Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis

Objective

The development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have been established, which has limited the development of effective therapies. T_1ρ and T₂ mapping techniques have the ability to provide highly accurate and quantitative measurements of articular cartilage degeneration in vivo. Relating these cartilaginous changes to high-resolution bone-densitometric evaluations of the late-stage osteoarthritic bone is crucial in elucidating the mechanisms of development of traumatic osteoarthritis (OA) and potential therapies for early- or late-stage intervention.

Methods

Twelve rabbits were monitored with in vivo magnetic resonance imaging (MRI) scans following ACL transection surgery with a contralateral leg sham operation. Six of the rabbits were treated with oral doxycycline for the duration of the experiment. At 12 weeks, the excised knees from three animals from each group (n=6 overall) were subjected to micro-computed tomography (CT) analysis.

Results

Consistent with previous studies, initial elevations in T_1ρ and T₂ values in ACL-transected animals were observed with relative normalization towards values see in sham-operated legs over the 12-week study. This biphasic pattern could hold diagnostic potential to differentiate osteoarthritic cartilage by tracking the relative proportions of T_1ρ and T₂ values as they rise with inflammation then fall as collagen and proteoglycan loss leads to further dehydration. The addition of doxycycline resulted in inconclusive, yet potentially interesting, cartilaginous changes in several compartments of the rabbit legs. Micro-CT studies demonstrated decreased bone densitometrics in ACL-transected knees. Correlation studies suggest that the cartilaginous changes may be associated with some aspects of bony change and the development of OA.

Conclusion

We conclude that there are definite relationships between cartilaginous changes as seen on MRI and late-stage microstructural bony changes after traumatic ACL injury in rabbits. In addition, doxycycline may show promise in mitigating early-stage cartilage damage that may serve to lessen late-stage osteoarthritic changes. This study demonstrates the ability to track OA progression and therapeutic efficacy with imaging modalities in vivo.     

Optimal sample preparation for nanoparticle metrology (statistical size measurements) using atomic force microscopy

Optimal deposition procedures are determined for nanoparticle size characterization by atomic force microscopy (AFM). Accurate nanoparticle size distribution analysis with AFM requires non-agglomerated nanoparticles on a flat substrate. The deposition of polystyrene (100 nm), silica (300 and 100 nm), gold (100 nm), and CdSe quantum dot (2–5 nm) nanoparticles by spin coating was optimized for size distribution measurements by AFM. Factors influencing deposition include spin speed, concentration, solvent, and pH. A comparison using spin coating, static evaporation, and a new fluid cell deposition method for depositing nanoparticles is also made. The fluid cell allows for a more uniform and higher density deposition of nanoparticles on a substrate at laminar flow rates, making nanoparticle size analysis via AFM more efficient and also offers the potential for nanoparticle analysis in liquid environments.     

Two new abietane diterpenes huperphlegmarins A and B from Huperzia phlegmaria

Two new abietane diterpenes, huperphlegmarin A–B (1–2), were isolated from the aerial parts of Huperzia phlegmaria (L.) Rothm. (Lycopodiaceae), in addition to five known compounds including lycoxanthol (3), 21β-hydroxyserrat-14-en-3β-yl acetate (4), 21α-hydroxyserrat-14-en-3β-yl acetate (5), 21α-hydroxyserrat-14-en-3β-ol (6), and fawcettidine (7). Their structures were determined by the combination analyses of spectroscopy, including 1D-, 2D-NMR, HRESIMS, CD and comparison with the reported data in the literature. Huperphlegmarin B (2) presented the rare 1,11-epoxy group in the molecule. Compounds 3, 4, 5 and 6 were performed for AChE inhibitory activity and compound 3 showed the inhibitory activity against AChE with IC₅₀ of 465.6 μg/mL.     

A Holographic Prism Based on Photo-Thermo-Refractive Glass: Requirements and Possibilities

A technology for multivalued holographic measurement of a plane angle—a holographic prism, which serves as the basis for a device for calibrating the testing tools for navigational equipment under rolling— has been developed. The holographic prism is a miniature sample of photosensitive material, which contains a system of superimposed holographic gratings, and a laser the radiation of which passes through gratings to form a fan of diffracted beams. The fan in a prism based on a calcium fluoride (fluorite) crystal with color centers contained six out-of-plane beams radiating from a region with a hard-to-localize center. This fact hindered calibration of the measure and its application in the testing device. The use of photothermo-refractive glass as a material for preparing a sample and recording a system of holograms in it makes it possible to eliminate the drawbacks of fluorite-based prism. The number of holograms rises up to 21, the fan becomes in-plane, and its center is localized in a small region, with a size of several tenths of the sample thickness (1–2 mm). The fan beams are energetically homogeneous, and each can be identified when using the fan in a testing device.     

The thermal-neutron-induced alpha-accompanied fission of235U investigation of the low energy part of the alpha spectrum

The energy spectrum of the α-particles emitted in the thermal-neutron induced fission of²³⁵U was measured from 11.5 MeV down to 2 MeV using the parabola mass spectrometer Lohengrin at the I.L.L. high flux reactor. This low energy part of the energy spectrum presents a smooth connection with the energy spectra which have been recently reported above 7 MeV. The overall energy spectrum, which is known to be quasi-gaussian above 12 MeV, is slightly asymmetric at low energy, where the observed particles are 6% more than expected from a gaussian shape. As a consequence, all the values reported for²³⁵U for the rate of α-accompanied fission compared to binary fission have to be multiplied by 1.06. This asymmetry is about 2 times less important than the one reported for²⁵²Cf. No evidence was seen for any intense low energy component as reported before. The possible reasons for the existence of this asymmetry are discussed.     

The application of a double voltage modulation technique to a glow discharge source with a supplementary electrode

The Ar spectral lines are suppressed in glow discharge source atomic emission spectroscopy by a double voltage modulation technique with a supplementary electrode. The voltage is modulated between two levels, typically 350 and 700 V. At the lower voltage level mainly the Ar emission occurs where at the higher voltage level both the Ar and the metal atoms sputtered from the sample contribute to the emission. The power supply of the supplementary electrode is switched on when the glow discharge passes from operation at 700 V to 350 V. The intensity of argon gase lines is regulated by the current applied to the supplementary electrode at that period. Therefore, there is no need for electronical amplification and lower voltage adjustment of two operation modes. This modified DVM technique has been applied to the determination of Si and Cu in Al- samples. The suppression of Ar lines is possible, and the elements can be determined without Ar interferences.     

Fission-fragment angular distributions for 230Th(n,f) in the vicinity of the 715 keV resonance

Fission-fragment angular distributions have been measured for the neutron-induced fission of ²³⁰Th in the vicinity of the 715 keV resonance with a 2.5 keV (FWHM) neutron energy resolution. An analysis was performed to find a set of fission barrier characteristics that reproduce simultaneously the present angular distribution data and the fission cross-section data of Blons et al. The analysis results show that the data for the 715 keV resonance could be fitted only if allowance is made for the existence of two rotational bands with opposite parities but with the same K quantum number. The moment of inertia parameter $\text{kh}{}^2\text{2}\text{I}$ extracted from the analysis has a value of 1.9 keV, which is compatible with the existence of a third minimum in the fission barrier at a quadrupole deformation of ε₂ = 0.85.     

THE PHOTOPHYSICAL AND PHOTOCHEMICAL PROCESSES OF TRYPTOPHAN IN INTERACTION WITH POLYNUCLEOTIDES: LASER FLASH PHOTOLYSIS STUDY

Abstract— The influence of nucleotides or polynucleotides on the photophysics and the photochemistry of tryptophan (Trp) derivatives has been investigated in aqueous solutions using the 265 nm laser flash photolysis technique. In solutions containing mixtures of N -acetyltryptophanamide and uridine monophosphate (UMP) or mercurated dUMP, the Trp triplet and the hydrated electron (e_aq) are quenched at almost diffusion controlled rates by the nucleotides leading to uracil reduction. Lysyl-tryptophyl-α-lysine (Lys-Trp-Lys) forms stable complexes in solution with normal or mercurated poly(uridylic acid) [poly(U)]. In the Poly(rU)-Lys-Trp-Lys complex the Trp triplet state is completely quenched, whereas the Trp triplet formation quantum yield is enhanced in complexes with mercurated poly(U). In this last case, the 'heavy atom effect' is characterized by a shortening of the Trp triplet lifetime in agreement with low temperature experiments. Our results also show that photoionization of Trp does occur in the complexed state with both polymers. The e_aq lifetime is however longer with the complexed than with the free peptide.     

Chloride ion catalyzed conformational inversion of carbocation intermediates in the hydrolysis of a benzo[a]pyrene 7,8-diol 9,10-epoxide

A highly efficient procedure for converting 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (1) to its trans-9,10-chlorohydrin (5) with excellent yield and purity by the reaction of anhydrous HCl in THF has been developed. The rate of reaction of 5 has been determined as a function of sodium chloride concentration in 1:1 dioxane-water solutions. A large common ion rate depression for the reaction of the chlorohydrin was observed, and the rate data are fit to a mechanism in which all of the tetrol products are formed by the reaction of water with the C-10 carbocation intermediate. Yet, the cis/trans ratio of tetrols from the reaction of the carbocation intermediate from the hydrolysis of chlorohydrin 5 is different than the cis/trans tetrol ratio from the acid-catalyzed hydrolysis of diol epoxide 1, which hydrolyzes via a carbocation with the same connectivity as that formed in the hydrolysis of 5. To rationalize these results, it is proposed that the S(N)1 reaction of chlorohydrin 5 yields a different distribution of carbocation conformations than that formed from the reaction of 1 with H(+). The energy barrier for the inversion of these carbocation conformations must be large relative to the energy barriers for the reaction of each carbocation conformation with water. In solutions containing sufficient concentrations of chloride ion, however, a lower energy pathway via a halohydrin exists for the interconversion of the carbocation conformations. Thus, chloride ion catalyzes the interconversion of these two carbocation conformations.