Right and Left Coronary and Conus Arteries Originating from Three Separate Ostia in the Right Valsalva Sinus in a Japanese Cadaver: A Case Study with Literature Review.

A rare case of an anomalous location of the orifice of the coronary artery was found in a 99-year-old male cadaver undergoing routine dissection. The presence of the right coronary artery (RCA), left coronary artery (LCA), and conus artery (conus branch) originating from the right Valsalva sinus are the characteristic findings of this case. Then, the LCA passed through the aorta and the pulmonary artery. The LCA and RCA branches were normal. These findings are useful for future surgical procedures, including cardiac catheterization.

Rare case of single left coronary artery in a Japanese cadaver.

A single left coronary artery with a single orifice in the left aortic sinus was observed during anatomical practice in an 81-year-old male Japanese cadaver. The single left coronary artery bifurcated into the anterior interventricular branch (IVa) and circumflex (CXa) branches. The IVa descended into the anterior interventricular sulcus to supply the apex of the heart, leaving a branch that traversed the upper part of the infundibulum to supply the anterior upper region of the right ventricle. The CXa curved leftward in the atrioventricular sulcus to reach the posterior surface, after which it continued to emerge into the anterior surface. The vascular running pattern showed that CXa directly supplied blood to the upper right ventricle (but not the conus branch), with three branches connected to the apex. The atrial arteries showed no anomalous distribution patterns. These findings are useful during surgical procedures, including cardiac catheterization.

Bag-1 Protects Nucleus Pulposus Cells from Oxidative Stress by Interacting with HSP70.

Bcl-2-associated athanogene 1 (Bag-1) is a multifunctional prosurvival protein that binds to several intracellular targets and promotes cell survival. HSP70 and Raf-1 are important targets of Bag-1; however, the protective function of Bag-1 in nucleus pulposus (NP) cells remains unclear. In this study, we determined the effects of Bag-1 on NP cells under oxidative stress induced by treatment with hydrogen peroxide (H2O2). We found that Bag-1 was bound to HSP70, but Bag-1-Raf1 binding did not occur in NP cells. Bag-1 overexpression in NP cells enhanced cell viability and mitochondrial function and significantly suppressed p38/MAPKs phosphorylation during oxidative stress, although NP cells treated with a Bag-1 C-terminal inhibitor, which is the binding site of HSP70 and Raf-1, decreased cell viability and mitochondrial function during oxidative stress. Furthermore, the phosphorylation of the ERK/MAPKs was significantly increased in Bag-1 C-terminal inhibitor-treated NP cells without H2O2 treatment but did not change with H2O2 exposure. The phosphorylation of Raf-1 was not influenced by Bag-1 overexpression or Bag-1 C-terminal binding site inhibition. Overall, the results suggest that Bag-1 preferentially interacts with HSP70, rather than Raf-1, to protect NP cells against oxidative stress.

Effect of Neonicotinoid Pesticides on Japanese Water Systems: Review with Focus on Reproductive Toxicity.

Neonicotinoid pesticides (NPs) are neurotoxic substances. They are highly effective as insecticides owing to their water solubility, permeability, and long-lasting activity. These molecules are structurally similar to nicotine and act as nicotinic acetylcholine receptor agonists. The administration of NPs to experimental animals reportedly causes neuromuscular and reproductive disorders. Moreover, recently reported problems caused by NPs include damage to land-dwelling creatures (such as mammals and birds), hydrobiology, and ecosystems. This review summarizes the recent reports on NP concentrations detected in river systems in several Japanese regions. These values were lower than the environmental standard values; however, seasonal variations were observed. Furthermore, reports on NP-induced testicular and ovarian toxicity were examined, revealing that the mechanism of injury is mainly driven by oxidative stress. The use of NPs is declining worldwide, except in Japan; therefore, continuous monitoring remains necessary.

Specific acupuncture stimulation of Shenshu (BL23) affects sympathetic nervous activity-associated plasma renin concentration changes.

OBJECTIVE: To examine whether specific stimulation of Shenshu (BL23) affects sympathetic nervous activity (SNA)-associated plasma renin concentration (PRC). METHODS: Eight healthy volunteers participated in three pattern conditions in random order: control (Cont), stimulation of Shenshu (BL23), and stimulation of sham point (Sham). All participants were initially in the supine position for > 60 min, and then remained in the standing position during the experimental procedure to increase SNA. An electrocardiogram was used to calculate low frequency/high frequency (LF/HF) ratio; blood was collected to analyze PRC. RESULTS: The LF/HF ratio was significantly increased in the standing position when compared with the supine position ( 0.01). There was no difference in LF/HF ratio during or after stimulation of Shenshu (BL23) in the standing position when compared with before the stimulation in the supine position; however, the LF/HF ratio was significantly increased in Cont and Sham conditions ( 0.01). There was no difference in PRC after stimulation of Shenshu (BL23) in the standing position when compared with before the stimulation in the supine position; however, there was a significant increase in PRC in the Cont and Sham conditions (Cont 0.05, Sham 0.01). CONCLUSION: Our results demonstrated that specific acupuncture stimulation of Shenshu (BL23) in the standing position decreased SNA-associated PRC, which was not observed during acupuncture stimulation of the sham point.

The Onset of Dental Erosion Caused by Food and Drinks and the Preventive Effect of Alkaline Ionized Water.

In recent years, the incidence of dental erosion caused by the ingestion of acidic foods and drinks, including sports drinks, has been increasing in Japan and elsewhere. Therefore, the problems associated with this injury can no longer be ignored in dental clinical practice. The ingestion of these foods and drinks is important from the viewpoint of overall health and disease prevention. For example, fermented foods, such as Japanese pickles, enhance the nutritional value of foodstuffs and promote the absorption of nutrients into the body, and sports drinks are useful for preventing heat stroke and dehydration. Therefore, eliminating these intakes is not a viable solution. In this paper, we outline the mechanism of dental erosion caused by acidic beverages and also describe the effectiveness of alkaline ionized water (AIW) at preventing acid erosion. Given the fact that the complete elimination of acidic beverage consumption is highly unlikely, remedies such as the use of alkaline ionized water (AIW) may be helpful.

Heat shock protein A4L is a potent autoantigen for testicular autoimmunity in mice.

Experimental autoimmune orchitis (EAO) may be used as a model to investigate immunological infertility in men. Murine EAO is induced via immunization with auto-immunogenic antigens (AIAgs) from testicular germ cells (TGCs). CD4 + T cells play a crucial role in EAO induction. However, whether AIAgs induce an immune response remains unclear. We aimed to identify self-antigens that induce EAO by screening a phage display library of random TGC peptides using IgG from EAO-induced A/J mice. Twenty TGC-specific AIAgs were detected, and G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) and heat shock protein A4L (HSPA4L) were identified as candidate AIAgs that induce EAO. Immunization with GIT1 or HSPA4L, emulsified in complete Freund's adjuvant, resulted in 66 % or 100 % incidence of EAO, respectively, indicating that HSPA4L is a most potent AIAg that induces EAO in mice. These findings may expectedly help improve the diagnostic procedures and treatment of immunological infertility in men.

Variation of insertion of the pectoralis major in a cadaveric study: A case report.

RATIONALE: Typically, the tendon of the pectoralis major inserts into the crest of the greater tubercle of the humerus. However, anomalous insertion sites of the pectoralis major tendons have been noted. PATIENT CONCERNS: The cadaver of a 95-year-old Japanese man was selected from the bodies used for gross anatomy practice at the Tokai University School of Medicine in 2018. DIAGNOSIS: In this cadaver, the left side of the pectoralis major tendon appeared to insert at the crest of the greater tubercle and lesser tubercle of the humerus, forming a tunnel measuring 2.5 cm in total length. INTERVENTION: We removed the fat and skin around the shoulder joint and upper extremity for observational purposes and carefully examined the structures during gross anatomy. OUTCOMES: The medial side of the insertion of the pectoralis major tendon was not into the humerus but had combined with the tendon of the latissimus dorsi, which then loosely inserted into the humerus. As the roof and both walls comprised the tendon of the pectoralis major and the floor was formed by the tendon of the latissimus dorsi and humerus, the structure formed a tunnel. LESSONS: This study is important for orthopedic and rehabilitation physicians in treating diseases of the long head of the biceps brachii tendon. As part of management, the condition of the tendon of the pectoralis major should be confirmed using magnetic resonance imaging or echocardiography.

Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis.

Busulfan is used as a chemotherapeutic drug to treat childhood and adult chronic myelogenous leukemia, and as an immunosuppressive agent before bone marrow transplantation. A key side effect of busulfan is the alteration of male reproductive function. Infertility caused by anti-cancer treatments has become a significant concern, but there are currently limited treatments for this condition. Recently, we demonstrated that Gosha-jinki-gan, a traditional Japanese medicine, completely reversed the spermatogenesis defects caused by cancer treatment in mice. Hochu-ekki-to and Hachimi-jio-gan are commonly used to treat male infertility, and Hachimi-jio-gan shares herbal ingredients with Gosha-jinki-gan. Therefore, in the present study, we administered Hachimi-jio-gan and Hochu-ekki-to alone or in combination to mice with severe aspermatogenesis caused by busulfan treatment. We performed testis weight measurements, quantitative histological assessments of the testes and the epididymis, and evaluated sperm counts and morphology. We also assessed the expression of immune mediators and macrophage markers. Treatment with a combination of both the medicines significantly reduced busulfan-induced testicular toxicity when compared to the lone treatment with either medicine. We demonstrated that treatment efficacy was related to a differential impact on testicular inflammation, and that the synergistic effect of co-administration completely reversed the busulfan-induced damage to the reproductive functions.

Prolonged Cold Ischemia Time in Mouse Heart Transplantation Using Supercooling Preservation.

BACKGROUND: Supercooling preservation techniques store a donor organ below 0°C without freezing. This has great advantages in inhibiting metabolism and preserving the organ in comparison to conventional preservation at 4°C. We developed a novel supercooling technique using a liquid cooling apparatus and novel preservation and perfusion solutions. The purpose of this study was to evaluate the preservation effect of our supercooling preservation technique in a mouse heart transplantation model. METHODS: Syngeneic heterotopic heart transplantation was performed in 3 groups of mice: (1) the nonpreservation group, in which the cardiac grafts were transplanted immediately after retrieval; (2) the conventional University of Wisconsin (UW) group, in which the cardiac grafts were stored in UW solution at 4°C for different periods of time; and (3) the supercooling group, in which the cardiac grafts were stored in a novel supercooling preservation solution at -8°C for different periods of time. The maximal preservation time was investigated. Twenty-four-hour sample data were collected and analyzed to compare supercooling preservation to conventional UW preservation. RESULTS: Our technique yielded a stable -8°C supercooling state. Cardiac graft revival was successfully achieved after supercooling preservation for 144 hours, and long-term survival was observed after supercooling preservation for 96 hours. Posttransplant outcomes, including myocardial ischemia-reperfusion injury, oxidative stress-related damage, and myocardial cell apoptosis, were improved in comparison to conventional 4°C UW preservation. CONCLUSIONS: Supercooling heart preservation at -8°C greatly prolonged the preservation time and improved the posttransplant outcomes in comparison to conventional 4°C UW preservation. Supercooling preservation is a promising technique for organ preservation.

Anatomy of the coronary arteries in fetal pigs: comparison with human anatomy.

In this study, 94 fetal pigs were used to comprehensively investigate the origins, number, location, and distribution of the coronary arteries to enrich knowledge on the coronary circulation in fetal pigs, and allow comparison with adult pigs and humans. In fetal pigs, the posterior interventricular sulcus branch always arose from the right coronary artery and the circumflex artery was rarely extended to the posterior interventricular sulcus, while it is variable in humans. In fetal pigs, there was sometimes anastomosis (8.5%) between the left and right conus branches as nutrient arteries of the pulmonary cone. Other branches were not significantly different between fetal pigs and humans, including the acute marginal branch, obtuse marginal branch, and sinoatrial nodal artery. Coronary dominance was also similar. In conclusion, compared with adult pigs, dissection of the coronary arteries in fetal pigs provided a more faithful overview of the porcine coronary circulation. The coronary arteries in fetal pigs were also more suitable for comparison with humans when pigs are used as experimental animals for studying the coronary vessels, which could be an important reference for investigation of clinical treatment of the coronary arteries. In summary, our data provide reliable information about the distribution and ramifications of the coronary arteries, and could be useful for clinicians and surgeons who wish to comprehensively understand coronary anatomy.

The effectiveness of traditional Japanese medicine Goshajinkigan in irradiation-induced aspermatogenesis in mice.

BACKGROUND: Infertility and gonadal dysfunction are well known side-effects by cancer treatment in males. In particularly, chemotherapy and radiotherapy induced testicular damage, resulting in prolonged azoospermia. However, information regarding therapeutics to treat spermatogenesis disturbance after cancer treatment is scarce. Recently, we demonstrated that Goshajinkigan, a traditional Japanese medicine, can completely rescue severe busulfan-induced aspermatogenesis in mice. In this study, we aimed to detect the effects of Goshajinkigan on aspermatogenesis after irradiation. METHODS: This is animal research about the effects of traditional Japanese medicine on infertility after cancer treatment. C57BL/6 J male mice received total body irradiation (TBI: a single dose of 6Gy) at 4 weeks of age and after 60 days were reared a Goshajinkigan (TJ107)-containing or TJ107-free control diet from day 60 to day 120. Then, two untreated females were mated with a single male from each experimental group. On day 60, 120 and 150, respectively, the sets of testes and epididymis of the mice in each group after deep anesthetization were removed for histological and cytological examinations. RESULTS: Histological and histopathological data showed that 6Gy TBI treatment decreased the fertility rate (4/10) in the control diet group; in contrast, in the TJ107-diet group, the fertility rate was 10/10 (p < 0.05 vs. 6Gy group). Supplementation with TJ107 was found to rescue the disrupted inter-Sertoli tight junctions via the normalization of claudin11, occludin, and ZO-1 expression and reduce serum anti-germ cell autoantibodies. CONCLUSIONS: These findings show the therapeutic effect on TBI-induced aspermatogenesis and the recovering disrupted gonadal functions by supplementation with TJ107.

Acupuncture Point "Hegu" (LI4) Is Close to the Vascular Branch from the Superficial Branch of the Radial Nerve.

The acupuncture point "Hegu" (LI4) has been used for treating peripheral circulatory failure, which is located in the area covered by the superficial branch of the radial nerve (SBRN). SBRN has branches reaching arteries, so-called vascular branches (VBs), which are thought to be involved in the arterial constriction. The distribution areas of the VBs from the SBRN have been reported, but the positional relationship between these distribution areas and the acupuncture points are not known. To examine the positional relationship between LI4 and VBs from the SBRN, forty hands were examined to assess the positional relationship between the acupuncture points "Erjian" (LI2), "Sanjian" (LI3), LI4, and "Yangxi" (LI5) in the Yangming Large Intestine Meridian of Hand, which are located in the area covered by SBRN, and the VBs from the SBRN. After the VBs were identified, the distances from the acupuncture points (LI2, LI3, LI4, and LI5) to the point where the VBs reached the radial artery or the first dorsal metacarpal artery were measured. VBs reaching the radial arteries were observed in all specimens. The mean distances from LI2, LI3, LI4, and LI5 to the point where the VBs reached the radial artery were 64.2 ± 8.2 mm, 42.0 ± 7.5 mm, 4.3 ± 4.3 mm, and 33.0 ± 4.8 mm, respectively. LI4 was significantly closer than the other acupuncture points (P<0.01). The nerve fibers of the VBs adjacent to the radial artery were confirmed using hematoxylin and eosin staining. Our findings provide anatomical evidence that stimulation at LI4 is used for treating peripheral circulatory failure such as Raynaud's disease. LI4 is significant because it is located at a source point, making it clinically important.

The distribution of nerves supplying the testis, epididymis and accessory sex glands of Suncus murinus.

Chronic testicular pain remains an important challenge for urologists. Investigation of the innervation of male gonads thus becomes essential for deepening our understanding of their regulatory roles in male reproductive physiology and pathophysiology. Studies of testicular innervation are mainly limited to the intratesticular peptidergic nerves of the testis by immunohistochemical and acetylcholinesterase histochemical investigations in some animals. Little is known about the detailed, overall distribution in general experimental animal testis. In this study, the distribution of nerves supplying the testis, epididymis and accessory sex glands of Suncus murinus was investigated by whole mount immunohistochemistry staining using a neurofilament protein antibody. Testicular nerves arose through three routes: nerves deriving from the mesenteric and renal plexuses accompanied the testicular artery, entering into the testicular hilum through the superior ligament of the testis. The nerves originating from the hypogastric plexus then ran along the internal iliac artery, deferential artery, and passed through the mesoductus deferens or mesoepididymis, innervating the cauda and corpus of the epididymis, the vas deferens and the inferior pole of the testis. The third route arose from the pelvic plexus, distributed in the seminal vesicle and the prostate. The density of nerve fibers was higher in the cauda epididymidis than in the testis, and more abundant in the vas deferens. The different origins and distribution densities of testicular nerves in S. murinus may serve different neuronal regulatory functions, and, therefore, S. murinus may be an important model animal for understanding the different characteristics of testicular pain.

Mammalian Susceptibility to a Neonicotinoid Insecticide after Fetal and Early Postnatal Exposure.

Neonicotinoids have become the most widely used class of insecticides world-wide. Although numerous studies have documented neonicotinoid toxicity in bees and other insects, the effects of exposure during early development in mammals remain largely unexplored. We assessed the effects of the neonicotinoid imidacloprid (IMI) in adult male and female mice after in utero and early postnatal exposure. Pregnant mice were infused with IMI (0.5 mg/kg/day) from gestational day 4 to the end of nursing at postnatal day 21. The young adult offspring were studied in a series of biochemical and behavioral tests. To assess reproducibility, the behavioral analyses were conducted in three separate studies using multiple exposed litters. Exposure to IMI reduced fecundity, and in adult offspring, decreased body weight in male but not female pups. Offspring from IMI-treated mothers displayed lower triglycerides, elevated motor activity, enhanced social dominance, reduced depressive-like behavior, and a diminution in social aggression compared to vehicle treated controls. Low levels of IMI were detected in the brains and livers of the treated mothers, while trace levels were detected in some offspring. Our results demonstrate that transient exposure to a neonicotinoid over the early developmental period induces long-lasting changes in behavior and brain function in mice.

Anatomical variants of dorsal scapular nerve in relation to the middle scalene muscle in Japanese population.

Dorsal scapular nerve (DSN) block is often performed in Japanese pain clinics to treat neck pain and katakori (a unique symptom in Japanese population characterized by myofascial pain syndromes such as shoulder girdle pain). However, to the best of our knowledge, there are only a few studies regarding anatomical variations in DSN paths around the middle scalene muscle (MSM) in Japanese population. Thus, we conducted a cadaveric study to examine anatomical variations in DSN paths around the MSM in Japanese population.DSN anatomies of 70 adult Japanese cadavers used for research and gross anatomy practice at the Tokai University School of Medicine between 2015 and 2016 were examined.In all cadavers, DSNs originated from the brachial plexus (BP) and innervated the rhomboid major, rhomboid minor, and levator scapulae muscles via the MSM. Two types of DSN paths were observed: piercing-type (piercing the MSM) and anterior-type (running in front of the MSM). We surveyed all 140 sides in 70 Japanese cadavers; of these, 95 sides had piercing-type and 45 had anterior-type paths. Of the 70 cadavers, 42 had piercing-type and 17 had anterior-type paths on both the sides. In 9 cadavers, the left and right sides had piercing-type and anterior-type paths, respectively. In the other 2 cadavers, the right and left sides had piercing-type and anterior-type paths, respectively.We found 2 distinct anatomical variants for DSN paths around the MSM in this Japanese cohort. Our results suggest that the rate of anterior-type DSN path is higher in Japanese population. Therefore, it is necessary to maintain caution while injecting anesthetic agents during a DSN block and the type of DSN should be considered.

Effects of interleukin-17A in nucleus pulposus cells and its small-molecule inhibitors for intervertebral disc disease.

Intervertebral discs (IVD) degeneration, which is caused by ageing or mechanical stress, leads to IVD disease, including back pain and sciatica. The cytokine interleukin (IL)-17A is elevated in NP cells during IVD disease. Here we explored the pharmacotherapeutic potential of IL-17A for the treatment of IVD disease using small-molecule inhibitors that block binding of IL-17A to the IL-17A receptor (IL-17RA). Treatment of NP cells with IL-17A increased expression of cyclooxygenase-2 (COX-2), IL-6, matrix metalloproteinase (MMP)-3 and MMP-13. These increases were suppressed by an IL-17A-neutralizing antibody, and small molecules that were identified as inhibitors by binding to the IL-17A-binding region of IL-17RA. IL-17A signalling also altered sulphated glycosaminoglycan deposition and spheroid colony formation, while treatment with small-molecule inhibitors of IL-17A attenuated this response. Furthermore, mitogen-activated protein kinase pathways were activated by IL-17A stimulation and induced IL-6 and COX-2 expression, while small-molecule inhibitors of IL-17A suppressed their expression. Taken together, these results show that IL-17A is a valid target for IVD disease therapy and that small-molecule inhibitors that inhibit the IL-17A-IL-17RA interaction may be useful for pharmacotherapy of IVD disease.

Gosha-Jinki-Gan Recovers Spermatogenesis in Mice with Busulfan-Induced Aspermatogenesis.

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.

Effect of acetamiprid on the immature murine testes.

Neonicotinoids, such as acetamiprid (ACE), a pesticide used worldwide, are believed to be safe for human use. These molecules are structurally similar to nicotine, act as nicotinic acetylcholine receptor (nAChR) agonists, and were shown to be associated with neuromuscular and reproductive disorders, but these experiments were primarily performed in mature animals. In this study, the effects of ACE on the testes of immature mice were examined. The exposure of 3-week-old mice to ACE-containing water for 180 days led to a decrease in body weight and mildly affected spermatogenesis. Additionally, the expression of testosterone-metabolism genes, nAChR subunit genes, and proliferation-associated genes decreased in the testes of ACE-treated mice. Our results show that immature rodents may be less sensitive to ACE than mature ones, that mice may be more likely to accumulate ACE than rats, and that the development of disorders may be affected by the accumulation of ACE in the testes.