Experimental and Numerical Characterization of the Mechanical Masseter Muscle Response During Biting.

Predictive simulations of the mastication system would significantly improve our understanding of temporomandibular joint (TMJ) disorders and the planning of cranio-maxillofacial surgery procedures. Respective computational models must be validated by experimental data from in vivo characterization of the mastication system's mechanical response. The present pilot-study demonstrates the feasibility of a combined experimental and numerical procedure to validate a computer model of the masseter muscle. An experimental setup is proposed that provides a simultaneous bite force measurement and ultrasound-based visualization of muscle deformation. The direct comparison of the experimentally observed and numerically predicted muscle response demonstrates the predictive capabilities of such anatomically accurate biting models. Differences between molar and incisor biting are investigated; muscle deformation is recorded for three different bite forces in order to capture the effect of increasing muscle fiber recruitment. The three-dimensional (3D) muscle deformation at each bite position and force-level is approximatively reconstructed from ultrasound measurements in five distinct cross-sectional areas (four horizontal and one vertical cross section). The experimental work is accompanied by numerical simulations to validate the predictive capabilities of a constitutive muscle model previously formulated. An anatomy-based, fully 3D model of the masseter muscle is created from magnetic resonance images (MRI) of the same subject. The direct comparison of experimental and numerical results revealed good agreement for maximum bite forces and masseter deformations in both biting positions. The present work therefore presents a feasible in vivo measurement system to validate numerically predicted masseter muscle contractions during mastication.

In vivo observations and in vitro experiments on the oral phase of swallowing of Newtonian and shear-thinning liquids.

In this study, an in vitro device that mimics the oral phase of swallowing is calibrated using in vivo measurements. The oral flow behavior of different Newtonian and non-Newtonian solutions is then investigated in vitro, revealing that shear-thinning thickeners used in the treatment of dysphagia behave very similar to low-viscosity Newtonian liquids during active swallowing, but provide better control of the bolus before the swallow is initiated. A theoretical model is used to interpret the experimental results and enables the identification of two dynamical regimes for the flow of the bolus: first, an inertial regime of constant acceleration dependent on the applied force and system inertia, possibly followed by a viscous regime in which the viscosity governs the constant velocity of the bolus. This mechanistic understanding provides a plausible explanation for similarities and differences in swallowing performance of shear-thinning and Newtonian liquids. Finally, the physiological implications of the model and experimental results are discussed. In vitro and theoretical results suggest that individuals with poor tongue strength are more sensitive to overly thickened boluses. The model also suggests that while the effects of system inertia are significant, the density of the bolus itself plays a negligible role in its dynamics. This is confirmed by experiments on a high density contrast agent used for videofluoroscopy, revealing that rheologically matched contrast agents and thickener solutions flow very similarly. In vitro experiments and theoretical insights can help designing novel thickener formulations before clinical evaluations.

A model experiment to understand the oral phase of swallowing of Newtonian liquids.

A model experiment to understand the oral phase of swallowing is presented and used to explain some of the mechanisms controlling the swallowing of Newtonian liquids. The extent to which the flow is slowed down by increasing the viscosity of the liquid or the volume is quantitatively studied. The effect of the force used to swallow and of the gap between the palate and the roller used to represent the contracted tongue are also quantified. The residual mass of liquid left after the model swallow rises strongly when increasing the gap and is independent of bolus volume and applied force. An excessively high viscosity results in higher residues, besides succeeding in slowing down the bolus flow. A realistic theory is developed and used to interpret the experimental observations, highlighting the existence of an initial transient regime, at constant acceleration, that can be followed by a steady viscous regime, at constant velocity. The effect of the liquid viscosity on the total oral transit time is lower when the constant acceleration regime dominates bolus flow. Our theory suggests also that tongue inertia is the cause of the higher pressure observed at the back of the tongue in previous studies. The approach presented in this study paves the way toward a mechanical model of human swallowing that would facilitate the design of novel, physically sound, dysphagia treatments and their preliminary screening before in vivo evaluations and clinical trials.

Design and application of water-in-oil emulsions for use in lipstick formulations.

The addition of water to lipsticks in the form of a water-in-oil emulsion is an attractive opportunity for cosmetics manufacturers to deliver hydrophilic molecules to the consumers, as well as improving the moisturizing properties. In this work, the effect of the emulsifier type and water content on the structural properties of the designed products was investigated. It has been shown that PGPR leads to smaller droplets than the other emulsifiers tested. This was attributed to the ability of PGPR to form elastic interfaces that slow the coalescence between droplets during the process. It was also observed that crystals of wax tend to form structures at the interface upon cooling that prevent coalescence during storage. These structures also prevent leakage of water into the continuous phase. No effect of the water content on the melting properties of the emulsions was observed. Upon addition of more than 10% water, softening of the material was measured, due to the overall decrease in solid content. Addition of crystalline material (hard paraffin) was successfully used to reinstate the material properties.

Transition metal complexes of L-cysteine containing di- and tripeptides.

Nickel(II), cobalt(II), zinc(II), and cadmium(II) complexes of Ala-Cys, Phe-Cys, and Ala-Ala-Cys were studied by potentiometric and spectroscopic methods. Ni(II) induces deprotonation and coordination of the amide nitrogens, and the stable monomeric or oligomeric complexes are formed, depending on the metal to ligand molar ratios. Formation of the stable bis-complexes with [S,O] coordination mode is characteristic for cobalt(II), zinc(II), and cadmium(II) ions.

Metal ion-tetracycline interactions in biological fluids. Part 8. Potentiometric and spectroscopic studies on the formation of Ca(II) and Mg(II) complexes with 4-dedimethylamino-tetracycline and 6-desoxy-6-demethyl-tetracycline.

Effects of metal ion-tetracycline (TC) interactions on both gastrointestinal absorption and pharmacological activity of these drugs are well documented. In particular, recent simulation studies based on newly determined complex stability constants have drawn attention to the potential influence of Ca2+ and Mg2+ ions on the bioavailability of various TC derivatives in blood plasma. Contrary to previous thoughts, it was demonstrated in these studies that the fraction of antibiotic not bound to proteins almost exclusively occurs as calcium and magnesium complexes. Among this fraction, predominant binuclear species are electrically charged, and as such cannot passively diffuse through cell membranes. It was thus postulated that the partial blocking of one of the potential coordination sites of the TC molecule, which would favor the formation of neutral mononuclear complexes, should result in a better tissue penetration of the drug. Such correlations were recently established for specific derivatives. Before possible modifications of the TC molecule can be envisaged, it is necessary that all the chelating sites involved in the relevant complexes be properly assigned. As tetracyclines are very complex ligands, the present paper first deals with the coordination of calcium and magnesium with two simpler parent substances, i.e., 4-dedimethylamino-tetracycline (DTC) and 6-desoxy-6-demethyl-tetracycline (DSC). After the quantitative investigation of the proton and metal complex equilibria involved, UV and circular dichroism spectroscopies are used to study the corresponding structural aspects. In DTC complexes, the BCD ring system acts as the exclusive coordination site for both metals. For DSC, however, the N4 atom plays a leading role in the metal binding and would be the only donor involved in 1:1 species; in ML2 complexes, the second ligand is thought to bind through the BCD ring system.

Isolation and two-dimensional 1H-NMR of peptide [1-24] of dog serum albumin and studies of its complexation with copper and nickel by NMR and CD spectroscopy.

The NH2-terminal peptide fragment [1-24] of dog serum albumin was obtained by controlled peptic digestion of the protein. The peptide was purified to homogeneity by gel filtration and ion-exchange chromatography. The NMR assignments of the protons of the individual amino acid residues were made by using two-dimensional correlation matrix, spin-decoupling experiments and analysis of the titration curves. The polypeptide itself has a random-coil conformation. There is a conformational change as a function of pH, but it does not arise from any direct involvement of the amino acid side chains. Complexation of the peptide fragment with Ni(II) and Cu(II) has been investigated by NMR and CD. The Ni(II) complex is in slow exchange with the free ligand on the NMR time scale. The complexation involves the alpha-NH2, three deprotonated amide nitrogens of Ala-2, Tyr-3 and Lys-4 residues. The phenolate oxygen of Tyr-3 is not involved in the metal binding; however, an interaction between the aromatic ring and the metal ion is likely. The CD results of Cu(II)-binding to this peptide suggest that the complexation takes place from the terminal NH2 and step by step to three deprotonated amide nitrogens. There is no major conformational change of the peptide fragment upon complexation.

Studies of copper(II) binding to glycylglycyl-L-tyrosine-N-methyl amide, a peptide mimicking the NH2-terminal copper(II)-binding site of dog serum albumin by analytical potentiometry, spectrophotometry, CD, and NMR spectroscopy.

Unlike human serum albumin (HSA), dog serum albumin (DSA) does not possess the characteristics of the specific first binding site for Cu(II). In DSA, the important histidine residue in the third position, responsible for the Cu(II)-binding specificity in HSA, is replaced by a tyrosine residue. In order to study the influence of the tyrosine residue in the third position of DSA, a simple model of the NH2-terminal native sequence tripeptide of DSA, glycylglycyl-L-tyrosine-N-methylamide (GGTNMA) was synthesized and its Cu(II)-binding properties studied by analytical potentiometry, spectrophotometry, CD, and NMR spectroscopy. The species analysis indicated the existence of five mono-complexes at different protonation states: MHA, MA, MH-1A, MH-2A, MH-3A, and only one bis-complex MH-2A-2. The complexing ability of GGTNMA to Cu(II) was found to be weaker than that of the Cu(II) binding peptide models of HSA. The visible absorption spectra of Cu(II)-GGTNMA complexes are similar to those observed in the case of DSA-Cu(II) complexes. The weaker binding and the spectral properties of Cu(II)-GGTNMA complexes are consistent with less specific Cu(II)-binding properties of the peptide of this sequence similar to what was noted with DSA. CD results are in excellent agreement with species analysis and visible spectra where it is clearly evident that Cu(II) binds to GGTNMA starting from the alpha-NH2 group and step by step to deprotonated amide nitrogens as the pH is raised. The absence of any charge transfer band around 400 nm strongly indicates that Cu(II) does not bind to the phenolate group. Furthermore, NMR results are consistent with the noninvolvement of the tyrosine residue of GGTNMA in Cu(II) complexation. Thus, it is clear that the low Cu(II)-binding affinity of DSA is due to the genetic substitution of tyrosine for histidine at the NH2-terminal region of the protein.