Effect of Mitomycin - C and Triamcinolone on Preventing Urethral Strictures

Urethral stricture is a common disease with high recurrence rate. Several manipulations were defined to prevent the recurrence but the results were disappointing. This study aimed to evaluate the efficacy of triamcinolone and mitomycin-C on urethral stricture formation and their effect on inhibition of urethral fibrosis. A total of 24 New Zealand rabbits were divided into 3 groups. Urethras of rabbits were traumatized with pediatric resectoscope. Resection area was irrigated with 10mL saline, swapped with a cotton wool soaked with 0.5mg/mL MMC and injected by 40mg triamcinolone in groups 1, 2 and 3 respectively. Retrograde urethrogram was performed at 28th day of procedure and the urethra was removed for histopathologic evaluation. There were significant differences in urethral diameters and in lumen reduction rate between the control and study groups (p< 0.001). Compared to control group, all treatment groups showed mild fibrosis, less collagen bundle irregularity, and lower numbers of fibroblasts (p= 0.003). The Tunnel assay showed that the number of apoptotic cells in the submucosal connective tissue was quantitatively higher in control groups (p= 0.034). In the view of efficacy and safety, MMC and triamcinolone have the potential to replace the use of stents, clean intermittent catheterization, or long term catheters following internal urethrotomy. There were no statistically significant differences between two agents in terms of preventing urethral stricture formation in the present study. Mitomycin C and triamcinolone decreased the recurrence rates of urethral stricture

Triad pattern algorithm for predicting strong promoter candidates in bacterial genomes

Abstract Background Bacterial promoters, which increase the efficiency of gene expression, differ from other promoters by several characteristics. This difference, not yet widely exploited in bioinformatics, looks promising for the development of relevant computational tools to search for strong promoters in bacterial genomes. Results We describe a new triad pattern algorithm that predicts strong promoter candidates in annotated bacterial genomes by matching specific patterns for the group I σ70 factors of Escherichia coli RNA polymerase. It detects promoter-specific motifs by consecutively matching three patterns, consisting of an UP-element, required for interaction with the α subunit, and then optimally-separated patterns of -35 and -10 boxes, required for interaction with the σ70 subunit of RNA polymerase. Analysis of 43 bacterial genomes revealed that the frequency of candidate sequences depends on the A+T content of the DNA under examination. The accuracy of in silico prediction was experimentally validated for the genome of a hyperthermophilic bacterium, Thermotoga maritima, by applying a cell-free expression assay using the predicted strong promoters. In this organism, the strong promoters govern genes for translation, energy metabolism, transport, cell movement, and other as-yet unidentified functions. Conclusion The triad pattern algorithm developed for predicting strong bacterial promoters is well suited for analyzing bacterial genomes with an A+T content of less than 62%. This computational tool opens new prospects for investigating global gene expression, and individual strong promoters in bacteria of medical and/or economic significance.</p

A Novel Phase Variation Mechanism in the Meningococcus Driven by a Ligand-Responsive Repressor and Differential Spacing of Distal Promoter Elements

Phase variable expression, mediated by high frequency reversible changes in the length of simple sequence repeats, facilitates adaptation of bacterial populations to changing environments and is frequently important in bacterial virulence. Here we elucidate a novel phase variable mechanism for NadA, an adhesin and invasin of Neisseria meningitidis. The NadR repressor protein binds to operators flanking the phase variable tract and contributes to the differential expression levels of phase variant promoters with different numbers of repeats likely due to different spacing between operators. We show that IHF binds between these operators, and may permit looping of the promoter, allowing interaction of NadR at operators located distally or overlapping the promoter. The 4-hydroxyphenylacetic acid, a metabolite of aromatic amino acid catabolism that is secreted in saliva, induces NadA expression by inhibiting the DNA binding activity of the repressor. When induced, only minor differences are evident between NadR-independent transcription levels of promoter phase variants and are likely due to differential RNA polymerase contacts leading to altered promoter activity. Our results suggest that NadA expression is under both stochastic and tight environmental-sensing regulatory control, both mediated by the NadR repressor, and may be induced during colonization of the oropharynx where it plays a major role in the successful adhesion and invasion of the mucosa. Hence, simple sequence repeats in promoter regions may be a strategy used by host-adapted bacterial pathogens to randomly switch between expression states that may nonetheless still be induced by appropriate niche-specific signals

Tratamento cirúrgico da otite média com efusão: tubo de ventilação versus aplicação tópica de mitomicina C Surgical treatment of otitis media with effusion: ventilation tube versus topical application of mitomycin C

O uso do tubo de ventilação (TV) da orelha média, tratamento cirúrgico eleito da otite média com efusão (OME), não é isento de complicações, promovendo ainda limitação social pela necessidade de abandono dos banhos de imersão. A mitomicina C (MMC) é um antineoblástico, cuja aplicação tópica retarda a fibrose e previne a estenose cicatricial. Em cobaias, retardou o fechamento de timpanotomias, permitindo maior tempo de aeração da orelha média, à semelhança dos tubos de ventilação. FORMA DE ESTUDO: Clínico prospectivo. OBJETIVO: Comparar a eficácia entre timpanotomia, aspirado da efusão e inserção de tubo de ventilação (grupo TV) versus timpanotomia, aspirado da efusão e aplicação tópica de mitomicina C (grupo MMC). Comparar o tempo de manutenção da timpanotomia e a incidência de complicações nos dois grupos. RESULTADOS: O grupo MMC apresentou eficácia significativamente menor (52% versus 80%) que o grupo TV (p= 0,34). A presença de timpanometria tipo "B" e a ausência de comprometimento do óstio faríngeo tubário pelo tecido adenóide no pré-operatório representaram fatores de mau prognóstico. A aplicação tópica de MMC nas bordas da timpanotomia proporcionou um tempo de abertura da membrana timpânica por duas a três semanas. No grupo TV, a otorréia foi observada em 13,3% dos pacientes. No grupo MMC, apesar da menor eficácia, nenhum paciente apresentou complicações nem sofreu prolongada proibição dos banhos de imersão. CONCLUSÃO: Apesar de concluirmos que o TV apresenta maior eficácia, novos estudos utilizando maior concentração, maior tempo de aplicação ou o uso seriado de MMC no tratamento da otite média com efusão devem ser realizados.<br>The insertion of the ventilation tube (VT), which is the surgical treatment for otitis media with effusion (OME), is not free from complications and also limits social life because of the need of abandoning immersion baths. Mitomycin C is an antineoblastic that delays fibrosis and avoids stenosis in scars by its topical use. It permitted a longer ventilation of the middle ear in guinea pigs by delaying tympanostomies closure similarly to the ventilation tubes. STUDY DESIGN: Prospective clinical trial. AIM: Observe and compare the efficacy of tympanostomy, effusion suction and insertion of the ventilation tube (VT group) versus results of tympanostomy, effusion suction and topic application of mitomycin C(MMC group), and also the duration of tympanotomy and incidence of complications in both groups. RESULTS: MMC group showed a significant lower efficacy (52% versus 80%) than that of VT group (p=0,34). The occurrence of type B curve in the tympanometry and tube pharyngeal ostium free from adenoid tissue in the preoperative period represent poor prognosis factors. The topic application of mitomycin on the tympanostomy permitted a patency period of two to three weeks. On the VT group, otorrhea was observed in 13,3 % of the patients. On the MMC group, despite its smaller efficacy, there were no complications or need of missing immersion baths. CONCLUSION: We concluded that VT showed better efficacy than mitomycin on this trial. However more study is needed specially focusing on higher mitomycin C concentrations, longer periods of application or its serial use, for the treatment of otitis media with effusion