Evidence suggesting that di-n-butyl phthalate has anti-androgenic effects in fish

This article is the pre-print version of the full and final published article.Phthalate ester plasticizers are anti-androgenic in mammals. High doses of certain phthalates consistently interfere with the normal development of male offspring exposed in utero, causing disrupted sperm production, abnormal development of the genitalia, and in some cases infertility. In the environment, phthalates are considered ubiquitous and are commonly measured in aquatic ecosystems at low ng to mu g per litre concentrations. Given the similarity between mammalian and teleost endocrine systems, phthalate esters may be able to cause anti-androgenic endocrine disruption in fish in the wild. In the present study, adult male three-spined sticklebacks (Gasterosteus aculetaus) (n = 8) were exposed to di-n-butyl phthalate (DBP) (0, 15, and 35 mu g DBP/L) for 22 d and analyzed for changes in nesting behavior, plasma androgen concentrations, spiggin concentrations, and steroidogenic gene expression. Plasma testosterone concentrations were significantly higher in males from the 35 mu g DBP/L group compared with the solvent control, whereas plasma 11-ketotestosterone concentrations were not significantly affected. Expression of steroid acute regulatory protein and 3 beta-hydroxysteroid dehydrogenase remained unchanged. Spiggin concentrations were significantly lower in the males exposed to 35 mu g DBP/L. Nest building appeared to be slower in some males exposed to DBP, but this was not statistically significant. These results suggest that DBP has anti-androgenic effects in fish. However, further research is required to firmly establish the consequences of chronic DBP exposure in fish

SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells

The mammalian Cdkn2a (Ink4a-Arf) locus encodes two tumor suppressor proteins (p16Ink4a and p19Arf) that respectively enforce the anti-proliferative functions of the retinoblastoma protein (Rb) and the p53 transcription factor in response to oncogenic stress. Although p19Arf is not normally detected in tissues of young adult mice, a notable exception occurs in the male germ line, where Arf is expressed in spermatogonia, but not in meiotic spermatocytes arising from them. Unlike other contexts in which the induction of Arf potently inhibits cell proliferation, expression of p19Arf in spermatogonia does not interfere with mitotic cell division. Instead, inactivation of Arf triggers germ cell-autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production. Arf deficiency also causes premature, elevated, and persistent accumulation of the phosphorylated histone variant H2AX, reduces numbers of chromosome-associated complexes of Rad51 and Dmc1 recombinases during meiotic prophase, and yields incompletely synapsed autosomes during pachynema. Inactivation of Ink4a increases the fraction of spermatogonia in S-phase and restores sperm numbers in Ink4a-Arf doubly deficient mice but does not abrogate γ-H2AX accumulation in spermatocytes or p53-dependent apoptosis resulting from Arf inactivation. Thus, as opposed to its canonical role as a tumor suppressor in inducing p53-dependent senescence or apoptosis, Arf expression in spermatogonia instead initiates a salutary feed-forward program that prevents p53-dependent apoptosis, contributing to the survival of meiotic male germ cells

Mesalazine: A Novel Etiology For Drug-Induced Urinary Calculi

We report the case of a 23-year-old woman treated by mesalazine for ulcerative colitis and who subsequently presented recurrent renal colic due to mesalazine urinary stones. This is the second case described in the literature.Mesalazine stones are soft, friable and have an orange-beige color. They are not visible on non-contrast computed tomography (CT). Their diagnosis is based on morpho-constitutional analysis and CT-urography. Patients treatedby mesalazine who present renal colic should undergo CT-urography in order to make the diagnosis

Hormone-Induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells

Cholesterol is the sole precursor of steroid hormones in the body. The import of cholesterol to the inner mitochondrial membrane, the rate-limiting step in steroid biosynthesis, relies on the formation of a protein complex that assembles at the outer mitochondrial membrane called the transduceosome. The transduceosome contains several mitochondrial and cytosolic components, including the steroidogenic acute regulatory protein (STAR). Human chorionic gonadotropin (hCG) induces de novo synthesis of STAR, a process shown to parallel maximal steroid production. In the hCG-dependent steroidogenic MA-10 mouse Leydig cell line, the 14-3-3γ protein was identified in native mitochondrial complexes by mass spectrometry and immunoblotting, and its levels increased in response to hCG treatment. The 14-3-3 proteins bind and regulate the activity of many proteins, acting via target protein activation, modification and localization. In MA-10 cells, cAMP induces 14-3-3γ expression parallel to STAR expression. Silencing of 14-3-3γ expression potentiates hormone-induced steroidogenesis. Binding motifs of 14-3-3γ were identified in components of the transduceosome, including STAR. Immunoprecipitation studies demonstrate a hormone-dependent interaction between 14-3-3γ and STAR that coincides with reduced 14-3-3γ homodimerization. The binding site of 14-3-3γ on STAR was identified to be Ser-194 in the STAR-related sterol binding lipid transfer (START) domain, the site phosphorylated in response to hCG. Taken together, these results demonstrate that 14-3-3γ negatively regulates steroidogenesis by binding to Ser-194 of STAR, thus keeping STAR in an unfolded state, unable to induce maximal steroidogenesis. Over time 14-3-3γ homodimerizes and dissociates from STAR, allowing this protein to induce maximal mitochondrial steroid formation

Antibiotic therapy impact on intravesical BCG therapy efficacy for high-risk localized bladder cancer treatment

Intravesical Bacillus Calmettes-Guerin (BCG) instillations is the gold standard adjuvant treatment for high and very high-risk non-muscle-invasive bladder cancer (NMIBC). Antibiotics may be required to treat asymptomatic bacteriuria before instillations or to prevent side effects. By modifying the bladder microbiota and through its bactericidal action, it could modify the efficacy of BCG. This study evaluates the impact of antibiotics received during BCG-induction treatment on the oncological outcomes for high and very high risk NMIBC. We retrospectively included all patients who received a full induction regimen of BCG therapy between January 2017 and June 2022. Clinical and tumor characteristics as well as tolerability were collected. Recurrence-free survival (RFS) and progression-free survival (PFS) were compared according to the prescription of antibiotics, its type and duration. A total of 126 patients were included, 86.5% of the tumors were high risk and 13.5% very high risk. The median follow-up was 31 months (7-60). 36% of the patients received antibiotics during BCG-induction treatment (among which 44% received fluoroquinolones). 21.4% of patients had tumor recurrence. There was no difference in RFS (p=0.902) or PFS (p=0.88) according to the duration or the type of antibiotics received. The use of a prolonged antibiotic treatment (> 7 days) significantly increased the duration of the BCG-induction treatment from 35 to 41,5 days (p=0,049) and the median number of delayed treatments by 1,5 [0-4]. Neither the use of antibiotics nor their duration modified the risk of recurrence or the intensity of side effects in multivariate analysis. Antibiotics received during BCG-induction immunotherapy did not influence oncological short-term outcomes or intensity of side effects

Évaluation du drainage par sonde double J après urétéroscopie pour maladie lithiasique

Objectives During ureteroscopy for urolithiasis, postoperative ureteral drainage with double J stent is frequently used. It may reduce acute postoperative pain and late ureteral stenosis. Double J stent can have negative impact on life quality. After uncomplicated intervention, double J stent is not mandatory. Objective of our study was to evaluate pain and complications after ureteroscopy with or without stent. Methods We retrospectively analyzed ureteroscopy performed between May 2014 and January 2017. Interventions were compared regarding ureteral drainage with double J stent or not. Our primary outcome was early postoperative pain evaluated with an oral pain scale form 1 to 10 on day one after intervention. Clinical characteristics, per- and postoperative data were collected. We also looked for risks factors of complications. Results Three hundred and sixty-six interventions were included, 259 (70.8%) with and 107 (29.2%) without double J stent. Stone burden was higher in stented group (18.3 vs 9.4 mm, P < 0.0001). Patients without postoperative stents had more ureteral preparation with double J stent (78.5% vs 62.5%, P = 0.0032) and had more ambulatory interventions (75.7% vs 52.5%, P < 0.0001). Postoperative pain was not different (22% vs 17.75%, P = 0.398). Complication rate was similar (29% vs 20.5%, P = 0.1181), so was rehospitalization rate (0.8% vs 0.9%, P = 1). In multivariate analysis, complications factors were unprepared ureter, experienced surgeons and access sheath. Conclusion Not stenting after ureteroscopy do not increase pain or complications. Stenting should not be used after uncomplicated interventions for centimetric stones

Laparoscopic Partial Nephrectomy After Selective Embolization and Robot-Assisted Partial Nephrectomy: A Comparison of Short-Term Oncological and Functional Outcomes

BACKGROUND: Partial nephrectomy (PN) is the standard treatment for localized renal tumors. Laparoscopic PN (LPN) after selective embolization of tumor (LPNE) in a hybrid operating room has been developed to make LPN easier and safer. The aim of this study was to compare outcomes of LPNE and robot-assisted PN (RAPN). PATIENTS AND METHODS: All patients who underwent an LPNE at Angers University Hospital between May 2015 and April 2017, and a RAPN at Diaconesses Croix Saint Simon hospital between October 2014 and April 2017 were prospectively included. The functional outcomes were evaluated using the change of estimated glomerular filtration rate (eGFR) at 1 month, and the oncological outcomes were evaluated using the positive surgical margin (PSM) rate. RESULTS: Fifty-seven patients underwent LPNE and 48 underwent RAPN. There was no difference between oncological and functional outcomes, with 2 PSM (4.4%) in the LPNE group and 4 PSM (10.3%) in the RAPN group (P = .32), and a mean change in eGFR at 1 month of -5.5% for LPNE and -8.3% for RAPN (P = .17). The mean surgical time was shorter in the LPNE group (150 vs. 195 minutes; P < .001), and mean estimated blood loss was less in the LPNE group (185 vs. 345 mL; P = .04). CONCLUSION: The short-term oncological and functional outcomes for LPNE were comparable with those for RAPN. A longer follow-up and a larger cohort of patients would be necessary to verify the benefits of LPNE, which appears to be a very interesting alternative to RAPN

Successful medical treatment of glans ischemia after voluntary buprenorphine injection

INTRODUCTION: The diverted use of synthetic opioid buprenorphine by drug addicts can be responsible for serious ischemic and infectious complications, particularly in the case of intravenous injection. AIM: We present a case of serious glans ischemia after buprenorphine injection directly into the deep dorsal vein of the penis. Analysis using new medical imaging techniques and treatments is detailed below. METHODS: A 26-year-old male drug addict presented with glans pain 4 days after self-injection of buprenorphine into the deep dorsal vein of the penis. The patient was apyretic and presented a urethral discharge. His glans was blue without discoloration on digital pressure. Additionally, his biologic and serologic tests were normal while bacteriology showed the presence of Enterobacter cloacae urethritis. RESULTS: After 48 hours of intravenous antibiotic treatment without improvement, a specific medical treatment using enoxaparin and ilomedin was initiated, with the assumption that there was an ischemic complication. Laser speckle contrast imaging allowed confirmation of the presence of distal penis ischemia and provided an accurate mapping of the ischemic zone. A 28-day treatment combining antibiotics, subcutaneous heparin at curative dose, antiplatelet drug, ilomedin, and hyperbaric oxygen therapy resulted in clinical improvement of the lesions with no functional complications. CONCLUSIONS: To date, no consensus exists on the proper diagnostic and treatment approach to severe glans ischemia due to buprenorphine injection into the deep dorsal vein of the penis. The results of laser speckle contrast imaging were of real interest during the process of diagnosis. In addition, the combination of ilomedin with hyperbaric oxygen therapy and anticoagulant and antiplatelet drugs appeared to be an effective therapy

Double-J ureteral stent under local anesthesia for women

INTRODUCTION: Ureteral stent placement is a key urologic procedure used to manage ureteral obstructions. It is usually performed under general anesthesia (GA) with its inherent risks. The objective was to evaluate safety, feasibility and tolerance of ureteral stent placement under local anesthesia (LA) in women. MATERIALS AND METHODS: From January 2010 to January 2013, we prospectively and consecutively reviewed all female patients who had an urgent retrograde ureteral stent placement under LA. Only primary stent placements were included in the study. Pain was assessed after surgery by Visual Analog Scale (VAS) and pain and comfort assessment during stent placement were reported. We compared outcomes and tolerance with patients under general anesthesia (GA) matched by age and operatives indications during the same period. RESULTS: We included 36 patients (18 under LA and 18 under GA) with a mean age of 59.4 +/- 22.4 years. The mean operative time was 24.4 +/- 12.9 min and 18.8 +/- 6.5 min in LA group and GA group (p = 0.110), respectively. One patient needed GA due to a poor tolerance. The mean perioperative VAS scores under LA and GA were 5.89 +/-2.95 and 2.06 +/- 2.67 (p < 0.0001), respectively. There were no intraoperative complications in either group. The procedure was painful for 16 (88.8%) patients from the LA group and 9 (50%) patients would not accept to undergo this intervention under LA again. CONCLUSION: Ureteral stent placement under LA in women can be performed safely and effectively. However, this procedure is painful and should be proposed only to selected cases