Background Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. Results The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (P < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. Conclusions Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.
Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.
The UVENTA achieved a higher clinical success rate than the Memokath 051. Our study demonstrated that the UVENTA is safe and effective in the management of benign and malignant ureteral obstruction. The complications were similar between the two metallic stents.
Polydimethylsiloxane (PDMS) is used in implantable medical devices; however, PDMS is not a completely biocompatible material for electronic medical devices in the bladder. To identify novel biocompatible materials for intravesical implanted medical devices, we evaluated the biocompatibility of polymethyl methacrylate (PMMA) by analyzing changes in the levels of macrophages, macrophage migratory inhibitory factor (MIF), and inflammatory cytokines in the bladder. A ball-shaped metal coated with PMMA or PDMS was implanted into the bladders of rats, and after intravesical implantation, the inflammatory changes induced by the foreign body reaction were evaluated. In the early period after implantation, increased macrophage activity and MIF in the urothelium of the bladder were observed. However, significantly decreased macrophage activity and MIF in the bladder were observed after implantation with PMMA- or PDMS-coated metal in the later period. In addition, significantly decreased inflammatory cytokines such as IL-1β, IL-6, and TNF-α were observed with time. Based on these results, we suggest that MIF plays a role in the foreign body reaction and in the biocompatible packaging with PMMA for the implanted medical devices in the bladder.
The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-β) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.
BackgroundIdiopathic infertility is a significant number of causes of male infertility. Empirical treatments are used for idiopathic male infertility, and antioxidant supplementation is a kind of management of oxidative stress related infertility. We investigated the antioxidant effects of the modified Ojayeonjonghwan (KH-204) in a rat model of cryptorchidism.MethodMale rats were divided into four groups (n = 8 in each): a normal control group, a cryptorchidism-induced control group and two cryptorchidism-induced groups treated p.o. with either 200 or 400 mg/kg, KH-204 for 4 weeks. The testes and epididymides from rats in all groups were removed, weighed and subjected to histological examination and semen analysis after surgery. Oxidative stress was assessed by measuring 8-hydroxy-20-deoxyguanosine (8-OHdG), superoxide dismutase (SOD) and heat shock protein (HSP) levels. Apoptosis was determined using a terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling assay.ResultsTreatment with the multi-herbal medicine KH-204 (1) increased the mean weight of the cryptorchid testes; (2) restored sperm counts, motility and germinal cell layer thickness; (3) decreased levels of 8-OHdG and increased levels of SOD; and (4) decreased HSP70 levels and apoptosis.ConclusionsKH-204 reduces the oxidative stress in an experimental rat model of cryptorchidism, and it may alleviate HSP expression and germ cell apoptosis.
The aim of the present study was to evaluate the efficacy and safety of the electromagnetic-type low-intensity extracorporeal shock wave therapy (Li-ESWT) in patients with erectile dysfunction (ED). Materials and Methods: The randomized, sham-controlled, double-blind prospective study was performed at two referral hospitals. Participants were randomized in a 1:1 ratio to receive sham or Li-ESWT for 6 weeks. ED was evaluated at screening and at 4 and 7 weeks after treatment. Participants were asked to complete the international index of erectile function-erectile function (IIEF-EF) domain questionnaire, erection hardness scale (EHS), and sexual encounter profile questionnaire (SEPQ 2 and 3). The development of complications was investigated. Results: Eighty-one of 96 patients completed the study. The median change in the IIEF-EF score in the Li-ESWT and sham groups was 5.1 and-2.2 (p<0.001), respectively, at the 7-week follow-up; 47.4% (18/38) patients had EHS <3, of which 77.8% (14/18) showed significant improvement in virtue of Li-ESWT treatment (p=0.001). A significant improvement was observed in the percentage of 'Yes" responses to SEPQ 2 and 3 in the Li-ESWT group vs. sham group from baseline to 7-week follow-up (91.3% vs. 69.4%; p=0.008 and 50.0% vs. 14.3%; p=0.002, respectively). No patients reported pain or other adverse events during treatment or follow-up. Conclusions: Thus, Li-ESWT could have a role in improving erectile function. Furthermore, it is safe. We believe that Li-ESWT is an attractive new treatment modality for patients with ED.
Purpose:The National Institutes of Health classification of prostatitis reported the proportion of chronic bacterial prostatitis, especially category II, at 3% to 10%. Because of the polymerase chain reaction (PCR) diagnosis technique, chronic prostatitis syndrome (CPS) with a known bacterial origin has increased recently. In this study, we evaluated the proportion of chronic bacterial prostatitis in a general hospital and a primary care clinic (PCC) in addition to the distribution of the microorganism in chronic bacterial prostatitis in Korea.Methods:Two hundred and ninety-three patients were enrolled in this study. One hundred and five patients in the general hospital and 188 patients in the PCC were enrolled in the study. Using a questionnaire, all patients were checked for symptoms of urinalysis, expressed prostate secretion (EPS), EPS or V3 culture and PCR of EPS or VB3 for Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genetalia, and Trichomatis vaginalis.Results:In routine EPS or VB3 culture, 12 of 105 patients (11.4%) in the general hospital showed positive culture, but 77 of 188 patients (40.9%) in the PCC showed a positive culture. Escherichia coli, Streptococcus faecalis, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus aureus, and Pseudomonas were isolated in routine culture. In the PCR diagnosis, 37 of 105 patients (35.2%) in the general hospital were PCR positive, and 65 of 188 patients (34.5%) in the PCC were PCR positive. In the general hospital, C. trachomatis was the most common (49%), followed by U. urealyticum (24%), M. genetalia (16%), M. hominis (10%), and T. vaginalis (2%). In the PCC, U. urealyticum was the most common (45%), followed by C. trachomatis (34%), M. hominis (13%), M. genetalia (7%) and T. vaginalis (1%). The proportions of chronic bacterial prostatitis were 46.6% (49/105) and 67.5% (127/188) in the general hospital and PCC, respectively.Conclusions:The total portion of chronic bacterial prostatitis was 59.3% (174/293). Culture-positive patients in the PCC were significantly higher than in the general hospital, but the number of PCR positive patients in the PCC was the same as in the general hospital.
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