Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits

ObjectiveParaplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.MethodsEighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4°C) and fasudil (group 2, n = 6, 4°C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.ResultsTwo days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.ConclusionThese results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.Clinical RelevanceParaplegia or paralysis caused by spinal cord ischemia remains a devastating and unpredictable complication after descending and thoracoabdominal aortic surgery. This study has revealed that fasudil has a neuroprotective effect against ischemic spinal cord injury in rabbits. Inhibition of the Rho/Rho kinase pathway by fasudil reduces the number of infiltrating cells in the ventral horn and prolongs the expression of eNOS. In the near future, Rho kinase may be an important therapeutic target for paraplegia induced by spinal cord ischemia

S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review

INTRODUCTION: Neurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling. METHODS: A Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated. RESULTS: A total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis. CONCLUSIONS: In such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values

Scoliosis in Patients with Severe Cerebral Palsy: Three Different Courses in Adolescents

Patients with cerebral palsy (CP) frequently present with scoliosis; however, the pattern of curve progression is difficult to predict. We aimed to clarify the natural course of the progression of scoliosis and to identify scoliosis predictors. This was a retrospective, single-center, observational study. Total of 92 CP patients from Asahikawasou Ryouiku Iryou Center in Okayama, Japan were retrospectively analyzed. Cobb angle, presence of hip dislocation and pelvic obliquity, and Gross Motor Function Classification System (GMFCS) were investigated. Severe CP was defined as GMFCS level IV or V. The mean observation period was 10.7 years. Thirtyfour severe CP patients presented with scoliosis and were divided into 3 groups based on their clinical courses: severe, moderate and mild. The mean Cobb angles at the final follow-up were 129°, 53°, and 13° in the severe, moderate, and mild groups, respectively. The average progressions from 18 to 25 years were 2.7°/year, 0.7°/year, and 0.1°/year in the severe, moderate, and mild curve groups, respectively. We observed the natural course of scoliosis and identified 3 courses based on the Cobb angle at 15 and 18 years of age. This method of classification may help clinicians predict the patients’ disease progression

Relationship between Displacement of the Psoas Major Muscle and Spinal Alignment in Patients with Adult Spinal Deformity

Study DesignCross sectional study.PurposeTo clarify the difference in position of the psoas muscle between adult spinal deformity (ASD) and lumbar spinal stenosis (LSS).Overview of LiteratureAlthough it is known that the psoas major muscle deviates in ASD patients, no report is available regarding the difference in comparison with LSS patients.MethodsThis study investigates 39 patients. For evaluating spinal alignment, pelvic tilt (PT), pelvic incidence (PI), sacral slope, lumbar lordosis (LL), PI–LL, Cobb angle, and the convex side, the lumbar curves were measured. For measuring the position of the psoas major at the L4/5 disk level, magnetic resonance imaging was used. The displacements of psoas major muscle were measured separately in the anterior–posterior and lateral directions. We examined the relationship between the radiographic parameters and anterior displacement (AD) and lateral displacement (LD) of the psoas major muscle.ResultsAD was demonstrated in 15 cases with ASD and nine cases with LSS (p>0.05). LD was observed in 13 cases with ASD and no cases with LSS (p<0.01). The Cobb angle was significantly greater in cases with AD than in those without AD (p=0.04). PT, LL, PI–LL, and Cobb angle were significantly greater in cases with LD (p<0.05). All cases with LD had AD, but no case without AD had LD (p<0.001). The side of greater displacement at L4/5 and the convex side of the lumbar curve were consistent in all cases.ConclusionsDespite AD being observed in LSS as well, LD was observed only in the ASD group. Radiographic parameters were worse when LD was seen, rather than AD

A Multidisciplinary Approach to the Management of Chronic Pain through a Self-managed Behavioral Exercise Program : A Pilot Study in Japan

We conducted this study to determine the short-term treatment outcomes of multidisciplinary approaches to chronic pain management for outpatients in Japan. We evaluated pain reduction and improvement in quality of life (QOL) after treatment. We analyzed 32 patients who had experienced intractable chronic pain for > 3 months. The patients received multidisciplinary therapeutic self-managed exercise instructions and then underwent evaluations 1 and 3 months after the treatment. We used the Pain Disability Short Form-36 (SF-36), Pain Catastrophizing Scale (PCS), and Pain Disability Assessment Scale (PDAS) to evaluate QOL. Although the pain levels were the same before and after the physical exercise program, the patients showed significant improvements in physical function on the SF-36 (48.5 vs. 54.5, 3 months vs. 1 month; p=0.0124), the magnification subscale on the PCS (6.8 vs. 5.9, 1 month vs. before; p=0.0164) and the PDAS (29.2 vs. 23.4, 3 months vs. before; p=0.0055). Chronic pain should be treated with a biopsychosocial approach, but time constraints and costs have limited the implementation of multidisciplinary and behavioral approaches to chronic pain management. Our findings demonstrate that clinical improvements are possible for patients with chronic pain, using multidisciplinary team resources widely available in Japanese clinical practice

Cell-by-cell dissection of phloem development links a maturation gradient to cell specialization

Publisher Copyright: Copyright © 2021 The Authors, some rights reserved;In the plant meristem, tissue-wide maturation gradients are coordinated with specialized cell networks to establish various developmental phases required for indeterminate growth. Here, we used single-cell transcriptomics to reconstruct the protophloem developmental trajectory from the birth of cell progenitors to terminal differentiation in the Arabidopsis thaliana root. PHLOEM EARLY DNA-BINDING-WITH-ONE-FINGER (PEAR) transcription factors mediate lineage bifurcation by activating guanosine triphosphatase signaling and prime a transcriptional differentiation program. This program is initially repressed by a meristem-wide gradient of PLETHORA transcription factors. Only the dissipation of PLETHORA gradient permits activation of the differentiation program that involves mutual inhibition of early versus late meristem regulators. Thus, for phloem development, broad maturation gradients interface with cell-type-specific transcriptional regulators to stage cellular differentiation.Peer reviewe

CK2 Phosphorylates Sec31 and Regulates ER-To-Golgi Trafficking

Protein export from the endoplasmic reticulum (ER) is an initial and rate-limiting step of molecular trafficking and secretion. This is mediated by coat protein II (COPII)-coated vesicles, whose formation requires small GTPase Sar1 and 6 Sec proteins including Sec23 and Sec31. Sec31 is a component of the outer layer of COPII coat and has been identified as a phosphoprotein. The initiation and promotion of COPII vesicle formation is regulated by Sar1; however, the mechanism regulating the completion of COPII vesicle formation followed by vesicle release is largely unknown. Hypothesizing that the Sec31 phosphorylation may be such a mechanism, we identified phosphorylation sites in the middle linker region of Sec31. Sec31 phosphorylation appeared to decrease its association with ER membranes and Sec23. Non-phosphorylatable mutant of Sec31 stayed longer at ER exit sites and bound more strongly to Sec23. We also found that CK2 is one of the kinases responsible for Sec31 phosphorylation because CK2 knockdown decreased Sec31 phosphorylation, whereas CK2 overexpression increased Sec31 phosphorylation. Furthermore, CK2 knockdown increased affinity of Sec31 for Sec23 and inhibited ER-to-Golgi trafficking. These results suggest that Sec31 phosphorylation by CK2 controls the duration of COPII vesicle formation, which regulates ER-to-Golgi trafficking