A Multi-modality Approach Towards Elucidation of the Mechanism for Human Achilles Tendon Bending during Passive Ankle Rotation

© 2018 The Author(s). The in vitro unconstrained Achilles tendon is nearly straight, while in vivo experiments reveal that the proximal region of the Achilles tendon, adjacent to Kager's fat pad, bends ventrally during plantarflexion but remains nearly straight during dorsiflexion. Tendon bending is an important factor in determining the displacement of the foot compared to the shortening of the muscle fibers. The objective of this study was to elucidate the various mechanisms that could cause tendon bending, which currently remain unknown. Examination of Thiel-embalmed cadavers, with preservation of native articular joint mobility, revealed that the Achilles tendon still bent ventrally even when its surrounding tissues, including the skin surface, Kager's fat pad, and distal portions of the soleus muscle were removed. Shear modulus and collagen fiber orientation were distributed homogeneously with respect to the longitudinal line of the tendon, minimizing their causative contributions to the bending. Given that tendon bending is not caused by either the nature of the deformations of the tissues surrounding the Achilles tendon or its physical properties, we conclude that it results from the geometric architecture of the Achilles tendon and its configuration with respect to the surrounding tissues

Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors

運動刺激に応答して生じる骨格筋間葉系前駆細胞（Fibro-adipogenic Progenitors: FAPs）の細胞老化が，骨格筋の再生に重要であることを明らかにした．一方で，慢性炎症性筋疾患モデルマウスではFAP の細胞老化が不十分で，運動がむしろ筋の線維化を悪化させることがわかった．さらに，慢性炎症性筋疾患モデルマウスに対して，運動刺激と薬物治療の併用でAMP-activated protein kinase（AMPK）の活性化とともにFAPs の細胞老化を誘導することで，高い治療効果を発揮できることを明らかにした．これらの成果は，運動刺激がなぜ，筋再生を促す場合と線維化や炎症を悪化させる場合があるかという，臨床上の問題点を解決する，新しいメカニズムのひとつを解明したものであり，慢性炎症性筋疾患に対する安全で効果的な治療につながることが期待できる

Interface between intramembranous and endochondral ossification in human foetuses

In the head and neck of human mid-term foetuses, the interface between areas of endochondral ossification and adjacent membranous (intramembranous) ossification is extensive. Using 8 foetal heads at 15–16 weeks, we have demonstrated differences in the matrices and composite cells between these 2 ossification processes, especially in the occipital squama and pterygoid process. Aggrecan-positive cartilage was shown to be invaded by a primitive bony matrix that was negative for aggrecan. At the interface, the periosteum was continuous with the perichondrium without any clear demarcation, but tenascin-c expression was restricted to the periosteum. In contrast, the interface between the epiphysis and shaft of the femur showed no clear localisation of tenascin-c. Versican expression tended to be restricted to the perichondrium. In the pterygoid process, the density of CD34-positive vessels was much higher in endochondral than in membranous ossification. The membranous part of the occipital was considered most likely to contribute to growth of the skull to accommodate the increased volume of the brain, while the membranous part of the pterygoid process seemed to be suitable for extreme flattening under pressure from the pterygoid muscles

Suppression of bone marrow-derived microglia in the amygdala improves anxiety-like behavior induced by chronic partial sciatic nerve ligation in mice

大脳辺縁系の一部である扁桃体は，不快情動の形成において重要な役割を担っている．我々は，神経障害性疼痛の慢性期に扁桃体中心核に集積する骨時由来ミクログリアが IL-1βを分泌して神経細胞に作用することで，慢性疼痛における不快情動の形成に関与することを明らかにした

Application of light microscopical and ultrastructural immunohistochemistry in the study of goblet cell carcinoid in the appendix

<p>Abstract</p> <p>Background</p> <p>Goblet cell carcinoids appear less frequently in the appendix than do other carcinoids. In the presented work a case with a goblet cell carcinoid of the appendix is described.</p> <p>Methods</p> <p>Routine histological and histochemical methods were employed, with a combination of histochemistry and immunohistochemistry on one section and light and electron microscopical immunohistochemisty on paraffin-embedded material, were applied to identify the type of the carcinoid and to reveal the fine structure of cell types in the tumour nests of the appendix.</p> <p>Results</p> <p>During the biopsy of a patient who had undergone appendectomy, an infiltration with clusters of goblet cells in the submucosa of the appendix was found. After a second operation of right-sided hemicolectomy, similar clusters of goblet cells were detected in the muscle layers of the caecum. After 18 months the patient died from cirrhosis and had not developed metastases or any recurrence. Immunohistochemically the serotonin-, somatostatin-, chromogranin A- and synaptophysin-positive endocrine cells were basally attached to mucin-secreting cells. The combined staining revealed simultaneously present endocrine cells (chromogranin-A-positive) and mucin-secreting cells (PAS- or alcian blue-positive). The ultrastructural immunohistochemistry showed that chromogranin A-positive cells had discoid and pleomorphic granules and were located in tumour nests or as single cells in the appendiceal wall.</p> <p>Conclusion</p> <p>The combined histochemical and immunohistochemical procedure and the ultrastructural immunohistochemistry on archival material could contribute in clarifying the diagnosis of goblet cell carcinoid.</p

Central neuropeptide Y receptors are involved in 3(rd )ventricular ghrelin induced alteration of colonic transit time in conscious fed rats

BACKGROUND: Feeding related peptides have been shown to be additionally involved in the central autonomic control of gastrointestinal functions. Recent studies have shown that ghrelin, a stomach-derived orexigenic peptide, is involved in the autonomic regulation of GI function besides feeding behavior. Pharmacological evidence indicates that ghrelin effects on food intake are mediated by neuropeptide Y in the central nervous system. METHODS: In the present study we examine the role of ghrelin in the central autonomic control of GI motility using intracerobroventricular and IP microinjections in a freely moving conscious rat model. Further the hypothesis that a functional relationship between NPY and ghrelin within the CNS exists was addressed. RESULTS: ICV injections of ghrelin (0.03 nmol, 0.3 nmol and 3.0 nmol/5 μl and saline controls) decreased the colonic transit time up to 43%. IP injections of ghrelin (0.3 nmol – 3.0 nmol kg(-1 )BW and saline controls) decreased colonic transit time dose related. Central administration of the NPY(1 )receptor antagonist, BIBP-3226, prior to centrally or peripherally administration of ghrelin antagonized the ghrelin induced stimulation of colonic transit. On the contrary ICV-pretreatment with the NPY(2 )receptor antagonist, BIIE-0246, failed to modulate the ghrelin induced stimulation of colonic motility. CONCLUSION: The results suggest that ghrelin acts in the central nervous system to modulate gastrointestinal motor function utilizing NPY(1 )receptor dependent mechanisms

Stretching positions for the coracohumeral ligament: Strain measurement during passive motion using fresh/frozen cadaver shoulders

<p>Abstract</p> <p>Background</p> <p>Contracture of the coracohumeral ligament is reported to restrict external rotation of the shoulder with arm at the side and restrict posterior-inferior shift of the humeral head. The contracture is supposed to restrict range of motion of the glenohumeral joint.</p> <p>Methods</p> <p>To obtain stretching position of the coracohumeral ligament, strain on the ligament was measured at the superficial fibers of the ligament using 9 fresh/frozen cadaver shoulders. By sequential measurement using a strain gauge, the ligament strain was measured from reference length (L0). Shoulder positions were determined using a 3 Space Tracker System. Through a combination of previously reported coracohumeral stretching positions and those observed in preliminary measurement, ligament strain were measured by passive external rotation from 10° internal rotation, by adding each 10° external rotation, to maximal external rotation.</p> <p>Results</p> <p>Stretching positions in which significantly larger strain were obtained compared to the L0 values were 0° elevation in scapula plane with 40°, 50° and maximum external rotation (5.68%, 7.2%, 7.87%), 30° extension with 50°, maximum external rotation (4.20%, 4.79%), and 30° extension + adduction with 30°, 40°, 50° and maximum external rotation (4.09%, 4.67%, 4.78%, 5.05%)(P < 0.05). No positive strain on the coracohumeral ligament was observed for the previously reported stretching positions; ie, 90° abduction with external rotation or flexion with external rotation.</p> <p>Conclusions</p> <p>Significant strain of the coracohumeral ligament will be achieved by passive external rotation at lower shoulder elevations, extension, and extension with adduction.</p

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions