55, 0.56, and 0.58 for SBP-FIR; respectively. AUCs of SBP-SD were significantly larger than those of SBP-TTR for major hemorrhage (P = 0.010) and all-cause death (P = 0.014), and SBP-FIR for major hemorrhage (P = 0.016). Conclusion: Among visit-to-visit BP variability/consistency indices, predictive ability of SBP-SD for major hemorrhage and all-cause death was superior to that of SBP-TTR and SBP-FIR in patients with NVAF

Quantitative Detection and Rapid Identification of Human Adenoviruses

We have established a method of quantitative detection and rapid identification of human adenoviruses (hAdVs). Using LightCycler PCR with a primer set, we were able to amplify 554 bp of the hexon gene from each of 51 prototype strains of hAdVs. The sensitivity of LightCycler PCR was 10 copies of hAdV DNA/reaction. When LightCycler PCR was performed using a set of primers, hAdV was positive for 74.4% (99 of 133) of conjunctivitis patients and for 27.3% (81 of 297) of respiratory infection patients. We also attempted to measure hAdV in the potentially contaminated eye drops used by patients, detecting 5.4 × 10(2) to 1.6 × 10(6) copies/ml of hAdV. We determined the 350-bp nucleotide sequence of the amplified hexon gene and compared it with the sequences of the 51 prototype strains. Phylogenetic analysis based on 350 bp of the hexon gene identified 99 positive conjunctival swabs as 24 cases of AdV type 3 (AdV-3), 14 cases of AdV-4, 1 case of AdV-8, 19 cases of AdV-19a, and 41 cases of AdV-37. The 81 sequences from pharyngeal or nasal mucus swabs were identified as 29 cases of AdV-2, 18 cases of AdV-1, 18 cases of AdV-5, 12 cases of AdV-4, 2 cases of AdV-37, 1 case of AdV-3, and 1 case of AdV-6. LightCycler PCR followed by phylogenetic analysis provides an effective tool for the rapid identification of hAdVs and for studying molecular epidemiology