A comparative study of zirconium and titanium implants in rat: osseointegration and bone material quality

Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments.     

Elastomeric Protein Bioactive Eutectogels for Topical Drug Delivery

Therapeutic deep eutectic solvents (THEDES) are an emerging family of eutectic mixtures gaining increasing interest in the biomedical space. The immobilization of THEDES into polymer networks allows bioactive eutectogels to expand their application scope to topical drug delivery. Herein, this work presents the first set of elastomeric eutectogels constructed by supporting a therapeutic eutectic system with skin permeation ability in a protein scaffold dynamically crosslinked by a natural polyphenol. In this ionic eutectic, gelatin undergoes gelation through an unexpected mechanism in striking contrast with classical hydrogels, which is herein thoroughly studied. Interestingly, the polyphenol controls the conformation of the protein structure, enabling tuning up the mechanical and viscoelastic behavior of the dynamic eutectogel networks from elastic to hyperelastic. The resultant protein eutectogels exhibit strain-hardening behavior, thermoreversible gel-to-sol transition, and excellent adhesive performance. Furthermore, these versatile materials retain the bioactivity of the liquid THEDES and favor skin occlusion, assisting the delivery of both hydrophilic and hydrophobic substances in ex vivo porcine skin in a time-dependent penetration process. These ultrastretchable eutectogels show new interplays between protein scaffolds and eutectic mixtures, paving the way for innovative therapeutic soft materials.     

Synthesis of a novel series of 2-methylsulfanyl fatty acids and their toxicity on the human K-562 and U-937 leukemia cell lines

The hitherto unknown 2-methylsulfanyldecanoic acid and 2-methylsulfanyldodecanoic acid were synthesized from methyl decanoate and methyl dodecanoate, respectively, through the reaction of lithium diisopropylamide and dimethyldisulfide in THF followed by saponification with potassium hydroxide in ethanol. Both α-methylsulfanylated FA were cytotoxic to the human chronic myelogenous leukemia K-562 and the human histiocytic lymphoma U-937 cell lines with EC₅₀ values in the 200–300 μM range, which makes them more cytotoxic to these cell lines than decanoic and/or dodecanoic acid. The cytotoxicity of the studied FA toward K-562 followed the order 2-SCH₃-12∶0>2-SCH₃-10∶0>10∶0>12∶0>2-OCH₃-12∶0, whereas toward U-937 the cytotoxicity was 2-SCH₃-10∶0>2-SCH₃-12∶0>12∶0>10∶0>2-OCH₃-12∶0. These results indicate that the α-methylsulfanyl substitution increases the cytotoxicity of the C₁₀ and C₁₂ FA toward the studied leukemia cell lines.     

Lipids and lipogenic enzymes in adipose tissue of castrated male goats

Male goats (“Criolla Argentina” breed), castrated at 45 days of age, showed altered lipid metabolism 180 days after castration as compared to control goats. Subcutaneous, perirenal and omental adipose tissues of castrated goats showed increases in fatty acid synthetase, glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase activities. Castration increased the amount of total lipids and triglycerides, but did not modify the amount of cholesterol, phospholipid and protein in the three types of adipose tissue. The incorporation of [1-¹⁴C]acetate into fatty acids of subcutaneous and perirenal adipose tissue was increased in castrated goats in relation to noncastrated goats. Our results suggest that removal of gonadal steroids increases significantly the rate of lipogenesis in adipose tissue of male goats.     

The (5Z)-5-Pentacosenoic and 5-Pentacosynoic Acids Inhibit the HIV-1 Reverse Transcriptase

Lipids - The natural fatty acids (5Z)-5-pentacosenoic and (9Z)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol...     

Mechanism of the toxic action of carbon monoxide

Our studies indicate that a high concentration of carboxyhemoglobin (COHb) does not interfere with the O2--carrying capacity of the blood. In dogs, both the transfusion of erythrocytes containing 80 percent COHb and the i.p. injection of carbon monoxide (CO) gas do not produce CO toxicity even though the COHb is above 50 percent. Dogs inhaling CO (13 percent in air) for 15 minutes died within 15 minutes to 65 minutes with an average COHb level of 65 percent. The probable toxic action of CO is on the cellular respiration taking place in the mitochondria when CO competes with O2 for cytochrome a3. The presence of dissolved CO in plasma, which is necessary for CO to enter the tissue, probably occurs when the exchange takes place between alveolar air and the blood in the lungs. When air containing CO is inhaled, there will be a significant CO tension in the blood when it leaves the lungs and when it reaches the organs especially the heart and brain. While COHb level is useful as a clinical measure of CO exposure, the most important mechanism by which CO causes toxicity is its combination with cytochrome oxidase.     

Spectroscopic characterization of a binuclear metal site in Bacillus cereus beta-lactamase II

The zinc metalloenzyme beta-lactamase II (betaLII) from Bacillus cereus has been overexpressed in Escherichia coli as a fusion protein with glutathione-S-transferase, and the metal binding properties of recombinant betaLII toward Zn(II) and Co(II) have been studied by fluorescence and activity measurements. The apoenzyme is able to bind two metal ion equivalents, which confer on betaLII its maximum enzymatic efficiency. The enzyme is partially active with one metal ion equivalent. The diCo(II) and a mixed Zn(II)Co(II) derivative of betaLII were obtained and probed by electronic and paramagnetic NMR spectroscopy. In the high-affinity site, the metal is bound to three His residues and a solvent molecule, adopting a tetrahedral geometry. A Cys, a His, and an Asp residue are coordinated to the low-affinity metal site, together with two or three solvent molecules. This coordination polyhedron resembles the binuclear metal site of the Bacteroides fragilis beta-lactamase [Concha, N., Rasmussen, B. A., Bush, K., and Herzberg, O. (1996) Structure 4, 823-836; Carfi, A., Duée, E., Paul-Soto, R., Galleni, M., Frère, J. M., and Dideberg, O. (1998) Acta Crystallogr. D54, 47-57] but differs from that resulting from the X-ray study of betaLII [Carfi, A., Pares, S., Duée, E., Galleni, M., Duez, C., Frère, J. M., and Dideberg, O. (1995) EMBO J. 14, 4914-4921]. These results suggest that this binuclear metal site may be a general feature of metallo-beta-lactamases.     

Control of <Emphasis Type="Italic">Penicillium Expansum</Emphasis> and <Emphasis Type="Italic">Botrytis Cinerea</Emphasis> on Apple Fruit by Mixtures of Bacteria and Yeast

Antagonistic activity of the mixtures Rahnella aquatilis–Rhodotorula glutinis and R. aquatilis–Cryptococcus laurentii was assessed against Penicillium expansum (cause of blue rot) and Botrytis cinerea (cause of grey rot) on apple fruit at 4 °C and 95% relative humidity (RH). Under these cold-storage conditions, the mixture R. aquatilis–R. glutinis inhibited the development of B. cinerea and P. expansum in apples stored for 40 days and reduced the incidence of disease produced by these moulds to nearly zero. The other mixture, R. aquatilis–C. laurentii, was less effective; the incidences of the grey rot and the blue rot were about 25% and 15%, respectively. Population dynamics of the mixtures showed that the growth of R. aquatilis was strongly stimulated by the presence of the yeast R. glutinis, but in the case of the mixture R. aquatilis–C. laurentii, the same effect could not be observed. In this study, it was demonstrated that the combination of two microorganisms with different requirements and antagonistic abilities resulted in a successful mixture against the two pathogen molds, B. cinerea and P. expansum. In addition, it was also proved that it is possible to improve the biocontrol of these pathogens without increasing the inoculum size of the antagonist (alone or in mixtures), which was always 10⁶cell/ml, despite the high concentration of the pathogen (10⁶ conidia/ml) utilized.