Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.

The mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses of less than 1 Pa resulting from interstitial-fluid flow induced by such passive head motions reduced the expression of the angiotensin II type-1 receptor in astrocytes in the rostral ventrolateral medulla, and the resulting antihypertensive effects were abrogated by hydrogel introduction that inhibited interstitial-fluid movement in the medulla. Our findings suggest that oscillatory mechanical interventions could be used to elicit antihypertensive effects.

[Minimally Invasive Direct Coronary Artery Bypass in a Patient with Osteopetrosis and Symptomatic Ischemic Heart Disease:Report of a Case].

Osteopetrosis is a heterogeneous group of heritable conditions. It varies greatly in severity, and fracture treatment remains a matter of controversy due to altered responses to fixation and the risk of osteomyelitis. Therefore, sternotomy outcomes in this condition are unclear. We report the case of a patient with osteopetrosis and coronary artery disease (CAD). A 78-year-old man with osteopetrosis presented with frequent chest pain. Coronary angiography revealed two-vessel CAD. Percutaneous coronary intervention was contraindication because of coronary aneurysm in the left main trunk. Considering risks in median sternotomy, we performed minimally invasive cardiac surgery through left minithoracotomy for coronary artery bypass grafting( CABG). But we needed to break the left fourth rib to obtain sufficient surgical views. To the best of our knowledge, this is the first case report on CABG for a patient with osteopetrosis and endoscopic surgery without rib retractor is recommended.

Application of Passive Head Motion to Generate Defined Accelerations at the Heads of Rodents.

Exercise is widely recognized as effective for various diseases and physical disorders, including those related to brain dysfunction. However, molecular mechanisms behind the beneficial effects of exercise are poorly understood. Many physical workouts, particularly those classified as aerobic exercises such as jogging and walking, produce impulsive forces at the time of foot contact with the ground. Therefore, it was speculated that mechanical impact might be implicated in how exercise contributes to organismal homeostasis. For testing this hypothesis on the brain, a custom-designed ''passive head motion'' (hereafter referred to as PHM) system was developed that can generate vertical accelerations with controlled and defined magnitudes and modes and reproduce mechanical stimulation that might be applied to the heads of rodents during treadmill running at moderate velocities, a typical intervention to test the effects of exercise in animals. By using this system, it was demonstrated that PHM recapitulates the serotonin (5-hydroxytryptamine, hereafter referred to as 5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) neurons of mice. This work provides detailed protocols for applying PHM and measuring its resultant mechanical accelerations at rodents' heads.

[Intraoperative Aortic Dissection during Mitral Valve Plasty:Report of a Case].

We report the case of a 74-year-old woman who underwent mitral valve plasty for mitral regurgitation. During the surgery, the ascending aorta was dilated and turned dark red after aortic cannulation. Intraoperative transesophageal echocardiography and direct epiaortic echography revealed type A aortic dissection. In addition to mitral valve plasty, replacement of the ascending aorta was performed under hypothermic circulatory arrest. The postoperative course was uneventful. Because intraoperative aortic dissection is a rare complication, its rapid identification and appropriate management is essential.

Mechanical load regulates bone growth via periosteal Osteocrin.

Mechanical stimuli including loading after birth promote bone growth. However, little is known about how mechanical force triggers biochemical signals to regulate bone growth. Here, we identified a periosteal-osteoblast-derived secretory peptide, Osteocrin (OSTN), as a mechanotransducer involved in load-induced long bone growth. OSTN produced by periosteal osteoblasts regulates growth plate growth by enhancing C-type natriuretic peptide (CNP)-dependent proliferation and maturation of chondrocytes, leading to elongation of long bones. Additionally, OSTN cooperates with CNP to regulate bone formation. CNP stimulates osteogenic differentiation of periosteal osteoprogenitors to induce bone formation. OSTN binds to natriuretic peptide receptor 3 (NPR3) in periosteal osteoprogenitors, thereby preventing NPR3-mediated clearance of CNP and consequently facilitating CNP-signal-mediated bone growth. Importantly, physiological loading induces Ostn expression in periosteal osteoblasts by suppressing Forkhead box protein O1 (FoxO1) transcription factor. Thus, this study reveals a crucial role of OSTN as a mechanotransducer converting mechanical loading to CNP-dependent bone formation.

Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats.

In the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR. Here, we hypothesized that early SSRI administration as a preemptive treatment strategy would effectively prevent the onset of spasticity. We used a rat model of contusive SCI and administered escitalopram during the first 4 weeks after injury, which is the period required for spasticity development in rodent models. We performed a swimming test to quantify spastic behaviors and conducted the Hoffman reflex test as well as histological analyses for 5-HT2AR and KCC2 expressions. Four weeks of escitalopram administration suppressed spastic behaviors during the swimming test and reduced the population of spasticity-strong rats. Moreover, the treatment resulted in decreased immunoreactivity of 5-HT2AR in the spinal motor neurons. Result of the H-reflex test and membrane expression of KCC2 were not significantly altered. In summary, early escitalopram administration could prevent the onset of spastic behaviors via regulation of 5-HT system after SCI, but could not modulate exaggerated spinal reflex. Our results suggest a novel application of SSRIs for preventative treatment of spasticity.

[Surgical Repair of Giant Coronary Artery Aneurysm Associated with Coronary-pulmonary Artery Fistulae;Report of a Case].

A 61-year-old woman was referred to our hospital with a complaint of chest compression. Coronary angiography revealed a giant coronary artery aneurysm, located in the middle of a coronary-pulmonary artery fistula originating from the right coronary artery. Another fistula was also shown between the left anterior descending artery and the pulmonary artery. Surgical correction was indicated due to the risks of the aneurysmal rupture and coronary events. Under cardiopulmonary bypass, suture-closure of the coronary artery aneurysm and ligations of the fistulae were carried. Postoperative coronary angiography showed no aneurysm or fistula, and she was discharged uneventfully on the 12th postoperative day.

[Giant Left Atrial Myxoma Found with Congestive Heart Failure;Report of a Case].

We report a case of giant left atrial myxoma in a 52-year-old woman who developed congestive heart failure. By echocardiography, not only the myxoma but moderate degree of mitral and tricuspid regurgitation was also found. The tumor was extensively attached to the left atrial endocardium, and was excised completely together with the endocardium. No valve surgery was added. Postoperative echocardiography showed no myxoma and no mitral valve regurgitation. She was discharged in good condition on postoperative day 14.

[Severe Calcification on Glutaraldehyde-treated Autologous Pericardium after Mitral Valve Repair by Leaflet Augmentation;Report of a Case].

We report a case of surgical treatment of mitral valve stenosis due to severe calcification on the glutaraldehyde-treated autologous pericardium. A 39-year-old woman presented with progressive dyspnea. She had undergone mitral valve repair by leaflet augmentation with a glutaraldehyde-treated autologous pericardium for mitral regurgitation 3 years before. Transthoracic echocardiography showed mitral valve stenosis with limited movement of the anterior leaflet. At redo surgery, severe calcification was observed of the glutaraldehyde-treated autologous pericardium patch on the anterior mitral leaflet. Mitral valve replacement was performed successfully, and she was discharged on postoperative day 14.

Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons.

Mechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) of rodents. PHM generates interstitial fluid movement that is estimated to exert shear stress of a few pascals on cells in the PFC. Fluid shear stress of a relevant magnitude on cultured neuronal cells induces ligand-independent internalization of 5-HT2A receptor, which is observed in mouse PFC neurons after treadmill running or PHM. Furthermore, inhibition of interstitial fluid movement by introducing polyethylene glycol hydrogel eliminates the effect of PHM on 5-HT2A receptor signaling in the PFC. Our findings indicate that neuronal cell function can be physiologically regulated by mechanical forces in the brain.

Application of Consistent Massage-Like Perturbations on Mouse Calves and Monitoring the Resulting Intramuscular Pressure Changes.

Massage is generally recognized to be beneficial for relieving pain and inflammation. Although previous studies have reported anti-inflammatory effects of massage on skeletal muscles, the molecular mechanisms behind are poorly understood. We have recently developed a simple device to apply local cyclical compression (LCC), which can generate intramuscular pressure waves with varying amplitudes. Using this device, we have demonstrated that LCC modulates inflammatory responses of macrophages in situ and alleviates immobilization-induced muscle atrophy. Here, we describe protocols for the optimization and application of LCC as a massage-like intervention against immobilization-induced inflammation and atrophy of skeletal muscles of mouse hindlimbs. The protocol that we have developed can be useful for investigating the mechanism underlying beneficial effects of physical exercise and massage. Our experimental system provides a prototype of the analytical approach to elucidate the mechanical regulation of muscle homeostasis, although further development needs to be made for more comprehensive studies.

[Surgical Treatment of Right Ventricular Perforation by a Transvenous Electrode Catheter;Report of a Case].

We report a case of surgical treatment of iatrogenic right ventricular perforation. An 86-year-old woman with sick sinus syndrome was treated by insertion of transvenous electrode catheters. She was transferred to our hospital due to chest pain 9 days after the insertion. We found the ventricular electrode catheter had perforated the right ventricle by computed tomography (CT). This perforated lesion was repaired under beating heart using 2-0 monofilament mattress sutures reinforced by felt pledgets. The perforation may have occurred because the apex portion of the right ventricle was fragile. Iatrogenic cardiac trauma is rare, and prompt recognition and treatment are essential.

[Surgery of Papillary Adenoma;Report of a Case].

A 59-year-old man consulted our hospital because of an abnormal shadow on a chest X-ray without any symptoms. A chest computed tomography (CT) revealed growing pulmonary nodule in the right lower lobe. Benign lung tumor was suspected and the patient underwent right lower lobe partial resection. Pathological examination demonstrated the tumor to be pulmonary papillary adenoma within round atelectasis.

Therapeutic strategy for acute pleural empyema: comparison between retrospective study and prospective study.

OBJECTIVES: The purpose of this study is to investigate the efficiency of therapeutic strategy for acute pleural empyema. METHODS: We retrospectively reviewed 121 acute empyema patients and evaluated the therapeutic strategy for acute pleural empyema. Then, we prospectively reviewed 114 acute pleural empyema patients based on the strategy. RESULTS: The duration from onset to hospitalization in our hospital is statistically shorter, and the mortality and the rate of stage 3 empyema patients are lower in the prospective study group (PSG) than in the retrospective study group (RSG). Retrospective study and prospective study found that surgical group (SG) had more favorable outcomes than non-surgical group (NSG). Although antibiotic treatment duration, hospital stay, and entire mortality were comparable in NSG of both study groups, mortality of patients with PS grade 4 was significantly lower in PSG. SG in PSG had more favorable outcomes than that in RSG, such as antibiotic treatment duration, hospital stay, complication, and mortality. CONCLUSIONS: The good outcomes may be mainly caused by shorter duration from onset to hospitalization and shorter duration from hospitalization to operation. Operative management is an effective procedure for selected patients, and it is important to refer for thoracic surgical consultation earlier.

Repetitive transient paraplegia caused by painless acute aortic dissection.

CASE: Making a precise diagnosis of type A acute aortic dissection (AAD) presenting with atypical symptoms might be challenging for clinicians. Misdiagnosis and misuse of thrombolytic therapy can have devastating consequences. OUTCOME: Herein, we report a case of painless type A AAD complicated by transient leg paresthesia, which was successfully treated with surgery. On admission, sudden onset of right leg numbness and muscle weakness was the only clue toward the correct final diagnosis. CONCLUSION: When patients present with vague neurological symptoms, physicians should not rule out the possibility of AAD until proven otherwise.

Cardiac tamponade due to rupture of a giant coronary artery aneurysm with a coronary arteriovenous fistula: a case report.

BACKGROUND: Coronary artery aneurysm (CAA) is defined as dilatation exceeding 1.5 times the width of the normal adjacent coronary artery segments. CAA usually causes few symptoms, and rupture is rare, but can be lethal due to cardiac tamponade when it does occur. CASE PRESENTATION: A 79-year-old woman presented with presyncope and back pain. Emergency surgery was performed based on a diagnosis of cardiac tamponade due to either rupture of coronary arteriovenous fistula or CAA. At surgery, a rupture site was located on the wall of the giant CAA, with a diameter of 55 mm, originating from the ostium of the right coronary artery. Suture closure of the inflow and outflow of the aneurysm was performed, and the aneurysmal cavity was obliterated by multiple sutures. The patient made an uneventful recovery and was discharged from hospital on postoperative day 13. CONCLUSION: On the basis of this case, we propose considering rupture of a CAA as one of the causes of cardiac tamponade.

Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Effects of Treadmill Training Combined with Serotonergic Interventions on Spasticity after Contusive Spinal Cord Injury.

Spasticity usually emerges during the course of recovery from spinal cord injury (SCI). While medications and physical rehabilitation are prescribed to alleviate spastic symptoms, the insufficiency of their effects remains an important problem to be addressed. Given the challenges associated with increasing the dose of medication, we hypothesized that a combination therapy with medication and physical rehabilitation can be effective. Therefore, we examined the effects of treadmill training (TMT) along with serotonergic medication using a spastic rat model after contusive injury. Spasticity-strong SCI rats were selected 4 weeks after SCI and received one of the following interventions for 2 weeks: only TMT, TMT with fluoxetine (a selective serotonin re-uptake inhibitor), TMT with cyproheptadine (a 5-HT2 receptor antagonist), only fluoxetine, or only cyproheptadine. We performed the swimming test to quantify the frequency of spastic behaviors. We also evaluated hindlimb locomotor functions every week. At the end of the intervention, we examined the Hoffman reflex from the plantar muscle and the immunoreactivity of the 5-HT2A receptor in spinal cord tissues. While the TMT group and cyproheptadine-treated groups showed decreased spastic behaviors and reduction in spinal hyperreflexia, the fluoxetine-treated group showed the opposite effect, even with TMT. Moreover, TMT suppressed the expression of the 5-HT2A receptor in the lumbar spinal motor neurons, while cyproheptadine treatment did not change it. We did not observe any differences in locomotor functions between the groups. Taken together, our findings indicate that TMT and cyproheptadine significantly alleviated spastic symptoms, but did not show synergistic or additive effects.

Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury.

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression after SCI. OPC-specific ablation of Chd7 in injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation. Ablation of Chd7 or Sox2 in cultured OPCs shows similar phenotypes to those observed in Chd7 knock-out mice. Chd7 and Sox2 form a complex in OPCs and bind to the promoters or enhancers of the regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) genes, thereby inducing their expression. The expression of Rgcc and PKCθ is reduced in the OPCs of the injured Chd7 knock-out mice. In cultured OPCs, overexpression and knock-down of Rgcc or PKCθ promote and suppress OPC proliferation, respectively. Furthermore, overexpression of both Rgcc and PKCθ rescues the Chd7 deletion phenotypes. Chd7 is thus a key regulator of OPC activation, in which it cooperates with Sox2 and acts via direct induction of Rgcc and PKCθ expression.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to oligodendrocyte (OL) loss and demyelination, along with neuronal death, resulting in impairment of motor or sensory functions. Oligodendrocyte precursor cells (OPCs) activated in response to injury are potential sources of OL replacement and are thought to contribute to remyelination and functional recovery after SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain largely unclear. We demonstrate here that the chromatin remodeler chromodomain helicase DNA binding protein 7 (Chd7) regulates the proliferation and identity of OPCs after SCI. We have further identified regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) as novel targets of Chd7 for OPC activation.