Seulah Lee

The prevalence of premature ejaculation and its clinical characteristics in Korean men according to different definitions

This study compared the prevalence of premature ejaculation (PE) diagnosed by the PE diagnostic tool (PEDT) score, self-reporting and stopwatch-recorded intravaginal ejaculation latency time (IELT). It examined the characteristics of males diagnosed with PE by each criterion. A questionnaire survey enrolled 2081 subjects from March to October, 2010. Stopwatch-recorded IELT was measured in 1035 of the 2081 subjects. We aimed to determine whether PE has an influence on the frequency and satisfaction of sexual intercourse, the degree of libido/erectile function and the satisfaction. These factors were evaluated according to different definitions of PE to assess whether the definition used yielded differences in the data. The prevalence of PE, based on a PEDT score of ⩾11, self-reporting and stopwatch-recorded IELT of ⩽1 min was 11.3%, 19.5% and 3%, respectively. The prevalence of PE diagnoses based on PEDT score and self-reporting increased with age, but stopwatch-recorded IELT-based diagnoses did not. Males experiencing PE showed lower levels of libido, erectile function and frequency and satisfaction of sexual intercourse compared with non-PE males. PE males felt that they did not satisfy their partners in terms of the partners’ sexual satisfaction and frequency of orgasm, in comparison with non-PE males. PE is a highly prevalent sexual dysfunction in males. Regardless of whether the PE diagnosis was made on the basis of self-reporting, PEDT score or stopwatch-recorded IELT, subjective symptoms were similar among PE males.

Safety and efficacy of the simultaneous administration of udenafil and an α-blocker in men with erectile dysfunction concomitant with BPH/LUTS

We evaluated the clinical efficacy and safety of administering udenafil (5-[2-propyloxy-5-(1-methyl-2-pyrollidinylethylamidosulphonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)-pyrimidin-7-one) in patients with comorbid benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). One hundred and twenty patients who had been undergoing stable α-blocker therapy for BPH were enrolled in this trial and they were administered 100 mg udenafil for 8 weeks. Changes in blood pressure (BP), heart rate (HR), the international prostatic symptom score (IPSS) and the international index of ED (IIEF-5) were evaluated every 4 weeks. At end point, there was no significant change in BP and HR, whereas the lower urinary tract symptoms (LUTS) and ED improved significantly compared with baseline (IPSS 14.3–11.5, IIEF-5 11.95–18.32, P<0.05). Most patients were tolerant to the treatment and there was no evidence of additional side effects related to coadministration. The coadministration of udenafil and an α-blocker in patients with comorbid BPH and ED was safe and gave significant improvements in both LUTS and ED.

Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells.

Hypercholesterolemia is a major risk factor for erectile dysfunction. To understand the mechanism(s) of hypercholesterolemia-induced erectile dysfunction, we studied the effect of lysophosphatidylcholine (LPC) on the membrane conductance of corporal smooth muscle cells. We used cultured human corporal smooth muscle cells. The intracelluar Ca2+ concentration ([Ca2+]i) and the influx of divalent cation was monitored by the ratio of fura-2 fluorescence (F340/380) and by the Mn2+-induced quenching rate of fura-2, respectively. The LPC-induced membrane current was characterized by the whole-cell patch-clamp technique and the molecular identity of suspected channels was probed by RT-PCR. LPC (20 μM) induced a statistically significant increase in F340/380 to 119.9±3.9% of initial control (n=6) in corporal smooth muscle cells. The addition of 20 μM LPC accelerated the quenching rate of F360 by 59.5±11.8% (n=5). LPC activated nonselective cationic current (ILPC), similar to the known effects of phenylephrine in corporal myocytes. The size of ILPC at −60 mV was −55.3±6.3 pA (n=8). The transcript of transient receptor potential channel 6 (TRPC6) was detected in human corporal myocytes. We also found one splicing variant of TRPC6, TRPC6α. In conclusion, the present study suggests that the LPC, a major component of oxidized low-density lipoprotiens, increases calcium in corporal smooth muscle cells probably through activation of a TRPC6 channel and the increased [Ca2+]i by LPC via TRP channels is one of mechanisms for hypercholesterolemia-induced erectile dysfunction.

Novel method for cell immobilization and its application for production of oligosaccharides from sucrose

Aims:  The purpose of the present investigation was to develop a novel method for cell immobilization.

Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity

The present study reports a renoprotective effect and the mechanism of action of lupane triterpenes isolated from Cornus walteri in cisplatin-induced renal toxicity. A phytochemical investigation of the MeOH extract of the stems and stem bark of C. walteri resulted in the isolation and identification of twelve lupane triterpenes. Among these, betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125 μM. Upregulated phosphorylation of JNK, ERK, and p38 following cisplatin treatment were markedly decreased after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. In addition, the protein expression level of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. These results show that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol isolated from C. walteri extract.

Protective effect of lanostane triterpenoids from the sclerotia of Poria cocos Wolf against cisplatin-induced apoptosis in LLC-PK1 cells

Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1-10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100μM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These results indicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.

Src/Syk-Targeted Anti-Inflammatory Actions of Triterpenoidal Saponins from Gac (Momordica cochinchinensis) Seeds

Momordica cochinchinensis Spreng (family Cucurbitaceae), also known as gac, or red melon, is an edible Southeast Asian fruit valued for its nutritional and medicinal properties. Specifically, Momordicae Semen, the seeds of the gac fruit, is used in traditional Chinese medicine to treat boils, rheumatic pain, muscle spasm, hemorrhoids, and hemangiomas. In this study, a chemical investigation into a gac seed ethanol (EtOH) extract resulted in the identification of three triterpenoidal saponins (1-3), which were investigated for their anti-inflammatory effects. Among the saponins, momordica saponin I (compound 3) reduced the production of nitric oxide (NO) in LPS-activated RAW264.7 cells without inducing cytotoxicity. The mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by momordica saponin I. Additionally, the translocation of p65 and p50 (subunits of the transcription factor NF-[Formula: see text]B) into the nucleus was remarkably inhibited. Furthermore, the phosphorylation levels of inflammatory signaling proteins (I[Formula: see text]B[Formula: see text], Src, and Syk) known to be upstream regulatory molecules of p65 were decreased under momordica saponin I-treated conditions. The molecular targets of momordica saponin I were confirmed in overexpression experiments and through immunoblot analyses with Src and Syk. This study provides evidence that momordica saponin I could be beneficial in treating inflammatory diseases, and should be considered a bioactive immunomodulatory agent with anti-inflammatory properties.

Lignans from the Twigs of Euonymus alatus (Thunb.) Siebold and Their Biological Evaluation.

A new sesquilignan, euonymolin A (1), and six known lignans, (−)‐de‐O‐methylmagnolin (2), (+)‐de‐O‐methylepimagnolin A (3), (+)‐syringaresinol (4), (+)‐pinoresinol (5), (+)‐medioresinol (6), and (+)‐lariciresinol 4′‐O‐β‐d‐glucopyranoside (7), were isolated from the twigs of Euonymus alatus (Thunb.) Siebold (Celastraceae). The structures of the isolated compounds were elucidated based on spectroscopic analyses, including extensive 1D‐ and 2D‐NMR techniques, HR‐MS analysis and circular dichroism (CD) data, and the literature data. All of the isolated compounds were evaluated for antiproliferative activity against A549, SK‐OV‐3, SK‐MEL‐2, and HCT‐15 cell lines and inhibition of nitric oxide (NO) production in a lipopolysaccharide (LPS)‐activated BV2 cell line. All compounds showed cytotoxicity against the SK‐MEL‐2 cell line with IC50 values of 23.24 – 48.14 μm and inhibited NO production in LPS‐activated BV‐2 cells with IC50 values of 6.75 – 23.53 μm.

Effects of ginsenoside on large-conductance K Ca channels in human corporal smooth muscle cells

Ginseng was known to be an effective natural product that enhances penile erection. However, the precise biological function and mechanisms of action of ginseng with regard to erectile function remain unknown. The principal objective of this study was to identify ginsenoside (principal molecular ingredients of ginseng)-induced activation of large-conductance KCa channel in human corporal smooth muscle cells, and to determine ginsengs mechanism of action on penile erection. Electrophysiological studies using cultured human corporal smooth muscle cells were conducted. We evaluated the effects of total ginsenosides (TGS) and ginsenoside Rg3 on large-conductance KCa channel by determining whole-cell currents and single-channel activities. There was an increase in outward current dependent on TGS concentration (at +60 mV, 1 μg ml−1; 168.3±59.3%, n=6, P<0.05, 10 μg ml−1; 173.2±36.8%, n=4, P<0.05, 50 μg ml−1; 295.3±62.3%, n=19, P<0.001, 100 μg ml−1; and 462.3±97.1%, n=5, P<0.001) and Rg3 concentration (at +60 mV, 1 μM (0.78 μg ml−1); 222.8±64.8%, n=11, P<0.0001, 10 μM; 672.6±137.1%, n=10, P<0.0001, 50 μM; and 1713.3±234.7%, n=15, P<0.001) in the solution that was blocked completely by tetraethylammonium (TEA). Channel opening in cell-attached mode and channel activity in the inside-out membrane patches was also increased significantly by 50 μg of TGS or 10 μM of Rg3. The results of this study suggested that the activation of large-conductance KCa channels by ginsenoside could be one mechanism of ginsenoside-induced relaxation in corporal smooth muscle.

Anti-Inflammatory Phenolic Metabolites from the Edible Fungus Phellinus baumii in LPS-Stimulated RAW264.7 Cells

The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (1–3), a sesquiterpene (4), two steroids (5–6), a fatty acid (7), and a cerebroside (8). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds 2, 4, 5, 7 and 8 were identified in P. baumii for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds 1, 2, 3, 5 and 7 inhibited LPS-stimulated NO production, and compounds 1–3 had IC50 values <10 μM. Treatment of LPS-stimulated RAW264.7 cells with compounds 1–3 inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds 1–3 reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds 1–3 inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, P. baumii is a potential source of natural anti-inflammatory agents, and active compounds 1–3 could be promising lead compounds for the development of novel anti-inflammatory agents.