Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure.

Long‐distance running (LDR) can induce transient lowering of the foot arch, which may be associated with mechanical fatigue of the plantar fascia (PF). However, this has not been experimentally tested in vivo. The purpose of this study was to test our hypothesis that LDR induces transient and site‐specific changes in PF stiffness and morphology and that those changes are related to the lowering of the foot arch. Ten male recreational long‐distance runners and 10 untrained men were requested to run overground for 10 km. Before and after running, shear wave velocity (SWV: an index of soft tissue stiffness) and thickness of PF at three different sites from its proximal to distal end were measured using supersonic shear imaging and B‐mode ultrasonography. Foot dimensions including the navicular height were measured using a three‐dimensional foot scanner. SWV at the proximal site of PF and navicular height was significantly decreased in both groups after running, with a higher degree in untrained men (−21.9% and −14.1%, respectively) than in runners (−4.0% and −6.3%, respectively). The relative change (%Δ) in SWV was positively correlated with %Δnavicular height in both groups (r = .69 and r = .65, respectively). Multiple regression analysis revealed that %ΔSWV at the proximal site solely explained 72.7% of the total variance in %Δnavicular height. It is concluded that LDR induces transient and site‐specific decreases in PF stiffness. These results suggest that the majority of running‐induced lowering of the foot arch is attributable to the reduction of PF stiffness at the proximal site.

Chronic subdural hematoma (CSDH) is an angiogenic disease that is involved with many inflammatory mediators. Tie2 is predominantly expressed in the embryonic endothelium and plays an important role in the maturation and stabilization of the vasculature. Angiopoietin (Ang)1 and Ang2 are well-known ligands of the Tie2 receptor. We examined the expression of Ang1 and Ang2 in CSDH fluid and the expression of Tie-2 receptor and components of the angiogenic signaling pathways in the outer membrane of CSDH. Twenty-five samples of CSDH fluid and eight samples of outer membrane of CSDH were included. The concentrations of Ang1 and Ang2 in the CSDH fluid were measured using enzyme-linked immunosorbent assay (ELISA) kits. The expression of Tie2, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) mechanistic target of rapamycin (mTOR), GβL, 70 kDa ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E (eIF-4E), and β-actin was examined by a Western blot analysis. The expression of Tie2, Akt, and mTOR was also examined by immunohistochemistry. The concentration of Ang2 in CSDH fluid was significantly higher than that in the serum or cerebrospinal fluid (CSF), and also higher than that of Ang1 in CSDH fluid. Tie2, PI3K, Akt, mTOR, GβL, p70S6K, and eIF-4E were detected in all cases. In addition, Tie2, Akt, and mTOR were localized in the endothelial cells of vessels in the CSDH outer membrane. Our data suggest that Ang2, although not Ang1, in CSDH fluid promotes angiogenesis in endothelial cells through the Tie2 receptor. The Ang2/Tie2 signaling pathway might therefore be a useful therapeutic target for treating the growth of intractable CSDH.

Busulfan is an anti-cancer chemotherapeutic drug and is often used as conditioning regimens prior to bone marrow transplant for treatment of chronic myelogenous leukemia. Male infertility, including spermatogenesis disturbance, is known to be one of the side effects of anticancer drugs. While hormone preparations and vitamin preparations are used for spermatogenesis disturbance, their therapeutic effects are low. Some traditional herbal medicines have been administered to improve spermatogenesis. In the present study, we administered Gosha-jinki-gan (TJ107; Tsumura Co., Ltd., Tokyo, Japan) to mice suffering from severe aspermatogenesis after busulfan treatment to determine whether TJ107 can recover spermatogenesis. Male 4-week-old C57BL/6J mice were administered a single intraperitoneal injection of busulfan, and they were then fed a normal diet for 60 days and then a TJ107 diet or TJ107-free normal diet for another 60 days. After busulfan treatment, the weight of the testes and the epididymal sperm count progressively decreased in the normal diet group. On the other hand, in the TJ107 group, these variables dramatically recovered at 120 days. These results suggest that busulfan-induced aspermatogenesis is irreversible if appropriate treatment is not administered. Supplementation of TJ107 can completely recover the injured seminiferous epithelium via normalization of the macrophage migration and reduction of the expressions of Tool-like receptor (TLR) 2 and TLR4, suggesting that TJ107 has a therapeutic effect on busulfan-induced aspermatogenesis.

The tubuli recti (TR) are immunologically special, because the lymphocytes preferably accumulate around them during the course of T-cell dependent testicular autoimmunity in mice. This finding implies that the testicular interstitium around the TR is where autoreactive lymphocytes can gain access to autoimmunogenic germ cell antigens. In the present study, the histoarchitecture of the TR was minutely examined in normal mice. Three-dimensional analysis showed that 14-16 TR appeared to be connected to the rete testis (RT). Electron microscopical analysis revealed that the epithelial cells in the TR formed protruding cytoplasmic strings, with active endocytosis of degenerated spermatozoa, and exhibited three different morphological characteristics. Furthermore, a few macrophages were found to have penetrated into the TR. Immunohistochemical image analysis revealed that more macrophages specifically accumulated around the TR than the RT or seminiferous tubules. These findings indicate that macrophages preferentially accumulate around the TR, where contact between germ cell antigens and macrophages may occur under normal and pathological conditions.