Proteomic analysis of urethral protein expression in an estrogen receptor α-deficient murine model of stress urinary incontinence.

PURPOSE: The roles of estrogen receptor α (ERα) in stress urinary incontinence (SUI) remain elusive. This study was conducted to understand the molecular mechanism of ERα against SUI. METHODS: Wild-type (ERα(+/+)) and ACTB-cre ERα knockout (ERα(-/-)) female mice were generated. Urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using the two-dimensional differential gel electrophoresis and liquid chromatography-mass spectrometry technology. Interaction between these ERα pathway proteins was further analyzed by using MetaCore. Lastly, Western blot and immunochemistry (IHC) were used to confirm the candidate protein expression levels and locations, respectively. RESULTS: Compared with the ERα(+/+) group, the LPP and MUCP values of the ERα(-/-) group were significantly decreased. Additionally, we identified 11 differentially expressed proteins in the urethra of ERα(-/-) female mice; five proteins were down-regulated and six were up-regulated. The majority of the ERα knockout-modified proteins were involved in muscle development, contraction, and regulation, as well as immune response (amphoterin signaling and phagocytosis), proteolysis, and cell adhesion (platelet aggregation and integrin-mediated cell-matrix adhesion). IHC and Western blot confirmed the down-regulation of tropomyosin and up-regulation of myosin in urethra. CONCLUSIONS: This is the first study to estimate protein expression changes in urethras from ERα(-/-) female mice. These changes could be related to the molecular mechanism of ERα in SUI.

Antipruritic effect of cold stimulation at the Quchi acupoint (LI11) in mice.

BACKGROUND: Acupuncture and moxibustion are used to treat pruritus and atopic dermatitis. However, whether cold stimulation (defined as that the temperature conducted under skin temperature) of acupoints affects itching in experimental murine models remains unclear. METHODS: The present study was designed to determine the therapeutic effects of different thermal stimulations at the Quchi acupoint (LI11) in a murine model in which scratching behaviour was elicited by subcutaneous injection with a pruritogenic agent (compound 48/80). Male ICR mice were divided into several groups as follows: control (saline), those receiving compound 48/80 and compound 48/80 with various thermal stimulations (5°C-45°C) at LI11 (n = 6 per group). The scratch response of each animal to these stimulations was recorded for 30 min. The antipruritic effect of the acupoint was further evaluated in LI11 and sham (non-acupoint) groups (n = 6 per group). RESULTS: Treatment with lower temperature (20°C) at the LI11 acupoint significantly attenuated compound 48/80-induced scratching; however, this antipruritic effect was not observed with stimulation at the sham point. The expression of c-fos in the neuron of the cervical spine induced by compound 48/80 was suppressed by cold stimulation at LI11. The antipruritic effect of cold stimulation was blocked by ruthium red (RR), a non-selective transient receptor potential (TRP) channel blocker, suggesting that TRP channels may play an important role in the antipruritic effect of cold stimulation at LI11 in mice. CONCLUSIONS: This study demonstrated that cold stimulation at LI11 attenuated compound 48/80-induced scratching behaviour in mice, possibly by a TRP-related pathway.

Efficacy of Frankincense and Myrrha in Treatment of Acute Interstitial Cystitis/Painful Bladder Syndrome.

OBJECTIVE: To investigate the efficacy of frankincense and myrrha in the treatment of acute interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: The effects of frankincense and myrrha on the proliferation and migration of primary human urothelial cells (HUCs) were assessed in vitro. In the animal study, 48 virgin female rats were randomized into 4 groups (12 in each group): (1) control group (saline-injected control); (2) cyclophosphamide (CYP) group (intraperitoneal injected 150 mg/kg CYP); (3) CYP + pentosan polysulfate sodium group (orally received 50 mg/kg pentosan polysulfate sodium); and (4) CYP + frankincense and myrrha group [orally received frankincense (200 mg/kg) and myrrha (200 mg/kg)]. Rats orally received pentosan polysulfate sodium or frankincense and myrrha on day 1, 2, and 3. The experiments were performed on day 4. Pain and cystometry assessment behavior test were performed. Voiding interval values were assessed in rats under anesthesia. Finally, immunohistochemistry and Western blot were used to confirm the location and level, respectively, of cell junction-associated protein zonula occludens-2 (ZO-2) expression. RESULTS: Low dose frankincense and myrrha increased cell proliferation and migration in HUCs compared with control (P<0.05). Rats with acute IC/PBS rats exhibited lower voiding interval values, pain tolerance, and ZO-2 expression (P<0.05). Voiding interval values and pain tolerance were higher in the frankincense and myrrha group than CYP group (P<0.05). ZO-2 expression in the bladder was increased in the CYP + pentosan polysulfate and frankincense + myrrha groups compared with the CYP-induced acute IC/PBS group (P<0.05). CONCLUSION: frankincense and myrrha modulate urothelial wound healing, which ameliorates typical features of acute IC/PBS in rats.

Platelet-Rich Plasma Ameliorates Cyclophosphamide-Induced Acute Interstitial Cystitis/Painful Bladder Syndrome in a Rat Model.

BACKGROUND: Interstitial cystitis/painful bladder syndrome (IC/PBS) could be treated to ameliorate urothelial injury. Here, we investigated the efficacy of intravesical instillation with platelet-rich plasma (PRP) and hyaluronic acid for acute IC/PBS. METHODS: The effects of PRP and hyaluronic acid on the proliferation of normal human fibroblast cells (HFCs) were assessed. Additionally, thirty virgin female rats were randomized into five groups: group 1, saline-injected control; group 2, cyclophosphamide (CYP) plus intravesical instillation with normal saline; group 3, CYP plus intravesical instillation with hyaluronic acid (1 mg/mL); group 4, CYP plus intravesical instillation with PRP; and group 5, CYP plus intravesical instillation with PRP plus hyaluronic acid. A cystometry and histological assessments were performed. The expression of cell junction-associated protein zonula occludens-2 (ZO-2) and inflammatory cytokine interleukin 6 (IL-6) was also measured. RESULTS: Low dose PRP increased proliferation in HFCs. The acute IC/PBS rats showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus intravesical instillation with PRP group than in the CYP-induced acute IC/PBS group. Additionally, the expression of ZO-2 was increased and IL-6 was decreased in the CYP plus intravesical instillation with PRP group compared with the CYP-induced acute IC/PBS group. CONCLUSION: These findings suggest that PRP modulate urothelial repair, which ameliorate the increase in urination frequency in rats treated with CYP. Overall, PRP may confer potential benefits by acting as urothelial repair modulators.

Traditional Chinese medicine decreases the obstructive uropathy risk in uterovaginal prolapse: A nationwide population-based study.

Traditional Chinese medicine (TCM) is a popular treatment for voiding dysfunction in Eastern countries. However, no previous studies have investigated the effects of TCM on preventing obstructive uropathy in uterovaginal prolapse women. We conducted a large-scale nationwide population-based cohort study to investigate the relationship between TCM and obstructive uropathy in uterovaginal prolapse women. This is a retrospective cohort study with the Taiwan National Health Insurance Research Database (NHIRD). The study population was newly diagnosed uterovaginal prolapse patients between 1997 and 2010 year. Among patients, 762 uterovaginal prolapse patients in this cohort. Significant adjusted HRs of urine retention or hydronephrosis in Cox proportional hazard models were uterovaginal prolapse (hazard ratio [HR]: 1.74, 95% confidence intervals [CI]: 1.43-2.14), age 40 to 64 years (1.51, 1.01-2.27), ≥60 years (3.52, 2.32-5.34), DM (1.52, 1.23-1.89), hypertension (1.38, 1.13-1.7), constipation (1.35, 1.05-1.75), urinary tract calculi (1.54, 1.06-2.23), and TCM users (0.34, 0.28-0.41). The Kaplan-Meier analysis showed a higher incidence rate of urine retention or hydronephrosis in the uterovaginal prolapse cohort compared with that of the without uterovaginal prolapse cohort. The results of this nationwide population-based study support a relationship between TCM and a reduced risk of obstructive uropathy in uterovaginal prolapse women.

Long-Term Therapy With Wu-Ling-San, a Popular Antilithic Chinese Herbal Formula, Did Not Prevent Subsequent Stone Surgery: A Nationwide Population-Based Cohort Study.

Traditional Chinese herbal medicine (CHM), which is widely used to treat pain and urolithiasis, is a promising therapy for urinary stone prevention. This study investigated the clinical efficacy of a popular CHM, Wu-Ling-San (WLS), in Taiwan for the prophylaxis of recurrent nephrolithiasis as assessed by surgical stone treatment via a nationwide population-based cohort study. The National Health Insurance Research Database, 2000-2010, which included one million patient records. All patients diagnosed with stone disease at the beginning of the study. The matched controls (4-fold the number of WLS patients) were stone patients who did not take WLS. Data analysis included the stone surgeries following the first treatment. We enrolled 11 900 patients with stone disease, and the incidence of stone patients in this database was 1.19%. The prevalence of comorbidities such as benign prostate hyperplasia, chronic kidney disease, diabetes mellitus, and urinary tract infection, but not hypertension, was significantly higher in WLS users. Several patients in both groups were prescribed potassium citrate. The stone treatment rate was significantly higher in WLS users (17.85%) than in the non-WLS users (14.47%). WLS users with an associated comorbidity had a higher treatment rate than the non-WLS users: 21.05% versus 16.70%, respectively. The surgery rate for upper urinary tract stones was higher in WLS users than in the non-WLS users (adjusted hazard ratio, 1.28; 95% confidence interval, 1.08-1.52; P < .05). The stone treatment rate (52.79%) was significantly higher in patients who used a very high amount of WLS (adjusted hazard ratio, 3.02; 95% confidence interval, 2.30-3.98). Stone patients using a high amount of WLS use had a high stone surgical rate. Long-term therapy with WLS did not have a preventive effect on stone surgical treatment. Long-term potassium citrate therapy as a preventive measure appeared to be underutilized in this study.

Traditional Chinese Medicine Decreases the Stroke Risk of Systemic Corticosteroid Treatment in Dermatitis: A Nationwide Population-Based Study.

Epidemiological studies have shown a strong association between dermatitis and stroke. Systemic corticosteroid, the mainstay treatment for dermatitis, could enhance the atherosclerotic process. Traditional Chinese Medicine (TCM) has been used for dermatitis to decrease the side effects of corticosteroid. However, the different stroke risk in dermatitis patients treated with systemic corticosteroid or TCM remains unclear. This study identified 235,220 dermatitis patients and same comorbidity matched subjects between 2000 and 2009 from database of NHRI in Taiwan. The two cohorts were followed until December 31, 2011. The primary outcome of interest was new diagnosis of stroke. The crude hazard ratio (HR) for future stroke among dermatitis patients treated with systemic corticosteroid was 1.40 (95% CI, 1.34-1.45; P < 0.0001) and TCM was 1.09 (95% CI, 1.05-1.13; P < 0.0001). The log-rank test showed a higher cumulative incidence of ischemic stroke in the patient treated with only systemic corticosteroid group than that treated with systemic corticosteroid and TCM, only TCM, and neither systemic corticosteroid nor TCM in the matched cohort during the follow-up period (P < 0.0001). We demonstrated that patients treated with systemic corticosteroid had an increased risk of stroke and that the risk probably decreased by TCM treatment.

Corrigendum to "an emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease".

[This corrects the article DOI: 10.1155/2014/972958.].

Irritant contact dermatitis risk of common topical traditional chinese medicines used for skin-lightening: a pilot clinical trial with 30 volunteers.

Topical traditional Chinese medicine- (TTCM-) related contact dermatitis is not uncommon but ignored. Patch and photopatch tests using 6 individual herbal ingredients and Bai-Zhi-Kao (BZK; ), a skin-lightening TTCM preparation, were conducted on 30 participants. Twenty-five subjects showed at least 1 positive reaction, including 6 (20.0%) participants who reacted to BZK. The majority reacted to Radix Ampelopsis japonica (Bai-Lian; ) (60.0%), whereas few reacted to Rhizoma Bletilla striata (Bai-Ji; ) (16.7%), Rhizoma Atractylodis macrocephalae (Bai-Zhu; ) (10.0%), Radix Angelicae dahuricae (Bai-Zhi; ) (3.3%), and Herba asari (Xi-Xin; ) (3.3%). In the photopatch test, 3 participants (10.0%) reacted positively to BZK and 10 to ≥1 constituent; however, all reacted to Radix Angelicae dahuricae (26.7%), Radix Ampelopsis japonica (13.3%), and Rhizoma Bletilla striata (3.3%). In contrast, no subjects showed positive reactions to Sclerotium Poria cocos (Bai-Fu-Ling; ). Thus, BZK and its constituents might present potential latent risk of contact dermatitis owing to the possible presence of Radix Ampelopsis japonica and Radix Angelicae dahuricae. Furthermore, TTCMs, particularly cosmetic products, must be used carefully, with ample warning of potential contact dermatitis risk.

An emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease.

Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx) formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG) as the lithogenic agent. The control group was fed with food only. After 3 weeks, flies (n ≥ 150 for each group) were killed using CO2 narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination of the crystals. The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0%, including Salviae miltiorrhizae, Paeonia lactiflora, and Carthami flos. Scutellaria baicalensis enhanced CaOx crystal formation. Two herbal drugs Commiphora molmol and Natrii sulfas caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. These useful medicinal plants can be further studied using other animal or human models to verify their effects.

Effect of Flos carthami Extract and α 1-Adrenergic Antagonists on the Porcine Proximal Ureteral Peristalsis.

Traditional Chinese medicine (TCM) has been proposed to prevent urolithiasis. In China, Flos carthami (FC, also known as Carthamus tinctorius) (Safflower; Chinese name: Hong Hua/) has been used to treat urological diseases for centuries. We previously performed a screening and confirmed the in vivo antilithic effect of FC extract. Here, ex vivo organ bath experiment was further performed to study the effect of FC extract on the inhibition of phenylepinephrine (PE) (10(-4) and 10(-3) M) ureteral peristalsis of porcine ureters with several α 1-adrenergic antagonists (doxazosin, tamsulosin, and terazosin) as experimental controls. The results showed that doxazosin, tamsulosin, and terazosin dose (approximately 4.5 × 10(-6) - 4.5 × 10(-1) µg/mL) dependently inhibited both 10(-4) and 10(-3) M PE-induced ureteral peristalsis. FC extract achieved 6.2% ± 10.1%, 21.8% ± 6.8%, and 24.0% ± 5.6% inhibitions of 10(-4) M PE-induced peristalsis at doses of 5 × 10(3), 1 × 10(4), and 2 × 10(4) µg/mL, respectively, since FC extract was unable to completely inhibit PE-induced ureteral peristalsis, suggesting the antilithic effect of FC extract is related to mechanisms other than modulation of ureteral peristalsis.