Time series analysis of jaw muscle contraction and tissue deformation during mastication in miniature pigs

Masticatory muscle contraction causes both jaw movement and tissue deformation during function. Natural chewing data from 25 adult miniature pigs were studied by means of time series analysis. The data set included simultaneous recordings of electromyography (EMG) from bilateral masseter (MA), zygomaticomandibularis (ZM) and lateral pterygoid muscles, bone surface strains from the left squamosal bone (SQ), condylar neck (CD) and mandibular corpus (MD), and linear deformation of the capsule of the jaw joint measured bilaterally using differential variable reluctance transducers. Pairwise comparisons were examined by calculating the cross-correlation functions. Jaw-adductor muscle activity of MA and ZM was found to be highly cross-correlated with CD and SQ strains and weakly with MD strain. No muscle’s activity was strongly linked to capsular deformation of the jaw joint, nor were bone strains and capsular deformation tightly linked. Homologous muscle pairs showed the greatest synchronization of signals, but the signals themselves were not significantly more correlated than those of non-homologous muscle pairs. These results suggested that bone strains and capsular deformation are driven by different mechanical regimes. Muscle contraction and ensuing reaction forces are probably responsible for bone strains, whereas capsular deformation is more likely a product of movement.

The influence of "C-factor" and light activation technique on polymerization contraction forces of resin composite

Objectives: This study evaluated the influence of the cavity configuration factor ("C-Factor") and light activation technique on polymerization contraction forces of a Bis-GMA-based composite resin (Charisma, Heraeus Kulzer). Material and Methods: Three different pairs of steel moving bases were connected to a universal testing machine (Emic DL 500): groups A and B - 2x2 mm (CF=0.33), groups C and D - 3x2 mm (CF=0.66), groups E and F - 6x2 mm (CF=1.5). After adjustment of the height between the pair of bases so that the resin had a volume of 12 mm(3) in all groups, the material was inserted and polymerized by two different methods: pulse delay (100 mW/cm(2) for 5 s, 40 s interval, 600 mW/cm(2) for 20 s) and continuous pulse (600 mW/cm(2) for 20 s). Each configuration was light cured with both techniques. Tensions generated during polymerization were recorded by 120 s. The values were expressed in curves (Force(N) x Time(s)) and averages compared by statistical analysis (ANOVA and Tukey's test, p<0.05). Results: For the 2x2 and 3x2 bases, with a reduced C-Factor, significant differences were found between the light curing methods. For 6x2 base, with high C-Factor, the light curing method did not influence the contraction forces of the composite resin. Conclusions: Pulse delay technique can determine less stress on tooth/restoration interface of adhesive restorations only when a reduced C-Factor is present.

Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats

Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardiovascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study, we hypothesize that inhibition of TLR4 decreases BP (blood pressure) and improves vascular contractility in resistance arteries from SHR (spontaneously hypertensive rats). TLR4 protein expression in mesenteric resistance arteries was higher in 15-week-old SHR than in age-matched Wistar controls or in 5-week-old SHR. To decrease the activation of TLR4, 15-week-old SHR and Wistar rats were treated with anti-TLR4 (anti-TLR4 antibody) or non-specific IgG control antibody for 15 days (1 mu g per day, intraperitoneal). Treatment with anti-TLR4 decreased MAP (mean arterial pressure) as well as TLR4 protein expression in mesenteric resistance arteries and IL-6 (interleukin 6) serum levels from SHR when compared with SHR treated with IgG. No changes in these parameters were found in treated Wistar control rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to NA (noradrenaline) compared with IgG-treated SHR. Inhibition of COX (cyclo-oxygenase)-1 and COX-2, enzymes related to inflammatory pathways, decreased NA responses only in mesenteric resistance arteries of SHR treated with IgG. COX-2 expression and TXA(2) (thromboxane A(2)) release were decreased in SHR treated with anti-TLR4 compared with IgG-treated SHR. Our results suggest that TLR4 activation contributes to increased BP, low-grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.

The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat

The modulation played by reactive oxygen species on the angiotensin II-induced contraction in type I-diabetic rat carotid was investigated. Concentration-response curves for angiotensin II were obtained in endothelium-intact or endothelium-denuded carotid from control or streptozotocin-induced diabetic rats, pre-treated with tiron (superoxide scavenger), PEG-catalase (hydrogen peroxide scavenger), dimethylthiourea (hydroxyl scavenger), apocynin [NAD(P) H oxidase inhibitor], SC560 (cyclooxygenase-1 inhibitor), SC236 (cyclooxygenase-2 inhibitor) or Y-27632 (Rho-kinase inhibitor). Reactive oxygen species were measured by flow cytometry in dihydroethidium (DHE)-loaded endothelial cells. Cyclooxygenase and AT1-receptor expression was assessed by immunohistochemistry. Diabetes increased the angiotensin II-induced contraction but reduced the agonist potency in rat carotid. Endothelium removal, tiron or apocynin restored the angiotensin II-induced contraction in diabetic rat carotid to control levels. PEG-catalase, DMTU or SC560 reduced the angiotensin II-induced contraction in diabetic rat carotid at the same extent. SC236 restored the angiotensin II potency in diabetic rat carotid. Y-27632 reduced the angiotensin II-induced contraction in endothelium-intact or -denuded diabetic rat carotid. Diabetes increased the DHE-fluorescence of carotid endothelial cells. Apocynin reduced the DHE-fluorescence of endothelial cells from diabetic rat carotid to control levels. Diabetes increased the muscular cyclooxygenase-2 expression but reduced the muscular AT1-receptor expression in rat carotid. In summary, hydroxyl radical, hydrogen peroxide and superoxide anion-derived from endothelial NAD(P) H oxidase mediate the hyperreactivity to angiotensin II in type I-diabetic rat carotid, involving the participation of cyclooxygenase-1 and Rho-kinase. Moreover, increased muscular cyclooxygenase-2 expression in type I-diabetic rat carotid seems to be related to the local reduced AT1-receptor expression and the reduced angiotensin II potency. (C) 2011 Elsevier B. V. All rights reserved.

Residual stresses in Y-TZP crowns due to changes in the thermal contraction coefficient of veneers

Objective. To test the hypothesis that the difference in the coefficient of thermal contraction of the veneering porcelain above (˛liquid) and below (˛solid) its Tg plays an important role in stress development during a fast cooling protocol of Y-TZP crowns. Methods. Three-dimensional finite element models of veneered Y-TZP crowns were developed. Heat transfer analyses were conducted with two cooling protocols: slow (group A) and fast (groups B–F). Calculated temperatures as a function of time were used to determine the thermal stresses. Porcelain ˛solid was kept constant while its ˛liquid was varied, creating different ˛/˛solid conditions: 0, 1, 1.5, 2 and 3 (groups B–F, respectively). Maximum ( 1) and minimum ( 3) residual principal stress distributions in the porcelain layer were compared. Results. For the slowly cooled crown, positive 1 were observed in the porcelain, orientated perpendicular to the core–veneer interface (“radial” orientation). Simultaneously, negative 3 were observed within the porcelain, mostly in a hoop orientation (“hoop–arch”). For rapidly cooled crowns, stress patterns varied depending on ˛/˛solid ratios. For groups B and C, the patterns were similar to those found in group A for 1 (“radial”) and 3 (“hoop–arch”). For groups D–F, stress distribution changed significantly, with 1 forming a “hoop-arch” pattern while 3 developed a “radial” pattern. Significance. Hoop tensile stresses generated in the veneering layer during fast cooling protocols due to porcelain high ˛/˛solid ratio will facilitate flaw propagation from the surface toward the core, which negatively affects the potential clinical longevity of a crown.

Computational Modeling of Cardiac Excitation-Contraction Coupling in Physiological and Pathological Conditions

The cardiomyocyte is a complex biological system where many mechanisms interact non-linearly to regulate the coupling between electrical excitation and mechanical contraction. For this reason, the development of mathematical models is fundamental in the field of cardiac electrophysiology, where the use of computational tools has become complementary to the classical experimentation. My doctoral research has been focusing on the development of such models for investigating the regulation of ventricular excitation-contraction coupling at the single cell level. In particular, the following researches are presented in this thesis: 1) Study of the unexpected deleterious effect of a Na channel blocker on a long QT syndrome type 3 patient. Experimental results were used to tune a Na current model that recapitulates the effect of the mutation and the treatment, in order to investigate how these influence the human action potential. Our research suggested that the analysis of the clinical phenotype is not sufficient for recommending drugs to patients carrying mutations with undefined electrophysiological properties. 2) Development of a model of L-type Ca channel inactivation in rabbit myocytes to faithfully reproduce the relative roles of voltage- and Ca-dependent inactivation. The model was applied to the analysis of Ca current inactivation kinetics during normal and abnormal repolarization, and predicts arrhythmogenic activity when inhibiting Ca-dependent inactivation, which is the predominant mechanism in physiological conditions. 3) Analysis of the arrhythmogenic consequences of the crosstalk between β-adrenergic and Ca-calmodulin dependent protein kinase signaling pathways. The descriptions of the two regulatory mechanisms, both enhanced in heart failure, were integrated into a novel murine action potential model to investigate how they concur to the development of cardiac arrhythmias. These studies show how mathematical modeling is suitable to provide new insights into the mechanisms underlying cardiac excitation-contraction coupling and arrhythmogenesis.

Functional aspects of distal oesophageal spasm: the role of onset velocity and contraction amplitude on bolus transit

Distal oesophageal spasm is a rare and under-investigated motility abnormality. Recent studies indicate effective bolus transit in varying percentages of distal oesophageal spasm patients.

Neuregulin-1 beta attenuates doxorubicin-induced alterations of excitation-contraction coupling and reduces oxidative stress in adult rat cardiomyocytes

Treatment of metastatic breast cancer with doxorubicin (Doxo) in combination with trastuzumab, an antibody targeting the ErbB2 receptor, results in an increased incidence of heart failure. Doxo therapy induces reactive oxygen species (ROS) and alterations of calcium homeostasis. Therefore, we hypothesized that neuregulin-1 beta (NRG), a ligand of the cardiac ErbB receptors, reduces Doxo-induced alterations of EC coupling by triggering antioxidant mechanisms. Adult rat ventricular cardiomyocytes (ARVM) were isolated and treated for 18-48 h. SERCA protein was analyzed by Western blot, EC coupling parameters by fura-2 and video edge detection, gene expression by RT-PCR, and ROS by DCF-fluorescence microscopy. At clinically relevant doses Doxo reduced cardiomyocytes contractility, SERCA protein and SR calcium content. NRG, similarly as the antioxidant N-acetylcystein (NAC), did not affect EC coupling alone, but protected against Doxo-induced damage. NRG and Doxo showed an opposite modulation of glutathione reductase gene expression. NRG, similarly as NAC, reduced peroxide- or Doxo-induced oxidative stress. Specific inhibitors showed, that the antioxidant action of NRG depended on signaling via the ErbB2 receptor and on the Akt- and not on the MAPK-pathway. Therefore, NRG attenuates Doxo-induced alterations of EC coupling and reduces oxidative stress in ARVM. Inhibition of the ErbB2/NRG signaling pathway by trastuzumab in patients concomitantly treated with Doxo might prevent beneficial effects of NRG in the myocardium.