Computational analysis followed by in vitro studies to explore cytokines (TNF-α, IL-6 and IL-1ß) inhibition potential of the new natural molecule polonilignan.

Targeting pro-inflammatory cytokines and their production is found to be of therapeutic benefit for the regulation of inflammation in various chronic autoimmune diseases. Our continued efforts to discover small molecular-weight pro-inflammatory cytokine inhibitors resulted in identifying a novel natural lignan molecule named polonilignan, isolated from the culture broth extract of an endophytic fungus Penicillium polonicum. An in silico study (molecular docking, ADME predictions, binding free energy calculation and molecular dynamics simulation) of the polonilignan over the pro-inflammatory cytokines proteins TNF-α, IL-6 and IL-1ß was performed using Schrodinger LLC software to understand the binding interactions, drug-like properties, and stability of the ligand-protein complex. Further, in-vitro testing of inhibition of TNF-α, IL-6 and IL-1ß by polonilignan was carried out using ELISA and RT-PCR on LPS-induced RAW 264.7 cell lines along with the testing of nitrite production effect (Griess assay) and cytotoxicity (MTT) analysis. Under the computational study, polonilignan revealed good docking scores, binding interactions, and stability under MDS and desirable in silico ADME results over the proteins TNF-α, IL-1ß and IL-6. Poloniligan showed significant inhibition of IL-1ß, IL-6 and TNF-α with IC50 values of 2.01 µM, 6.59 µM and 42.10 µM, respectively. Also, it reduced the translocation of the NF-κB subunit p65 to the nucleus (confocal microscopy). The mRNA expression levels of pro-inflammatory markers IL-1ß, TNF-α and IL-6 levels were lowered significantly (p < .001) by the compound, and the diminution was higher with IL-1ß. Further, the lignan was non-cytotoxic and effective in attenuating nitrite release (IC50 48.56 µM). Thus, polonilignan has been identified as a new pan-cytokine and NO inhibitor, it is recommended to optimise a method for the synthesis of this small molecular weight lignan and explore its pharmacokinetic characteristics, toxicity and therapeutic effect under various chronic inflammatory disease models.

Short-segment spinal fusion for chronic low back pain with bone marrow edema adjacent to the vertebral endplate in adult spinal deformity.

PURPOSE: Corrective long spinal fusion is a widely accepted surgical method for patients with adult spinal deformities. However, instrumented long fusion is associated with a significant risk of complications. Therefore, we aimed to assess the success of short-segment spinal fusion, particularly for bone marrow edema (BME) adjacent to the vertebral endplate, in patients with low back pain (LBP) and spinal deformity. METHODS: A prospective study was performed at multiple hospitals wherein we monitored patients with spinal deformities and accompanying LBP. Patients aged ≥ 50 years with a minimum LBP severity score of 40 mm on the visual analog scale (VAS) were included in the study. We also included patients with lumbar BME on magnetic resonance imaging. Short spinal fusion was performed on segments with BME. Clinical evaluations of LBP on VAS and Oswestry Disability Index (ODI), and radiological parameters for sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL) and pelvic tilt (PT) were carried out. RESULTS: Overall, 35 patients (22 men and 13 women), with a mean age of 66.7 years and a mean follow-up period of 32 months, were included in the study. The mean VAS and ODI scores were 72.4 mm and 49.0% before surgery and 25.5 mm and 29.9% at the final follow-up, respectively; these parameters significantly improved after surgery. The SVA, PI-LL, and PT scores were 70.1 mm, 20.9°, and 22.8° before surgery and 85.4 mm, 13.8°, and 22.7° at the final follow-up, respectively. The spinal alignment parameters did not change significantly after surgery. CONCLUSIONS: Short-segment spinal fusion is effective for treating LBP and spinal deformity with BME adjacent to the vertebral endplate without spinal correction.

Physical Signs and Clinical Features of Cervical Myelopathy in Elderly Patients, Especially 80 Years or Older: Comparison of 100 Consecutive Operative Cases across Three Age Groups.

STUDY DESIGN: Retrospective cohort study. PURPOSE: The present study aimed to examine the characteristics of physical signs in elderly patients with cervical myelopathy (CM) and to compare the findings in three different age groups. OVERVIEW OF LITERATURE: As the global population ages, the incidence of CM in elderly patients is increasing. METHODS: We evaluated 100 consecutive surgical patients with CM and divided them into the following groups: 80s (34 patients; mean age, 83.9 years), 70s (33 patients; mean age, 73.9 years), and 69 or younger (33 patients; mean age, 60.9 years). The clinical symptoms and physical signs were evaluated and recorded. RESULTS: Although the recovery rate decreased with increasing age, all groups demonstrated a significant improvement in clinical symptoms relative to preoperative values. The Hoffman sign and hyperreflexia of the triceps tendon were, respectively, present in 82% and 88% of patients in the 80s group, 74% and 64% of those in the 70s group, and 69% and 82% of those in the 69 or younger group, with no significant difference among the groups. In contrast, the rates of hyperreflexia of the patellar and Achilles tendons were, respectively, 59% and 32% in the 80s group, 85% and 48% in the 70s group, and 91% and 70% in the 69 or younger group, with significant differences. CONCLUSIONS: The positivity rate of the lower extremity hyperreflexia decreased significantly with increasing age in patients with CM. The absence of hyperreflexia, particularly lower extremity, is not uncommon in elderly patients with suspected CM.

Balancing ability of patients with lumbar spinal canal stenosis.

PURPOSE: To determine the relationship between postural sway and the severity of lumbar spinal canal stenosis as well as the effect on postoperative improvement. METHODS: Stabilometry was performed before and 6 months after surgery in 52 patients (29 men and 23 women; mean age, 74.1 ± 7.8 years) who underwent decompression surgery for lumbar spinal canal stenosis. The environmental area (EA; the area surrounding the circumference of the stabilogram) and locus length per EA (L/EA) were evaluated. The patients were divided into moderate (n = 22) and severe (n = 30) groups according to the severity of canal stenosis. Patient characteristics and parameters were compared between the groups before and after surgery, including the visual analog scale (VAS) score for leg pain, Oswestry Disability Index (ODI), EA, and L/EA. In addition, factors affecting EA and L/EA were evaluated using multiple regression analysis. RESULTS: Age (p = 0.031), preoperative EA (p < 0.001), preoperative L/EA (p = 0.032), and sagittal vertical axis (p = 0.033) were significantly different between groups. The VAS score and ODI significantly improved postoperatively in both groups (p < 0.001). The EA significantly improved postoperatively only in the severe group (p < 0.001), whereas the L/EA did not significantly improve in either group. Multiple regression analysis showed that only the severity of canal stenosis was significantly associated with preoperative EA (p = 0.030), whereas age (p = 0.040) and severity of canal stenosis (p = 0.030) were significantly associated with preoperative L/EA. Diabetes was significantly associated with postoperative EA (p = 0.046) and L/EA (p = 0.030). CONCLUSION: The severity of canal stenosis affected abnormal postural sway, which improved after decompression surgery.

Prognostic factors of balloon kyphoplasty for osteoporotic vertebral fractures with diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: The authors aimed to determine the poor prognostic factors of balloon kyphoplasty for the treatment of fractures of the most distal or distal-adjacent vertebrae in ankylosing spines with diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Eighty-nine patients with fractures of the most distal or distal-adjacent vertebrae of ankylosing spines with DISH were included and divided into two groups: those with (n = 51) and without (n = 38) bone healing 6 months postoperatively. Clinical evaluation included age, sex, time from onset to surgery, the visual analog scale score for low-back pain, and the Oswestry Disability Index (ODI). The VAS scores and ODI were measured both preoperatively and at 6 months postoperatively. Radiological evaluations included bone density; wedge angles of the fractured vertebrae in the supine and sitting positions on lateral radiographs; differences in the wedge angles (change in wedge angle); and the amount of polymethylmethacrylate used. RESULTS: The preoperative ODI, vertebral wedge angles in the supine and sitting positions, change in wedge angle, and amount of polymethylmethacrylate were significantly different between the two groups and were significantly associated with delayed bone healing in univariate logistic regression analysis. Multivariate logistic regression analysis showed that only a change in the wedge angle was significantly associated with delayed healing, with a cutoff value of 10°, sensitivity of 84.2%, and specificity of 82.4%. CONCLUSIONS: Treatment with balloon kyphoplasty alone should be avoided in patients with a difference ≥ 10° in the wedge angle of the fractured vertebrae between the supine and sitting positions.

New natural pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and iNOS inhibitors identified from Penicillium polonicum through in vitro and in vivo studies.

Overexpression of pro-inflammatory cytokines and iNOS have been found to be concomitant with several chronic inflammatory diseases and hence targeting their inhibition would be a useful therapy for inflammation. In view of this, study on discovery of natural pro-inflammatory cytokines inhibitory lead molecules from Penicillium polonicum, an endophytic fungus isolated from the fresh fruits of Piper nigrum was performed. When the culture broth extract of P. polonicum (EEPP) was subjected to LPS-induced cytokines expression (ELISA in RAW 264.7 cells), it exhibited inhibition of TNF-α, IL-6 and IL-1ß and this encouraged us to do chemical investigation on EEPP to explore the bioactive components. Four compounds isolated and characterised as 3,5-di-tert-butyl-4-hydroxy-phenyl propionic acid (1), 2,4-di-tert-butyl phenol (2), indole 3-carboxylic acid (3) and tyrosol (4) were tested for their effect on the production of TNF-α, IL-1ß and IL-6 in RAW 264.7 cells (ELISA). All the compounds exhibited a highly significant (P < 0.0001) inhibition effect, particularly against IL-1ß (IC50: 4-0.91 µM, 1-2.81 µM, 3-4.38 µM, and 2-5.54 µM). Tyrosol (4) was most active with IC50 values of 0.91, 2.67 and 4.60 µM against IL-1ß, IL-6 and TNF-α, respectively. On observing the potential activity of the compounds, two compositions C1 and C2 were prepared by mixing equimolar concentrations of compounds 1, 2, 3 & 4 (C1) and compounds 1, 2, 3, 4 & piperine (C2) in equal ratio. A synergistic effect was observed with C1 exhibiting potential suppression of IL-6 secretion (IC50 1.91 µM) and C2 against IL-1ß (IC50 5.98 µM). Also, the individual compounds and C1 were effective in controlling iNOS expressions in RAW 264.7 cells (RTPCR). Further, the in vivo performance of the compounds and compositions were studied under two in vivo inflammatory models (LPS-induced endotoxaemia and carrageenan-induced paw oedema). Compounds 1, 2, 3, 4, C1 and C2 at 50 mg/kg oral dose showed a significant control over the LPS-stimulated TNF-α, IL-1ß and IL-6 levels in plasma. C1, C2 and 1 exhibited > 50% pan-cytokine inhibition effect. Under the carrageenan-induced anti-inflammatory model, a significant reduction in the paw oedema measured in terms of the difference in the paw thickness was observed. Further, attenuation of pro-inflammatory cytokines levels following ELISA and RT-PCR experiments in the paw tissue homogenate was in agreement with paw thickness results. All compounds and C1 decreased the iNOS gene expression levels, and also the MPO activity and NO production in the paw tissue homogenate with tyrosol (4) as the most active molecule. Further, the mechanism of action was explored by testing the effect of the compounds on the expression of inflammatory markers using western blot analysis (in vitro). They were found to regulate the expression of pro-form and matured-form of IL-1ß by inhibiting NFκB. Also, the compounds reduced the translocation of the NF-κB subunit p65 to the nucleus. Thus, compounds 3,5-di-tert-butyl-4-hydroxy-phenyl propionic acid (1), 2,4-di-tert-butyl phenol (2), indole 3-carboxylic acid (3) and tyrosol (4) are reported as new natural multiple pro-inflammatory cytokines inhibitory leads. The interesting results of C1 might lay a footing for the development of a new anti-inflammatory composition.

Oryzanigral: a new polyketide from an endophytic fungus Nigrospora oryzae isolated from Coccinia grandis.

A new heptaketide named oryzanigral (1) was isolated from the fermentation extract of the endophytic fungus Nigrospora oryzae isolated from the leaves of Coccinia grandis, along with five known compounds, (R)-mellein, (R)-O-methylmellein, (3R,4R)-4-hydroxymellein, (3R,4S)-4-hydroxymellein and abscisic acid. The structure of oryzanigral was elucidated by spectroscopic analyses including 2D-NMR. A plausible biosynthetic pathway involving Diels-Alder reaction was proposed for compound 1 and related polyketides previously reported. In addition, structure revision of the double bond geometry for coicenal A was described.

A New Lignan (Polonilignan) and Inhibitors of Nitric Oxide Production from Penicillium polonicum, an Endophytic Fungi of Piper nigrum.

Inhibiting nitric oxide (NO) or its production is found to be of therapeutic benefit. To discover natural small molecule inhibitors of NO production, a bioassay- and LC/MS-guided chemical investigation was done on the metabolites of endophytic fungus isolated from fresh Piper nigrum fruits. The isolated pure strain was identified as Penicillium polonicum by 16S rDNA sequence comparison. The culture broth extract of P. polonicum (EEPP) exhibited a significant reduction of NO production (Griess method) in LPS-stimulated RAW 264.7 cells (P<0.0001). To understand the chemical constituents of bioactive EEPP, column chromatography and p-TLC studies were carried out, which yielded eight pure compounds. They were characterised as botryosphaeridione (1), 3-(3,5-di-tert-butyl-4-hydroxy)phenylpropionic acid (2), variabilone (3), 2,4-di-tert-butylphenol (4), indole-3-carboxylic acid (5), tyrosol (6), ethyl ferulate (7) and a new lignan (8) based on the spectral analysis. The structure elucidation of the new lignan, named polonilignan (8), was based on HR-MS, 1 H- & 13 C-NMR, H-H COSY, HSQC and HMBC spectra. Compounds 2, 4, 5 and 6 showed a significant decrease (P<0.0001) in the production of NO in LPS-induced RAW 264.7 cells. Tyrosol (6) and indole-3-carboxylic acid (5) controlled nitrite release with IC50 values of 22.84 and 55.01 µM, respectively. This is the first report of (i) P. polonicum as an endophytic fungus of pepper fruits, (ii) isolation of compounds 1-8 except 6 from P. polonicum culture broth extract and (iii) NO inhibition effect of 2, 4, 5 and 6.

Percutaneous Intervertebral-Vacuum Polymethylmethacrylate Injection for Foraminal Stenosis with Degenerative Lumbar Scoliosis.

BACKGROUND: Percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) is a minimally invasive procedure for low back pain in elderly patients with degenerative lumbar scoliosis (DLS). Patients with DLS often have radiculopathy as a result of foraminal stenosis in addition to low back pain. The purpose of this study was to evaluate the clinical and radiologic results of PIPI for foraminal stenosis with radiculopathy in elderly patients with DLS. METHODS: We included patients with de novo DLS aged 65 years or older who underwent PIPI. The presence of an intervertebral vacuum on computed tomography and bone marrow edema on magnetic resonance imaging was required for inclusion. The intersegmental radiologic parameters on plain radiographs and computed tomography and the extent of bone marrow edema on magnetic resonance imaging were measured. The clinical outcomes were evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI). RESULTS: We enrolled 40 patients with DLS who underwent PIPI. There were 16 men and 24 women, and the mean age was 79.0 ± 6.3 years. The mean foraminal height and extent of bone marrow edema showed a significant increase and reduction, respectively, after PIPI (P < 0.05). VAS score for radiculopathy and ODI significantly improved after PIPI (P < 0.01). The minimum clinically important differences in VAS score for radiculopathy and ODI at the final follow-up were 73.9% and 63.6%, respectively. CONCLUSIONS: PIPI is a minimally invasive procedure not only for low back pain but also for radiculopathy in elderly patients with DLS. It leads to intervertebral stabilization and indirect decompression of the foramen.

Spinous Process Fractures in Osteoporotic Vertebral Fractures: A Cross-Sectional Study.

Introduction: The purpose of this study was to assess radiological features and clinical scores of osteoporotic vertebral fracture (OVF) accompanied by spinous process fracture (SPF). Methods: We included painful patients with single-level OVF with intravertebral cleft. SPF was detected using magnetic resonance imaging (MRI) and/or computed tomography (CT). The plain radiographs of the vertebral fractures were evaluated based on the wedging angle of the fractured vertebrae and vertebral instability. We investigated the clinical parameters of age, gender, visual analog scale (VAS) score for low back pain (LBP), Oswestry Disability Index (ODI), and the period from the onset of acute fracture. Results: MRI and/or CT indicated among 195 patients of OVF with LBP, 41 patients (20.5%) had SPFs. SPFs were observed one level above the fractured vertebral body in 35 patients (85.4%) and at the same level as the fractured vertebral body in 6 patients (14.6%). The prevalence of vertebral fracture of thoracic spine in the SPF-positive group was significantly greater than that in the SPF-negative group. There were no significant differences in age, gender, VAS, ODI, the time period from the onset of acute LBP, wedging angle, and vertebral instability between the presence or absence of SPFs. Conclusions: SPFs occurred in 20.5% of patients with OVF and LBP. In addition, SPFs often occurred one level above the fractured vertebra, and SPFs with OVF tended to be located in the thoracic spine.

Radiographic Factors for Adjacent Vertebral Fractures and Cement Loosening Following Balloon Kyphoplasty in Patients with Osteoporotic Vertebral Fractures.

Introduction: Balloon kyphoplasty (BKP) is a minimally invasive surgical approach for the treatment of osteoporotic vertebral fractures (OVF). Some risks have been reported after treatment with BKP; therefore, it is necessary to determine when BKP does not work. Thus, in this study, we aim to clarify the radiographic predictors of secondary vertebral fractures and cement loosening after BKP for OVF. Methods: This study enrolled patients with single-level OVF at the thoracolumbar junction (T11-L2) who underwent BKP for the first time between January 2011 and March 2014. The clinical outcomes were evaluated using the visual analog scale (VAS) and a modified Oswestry Disability Index (ODI) at 1 week and 1, 3, 6, and 12 months after surgery. Radiographic assessments were performed preoperatively and within 1 year after BKP using plain radiography and computed tomography. Results: The 85 patients who met the inclusion criteria underwent BKP. The average age of participants (21 men, 64 women) was 77.8 years (range, 57-92 years). Postoperative VAS and ODI scores were all significantly better than preoperative scores. Polymethyl methacrylate (PMMA)-cement leakage was observed in 18 patients (21.2%) but was asymptomatic in all cases. Secondary vertebral fractures were detected in 20 patients (23.5%), including adjacent levels in 15 patients (17.6%) and non-adjacent levels in 5 patients (5.9%). Rostral bridging osteophyte formation was found to be significantly associated with the occurrence of adjacent vertebral fractures (odds ratio 12.746; p=0.010). PMMA-cement loosening was observed in three patients (3.5%). A high prevalence (100%) of bridging osteophytes, vacuum clefts, and spinous process fractures was observed in patients with PMMA-cement loosening. PMMA-cement loosening was found in 3 out of 10 patients with all three of these factors. Conclusions: Rostral bridging osteophyte formation was determined to be a risk factor for both adjacent vertebral fractures and PMMA-cement loosening.Level of Evidence: 3.

Prognostic factors for spontaneous spinal epidural hematoma: a multicenter case-control study.

BACKGROUND: To determine the optimal treatment for spontaneous spinal epidural hematoma (SSEH). The aim of this study was to identify factors associated with SSEH. METHODS: In 62 patients with SSEH, several patient-related parameters were analyzed as candidate factors associated with Frankel grade before treatment or at the last follow-up. These parameters were compared between patients with and without surgery. In addition, multivariate ordinal logistic regression analysis was used to identify factors significantly associated with Frankel's grade before treatment or at the last follow-up. RESULTS: There were significant differences in age, location of the hematoma, and Frankel grade before treatment and at the last follow-up between surgical and nonsurgical cases in all patients, but there were no significant differences in any of these parameters when comparing patients with pre-treatment Frankel grade C. The location of the hematoma was significantly associated with the severity of paralysis before treatment. In surgical cases, the time from onset to surgery and the location of the hematoma was significantly associated with the prognosis. When the time from onset to surgery was evaluated using the criteria of 12, 24, and 48 h, 24 and 48 h had a significant impact on the prognosis. In the analysis of nonsurgical cases, only the vertical size of the hematoma was significantly associated with prognosis. CONCLUSION: The time from onset to surgery and the location of the hematoma were prognostic factors in surgical cases, while the vertical size of the hematoma was a prognostic factor in nonsurgical cases.

Tectonaquinones A, B and C: three new naphthoquinone derivatives from the heartwood of Tectona grandis.

Chemical investigation of the chloroform extract of heartwood of Tectona grandis L. f. led to the isolation of three new naphthoquinone derivatives, tectonaquinones A (1), B (2) and C (3), along with six known compounds: barleriaquinone-I (4), tectoquinone (5), tecomaquinone I (6), lapachol (7), obtusifolin (8) and 2-hydroxy-3-methyl anthraquinone (9). The structures of the new compounds were elucidated by spectroscopic methods including 2 D NMR experiments. Tectonaquinone B is the first natural compound that has a hexa-cyclic dinaphthofuran-dione scaffold. Tectonaquinone C has a bicyclic acetal motif that is unusual in nature.

Quantifying Bone Marrow Edema Adjacent to the Lumbar Vertebral Endplate on Magnetic Resonance Imaging: A Cross-Sectional Study of Patients with Degenerative Lumbar Disease.

STUDY DESIGN: Cross-sectional study. PURPOSE: We aimed to quantitatively assess bone marrow edema (BME) on magnetic resonance imaging (MRI) for patients with degenerative lumbar diseases. OVERVIEW OF LITERATURE: BME adjacent to a sclerotic endplate of the lumbar spine, detected using T2-weighted fat-saturated MRI, is closely associated with low back pain in patients with degenerative lumbar diseases. However, currently, there no quantitative evaluation methods for BME adjacent to the vertebral endplate. METHODS: Patients with degenerative lumbar diseases, whose MRIs detected BME, were enrolled. On a T2-weighted fat-saturated MRI, BME appeared as a high-intensity region adjacent to the vertebral endplate. We calculated the contrast ratios (CRs) of BME and normal bone marrow using the signal intensities of BME, normal bone marrow, and the spinal cord. On computed tomography, we calculated Hounsfield unit (HU) values in the same area as BME, the sclerotic endplate, and normal bone marrow to assess bone density. RESULTS: There were 16 men and 14 women, with an average age of 73.5 years. The mean CRs of BME and normal bone marrow were -0.015±0.056 and -0.407±0.023, respectively. BME's CR was significantly higher than that of normal bone marrow (p<0.01). The HU values in the same area as BME, the sclerotic endplate, and normal bone marrow were 251.9±24.6, 828.3±35.6, and 98.1±9.3, respectively; these values were significantly different from each other (p<0.01). CONCLUSIONS: The CR on MRI is a useful quantitative assessment tool for BME in patients with degenerative lumbar diseases.

Surgical outcomes of cervical myelopathy in patients with athetoid cerebral palsy.

PURPOSE: Surgical treatment for cervical myelopathy with athetoid cerebral palsy remains unestablished. Instrumented fusion is reported to have good clinical results; however, there are no data of decompression surgery for this pathology in recent years. This study aimed to assess the surgical outcomes of laminoplasty with or without posterior instrumented fusion for cervical myelopathy in patients with athetoid cerebral palsy. METHODS: A multi-centre surgical series of patients with cervical myelopathy and athetoid cerebral palsy were enrolled in this study. All patients showed symptoms and signs suggestive of cervical myelopathy and underwent laminoplasty with or without instrumented fusion. The Japanese Orthopaedic Association (JOA) score, Barthel index (BI), and changes in the C2-C7 sagittal Cobb angle in the lateral plain radiograph were analysed. RESULTS: There were 25 patients (16 men and 9 women; mean age, 54.4 ± 10.8 years) with cervical myelopathy and athetoid cerebral palsy who underwent surgical treatment. The mean follow-up period was 41.9 ± 35.6 months. Overall, the BI significantly improved after surgery, whereas the JOA score and C2-C7 angle did not improve postoperatively. The recovery rate of the JOA score in the laminoplasty group was significantly higher than that of the fusion group (P = 0.02). CONCLUSIONS: Cervical laminoplasty with or without instrumented fusion for treating cervical myelopathy due to athetoid cerebral palsy is effective in improving activities of daily living. Cervical laminoplasty may be an effective and less invasive surgical method for selective patients, especially for those with small involuntary movements and no remarkable cervical kyphosis nor instability.

Quantitative evaluation of abnormal finger movements in myelopathy hand during the grip and release test using gyro sensors.

Previous studies have reported qualitative characteristics of myelopathy hand, but few studies have reported quantitative kinematic parameters of this condition. Our purpose of this study was to quantitatively evaluate the abnormal finger movements in patients with cervical compressive myelopathy (CCM) (termed myelopathy hand) and to understand the characteristics of myelopathy hand during the grip and release test (GRT) using gyro sensors. Sixty patients with CCM (severe: n = 30; mild-to-moderate: n = 30) and sixty healthy adults (age-matched control: n = 30; young control: n = 30) were included in this study. All participants performed the GRT. The index and little fingers' and the wrist's movements during the GRT were recorded using three gyro sensors. The number of cycles, switching time-delay, time per cycle, and peak angular velocity were calculated and compared between groups. Patients with severe CCM had the lowest number of cycles and longest switching time-delays, followed by patients with mild-to-moderate CCM, the age-matched control group, and the young control group. The time per cycle and the peak angular velocities of fingers in participants with severe CCM were significantly lower than those in participants with mild-to-moderate CCM; however, there were no significant differences between the control groups. The peak angular velocities of fingers were significantly lower during extension motions than during flexion motions in participants with CCM. Participants with CCM have lower peak angular velocities during finger movement. Finger extension also is impaired in participants with CCM. Abnormal finger movements and the severity of myelopathy in participants with CCM can be assessed using gyro sensors.

Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis.

PURPOSE: Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. METHODS: Patients with de novo DLS, aged ≥ 65 years, who had LBP with visual analog scale (VAS) of ≥ 50 for ≥ 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. RESULTS: One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 ± 32.4 and 43.9 ± 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. CONCLUSION: Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.

Halodule pinifolia (Seagrass) attenuated lipopolysaccharide-, carrageenan-, and crystal-induced secretion of pro-inflammatory cytokines: mechanism and chemistry.

OBJECTIVES: The study aimed to explore the anti-inflammatory effect, underlying mechanism, and chemistry of Halodule pinifolia extract. METHODS: The ethyl acetate (EHP) and methanol (MHP) extracts of Halodule pinifolia were screened for pro-inflammatory cytokine inhibition effect under various in vitro (LPSand crystal-induced inflammation) and in vivo models (LPS-induced endotoxaemia model, carrageenan-induced paw oedema model, and oxalate-induced renal nephropathy model of inflammation). The effect of EHP on the expression of inflammatory markers using western blot analysis (in vitro) was investigated. Chemical constituents of bioactive EHP were isolated through chromatography and characterised using NMR spectroscopy. Furthermore, EHP was standardised for rosmarinic acid, vanillic acid, and ethyl protocatechuate using HPLC. Also, total phytosterols, phenolic, and flavonoid content of EHP were determined by UV spectroscopy. KEY FINDINGS: EHP was comparatively more effective than MHP in inhibiting cytokines secretions under LPS-induced in vitro models. Furthermore, EHP was screened under endotoxaemia in vivo model, EHP (250 mg/kg) reduced plasma IL-6, TNF-α, and IL-1ß levels by 88.3%, 78.2%, and 74.5%, respectively. In the carrageenan-induced oedema model, EHP (200 mg/kg) reduced paw volume and release of TNF-α (69.3%) and IL-1ß (43.1%). EHP (200 mg/kg) further controlled renal nephropathy by inhibiting plasma IL-1ß and BUN levels. Also, a significant reduction of mRNA expressions of TNF-α and IL-1ß and KIM-1 in renal tissues was observed. Through western blot, EHP was identified to regulate the expression of pro-form as well as mature-form of IL-1ß and caspase-1. EHP constituted rosmarinic acid (RA), vanillic acid (VA), ethyl protocatechuate (EP), sitosterol, stigmasterol, campesterol, and dihydrobrassicasterol. It was determined that 4.6 mg/g of RA, 2.92 mg/g of VA, 0.76 mg/g of EP, 21.7 mg/g of total phenolics, 29.8 mg/g of total flavonoids, and 48.2 mg/g of total phytosterols were present in dry EHP. The presence of anti-inflammatory constituents such as RA, VA, and PE in EHP corroborated the in vitro and in vivo anti-inflammatory activity of EHP. CONCLUSION: The anti-inflammatory property of EHP and its action through attenuation of pan-cytokines suggest that it can be developed into an oral pharmaceutical drug.

New synthetic coumarinolignans as attenuators of pro-inflammatory cytokines in LPS-induced sepsis and carrageenan-induced paw oedema models.

OBJECTIVES: The aim of the study was to explore the inhibition efficacy of new synthetic coumarinolignans (SCLs) against the secretion of pro-inflammatory cytokines in two in vivo models of inflammation. METHODS: Four SCLs 1-4 were screened for their pro-inflammatory cytokine inhibitory potential through oral administration at a dose of 50 mg/kg body weight in lipopolysaccharide-induced mouse endotoxaemia and carrageenan-induced mouse paw oedema models. Levels of pro-inflammatory cytokines (IL-1ß, TNFα and IL-6) in blood and paw tissue samples were estimated using ELISA. Paw oedema was measured using a plethysmometer. Results were compared with a natural coumarinolignan, cleomiscosin A (5), and the structure-activity relationship (SAR) was interpreted. RESULTS AND DISCUSSION: Compound 2 had the greatest potential in the endotoxaemia model, exhibiting 66.41%, 62.56% and 43.15% inhibition of plasma IL-1ß, TNFα and IL-6 secretions, respectively. Further dose-dependent study revealed its anti-inflammatory potential even at dose of 10 mg/kg body weight with 24.42% decline in the level of IL-1ß. Nevertheless, SCLs 1, 3 and 4 showed marked inhibitory activity with 57.54%, 51.48% and 62.46% reduction in the levels of IL-1ß, respectively. Moreover, compound 2 decreased the plasma TNFα and IL-1ß levels to 50.03% and 36.58% along with the reduction of paw oedema volume in the local inflammation induced by carrageenan. All compounds including cleomiscosin A (5) were more effective against IL-1ß. By studying SAR, the presence of dihydroxyl groups in the phenyl ring of lignans was identified to be essential for the activity. Also, esterification of lignans and presence of a 4-methyl substituent in the coumarin nucleus were found to play some role in enhancing the activity. CONCLUSION: All four SCLs, especially compound 2, have shown vast potential to emerge out as promising anti-inflammatory drugs.