Urinary Stents Soria, Federico; Rako, Duje; de Graaf, Petra
2022, 2022-08-20
eBook
Open access
This open access book provides a concise overview of a range of aspects related to urinary stents. Sections within the work cover clinical and recent technological advancements in the field. Chapters ...feature detailed coverage of the different surgical, pharmacological and palliative treatments currently available. Insight is also given on current limitations of urinary stents and how these can be overcome by utilizing anti-biofilm coatings; new biomaterials, drug-eluting stents, and biodegradable stents. Therefore, enabling the reader to systematically gain a detailed understanding of the subject. Urinary Stents is a practical, multi-disciplinary focused resource on the complications and applications of ureteral, urethral and prostatic stents in day-to-day clinical practice. A vital read for all medical professionals and researchers who work in this area.
The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes such as enhancers and promoters differ in their extent of ...methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in mouse embryonic stem cells and in neuronal progenitor cells. Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our data indicate that by restricting H3K4me3 modification at core promoters, Kdm5c dampens transcription, but at enhancers Kdm5c stimulates their activity. Remarkably, an impaired enhancer function activates the intrinsic promoter activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c demethylase plays a crucial and dynamic role in the functional discrimination between enhancers and core promoters.
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► The H3K4me3/2 demethylase Kdm5c interacts with gene-specific transcription factors ► Genomic profiles of Kdm5c in ESCs reveal promoter-proximal and -distal binding ► Kdm5c represses promoter activity but stimulates enhancer function ► Dynamic H3K4me3/2 thus modulates promoter and enhancer function
Regulatory regions of eukaryotic genomes such as enhancers and promoters differ in their extent of methylation of histone H3 at lysine 4 (H3K4). Using embryonic stem cells, Timmers and colleagues report that the Kdm5c/Jarid1c/SMCX demethylase controls H3K4 mono- and trimethylation with different transcriptional outcomes. At promoters, Kdm5c dampens transcription, but at enhancers, Kdm5c stimulates their activity. Impairment of enhancer function activates an intrinsic promoter activity of Kdm5c sites. This demonstrates that Kdm5c plays a dynamic role in the functional discrimination between genomic elements.
Urinary stents, be it urethral or ureteral, polymeric, metallic or biodegradable, are one of the most frequently used tools in urology and they have been used for decades in prophylactic and ...therapeutic setting. Although relatively low invasive, they are prone to complications and adverse effects so much that complication rates up to 100% have been described. Many reviews have focused either on specific groups of patients or particular stent types, materials or designs but so far, no comprehensive review on complications has been published. To tackle this issue, a working group was set up within ENIUS (European Network of multidisciplinary research to Improve Urinary Stents) tasked with literature search in order to screen for and systematically review published stent complications in urethra (male only) and ureters (polymeric and metallic ureteral stents in both sexes) when used in obstructed systems. In this paper, we review, catalogue and summarize complications published for metallic urethral and ureteral stents.Urinary stents, be it urethral or ureteral, polymeric, metallic or biodegradable, are one of the most frequently used tools in urology and they have been used for decades in prophylactic and therapeutic setting. Although relatively low invasive, they are prone to complications and adverse effects so much that complication rates up to 100% have been described. Many reviews have focused either on specific groups of patients or particular stent types, materials or designs but so far, no comprehensive review on complications has been published. To tackle this issue, a working group was set up within ENIUS (European Network of multidisciplinary research to Improve Urinary Stents) tasked with literature search in order to screen for and systematically review published stent complications in urethra (male only) and ureters (polymeric and metallic ureteral stents in both sexes) when used in obstructed systems. In this paper, we review, catalogue and summarize complications published for metallic urethral and ureteral stents.
Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. ...Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs.
To review recent literature on tissue engineering for human urethral reconstruction.
A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language.
A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial.
Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.
Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure shows an unsatisfying stricture ...recurrence rate which could be improved by addition of local therapies. To provide an overview of both preclinical and clinical studies in order to investigate current level of evidence on the addition of local therapy to improve urethral stricture recurrence rates after endoscopic procedures. We performed a literature search in December 2020 and August 2021 using Cochrane, Embase, PubMed, Scopus and Web of Science and identified articles through combinations of search terms for 'urethral stricture disease', 'stricture formation' and 'local interventions'. We used the SYRCLE, RoB-2 and ROBINS-I tools to assess risk of bias across included studies. We did not perform a meta-analysis due to methodological differences between studies. We included 32 articles in the qualitative analysis, 20 of which were preclinical studies and 12 clinical studies. Regarding preclinical articles using an animal model, nearly all interventions showed to have a positive effect on either urethral fibrosis, urethral stricture formation and/or fibrotic protein expression levels. Here, immunosuppressants and chemotherapeutics seemed most promising for possible clinical purposes. Regarding clinical studies, mitomycin-C and hyaluronic acid and carboxymethylcellulose showed positive effects on urethral stricture recurrence rates with low to intermediate risk of bias across studies. However, the positive clinical effects of mitomycin-C and steroids seemed to decrease in studies with a longer follow-up time. Although local adjuvant use of mitomycin-C or hyaluronic acid and carboxymethylcellulose may carry clinical potential to improve urethral structure recurrence rates after endoscopic procedures, we believe that a large, well-designed RCT with a yearlong follow-up time is necessary to identify the true clinical value.
PRMT6 belongs to the family of Protein Arginine Methyltransferase (PRMT) enzymes that catalyze the methylation of guanidino nitrogens of arginine residues. PRMT6 has been shown to modify the tail of ...histone H3, but the in vivo function of PRMT6 is largely unknown. Here, we show that PRMT6 regulates cell cycle progression. Knockdown of PRMT6 expression in the human osteosarcoma cell line U2OS results in an accumulation of cells at the G2 checkpoint. Loss of PRMT6 coincides with upregulation of p21 and p27, two members of the CIP/KIP family of cyclin-dependent kinase (CDK) inhibitors. Gene expression and promoter analysis show that p21 and p27 are direct targets of PRMT6, which involves methylation of arginine-2 of histone H3. Our findings imply arginine methylation of histones by PRMT6 in cell cycle regulation.
Maintenance of genomic stability depends on the DNA damage response, an extensive signaling network that is activated by DNA lesions such as double-strand breaks (DSBs). The primary activator of the ...mammalian DSB response is the nuclear protein kinase ataxia-telangiectasia, mutated (ATM), which phosphorylates key players in various arms of this network. The activation and stabilization of the p53 protein play a major role in the DNA damage response and are mediated by ATM-dependent posttranslational modifications of p53 and Mdm2, a ubiquitin ligase of p53. p53's response to DNA damage also depends on Mdm2-dependent proteolysis of Mdmx, a homologue of Mdm2 that represses p53's transactivation function. Here we show that efficient damage-induced degradation of human Hdmx depends on functional ATM and at least three sites on the Hdmx that are phosphorylated in response to DSBs. One of these sites, S403, is a direct ATM target. Accordingly, each of these sites is important for Hdm2-mediated ubiquitination of Hdmx after DSB induction. These results demonstrate a sophisticated mechanism whereby ATM fine-tunes the optimal activation of p53 by simultaneously modifying each player in the process.
Gene transcription in mammalian cells is a dynamic process involving regulated assembly of transcription complexes on chromatin in which the TATA-binding protein (TBP) plays a central role. Here, we ...investigate the dynamic behaviour of TBP by a combination of fluorescence recovery after photobleaching (FRAP) and biochemical assays using human cell lines of different origin. The majority of nucleoplasmic TBP and other TFIID subunits associate with chromatin in a highly dynamic manner. TBP dynamics are regulated by the joint action of the SNF2-related BTAF1 protein and the NC2 complex. Strikingly, both BTAF1 and NC2 predominantly affect TBP dissociation rates, leaving the association rate unchanged. Chromatin immunoprecipitation shows that BTAF1 negatively regulates TBP and NC2 binding to active promoters. Our results support a model for a BTAF1-mediated release of TBP-NC2 complexes from chromatin.
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