We aimed to compare the results of long-term use of two types of metal stent for chronic benign ureteral strictures.Our study included 46 ureter units (UUs) that underwent metal stent placement from 2010 to 2017. We included benign ureteral strictures causes by variety reasons that could not be solved by other treatment and malignant obstructions were excluded. Covered mesh stent (Uventa™) and a thermo-expandable stent (Memokath 051™) were used. Primary success was defined as maintaining patency without procedures and overall success was defined as maintaining patency with additional procedures.We placed covered mesh stents in 25 UUs and thermo-expandable stents in 21 UUs. The mean follow-up duration of each stent was 41.4 ± 23.1 and 34.4 ± 16.5 months (p = 0.250). In the first year of stent insertion, primary success was achieved in 54.9 and 70.4% (p = 0.204). Overall success was achieved in 78.7 and 75.4% in same duration, respectively (p = 0.586). Longer stent placement had positive predictive value on both success rates (HR = 0.185, p = 0.047 and HR = 0.111, p = 0.018). Prior radiation therapy and non-pelvic ureter stricture both adversely affected the overall success rate (HR = 5.412, p = 0.048 and HR = 4.203, p = 0.030). Previous PCN status had negative predictive value for both success rates (HR = 4.014, p = 0.003 and HR = 3.064, p = 0.035).The treatment outcomes of two types of metal stent were comparable, especially in the first year of stent insertion.

Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.

Ureteral stents often cause significant patient morbidity that can be difficult to treat. Drug-eluting stent technology allows the local delivery of a drug. Our previous work demonstrated that ketorolac instilled intravesically at the time of ureteral stent insertion significantly decreased flank pain compared with controls. We sought to determine the safety of a novel ketorolac-eluting ureteral stent.A total of 92 Yorkshire pigs were randomized to 1 of 5 groups. The oral control group consisted of 12 animals with transurethrally inserted control ureteral stents and 5 days of oral ketorolac. Twenty animals in each of the remaining groups received a control stent, or 15%, 13%, or 7% ketorolac-loaded stents. Ketorolac levels were measured in plasma, urine, and tissue sampled from ureters, bladder, kidneys, and liver using high performance liquid chromatography. Necropsies were performed to evaluate tissue pathology.The majority of ketorolac was released within the first 30 days. The highest levels of ketorolac in plasma, kidney, and liver occurred in the oral control group. The highest levels of ketorolac found in ureteral and bladder tissues occurred in the ketorolac-stent groups in a dose-dependent fashion. No adverse events were noted in any of the ketorolac-stent groups. Gastric ulcerations were identified only in the oral control group. No abnormalities were identified in any other internal organs in any group.The use of ketorolac-eluting ureteral stents has proven to be safe in a porcine model. The ketorolac-stent group had less than 12% of the ketorolac concentration in plasma, kidney, and liver tissues compared with the oral ketorolac group. Ureteral tissues displayed the highest levels of ketorolac. Clinical studies are needed to determine if ketorolac-elution reduces stent symptoms.

We evaluated the short-term safety and efficacy of a ketorolac loaded ureteral stent compared to a standard stent (control).In this prospective, multicenter, double-blind study patients were randomized 1:1 to ketorolac loaded or control stents after ureteroscopy. The primary end point was an intervention for pain defined as unscheduled physician contact, change in pain medication or early stent removal. Secondary end points included medication use and pain visual analog score. A total of 20 patients underwent serum safety testing for ketorolac levels.None of the safety cohort had detectable serum ketorolac levels. Among the 276 patients there was no difference in primary (9.0% ketorolac loaded vs 7.0% control, p = 0.66) or secondary (22.6% ketorolac loaded vs 25.2% control, p = 0.67) intervention rates. Mean pain pill count at day 3 was lower in the ketorolac loaded stent group than in the control group (p <0.05). A higher number (p = 0.057) of patients with ketorolac loaded (32%) stents used no or limited pain medications compared to controls (22%). A higher number of male patients with ketorolac loaded stents used no pain medication on days 3 and 4 compared to female patients with ketorolac loaded stents, and male and female control patients (p <0.05).The overall safety of the ketorolac loaded stent was confirmed. Although there was no significant difference in primary or secondary intervention rates, a trend toward a treatment benefit was noted for patients receiving drug loaded stents. Specifically young male patients appeared to require less pain medication when the ketorolac loaded stent was used. Future studies with higher drug concentrations or alternative drug eluting stents may prove beneficial.2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The number of bacterial pathogens resistant to the currently available antibiotics has dramatically increased, with antimicrobial peptides (AMPs) being among the most promising potential new drugs. In this study, the applicability and mechanisms of action of Pa-MAP 2 and Pa-MAP 1.9, two AMPs synthetically designed based on a natural AMP template, were evaluated.Pa-MAP 2 and Pa-MAP 1.9 were tested against a clinically isolated multidrug-resistant (MDR) Escherichia coli strain. Biophysical approaches were used to evaluate the preference of both peptides for specific lipid membranes, and bacterial surface changes imaged by atomic force microscopy (AFM). The efficacy of both peptides was assessed both in vitro and in vivo.Experimental results showed that both peptides have antimicrobial activity against the E. coli MDR strain. Zeta potential and surface plasmon resonance assays showed that they interact extensively with negatively charged membranes, changing from a random coil structure, when free in solution, to an α-helical structure after membrane interaction. The antibacterial efficacy was evaluated in vitro, by several techniques, and in vivo, using a wound infection model, showing a concentration-dependent antibacterial effect. Different membrane properties were evaluated to understand the mechanism underlying peptide action, showing that both promote destabilization of the bacterial surface, as imaged by AFM, and change properties such as membrane surface and dipole potential.Despite their similarity, data indicate that the mechanisms of action of the peptides are different, with Pa-MAP 1.9 being more effective than Pa-MAP 2. These results highlight their potential use as antimicrobial agents against MDR bacteria.© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Permanent antibacterial coatings have been developed by brush-like polyethyleneimine (PEI) on polyurethane (PU) ureteral stents since bacterial adhesion and biofilm formation with the following encrustation on stent surface limit their long term usage. In order to control or prevent bacterial infections; PEI chains with two different molecular weights (Mn: 1800 or 60,000 Da) were covalently attached on the polyurethane (PU) surface by "grafting to" approach to obtain a brush-like structure. Then, PEI brushes were alkylated with bromohexane to enhance the disruption of bacterial membranes with increasing polycationic character. X-ray Photoelectron and Infrared Spectroscopy investigations confirmed that PEI grafting and alkylation steps were performed successfully. Surface roughness in dry state increased dramatically from 65.8 nm to 277.7 nm and 145.2 nm for short chain PEI and long chain PEI grafted samples, respectively. Both low and high molecular weight PEI grafts exhibited a brush-like structure and potent antibacterial activity by lowering the adherence of Klebsiella pneumonia, Escherichia coli and Proteus mirabilis species up to two orders of magnitude without any cytotoxic effect on L929 and G/G cells. Thus, permanent bactericidal activity was achieved by the contact-active strategy of dynamic PEI brush-like structures on polyurethane ureteral stent.Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The foreign body response (FBR) to implantable materials can negatively impact performance of medical devices such as the cochlear implant. Engineering surfaces that resist the FBR could lead to enhanced functionality including potentially improving outcomes for cochlear implant recipients through reduction in fibrosis. In this work, we coat poly(dimethylsiloxane) (PDMS) surfaces with two zwitterionic polymers, poly(sulfobetaine methacrylate) (pSBMA) and poly(carboxybetaine methacrylate) (pCBMA), using a simultaneous photografting/photo-cross-linking process to produce a robust grafted zwitterionic hydrogel. reduce nonspecific protein adsorption, the first step of the FBR. The coating process uses benzophenone, a photografting agent and type II photoinitiator, to covalently link the cross-linked zwitterionic thin film to the PDMS surface. As the concentration of benzophenone on the surface increases, the adhesive strength of the zwitterionic thin films to PDMS surfaces increases as determined by shear adhesion. Additionally, with increased concentration of the adsorbed benzophenone, failure of the system changes from adhesive delamination to cohesive failure within the hydrogel, demonstrating that durable adhesive bonds are formed from the photografting process. Interestingly, antifouling properties of the zwitterionic polymers are preserved with significantly lower levels of nonspecific protein adsorption on zwitterion hydrogel-coated samples compared to uncoated controls. Fibroblast adhesion is also dramatically reduced on coated substrates. These results show that cross-linked pSBMA and pCBMA hydrogels can be readily photografted to PDMS substrates and show promise in potentially changing the fibrotic response to implanted biomaterials.

To reduce the risk of implant-associated infections, we previously designed and developed a series of medical copper (Cu)-bearing titanium alloys that release Cu ions and hence play an antibacterial role. However, both excessive and deficient Cu levels adversely affect human health; therefore, the aim of the present study was to comprehensively evaluate the short- and long-term biosafety of Cu-bearing titanium alloys (Ti6Al4V-Cu and Ti-Cu) both in vitro and in vivo. Moreover, the predominant kinetic mechanism of Cu ions release and its effect on biosafety were also investigated. The results indicate that the biocompatibility of the Cu-bearing titanium alloys meets the requirements of ISO standards and the Cu ion release kinetics display a good correlation over the entire time period in the normal zero-order model with an almost constant release rate. The release rate maintained at a parts per billion level safe for humans; consequently, we can conclude that our Cu-bearing titanium alloys have satisfactory biocompatibility.

Cu-bearing stainless steel has been found to have obvious inhibition performance against encrustation in vitro. This study was aiming to further investigate the inhibitory effect of a Cu-bearing stainless steel (316L-Cu SS) on the infectious encrustation based on its antimicrobial activity. The encrustation in presence of bacteria, antibacterial performance, urease production and Ca and Mg precipitation were examined by scanning electron microscopy, antibacterial assay, enzyme-linked immunosorbent assay and inductively coupled plasma-mass spectrometry, respectively. It was found that 316L-Cu SS could inhibit the formation of bacterial biofilm due to the release of Cu2+ ions and then decrease the urease amount splitting by bacteria, which produced a neutral environment with pH around 7. However, more encrustations coupled with bacterial biofilms on the surface of comparison stainless steel (316L SS) with an alkaline environment were recorded. It can thus be seen that the 316L-Cu SS highlights prominent superiority against encrustation in the presence of microorganisms.

In order to solve the infection caused by the indwelling catheter, an anti-infective Cu-bearing chitosan coating was prepared on the silicone rubber surface. But it is difficult to prepare a coating on the surface of silicone rubber due to its biological inertness. Therefore, chemical grafting was used to activate the silicone rubber by the dopamine pretreatment, which provides abundant functional groups on the activated silicone rubber surface. The surface morphology and surface properties of the silicone rubber after surface activation pretreatment were characterized by the active functional groups. Onto which, subsequently, the Cu-bearing chitosan coating could be chemically grafted, and then the surface morphology was compared for the coatings before and after immersion test. The effectiveness of pretreatment process was assessed by the bonding force between the functionalized coating and the silicone rubber. It follows that the abundant functional groups offered by the pretreatment on the activated silicone rubber surface may be beneficial for enhancing the adhesive strength of the functionalized coating to the silicon rubber. Thereby, the Cu-bearing chitosan coating makes the silicone rubber catheter have good antibacterial function.

在硅橡胶表面制备一种具有抗感染功能的涂层—壳聚糖载铜凝胶涂层。为了克服硅橡胶的生物惰性,在其表面制备涂层,先用逐步化学接枝法对其表面进行活化预处理,然后化学接枝壳聚糖载铜凝胶涂层。对比浸泡前后涂层的形貌,研究了活化预处理对功能化涂层与硅橡胶基体之间结合性能的影响。结果表明,用化学接枝法可在硅橡胶表面生成丰富的活性官能团从而提高了功能化涂层与硅橡胶的结合强度。载铜功能化涂层使硅橡胶导管具有良好的抗菌功能。

Metallic copper surfaces have strong antimicrobial properties and kill bacteria, such as Escherichia coli, within minutes in a process called contact killing. These bacteria are exposed to acute copper stress under dry conditions which is different from chronic copper stress in growing liquid cultures. Currently, the physiological changes of E. coli during the acute contact killing process are largely unknown. Here, a label-free, quantitative proteomic approach was employed to identify the differential proteome profiles of E. coli cells after sub-lethal and lethal exposure to dry metallic copper. Of the 509 proteins identified, 110 proteins were differentially expressed after sub-lethal exposure, whereas 136 proteins had significant differences in their abundance levels after lethal exposure to copper compared to unexposed cells. A total of 210 proteins were identified only in copper-responsive proteomes. Copper surface stress coincided with increased abundance of proteins involved in secondary metabolite biosynthesis, transport and catabolism, including efflux proteins and multidrug resistance proteins. Proteins involved in translation, ribosomal structure and biogenesis functions were down-regulated after contact to metallic copper. The set of changes invoked by copper surface-exposure was diverse without a clear connection to copper ion stress but was different from that caused by exposure to stainless steel. Oxidative posttranslational modifications of proteins were observed in cells exposed to copper but also from stainless steel surfaces. However, proteins from copper stressed cells exhibited a higher degree of oxidative proline and threonine modifications.

The purpose of this study was to see whether it is possible to prevent bacterial adherence to bioabsorbable self-reinforced L-lactic acid polymer (SR-PLLA) urological stents. The SR-PLLA stents were coated with silver nitrate blended epsilon-caprolactone/L-lactide copolymer. The adherence of five bacterial strains (Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis and two strains of Escherichia coli) to coated and non-coated SR-PLLA wires were tested. It was found that silver nitrate coating prevented the adherence of bacteria (except E. faecalis) to SR-PLLA stents. The preventive effect correlated with the silver nitrate concentration. It was also found that silver nitrate coating reduced the amount of bacteria in ambient urine. In conclusion, silver nitrate coating may reduce stent-associated bacterial infections by preventing the adherence of bacteria. Further studies are needed to confirm its efficacy and safety in clinical practice.

Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until 1978. We now understand that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health. Using tools such as the scanning electron microscope and, more recently, the confocal laser scanning microscope, biofilm researchers now understand that biofilms are not unstructured, homogeneous deposits of cells and accumulated slime, but complex communities of surface-associated cells enclosed in a polymer matrix containing open water channels. Further studies have shown that the biofilm phenotype can be described in terms of the genes expressed by biofilm-associated cells. Microorganisms growing in a biofilm are highly resistant to antimicrobial agents by one or more mechanisms. Biofilm-associated microorganisms have been shown to be associated with several human diseases, such as native valve endocarditis and cystic fibrosis, and to colonize a wide variety of medical devices. Though epidemiologic evidence points to biofilms as a source of several infectious diseases, the exact mechanisms by which biofilm-associated microorganisms elicit disease are poorly understood. Detachment of cells or cell aggregates, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are all biofilm processes which could initiate the disease process. Effective strategies to prevent or control biofilms on medical devices must take into consideration the unique and tenacious nature of biofilms. Current intervention strategies are designed to prevent initial device colonization, minimize microbial cell attachment to the device, penetrate the biofilm matrix and kill the associated cells, or remove the device from the patient. In the future, treatments may be based on inhibition of genes involved in cell attachment and biofilm formation.

Urinary catheters often become encrusted and blocked by crystalline Proteus mirabilis biofilms. Results of experiments in a laboratory model of a Foley catheterised bladder infected with P mirabilis showed that when retention balloons were inflated with a solution of triclosan (10 g/L), the catheters drained freely for at least 7 days. Triclosan became impregnated throughout the silicone catheter material and completely inhibited the formation of crystalline biofilm, whereas catheters inflated with water became blocked in 24 h. Our observations suggest a way to control a common complication in patients with long-term indwelling bladder catheters.