Ischemia-Reperfusion Injury of the Cochlea: Pharmacological Strategies for Cochlear Protection and Implications of Glutamate and Reactive Oxygen Species

A large amount of energy produced by active aerobic metabolism is necessary for the cochlea to maintain its function. This makes the cochlea vulnerable to blockade of cochlear blood flow and interruption of the oxygen supply. Although certain forms of human idiopathic sudden sensorineural hearing loss reportedly arise from ischemic injury, the pathological mechanism of cochlear ischemia-reperfusion injury has not been fully elucidated. Recent animal studies have shed light on the mechanisms of cochlear ischemia-reperfusion injury. It will help in the understanding of the pathology of cochlear ischemia-reperfusion injury to classify this injury into ischemic injury and reperfusion injury. Excitotoxicity, mainly observed during the ischemic period, aggravates the injury of primary auditory neurons. On the other hand, oxidative damage induced by hydroxyl radicals and nitric oxide enhances cochlear reperfusion injury. This article briefly summarizes the generation mechanisms of cochlear ischemia-reperfusion injury and potential therapeutic targets that could be developed for the effective management of this injury type

One-step generation of multiple transgenic mouse lines using an improved Pronuclear Injection-based Targeted Transgenesis (i-PITT)

Ohtsuka, M., Miura, H., Mochida, K. et al. One-step generation of multiple transgenic mouse lines using an improved Pronuclear Injection-based Targeted Transgenesis (i-PITT). BMC Genomics 16, 274 (2015). https://doi.org/10.1186/s12864-015-1432-

Long-term outcomes of shelf acetabuloplasty for developmental dysplasia of the hip in adults: a minimum 20-year follow-up study

AbstractBackgroundShelf acetabuloplasty has been applied to secondary osteoarthritis of the hip due to congenital dislocation or acetabular dysplasia; however, there are few reports on the long-term outcomes of this operation. Here, we aimed to investigate the long-term effects of our shelf acetabuloplasty for developmental dysplasia of the hip in adults.MethodsOutcomes for 28 hips (7 with pre-arthrosis, 21 with initial stage of arthrosis) were retrospectively reviewed clinically and radiologically at a minimum of 20 years after operation. Mean age of the patients at operation was 34 years (range 17–54 years), and the mean follow-up period was 25 years (range 20–32 years).ResultsMean Japanese Orthopaedic Association hip score improved from 76 points preoperatively to 82 points, and mean pain score improved from 24 points preoperatively to 33 points at 20 years. Mean Sharp angle improved from 51° preoperatively to 37° immediately after the operation. Similarly, the mean center-edge angle improved from −4° to 38°, and the mean acetabulum head index improved from 52 to 99%. More than 50% of the hips showed no change in joint space width at 20 years. Survival rates were 100% at 10 years, 93% at 20 years and 71% at 32 years, with conversion to total hip replacement as the endpoint.ConclusionLong-term outcomes of our shelf acetabuloplasty were comparable to other reports, and the clinical outcomes and survivorship revealed positive long-term effects of our procedure over approximately 20 years

Therapeutic Effect of Anti-TNF-α Antibody and Levofloxacin(LVFX)in a Mouse Model of Enterohemorrhagic Escherichia coli O157 Infection

マウスに腸管出血性大腸菌O157を感染させ、抗TNF-α抗体投与による感染防御効果を調べた。抗TNF-α抗体単独投与群では感染による症状の発現及び組織学的な変化は観察されなかったが、糞便中に少量のO157が証明された。本抗体にLVFXを併用した場合には糞便中のO157は完全に除去されたので、両者の併用により良好な治療結果が得られると考える

Outcomes of Charnley total hip arthroplasty using improved cementing with so-called second- and third-generation techniques

AbstractBackgroundTechniques of cemented total hip arthroplasty have developed over time. We present the outcomes of Charnley total hip arthroplasty performed using improved second- and third-generation cementing techniques.MethodsWe reviewed the radiologic results of 91 Charnley total hip arthroplasties performed using second- and third-generation cementing techniques. Second-generation techniques involved making multiple anchor holes, a double-cementing method on the acetabular side and an intramedullary plug, and retrograde filling with a cement gun on the femoral side in 57 hips. Third-generation techniques involved additional vacuum mixing and cement pressurization in 34 hips.ResultsJoint survival rates at 20years when using second-generation techniques were 89% for the socket and 94% for the stem with aseptic loosening as the end point; the survival rates at 10years when using third-generation techniques were 97 and 100%, respectively. According to our radiographic evaluation system for the clear zone at 5years, there was less clear zone in the acetabular side with the third-generation techniques than with second-generation techniques. In the femoral side, there was very little development of the clear zone, but the difference between generations was not significant.ConclusionsSecond- and third-generation cementing techniques showed excellent survivorship. The clear zone scores at 5years indicated that third-generation techniques were effective, especially in the acetabular side, and may produce better long-term results than second-generation techniques

Postural change for supine position does not disturb toddlers\u27 nap

This study examined whether forced postural change from prone to supine during toddlers’ nap, a preventative measure taken in Japan for sudden unexplained death in childhood (SUDC), disturbs toddlers’ sleep. When the "Back to Sleep" campaign (BSC) was introduced to Japan in 1996, its recommendations were also applied to infants aged 1 year old and over with the expectation that the BSC recommendations may also contribute to a decrease in the occurrence rate of SUDC. Since then, Japanese nurseries have routinely conducted sleeping position checks and positional adjustments of toddlers every 5–10 min during naps. A total of 52 toddlers (age 18.4 ± 3.3 months, means ± SD) were continuously monitored for 8 h during daytime at nursery schools for wake-sleep status and body position (prone, supine and lateral) with actigraphs and 3-orthogonal-axis accelerometers. Out of the 52 toddlers, 24 toddlers adopted prone positions during naps, which were adjusted by nursery staff back to supine. When nursery staff manually changed the toddlers position from prone to supine, the toddlers either did not wake or woke only briefly (3.1 ± 4.9 min) and returned to sleep soon after the positional change. Our study indicates that manual change of toddlers’ sleeping position from prone to supine, a potential SUDC prevention method, does not disturb toddlers’ sleep during their naps

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

A High-Speed Congenic Strategy Using First-Wave Male Germ Cells

BACKGROUND: In laboratory mice and rats, congenic breeding is essential for analyzing the genes of interest on specific genetic backgrounds and for analyzing quantitative trait loci. However, in theory it takes about 3-4 years to achieve a strain carrying about 99% of the recipient genome at the tenth backcrossing (N10). Even with marker-assisted selection, the so-called 'speed congenic strategy', it takes more than a year at N4 or N5. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new high-speed congenic system using round spermatids retrieved from immature males (22-25 days of age). We applied the technique to three genetically modified strains of mice: transgenic (TG), knockin (KI) and N-ethyl-N-nitrosourea (ENU)-induced mutants. The donor mice had mixed genetic backgrounds of C57BL/6 (B6):DBA/2 or B6:129 strains. At each generation, males used for backcrossing were selected based on polymorphic marker analysis and their round spermatids were injected into B6 strain oocytes. Backcrossing was repeated until N4 or N5. For the TG and ENU-mutant strains, the N5 generation was achieved on days 188 and 190 and the proportion of B6-homozygous loci was 100% (74 markers) and 97.7% (172/176 markers), respectively. For the KI strain, N4 was achieved on day 151, all the 86 markers being B6-homozygous as early as on day 106 at N3. The carrier males at the final generation were all fertile and propagated the modified genes. Thus, three congenic strains were established through rapid generation turnover between 41 and 44 days. CONCLUSIONS/SIGNIFICANCE: This new high-speed breeding strategy enables us to produce congenic strains within about half a year. It should provide the fastest protocol for precise definition of the phenotypic effects of genes of interest on desired genetic backgrounds

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives

The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN®) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-β or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers