Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.

The post-transcriptional modifier tRNA-(N1G37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question.

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis.

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage Plasmodium falciparum and Cryptosporidium parvum in cell-culture studies. Target deconvolution in P. falciparum has shown that cladosporin inhibits lysyl-tRNA synthetase (PfKRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both PfKRS1 and C. parvum KRS (CpKRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED90 = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between PfKRS1 and CpKRS. This series of compounds inhibit CpKRS and C. parvum and Cryptosporidium hominis in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for PfKRS1 and CpKRS vs. (human) HsKRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis.

Repeat Prostatic Artery Embolization for Patients with Benign Prostatic Hyperplasia.

PURPOSE: To evaluate the safety and efficacy of repeat prostatic artery (PA) embolization (PAE) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A single-center retrospective study was conducted from 2009 to 2018 in 108 patients with symptomatic BPH treated with repeat PAE: group A (n = 39; 36.1%) were patients who never showed a response to PAE, and group B (n = 69; 63.9%) were patients who had clinical improvement in the first 6 months following PAE but relapsing symptoms afterward. The main patterns of revascularization were 75% from the previously embolized PA and 25% from collateral vessels (superior vesical, posterior-lateral PA, penile branches). Technical outcomes and adverse events were registered. International Prostate Symptom Score (IPSS), quality of life (QOL), and clinical success were compared between groups. RESULTS: Median follow-up was 18 months (range, 1-36 mo); median interval between PAE and repeat PAE was 420 days (range, 77-2,240 d). Mean procedural time was significantly longer for repeat PAE vs initial PAE (81.1 min vs 67.4 min; P = .0007). There were no major complications and no urinary incontinence. Mean IPSS/QOL improvements were greater in group B vs group A: 9.51 vs 6.13 and 1.30 vs 0.56, respectively (P < .001). The cumulative probability of clinical success after repeat PAE was higher in group B than in group A (P = .0001): 84.1% vs 46.2% at 1 month, 56.7% vs 28.2% at 12 months, and 51.9% vs 16.9% at 24-36 months. CONCLUSIONS: Repeat PAE is safe and effective for recurrence of lower urinary tract symptoms caused by BPH but has limited impact in patients who did not show a response to initial PAE.

Prostatic Artery Embolization for Benign Prostatic Hyperplasia: Prospective Randomized Trial of 100-300 µm versus 300-500 µm versus 100- to 300-µm + 300- to 500-µm Embospheres.

PURPOSE: This study compared the safety and efficacy of prostatic arterial embolization (PAE) with that of trisacryl gelatin microspheres of different sizes for treatment of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: This study consisted of a single-center, randomized controlled clinical trial in 138 patients who underwent PAE for BPH between July 2015 and December 2016. Patients were randomized to PAE using microspheres of different sizes: group A patients were treated with microspheres 100-300 µm, group B with 300-500 µm, and group C with 100-300 µm followed by 300-500 µm. All patients were evaluated before and at 1, 3, 6, 12, and 18 months after PAE. Baseline data were comparable across the 3 groups, using the following mean International Prostate Symptom Score/quality of life (IPSS/QoL); prostate volume (PV) scores, respectively: 23.0/4.14; 87.9 cm3 (group A); 23.0/4.09; 89.0 cm3 (group B); and 24.2/4.29; 81.0 cm3 (group C) (P > 0.05). RESULTS: Mean IPSS/QoL scores; PV after PAE were: 9.98/2.49; 65.1 cm3 (group A); 8.24/2.26; 63.1 cm3 (group B); and 10.1/2.69; 53.1 cm3 (group C) (P = 0.23; P = 0.39; P = 0.24). There were 26 clinical failures. The cumulative probabilities of clinical success at 18 months were 76.7% in group A, 82.6% in group B, and 83.3% in group C (P = 0.68). Nontarget embolization was prevented in 6 patients by coil embolization. All adverse events were mild and self-limited with rates of 86.0% in group A (37 of 43); 41.3% in group B (19 of 46); and 58.3% in group C (28 of 48) (P < 0.001). Dysuria was the most frequent adverse event (28 of 137 [20.4%]). CONCLUSIONS: PAE outcomes were not significantly different among microspheres of different sizes. The use of 100- to 300-µm microspheres was associated with an increased risk of minor adverse events.

Randomized Clinical Trial of Balloon Occlusion versus Conventional Microcatheter Prostatic Artery Embolization for Benign Prostatic Hyperplasia.

PURPOSE: To compare balloon occlusion prostatic artery embolization (bPAE) with conventional microcatheter PAE (cPAE). MATERIALS AND METHODS: In this single-center trial, between November 2017 and November 2018, 89 patients with symptomatic benign prostatic hyperplasia were randomly assigned to cPAE (n = 43) or bPAE (n = 46). All patients received embolization with 300-500 µm Embosphere microspheres and were evaluated before and 1 and 6 months after PAE. Primary outcome measure was change from baseline in International Prostate Symptom Score (IPSS). Student t test was used for between-group comparisons of change from baseline, and paired t test was used for within-group comparisons. RESULTS: At baseline, groups were identical (P > .05). Unilateral PAE was performed in 4 patients receiving cPAE and 3 patients receiving bPAE (9.30% and 6.52%, P = .708). Procedural and fluoroscopy times, dose area product, air kerma, embolic volume, and mean prostate-specific antigen (PSA) 24 hours after PAE did not differ between groups (P > .05). Coils were used in 6 patients receiving cPAE and 4 patients receiving bPAE (14.0% and 8.70%, P = .51). Assessments at 6 months after PAE showed mean IPSS reduction was 7.58 ± 6.88 after cPAE and 8.30 ± 8.12 after bPAE (P = .65); mean prostate volume reduction was 21.9 cm3 ± 51.6 (18.2%) after cPAE and 6.15 cm3 ± 14.6 (7.3%) after bPAE (P = .05); mean PSA reduction was 0.9 ng/mL ± 2.22 after cPAE and 0.22 ng/mL ± 1.65 after bPAE (P = .10). Penile skin lesions (n = 3) and rectal bleeding (n = 2) were documented only in patients receiving cPAE (11.9%, P = .01). No major adverse events occurred. CONCLUSIONS: bPAE is as effective as cPAE in treating benign prostatic hyperplasia with a potential to reduce nontarget embolization.

Safety and Efficacy of Prostatic Artery Chemoembolization for Prostate Cancer-Initial Experience.

PURPOSE: To evaluate outcome of prostatic artery chemoembolization for patients with prostate cancer (PCa). MATERIALS AND METHODS: This single-center prospective cohort study was conducted between August 2013 and July 2016 in 20 patients with PCa who underwent chemoembolization. Mean patient age was 67.5 years ± 6.4. Gleason score was 6-10, and staging was T2N0M0. Fifteen patients refused prostatectomy and 5 wanted to stop hormonal therapy because of side effects. For chemoembolization, Chelidonium majus mother tincture 1 mL was slowly injected into the prostatic arteries. Docetaxel 1 mL and 150-300 µm Embosphere (Merit Medical Systems, Inc, South Jordan, Utah) microspheres 0.5 mL were thoroughly mixed, and the mixture was slowly injected by the same route. Embolization of prostatic arteries was finished with 150-300 µm Embosphere microspheres. Technical success was defined as bilateral prostatic artery embolization. Biochemical failure was defined as prostate specific antigen (PSA) decrease to < 2 ng/mL followed by recurrence when PSA increased to > 2 ng/mL within 1 month after success. RESULTS: Technical success was 80.0% (16/20 patients). Biochemical failure was 18.7% (3/16 patients). There was 1 short-term biochemical recurrence at 4 months and 2 midterm recurrences (12-18 months). Biochemical success at 12-18 months was 62.5% (10/16 patients). Adverse events (31.3%) included a small area (2 cm2) of bladder wall ischemia, which was removed by surgery (n = 1); transient acute urinary retention (n = 1) and urinary urgency (n = 1) for 1 week; sexual dysfunction (n = 2), which completely recovered after 10 and 12 months, respectively. CONCLUSIONS: Prostatic artery chemoembolization allowed a biochemical response in patients with localized PCa and is a promising treatment.

Spontaneous Pregnancy with a Live Birth after Conventional and Partial Uterine Fibroid Embolization.

Purpose To determine pregnancy rates after conventional and partial uterine fibroid embolization (UFE). Materials and Methods The study received institutional review board approval and all patients gave written informed consent. A retrospective analysis of data collected prospectively was performed between June 2004 and June 2014 in a cohort of 359 women (mean age, 35.9 years ± 4.8) with uterine fibroids and/or adenomyosis who were unable to conceive. The median follow-up period was 69 months (range, 6-126 months). Under local anesthesia, both uterine arteries were embolized. In 160 patients, partial embolization was intentionally performed to preserve fertility, which may be decreased after conventional UFE. In partial UFE, only the small arterial vessels to the fibroids were embolized, leaving the large vessels of the fibroids patent. The Kaplan-Meier method and Cox regression were used for the statistical analysis. Results During follow-up, 149 women became pregnant, 131 women had live births, and 16 women had several pregnancies, resulting in a total of 150 live newborns. It was the first pregnancy for 85.5% (112 of 131) of women. Spontaneous pregnancy rates at 1 year and 2 years after UFE were 29.5% and 40.1%, respectively. The probability of successful pregnancy with live birth at 1 year and 2 years was 24.4% and 36.7%, respectively. Clinical success for fibroid-related symptoms was 78.6% (282 of 359). A dominant submucosal fibroid and ischemia greater than or equal to 90% had greater likelihood of spontaneous pregnancy. Complication rates in patients treated with partial UFE (14.6%) were not greater than rates in patients treated with conventional UFE (23.1%, P = .04). Conclusion Conventional and partial UFE may be safe and effective outpatient procedures for women with uterine fibroids who want to conceive. © RSNA, 2017.

Predictors of Clinical Outcome after Prostate Artery Embolization with Spherical and Nonspherical Polyvinyl Alcohol Particles in Patients with Benign Prostatic Hyperplasia.

Purpose To assess predictors of outcome after prostate artery embolization (PAE) for benign prostatic hyperplasia with spherical particle polyvinyl alcohol (sPVA) and compare outcomes with the use of nonspherical particle polyvinyl alcohol (nsPVA). Materials and Methods This was a single-center retrospective institutional review board-approved study conducted from 2009 to 2015 in patients undergoing PAE with sPVA (n = 186; mean age ± standard deviation, 65.5 years ± 7.7) and nsPVA (n = 300; mean age, 65.3 years ± 7.6). The two cohorts were compared and analyzed for predictors of outcome with a Cox proportional hazards model and linear regression. Post-PAE prostate ischemia was measured with contrast material-enhanced magnetic resonance (MR) imaging in 23 patients with nsPVA and 25 patients with sPVA. The 24-hour post-PAE prostate-specific antigen (PSA) level was registered in 133 patients with sPVA. Prognostic values of MR imaging and PSA levels 24 hours after PAE were assessed with Cox and random-effects regressions. Results Predictors of clinical failure were older age (age over 65 years, P = .002), unilateral procedure (P = .002), and higher baseline International Prostate Symptom Score (IPSS, P = .033). Adjusted hazard ratio for clinical failure of sPVA was 1.273 (P = .16). Acute urinary retention was a predictor of lower IPSS after PAE (P = .002). The mean proportion of prostate ischemia was 11% with sPVA and 10% with nsPVA (P = .65). Lower IPSS after PAE was associated with a higher proportion of prostate ischemia (P = .009). Patients with a PSA level of at least 75 ng/mL (75 µg/L) 24 hours after PAE had a greater decrease in IPSS (P = .01). Prostate ischemic volume and PSA level 24 hours after PAE were correlated (Pearson r = 0.64, P = .014). Conclusion Clinical outcome was similar after PAE with sPVA and nsPVA. Younger age (up to 65 years), bilateral PAE, lower baseline IPSS, and acute urinary retention were predictors of better clinical outcome. The PSA level 24 hours after PAE correlated with prostate ischemia, and both correlated with clinical outcome. (©) RSNA, 2016.

Meta-Analysis of Prostatic Artery Embolization for Benign Prostatic Hyperplasia.

PURPOSE: To perform meta-analysis of available data on prostatic artery embolization (PAE). MATERIALS AND METHODS: Meta-analysis was conducted on articles published between November 2009 and December 2015. Peer-reviewed studies with > 5 patients and standard deviations and/or individual-level data on one or more of the following outcomes were included: prostate volume (PV), peak flow rate (Qmax), postvoid residual (PVR), International Prostate Symptom Score (IPSS), quality of life (QOL) score, International Index of Erectile Function (IIEF) score, and prostate-specific antigen (PSA) level. A random-effects meta-analysis was performed on the outcomes at 1, 3, 6, and 12 months after PAE compared with baseline values, with a P < .05 decision rule as the null hypothesis rejection criterion. RESULTS: Nineteen of 268 studies were included in data collection, with 6 included in the meta-analysis. At 12 months, PV decreased by 31.31 cm3 (P < .001), PSA remained unchanged (P = .248), PVR decreased by 85.54 mL (P < .001), Qmax increased by 5.39 mL/s (P < .001), IPSS improved by 20.39 points (P < .001), QOL score improved by -2.49 points (P < .001), and IIEF was unchanged (P = 1.0). There were a total of 218 adverse events (AEs) among 662 patients (32.93%), with 216 being Society of Interventional Radiology class A/B (99%). The most common complications were rectalgia/dysuria (n = 60; 9.0%) and acute urinary retention (n = 52; 7.8%). No class D/E complications were reported. CONCLUSIONS: PAE provided improvement in Qmax, PVR, IPSS, and QOL endpoints at 12 months, with a low incidence of serious AEs (0.3%), although minor AEs were common (32.93%). There was no adverse effect on erectile function.

Medium- and Long-Term Outcome of Prostate Artery Embolization for Patients with Benign Prostatic Hyperplasia: Results in 630 Patients.

PURPOSE: To confirm that prostatic artery embolization (PAE) has a positive medium- and long-term effect in symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Between March 2009 and October 2014, 630 consecutive patients with BPH and moderate-to-severe lower urinary tract symptoms refractory to medical therapy for at least 6 months or who refused any medical therapy underwent PAE. Outcome parameters were evaluated at baseline; 1, 3, and 6 months; every 6 months between 1 and 3 years; and yearly thereafter up to 6.5 years. RESULTS: Mean patient age was 65.1 years ± 8.0 (range, 40-89 y). There were 12 (1.9%) technical failures. Bilateral PAE was performed in 572 (92.6%) patients and unilateral PAE was performed in 46 (7.4%) patients. The cumulative clinical success rates at medium- and long-term follow-up were 81.9% (95% confidence interval [CI], 78.3%-84.9%) and 76.3% (95% CI, 68.6%-82.4%). There was a statistically significant (P < .0001) change from baseline to last observed value in all clinical parameters: International Prostate Symptom Score (IPSS), quality-of-life (QOL), prostate volume, prostate-specific antigen, urinary maximal flow rate, postvoid residual, and International Index of Erectile Function. There were 2 major complications without sequelae. CONCLUSIONS: PAE had a positive effect on IPSS, QOL, and all objective outcomes in symptomatic BPH. The medium- (1-3 y) and long-term (> 3-6.5 y) clinical success rates were 81.9% and 76.3%, with no urinary incontinence or sexual dysfunction reported.

Prostate Embolization as an Alternative to Open Surgery in Patients with Large Prostate and Moderate to Severe Lower Urinary Tract Symptoms.

PURPOSE: To evaluate efficacy of prostate artery embolization (PAE) in patients with benign prostatic hyperplasia (BPH), prostate volume (PV) > 100 cm(3). MATERIALS AND METHODS: This was a single-center retrospective cohort study. Between March 2009 and September 2014, PAE was performed in patients with a diagnosis of BPH, PV > 100 cm(3), and moderate to severe lower urinary tract symptoms (LUTS) refractory to medical treatment for at least 6 months or who had acute urinary retention. Success was defined as improved symptoms (International Prostate Symptom Score ≤ 15 and decrease of ≥ 25% from baseline score), improved quality of life (measured as score of ≤ 3 points or decrease of ≥ 1 point from baseline), and no need for additional treatment. RESULTS: PAE was performed in 152 patients 48-87 years old (mean ± SD 67.4 y ± 7.5) with mean PV of 134.2 cm(3) ± 41.8 (range, 101-383 cm(3)). PAE was technically successful in 149 patients (98.0%). Symptomatic control was achieved for a median of 18 months ± 15.5 (range, 3-66 mo). There were 33 clinical failures (23.6%); 23 occurred in the short-term (≤ 6 mo), and 10 occurred in the medium-term (6-24 mo); there were no long-term failures (> 36 mo). Cumulative clinical success rates were 90%, 87.9%, 83.5%, 81.1%, and 77.8% at 1, 3, 6, 12, and 18 months and 72.4% thereafter to 66 months (5.5 y). CONCLUSIONS: PAE provides sustained short-, medium-, and long-term control for LUTS in patients with BPH and PV > 100 cm(3).

The role of accessory obturator arteries in prostatic arterial embolization.

In 9 of 491 patients (1.8%) who underwent prostatic arterial embolization (PAE) for benign prostatic hyperplasia from March 2009-November 2013, prostatic arteries arose from the external iliac artery via an accessory obturator artery (AOA). Computed tomography angiography performed before the procedure identified the variant and allowed planning before the procedure. The nine AOAs were catheterized from a contralateral femoral approach. Bilateral PAE was technically successful in the nine patients. There was a mean decrease in international prostate symptom score of 6.5 points and a mean prostate volume reduction of 15.1% (mean follow-up, 4.8 mo) in the nine patients.

Angiographic anatomy of the male pelvic arteries.

OBJECTIVE: The purpose of this article is to review the CT angiographic and digital subtraction angiographic features of the male pelvic arteries. CONCLUSION: An increasing number of vascular procedures are being performed in the male pelvis that require profound knowledge of the angiographic anatomy of the internal iliac artery (IIA). The major branches of the IIA in men can be used to classify the branching patterns. After the larger IIA branches are identified, identification of the smaller arteries or relevant anatomic variants becomes easier.

Leiomyoma and the importance of genetic variation on genes related to the vasculature system - CßS, MTHFR, NOS3, CYBA, and ACE1.

OBJECTIVE: The link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CßS (844ins68), MTHFR (677C > T), NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes. METHODS: DNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher's exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05. RESULTS: Results revealed that CßS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114-2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416-0.824] and p = 0.003, OR = 0.527 [0.346-0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411-0.992]) genes are associated with leiomyoma onset. NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CßS; p = 0.003), 4b4b (NOS3; p = 0.006, OR = 2.050 [1.223-3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438-3.880]) were shown to be associated with the disease, while 4a presence (NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214-0.930]). CONCLUSIONS: We conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.

Prostatic arterial embolization for benign prostatic hyperplasia: short- and intermediate-term results.

PURPOSE: To evaluate the safety, morbidity, and short- and intermediate-term results of prostatic arterial embolization (PAE) for benign prostatic hyperplasia (BPH) after failure of medical treatment. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and informed consent was obtained from all participants. Men older than 50 years with a diagnosis of BPH and moderate-to-severe lower urinary tract symptoms that were refractory to medical treatment for 6 months were eligible. PAE with nonspherical 80-180-µm (mean, 100-µm) and 180-300-µm (mean, 200-µm) polyvinyl alcohol particles was performed by means of a single femoral approach in most cases. Effectiveness variables of International Prostate Symptom Score (IPSS), quality of life (QOL) score, peak urinary flow, postvoid residual volume, International Index Erectile Function (IIEF) score, prostate volume, and prostate-specific antigen level were assessed for up to 24 months after the procedure. Statistical analysis included the Kaplan-Meier method and random-effects generalized least squares regression with autoregressive disturbance. RESULTS: Eighty-nine consecutive patients (mean age, 74.1 years) were included. PAE was technically successful in 86 of the 89 patients (97%). Cumulative rates of clinical improvement in these patients were 78% in the 54 patients evaluated at 6 months and 76% in the 29 patients evaluated at 12 months. At 1-month follow-up, IPSS decreased by 10 points, QOL score decreased by 2 points, peak urinary flow increased by 38%, prostate volume decreased by 20%, postvoid residual volume decreased by 30 mL, and IIEF score increased by 0.5 point (all differences were significant at P < .01). These changes were sustained throughout the observation period. There was one major complication: Intraluminal necrotic tissue attached to the bladder, which was removed with simple surgery and did not necessitate wall reconstruction. CONCLUSION: PAE is a safe and effective procedure, with low morbidity, no sexual dysfunction, and good short- and intermediate-term symptomatic control associated with prostate volume reduction.

Embolisation of prostatic arteries as treatment of moderate to severe lower urinary symptoms (LUTS) secondary to benign hyperplasia: results of short- and mid-term follow-up.

OBJECTIVES: To evaluate the short- and medium-term results of prostatic arterial embolisation (PAE) for benign prostatic hyperplasia (BPH). METHODS: This was a prospective non-randomised study including 255 patients diagnosed with BPH and moderate to severe lower urinary tract symptoms after failure of medical treatment for at least 6 months. The patients underwent PAE between March 2009 and April 2012. Technical success is when selective prostatic arterial embolisation is completed in at least one pelvic side. Clinical success was defined as improving symptoms and quality of life. Evaluation was performed before PAE and at 1, 3, 6 and every 6 months thereafter with the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), uroflowmetry, prostatic specific antigen (PSA) and volume. Non-spherical polyvinyl alcohol particles were used. RESULTS: PAE was technically successful in 250 patients (97.9 %). Mean follow-up, in 238 patients, was 10 months (range 1-36). Cumulative rates of clinical success were 81.9 %, 80.7 %, 77.9 %, 75.2 %, 72.0 %, 72.0 %, 72.0 % and 72.0 % at 1, 3, 6, 12, 18, 24, 30 and 36 months, respectively. There was one major complication. CONCLUSIONS: PAE is a procedure with good results for BPH patients with moderate to severe LUTS after failure of medical therapy. KEY POINTS: • Prostatic artery embolisation offers minimally invasive therapy for benign prostatic hyperplasia. • Prostatic artery embolisation is a challenging procedure because of vascular anatomical variations. • PAE is a promising new technique that has shown good results.

Does polyvinyl alcohol particle size change the outcome of prostatic arterial embolization for benign prostatic hyperplasia? Results from a single-center randomized prospective study.

PURPOSE: To evaluate whether different polyvinyl alcohol (PVA) particle sizes change the outcome of prostatic arterial embolization (PAE) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A randomized prospective study was undertaken in 80 patients (mean age, 63.9 y; range, 48-81 y) with symptomatic BPH undergoing PAE between May and December 2011. Forty patients underwent PAE with 100-µm (group A) and 200-µm PVA particles (group B). Visual analog scales were used to measure pain, and rates of adverse events were recorded. PAE outcomes were evaluated based on International Prostate Symptom Score (IPSS) and quality-of-life (QoL) questionnaires, prostate volume (PV), prostate-specific antigen (PSA) levels, and peak flow rate measurements at baseline and 6 months. RESULTS: No differences between groups regarding baseline data, procedural details, or adverse events were noted. Mean pain scores were as follows: during embolization, 3.2 ± 2.97 (group A) versus 2.93 ± 3.28 (group B); after embolization, 0.10 ± 0.50 (group A) versus 0 (group B; P = .20); and the week after PAE, 0.85 ± 1.65 (group A) versus 0.87 ± 1.35 (group B; P = .96). Patients in group B had greater decreases in IPSS (3.64 points; P = .052) and QoL (0.57 points; P = .07). Patients in group A had a greater decrease in PV (8.75 cm(3); P = .13) and PSA level (2.09 ng/mL; P < .001). CONCLUSIONS: No significant differences were found in pain scores and adverse events between groups. Whereas PSA level and PV showed greater reductions after PAE with 100-µm PVA particles, clinical outcome was better with 200-µm particles.

Middle rectal artery: myth or reality? Retrospective study with CT angiography and digital subtraction angiography.

This work aimed to study the prevalence and radiologic anatomy of the middle rectal artery (MRA) using computed tomographic angiography (CTA) and digital subtraction angiography (DSA). The retrospective study (October 2010-February 2012) focused in 167 male patients with prostate enlargement (mean age 64.7 years, range 47-81 years) who underwent selective pelvic arterial embolization for the relief of lower urinary tract symptoms. All patients underwent CTA previously to DSA to evaluate the vascular anatomy of the pelvis and to plan the treatment. MRAs were identified and classified according to their origin, trajectory, termination and relationship with surrounding arteries. We found MRAs in 60 (35.9 %) patients (23.9 % of pelvic sides, n = 80) and of those, 20 (12 %) had bilateral MRAs; 24 MRAs (30 %) were independent of neighbouring arteries and 56 MRAs (70 %) had common origins with prostatic arteries (prostato-rectal trunk). The most frequent MRA origin was the internal pudendal artery (60 %, n = 48), followed by the inferior gluteal artery (21.3 %, n = 17) and common gluteal-pudendal trunk (16.2 %, n = 13). In 2 patients the MRA originated from the obturator artery (2.5 %). Anastomoses to the superior rectal and inferior mesenteric arteries were found in 87.5 % of cases (n = 70). We concluded that MRAs are anatomical variants present in less than half of male patients; have variable origins and frequently share common origins with prostatic arteries. Their correct identification is likely to contribute to improve interventional radiology procedures and prostatic or rectal surgeries.

Genetic Contribution of the Adrenergic, Cholinergic, and Serotonergic Systems to Leiomyoma Development and Treatment.

The link between the autonomic nervous system and tumor biology is being unfold. We aim to study the contribution of genes of the adrenergic (ADBR2 - rs1042713, NM_000024.6:c.46G>A, NP_000015.2:p. Gly16Arg), cholinergic (CHRNA5 - rs16969968, NM_000745.3:c.1192G>A, NP_000736.2:p.Asp398Asn), and serotonergic systems (SLC6A4 - 5-HTTVNTR-intron2, HTR2A - rs6313, NM_000621.5:c.102C>T, NP_ 001365853 .1: p. Ser 34=) to gynecological tumorigenesis and their treatment by embolization. A total of 517 DNA samples from women were analyzed. Samples were genotyped by PCR, PCR-RFLP and EndPoint genotyping. Results show a statistically significant association between the AA genotype of the ADBR2 gene and GG genotype of the CHRNA5 gene with leiomyoma (OR = 2.311; p = 0.003 and OR = 2.165; p = 0.001, respectively), and the epistatic interaction between genotypes increases the risk (OR = 2.458; p= 0.043). The GG genotype (CHRNA5) shows a lower reduction of the volume of the main leiomyoma after treatment (p=0.015). Combination of the genotypes 12/12-AA (SLC6A4 - ADBR2) increases the risk to leiomyoma (OR = 2.540, p= 0.030). TT genotype of HTR2A gene in combination with any of the two risk genotypes (of ADBR2 or CHRNA5) increases substantially the risk (OR = 5.266, p = 0.006; OR = 6.364, p=0.007, respectively). We conclude that ADBR2 and CHRNA5 genes have a relevant role that is enhanced by the epistatic relationship with the genes HTR2A and SLC6A4. CHRNA5 gene may also be a modulator of the success of embolization. We confirm the contribution of the genetics of Autonomous Nervous System to tumor biology.

Mechanism of feedback allosteric inhibition of ATP phosphoribosyltransferase.

MtATP-phosphoribosyltransferase catalyzes the first and committed step in l-histidine biosynthesis in Mycobacterium tuberculosis and is therefore subjected to allosteric feedback regulation. Because of its essentiality, this enzyme is being studied as a potential target for novel anti-infectives. To understand the basis for its regulation, we characterized the allosteric inhibition using gel filtration, steady-state and pre-steady-state kinetics, and the pH dependence of inhibition and binding. Gel filtration experiments indicate that MtATP-phosphoribosyltransferase is a hexamer in solution, in the presence or absence of l-histidine. Steady-state kinetic studies demonstrate that l-histidine inhibition is uncompetitive versus ATP and noncompetitive versus PRPP. At pH values close to neutrality, a K(ii) value of 4 µM was obtained for l-histidine. Pre-steady-state kinetic experiments indicate that chemistry is not rate-limiting for the overall reaction and that l-histidine inhibition is caused by trapping the enzyme in an inactive conformation. The pH dependence of binding, obtained by nuclear magnetic resonance, indicates that l-histidine binds better as the neutral α-amino group. The pH dependence of inhibition (K(ii)), on the contrary, indicates that l-histidine better inhibits MtATP-phosphoribosytransferase with a neutral imidazole and an ionized α-amino group. These results are combined into a model that accounts for the allosteric inhibition of MtATP-phosphoribosyltransferase.