ABSTRACT
This study was to investigate the effects of micro-nano titanium implant surface on the osseointegration. A total of 36 screw-shaped implants were used. The implant surfaces were classified into 3 groups (n = 12): machined surface (M group), nanosurface which is nanotube formation on the machined surface (MA group) and nano-micro surface which is nanotube formation on the RBM surface (RA group). Anodic oxidation was performed at a 20 V for 10 min with 1 M H3PO4 and 1.5 wt% HF solutions. The implants were installed on the humerus on 6 beagles. After 4 and 12 weeks, the morphometric analysis with micro CT (skyscan 1172, SKYSCAN, Antwerpen, Belgium) was done. The data were statistically analyzed with two-way ANOVA. Bone mineral density and bone volume were significantly increased depending on time. RA group showed the highest bone mineral density and bone volume at 4 weeks and 12 weeks significantly. It indicated that nano-micro titanium implant surface showed faster and more mature osseointegration.
Subject(s)
Bone Substitutes/chemistry , Bone Substitutes/pharmacology , Nanotubes/chemistry , Osseointegration/drug effects , Titanium/chemistry , Animals , Dogs , Humerus/surgery , Male , Surface Properties , X-Ray MicrotomographyABSTRACT
We investigated maternal and fetal tissue distribution of DW-116, a newly developed fluoroquinolone with a broad antibacterial spectrum against both G(+) and G(-) bacteria, in pregnant rats. After oral administration of [14C]-DW-116 (labeled 1 mg and unlabeled 500 mg/kg) to female rats on the 18th day of gestational, groups of three rats were killed at various time points up to 24 h, and plasma and tissues were collected, processed and analyzed. [14C]-DW-116 was rapidly absorbed, and distributed into the maternal and fetal tissues, and it declined in a biphasic manner with elimination half-lives (t(1/2)) of 10-15 h and mean residence times (MRT(0-24 h)) of 4-9 h. The radioactivity in most tissues of both dams and fetus reached its peak within 1 h and radioactivity levels of up to 10-25% of the peak level were maintained until 24 h after dosing. Among various tissues, the radioactivity in the maternal lungs was the highest (27 times that of plasma) at the C(max). Radioactivity in other tissues including liver, kidney, heart, lung, brain, spleen, mammary gland, placenta, ovary and uterus was higher than that in the maternal plasma (one- to three-fold). The tissue-to-plasma partition coefficient (K(p), AUC(0-24 h,tissue)/AUC(0-24 h,plasma)) of [14C]-DW-116 in maternal tissues was highest in the lung (K(p)=3.7), followed by the spleen (2.2), kidney (2.0), liver (1.8), heart (1.5), placenta (1.3), brain (1.3), ovary (1.1), uterus (1.1), and mammary gland (1.0). The tissue-to-plasma partition coefficient values in fetal tissues were heart (K(p)=2.2), kidney (2.1), liver (1.9), lung (1.6) and brain (1.4). When lactating rats were given a single oral dose of [14C]-DW-116, the radioactivity was rapidly secreted into the milk with K(p) of 1.7 at T(max) (0.5 h). These results indicate that DW-116 or its related metabolite(s) rapidly cross the blood-placenta and blood-milk barrier, extensively distribute into the fetal tissues, and are eliminated from the body in a prolonged manner. This study sheds insights into the maternal and fetal tissue distribution of DW-116 and will be useful for assessing both therapeutic and toxicological relevance of DW-116 in pregnant subjects.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Fetus/metabolism , Fluoroquinolones , Fluoroquinolones/pharmacokinetics , Maternal-Fetal Exchange , Piperazines/pharmacokinetics , Quinolones/pharmacokinetics , Administration, Oral , Animals , Animals, Newborn , Anti-Bacterial Agents/administration & dosage , Area Under Curve , Carbon Radioisotopes , Female , Fetus/drug effects , Fluoroquinolones/administration & dosage , Lactation , Piperazines/administration & dosage , Pregnancy , Quinolones/administration & dosage , Rats , Rats, Sprague-Dawley , Specific Pathogen-Free Organisms , Tissue DistributionABSTRACT
The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with potent antibacterial activity, were compared with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin. Against gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis, the in vitro activity of DW286 was stronger than that of any other reference antibiotic. Against gram-negative bacteria, the activity of DW286 was similar to those of trovafloxacin and gemifloxacin but was weaker than that of ciprofloxacin. In a mouse systemic infection caused by three S. aureus strains, including methicillin-resistant S. aureus and quinolone-resistant S. aureus (QRSA), DW286 demonstrated the most potent activity, as found in vitro. Specially, DW286 is >or=8-fold more active against QRSA than the other fluoroquinolones. And the 50% protective doses for DW286 were correspondent with the in vitro activities.