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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.
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Cadáver , Seno Aórtico , Anciano de 80 o más Años , Humanos , Masculino , Anomalías de los Vasos Coronarios , Vasos Coronarios/anatomía & histología , Pueblos del Este de Asia , Japón , Seno Aórtico/anomalías , Seno Aórtico/diagnóstico por imagenRESUMEN
Endoplasmic reticulum (ER) stress is shown to promote nucleus pulposus (NP) cell apoptosis and intervertebral disc degeneration. However, little is known about ER stress regulation by the hypoxic disc microenvironment and its contribution to extracellular matrix homeostasis. NP cells were cultured under hypoxia (1% partial pressure of oxygen) to assess ER stress status, and gain-of-function and loss-of-function approaches were used to assess the role of hypoxia-inducible factor (HIF)-1α in this pathway. In addition, the contribution of ER stress induction on the NP cell secretome was assessed by a nontargeted quantitative proteomic analysis by sequential windowed data independent acquisition of the total high-resolution mass spectra-mass spectrometry. NP cells exhibited a lower ER stress burden under hypoxia. Knockdown of HIF-1α increased C/EBP homologous protein, protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) levels, whereas HIF-1α stabilization decreased the expression of ER stress markers Ddit3, Hsp5a, Atf6, and Eif2a. Interestingly, ER stress inducers tunicamycin and thapsigargin induced HIF-1α activity under hypoxia while promoting the unfolded protein response. NP cell secretome analysis demonstrated an impact of ER stress induction on extracellular matrix secretion, with decreases in collagens and cell adhesion-related proteins. Moreover, analysis of transcriptomic data of NP tissues from aged mice and degenerated human discs showed higher levels of unfolded protein response markers and decreased levels of matrix components. Our study shows, for the first time, that hypoxia and HIF-1α attenuate ER stress responses in NP cells, and ER stress promotes inefficient extracellular matrix secretion under hypoxia.
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Estrés del Retículo Endoplásmico , Proteínas de la Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/fisiopatología , Núcleo Pulposo/patología , Animales , Proteínas de la Matriz Extracelular/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Ratones Endogámicos C57BL , Núcleo Pulposo/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Lateral femoral cutaneous nerve (LFCN) injury after total hip arthroplasty causes patient dissatisfaction. This cadaveric study aimed to assess the risk for LFCN injury after the direct anterior approach (DAA) and anterolateral supine approach (ALS) with a focus on the anatomical variations of the LFCN. METHODS: Thirty-seven hemipelves from 20 formalin-preserved cadavers (10 males and 10 females) were dissected to identify the LFCN, evaluate variations, and measure the distance from the LFCN to each approach. The LFCN was classified as classical, late, multi trunk, or primary femoral. RESULTS: There were no significant variations in the LFCN between the sexes. The distance from the LFCN to DAA incision (10 [0-17.8] mm) was significantly less than that from the LFCN to ALS incision (27 [0-40] mm); moreover, 64.9% of DAA incisions crossed the LFCN. The classical type LFCN was closest to the DAA incision. The DAA incision most frequently crossed the LFCN at the proximal third, and the frequency of intersection of the LFCN and DAA incisions decreased by 25% by a 10-mm shortening of the DAA proximal incision. In contrast, 27% of ALS incisions crossed the LFCN. Multi trunk type LFCN was closest to the ALS incision. There were no significant differences between each approach and LFCN variations, and the frequency of intersection of the LFCN and ALS incisions decreased by 20% by a 10-mm shortening of the ALS proximal incision. CONCLUSIONS: The intersection rates between the LFCN and the DAA and between the LFCN and the ALS were approximately 65 and 30%, respectively. Approximately 20-25% of these injuries may be avoidable by a 10-mm shortening of the proximal incision.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Cadera/efectos adversos , Femenino , Nervio Femoral/lesiones , Fémur , Humanos , Masculino , MusloRESUMEN
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.
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Insecticidas , Plaguicidas , Receptores Nicotínicos , Contaminantes Químicos del Agua , Animales , Ecosistema , Insecticidas/farmacología , Japón , Mamíferos , Neonicotinoides/toxicidad , Nicotina , Plaguicidas/análisis , Plaguicidas/toxicidad , Agua , Contaminantes Químicos del Agua/toxicidadRESUMEN
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.
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Busulfano/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional/métodos , Animales , Antineoplásicos Alquilantes/efectos adversos , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Medicina Tradicional de Asia Oriental , Ratones , Recuento de Espermatozoides , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismoRESUMEN
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.
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Azoospermia/patología , Medicamentos Herbarios Chinos/farmacología , Traumatismos Experimentales por Radiación/patología , Protectores contra Radiación/farmacología , Espermatogénesis , Animales , Epidídimo/citología , Epidídimo/patología , Epidídimo/efectos de la radiación , Femenino , Japón , Masculino , Medicina Tradicional de Asia Oriental , Ratones , Ratones Endogámicos C57BL , Espermatogénesis/efectos de los fármacos , Espermatogénesis/efectos de la radiación , Testículo/citología , Testículo/patología , Testículo/efectos de la radiaciónRESUMEN
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.
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Interleucina-17/genética , Degeneración del Disco Intervertebral/tratamiento farmacológico , Desplazamiento del Disco Intervertebral/tratamiento farmacológico , Receptores de Interleucina-17/genética , Bibliotecas de Moléculas Pequeñas/farmacología , Adolescente , Adulto , Hipoxia de la Célula/genética , Ciclooxigenasa 2/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-17/antagonistas & inhibidores , Disco Intervertebral/metabolismo , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral/genética , Desplazamiento del Disco Intervertebral/metabolismo , Desplazamiento del Disco Intervertebral/patología , Masculino , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/genética , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/metabolismo , Cultivo Primario de Células , Unión Proteica/efectos de los fármacos , Receptores de Interleucina-17/antagonistas & inhibidores , Adulto JovenRESUMEN
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.
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Antineoplásicos/farmacología , Busulfano/farmacología , Medicamentos Herbarios Chinos/farmacología , Espermatogénesis/efectos de los fármacos , Animales , Antineoplásicos/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Medicina Tradicional de Asia Oriental , RatonesRESUMEN
After traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI, its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress-induced cell death and OPC survival. Hindlimb function in rats with spinal cord contusion significantly improved after amiloride administration. Amiloride significantly decreased the expression of the pro-apoptotic transcription factor CHOP in the injured spinal cord and significantly increased the expression of the ER chaperone GRP78, which protects cells against ER stress. In addition, amiloride treatment led to a significant decrease in ER stress-induced apoptosis and a significant increase of NG2-positive OPCs in the injured spinal cord. Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress-induced cell death in the acute phase of SCI.
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Amilorida/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Amilorida/farmacología , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Proteínas de Choque Térmico/metabolismo , Fármacos Neuroprotectores/farmacología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Ratas , Ratas Sprague-Dawley , Vértebras TorácicasRESUMEN
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.
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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.
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It has been reported that degenerated and herniated lumbar intervertebral discs show high expression of IL-17, suggesting that local immune reactions occur in patients with low back pain. While clinical sample analyses from different laboratories confirm this, it is not deeply not known on how IL-17 is induced in the pathology and their interactions with other inflammatory responses. This conscience review organizes current laboratory findings on this topic and present trajectory for full understanding on the role of IL-17 in pathology of intervertebral disc disease.
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The involvement of intervertebral disc (IVD) tissues, whole blood (WB) cytokines, and chemokines in pain in patients with lumbar degenerative disc disease (LDD) is unknown. We investigated the relationships between inflammatory cytokines and chemokines in human IVD tissues and WB samples and their association with pain. Expression levels of chemokines and cytokine gene expression were measured in samples from 20 patients with LDD and compared between IVD tissues and WB samples. The associations between WB chemokine and cytokine gene expression levels and pain intensity (numeric rating scale) were also analyzed. The mRNA of C-C chemokine ligand 20 (CCL20), C-C chemokine receptor 6 (CCR6), interleukin-6 (IL-6), IL-1ß, IL-17, and tumor necrosis factor-α (TNF-α) was expressed in degenerated IVD tissues. Pearson's product-moment correlation analysis produced positive correlations between CCR6 and IL-6 expression levels in IVD tissues (r = 0.845, p < 0.001) and WB samples (r = 0.963, p < 0.001). WB IL-6 and CCR6 mRNA expression levels correlated significantly with present pain, maximum pain, and average pain. By contrast, low back pain (LBP) did not correlate with serum chemokine/cytokine expression. This is the first study to report correlations between chemokine and inflammatory cytokine gene expression levels in IVD tissues and WB samples in patients with LDD in relation to pain intensity. WB CCR6 and IL-6 gene expression levels correlated significantly with present pain, maximum pain, and average pain, but not with LBP. These data provide a new understanding of the role of chemokines and inflammatory cytokines in patients with LDD and may lead to new treatment strategies for pain.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Dolor de la Región Lumbar , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Interleucina-6/metabolismo , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral , Dolor de la Región Lumbar/etiología , ARN Mensajero/metabolismoRESUMEN
Alkylating agents and irradiation induce testicular damage, which results in prolonged azoospermia. Even very low doses of radiation can significantly impair testis function. However, re-irradiation is an effective strategy for locally targeted treatments and the pain response and has seen important advances in the field of radiation oncology. At present, little is known about the relationship between the harmful effects and accumulated dose of irradiation derived from continuous low-dose radiation exposure. In this study, we examined the levels of mRNA transcripts encoding markers of 13 markers of germ cell differentiation and 28 Sertoli cell-specific products in single- and re-irradiated mice. Our results demonstrated that re-irradiation induced significantly decreased testicular weights with a significant decrease in germ cell differentiation mRNA species (Spo11, Tnp1, Gfra1, Oct4, Sycp3, Ddx4, Boll, Crem, Prm1, and Acrosin). In the 13 Sertoli cell-specific mRNA species decreased upon irradiation, six mRNA species (Claudin-11,Espn, Fshr, GATA1, Inhbb, and Wt1) showed significant differences between single- and re-irradiation. At the same time, different decreases in Sertoli cell-specific mRNA species were found in single-irradiation (Aqp8, Clu, Cst12, and Wnt5a) and re-irradiation (Tjp1, occludin,ZO-1, and ZO-2) mice. These results indicate that long-term aspermatogenesis may differ after single- and re-irradiated treatment.
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Regulación de la Expresión Génica/efectos de la radiación , ARN Mensajero/metabolismo , Reirradiación/métodos , Células de Sertoli/metabolismo , Espermatogénesis , Testículo/metabolismo , Animales , Perfilación de la Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/genética , Células de Sertoli/efectos de la radiación , Testículo/efectos de la radiaciónRESUMEN
With the increase in survival rates of cancer patients in recent years, infertility caused by anticancer treatments has become a significant concern for cancer survivors. Some studies have suggested that Sertoli cells play a key role in mediating testicular immunology in busulfan-induced aspermatogenesis. We recently demonstrated that Gosha-jinki-gan (TJ107), a traditional Japanese medicine, can completely recover injured spermatogenesis in mice 60 days after busulfan injection. In the present study, we sought to examine the levels of mRNA transcripts encoding markers of 25 Sertoli cell-specific products and 10 markers of germ cell differentiation. Our results demonstrated that only supplementation of TJ107 at day 60 after busulfan injection could significantly recover the increase in five mRNA species (Amh, Clu, Shbg, Testin, and Il1a) and the decrease in four mRNA species (Aqp8, CST9, Wnt5a, and Tjp1) in response to Busulfan (BSF) at day 120, with the increase of all examined spermatogenic markers.
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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 2.5âcm 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.
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Músculos Pectorales/anatomía & histología , Músculos Superficiales de la Espalda/anatomía & histología , Tendones/anomalías , Anciano de 80 o más Años , Puntos Anatómicos de Referencia , Cadáver , Disección , Humanos , MasculinoRESUMEN
INTRODUCTION: Intervertebral disc degeneration is strongly associated with low back pain. Cell transplantation has been extensively studied as a treatment option for intervertebral disc degeneration. It is often necessary to perform cell culture prior to cell transplantation; however, during cell expansion, the cells tend to dedifferentiate and lose their potency. Although the ability to suppress dedifferentiation by ROCK inhibitor (ROCKi) has recently been reported for chondrocytes, its effects on nucleus pulposus cells are still largely unknown. METHODS: Rat nucleus pulposus cells were cultured with or without the addition of ROCKi (Y-27632), and cell proliferation; CD24 positivity; expression of SOX9, COL2A1, Aggrecan, and COL1A1; and cell redifferentiation ability in pellet culture were evaluated. RESULTS: Although the addition of ROCKi tended to slightly increase the cell proliferative capacity, no significant differences were observed between treated and untreated conditions. The addition of ROCKi showed a trend of minimally increased COL2A1, ACAN, and SOX9 expression. Increases in COL1A1 expression was slightly suppressed by ROCKi. In pellet culture, strong increase in type II collagen deposition was observed by the addition of ROCKi. The addition of ROCKi did not significantly change the levels of CD24 positivity. The supplementation of ROCKi did not significantly enhance nucleus pulposus cell marker expression during monolayer expansion. However, ROCKi addition did result in an increased type II collagen deposition in 3D pellet culture. CONCLUSIONS: Taken together, the results suggest a minimal effect by ROCKi on nucleus pulposus cell phenotype maintenance.
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OBJECT: Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin debris. The object of this study was to investigate the mechanisms underlying the failure of significant remyelination after SCI. METHODS: The authors investigated macrophage recruitment and related factors in rats by comparing a contusion model (representing contusive SCI with residual myelin debris and failure of remyelination) with a model consisting of chemical demyelination by lysophosphatidylcholine (representing multiple sclerosis with early clearance of myelin debris and remyelination). The origin of infiltrating macrophages was investigated using mice transplanted with bone marrow cells from green fluorescent protein-transfected mice. The changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining at 2, 4, and 7 days postinjury. To investigate various factors that might be involved, the authors also investigated gene expression of macrophage chemotactic factors and adhesion factors. RESULTS: Activated macrophages coexpressing green fluorescent protein constituted the major cell population in the lesions, indicating that the macrophages in both models were mainly derived from the bone marrow, and that very few were derived from the intrinsic microglia. Immunostaining showed that in the contusion model, myelin debris persisted for a long period, and the infiltration of macrophages was significantly delayed. Among the chemotactic factors, the levels of monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor were lower in the contusion model at 2 and 4 days postinjury. CONCLUSIONS: The results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination.
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Activación de Macrófagos/fisiología , Macrófagos/fisiología , Vaina de Mielina/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Animales , Trasplante de Médula Ósea , Quimiocina CCL2/análisis , Contusiones/fisiopatología , Citocinas/análisis , Enfermedades Desmielinizantes/fisiopatología , Modelos Animales de Enfermedad , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Molécula 1 de Adhesión Intercelular/análisis , Proteínas Inflamatorias de Macrófagos/análisis , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Microglía/fisiología , Esclerosis Múltiple/fisiopatología , Fagocitosis/fisiología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta/análisis , Cicatrización de Heridas/fisiologíaRESUMEN
After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER) stress. In this study, we tested the effects of amiloride treatment on the fate of OPCs during secondary injury in rats. Amiloride is an FDA-approved diuretic for treating hypertension, which in rats enhances ER stress response and suppresses the apoptosis of glial cells after SCI. A severe contusive SCI was induced in Sprague-Dawley rats using an infinite horizon (IH)-impactor (200 kdyne). Beginning 24 h after SCI, 10 mg/kg of amiloride or phosphate buffered saline (PBS) was intraperitoneally administered daily for a period of 14 days. At 7, 14, 28, and 56 days after SCI, animals were subsequently euthanized in order to analyze the injured spinal cord. We labeled proliferating OPCs and demonstrated that amiloride treatment led to greater numbers of OPCs and oligodendrocytes in the injured spinal cord. Increased myelin basic protein (MBP) expression levels were observed, suggesting that increased numbers of mature oligodendrocytes led to improved remyelination, significantly improving motor function recovery.
RESUMEN
INTRODUCTION: In general, the long head of the biceps brachii (LHB) tendon arises from the supraglenoid tubercle in the shoulder joint, and it has an important stabilizing mechanism for the humeral head in the shoulder joint. This case demonstrates that even if the LHB tendon can be palpated outside of the shoulder joint, it may disappear in the intertubercular sulcus (IS) and in the glenohumeral (GH) joint because of abnormal articulation. PATIENT CONCERNS: This case involved the cadaver of an 82-year-old Japanese man (number 1936, cause of death: hepatocellular tumor), who was selected from the bodies used for gross anatomy practice at the Tokai University School of Medicine in 2017. INTERVENTION: We removed the fat and skin around the shoulder joint for observational purposes and carefully examined the gross anatomy of the structures. DIAGNOSIS: We suspected that the long head of the biceps brachii tendon arose from the lesser tubercle (LT) in the cadaver. In our case, it was found that the upper part of the subscapularis (SSC) tendon was torn first, and the succeeding degenerative changes and rupture of the LHB tendon were intra-articular. OUTCOMES: The long head of the biceps brachii tendon was found to be ruptured in the GH joint, and scar tissue developed between the distal stump of the tendon and the articular capsule, resulting in fusion with the LT. CONCLUSIONS: This case necessitates confirmation that the LHB tendon is present in the IS and in the GH joint to treat cases wherein failure of the dynamic stabilizing mechanism for the humeral head occurs.