Gallium-Containing Materials and Their Potential within New-Generation Titanium Alloys for Biomedical Applications.

With the rising demand for implantable orthopaedic medical devices and the dominance of device-associated infections, extensive research into the development of novel materials has been prompted. Among these, new-generation titanium alloys with biocompatible elements and improved stiffness levels have received much attention. Furthermore, the development of titanium-based materials that can impart antibacterial function has demonstrated promising results, where gallium has exhibited superior antimicrobial action. This has been evidenced by the addition of gallium to various biomaterials including titanium alloys. Therefore, this paper aims to review the antibacterial activity of gallium when incorporated into biomedical materials, with a focus on titanium-based alloys. First, discussion into the development of new-generation Ti alloys that possess biocompatible elements and reduced Young's moduli is presented. This includes a brief review of the influence of alloying elements, processing techniques and the resulting biocompatibilities of the materials found in the literature. The antibacterial effect of gallium added to various materials, including bioglasses, liquid metals, and bioceramics, is then reviewed and discussed. Finally, a key focus is given to the incorporation of gallium into titanium systems for which the inherent mechanical, biocompatible, and antibacterial effects are reviewed and discussed in more detail, leading to suggestions and directions for further research in this area.

Puerarin facilitates osteogenesis in steroid-induced necrosis of rabbit femoral head and osteogenesis of steroid-induced osteocytes via miR-34a upregulation.

The present study investigated the effect of puerarin on promoting the osteogenesis in steroid-induced necrosis of the femoral head (SONFH). New Zealand rabbits were administrated with horse serum and methylprednisolone (MPS) for establishing SONFH in vivo model, which was then treated with puerarin treatment. Histo-morphological changes in the femoral head were examined by hematoxylin-eosin staining. Osteoblasts were isolated from healthy rabbits and treated by individual or combined administration of dexamethasone and puerarin. Osteoblast viability was measured by CCK-8 assay. Mineralized nodule formation was evaluated by alizarin red assay. Expressions of RUNX family transcription factor 2 (RUNX2), Type-I collagen α 1 (COL1A1), ALP and miR-34a in the femoral head were determined by qRT-PCR and Western blot. Puerarin attenuated the effect of SONFH on promoting histopathological abnormalities and counteracted SONFH inhibition on the expressions of ALP, RUNX2, COL1A1 and miR-34a in the rabbits. Rabbit osteoblasts were successfully isolated, as they showed red mineralized nodules. Dexamethasone exposure decreased osteoblast viability, which was increased by puerarin treatment. Furthermore, puerarin treatment attenuated dexamethasone-induced inhibition on the viability, osteoblastic differentiation, and the expressions of ALP, RUNX2, COL1A1 and miR-34a in the osteoblasts. Puerarin facilitated osteogenesis of steroid-induced necrosis of rabbit femoral head and osteogenesis of steroid-induced osteocytes via miR-34a upregulation.

Acute and 30-day oral toxicity studies of a novel coccidiostat - ethanamizuril.

Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg-1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg-1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg-1 groups. Histopathological observations revealed that 60 and 120 mg kg-1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg-1 feed.

Pinoresinol promotes MC3T3­E1 cell proliferation and differentiation via the cyclic AMP/protein kinase A signaling pathway.

Estradiol (E2) is a first­line drug for osteoporosis (OP) treatment via promotion of osteoblastic proliferation and differentiation. However, a long­term use of E2 would produce side effects thus, it is imperative to discover safer and more effective drugs. Pinoresinol (PINO) has a similar chemical structure to E2. The present study aimed to investigate whether PINO could promote osteoblastic proliferation and differentiation and the potential mechanisms. After treatment with 0.1 µg/l PINO for 2 days, MC3T3­E1 cell migration was assessed by wound healing assay. Estrogen (E2) treatment served as a positive control. RT­qPCR and western blotting were used for mRNA and protein expression analyses. Alkaline phosphatase (ALP) activity assay and Alizarin red staining were performed to investigate the calcification and mineralization, and the cyclic AMP (cAMP) level was detected by enzyme­linked immunosorbent assay (ELISA). H89, an inhibitor of protein kinase A (PKA), was introduced to verify the role of cAMP/PKA in the effect of PINO on MC3T3­E1 cells. Cell viability was the highest under 48 h of 0.1 µg/l PINO treatment. After treatment with PINO, a significant increase was observed in the migration rate and the expression of collagen type I (Col­I), ALP, osteopontin (OPN), runt­related transcription factor 2 (Runx2) and bone morphogenetic protein­2 (BMP­2) (P<0.01). The ALP activity and Alizarin red size in PINO and E2 groups were notably increased. The increased cAMP, PKA and phosphorylated cAMP response element­binding protein (CREB) levels were also observed in the PINO group. Furthermore, H89 co­treatment abolished the positive effects of PINO on cell viability and migration. PINO had similar effects to E2 on the osteoblastic proliferation and differentiation, and these positive effects may be attributed to the regulation of the cAMP/PKA signaling pathway.

Effect of niobium content on the microstructure and Young's modulus of Ti-xNb-7Zr alloys for medical implants.

New generation titanium alloys with low elastic moduli are promising materials for medical implants, particularly load-bearing orthopaedic implants. In this paper, the effect of niobium content on the microstructure and mechanical properties of new Ti alloys including Ti-23Nb-7Zr, Ti-28Nb-7Zr and Ti-33Nb-7Zr (wt%) is studied. Ti-23Nb-7Zr was found to mainly form α΄ and α″- phases, while both the Ti-28Nb-7Zr and Ti-33Nb-7Zr consisted of α″ and ß-phases with an increased amount of ß-phase in the alloy with 33 wt% of Nb. X-ray diffraction and microstructural analyses showed that the addition of Nb stabilises the ß-phase in the solution treated condition with the depleting amount of α΄ and α″- phases. The hardness and Young's modulus values were highest in Ti-23Nb-7Zr which is attributed to the high fraction of α΄- phase in this alloy. The Young's moduli achieved for the three alloys through nanoindentation were 35.9, 29.1 and 29.0 GPa, respectively. The new alloys are encouraging candidates for orthopaedic implants due to their low elastic modulus which can help inhibit stress shielding, although biocompatibility tests (in-vitro and in-vivo) are suggested for future work.

The Dependence of Isothermal ω Precipitation on the Quenching Rate in a Metastable ß-Ti Alloy.

The precipitation behavior of the α strengthening phase in metastable ß-Ti alloys is highly dependent on heat treatment parameters such as quenching rate, heating rate and ageing temperature. In this paper we have investigated the influence of quenching rate on the formation of isothermal ω precipitates that have been regarded as potent nucleant sites for α precipitation. The results show that the ß-solutionized alloy contains a ß matrix with a layer structured morphology. Regular atomic movement of the (002)ß plane along the <002> direction was observed in the alloy. The increase in quenching rate refines the thickness of layers, subsequently influencing the nucleation and growth of isothermal ω precipitates after ageing treatment. The high quenching rate promotes the occurrence of ω precipitation, broadens the stage of ω precipitation and increases the number density of ω precipitates. Since the isothermal ω phase provides a heterogeneous nucleation site for α precipitates, it is inferred that the quenching rate may indirectly influence the mechanical properties of metastable ß-Ti alloy.

Acute and subchronic toxicity of arprinocid in Sprague-Dawley rats.

We subjected Sprague-Dawley rats to an acute and 13-week subchronic oral toxicity of arprinocid, a nucleoside analogue used as a coccidiostat, according to toxicological guidelines as part of its safety assessment. In the acute study, arprinocid was administered once by oral gavage to rats at doses ranging from 292.4 to 506.0mg/kgb.w. The calculated LD50 was 442.9mg/kgb.w. in males and 378.7mg/kgb.w. in females. In the subchronic study, male and female rats were fed with diets supplemented with 0, 25, 187.5 or 500ppm arprinocid for 13weeks. Significantly lower body weights were noted in the 500ppm group females. The mean body weights of the 500ppm group females were 12.9% lower than that of the controls. Significant differences in haematological and biochemical parameters as well as organ weights were detected between the 500 and 187.5ppm groups. Histopathological observations revealed that 500 and 187.5ppm arprinocid could induce hepatic steatosis and focal hepatocellular necrosis. Slight protein cast in some renal tubules and tubular regeneration were observed in the high dose group of both genders. The dietary no-observed-adverse-effect level (NOAEL) of arprinocid in rats for 13weeks is 25ppm (approximately 1.7mg/kgb.w./day).

Preparation, mechanical and degradation properties of Mg-Y-based microwire.

Mg-Y-based microwire which offers high strength in combination of low degradation rate has been prepared for the first time by a modified melt extraction technique. A circular Mg-Y-based microwire is achieved with an extraction rate of 40m/s, which is composed of Mg matrix and an amorphous phase, and exhibits higher basal texture than that of as-cast sample. The outstanding tensile strength accompanying with an acceptable elongation is obtained with an extraction rate of 40m/s. The improved strength is mainly attributed to high solid solution strengthening, fine grain and the presence of an amorphous phase. In addition, the reduction of secondary phase and homogenous microstructure after melt extraction eliminate both pitting corrosion and micro-galvanic corrosion. A low degradation rate of 0.366mm/y is attained in a simulated body fluid, which is less than 1/10 of that of as-cast sample. These excellent mechanical properties and low degradation rate provide some prerequisites to develop bio-Mg implants. It reveals that this modified extraction technique is one of effective approaches to prepare microwire, which can be directly used for Mg-based stent self-assembly.

Epidemiological and viral genome characteristics of the first human H7N9 influenza infection in Guangdong Province, China.

BACKGROUND: The first H7N9 human case in south of China was confirmed in Guangdong Province on August 2013, outside of the typical influenza season. For investigating the H7N9 virus source and transmission in the local community, we analyze the epidemiology and genome features of the virus isolated from the first human infection detected in Guangdong Province. METHODS: The data including medical records, exposure history and time line of events for the H7N9 patient and close contacts was collected. Variation and genetic signatures of H7N9 virus in Guangdong was analyzed using ClustalW algorithm and comparison with mutations associated with changes in biological characteristics of the virus. RESULTS: The female patient had a history of poultry exposure, and she was transferred from a local primary hospital to an intensive care unit (ICU) upon deterioration. No additional cases were reported. Similar to previous infections with avian influenza A (H7N9) virus, the patient presented with both upper and lower respiratory tract symptoms. Respiratory failure progressed quickly, and the patient recovered 4 weeks after the onset of symptoms. Genome analysis of the virus indicated that the predicted antigen city and internal genes of the virus are similar to previously reported H7N9 viruses. The isolated virus is susceptible to neuraminidase (NA) inhibitors but resistant to adamantine. Although this virus contains some unique mutations that were only detected in avian or environment-origin avian influenza A (H7N9) viruses, it is still quite similar to other human H7N9 isolates. CONCLUSIONS: The epidemiological features and genome of the first H7N9 virus in Guangdong Province are similar to other human H7N9 infections. This virus may have existed in the environment and live poultry locally; therefore, it is important to be alert of the risk of H7N9 re-emergence in China, including emergence outside the typical influenza season.