Biomechanical tensile strength analysis for medial patellofemoral ligament reconstruction.

BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction is a surgery for acute and chronic dislocating patella. Several surgical techniques have been described. No biomechanical study has compared suture anchors, interference screws, and suspensory cortical fixation for MPFL reconstruction using human gracilis allograft. METHODS: Twelve human cadaver knees were used for the analysis of five MPFL reconstruction techniques on the femur (F) and patella (P): suspensory cortical (SC), interference screw (IS) and suture anchor (SA) fixation (SC-F/SC-P, SC-F/IS-P, SC-F/SA-P, IS-F/SC-P, IS-F/IS-P). Each method was examined six times, each using a new human gracilis allograft. The force necessary for 50% patellar displacement and 100% patellar displacement were recorded for each method. Additionally, we examined the peak force to fixation failure for all methods. Patella dislocation or loss of fixation was considered failure. RESULTS: SC-F/SC-P, IS-F/SC-P, and SC-F/IS-P required force to failure greater than that of the native MPFL. The SC-F/IS-P required the largest force to failure. The SC-F/SA-P fixation technique required significantly less force to failure (P<0.05) than the native MPFL and significantly less force to failure (P<0.05) than all four other fixation techniques. All methods of fixation employing an interference screw failed secondary to graft pullout at the interference screw-bone interface. Methods employing suture anchors and two suspensory cortical fixations failed at the graft-suture anastomosis. CONCLUSION: SC-F/SC-P, IS-F/SC-P, and SC-F/IS-P fixations were found to be stronger than the native MPFL, with the strongest being SC-F/IS-P.

Effects of hyaluronic acid on mitochondrial function and mitochondria-driven apoptosis following oxidative stress in human chondrocytes.

Hyaluronic acid is widely used in the treatment of osteoarthritis and exerts significant chondroprotective effects. The exact mechanisms of its chondroprotective action are not yet fully elucidated. Human articular chondrocytes actively produce reactive oxygen and nitrogen species capable of causing cellular dysfunction and death. A growing body of evidence indicates that mitochondrial dysfunction and mitochondrial DNA damage play a causal role in disorders linked to excessive generation of oxygen free radicals. We hypothesized that the chondroprotective effects of hyaluronic acid on oxidatively stressed chondrocytes are due to preservation of mitochondrial function and amelioration of mitochondria-driven apoptosis. When primary human chondrocyte cultures were exposed to reactive oxygen or nitrogen species generators, mitochondrial DNA damage along with mitochondrial dysfunction and mitochondria-driven apoptosis accumulated as a consequence. In addition, cytokine-treated primary human chondrocytes showed increased levels of mitochondrial DNA damage. Pretreatment of chondrocytes with hyaluronic acid caused a decrease of mitochondrial DNA damage, enhanced mitochondrial DNA repair capacity and cell viability, preservation of ATP levels, and amelioration of apoptosis. The results of these studies demonstrate that enhanced chondrocyte survival and improved mitochondrial function under conditions of oxidative injury are probably important therapeutic mechanisms for the actions of hyaluronic acid in osteoarthritis.

Products of the Escherichia coli acid fitness island attenuate metabolite stress at extremely low pH and mediate a cell density-dependent acid resistance.

Escherichia coli has an ability, rare among the Enterobacteriaceae, to survive extreme acid stress under various host (e.g., human stomach) and nonhost (e.g., apple cider) conditions. Previous microarray studies have exposed a cluster of 12 genes at 79 centisomes collectively called an acid fitness island (AFI). Four AFI genes, gadA, gadX, gadW, and gadE, were already known to be involved in an acid resistance system that consumes an intracellular proton through the decarboxylation of glutamic acid. However, roles for the other eight AFI gene products were either unknown or subject to conflicting findings. Two new aspects of acid resistance are described that require participation of five of the remaining eight AFI genes. YhiF (a putative regulatory protein), lipoprotein Slp, and the periplasmic chaperone HdeA protected E. coli from organic acid metabolites produced during fermentation once the external pH was reduced to pH 2.5. HdeA appears to handle protein damage caused when protonated organic acids diffuse into the cell and dissociate, thereby decreasing internal pH. In contrast, YhiF- and Slp-dependent systems appear to counter the effects of the organic acids themselves, specifically succinate, lactate, and formate, but not acetate. A second phenomenon was defined by two other AFI genes, yhiD and hdeD, encoding putative membrane proteins. These proteins participate in an acid resistance mechanism exhibited only at high cell densities (>10(8) CFU per ml). Density-dependent acid resistance does not require any demonstrable secreted factor and may involve cell contact-dependent activation. These findings further define the complex physiology of E. coli acid resistance.

CXCR3, IP-10, and Mig are required for CD4+ T cell recruitment during the DTH response to HSV-1 yet are independent of the mechanism for viral clearance.

Sensitized CD4+ T cells play an essential role in delayed type hypersensitivity (DTH) elicited by HSV-1 antigen. As activated CD4+ T cells express CXCR3, we investigated whether this chemokine receptor was involved in their recruitment. Antibody blockade of CXCR3 suppressed DTH, whereas ear pinna swelling was not impaired in mice lacking the gene for CCR5, another frequently expressed chemokine receptor. CXCR3 ligands IP-10 and Mig were elevated at the DTH site. Their neutralization significantly reduced DTH ear swelling and CD4+ T cell influx. Furthermore, CXCR3 ligand expression was abrogated and DTH diminished in mice unable to make IFN-gamma, a potent inducer of IP-10 and Mig. Interestingly, neutralization of CXCR3 or its ligands did not compromise host resistance to virus replication. Collectively, these results suggest that in the sensitized host, CXCR3, IP-10, and Mig are required for optimal DTH responsiveness but are not essential for containing HSV-1 replication in the ear pinna.