Compressive Follower Load Influences Cervical Spine Kinematics and Kinetics During Simulated Head-First Impact in an in Vitro Model

2013 ◽  
Vol 135 (11) ◽  
Author(s):  
Amy Saari ◽  
Christopher R. Dennison ◽  
Qingan Zhu ◽  
Timothy S. Nelson ◽  
Philip Morley ◽  
...  
Keyword(s):  
Cervical Spine ◽  
Injury Risk ◽  
Muscle Activation ◽  
Ex Vivo ◽  
Reaction Force ◽  
Experimental Studies ◽  
Follower Load ◽  
Muscle Forces

Current understanding of the biomechanics of cervical spine injuries in head-first impact is based on decades of epidemiology, mathematical models, and in vitro experimental studies. Recent mathematical modeling suggests that muscle activation and muscle forces influence injury risk and mechanics in head-first impact. It is also known that muscle forces are central to the overall physiologic stability of the cervical spine. Despite this knowledge, the vast majority of in vitro head-first impact models do not incorporate musculature. We hypothesize that the simulation of the stabilizing mechanisms of musculature during head-first osteoligamentous cervical spine experiments will influence the resulting kinematics and injury mechanisms. Therefore, the objective of this study was to document differences in the kinematics, kinetics, and injuries of ex vivo osteoligamentous human cervical spine and surrogate head complexes that were instrumented with simulated musculature relative to specimens that were not instrumented with musculature. We simulated a head-first impact (3 m/s impact speed) using cervical spines and surrogate head specimens (n = 12). Six spines were instrumented with a follower load to simulate in vivo compressive muscle forces, while six were not. The principal finding was that the axial coupling of the cervical column between the head and the base of the cervical spine (T1) was increased in specimens with follower load. Increased axial coupling was indicated by a significantly reduced time between head impact and peak neck reaction force (p = 0.004) (and time to injury (p = 0.009)) in complexes with follower load relative to complexes without follower load. Kinematic reconstruction of vertebral motions indicated that all specimens experienced hyperextension and the spectrum of injuries in all specimens were consistent with a primary hyperextension injury mechanism. These preliminary results suggest that simulating follower load that may be similar to in vivo muscle forces results in significantly different impact kinetics than in similar biomechanical tests where musculature is not simulated.

Robotic Simulation of an Eccentric Lever Arm Protocol and a Novel Head Weight Protocol for Evaluation of the Subaxial Cervical Spine: An In Vitro Biomechancial Comparison

2011 ◽  
Author(s):  
Daniel M. Wido ◽  
Denis J. DiAngelo ◽  
Brian P. Kelly
Keyword(s):  
Cervical Spine ◽  
Muscle Activation ◽  
Vertical Force ◽  
Follower Load ◽  
Testing Platform ◽  
Lever Arm ◽  
Subaxial Cervical Spine ◽  
Head Weight ◽  
Robotic Testing

In vitro testing provides a critical tool for understanding the biomechanics of the subaxial cervical spine. Previous common testing protocols used to evaluate the subaxial cervical spine include pure moment, follower load, and eccentric lever arm (EL) loading methods [1,2,3]. Although these methods are widely accepted, there is always a goal to try to better simulate physiologic loading conditions. While the follower load attempts to simulate compression due to muscle activation, no previous protocol has taken into account the constant vertical force vector applied to C2 produced by the weight of the human head. Furthermore, we are unaware of previous direct protocol to protocol comparisons using the same testing platform and test specimens. Our multi-axis programmable robotic testing platform (Spine Robot) provides the means to explore such comparisons. The objectives of this study were: 1) to develop a novel head weight influenced loading protocol (HWL), 2) simulate and compare the EL protocol and the HWL protocol on a single programmable robotic testing frame with a consistent specimen sample group.

scholarly journals Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

2019 ◽  
Vol 9 (3-4) ◽  
pp. 559-567
Author(s):  
G. N. Leonova ◽  
O. S. Majstrovskaya ◽  
V. A. Lubova ◽  
N. B. Sanina
Keyword(s):  
Ex Vivo ◽  
Experimental Studies ◽  
Encephalitis Virus ◽  
Virus Elimination ◽  
Specific Antibodies ◽  
Tick Borne Encephalitis ◽  
Antibody Titers ◽  
Tick Borne Encephalitis Virus

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE.

scholarly journals Intracellular Activity of Antibiotics against Staphylococcus aureus in a Mouse Peritonitis Model

2009 ◽  
Vol 53 (5) ◽  
pp. 1874-1883 ◽  
Author(s):  
Anne Sandberg ◽  
Jonas H. R. Hessler ◽  
Robert L. Skov ◽  
Jens Blom ◽  
Niels Frimodt-Møller
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Experimental Studies ◽  
In Vitro Models ◽  
Response To Therapy ◽  
In Vivo Model ◽  
Poor Correlation ◽  
Intracellular Activity

ABSTRACT Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response to therapy and the high frequency of infection recurrence. The intracellular persistence of staphylococci has been recognized and could offer a good explanation for these treatment difficulties. Knowledge of the interplay between intracellular antibiotic activity and the overall outcome of infection is therefore important. Several intracellular in vitro models have been developed, but few experimental animal models have been published. The mouse peritonitis/sepsis model was used as the basic in vivo model exploring a quantitative ex vivo extra- and intracellular differentiation assay. The intracellular presence of S. aureus was documented by electron microscopy. Five antibiotics, dicloxacillin, cefuroxime, gentamicin, azithromycin, and rifampin (rifampicin), were tested in the new in vivo model; and the model was able to distinguish between their extra- and intracellular effects. The intracellular effects of the five antibiotics could be ranked as follows as the mean change in the log10 number of CFU/ml (Δlog10 CFU/ml) between treated and untreated mice after 4 h of treatment: dicloxacillin (3.70 Δlog10 CFU/ml) > cefuroxime (3.56 Δlog10 CFU/ml) > rifampin (1.86 Δlog10 CFU/ml) > gentamicin (0.61 Δlog10 CFU/ml) > azithromycin (0.21 Δlog10 CFU/ml). We could also show that the important factors during testing of intracellular activity in vivo are the size, number, and frequency of doses; the time of exposure; and the timing between the start of infection and treatment. A poor correlation between the intracellular accumulation of the antibiotics and the actual intracellular effect was found. This stresses the importance of performing experimental studies, like those with the new in vivo model described here, to measure actual intracellular activity instead of making predictions based on cellular pharmacokinetic and MICs.

Multilevel Validation of a Male Neck Finite Element Model With Active Musculature

2020 ◽  
Vol 143 (1) ◽  
Author(s):  
Jeffrey B. Barker ◽  
Duane S. Cronin
Keyword(s):  
Cervical Spine ◽  
Injury Risk ◽  
Muscle Activation ◽  
Computational Models ◽  
Soft Tissues ◽  
Motor Vehicle ◽  
Experimental Studies ◽  
Tissue Level ◽  
Open Loop ◽  
Frontal Impact

Abstract Computational models of the human neck have been developed to assess human response in impact scenarios; however, the assessment and validation of such models is often limited to a small number of experimental data sets despite being used to evaluate the efficacy of safety systems and potential for injury risk in motor vehicle collisions. In this study, a full neck model (NM) with active musculature was developed from previously validated motion segment models of the cervical spine. Tissue mechanical properties were implemented from experimental studies, and were not calibrated. The neck model was assessed with experimental studies at three levels of increasing complexity: ligamentous cervical spine in axial rotation, axial tension, frontal impact, and rear impact; postmortem human subject (PMHS) rear sled impact; and human volunteer frontal and lateral sled tests using an open-loop muscle control strategy. The neck model demonstrated good correlation with the experiments ranging from quasi-static to dynamic, assessed using kinematics, kinetics, and tissue-level response. The contributions of soft tissues, neck curvature, and muscle activation were associated with higher stiffness neck response, particularly for low severity frontal impact. Experiments presenting single-value data limited assessment of the model, while complete load history data and cross-correlation enabled improved evaluation of the model over the full loading history. Tissue-level metrics demonstrated higher variability and therefore lower correlation relative to gross kinematics, and also demonstrated a dependence on the local tissue geometry. Thus, it is critical to assess models at the gross kinematic and the tissue levels.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Organische Nitrate und Thrombozytenfunktion

1988 ◽  
Vol 08 (02) ◽  
pp. 90-99 ◽  
Author(s):  
H. Schröder ◽  
K. Schrör
Keyword(s):  
Endothelial Cell ◽  
Angina Pectoris ◽  
Ex Vivo

ZusammenfassungOrganische Nitrate unterschiedlicher chemischer Struktur sowie Nitroprussidnatrium und Molsidomin (bzw. ihre biologisch aktiven Metaboliten) können die (primäre) Aggregation und Sekretion von Humanthrombozyten in vitro und ex vivo hemmen. Eine solche Wirkung wird für Molsidomin (SIN-1) und Nitroprussidnatrium in vitro in Konzentrationen beobachtet, die in der gleichen Größenordnung liegen wie die vasodilatierenden Effekte der Substanzen. Dagegen sind für eine direkte Antiplättchenwirkung organischer Nitrate (Glyzeryltrinitrat, Isosorbiddinitr at, Isosorbidmononitrate, Teopranitol) in vitro Konzentrationen erforderlich, die ca. 100- bis 1000fach höher sind als die Plasmaspiegel der Substanzen nach therapeutischer Dosierung bzw. die Konzentrationen, die isolierte Gefäßstreifen relaxieren. Als gemeinsamer Wirkungsmechanismus der direkten thrombozy-tenfunktionshemmenden und gefäßerweiternden Wirkung all dieser Substanzen kann heute eine Stickoxid-(NO)-vermittelte Stimulation der cGMP-Bildung angenommen werden, das aus organischen Nitraten als »Pro-drug« entsteht. Die Freisetzung von NO, eines »endothelial cell-derived relaxing factors« (EDRF) aus Nitroprussidnatrium und SIN-1 erfolgt spontan. Dagegen erfordert die Freisetzung von NO aus organischen Nitraten einen enzymatischen Stoffwechselweg, der in isolierten Thrombozyten nicht vorhanden ist. Eine Antiplättchenwirkung organischer Nitrate in vivo bzw. ex vivo wird daher über die Stimulation eines endothelialen, thrombozyteninhibitorischen Faktors erklärt. Hierbei sind Prostazyklin sowie ein bisher unbekannter Endothel-zellfaktor neben einer synergistischen Wirkung organischer Nitrate mit endogenem Prostazyklin in Diskussion. Eine thrombozytenfunktionshemmen-de Wirkung organischer Nitrate könnte in Kombination mit ihren hämody-namischen Effekten auch für die an-tianginöse Wirkung in der Klinik bedeutsam sein, insbesondere zur Verhinderung vasospastischer Zustände bei der instabilen Angina pectoris.

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