Biomedical Engineering Reference
In-Depth Information
controls showed no difference in pain scores except in young males who had less symptoms
with the ketorolac eluting stent (Krambeck, Walsh et al. 2010).
Liatsikos
et al
have tested paclitaxel eluting metal stents in the pig ureter to examine the
tissue effects and stricture formation.(Liatsikos, Karnabatidis et al. 2007) Paclitaxel eluting
stents produced less ureteral inflammation and hyperplasia of the surrounding tissue
compared to the bare metal stents. Ureteral patency was lost in the control stents and
maintained by the Paclitaxel eluting stents. These studies were carried out over a 21 day
period and require further validation via long term animal trials.
Stent encrustation worsens with increased indwelling time and concurrent infection with
urease-producing organisms. Oxalate is normally broken down in the gastrointestinal tract
by the enzyme oxalate decarboxylase, which is found in a commensal organism
Oxalobacter
formigenes
. Oxalate that escapes degradation and fecal excretion is absorbed into the
bloodstream and filtered in the kidneys where, under certain conditions, it can combine
with calcium to form calcium oxalate stones. Watterson
et al
. coated silicone disks with
oxalate decarboxylase and implanted these into rabbit bladders.(Watterson, Cadieux et al.
2003) After 30 days, the oxalate decarboxylase-coated disks were significantly less encrusted
than control disks. Coating ureteral stents with such an enzyme could theoretically prevent
encrustation as the stent would elute an enzyme to degrade urinary oxalate.
9. Identifying potential targets in stent design
When considering the design of new indwelling ureteral devices such as stents or catheters,
the sequential steps triggering a given side effect should be taken into consideration,
however this has been complicated by the complexity of mechanisms involved. Rational
drug design hypothesizes that the alteration of a biological target has therapeutic value and
forms the basis for the invention of new medications predicated on the identification and
knowledge of a specific biological target. The first step involves turning to basic science and
considering the molecular and biochemical pathways involved in the condition to identify
specific targets for drug design. Once a target has been identified, its molecular structure is
determined and a suitable drug that will alter it in a favorable manner is designed. Usually
the target is a key molecule in a metabolic or signaling pathway specific to a disease
condition or pathology (Mandal, Moudgil et al. 2009).
We believe that the same principals can also be applied to the design of ureteral stents, as
the current stent designs have failed to live up to their expectations in the complex
environment of the urinary tract. Given the fact that the mechanisms causing stent
symptoms are unknown makes it difficult to identify a key target in the context of rational
drug design to relieve patient symptoms. The identification of such a target in the urinary
tract would be beneficial, as it will allow for the reduction or elimination of stent symptoms
by targeting a single mechanism. However, in order for that to become a possibility, key
steps in the mechanisms surrounding stent-related symptoms need to be identified to allow
for their inhibition.
Although identifying a single receptor or enzyme target in the development of stent
encrustation and infection is unlikely, a more solid understanding of the mechanism
involved in this process is required. Several processes occur following stent insertion and
the cumulative effect can result in stent associated symptoms suffered by the patient. It has
been well documented that a urinary conditioning film deposits on the stent surface shortly
following device insertion that consists of urinary components (Tieszer, Reid et al. 1998).
