Update on the Biomechanics of the Craniocervical Junction—Part I: Transverse Atlantal Ligament in the Elderly

Study Design: In vitro biomechanical study. Objective: The transverse ligament is the strongest ligament of the craniocervical junction and plays a critical role in atlanto-axial stability. The goal of this cadaveric study, and the subsequent study (part II), was to reevaluate the force required for the transverse ligament and alar ligament to fail in a more physiological biomechanical model in elderly specimens. Methods: Twelve C1-2 specimens were harvested from fresh-frozen Caucasian cadavers with a mean age at death of 81 years (range 68-89 years). Only the transverse ligament was preserved, and the bony C1-2 complex was left intact. The dens was pulled away from the anterior arch of C1 using a strength test machine that applies controlled increasing force. After testing, the axis was split in half to check for hidden pathologies and osteoporosis. The differences in the failure force between sex and age groups (group 1: <80 years, group 2: >80 years) were compared. Results: The mean force required for the transverse ligament to fail was 236.2 ± 66 N (range 132-326 N). All but 2 specimens had significant osteoporotic loss of trabecular bone. No significant differences between sex and age groups were found. Conclusions: The transverse ligament’s failure in elderly specimens occurred at an average force of 236 N, which was lower than that reported in the previous literature. The ligament’s failure force in younger patients differs and may be similar to the findings published to date.

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Update on the Biomechanics of the Craniocervical Junction, Part II: Alar Ligament

Global Spine Journal ◽

10.1177/2192568220941452 ◽

2020 ◽

pp. 219256822094145

Author(s):

Basem Ishak ◽

Alexander von Glinski ◽

Graham Dupont ◽

Stefan Lachkar ◽

Emre Yilmaz ◽

...

Keyword(s):

Tensile Strength ◽

Biomechanical Model ◽

Biomechanical Study ◽

Occipital Condyle ◽

Transverse Ligament ◽

Alar Ligament ◽

Axial Complex ◽

Average Force ◽

The Right

Study Design: In vitro biomechanical study. Objective: The strength of the alar ligament has been described inconsistently, possibly because of the nonphysiological biomechanical testing models, and the inability to test the ligament with both attachments simultaneously. The purpose of this biomechanical model was to reevaluate the alar ligament’s tensile strength with both bony attachments, while also keeping the transverse ligament intact, all in a more physiological biomechanical model that mimics the mechanism of traumatic injury closely. Methods: Eleven fresh-frozen occipito-atlanto-axial (C0-C1-C2) specimens were harvested from individuals whose mean age at death was 77.4 years (range 46-97 years). Only the alar and transverse ligaments were preserved, and the bony C0-C1-C2 complex was left intact. Axial tension was exerted on the dens to displace it posteriorly, while the occipito-axial complex was fixed anteriorly. A device that applies controlled increasing force was used to test the tensile strength (M2-200, Mark-10 Corporation). Results: The mean force required for the alar ligament to fail was 394 ± 52 N (range 317-503 N). However, both the right and left alar ligaments ruptured simultaneously in 10 specimens. The ligament failed most often at the dens (n = 10), followed by occipital condyle rupture (n = 1). The transverse ligament remained intact in all specimens. Conclusions: When both the right and left alar ligament were included, the total alar ligament failure occurred at an average force of 394 N. The alar ligament failed before the transverse ligament.

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Evaluating stability of the craniovertebral junction after unilateral C1 lateral mass resection: implications for the direct lateral approach

Journal of Neurosurgery Spine ◽

10.3171/2021.4.spine21226 ◽

2021 ◽

pp. 1-7

Author(s):

Pranay Soni ◽

Jeremy G. Loss ◽

Callan M. Gillespie ◽

Robb W. Colbrunn ◽

Richard Schlenk ◽

...

Keyword(s):

Axial Rotation ◽

Craniovertebral Junction ◽

Craniocervical Junction ◽

Lateral Approach ◽

Biomechanical Study ◽

Lateral Mass ◽

Internal Stabilization ◽

Flexion Extension ◽

Direct Lateral Approach

OBJECTIVE The direct lateral approach is an alternative to the transoral or endonasal approaches to ventral epidural lesions at the lower craniocervical junction. In this study, the authors performed, to their knowledge, the first in vitro biomechanical evaluation of the craniovertebral junction after sequential unilateral C1 lateral mass resection. The authors hypothesized that partial resection of the lateral mass would not result in a significant increase in range of motion (ROM) and may not require internal stabilization. METHODS The authors performed multidirectional in vitro ROM testing using a robotic spine testing system on 8 fresh cadaveric specimens. We evaluated ROM in 3 primary movements (axial rotation [AR], flexion/extension [FE], and lateral bending [LB]) and 4 coupled movements (AR+E, AR+F, LB + left AR, and LB + right AR). Testing was performed in the intact state, after C1 hemilaminectomy, and after sequential 25%, 50%, 75%, and 100% C1 lateral mass resection. RESULTS There were no significant increases in occipital bone (Oc)–C1, C1–2, or Oc–C2 ROM after C1 hemilaminectomy and 25% lateral mass resection. After 50% resection, Oc–C1 AR ROM increased by 54.4% (p = 0.002), Oc LB ROM increased by 47.8% (p = 0.010), and Oc–C1 AR+E ROM increased by 65.8% (p < 0.001). Oc–C2 FE ROM increased by 7.2% (p = 0.016) after 50% resection; 75% and 100% lateral mass resection resulted in further increases in ROM. CONCLUSIONS In this cadaveric biomechanical study, the authors found that unilateral C1 hemilaminectomy and 25% resection of the C1 lateral mass did not result in significant biomechanical instability at the occipitocervical junction, and 50% resection led to significant increases in Oc–C2 ROM. This is the first biomechanical study of lateral mass resection, and future studies can serve to validate these findings.

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The Effect of Volarly Angulated Distal Radius Fractures on Forearm Rotation: In Vitro Biomechanical Study

Journal of Wrist Surgery ◽

10.1055/s-0035-1544221 ◽

2015 ◽

Vol 04 (S 01) ◽

Author(s):

Masao Nishiwaki ◽

Mark Welsh ◽

Louis Ferreira ◽

James Johnson ◽

Graham King ◽

...

Keyword(s):

Distal Radius ◽

Biomechanical Study ◽

Distal Radius Fractures ◽

Radius Fractures ◽

Forearm Rotation

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Fibrin Polymerization Defect in HIV-infected Patients-Evidence for a Critical Role of Albumin in the Prolongation of Thrombin and Reptilase Clotting Times

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653779 ◽

1995 ◽

Vol 73 (03) ◽

pp. 349-355 ◽

Cited By ~ 4

Author(s):

Pierre Toulon ◽

Elyane Frere ◽

Claude Bachmeyer ◽

Nathalie Candia ◽

Philippe Blanche ◽

...

Keyword(s):

Critical Role ◽

Human Albumin ◽

Albumin Level ◽

Final Concentration ◽

Albumin Concentration ◽

Clotting Time ◽

Fibrin Polymerization ◽

Small Series ◽

Group 1

SummaryThrombin clotting time (TCT) and reptilase clotting time (RCT) were found significantly prolonged in a series of 72 HIV-infected patients drawn for routine coagulation testing. Both TCT and RCT were highly significantly correlated with albumin (r = -0.64, and r = -0.73 respectively, p<0.0001). TCT and RCT were significantly higher (p<0.0001) in a series of 30 other HIV-infected patients selected on their albumin level below 30.0 g/l (group l) than in 30 HIV-infected patients with albumin level above 40.0 g/l or in 30 HIV-negative controls; the two latter groups were not different. In vitro supplementation of plasma from group 1 patients with purified human albumin up to 45.0 g/l (final concentration) lead to a dramatic shortening effect on both TCT and RCT, which reached normal values. The TCT and RCT of the purified fibrinogen solutions (2.0 g/l final concentration) were not different in the three groups, and normal polymerization curves were obtained in all cases. This further ruled out the presence of any dysfibrinogenemia in the plasma from group 1 patients. Using purified proteins, highly significant correlations were demonstrated between the albumin concentration and the prolongations of both TCT and RCT, which were of the same magnitude order than those found in the patients plasma. These results suggest that hypo-albuminemia is responsible for the acquired fibrin polymerization defect reported in HIV-infected patients. The pathophysiological implication of the low albumin levels was suggested by the finding of decreased albumin levels (associated with prolonged TCT and RCT) in a small series of the eight HIV-infected patients who developed thrombotic complications.

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Rhenium-188 labeled recombinant human plasminogen kringle5 (rhk5) and preliminary biodistribution

Nuklearmedizin ◽

10.3413/nukmed-0349-10-09 ◽

2011 ◽

Vol 50 (06) ◽

pp. 234-239 ◽

Cited By ~ 3

Author(s):

R. Guo ◽

Y. Ma ◽

R. Zhang ◽

S. Liang ◽

H. Shen ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Human Serum ◽

Critical Role ◽

Angiogenesis Inhibitor ◽

Simple Method ◽

Tumour Formation ◽

Human Plasminogen ◽

Specificity Of Binding ◽

A549 Lung

Summary Aim: Angiogenesis plays a critical role in tumour formation and metastasis. Suitable radiolabeled angiogenesis inhibitor can be used for noninvasive imaging of angiogenesis and radionuclide therapy. Here we prepare rhenium-188 labeled recombinant human plasminogen kringle5 (188Re-rhk5) in a convenient manner than evaluate its properties in A549 lung adenocarcinoma. Methods: 188Rerhk5 was obtained by conjugating His group at the C end of rhk5 with fac- [188Re(H2O)3(CO)3]+. Chelating efficiency of fac-[188Re(H2O)3(CO)3]+ and radiolabeling efficiency of 188Re-rhk5 were measured by radio thin-layer chromatography (RTLC). In vitro stability of 188Re-rhk5 was determined in human serum at 37°C and analyzed by RTLC. Competition test was also performed to verify the specificity of binding. A biodistribution study was carried out in nude mice bearing A549 lung adenocarcinoma. Results: 188Rerhk5 was obtained with a radiolabel efficiency of 66.1%, the radiochemical purity (RCP) can marreach 95.2% after purification. 188Re-rhk5 showed high stability in human serum, the RCP was more than 80% even 12 h after incubation. Competition test showed a high binding specificity. Furthermore, this radio-complex was excreted mainly through kidneys and showed specific tumour uptake in mice bearing A549 tumours. Conclusion: 188Re-rhk5 was prepared by a simple method. Preliminary biodistribution results showed its potential as an agent for possible tumour imaging, therapy and encouraged further investigation.

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Role of the anconeus in the stability of a lateral ligament and common extensor origin–deficient elbow: an in vitro biomechanical study

Journal of Shoulder and Elbow Surgery ◽

10.1016/j.jse.2018.11.040 ◽

2019 ◽

Vol 28 (5) ◽

pp. 974-981 ◽

Cited By ~ 1

Author(s):

Armin Badre ◽

David T. Axford ◽

Sara Banayan ◽

James A. Johnson ◽

Graham J.W. King

Keyword(s):

Biomechanical Study ◽

Lateral Ligament ◽

The Stability

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RNF141 interacts with KRAS to promote colorectal cancer progression

Oncogene ◽

10.1038/s41388-021-01877-4 ◽

2021 ◽

Author(s):

Jiuna Zhang ◽

Xiaoyu Jiang ◽

Jie Yin ◽

Shiying Dou ◽

Xiaoli Xie ◽

...

Keyword(s):

Colorectal Cancer ◽

Plasma Membrane ◽

Tumor Growth ◽

Cancer Progression ◽

Critical Role ◽

Ring Finger ◽

Immunohistochemical Analysis ◽

Bimolecular Fluorescence Complementation

AbstractRING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.

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NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽

10.3390/cancers13122999 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2999

Author(s):

Deborah Reynaud ◽

Roland Abi Nahed ◽

Nicolas Lemaitre ◽

Pierre-Adrien Bolze ◽

Wael Traboulsi ◽

...

Keyword(s):

Immune Response ◽

Tumor Cells ◽

Major Gene ◽

Critical Role ◽

Orthotopic Model ◽

Independent Manner ◽

Maternal Immune Response ◽

The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

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Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽

10.3390/cancers13040668 ◽

2021 ◽

Vol 13 (4) ◽

pp. 668

Author(s):

Concetta Altamura ◽

Maria Raffaella Greco ◽

Maria Rosaria Carratù ◽

Rosa Angela Cardone ◽

Jean-François Desaphy

Keyword(s):

Ovarian Cancer ◽

Ion Channels ◽

Transient Receptor Potential ◽

Critical Role ◽

Gynecologic Cancer ◽

Receptor Potential ◽

Transient Receptor Potential Channels ◽

Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

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Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease

Cell Death and Differentiation ◽

10.1038/s41418-020-00685-9 ◽

2021 ◽

Author(s):

Wen-Dai Bao ◽

Pei Pang ◽

Xiao-Ting Zhou ◽

Fan Hu ◽

Wan Xiong ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Impairment ◽

Iron Homeostasis ◽

Critical Role ◽

Gene Set Enrichment Analysis ◽

Molecular Characteristics ◽

Intracellular Iron

AbstractIron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

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