Does the condylar lift-off method or the separation method better detect loss of contact between tibial and femoral implants based on analysis of single-plane radiographs following total knee arthroplasty?

BackgroundLoss of contact between the femoral and tibial implants following total knee arthroplasty (TKA) has been related to accelerated polyethylene wear and other complications. Two methods have been used to detect loss of contact in single-plane fluoroscopy, the condylar lift-off method and the separation method. The objectives were to assess the ability of each method to detect loss of contact.MethodsTKA was performed on ten cadaveric knee specimens. Tibial force was measured in each compartment as specimens were flexed from 0° to 90° while internal-external and varus-valgus moments were applied. Single-plane radiographs taken simultaneously with tibial force were analyzed for loss of contact using the two methods. Receiver operating characteristic (ROC) and optimum threshold distances were determined.ResultsFor the lift-off method and the separation method, the areas under the ROC curves were 0.89 vs 0.60 for the lateral compartment only and 0.81 vs 0.70 for the medial compartment only, respectively. For the lift-off method, the optimum threshold distances were 0.7 mm in the lateral compartment only and 0.1 mm in the medial compartment only but the false positive rate for the medial compartment only almost doubled. For both compartments jointly, the areas under the ROC curves decreased to 0.70 and 0.59 for the lift-off and separation methods, respectively.ConclusionWhen detecting loss of contact using single-plane fluoroscopy, the lift-off method is useful for the lateral compartment only but not for the medial compartment only and not for both compartments jointly. The separation method is not useful.     

The human patellar tendon moment arm assessed in vivo using dual-energy X-ray absorptiometry

Accurate assessment of muscle–tendon forces in vivo requires knowledge of the muscle–tendon moment arm. Dual-energy X-ray absorptiometry (DXA) can produce 2D images suitable for visualising both tendon and bone, thereby potentially allowing the moment arm to be measured but there is currently no validated DXA method for this purpose. The aims of this study were (i) to compare in vivo measurements of the patellar tendon moment arm (d_PT) assessed from 2D DXA and magnetic resonance (MR) images and (ii) to compare the reliability of the two methods. Twelve healthy adults (mean±SD: 31.4±9.5 yr; 174.0±9.5 cm; 76.2±16.6 kg) underwent two DXA and two MR scans of the fully extended knee at rest. The tibiofemoral contact point (TFCP) was used as the centre of joint rotation in both techniques, and the d_PT was defined as the perpendicular distance from the patellar tendon axis to the TFCP. The d_PT was consistently longer when assessed via DXA compared to MRI (+3.79±1.25 mm or +9.78±3.31%; P<0.001). The test–retest reliability of the DXA [CV=2.13%; ICC=0.94; ratio limits of agreement (RLA)=1.01 (?/÷1.07)] and MR [(CV=2.27%; ICC=0.96; RLA=1.00 (?/÷1.07)] methods was very high and comparable between techniques. Moreover, the RLA between the mean DXA and MRI d_PT values [1.097 (?/÷1.061)] demonstrated very strong agreement between the two methods. In conclusion, highly reproducible d_PT measurements can be determined from DXA imaging with the knee fully extended at rest. This has implications for the calculation of patellar tendon forces in vivo where MR equipment is not available.     

A novel in vivo regulatory role of P-glycoprotein in alloimmunity

P-glycoprotein (P-gp) is required for adaptive immunity through defined functions in T cell activation and antigen presenting cell (APC) maturation. The potential role of P-gp as an in vivo regulator of alloimmunity is currently unknown. Here we show that P-gp blockade prolongs graft survival in a murine heterotopic cardiac allotransplantation model through in vivo inhibition of the T helper 1 (Th1) cytokine IFN-γ and the Th2 product IL-4, and via downregulation of the APC-expressed positive costimulatory molecule CD80. In vitro, the P-gp antagonist PSC833, a non-calcineurin-inhibitory cyclosporine A analogue, specifically inhibited cellular efflux of the P-gp substrate rhodamine-123 in wild-type CD3⁺ T cells and MHC class II⁺ APCs but not their P-gp knockout counterparts that lacked rhodamine-123 efflux capacity. Additionally, P-gp blockade significantly inhibited murine alloimmune T cell activation in a dose-dependent fashion. In vivo, P-gp blockade significantly prolonged graft survival in Balb/c recipients of C57BL/6 cardiac allografts from 8.5 ± 0.5 to 11.7 ± 0.5 days (P < 0.01), similar in magnitude to the effects of monotherapy with cyclosporine A. Moreover, P-gp blockade, compared to controls, attenuated intragraft expression of CD3 and CD80, but not CD86, and inhibited IFN-γ and IL-4 production (P < 0.05). In the setting of systemic CD86 inhibition, P-gp blockade suppressed IFN-γ and IL-4 production significantly further (to 98% and 89% inhibition, respectively) compared to either P-gp or anti-CD86 blockade alone, and markedly prolonged allograft survival compared to anti-CD86 blockade alone (40.5 ± 4.6 versus 22.5 ± 2.6 days, respectively, P < 0.01). Our findings define a novel in vivo regulatory role of P-gp in alloimmunity and identify P-gp as a potential therapeutic target in allotransplantation.     

Thermogenic characteristics and evaporative water loss in the tree shrew (Tupaia belangeri)

Thermogenic characteristics and evaporative water loss were measured at different temperatures in Tupaia belangeri. The thermal neutral zone (TNZ) of T. belangeri was 30–35 °C. Mean body temperature was 39.76±0.27 °C and mean body mass was 100.86±9.09 g. Basal metabolic rate (BMR) was 1.38±0.03 ml O₂/g h. Average minimum thermal conductance (C_m) was 0.13±0.01 ml O₂/g h °C. Evaporative water loss in T. belangeri increased when the temperature rose; the maximal evaporative water loss was 3.88±0.41 mg H₂O/g h at 37.5 °C. The results may reflect features of small mammals in the sub-tropical plateau region: T. belangeri had high basal metabolic rate and high total thermal conductance, compared with the predicted values based on their body mass whilst their body temperatures are relatively high; T. belangeri has high levels of evaporative water loss and poor water-retention capacity. Evaporative water loss plays an important role in temperature regulation.     

Accuracy of in vivo and ex vivo ultrasonographic evaluation of ovarian follicles and corpora lutea in sows

Current study determined, in sows, the accuracy of ultrasonography for in vivo (n = 8) and ex vivo (n = 7) evaluation of corpora lutea (CLs) and follicles ≥1.5 mm in size, by comparison with macroscopic findings in sliced ovaries. The accuracy for ex vivo detection of follicles increased with follicle size (P < 0.05), being low for 1.5-1.9 mm follicles (65.9%) and higher for ≥6 mm follicles (93.3%); differences between ultrasonographic and macroscopic observations were significant only for follicles smaller than 3.9 mm (P < 0.05), due to underestimation. Ex vivo observation succeeded to detect presence or absence of CLs in all the ovaries; the efficiency for determining the exact number of CLs being 94.4%. The accuracy for in vivo detection of follicles also increased with follicle size (P < 0.05), dropping to values lower than 40% for 1.5-1.9 mm follicles; therefore, there were significant differences between ultrasonographic and macroscopic observations (P < 0.05). On the other hand, accuracy remained around 92% for ≥6 mm follicles. Ultrasonography was useful again for detecting presence of CLs in all the ovaries; the efficiency for determining CLs number reached 86.7%, due to underestimation in ovaries with higher number of CLs (P < 0.05). Overall, there were no significant differences when comparing the accuracy of ex vivo and in vivo scannings for determination neither of the number of follicles in each size-category larger than 1.9 mm nor of the presence of ovulations or of the CLs number in each ovary. In conclusion, the use of ultrasonography allows an accurate detection of the presence and number of CLs and follicles ≥2 mm of diameter in sows, without significant differences between in vivo and ex vivo observations.     

Pharmacological interactions of essential oil constituents on the in vitro growth of Plasmodium falciparum

The pharmacological properties of essential oils have been widely studied. However the interaction and contribution of the individual constituents assayed singularly and in combination remains relatively unexplored. To investigate these possible interactions, various essential oil constituents (EOC's) were combined and the interactions on their antimalarial and toxicity properties determined using the tritiated hypoxanthine incorporation and the tetrazolium-based cellular viability assays, respectively. In combination, two inactive EOC's (IC50 values greater than 1 mM), ρ-cymene and carvacrol interacted in a synergistic manner (∑ FIC = 0.02) against a chloroquine-resistant strain of Plasmodium falciparum. This interaction was comparable to that between the potent E- and Z-(±)-nerolidol (IC50 value: 0.9 ± 0.3 μM) and the standard antimalarial, quinine (IC50 value: 0.13 ± 0.04 μM) (∑ FIC = 0.01). However, this latter combination also potentiated the toxicity (∑ FIC = 0.001) of each molecule. A similar increase in toxicity was noted between ρ-cymene and γ-terpinene, as well as E- and Z-(±)-nerolidol and (−)-pulegone. These results show that the pharmacological activities of individual EOC's can vary greatly when used in combination, and show potential as adjuvants in the elimination of malaria infections.     

Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as μ-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 ± 50 vs 147 ± 54, p < 0.05), and hearts (1583 ± 277 vs 191 ± 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 ± 37 vs 18 ± 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.     

The in vitro and in vivo apoptotic effects of Mahonia oiwakensis on human lung cancer cells

Both the root and stem bark of Mahonia species were popular folk medicines. The plant has several proven biological activities including anti-bacterial, anti-fungal, and anti-inflammatory effects. However, Mahonia has not been studied for its anticancer effects. In the present study, we made extracts from Mahonia oiwakensis (MOE), a selected species in Taiwan, and investigated their effects on various human lung cells. We found that MOE-induced apoptotic death in human A549 non-small-cell lung carcinoma (NSCLC) cells in a dose- and time-dependent manner. Treatment with the extracts also caused an increase in the sub-G1 fraction of cells, chromosome condensation, and DNA fragmentation. The mitochondrial-mediated pathway was implicated in this MOE-induced apoptosis as evidenced by the activation of the caspase cascade, cleavage of poly (ADP-ribose) polymerase (PARP), disruption of mitochondrial membrane potential, and release of cytochrome C. A higher ratio of Bax/Bcl-2 proteins and cleavage of Bid were also observed in MOE-induced cell apoptosis. In A549 tumor-xenografted nude mice, MOE also retarded in vivo proliferation (P < 0.05) and induced apoptosis in tumor cells, as shown by a decrease in Ki-67-positive staining (P < 0.05) and increased transferase-mediated dUTP nick-end labeling (TUNEL)-positive staining (P < 0.05). In conclusion, MOE inhibits the growth of human lung cancer cells in vitro and in vivo, suggesting that it may have therapeutic potential against human lung cancer.     

In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB1 receptor antagonist for the management of obesity

Cannabinoid CB₁ receptor antagonists exhibit pharmacologic properties favorable for the treatment of metabolic disease. CP-945,598 (1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylamino piperidine-4-carboxylic acid amide hydrochloride) is a recently discovered selective, high affinity, competitive CB₁ receptor antagonist that inhibits both basal and cannabinoid agonist-mediated CB₁ receptor signaling in vitro and in vivo. CP-945,598 exhibits sub-nanomolar potency at human CB₁ receptors in both binding (K_i = 0.7 nM) and functional assays (K_i = 0.2 nM). The compound has low affinity (K_i = 7600 nM) for human CB₂ receptors. In vivo, CP-945,598 reverses four cannabinoid agonist-mediated CNS-driven responses (hypo-locomotion, hypothermia, analgesia, and catalepsy) to a synthetic cannabinoid receptor agonist. CP-945,598 exhibits dose and concentration-dependent anorectic activity in two models of acute food intake in rodents, fast-induced re-feeding and spontaneous, nocturnal feeding. CP-945,598 also acutely stimulates energy expenditure in rats and decreases the respiratory quotient indicating a metabolic switch to increased fat oxidation. CP-945,598 at 10 mg/kg promoted a 9%, vehicle adjusted weight loss in a 10 day weight loss study in diet-induced obese mice. Concentration/effect relationships combined with ex vivo brain CB₁ receptor occupancy data were used to evaluate efficacy in behavioral, food intake, and energy expenditure studies. Together, these in vitro, ex vivo, and in vivo data indicate that CP-945,598 is a novel CB₁ receptor competitive antagonist that may further our understanding of the endocannabinoid system.     

Antihypertensive effect of insect cells: In vitro and in vivo evaluation

In this study, we investigated the in vitro ACE inhibitory and in vivo antihypertensive effect of insect cell extracts. The IC₅₀ of three insect cell lines from different type and insect species origin: S2 (embryo, Drosophila melanogaster), Sf21 (ovary, Spodoptera frugiperda) and Bm5 (ovary, Bombyx mori), were evaluated. Most interesting results were that the IC₅₀ values ranged between 0.4 and 0.9 mg/ml, and that an extra hydrolysis with gastrointestinal enzymes did not increase the ACE inhibitory activity conspicuously. Finally, a single oral administration with a gavage of 150 mg cell extract/kg BW to spontaneous hypertensive rats (SHR) significantly decreased (p < 0.05) their systolic blood pressure (SBP) with 5-6% (9-12 mm Hg) compared to the controls at 6 h post-administration. Here the undigested and digested insect S2 cell extracts were equal in activity to lower the SBP. To the best of our knowledge, this is the first report of in vivo antihypertensive activity of insect cell extracts and this without an extra digestion requirement.     

Sulfated polysaccharides from Laminaria angustata: Structural features and in vitro antiviral activities

Sulfated polysaccharides potently inhibit the infectivity of herpes simplex virus (HSV) in cultured cells. In this study, we have analyzed sulfated xylogalactofucan and alginic acid containing fractions generated from Laminaria angustata, a marine alga. The xylogalactofucan that has apparent molecular mass of 56 ± 5 kDa and unusually low sulfate content contains, inter alia, 1,3-, 1,4- and 1,2-linked fucopyranosyl residues. The algin (molecular mass: 32 ± 5 kDa) contains gulo- (55.5%) and mannuronic (44.5%) acid residues. Introduction of sulfate groups enhanced the macromolecules capability to inhibit the infection of cells by HSV-1. The 50% inhibitory concentration (IC₅₀) values of these macromolecules against HSV-1 were in the range of 0.2-25 μg ml⁻¹ and they lacked cytotoxicity at concentrations up to 1000 μg ml⁻¹. The sulfate content appeared to be an important hallmark of anti-HSV-1 activity. Our results suggest the feasibility of inhibiting HSV attachment to cells by direct interaction of polysaccharides with viral particles.     

Optimisation of exopolysaccharide production by Gomphidius rutilus and its antioxidant activities in vitro

The production conditions of the Gomphidius rutilus exopolysaccharides (GREP) in submerged culture were optimised, and the antioxidant activities of GREP in vitro were evaluated. The optimal culture medium constituents were determined as follows: 30 g/L sucrose, 3.0 g/L soybean meal, 0.25 g/L MgSO₄, 1.5 g/L K₂HPO₄, 0.5 g/L KH₂PO₄, 0.03 g/L ZnSO₄, and 0.01 g/L FeSO₄. The optimum parameters for the liquid fermentation were as follows: temperature, 25 °C; cultivation time, 6 d; initial pH, 8.0; volume of medium, 150 mL; and rotary speed, 180 rpm. GREP content and dry cell weight in optimised conditions were 540.1 ± 15.9 mg/L and 8.2 ± 0.3 g/L, respectively. GREP content under the optimised conditions was 2.5 times than that under the basic culture medium and initial conditions. GREP demonstrated positive antioxidant potential on superoxide anion radical, 1,1-diphenyl-2-picrylhydrazyl, and hydroxyl radical scavenging, and reducing power.     

Reproduction and recruitment of the seagrass Halophila stipulacea

The small seagrass species, Halophila stipulacea is abundant in the subtidal zone of the Bay of Eilat, Red Sea, southern Israel. Early life history characteristics of this species were investigated in summer 2002 by means of field surveys and outdoor experiments. Monospecific stands were found at depths of between 2 and 20 m. Reproduction began in late May and ripe pericarps were found for 1 month starting from the beginning of August. The ratios of female versus male plants were 0.9 at depths of between 2.5 and 10 m and 0.5 at depths of between 12.5 and 15 m. The proportion of reproductive branches was significantly larger in the shallow (2–5 m) than in the deep (7–15 m) populations, i.e., 20 ± 11% versus 6 ± 10%, respectively. Ripe seeds were predominantly produced at depths of between 2 and 5 m. Experimental studies demonstrated that full sunlight completely inhibited seedling growth at a depth of 30 cm; no macroscopic seedlings could be observed after 40-day exposure to full sunlight. If exposed to 90% photosynthetic active radiation (PAR) but protected from ultraviolet radiation (UVR), the number of macroscopic seedlings increased to 7.4 ± 2.3% of the planted seeds. If protected from both UVR and 80% of the PAR, the number of macroscopic seedlings increased to 22.5 ± 4.0% of the planted seeds. UVR exclusion and 80% PAR reduction also significantly increased the rhizome growth rates of seedlings in the first month after germination (0.14 ± 0.04 mm day⁻¹) compared with only UVR exclusion (0.04 ± 0.02 mm day⁻¹). The absence of H. stipulacea from the uppermost part of the subtidal zone (depths of 0–2 m) may be due to light inhibition of germling growth and uprooting by occasional storms.     

The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage

Purpose

In this study, we set out to establish an in vivo animal model of oxidative stress in the retinal ganglion cells (RGCs) and determine whether there is a link between oxidative stress in the RGCs and the activation of calpain, a major part of the apoptotic pathway.

Materials and methods

Oxidative stress was induced in the RGCs of C57BL/6 mice by the intravitreal administration of 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH, 30 mM, 2 μl). Control eyes were injected with 2 μl of vehicle. Surviving Fluorogold (FG)-labeled RGCs were then counted in retinal flat mounts. Double staining with CellROX and Annexin V was performed to investigate the co-localization of free radical generation and apoptosis. An immunoblot assay was used both to indirectly evaluate calpain activation in the AAPH-treated eyes by confirming α-fodrin cleavage, and also to evaluate the effect of SNJ-1945 (a specific calpain inhibitor: 4% w/v, 100 mg/kg, intraperitoneal administration) in these eyes.

Results

Intravitreal administration of AAPH led to a significant decrease in FG-labeled RGCs 7 days after treatment (control: 3806.7 ± 575.2 RGCs/mm², AAPH: 3156.1 ± 371.2 RGCs/mm², P < 0.01). CellROX and Annexin V signals were co-localized in the FG-labeled RGCs 24 h after AAPH injection. An immunoblot assay revealed a cleaved α-fodrin band that increased significantly 24 h after AAPH administration. Intraperitoneally administered SNJ-1945 prevented the cleavage of α-fodrin and had a neuroprotective effect against AAPH-induced RGC death (AAPH: 3354.0 ± 226.9 RGCs/mm², AAPH+SNJ-1945: 3717.1 ± 614.6 RGCs/mm², P < 0.01).

Conclusion

AAPH administration was an effective model of oxidative stress in the RGCs, showing that oxidative stress directly activated the calpain pathway and induced RGC death. Furthermore, inhibition of the calpain pathway protected the RGCs after AAPH administration.     

Biotic and abiotic regulation of resting spore formation in vivo of obligate aphid pathogen Pandora nouryi: Modeling analysis and biological implication

Entomophthoralean fungus Pandora nouryi is an obligate aphid pathogen that enables to produce resting spores (azygospores) for surviving host absence. To explore possible mechanisms involved in the regulation of resting spore formation in vivo, host cohorts consisting of 40-60 nymphs of green peach aphid Myzus persicae produced within 24 h on cabbage leaf discs in petri dishes were exposed to spore showers of P. nouryi at the concentrations (C) from a very few to nearly 2000 conidia/mm² and then reared for 7-11 days at the regimes of 10-25 °C (T) and 8-16 h daylight (H_L) or ambient (17.5 ± 3.1 °C, 13:11 L:D). Aphid mortalities observed from 35-83 cohorts (showered separately) at each regime showed typical sigmoid trend and fit well a general logistic equation (0.79 ? r² ? 0.88), yielding similar LC₅₀ estimates of 1.7-6.1 conidia/mm². The proportions (P) of cadavers forming resting spores in the cohorts also fit the same equation (0.73 ? r² ? 0.85) at all tested regimes except at 10 °C, a low temperature for the host-pathogen interaction. This indicates the dependence of resting spore formation on the spore concentration. The effects of T and H_L on P over C were well elucidated by the fitted modified logistic equations P = 0.578/{1 + exp[1.710 − (0.136 − 0.0053T)C]} and P = 0.534/{1 + exp[1.639 + (0.034 − 0.0053H_L)C]} (both r² = 0.79). Our results highlight that the resting spore formation in vivo of P. nouryi is regulated primarily by the concentration of host-infecting conidia discharged from cadavers and facilitated by lower temperature and longer daylight.     

Endogenous isoflavone methylation correlates with the in vitro rooting phases of Spartium junceum L. (Leguminosae)

Spartium junceum L. (Leguminosae) is a perennial shrub, native to the Mediterranean region in southern Europe, widespread in all the Italian regions and, as a leguminous species, it has a high isoflavone content. An in vitro culture protocol was developed for this species starting from stem nodal sections of in vivo plants, and isoflavone components of the in vitro cultured tissues were studied by means of High Performance Liquid Chromatography (HPLC) analytical techniques. Two main isoflavones were detected in the S. junceum tissues during the in vitro propagation phases: Genistein (4′,5,7-Trihydroxyisoflavone), already reported in this species, and its methylated form 4′,5,7-Trimethoxyisoflavone, detected for the first time in this plant species (0.750 ± 0.02 mg g⁻¹ dry tissue). The presence of both of these compounds in S. junceum tissues was consistently detected during the in vitro multiplication phase. The absence of the methylated form within plant tissues in the early phases of the in vitro adventitious root formation was correlated with its negative effect displayed on root induction and initiation phases, while its presence in the final “root manifestation” phase influenced positively the rooting process. The unmethylated form, although detectable in tissues in the precocious rooting phases, was no longer present in the final rooting phase. Its effect on rooting, however, proved always to be beneficial.     

Impulse-dependent extracellular resting dopamine concentration in rat striatum in vivo

The ambient resting dopamine (DA) concentration in brain regulates cognition and motivation. Despite its importance, resting DA level in vivo remains elusive. Here, by high-frequency stimulation of the medial forebrain bundle and immediately following the stimulus-induced DA overflow, we recorded a DA “undershoot” which is a temporal reduction of DA concentration to a level below the baseline. Based on the DA undershoot, we predicted a resting DA concentration of ∼73 nM in rat striatum in vivo. Simulation studies suggested that removing basal DA by DAT during the post-stimulation inhibition of tonic DA release caused the DA undershoot, and the resting concentration of DA modulated the kinetics of the evoked DA transient. The DA undershoot was eliminated by either blocking D2 receptors with haloperidol or blocking the DA transporter (DAT) with cocaine. Therefore, the impulse-dependent resting DA concentration is in the tens of nanomolar range and is modulated by the presynaptic D2 receptors and the DAT in vivo.     

Finite Element Analysis of Tibial Implants — Effect of Fixation Design and Friction Model

Abstract

A three dimensional nonlinear finite element model was developed to investigate tibial fixation designs and friction models (Coulomb's vs nonlinear) in total knee arthroplasty in the immediate postoperative period with no biological attachment. Bi-directional measurement-based nonlinear friction constitutive equations were used for the bone-porous coated implant interface. Friction properties between the polyethylene and femoral components were measured for this study. Linear elastic isotropic but heterogeneous mechanical properties taken from literature were considered for the bone. The Tensile behaviour of polyethylene was measured and subsequently modeled by an elasto-plastic model. Based on the earlier finite element and experimental pull-out studies, pegs and screws were also realistically modeled. The geometry of every component was obtained through measurement. The PCA tibial baseplate with three different configurations was considered; one with three screws, one with one screw and two short inclined porous-coated pegs, and a third one with no fixation for the sake of comparison. The axial load of 2000N was applied through the femoral component on the medial plateau of articular insert. It was found that Coulomb's friction significantly underestimates the relative micromotion at the bone-implant interface. The lowest micromotion and lift-off were found for the design with screws. Relative micromotion and stress transfer at the bone-implant interface depended significantly on the friction model and on the baseplate anchorage configuration. Cortical and cancellous bones carried, respectively, 10–13% and 65–86% of the axial load depending on the fixation configuration used. The remaining portion was transmitted as shear force by screws and pegs. Normal and Mises stresses as well as contact area in the polyethylene insert were nearly independent of the baseplate fixation design. The Maximum Mises stress in the polyethylene exceeded yield and was found 1–2 mm below the contact surface for all designs.     

Neolignan Licarin A presents effect against Leishmania (Leishmania) major associated with immunomodulation in vitro

Leishmaniasis’ treatment is based mostly on pentavalent antimonials or amphotericin B long-term administration, expensive drugs associated with severe side effects. Considering these aforementioned, the search for alternative effective and safe leishmaniasis treatments is a necessity. This work evaluated a neolignan, licarin A anti-leishmanial activity chemically synthesized by our study group. It was observed that licarin A effectively inhibited Leishmania (Leishmania) major promastigotes (IC₅₀ of 9.59 ± 0.94 μg/mL) growth, by inducing in these parasites genomic DNA fragmentation in a typical death pattern by apoptosis. Additionally, the neolignan proved to be even more active against intracellular amastigotes of the parasite (EC₅₀ of 4.71 ± 0.29 μg/mL), and significantly more effective than meglumine antimoniate (EC₅₀ of 216.2 ± 76.7 μg/mL) used as reference drug. The antiamastigote activity is associated with an immunomodulatory activity, since treatment with licarin A of the infected macrophages induced a decrease in the interleukin (IL)-6 and IL-10 production. This study demonstrates for the first time the antileishmanial activity of licarin A and suggests that the compound may be a promising in the development of a new leishmanicidal agent.