There is an increasing interest in biodegradable metal implants made from magnesium (Mg), iron (Fe), zinc (Zn) and their alloys because they are well tolerated in vivo and have mechanical properties that approach those of non-degradable metals. In particular, Zn and its alloys show the potential to be the next generation of biodegradable materials for medical implants. However, Zn has not been as well-studied as Mg, especially for stent applications. Manufacturing stents by laser cutting has become an industry standard. Nevertheless, the use of this approach with Zn faces some challenges, such as generating thermal stress, dross sticking on the device, surface oxidation, and the need for expensive thin-walled Zn tubing and post-treatment. All of these challenges motivated us to employ photo-chemical etching for fabricating different designs of Zn (99.95% pure) stents. The stents were constructed with different strut patterns, made by photo-chemical etching, and mechanically tested to evaluate radial forces. Stents with rhombus design patterns showed a promising 0.167N/mm radial force, which was comparable to Mg-based stents. In vitro studies were conducted with uncoated Zn stents as control and Parylene C-coated Zn stents to determine corrosion rates. The Parylene C coating reduced the corrosion rate by 50% compared to uncoated stents. In vivo studies were carried out by implanting photo-chemically etched, uncoated Zn stent segments subcutaneously in a C57BL/6 mice model. Histological analyses provided favorable data about the surrounding tissue status, as well as nerve and blood vessel responses near the implant, providing insights into the in vivo degradation of the metal struts. All of these experiments confirmed that Zn has the potential for use in biodegradable stent applications.
A single subanesthetic infusion of ketamine can rapidly alleviate symptoms of treatment-resistant major depression. Since repeated administration is required to sustain symptom remission, it is important to characterize the potential untoward effects of prolonged ketamine exposure. While studies suggest that ketamine can alter cognitive function, it is unclear to what extent these effects are modulated by the frequency or chronicity of treatment. To test this, male and female adolescent (postnatal day [PD] 35) and adult (PD 60) BALB/c mice were treated for four consecutive weeks, either daily or thrice-weekly, with (R,S)-ketamine (30 mg/kg, intraperitoneal) or its biologically active metabolite, (2R,6R)-hydroxynorketamine (HNK; 30 mg/kg, intraperitoneal). Following drug cessation, memory performance was assessed in three operationally distinct tasks: (1) novel object recognition to assess explicit memory, (2) Y-maze to assess working memory, and (3) passive avoidance to assess implicit memory. While drug exposure did not influence working memory performance, thrice-weekly ketamine and daily (2R,6R)-HNK led to explicit memory impairment in novel object recognition independent of sex or age of exposure. Daily (2R,6R)-HNK impaired implicit memory in the passive-avoidance task whereas thrice-weekly (2R,6R)-HNK tended to improve it. These differential effects on explicit and implicit memory possibly reflect the unique mechanisms by which ketamine and (2R,6R)-HNK alter the functional integrity of neural circuits that subserve these distinct cognitive domains, a topic of clinical and mechanistic relevance to their antidepressant actions. Our findings also provide additional support for the importance of dosing frequency in establishing the cognitive effects of repeated ketamine exposure.
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