A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.@*RESULTS@#CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).@*CONCLUSION@#The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Estudio farmacognóstico preliminar de tallo y raíz de la especie Moringa Oleífera lam cosechada en Machala / Preliminary pharmacognostic study of the stem and root of the species Moringa Oleifera lam grown in Machala

Introducción: la composición química de las especies vegetales está sujeta a cambios, dependiendo, entre otros factores, de la localización geográfica. Moringa oleífera Lam., que crece en Machala, Ecuador, puede diferir de especies de otras regiones geográficas. Objetivo: realizar un estudio farmacognóstico preliminar del tallo y raíz (corteza y pulpa) de la planta M. oleífera cultivada en las áreas de la Unidad Académica de Ciencias Agropecuarias, de la Universidad Técnica de Machala. Métodos: se desarrolla el control de la calidad de la droga cruda según la metodología establecida por la Organización Mundial de la Salud, mediante determinación de la humedad residual, el porciento de cenizas y el porciento de sustancias solubles en el tallo y la raíz. Se cuantificaron algunos metales mediante espectrometría de emisión óptica con plasma acoplado inductivamente. El estudio químico preliminar se efectuó a través de ensayos de tamizaje fitoquímico y mediante cromatografía en capa delgada. Resultados: la humedad residual para ambos órganos y los valores de cenizas obtenidos para la raíz se encuentran dentro de los límites establecidos. Las cenizas totales para el tallo resultaron elevadas. La determinación de metales descartó la presencia de metales tóxicos en los órganos estudiados. Los valores de sustancias solubles indicaron mayor poder extractivo para el agua. La evaluación mediante tamizaje fitoquímico sugirió triterpenos y esteroides, azúcares reductores, alcaloides, flavonoides, aminoácidos y saponinas, en los extractos de la raíz. En el tallo se detectaron, además, catequinas, mucílagos y compuestos fenólicos, no así flavonoides. La cromatografía en capa delgada sugirió la existencia de alcaloides derivados de la fenilmetilamina. Conclusiones: el estudio permitió establecer parámetros de calidad de la droga cruda para la especie estudiada; sugerir, en principio, semejanzas en composición química de la planta analizada con otras de orígenes geográficos diferentes, y comprobar la ausencia de metales tóxicos en los órganos estudiados(AU)

Introduction: The chemical composition of plant species is subject to changes which depend, among other factors, on their geographic location. The Moringa oleifera Lam. growing in Machala, Ecuador, may differ from species from other geographic regions. Objective: Conduct a preliminary pharmacognostic study of the stem and root (bark and pulp) of the plant M. oleifera grown in areas from the Agricultural Sciences Academic Unit of the Technical University of Machala. Methods: Quality control was performed of the crude drug following the methodology set up by the World Health Organization to determine residual humidity, percentage of ashes and percentage of soluble substances in the stem and the root. Several metals were quantified by inductively coupled plasma atomic emission spectroscopy. The preliminary chemical study was conducted by phytochemical screening testing and thin layer chromatography. Results: Both the residual humidity for both organs and the ash values obtained for the root are within the limits established. Total ashes for the stem were high. Metal determination discarded the presence of toxic metals in the organs studied. Values for soluble substances awarded a greater extraction capacity to water. Phytochemical screening pointed to the presence of triterpenes and steroids, reducing sugars, alkaloids, flavonoids, amino acids and saponins in root extracts. The stem was found to also contain catechins, mucilages and phenolic compounds, but not flavonoids. Thin layer chromatography pointed to the presence of alkaloids derived from phenyl methylamine. Conclusions: The study made it possible to set up crude drug quality parameters for the study species, make preliminary suggestions about similarities between the chemical composition of the plant analyzed and other plants of different geographic origin, and verify the absence of toxic metals in the organs studied(AU)

Expression of LXR-β in human gastric cancer tissue and the effect of GW3965 on the proliferation of gastric cancer cell line SGC-7901 / 中南大学学报(医学版)

OBJECTIVE@#To examine the expression of liver X receptor-β (LXR-β) in human gastric cancer tissue, and to explore the effect of GW3965, an agonist of LXRs, on proliferation of gastric cancer cell line SGC-7901.
@*METHODS@#The immunohistochemical assay was used to detect the expression of LXR-β, activating transcription factor 4 (ATF4) in gastric cancer tissues and the corresponding pericarcinoma tissues in 114 patients. Real-time quantitative PCR and Western blot were used to determine mRNA and protein levels of ATF4 and ATP-binding cassette 1 (ABCA1), one of the downstream target genes of LXRs, in SGC-7901 cells with or without GW3965 treatment. Cell counting kit-8 (CCK-8) assay was performed to detect cell proliferation. The expression of ATF4 was silenced by short hairpin RNA (shRNA).
@*RESULTS@#The expressions of LXR-β and ATF-4 were obviously down-regulated in the gastric cancer tissues than that in the corresponding pericarcinoma tissues (both P<0.05). Compared with the control cells, GW3965 treatment inhibited proliferation of SGC-7901 cells and up-regulated ATF4 and ABCA1 expressions (both P<0.05). Knockdown of ATF4 can reverse the antiproliferative effect of GW3965 on SGC-7901 cells.
@*CONCLUSION@#The expression of LXR-β is decreased in human gastric cancer tissues, and activation of LXRs by GW3965 could inhibit the proliferation of SGC-7901 cells via ATF4.

Efficacy and safety of dapoxetine in the treatment of premature ejaculation / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effect and safety of dapoxetine in the treatment of premature ejaculation (PE).</p><p><b>METHODS</b>We randomly assigned 116 PE patients to receive dapoxetine on demand at 30 mg qd (dapoxetine group, n = 60, aged 23-49 years) or oral tamsulosin at 20 mg qd (control group, n = 56, aged 24-46 years). After 4 weeks of medication, we compared the clinical global impression of change (CGIC) , PE profile (PEP) scores, intravaginal ejaculation latency time (IELT) , and adverse reactions between the two groups of patients.</p><p><b>RESULTS</b>Compared with the baseline, the IELT was remarkably prolonged after treatment both in the dapoxetine group ([0.86 ± 0.17] vs [4.32 ± 2.23] min, P < 0.05) and the control ([0.88 ± 0.15] vs [4.17 ± 2.26] min, P < 0.05), with no statistically significant difference between the two groups (P > 0. 05). The post-treatment rate of CGIC in the dapoxetine group had no statistically significant difference from that in the control (85.00% vs 82.14%, P > 0.05). In comparison with pre-treatment, the patients of both the dapoxetine and control groups showed dramatically improved scores after medication in perceived control over ejaculation (0.85 ± 0.23 vs 2.13 ± 0.97 and 0.88 ± 0.21 vs 2.06 ± 0.34, both P < 0.05), ejaculation-related personal distress (1.15 ± 0.64 vs 2.89 ± 0.26 and 1.19 ± 0.53 vs 2.82 ± 0.69, both P < 0.05), satisfaction with sexual intercourse (0.81 ± 0.33 vs 2.58 ± 0.37 and 0.79 ± 0.28 vs 2.45 ± 0.32, both P < 0.05), and ejaculation-related interpersonal difficulty (2.05 ± 0.61 vs 3.24 ± 0.35 and 2.03 ± 0.65 vs 3.18 ± 0.76, both P < 0.05), with no significant differences between the two groups (P > 0.05). The incidence of adverse reactions was significantly lower in the dapoxetine than in the control group (3.33% vs 30.36%, P < 0.05).</p><p><b>CONCLUSION</b>Dapoxetine is effective for the treatment of PE, with its advantages of prolonging the intravaginal ejaculation latency time, improving the quality of sexual life, and low incidence of adverse reactions.</p>

Efficacy and safety of Yimusake Tablets plus dapoxetine hydrochloride in the treatment of premature ejaculation / 中华男科学杂志

<p><b>Objective</b>To evaluate the effect and safety of Yimusake Tablets combined with dapoxetine hydrochloride and either of them used alone in the treatment of premature ejaculation (PE).</p><p><b>METHODS</b>We randomly assigned 180 PE patients to oral medication of Yimusake Tablets at 1.5 g per night (group A), dapoxetine hydrochloride at 30 mg at 1－3 hours before anticipated sexual activity (group B), the Yimusake Tablets plus dapoxetine hydrochloride simultaneously (group C), all for 8 weeks. After 4 and 8 weeks of medication, we recorded and compared the changes in the intravaginal ejaculation latency time (IELT), measures of the PE profile (PEP), and adverse events among the three groups of patients.</p><p><b>RESULTS</b>The treatment was accomplished and complete data obtained from 154 of the patients, 56 in group A, 52 in group B, and 46 in group C. After 4 and 8 weeks of medication, the mean IELT was dramatically prolonged in all the three groups as compared with the baseline (P<0.01), most significantly at 8 weeks in group C (［2.08±0.68］ min), followed by B (［1.76±0.52］ min) and A (［1.47±0.44］ min), with statistically significant differences among the three groups (P<0.01). The PEP measures were remarkably improved in group A at 8 weeks (P<0.05), and both in B and C at 4 and 8 weeks (P<0.05), most significantly at 8 weeks in group C (P<0.05), in which the patients scored 1.96±0.77 in perception of control over ejaculation, 2.62±0.98 in satisfaction with sexual intercourse, 3.04±0.62 in PE-related distress, and 3.57±0.80 in PE-induced difficult relationship with their partners, all markedly improved as compared with groups A and B (P<0.05). Adverse reactions were observed in 2 cases (3.6%) in group A, 6 cases (9.6%) in B, and 5 cases (10.9%) in C. No severe adverse events occurred in any of the patients during the study.</p><p><b>CONCLUSIONS</b>Combined medication of Yimusake Tablets and dapoxetine hydrochloride, with its advantages of effectiveness and safety, deserves to be recommended for the treatment of PE.</p>

Static compression regulates OPG expression in periodontal ligament cells via the CAMK II pathway

ABSTRACT Objective This study aimed to investigate the potential role of CAMK II pathway in the compression-regulated OPG expression in periodontal ligament cells (PDLCs). Material and Methods The PDL tissue model was developed by 3-D culturing human PDLCs in a thin sheet of poly lactic-co-glycolic acid (PLGA) scaffolds, which was subjected to static compression of 25 g/cm2 for 3, 6 and 12 h, with or without treatment of KN-93. After that, the expression of OPG, RANKL and NFATC2 was investigated through real-time PCR and western blot analysis. Results After static compression, the NFATC2 and RANKL expression was significantly up-regulated, while partially suppressed by KN-93 for 6 and 12 h respectively. The OPG expression was significantly down-regulated by compression in 3 h, started to elevate in 6 h, and significantly up-regulated in 12 h. The up-regulation after 12 h was significantly suppressed by KN-93. Conclusions Long-term static compression increases OPG expression in PDLCs, at least partially, via the CAMK II pathway.

Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation.</p><p><b>METHODS</b>We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups.</p><p><b>RESULTS</b>IELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group.</p><p><b>CONCLUSION</b>On-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.</p>

Dapoxetine for premature ejaculation: Advances in clinical studies / 中华男科学杂志

Premature ejaculation (PE) is a most common sexual dysfunction, for which dapoxetine, a novel selective serotonin (5-HT) re-uptake inhibitor (SSRI), is the only licensed oral medicine at present. With the advantages of fast absorption, rapid action, on-demand medication, and short half-life time, dapoxetine has been proved by clinical trials to be effective in prolonging the intravaginal ejaculation latency time (IELT) and improving the overall condition of PE patients in various areas and populations. Compared with the traditional SSRIs, dapoxetine has a better safety and tolerability. The most frequently reported dapoxetine-related adverse events include nausea, diarrhea, headache and dizziness, but with very few severe or serious cases.

A case of Tinea nigra associated to a bite from a European rabbit (Oryctolagus cuniculus, Leporidae): the role of dermoscopy in diagnosis

We report a case of Tinea nigra in an adolescent living in Itapema, Santa Catarina, Brazil, who presented a hyperchromic macule on the palm of the left hand, close to another erythematous macule caused by a rabbit bite. The patient received guidance on accidents and animal bites and evolved well treated with topical butenafine for the dermatomycosis. The authors also highlight the efficacy of the dermoscopic exam in diagnosing Tinea nigra with animal bite lesions and other traumas.

KN-93, A CaMKII inhibitor, suppresses ventricular arrhythmia induced by LQT2 without decreasing TDR / 华中科技大学学报（医学）（英德文版）

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10(-8)~10(-6) M) decreased the contractile responses induced by PE (10(-9)~10(-4) M) and Ach (10(-9)~10(-4) M) in a dose-dependent manner. Melatonin (10(-7) M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10(-7) M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10(-11)~10(-7) M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

Effects of calmodulin-dependent protein kinase II inhibitor, KN-93, on electrophysiological features of rabbit hypertrophic cardiac myocytes / 华中科技大学学报（医学）（英德文版）

Cardiac hypertrophy is an independent risk factor for sudden cardiac death in clinical settings and the incidence of sudden cardiac death and ventricular arrhythmias are closely related. The aim of this study was to determine the effects of the calmodulin-dependent protein kinase (CaMK) II inhibitor, KN-93, on L-type calcium current (I(Ca, L)) and early after-depolarizations (EADs) in hypertrophic cardiomyocytes. A rabbit model of myocardial hypertrophy was constructed through abdominal aortic coarctation (LVH group). The control group (sham group) received a sham operation, in which the abdominal aortic was dissected but not coarcted. Eight weeks later, the degree of left ventricular hypertrophy (LVH) was evaluated using echocardiography. Individual cardiomyocyte was isolated through collagenase digestion. Action potentials (APs) and I(Ca, L) were recorded using the perforated patch clamp technique. APs were recorded under current clamp conditions and I(Ca, L) was recorded under voltage clamp conditions. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were observed under the conditions of low potassium (2 mmol/L), low magnesium (0.25 mmol/L) Tyrode's solution perfusion, and slow frequency (0.25-0.5 Hz) electrical stimulation. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were also evaluated after treatment with different concentrations of KN-92 (KN-92 group) and KN-93 (KN-93 group). Eight weeks later, the model was successfully established. Under the conditions of low potassium, low magnesium Tyrode's solution perfusion, and slow frequency electrical stimulation, the incidence of EADs was 0/12, 11/12, 10/12, and 5/12 in sham group, LVH group, KN-92 group (0.5 μmol/L), and KN-93 group (0.5 μmol/L), respectively. When the drug concentration was increased to 1 μmol/L in KN-92 group and KN-93 group, the incidence of EADs was 10/12 and 2/12, respectively. At 0 mV, the current density was 6.7±1.0 and 6.3±0.7 PA·PF(-1) in LVH group and sham group, respectively (P>0.05, n=12). When the drug concentration was 0.5 μmol/L in KN-92 and KN-93 groups, the peak I(Ca, L) at 0 mV was decreased by (9.4±2.8)% and (10.5±3.0)% in the hypertrophic cardiomyocytes of the two groups, respectively (P>0.05, n=12). When the drug concentration was increased to 1 μmol/L, the peak I(Ca, L) values were lowered by (13.4±3.7)% and (40±4.9)%, respectively (P<0.01, n=12). KN-93, a specific inhibitor of CaMKII, can effectively inhibit the occurrence of EADs in hypertrophic cardiomyocytes partially by suppressing I(Ca, L), which may be the main action mechanism of KN-93 antagonizing the occurrence of ventricular arrhythmias in hypertrophic myocardium.

Meta-analysis of dapoxetine on demand in the treatment of premature ejaculation / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the efficacy of dapoxetine on demand for premature ejaculation and provide evidence for clinical decision-making.</p><p><b>METHODS</b>We searched PubMed, Embase, BIOSIS Previews, Cochrane Library, CNKI Database and Wanfang Database for literature on dapoxetine on demand for premature ejaculation. We performed meta-analysis on the identified publications and evaluated its therapeutic efficacy based on the intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGI), and composite PRO criteria for clinical benefit (CCCB).</p><p><b>RESULTS</b>Four relevant studies were included involving 6 081 cases of premature ejaculation. Compared with the placebo controls, the patients treated with dapoxetine on demand showed significant improvement in IELT (WMD = 1.39, 95% CI [1.23, 1.55], P < 0.000 01), PGI (OR = 2.59, 95% CI [2.21, 3.04], P < 0. 000 01), and CCCB (OR = 2.59, 95% CI [1.98, 3.39], P < 0.000 01). There were significant differences between the 60 mg and 30 mg dapoxetine groups in IELT (WMD = 0.46, 95% CI [0.19, 0.74], P = 0.001 0) and PGI (OR = 1.32, 95% CI [1.06, 1.64], P = 0.01), but not in CCCB (OR = 1.39, 95% CI [0.90, 2.15], P = 0.13).</p><p><b>CONCLUSION</b>Dapoxetine on demand can prolong IELT and improve PGI and CCCB, either at the dose of 60 mg or 30 mg, and has an even better efficacy in prolonging IELT and improving PGI at 60 mg.</p>

1400W blocks death pathway of LPS-induced activated-microglia to preOLs / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the efficacy of inductible nitric oxide synthase (iNOS) inhibitor 1400W in vivo in blocking the death pathway of lipopolysaccharide (LPS)-induced activated-microglia to preoligodendrocytes (preOLs) in neonatal rats with infective-type periventricular leukomalacia (PVL) induced by LPS.</p><p><b>METHODS</b>Two-day-old neonatal rats were randomly divided into: a sham-operated group, an untreated PVL group, and four 1400W-treated PVL groups that were subcutaneously administrated with 20 mg/kg of 1400W at 0 h, 8 hrs, 16 hrs, and 24 hrs after LPS induction, respectively. The brain specimens were obtained 5 days after LPS induction. The pathological assessment of cerebral white matter was performed under a light microscope. Concentrations of nitric oxide (NO) were measured by nitric acid-deoxidize colorimetry. Synthesis of iNOS was determined by Western blot analysis. Peroxynitrite (ONOO(-)) level and the amount of preOLs were determined by immunocytochemistry. RETHODS: The obvious injuries of periventricular white matter, massive loss of positive O4-labelled preOLs, and increased levels of NO, ONOO(-) and iNOS were observed in neonatal rats with PVL. Compared to the untreated PVL group, the use of 1400W at 0 h, 8 hrs and 16 hrs after LPS induction significantly improved white matter injuries, reduced the levels of NO, ONOO(-) and iNOS, and increased the amount of O4-labelled preOLs. However, the use of 1400W at 24 hrs after LPS induction did not result in the improvements.</p><p><b>CONCLUSIONS</b>iNOS inhibitor 1400W can effectively block the toxicity of LPS-activated microglia to preOLs and protect cerebral white matter through inhibiting iNOS and reducing the production of NO and ONOO(-). The use of 1400W within 16 hrs after LPS induction may provide cerebral protections in neonatal rats with PVL.</p>

Selective Serotonin Reuptake Inhibitors for the Treatment of Premature Ejaculation / 대한남성과학회지

Premature ejaculation (PE) affects the 20~30% men among general population regardless of their age. PE may be classified as lifelong (primary) or acquired (secondary) type. Diagnosis of PE is mainly based on subjective complaints of sexual symptoms. Recently proposed diagnostic system of PE is based on many aspects; intravaginal ejaculatory latency time (IELT), control over ejaculation, stress and interpersonal difficulty according to the PE problem. Standard treatment of lifelong PE is mainly pharmacotherapy. Among many treatment options, selective serotonin reuptake inhibitors (SSRIs) are recommended for off-label use by American Urologic Association and International Consultation on Sexual Medicine. SSRIs were reported to improve the PE symptom by lengthening IELT. However, daily intake of SSRIs often increases the possibility of adverse effects, such as nausea, diarrhea, loss of libido, and even erectile dysfunction. Recently, dapoxetine hydrochloride, newer SSRI with short half life, was tailored to target the PE. Dapoxetine was proved its efficacy on PE over placebo. Clinicians should keep in mind that the sexual dysfunction can be the primary complaints or the results of the intake of antidepressants at the same time.

Effect of 1400W, an inhibitor of inducible nitric oxide synthetase, on blocking the toxicity of lipopolysaccharide-induced activated microglia to preoligodendrocytes / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes (preOLs) and the effect of 1400W, a selective inhibitor of inducible nitric oxide synthetase (iNOS), on the blockage of the toxicity.</p><p><b>METHODS</b>Co-cultured microglia and preOLs obtained from two-day-old Sprague-Dawley (SD) rats were divided into three groups: co-culture control group, co-culture LPS group and co-culture LPS plus 1400W group. After cultured cells were induced by LPS (100 ng/ml) for 48 hours, the concentration of nitric oxide (NO) was measured by nitric acid-oeoxidize-colorimetry, the level of peroxynitrite (ONOO(-)) was determined by immunocytochemistry, and the synthetic level of iNOS was detected by Western blotting, respectively. The morphologic observation of apoptotic preOLs stained with Hoechst 33342/PI and the apoptotic rate of preOLs detected by flow cytometry were processed simultaneously. Data were analyzed with SPSS 11.0 software.</p><p><b>RESULTS</b>Compared to co-culture control group, there was significant increase in levels of NO [(82.27+/-3.41) micromol/L vs. (167.86+/-9.87) micromol/L, t=8.593, P<0.01], ONOO(-)[(6.14+/-1.27) x 10(7)/L vs. (34.38+/-7.75) x 10(7)/L, t=5.892, P<0.01], and iNOS [(0.18+/-0.027) vs. (0.79+/-0.068), t=9.26, P<0.01] induced by LPS in co-culture LPS group, and with a higher apoptotic rate of preOLs [(6.73+/-1.39)% vs. (24.77+/-2.05)%, t=12.619, P<0.01]. However, all levels of NO [(69.55+/-5.07) micromol/L, t=8.896, P<0.01], ONOO(-) [(10.33+/-3.47) x 10(7)/L, t=14.96, P<0.01] and iNOS (0.35+/-0.042, t=5.506, P<0.01) decreased significantly with the use of 1400W at a dose of 10 micromol/L in co-culture LPS plus 1400W group, and the apoptotic rate of preOLs [(11.8+/-2.06)%, t=7.715, P<0.01] was also reduced evidently.</p><p><b>CONCLUSIONS</b>NO, ONOO(-) and iNOS, etc. play important roles in the death pathway of preOLs induced by LPS. 1400W can block effectively the toxicity of LPS-activated microglia toxicity to preOLs through inhibiting iNOS selectively and reducing the production of NO and ONOO(-), and improve the survival rate of preOLs.</p>

New Approach and Treatment of Premature Ejaculation / 대한남성과학회지

Premature ejaculation (PE) is the most common form of male sexual dysfunction. Until very recently, scientific investigation of PE has been hampered by a lack of standardized definitions and objective, validated questionnaires. In recent years both the definition and the management of PE have changed from the traditional authority-based to a more evidence-based approach. In 2007, the International Society for Sexual Medicine (ISSM) established an ad hoc committee consisting of 21 internationally recognized experts, to establish a new definition of PE including intravaginal ejaculation latency time (IELT). As diagnostic tools, a brief self-administered questionnaire, the premature ejaculation diagnostic tool (PEDT), was developed and validated. Current accepted treatment options of PE include behavior therapy, topical desensitizing agents, selective serotonin reuptake inhibitors (SSRIs), clomipramine, tramadol, PDE-5 inhibitors. However, it should be noted that all of the medications currently used for treatment of PE were originally developed to treat other medical disorders such as depression or erectile dysfunction. Dapoxetine, a new SSRI, has a unique pharmacokinetic profile, with a short time to maximum serum concentration, and rapid elimination. By 24 hours, plasma concentrations are less than 5% of peak values. These attributes make Dapoxetine suitable for on-demand therapy of PE. This paper reviewed new diagnostic tools and treatment options for PE.

1,4-Thioarialkylation and/or amination of E-3- [4-bromebenzoyl] acrylic acid and some studies with the products

Recently[1], it was reported that 3-[4-bromobenzoyl] acrylic acid has antibacterial activity towards Staphilococcus aureus, Escherichia coli and Kllebsiella, this was ascribed to the presence of the highly conjugated benzoylacrylic system, which may react with biologically essential-SH groups. This prompted us to investigate the behaviour of 3[4-bromobenzoyl] acrylic acid [1] towards compounds bearing the sulphhydryl group. Thus, when compound [1], was allowed to react with thiophenol and/or thioglycolic acid in dry benzene in the presence of few drops of piperidine is a catalyst[2], it afforded 2-phenyhmercapto-3-[4-bromobenzoyl] propionic acid, and 2-carboxymethyl mercapto-3-[4-bromobenzoyl] propionic acid [2 a and b], respectively. The structure of the acids 2 was proved from their infrared spectra, which show absorptions at 1674, 1683 cm[-1] [V[C=O] of ketone], 1700 and 1725 cm[-1] [V[c=o] of carboxylic acid] and broad basin peak centered at 3300 cm[-1]1 [V[OH] of acids] the electron impact fragmentation of compound 2a exhibits m/e =348[M[+]-18]. The [1]H-NMR spectrum of compound 2b in DMSO exhibits signals at 2.3 [S, 2H, S-CH[2]-COO], 3.1 [octet, 2H, C-CH[2]-] nonequivalent diasterotopic methylene protons, 4[quartet, -CH, methane proton], 7.7-7.9 [m, 4H, Ar-H], 12.79 [broad singlet, OH protons which disappear in D[2]O]

Pharmacological Management of Male Sexual Dysfunction

The erectile dysfunction (ED) and premature ejaculation (PE) are common medical conditions of male sexual dysfunction that affects the sexual lives of millions of men. While many drugs are now available for treating ED and PE, oral pharmacotherapy represents the first-line option for most patients. Phosphodiesterase type-5 (PDE5) inhibitors are currently the most widely prescribed oral agent and have a very satisfactory efficacy-safety profile in all ED patients' categories. Continuous treatments using PDE5 inhibitors and new agents including fast acting PDE5 inhibitors or other intracellular modulators are now under investigation. ED patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal injection therapy of which efficacy is high but the attrition rate remains significant. Since the pathophysiology of PE is still unclear and there is no approved treatment, it remains to be underdiagnosed and under-treated. The first-line pharmacotherapy for most PE patients is selective serotonin reuptake inhibitors (SSRI) because central 5-hydroxy tryptamine has been implicated as a key mediator of ejaculatory control. Topical anesthetics have also shown varying degrees of efficacy and tolerability. New agents being considered for the on-demand treatment of PE include tramadol and dapoxetine. Therapies for ED or PE will continue to develop as the understanding of those conditions expands. The purpose of this review is to describe the major recent novel advances in the field of medical therapy for the treatment of ED and PE.