Enhance the Antimycobacterial Activity of Streptomycin with Ebselen as an Antibiotic Adjuvant Through Disrupting Redox Homeostasis.

Purpose: Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs. Methods: Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model. Results: The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity. Conclusion: The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.

Longitudinal association between the dynamic nature of depression with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH).

BACKGROUND: Depression is associated with an increased risk of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Whether the dynamic nature of depression affects the incidence of LUTS/BPH remains unknown. A four-year cohort study based on the China Health and Retirement Longitudinal Study (CHARLS) was conducted to assess their association. METHODS: This study included 3433 Chinese men from the CHARLS 2011, representative of > 95 million individuals. All eligible individuals underwent three assessments of LUTS/BPH and depression in 2011, 2013 and 2015. The dynamic nature of depression was classified as acute depression with remission, acute depression with recurrence, or chronic major depression. Weighted, generalized additive analyses with three binomial models were used to investigate the relationship between LUTS/BPH and the dynamic nature of depression. RESULTS: During the four-year follow-up, 11.5% (95% confidence interval [95% CI] = 9.5-13.3%) of Chinese men were diagnosed with newly incident LUTS/BPH. Meanwhile, there were 60.6% (95% CI = 58.5-62.7%) of the individuals without depression and 8.9% (95% CI = 7.9-10%) of the individuals with chronic major depression. A total of 25.1% (95% CI = 23.4-26.9%) and 5.4% (95% CI = 4.6-6.3%) of the individuals were categorized as acute depression with remission and recurrence. After weighted, adjusted all included confounding risk factors, chronic major depression (RR = 1.63, 95% CI = 1.14-2.33, P < 0.01) but not acute depression with remission (RR = 1.2, 95% CI = 0.92-1.56, P = 0.18) and recurrence (RR = 1.32, 95% CI = 0.82-2.10, P = 0.26) significantly increased the incidence of LUTS/BPH compared with no depression. The subgroup analysis showed that the above relationships appeared to be evident among Chinese men < 60 years. CONCLUSIONS: Our results suggest that the dynamic nature of depression has a different effect on the incidence of LUTS/BPH. The monitoring and treatment of depression are important in preventing LUTS/BPH.

Relationship of mTORC1 and ferroptosis in tumors.

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis.

BACKGROUND: The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. METHODS: Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. RESULTS: We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=-3.32, 95% CI (-4.57, -2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=-69.99, 95% CI (-91.05, -48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. CONCLUSIONS: This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions.

The Assessment on Synergistic Activity of Ebselen and Silver Ion Against Yersinia pseudotuberculosis.

Yersinia pseudotuberculosis is a foodborne zoonotic bacterium that is pathogenic to guinea pigs, rabbits, and mice. It also causes pseudotuberculosis in humans. However, it still lacked the scientific basis for control. Here, we found out that Ebselen (EbSe) exhibited synergistic antibacterial activity with silver nitrate (Ag+) against Y. pseudotuberculosis YpIII strain with high efficacy in vitro using UV-visible light absorption spectrum, 5,5'-dithiobis-(2-nitrobenzoic acid), laser scanning confocal microscope, flow cytometry, transmission electron microscopy and Western blotting assays. The depletion of total glutathione (GSH) amount and inhibition of thioredoxin reductase (TrxR) activity in thiol-dependent redox system revealed the destructiveness of EbSe-Ag+-caused intracellular oxidative stress. Furthermore, a YpIII-caused mice gastroenteritis model was constructed. EbSe-Ag+ significantly reduced bacterial loads with low toxicity. It also down-regulated the expression levels of interferon (IL)-1ß and tumor necrosis factor-α, up-regulated the expression level of IL-10 on-site. All the in vivo results demonstrated the antibacterial activity and immune-modulatory property of EbSe-Ag+. Collectively, these results provided academic fundament for further analysis and development of EbSe-Ag+ as the antibacterial agents for pseudotuberculosis control.

Erectile Functional Restoration With Genital Branch of Genitofemoral Nerve to Pelvic Nerve Transfer After Spinal Root Transection in Rats.

OBJECTIVE: To investigate the feasibility of erectile function restoration by the genitofemoral nerve to pelvic nerve transfer in rats. METHODS: Thirty-six male rats were included in this study. Rats in the nerve transfer group (n = 12) were subjected to pelvic nerve, sacral roots, and L6 roots transection and then bilateral genitofemoral nerve to pelvic nerve transfer, rats in the nerve resection group (n = 12) were subjected to pelvic nerve, sacral roots, and L6 roots transection without nerve transfer, and rats in the control group (n = 12) served as controls. After reinnervation, intracavernous pressure (ICP) assessment was performed. Fluoro-Gold was injected into the corpus cavernosum. Immediately before euthanasia, transferred nerves were stimulated to test penile intracavernous pressure. The L6, S1, and L1-2 spinal cord segments were used for retrogradely labeled neurons. Regenerative nerve morphologic examination assessment was performed. RESULTS: Genitofemoral nerve stimulation induced an increase in ICP in the nerve transfer group. The mean ICP in this group was (33.8 ± 9.4 mm Hg), which is higher than the mean value in the nerve resection group (3.9 ± 1.0 mm Hg) but lower than that in the control group (69.8 ± 12.2 mm Hg; P < .05). The formation of new neural pathways was confirmed by the appearance of Fluoro-Gold labeled neurons in the L-1 and L-2 spinal cord segments in the nerve transfer group. Regenerative nerve morphologic examination showed good axonal regeneration after genitofemoral nerve transfer. CONCLUSION: Nerve regeneration can be obtained by genitofemoral nerve to pelvic nerve transfer, and erectile function can be restored.

Mechanisms of ebselen as a therapeutic and its pharmacology applications.

Ebselen is a synthetic organoselenium radical scavenger compound that possesses glutathione peroxidase-like activity and its own unique bioactivity by reacting with thiols, hydroperoxides and peroxynitrites. Owing to its high affinity toward several essential reactions, ebselen protects cellular components from oxidative and free radical damage, and it has been employed as a useful tool for studying redox-related mechanisms. Based on numerous in vitro and in vivo research, mechanisms are proposed to understand the biomedical and molecular actions of ebselen in health and disease, and it is currently under clinical trials for the prevention and treatment of various human disorders. Based on these outstanding discoveries, this review summarizes the current understanding of the biochemical and molecular characteristics, pharmacological applications and future directions of ebselen.

Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion.

Ebselen, an organo-selenium compound with well-characterized toxicology and pharmacology, recently exhibited potent antibacterial activity against glutathione (GSH)-negative bacteria by disrupting redox homeostasis. In this paper, we show that ebselen and silver ion in combination exert strong bactericidal activity against multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) BC1, a model MDR GSH-positive bacterium. The mechanisms were found to involve consumption of total intracellular GSH and inhibition of thioredoxin reductase activity, which was highly related to reactive oxygen species up-regulation. Furthermore, the therapeutic efficacy of ebselen and silver ion against UPEC-induced cystitis was assessed in a mouse model. Treatment with ebselen and silver ion significantly reduced bacterial loads, down-regulated the expression levels of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on-site and decreased white/red blood cell counts in mild cystitis model mice, which demonstrated the anti-inflammatory property of these agents. In addition, ebselen and silver ion also exhibited significantly high protective ability (100%) against acute cystitis infections. These results together may lay the foundation for further analysis and development of ebselen and silver ion as antibacterial agents for treatment of MDR UPEC infections.

Synergistic therapeutic efficacy of ebselen and silver ions against multidrug-resistant Acinetobacter baumannii-induced urinary tract infections.

Ebselen (EbSe), an organo-selenium compound with well-characterized toxicology and pharmacology, exhibited potent antibacterial activity against glutathione (GSH)-positive bacteria when combined with silver ions (Ag+). In this paper, the strong bactericidal activity of EbSe-Ag+ against multidrug-resistant (MDR) Acinetobacter baumannii has been confirmed, and its efficacy was mainly based on the inhibition of thioredoxin reductase (TrxR) activity and the depletion of the total GSH amount. Moreover, the therapeutic effect of EbSe-Ag+ on urinary tract infection was assessed in a mouse model induced with A. baumannii 0361# strain. The treatment with EbSe-Ag+ significantly reduced the bacterial load and expression levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in bladder lesions; meanwhile, the pathological experiment showed that A. baumannii-induced changes in EbSe-Ag+ treated mice were much attenuated than that in the control group. Thus, all the results obtained here may lay the foundation for further analysis and development of EbSe-Ag+ as potential antibacterial agents for MDR A. baumannii-induced urinary tract infection treatment.

Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase.

As a thiol-dependent enzyme, thioredoxin reductase (TrxR) is a promising antibacterial drug target. Ebselen, an organo-selenium with well-characterized toxicology and pharmacology, was recently reported to have potent antibacterial activity against Staphylococcus aureus. In this paper, we demonstrated that ebselen has strong bactericidal activity against multidrug-resistant (MDR) S. aureus based on taking TrxR as a major target and disruption of the redox microenvironment. Further, the topical therapeutic efficacy of ebselen for staphylococcal skin infections was assessed in a rat model. Treatment with ebselen significantly reduced the bacterial load and the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1ß) in S. aureus skin lesions; further, wound healing and pathological changes were obvious improved in ebselen-treated rats compare to controls. Finally, ebselen was found to sensitize S. aureus to curcumin, which may be due to their synergistic effects in inhibiting bacterial TrxR. Altogether, ebselen is an effective topical antibacterial agent in animal model of MDR S. aureus LT-1 skin infection. This may lay the foundation for further analysis and development of ebselen as an antibacterial agent for topical treatment of MDR staphylococcal infections.

Reinnervation of the rectum with transfer of the genital branch of the genitofemoral nerve to the pelvic nerve in rats.

OBJECTIVE The purpose of this study was to determine the feasibility of rectum reinnervation with transfer of a primarily genitofemoral nerve to the pelvic nerve in the rat. METHODS Thirty-six male rats were randomly divided into 3 groups: rats in the nerve transfer group (n = 12) were subjected to rectal denervation and then bilateral genitofemoral nerve-pelvic nerve transfer; rats in the nerve resection group (n = 12) underwent rectum denervation without nerve transfer; and rats in the control group (n = 12) underwent sham surgery. Rectum denervation was achieved by transection of the L-6 spinal nerves, the spinal nerves below L-6, and the pelvic nerve. Four months postoperatively, retrograde nerve tracing, regenerative nerve morphological examination, and rectal manometry assessment were performed. RESULTS Regenerative nerve morphological examination showed good axonal regeneration after genitofemoral nerve transfer. Nerve stimulation induced increased rectal pressures in 10 of 12 rats in the nerve transfer group. The mean rectal pressure in this group was 54.9 ± 7.1 mm Hg, which is higher than the mean value in the nerve resection group (5.5 ± 2.0 mm Hg) but lower than that in the control group (70.6 ± 8.5 mm Hg) (p < 0.05). The appearance of FluoroGold-labeled neurons in the L-1 and L-2 spinal cord segments in the nerve transfer group confirmed the formation of new neural pathways. CONCLUSIONS The results have demonstrated that genitofemoral nerve-pelvic nerve transfer can achieve nerve regeneration. In this animal model, the authors were able to reinnervate the rectum by nerve transfer.

SREBP1-driven lipid desaturation supports clear cell renal cell carcinoma growth through regulation of NF-κB signaling.

Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancers, is an incurable and lethal disease. Although great progresses have been made in understanding the mechanism of ccRCC, metabolic reprogramming in ccRCC remains largely unclear. Here, we showed that lipid desatutation might be a metabolic hallmark of ccRCC. We demonstrated sterol regulatory element-binding protein 1 (SREBP1) is overexpressed in ccRCC cell lines and positively correlated with NF-κB activation. Further, SREBP1 is required for lipid desaturation and cell growth in ccRCC. Mechanistically, we demonstrated that SREBP1-driven lipid desaturation promotes NF-κB activation. Our finding reveals a crucial roles for SREBP1 in lipid desaturation of ccRCC through regulation of NF-κB signaling, which provides not only new insights in regulatory mode of NF-κB signaling but also a novel target for potential metabolic therapies.

Antibiotic Susceptibility and Molecular Characterization of Escherichia coli O157 Isolates from Urinary Tract Infections.

BACKGROUND: Escherichia coli O157 is an important food-borne pathogen that can cause diarrhoea, hemorrhagic colitis, and hemolytic uraemic syndrome. Enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) and multilocus sequence typing (MLST) are good methods for molecular typing and the extensive use of antibiotics is a contributing factor to the increasing incidence of antimicrobial-resistant for these strains. OBJECTIVES: The aim of this study was to determine the prevalence, antimicrobial resistance, and genetic diversity of E. coli O157 based on the prevalence of urinary tract infection (UTI) in Hubei, China. RESULTS: We obtained 23 (8.07%) E. coli O157 isolates from 285 UTI patients in Hubei, China. All isolates were subjected to antibiotic susceptibility analysis, and molecular typing was performed using ERIC-PCR and MLST. Antimicrobial susceptibility results indicated that most strains were resistant to penicillin (95.65%), chloramphenicol (73.91%), and ampicillin (69.57%). All isolates were discovered to be multiresistant (resistance to more than 3 antibiotics). Genetic variability analysis showed that all of the isolates were grouped into 4 clusters both by ERIC-PCR and MLST. CONCLUSION: Our findings demonstrated the presence of E. coli O157 in UTIs, provided insights into the dissemination of antibiotic-resistant strains, and improved our knowledge of E. coli O157 risk assessment in UTIs.

Urethral Reconstruction Using Everted Saphenous Vein Graft in a Rabbit Model: One-Year Outcomes.

OBJECTIVE: To investigate the efficacy of using everted saphenous vein graft for urethral reconstruction. MATERIALS AND METHODS: Thirty-five adult male rabbits were divided into 7 groups randomly: experimental group A, B, C, D, E, stricture control group and normal control group (n = 5). In experimental groups and the stricture control group, a urethral mucosa defect (1.5 × 0.8 cm) was created in each rabbit. In experimental groups, a 2-cm long saphenous vein graft was harvested and incised longitudinally and urethral reconstruction was carried out using the everted saphenous vein patch. Rabbits in experimental group A-E were killed respectively at 1 week, 2 weeks, 1 month, 3 months, and 1 year postoperatively, and the specimens were obtained for histo-pathological examination. Retrograde urethrography was performed to evaluate urethral patency before sacrifice in group D and the stricture control group. RESULTS: In the histo-pathological study, the vein grafts were visible within first week. The vein graft was completely covered by epithelium 1 month postoperatively. Retrograde urethrograms showed the urethral caliber of experimental rabbits were similar to those of normal. While the stricture control group showed a narrow urethral lumen and urothelium defect. CONCLUSIONS: For urethral reconstruction, everted saphenous vein graft can be an ideal substitute material because of its longer survival time and rapid epithelization capacity.

Functional Restoration of Erectile Function Using End-to-side Autonomic-to-somatic Neurorrhaphy in Rats.

OBJECTIVE: To investigate the feasibility of erectile function rehabilitation using end-to-side autonomic-to-somatic neurorrhaphy in rats. MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were divided into 3 groups (n = 12 per group): in the end-to-side coaptation group, the left L6 and S1 spinal nerves were transected, and the distal stump of L6 ventral root was sutured to L4 ventral root through end-to-side neurorrhaphy; in the no-coaptation group, the rats did not undergo coaptation; and in the control group, the left L6 and S1 spinal nerves were transected, but L6 ventral root was preserved. After 4 months, retrograde tracing, histomorphological technique, mating test, and evaluation of functional properties of the regenerated nerve were performed. RESULTS: Mating test showed a significantly higher intromission behavior rate in the end-to-side coaptation group (41.7%) and control group (58.3%) than in the no-coaptation group (0%) (P < .001). Intracavernous pressure in end-to-side coaptation group was 31.6 ± 12.0 mmHg, significantly higher than in the no-coaptation group (3.1 ± 1.4 mmHg), but lower than in the control group (67.9 ± 18.0 mmHg) (P < .0001). Retrograde tracing indicated the establishment of the new neural pathway. Axon counting and ultrastructure observation confirmed axonal regeneration in the end-to-side coaptation group. The bilateral tibialis anterior muscles wet weight in the end-to-side coaptation group were 0.6686 ± 0.0427 g and 0.6707 ± 0.0515 g (P = .93). The wet weight and morphology of the tibialis anterior muscles revealed no detrimental effect on the donor nerve. CONCLUSION: Nerve regeneration can be achieved using end-to-side autonomic-to-somatic neurorrhaphy, and erectile function can be restored without the functional impairment of the donor somatic nerve.

Erectile functional restoration with genital branch of genitofemoral nerve to cavernous nerve transfer after bilateral cavernous nerve resection in the rat.

OBJECTIVE: To investigate the feasibility of erectile function restoration by genital branch of genitofemoral nerve (GN) to cavernous nerve (CN) transfer in rats. MATERIALS AND METHODS: Thirty adult (3 months) male Sprague-Dawley rats were divided into 3 groups (n = 10 per group). Rats in sham group underwent sham operation, rats in nerve resection (NR) group underwent bilateral GN and CN resection to make a 2.5-mm gap, and rats in nerve transfer (NT) group underwent nerve anastomosis bilaterally between proximal stump of GN and distal stump of CN after nerve resection. RESULTS: Three months postoperatively, mating test observed 70% rats with intromission behaviors in NT group but only 10% rats in NR group. Electrostimulating the GN of NT group rats resulted in a significant increase in intracavernous pressure, and the ratio of intracavernous pressure increase to mean arterial pressure in NT group was significantly higher than that in NR group. Seven days after Fluoro-Gold injection into the penile crus, Fluoro-Gold-labeled neurons were found in ventral horn of L1 and L2 in NT group, indicating that a new erectile efferent pathway might be established. Axon counting and ultrastructure observation confirmed axonal regeneration in NT group. Furthermore, NT group had a higher expression of nitric oxide synthase in the dorsal penile nerve than that in NR group. CONCLUSION: The results have demonstrated that nerve regeneration can be obtained, and erectile function may be restored after GN to CN nerve transfer in bilateral CN resection rats, which provides an innovative and promising treatment for neurogenic erectile dysfunction.

Successful removal of metal objects causing penile strangulation by a silk winding method.

Penile strangulation is a challenge to urologists. The decompression of the penis is required to prevent long-term complications. Metal objects are difficult to remove. Cutting is the most common method described. Appropriate cutting tools may be difficult to obtain, and the process may be time-consuming with the possibility of iatrogenic penile injury. In this paper, we will present a simple method to remove such objects by use a silk winding method and subcutaneous puncture.

Reconstruction of anorectal function through end-to-side neurorrhaphy by autonomic nerves and somatic nerve in rats.

BACKGROUND: End-to-side nerve repair is a new tool in managing certain nerve injuries. In previous studies, it was limited to somatic nerves. Herein, we evaluate the feasibility of anorectal reinnervation after end-to-side coaptation of autonomic nerve to somatic nerve. MATERIALS AND METHODS: Forty adult male Sprague-Dawley rats were randomly divided into three groups: end-to-side coaptation group (n = 16), the left L6 and S1 spinal nerves were transected, and the distal stump of L6 ventral root (L6VR) was sutured to L4VR (L4VR) through end-to-side neurorrhaphy; no coaptation group (n = 12), rats received the same operation as the end-to-side coaptation group but without coaptation; and control group (n = 12), rats received the same operation as the end-to-side coaptation group but the L6VR was preserved. At 16 wk, using double retrograde tracing and histomorphological technique and anorectal manometry, morphological and functional properties of regenerated nerve were investigated. RESULTS: Retrograde tracing indicated that the new neural pathway was established and the main nerve regeneration mechanism was axon collateral sprouting. Histology showed good axonal regeneration with end-to-side neurorrhaphy. The wet weight and morphology of left tibialis anterior muscles appeared no detrimental effect on donor nerve. Anorectal manometry showed good anorectal functional recovery. CONCLUSIONS: These results suggest that the somatic motor axon ingrowth into autonomic nerve could be through collateral sprouting after end-to-side coaptation of autonomic nerve to somatic nerve. Our innovative technique of end-to-side coaptation may be of great value in anorectal reinnervation without functional impairment of the donor somatic nerve.

Re-innervation of the bladder through end-to-side neurorrhaphy of autonomic nerve and somatic nerve in rats.

End-to-side neurorrhaphy is widely used in the peripheral nervous system for nerve repair; however, the application of this technique has been limited to somatic nerves. The feasibility of nerve regeneration through end-to-side neurorrhaphy between autonomic and somatic nerves with different characteristics in the peripheral nervous system is still undetermined. In this study, rats were divided into three groups for different treatments (n=10 per group). In the end-to-side neurorrhaphy group, left L6 and S1 were transected in the dura, and the distal stump of L6 ventral root was sutured to the lateral face of L4 ventral root through end-to-side coaptation. In the no repair group, the rats did not undergo neurorrhaphy. In the control group, the left L6 dorsal root and S1 roots were transected, respectively, but the L6 ventral root was kept intact. After 16 weeks, the origin and mechanism of nerve regeneration was evaluated by retrograde double labeling technique as well as histological examination and intravesical pressure measurement. Retrograde double labeling indicated that the reconstructed reflex pathway was successfully established and the primary regeneration mechanism involved axon collateral sprouting. Morphological examination and intravesical pressure measurement indicated prominent nerve regeneration and successful re-innervation of the bladder in the neurorrhaphy group, compared with the "no repair" group (p<0.05). No significant changes were observed in the histology of the donor nerve and the bilateral extensor digitorum longus muscles in the neurorrhaphy group. Nerve regeneration may be achievable for nerve repair through end-to-side neurorrhaphy between autonomic and somatic nerves without apparent impairment of donor somatic nerve.

Long-term safety, tolerability, and efficacy of α1-adrenergic blocker in young men with primary bladder neck obstruction: results from a single centre in China.

OBJECTIVE: Primary bladder neck obstruction (PBNO) is a nonneurogenic voiding disorder and frequently overlooked in young men. Prior studies have reported the efficacy of α-blockers only in the short-term for male patients with PBNO. We hereby report our long-term results using α1-blocker therapy in young men with PBNO. METHODS: Between January 2005 and December 2009, PBNO was diagnosed in 30 young men (mean age 27.3 years, range 18-35) at our institution. Doxazosin 4 mg once daily was administered for at least 12 months. Safety and tolerability were assessed, and efficacy was evaluated from International Prostate Symptom Score (I-PSS), Quality of Life (QOL), uroflowmetry, and post-void residual following 3- and 12-month treatment. Successful treatment was defined as at least 3 ml per second increase in the maximum flow rate and more than a 40% decrease in I-PSS. RESULTS: In all 30 patients, Mean symptom duration was 26.4 (3-65) months. The most common symptoms were hesitancy (93.3%), weak stream (76.7%), and frequency (66.7%). A total of 24 patients (80%, 24/30) successfully completed the 12 month of treatment. The medication period was 15.2 months, and follow-up duration was 16.3 months. Doxazosin was safe and well tolerated. The efficacy of doxazosin was maintained over the 12-month treatment period. Relative to baseline, there were reductions in the number of mean I-PSS (from 17.7 ± 4.2 to 10.4 ± 4.8), mean QOL (from 4.2 ± 1.1 to 2.4 ± 1.3), and mean post-void residual urine (from 79.3 ± 33.4 to 47.1 ± 21.3), and an increase in mean maximum flow rate (from 11.4 ± 2.9 to 15.1 ± 3.2 ml) after 12-month treatment. Treatment was successful in 16 patients (66.7%, 16/24) according to the improvement in both symptoms and maximum urine flow. CONCLUSIONS: α1-blocker therapy displayed a favorable safety, tolerability, and efficacy profile during 12-month treatment in young male patients with PBNO.