Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis.

Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretin-negative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.

Validity of E-PASS System for Postoperative Morbidity of Spinal Surgery.

STUDY DESIGN: A single-center retrospective cohort study. OBJECTIVE: To evaluate the ability of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) system to predict postoperative risk in patients scheduled for spinal surgery. SUMMARY OF BACKGROUND DATA: The E-PASS system is a surgical audit to predict postoperative morbidity and mortality in general surgery. It is currently not applied in patients with spinal disorders. METHODS: The E-PASS system is comprised of a preoperative risk score (PRS), a surgical stress score (SSS), and a comprehensive risk score (CRS). The latter reflects both the PRS and SSS. We calculated the E-PASS scores for 275 consecutive patients who underwent spinal surgery and evaluated the relationship between the incidence of postoperative complications and each score of the E-PASS system and their ability to predict postoperative morbidity. RESULTS: Postoperative complications developed in 31 patients (11.3%). All E-PASS scores were significantly higher in patients with postoperative complications and they were linearly correlated with the overall incidence of postoperative complications. In particular, PRS was correlated with complications at nonsurgical sites and SSS with surgical site complications. The area under the receiver operating characteristic curve (AUC) for PRS and SSS was higher in patients with complications at nonsurgical and surgical sites, respectively. The AUC for CRS exhibited good predictive power for both types of complication. CONCLUSIONS: The E-PASS system correctly predicted morbidity. The predictive ability of CRS was good for overall morbidity. The E-PASS system is useful for the accurate prediction of the risk for in-hospital morbidity in individual patients scheduled for spinal surgery.

Immediate Effects, Detailed Clinical Outcomes, and Prognostic Factors of Chemonucleolysis Using Condoliase for Lumbar Disc Herniation.

Chemonucleolysis utilizing condoliase is a minimally invasive treatment for lumbar disc herniation (LDH) aimed at reducing intervertebral disc pressure and enhancing symptoms. In this study, lower limb pain was measured using the numeric rating scale (NRS) the day after treatment and 1 and 3 months after treatment. Prognostic factors were assessed, categorizing participants into an improvement group (I-group) for NRS lower limb pain scores of ≥3.5 and a non-improvement group (N-group) for scores of <3.5. This study included a total of 225 patients treated between April 2020 and March 2023. The mean age was 46.5 ± 16.5 years, with 151 males. The mean duration of illness was 6.2 ± 8.52 months. As of the day after treatment, 60 cases were classified into the I-group, 118 cases at 1 month after surgery, and 152 cases at 3 months after surgery. The disease duration before treatment was significantly shorter in the I-group at 1 (8.19 ± 8.74 [I-group] vs. 5.17 ± 8.04 [N-group] months) and 3 months (8.51 [I-group] ± 7.35 vs. 5.69 ± 8.87[N-group] months) after treatment. The comparison of baseline leg pain NRS shows a difference in leg pain NRS in the I-group when compared on the day after treatment (6.02 ± 2.64 [I-group] vs. 7.50 ± 1.79 [N-group]), 1 (5.13 ± 2.69 [I-group] vs. 7.58 ± 1.66 [N-group]), and 3 months (4.42 ± 2.70 [I-group] vs. 7.34 ± 1.77 [N-group]). Chemonucleolysis using condoliase for LDH can improve symptoms the day after treatment and can be a minimally invasive treatment to avoid surgery.

Usefulness and Safety of Gelatin-Thrombin Matrix Sealants in Minimally Invasive Microscopic Discectomy.

Objective This study aimed to evaluate the usefulness and safety of gelatin-thrombin matrix sealants (GTMSs) in minimally invasive microscopic discectomy, a surgical procedure commonly used to treat lumbar disc herniation. Materials and Methods Out of 484 patients who underwent minimally invasive microscopic discectomy between April 2018 and December 2022, 35 patients with a history of surgery at the same level were excluded, resulting in a total of 449 patients included in the study. Among them, 316 patients were treated using GTMS, whereas 133 were treated using collagen-based absorbable local hemostatic agents. Patient characteristics, surgical duration, intraoperative blood loss, postoperative drainage volume, intraoperative dural injury, and incidence of postoperative epidural hematoma were analyzed and compared between the two groups. Results No significant differences in patient demographics were observed between the two groups, except for activated partial thromboplastin time and prothrombin time. Although there were no significant differences in the mean surgical time and intraoperative blood loss between the two groups, they tended to be shorter and less in the GTMS group (56.3 ± 20.2 vs. 58.2 ± 20.4 minutes [ p = 0.36] and 10.0 ± 15.4 vs. 11.8 ± 8.3 g [ p = 0.20]). The volume of postoperative drainage was significantly lower in the GTMS group than that in the comparison group (35.3 ± 21.8 vs. 49.5 ± 34.1 g [ p < 0.01]). There was a trend indicating a difference in the number of intraoperative dural injuries and the need for reoperation due to postoperative epidural hematoma (2 vs. 3 ± 20.4 minutes [ p = 0.21] and 1 vs. 2 [ p = 0.16]). Conclusion The use of a GTMS in minimally invasive microscopic discectomy appears to be beneficial in reducing postoperative drainage volume. It has also been shown that it may improve clinical outcomes such as intraoperative dural injury and postoperative epidural hematoma. Furthermore, further consideration of the medical economic impact is required.

Usefulness of diffusion-weighted imaging for differentiating between desmoid tumors and malignant soft tissue tumors.

PURPOSE: To evaluate the usefulness of diffusion-weighted imaging (DWI) for differentiating between desmoid tumors and malignant soft tissue tumors. MATERIALS AND METHODS: Conventional MRI and DWI were performed for 8 desmoid tumors and 74 malignant soft tissue tumors. DWI was obtained with a single-shot echo-planar imaging sequence using a 1.5 Tesla (T) MR imager. DW images were acquired with motion-probing gradient pulses applied along three directions (x, y, and z axes) with three b-factors (0, 500, and 1000 s/mm²). Two observers blinded to clinical information measured three regions of interest within the solid tumor and selected a minimum apparent diffusion coefficient () in each lesion. The mean ADC of desmoid tumors was calculated and compared with that of malignant soft tissue tumors using the Mann-Whitney U test. RESULTS: The mean ADC of desmoid tumors and malignant soft tissue tumors was 1.36 ± 0.48 × 10⁻³ mm² /s and 0.88 ± 0.20 × 10⁻³ mm² /s (mean ± SD), respectively. The mean ADC of the desmoid tumors was significantly higher than that of malignant soft tissue tumors (P < 0.01). CONCLUSION: DWI is considered to be useful for differentiating between desmoid tumors and malignant soft tissue tumors. In the future, further investigation in a large series is necessary.

Minimum standards of clinical practice for physical therapists working in intensive care units in Japan.

OBJECTIVE: Early mobilization and rehabilitation has become common and expectations for physical therapists working in intensive care units have increased in Japan. The objective of this study was to establish consensus-based minimum clinical practice standards for physical therapists working in intensive care units in Japan. It also aimed to make an international comparison of minimum clinical practice standards in this area. METHODS: In total, 54 experienced physical therapists gave informed consent and participated in this study. A modified Delphi method with questionnaires was used over three rounds. Participants rated 272 items as "essential/unknown/non-essential". Consensus was considered to be reached on items that over 70% of physical therapists rated as "essential" to clinical practice in the intensive care unit. RESULTS: Of the 272 items in the first round, 188 were deemed essential. In round 2, 11 of the 62 items that failed to reach consensus in round 1 were additionally deemed essential. No item was added to the "essential" consensus in round 3. In total, 199 items were therefore deemed essential as a minimum standard of clinical practice. Participants agreed that 42 items were not essential and failed to reach agreement on 31 others. Identified 199 items were different from those in the UK and Australia due to national laws, cultural and historical backgrounds. CONCLUSIONS: This is the first study to develop a consensus-based minimum clinical practice standard for physical therapists working in intensive care units in Japan.

The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon.

METHODS: We investigated the effect of application of fibroblast growth factor (FGF)-2 on the tendon-to-bone remodeling of repaired supraspinatus tendon in rats subjected to bilateral detachment. FGF-2 (100 mg/kg) in a fibrin sealant or sealant alone was applied on the right and left shoulders, respectively. Twelve animals each at 2, 4, and 6 weeks after surgery were sacrificed for histological analysis (n = 5) and biomechanical Q1 testing (n = 7). RESULTS: Histologically, at 2 weeks, FGF-treated specimens had significantly higher tendon-to-bone insertion maturing scores then untreated specimens (P < .002). At 4 and 6 weeks, the scores of FGF-treated and untreated specimens were similar (P > .05). Biomechanically, FGF-treated specimens were stronger at 2 weeks (P = .001); at 4 and 6 weeks, both specimens exhibited similar strength (P > .05). CONCLUSIONS: The initial tendon-to-bone remodeling was accelerated by a local application of FGF-2. This may represent a clinically important improvement in rotator cuff repair.

Angiopoietin-Like Protein 2 Induces Synovial Inflammation in the Facet Joint Leading to Degenerative Changes via Interleukin-6 Secretion.

STUDY DESIGN: Experimental human study. PURPOSE: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. OVERVIEW OF LITERATURE: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is highly expressed in degenerative FJ synovial tissue and is responsible for local chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, promotes the expression of IL-6 in many cells. METHODS: FJ tissues were harvested from five patients who had undergone lumbar surgery. Immunohistochemistry for ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After cultured synoviocytes from the FJ tissues were subjected to mechanical stress, ANGPTL2 expression and secretion were measured quantitatively using real-time quantitative reverse-transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in the FJ synoviocytes, anti-nuclear factor-κB (NF-κB) activation was investigated using immunocytochemistry, and IL-6 expression and secretion were assayed quantitatively with or without NF-κB inhibitor. Moreover, we assessed whether ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. RESULTS: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ synoviocytes increased in response to stimulation by mechanical stretching. ANGPTL2 protein promoted the nuclear translocation of NF-κB and induced IL-6 expression and secretion in the FJ synoviocytes. This effect was reversed following treatment with NF-κB inhibitor. Furthermore, ANGPTL2-induced IL-6 upregulated the MCP-1 expression in the FJ synoviocytes. CONCLUSIONS: Mechanical stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.

[Multiresidue determination of quinolones in animal and fishery products by HPLC].

A simple and rapid multiresidue method was developed for the determination of twelve quinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, nalidixic acid, norfloxacin, ofloxacin, orbifloxacin, oxolinic acid and sarafloxacin) in muscle, liver, chicken eggs, milk, prawn and rainbow trout. The quinolones were extracted from a sample with acetonitrile-water (95 : 5). A fifth part of the filtered extract was diluted with water to keep the acetonitrile ratio at ca. 60%, and passed through a C18 mini-column. The eluate was evaporated to dryness, and the residues were dissolved in methanol-water (30 : 70) for HPLC analysis. The quinolones were separated on a Inertsil ODS-3V column (4.6 mm i.d.x250 mm) with a gradient system of 0.1% phosphoric acid-acetonitrile as the mobile phase, with fluorescence detection.No interfering peak was found on the chromatograms of animal and fishery products, except for milk. The recoveries of the quinolones were over 60% from the animal and fishery products fortified at 0.1 microg/g, and the quantification limits of the quinolones were 0.005 microg/g. This proposed method was found to be effective and suitable for the screening of the quinolones in animal and fishery products.

Matrix metalloproteinase promotes elastic fiber degradation in ligamentum flavum degeneration.

Ligamentum flavum (LF) hypertrophy in lumbar spinal canal stenosis (LSCS) is characterized by a loss of elastic fibers and fibrosis. Chronic inflammation is thought to be responsible for the histological change but the mechanism underlying elastic fiber degradation remains unclear. Given that matrix metalloproteinase (MMP)-2 and -9 have elastolytic activity and are partly regulated by inflammatory cytokines such as interleukin (IL)-6, in this study, we investigated whether MMPs mediate LF degeneration using 52 LF samples obtained during lumbar surgery, including 31 LSCS and 21 control specimens. We confirmed by histological analysis that the LSCS samples exhibited severe degenerative changes compared with the controls. We found that MMP-2 was upregulated in LF tissue from patients with LSCS at the mRNA and protein levels, whereas MMP-9 expression did not differ between the two groups. The MMP-2 level was positively correlated with LF thickness and negatively correlated with the area occupied by elastic fibers. IL-6 mRNA expression was also increased in LF tissue from patients with LSCS and positively correlated with that of MMP-2. Signal transducer and activator of transcription (STAT)3, a component of the IL-6 signaling pathway, was activated in hypertrophied LF tissues. Our in vitro experiments using fibroblasts from LF tissue revealed that IL-6 increased MMP-2 expression, secretion, and activation via induction of STAT3 signaling, and this effect was reversed by STAT3 inhibitor treatment. Moreover, elastin degradation was promoted by IL-6 stimulation in LF fibroblast culture medium. These results indicate that MMP-2 induction by IL-6/STAT3 signaling in LF fibroblasts can degrade elastic fibers, leading to LF degeneration in LSCS.

[Multi-residue method for determination of veterinary drugs and feed additives in meats by HPLC].

A simple and rapid multi-residue method was developed for the determination of 28 kinds of veterinary drugs and feed additives (drugs) in muscle of cattle, pig and chicken. The drugs were extracted with acetonitrile-water (95:5) in a homogenizer and ultrasonic generator. The extracted solution was poured into an alumina column and the drugs were eluted with acetonitrile-water (90:10). The eluate was washed with n-hexane saturated with acetonitrile and then evaporated. The drugs were separated on a Inertsil ODS-3V column (4.6 mm i.d. x 250 mm) with a gradient system of 0.1% phosphoric acid-acetonitrile as the mobile phase, with monitoring at 280 and 340 nm. The recoveries of the 26 kinds of drugs were over 60% from the meats fortified at 0.1 microg/g, and the quantification limits of most drugs were 0.01 microg/g. This proposed method was found to be effective and suitable for the screening of the above drugs in meats.

Patient outcomes for a minimally invasive approach to treat lumbar spinal canal stenosis: is microendoscopic or microscopic decompressive laminotomy the less invasive surgery?

OBJECTIVE: We performed a study to compare the severity of surgical stress between microscopic and microendoscopic decompressive laminotomy performed via a unilateral approach in patients with lumbar spinal canal stenosis (LSCS). MATERIALS AND METHODS: A total of 41 patients received decompressive laminotomy for lumbar spinal stenosis. Twenty patients received microscopic decompressive laminotomy (MDL), and 21 patients received microendoscopic decompressive laminotomy (MEDL). The pre- and postoperative Japanese Orthopaedic Association (JOA), and Visual Analogue Scale (VAS) lower leg pain scores were evaluated. The other variables studied were the length of the operation, blood loss, length of hospital stay, the reaction of the CRP and WBC levels, the dosage of non-steroidal anti-inflammatory drugs (NSAIDs) used and surgical complications. RESULTS: The clinical analyses of the surgical outcomes were evaluated after a minimum two-year follow-up. The pre-and postoperative JOA scores and VAS in the MDL and MEDL groups were statistically similar. There were statistically significant differences found between the lengths of the operation time, blood loss, length of hospital stay, the reaction of CRP, and the pain indicated by the dosage of NSAIDs. The length of the operation time was longer in the MEDL group, and the other variables were greater in the MDL group. CONCLUSIONS: The MEDL procedure is less invasive and safer than the MDL procedure. Hence, MEDL is an effective technique for treating symptomatic LSCS patients.

Effects of the water-holding capability of polyvinyl formal sponges on osteogenic ability in in vivo experiments.

In this study, dextran-coated polyvinyl formal (PVF) sponges with high water-holding capability were developed to increase the osteogenic response in the PVF sponge. The study aimed to estimate the effect of the increased water-holding capability of the sponges on osteogenic capacity at a bone defect site in the rabbit femur epiphysis. Bone formation was evaluated using radiography, microcomputed tomography (CT), and histological analysis at 2, 4, and 6 weeks after implantation. As shown by radiography and micro-CT findings, the dextran-coated PVF sponge without water-holding capability showed little bone formation at all evaluated time points. However, the dextran-coated PVF sponge with high water-holding capability showed increasing bone formation around the implant at 4 and 6 weeks after implantation. Furthermore, as shown by micro-CT quantitative analysis, the grafted PVF sponge with high water-holding capability showed significantly greater values for percentage of bone volume per total volume and mean bone mineral density compared with the grafted PVF sponge without water-holding capability at 4 and 6 weeks after implantation. These results suggest that the dextran-coated PVF sponge with high water-holding capability promoted osteogenesis in vivo. The PVF sponge might be a new biomaterial to be used as a fill material for bone defects.

Intracellular conversion of irinotecan to its active form, SN-38, by native carboxylesterase in human non-small cell lung cancer.

The anticancer agent irinotecan (CPT-11) is a prodrug converted to its active form, SN-38, by human carboxylesterase (hCE) and the SN-38 is further metabolized to its inactive form, SN-38G. We investigated the expression of hCE in human lung cancer cells as well as the ability of these cells to convert CPT-11 to SN-38 using surgically resected tumor samples and cultured cell lines. SN-38 was 40- to 3,000-fold more toxic to lung cancer cell lines than CPT-11, which acted more time-dependently than SN-38. Although human lung cancer cells expressed hCE in the cytoplasm, hCE expression levels in cancer cells were not correlated with their drug sensitivities. Although intracellular CPT-11 and SN-38 levels continuously increased within 60 min of CPT-11 exposure, SN-38 levels in cells exposed to SN-38 decreased. Cells with the ability to metabolize SN-38 to SN-38G were more resistant to extracellular SN-38 than cells lacking the ability. Of 25 squamous cell carcinomas, 15 were strongly positive for hCE and six were negative. Of 25 adenocarcinomas, four were strongly positive for hCE and 16 were positive, while five were negative. Thus, 70% of non-small cell lung cancers expressed hCE. From these results, we conclude that human lung cancer cells expressed the enzyme which can convert CPT-11 to SN-38 and that intracellular SN-38 converted from CPT-11 may act as a chemotherapeutic agent together with SN-38 absorbed from the outside and augment the dose intensity of SN-38. Therefore, to assess the effects of CPT-11 prior to chemotherapy, it is important to check if lung cancer cells express hCE.

Predictive value of E-PASS and POSSUM systems for postoperative risk assessment of spinal surgery.

OBJECT: The Estimation of Physiological Ability and Surgical Stress (E-PASS) and Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) systems are surgical risk scoring systems that take into account both the patient's preoperative condition and intraoperative variables. While they predict postoperative morbidity and mortality rates for several types of surgery, spinal surgeries are currently not included. The authors assessed the usefulness of E-PASS and POSSUM algorithms and compared the predictive ability of both systems in patients with spinal disorders considered for surgery. METHODS: The E-PASS system includes a preoperative risk score, a surgical stress score, and a comprehensive risk score that is determined by both the preoperative risk score and surgical stress score. The POSSUM system is composed of a physiological score and an operative severity score; its total score is based on both the physiological score and operative severity score. The authors calculated the E-PASS and POSSUM scores for 601 consecutive patients who had undergone spinal surgery and investigated the relationship between the individual scores of both systems and the incidence of postoperative complications. They also assessed the correctness of the predicted morbidity rate of both systems. RESULTS: Postoperative complications developed in 64 patients (10.6%); there were no in-hospital deaths. All EPASS scores (p ≤ 0.001) and the operative severity score and total score of the POSSUM (p < 0.03) were significantly higher in patients with postoperative complications than in those without postoperative complications. The morbidity rates correlated linearly and significantly with all E-PASS scores (p ≤ 0.001); their coefficients (preoperative risk score, ρ = 0.179; surgical stress score, ρ = 0.131; and comprehensive risk score, ρ = 0.198) were higher than those for the POSSUM scores (physiological score, ρ = 0.059; operative severity score, ρ = 0.111; and total score, ρ = 0.091). The area under the receiver operating characteristic curve for the predicted morbidity rate was 0.668 for the E-PASS and 0.588 for the POSSUM system. CONCLUSIONS: As E-PASS predicted morbidity more correctly than POSSUM, it is useful for estimating the postoperative risk of patients considered for spinal surgery.

Effects of water-holding capability of the PVF sponge on the adhesion and differentiation of rat bone marrow stem cell culture.

The aim of the study is to estimate the effects of the water-holding capability of the polyvinyl formal (PVF) sponges on osteogenic response in vitro experiments. The rat bone marrow stem cells (BMCs) were seeded and cultured for up to 4 weeks under static conditions in osteogenic media to evaluate the adhesion, proliferation, differentiation, and mineralization on the Dextran-coated PVF sponges with or without water-holding capability. The BMCs seeded onto the PVF sponges with water-holding capability showed more significant increases in DNA content, alkaline phosphatase (ALP) activity, osteocalcin content, and calcium deposition than those without water-holding capability. These results suggest that the Dextran-coated PVF sponges with high water-holding capability would have potential uses as both a new scaffold to bone tissue engineering and as a new biomaterial.

Angiopoietin-like protein 2 induced by mechanical stress accelerates degeneration and hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis.

Chronic inflammation and subsequent fibrosis induced by mechanical stress play an important role in ligamentum flavum (LF) hypertrophy and degeneration in patients with lumbar spinal canal stenosis (LSCS). Angiopoietin-like protein 2 (Angptl2) is a chronic inflammatory mediator induced under various pathological conditions and increases the expression of TGF-ß1, which is a well-characterized mediator in LF hypertrophy. We investigated whether Angptl2 is induced by mechanical stress, and whether it contributes to LF hypertrophy and degeneration by activating the TGF-ß1 signaling cascade. In this study, we investigated human LF tissue and LF fibroblasts isolated from patients who underwent lumbar surgery. We found that Angptl2 was abundantly expressed in fibroblasts of hypertrophied LF tissues at both the mRNA and protein levels. This expression was not only positively correlated with LF thickness and degeneration but also positively correlated with lumbar segmental motion. Our in vitro experiments with fibroblasts from hypertrophied LF tissue revealed that mechanical stretching stress increases the expression and secretion of Angptl2 via activation of calcineurin/NFAT pathways. In hypertrophied LF tissue, expression of TGF-ß1 mRNA was also increased and TGF-ß1/Smad signaling was activated. Angptl2 expression in LF tissue was positively correlated with the expression of TGF-ß1 mRNA, suggesting cooperation between Angptl2 and TGF-ß1 in the pathogenesis of LF hypertrophy. In vitro experiments revealed that Angptl2 increased levels of TGF-ß1 and its receptors, and also activated TGF-ß1/Smad signaling. Mechanical stretching stress increased TGF-ß1 mRNA expression, which was partially attenuated by treatment with a calcineurin/NFAT inhibitor or Angptl2 siRNA, indicating that induction of TGF-ß1 expression by mechanical stretching stress is partially mediated by Angptl2. We conclude that expression of Angptl2 induced by mechanical stress in LF fibroblasts promotes LF tissue degeneration by activation of TGF-ß1/Smad signaling, which results in LF hypertrophy in patients with LSCS.

Corresponding scapular pain with the nerve root involved in cervical radiculopathy.

PURPOSE: To correspond scapular pain with the nerve root involved in cervical radiculopathy. METHODS: In the anatomic study, 11 Japanese adult cadavers were dissected to examine the numbers and courses of the cutaneous nerves from C3 to C8 dorsal rami. In the clinical study, 14 men and 11 women aged 34 to 77 years who presented with scapular pain as well as pain, numbness or motor weakness in the upper limbs secondary to cervical radiculopathy were assessed. The involved nerve roots were identified based on the symptoms and signs in the arm and/ or fingers, the radiological diagnosis, and the pain response to cervical nerve root blocks. The sites and characteristics of radicular pain were assessed. RESULTS: In the anatomic study of 22 cutaneous nerves from medial branches of dorsal rami, 18 involved the C5 nerve root, 0 the C6 root, one the C7 root, and 8 the C8 root. In the clinical study, the radicular pain often occurred in the suprascapular region involving the C5 root, in the suprascapular to posterior deltoid region involving the C6 root, in the interscapular region involving the C7 root, and in the interscapular and scapular regions involving the C8 root. All patients with C5 or C8 radiculopathy had both superficial and deep pain, whereas almost all patients with C6 or C7 radiculopathy had deep pain only. No patient had superficial pain only. CONCLUSION: Cervical radiculopathy can cause scapular pain. Pain sites and characteristics are related to the affected nerve root.