The effect of medical biodegradable magnesium alloy in vivo degradation and bone response in a rat femur model with long-term fixation.

BACKGROUND: It is of great significance to understand the effect of the different corrosion behaviors of magnesium (Mg) alloys manufactured using different casting methods and implanted with different methods on the long-term implantation to expand the application of Mg-based biomedical implants. OBJECTIVE: The effects of four different casting and rolling speeds on the microstructure of an Mg-rare earth (Mg-Re) alloy were analyzed using electron backscatter diffraction (EBSD). METHOD: Four Mg alloys were obtained using vertical two-roll casting (TRC) at 10 m/min, 16 m/min, 24 m/min, and 30 m/min, and their microstructure, corrosion behavior and bone reaction in vivo were studied. RESULTS: The corrosion resistance of the alloy increases with an increase in casting speed and finer grain size of the cast-rolled parts. The Mg-Re alloys with TRC-10 m/min and TRC-30 m/min were selected for animal experiments. The two Mg alloys were made into metal rods and inserted into the rat femur to simulate the effect of Mg-Re on femoral healing under an injury condition. The rods were implanted for a long time to judge the effects of the Mg-Re alloy on the body. The TRC-30 m/min implants obtained highly mature new bone tissue in the case of bone injury. CONCLUSION: The in vivo experiments showed that the corrosion resistance of the TRC-30 m/min implant was better than that of the TRC-10 m/min implant. After 32 weeks of implantation, there were no pathological changes in the liver, heart, or kidney of rats in the TRC-30 m/min group, and the cell structure was normal.

In vivo degradation and bone reaction of long-term fixation with a magnesium alloy made by twin-roll casting in a rat femur model.

BACKGROUND: The effect of casting parameters on the microstructure and corrosion resistance of Mg alloys is still limited, especially in clinical animal experiments. OBJECTIVE: We prepared a new magnesium rare earth alloy (Mg-Re, where Re is Ce or La) by vertical two-roll casting and Mg-A by further rolling. The microstructure characteristics, degradation behavior, and bone reaction of the two alloys were studied. METHOD: Ti, Mg-Re, and Mg-A alloy plates were implanted in a rat femur model, and their degradation behavior was observed 48 weeks later. RESULTS: In vivo experiments showed no significant changes around the femur in the Ti group, excluding external factors that may cause bone remodeling and lead to new bone formation. Mg-A induces more new bone formation than Mg-Re, which meets the necessary conditions to prevent pathological fracture. The specimen staining and sectioning showed that the liver and heart of rats implanted with magnesium alloys had no pathological changes and the cell structure was normal, similar to that of rats without a magnesium alloy. CONCLUSION: Mg-A alloy has good healing potential as a biodegradable implant material.

Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances.

We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions.

Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed.

Class-IA phosphoinositide 3-kinase p110ß Triggers GPCR-induced superoxide production in p110γ-deficient murine neutrophils.

Studies with knockout mice have indicated that the only isoform of phosphoinositide 3-kinase (PI3K) functioning in the oxidative burst of mouse neutrophils in response to heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) agonists is a class-IB PI3K, p110γ. In the present study, we observed that the cells from p110γ(-/-) mice gain a response to N-formyl-Met-Leu-Phe (fMLP) after priming with cytochalasin E. Even the unprimed cells, which show no response to fMLP, produce a significant amount of superoxide, when an effective agonist of the mouse-type fMLP receptors, Trp-Lys-Tyr-Met-Val-D-Met, is used to stimulate the cells. These results suggested that the class-IA isoforms (p110α, p110ß, and p110δ) of PI3K are sufficient to trigger and maintain superoxide production. Examination of the effects of isoform-specific inhibitors suggested that the p110ß isoform is the primary PI3K triggering the response to GPCR agonists when p110γ is absent.

Hypertonicity augments bullfrog taste nerve responses to inorganic salts.

The tonicity of taste stimulating solutions has been usually ignored, though taste substances themselves yielded the tonicity. We investigated the effect of hypertonicity on bullfrog taste nerve responses to inorganic salts by adding nonelectrolytes such as urea and sucrose that elicited no taste nerve responses. Here, we show that hypertonicity alters bullfrog taste nerve-response magnitude and firing pattern. The addition of urea or sucrose enhances the taste nerve-response magnitude to NaCl and shifts the concentration-response curve to the left. The effect of hypertonicity on responses to CaCl(2) is bimodal; hypertonicity suppresses CaCl(2) responses at concentrations less than ~30 mM and enhances them at concentrations greater than ~30 mM. The hypertonicity also enhances response magnitude to other monovalent salts. The extent of the enhancing effects depends on the difference between the mobility of the cation and anion in the salt. We quantitatively suggest that both the enhancing and suppressing effects result from the magnitude and direction of local circuit currents generated by diffusion potentials across tight junctions surrounding taste receptor cells.