Deconstructing the traditional Japanese medicine “Kampo”: compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism

Prevalence and Distribution of Ossified Lesions in the Whole Spine of Patients with Cervical Ossification of the Posterior Longitudinal Ligament A Multicenter Study (JOSL CT study)

Ossification of the posterior longitudinal ligament (OPLL) can cause severe and irreversible paralysis in not only the cervical spine but also the thoracolumbar spine. To date, however, the prevalence and distribution of OPLL in the whole spine has not been precisely evaluated in patients with cervical OPLL. Therefore, we conducted a multi-center study to comprehensively evaluate the prevalence and distribution of OPLL using multi-detector computed tomography (CT) images in the whole spine and to analyze what factors predict the presence of ossified lesions in the thoracolumbar spine in patients who were diagnosed with cervical OPLL by plain X-ray. Three hundred and twenty-two patients with a diagnosis of cervical OPLL underwent CT imaging of the whole spine. The sum of the levels in which OPLL was present in the whole spine was defined as the OP-index and used to evaluate the extent of ossification. The distribution of OPLL in the whole spine was compared between male and female subjects. In addition, a multiple regression model was used to ascertain related factors that affected the OP-index. Among patients with cervical OPLL, women tended to have more ossified lesions in the thoracolumbar spine than did men. A multiple regression model revealed that the OP-index was significantly correlated with the cervical OP-index, sex (female), and body mass index. Furthermore, the prevalence of thoracolumbar OPLL in patients with a cervical OP-index ≥ 10 was 7.8 times greater than that in patients with a cervical OP-index ≤ 5. The results of this study reveal that the extent of OPLL in the whole spine is significantly associated with the extent of cervical OPLL, female sex, and obesity

Enhancing percutaneous pedicle screw fixation with hydroxyapatite granules: A biomechanical study using an osteoporotic bone model.

INTRODUCTION:Percutaneous pedicle screw (PPS) can provide internal fixation of the thoracolumbar spine through a minimally invasive surgical procedure. PPS fixation has been widely used to treat various spinal diseases. Rigid fixation of PPS is essential for managing osteoporotic spine in order to prevent the risks of screw loosening and implant failure. We recently developed a novel augmentation method using hydroxyapatite (HA) granules for PPS fixation. The aim of this study was to evaluate the strength and stiffness of PPS fixation augmented with HA granules using an osteoporotic bone model. METHODS:Screws were inserted into uniform synthetic bone (sawbones) with and without augmentation. The uniaxial pullout strength and insertion torque of the screws were evaluated. In addition, each screw underwent cyclic toggling under incrementally increasing physiological loads until 2 mm of screwhead displacement occurred. The maximal pullout strength (N), maximal insertion torque (N·cm), number of toggle cycles and maximal load (N) required to achieve 2-mm screwhead displacement were compared between the screws with and without augmentation. RESULTS:The maximal pullout strength was significantly stronger for screws with augmentation than for those without augmentation (302 ± 19 N vs. 254 ± 17 N, p < 0.05). In addition, the maximal insertion torque was significantly increased in screws with augmentation compared to those without augmentation (48 ± 4 N·cm vs. 26 ± 5 N·cm, p < 0.05). Furthermore, the number of toggle cycles and the maximal load required to reach 2 mm of displacement were significantly greater in screws with augmentation than in those without augmentation (106 ± 9 vs. 52 ± 10 cycles; 152 ± 4 N vs. 124 ± 5 N, p < 0.05). CONCLUSIONS:Augmentation using HA granules significantly enhanced the rigidity of PPS fixation in the osteoporotic bone model. The present study suggested that novel augmentation with HA granules may be a useful technique for PPS fixation in patients with osteoporotic spine

A Novel Intraoperative CT Navigation System for Spinal Fusion Surgery in Lumbar Degenerative Disease: Accuracy and Safety of Pedicle Screw Placement

Background: In recent years, intraoperative computed tomography (CT) navigation has become widely used for the insertion of pedicle screws in spinal fusion surgery. However, conventional intraoperative CT navigation may be impaired by infrared interference between the infrared camera and surgical instruments, which can lead to the misplacement of pedicle screws. Recently, a novel intraoperative CT navigation system, NextAR, has been developed. It uses a small infrared camera mounted on surgical instruments within the surgical field. NextAR navigation can minimize the problem of infrared interference and be expected to improve the accuracy of pedicle screw placement. Methods: This study investigated the accuracy of pedicle screw insertion under NextAR navigation in spinal fusion surgery for lumbar degenerative diseases. The accuracy of pedicle screw placement was evaluated in 15 consecutive patients using a CT grading scale. Results: Screw perforation occurred in only 1 of the total 70 screws (1.4%). Specifically, there was one grade 1 perforation within 2 mm, but no perforations larger than 2 mm. There were no reoperations or neurological complications due to screw misplacement. Conclusions: NextAR navigation can provide high accuracy for pedicle screw insertion and help ensure safe spinal fusion surgery for lumbar degenerative diseases

Innovation of Surgical Techniques for Screw Fixation in Patients with Osteoporotic Spine

Osteoporosis is a common disease in elderly populations and is a major public health problem worldwide. It is not uncommon for spine surgeons to perform spinal instrumented fusion surgeries for osteoporotic patients. However, in patients with severe osteoporosis, instrumented fusion may result in screw loosening, implant failure or nonunion because of a poor bone quality and decreased pedicle screw stability as well as increased graft subsidence risk. In addition, revision surgeries to correct failed instrumentation are becoming increasingly common in patients with osteoporosis. Therefore, techniques to enhance the fixation of pedicle screws are required in spinal surgeries for osteoporotic patients. To date, various instrumentation methods, such as a supplemental hook, sublaminar taping and sacral alar iliac screws, and modified screwing techniques have been available for reinforcing pedicle screw fixation. In addition, several materials, including polymethylmethacrylate and hydroxyapatite stick/granules, for insertion into prepared screw holes, can be used to enhance screw fixation. Many biomechanical tests support the effectiveness of these augmentation methods. We herein review the current therapeutic strategies for screw fixation and augmentation methods in the surgical treatment of patients with an osteoporotic spine

Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Autophagy is an important function that mediates the degradation of intracellular proteins and organelles. Chaperone-mediated autophagy (CMA) degrades selected proteins and has a crucial role in cellular proteostasis under various physiological and pathological conditions. CMA dysfunction leads to the accumulation of toxic protein aggregates in the central nervous system (CNS) and is involved in the pathogenic process of neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. Previous studies have suggested that the activation of CMA to degrade aberrant proteins can provide a neuroprotective effect in the CNS. Recent studies have shown that CMA activity is upregulated in damaged neural tissue following acute neurological insults, such as cerebral infarction, traumatic brain injury, and spinal cord injury. It has been also suggested that various protein degradation mechanisms are important for removing toxic aberrant proteins associated with secondary damage after acute neurological insults in the CNS. Therefore, enhancing the CMA pathway may induce neuroprotective effects not only in neurogenerative diseases but also in acute neurological insults. We herein review current knowledge concerning the biological mechanisms involved in CMA and highlight the role of CMA in neurodegenerative diseases and acute neurological insults. We also discuss the possibility of developing CMA-targeted therapeutic strategies for effective treatments

Reinforcement of Percutaneous Pedicle Screw Fixation with Hydroxyapatite Granules in Patients with Osteoporotic Spine: Biomechanical Performance and Clinical Outcomes

In percutaneous pedicle screw (PPS) fixation of the osteoporotic spine, rigid screw fixation obtaining strong stabilization is important for achieving successful treatment outcomes. However, in patients with severe osteoporosis, it is difficult to obtain PPS fixation with sufficient stability. PPS fixation has potential disadvantages with respect to maintaining secure stabilization in comparison to conventional pedicle screw fixation. In PPS fixation, bone grafting to achieve posterior spine fusion is generally not applicable and transverse connectors between the rods cannot be used to reinforce the fixation. Various augmentation methods, including additional hooks, sublaminar bands, and hydroxyapatite (HA) sticks, are available for conventional pedicle screw fixation. On the other hand, there has been no established augmentation method for PPS fixation. Recently, we developed a novel augmentation technique for PPS fixation using HA granules. This technique allows the percutaneous insertion of HA granules into the screw hole along the guidewire prior to insertion of the PPS. We have used this augmentation technique for PPS fixation in various spine surgeries in patients with osteoporosis. In our previous studies, biomechanical analyses demonstrated that PPS fixation was significantly enhanced by augmentation with HA granules in the osteoporotic lumbar spine. Furthermore, augmentation with HA granules was considered to decrease the incidence of screw loosening and implant failure following PPS fixation in patients with osteoporotic spine. In this article, we describe the surgical procedures of the augmentation method using HA granules and summarize our data from the biomechanical analysis of augmentation for PPS fixation. We also review the surgical outcomes of PPS fixation with augmentation using HA granules