Deformation of the Durom Acetabular Component and Its Impact on Tribology in a Cadaveric Model—A Simulator Study

Background

Recent studies have shown that the acetabular component frequently becomes deformed during press-fit insertion. The aim of this study was to explore the deformation of the Durom cup after implantation and to clarify the impact of deformation on wear and ion release of the Durom large head metal-on-metal (MOM) total hips in simulators.

Methods

Six Durom cups impacted into reamed acetabula of fresh cadavers were used as the experimental group and another 6 size-paired intact Durom cups constituted the control group. All 12 Durom MOM total hips were put through a 3 million cycle (MC) wear test in simulators.

Results

The 6 cups in the experimental group were all deformed, with a mean deformation of 41.78±8.86 µm. The average volumetric wear rate in the experimental group and in the control group in the first million cycle was 6.65±0.29 mm³/MC and 0.89±0.04 mm³/MC (t = 48.43, p = 0.000). The ion levels of Cr and Co in the experimental group were also higher than those in the control group before 2.0 MC. However there was no difference in the ion levels between 2.0 and 3.0 MC.

Conclusions

This finding implies that the non-modular acetabular component of Durom total hip prosthesis is likely to become deformed during press-fit insertion, and that the deformation will result in increased volumetric wear and increased ion release.

Clinical Relevance

This study was determined to explore the deformation of the Durom cup after implantation and to clarify the impact of deformation on wear and ion release of the prosthesis. Deformation of the cup after implantation increases the wear of MOM bearings and the resulting ion levels. The clinical use of the Durom large head prosthesis should be with great care.     

The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4^th and 8^th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca²⁺ level, mitochondrial Ca²⁺ level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca²⁺ level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca²⁺ level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca²⁺ level was higher than controls at baseline. The cytoplasmic Ca²⁺ level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca²⁺ level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions.     

Comparative studies on the ‘5′-cap’ and in vitro translational activity of cytoplasmic and nuclear poly A(+) RNA

Summary Recent advances in the studies of the aggregation of G-actin monomers, containing one molecule of ATP, to long filaments of F-actin, with a concomitant hydrolysis of the nucleotide to ADP, are reviewed. With the aid of -ATP, the association and dissociation rate constant of the nucleotide could be determined. The binding of the nucleotide is enhanced by the binding of one Ca⁺⁺ ion, probably at a different site. The G value of the Mg⁺⁺ or Ca⁺⁺ induced polymerization has been determined to –39 to –59 kJ/mole, the critical protein concentration for the ATP-G-actin to ADP-F-actin conversion is very strongly influenced by the concentration of bivalent cations. The rate constants of the protein monomers, and the rate and equilibrium constants for the propagation step show the process to be extremely cooperative. Actin shows the interesting phenomenon of translocational head-to-tail polymerization, which may be regulated by ATP.The contact sites between the monomers in F-actin have been labeled by chemical modification. Two tryosine residues, 53 and 69, are probably close to one of the two sites. The ATP binding site has been labeled by an ATP analog, and there is evidence that it is close to the contact site.An invited article     

Effects of 5-bromo-2′-deoxyuridine on arachidonic acid metabolism of neuroblastoma and leukemia cells in culture: A possible role of endogenous prostaglandins in tumor cell proliferation and differentiation

Effects of 5-bromo-2′-deoxyuridine (BrdU) were studied on two neuroblastoma and two leukemia cell lines, in terms of the relationship between prostaglandin (PG) synthesis and cell growth/differentiation. After treatment with BrdU (5 μg/ml), cell growth of the 4 cell lines was inhibited and one neuroblastoma cell line (GOTO) showed flattened morphology with positive S-100 protein, one of the differentiation markers for Schwann or glial cells. In the 4 cell lines, BrdU treatment reduced [1-¹⁴C]-arachidonic acid incorporation into phosphatidylinositol and phosphatidylethanolamine and was associated with an increase into phosphatidylcholine and triglyceride. BrdU treatment also increased fractions of 6-keto-PGF_1α and PGF_2α , with a decreased TXB₂ fraction. The decreased ratio of TXB₂ /6-keto-PGF_1α or increased 6-keto-PGF_1α fraction correlated significantly with cell growth inhibition, suggesting that the changes in the balance of endogenous PGs might be associated with BrdU-induced cell growth inhibition with or without differentiation of neuroblastoma and leukemia cells in culture.     

Influence of the xyloadenosine analogue of 2′,5′-oligoriboadenylate on poly(A)-specific, 2′,5′-oligoriboadenylate degrading 2′,3′-exoribonuclease and further enzymes involved in poly(A)(+)mRNA metabolism

The homogeneous poly(A)-specific 2,3-exoribonuclease from calf thymus gland, which cleaves both 3,5-and 2,5-linked oligoriboadenylates, does not degrade (xyloA2'p)₂ xyloA, the xylofuranosyladenosine analogue of the 2-5A core. This oligonucleotide, which is supposed to enter intact cells rapidly, was found to possess an increased stability and an enhanced antiherpesvirus activity compared to the natural (A2'p)₂A (Eppstein, D. A., Barnett, J. W., Marsh, Y. V., Gosselin, G. and Imbach, J.-L. (1983) Nature 302, 723–724). The poly(A) anabolic enzyme, poly(A) polymerase (Mn²⁺-dependent), from the same source, which is initiated by (A3'p)₂A and its higher oligomers, does not accept 2–5A core and its xyloadenosine analogue as primer. Both oligonucleotides exert no influence on endoribonuclease IV and on the integrity of the poly(A)-ribonucleoprotein complex.Abbreviations 2-5A ppp(A2'p)_nA(n2). 5-triphospho-oligo [(2–5)adenylyl]adenosine - 2-5A core (A2'p)₂A, adenylyl(2–5) adenylyl(2–5)adenosine - xyto 2-tA core (xyloA2'p)₂ xyloA, xyloadenylyl(2–5)xyloadenylyl(2–5)xyloadenosine The other abbreviations are according to the recommendations of the Commission on Biochemical Nomenclature, see Europ. J. Biochem.15 (1970) 203–208.     

Studies on the Chemical Synthesis of Potential Antimetabolites. 31.1 A Novel Synthesis of 1-Deazaadenosine and Its Conversion to 5′-Deoxy-5′-Isobutylthio-1-Deazaadenosine (1-Deaza-Siba) and S-(1-Deazaadenosyl)-Homocysteine (1-DEAZA-SAH)

Abstract

A novel route for the preparation of 7-amino-3-(β-D-ribofuranosyl)-3H-imidazo [4,5-b] pyridine (1-deazaadenosine) has been developed. Synthesis of 5′-deoxy-5′-isobutylthio-1-deazaadenosine (1-deazaSIBA) and S-(1-deazaadenosyl)-homocysteine (1-deazaSAH) is also described.     

Impact of the Superoxide Dismutase 2 Val16Ala Polymorphism on the Relationship between Valproic Acid Exposure and Elevation of γ-Glutamyltransferase in Patients with Epilepsy: A Population Pharmacokinetic-Pharmacodynamic Analysis

Background

There has been accumulating evidence that there are associations among γ-glutamyltransferase (γ-GT) elevation and all-cause mortality, cardiovascular diseases and metabolic diseases, including nonalcoholic fatty liver disease. The primary objective of this study was to evaluate the impact of the most common and potentially functional polymorphisms of antioxidant enzyme genes, i.e. superoxide dismutase 2 (SOD2), glutathione S-transferase M1 and glutathione S-transferase T1, on the γ-GT elevation during valproic acid (VPA) therapy.

Methods and Findings

This retrospective study included 237 and 169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, respectively. A nonlinear mixed-effect model represented the pharmacokinetics of VPA and the relationships between VPA exposure and γ-GT elevation. A one-compartment model of the pharmacokinetic parameters of VPA adequately described the data; while the model for the probability of the γ-GT elevation was fitted using a logistic regression model, in which the logit function of the probability was a linear function of VPA exposure. The SOD2 Val16Ala polymorphism and complication with intellectual disability were found to be significant covariates influencing the intercept of the logit function for the probability of an elevated γ-GT level. The predicted mean percentages of the subjects with γ-GT elevation were about 2- to 3-fold, 3- to 4-fold and 4- to 8-fold greater in patients with the SOD2 Val/Val genotype but without any intellectual disability, those with the SOD2 Val/Ala or Ala/Ala genotype and intellectual disability and those with the SOD2 Val/Val genotype and intellectual disability, respectively, compared to those with the SOD2 Val/Ala or Ala/Ala genotype without intellectual disability.

Conclusion

Our results showed that the SOD2 Val16Ala polymorphism has an impact on the relationship between VPA exposure and γ-GT elevation in patients with epilepsy. These results suggest that determining the SOD2 genotype could be helpful for preventing the VPA-induced γ-GT elevation.