Although premature ejaculation (PE) is a common type of male sexual dysfunction, to date we lack a unified definition of PE. The multidimensional definition of PE has been accepted by more and more clinicians. Intravaginal ejaculatory latency time (IELT) is one of the three important dimensions (time to ejaculation, inability to control or delay ejaculation, and negative consequences) for defining PE. Rapid ejaculation is one of the core symptoms of PE and IELT is an objective measurement as well as an important tool for the evaluation of PE. This article reviews estimated IELT, stopwatch-measured IELT, the correlation between estimated and stopwatch-measured IELT, and the factors affecting IELT in the general male population, PE patients, and those complaining of PE.
Coitus ; Ejaculation ; physiology ; Humans ; Male ; Premature Ejaculation ; etiology ; physiopathology ; Reaction Time ; physiology ; Time Factors

Gout ; therapy ; Humans ; Integrative Medicine

OBJECTIVETo investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.

METHODSWhole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.

RESULTSMidazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.

CONCLUSIONMidazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.

Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; drug effects ; HEK293 Cells ; Humans ; Midazolam ; pharmacology ; Mutation ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology

BACKGROUND: Learning and memory disorder exist in diabetic rats,which can be improved by APP 17-mer peptide. However, it is unclear whether learning and memory disorder in diabetes mellitus is caused by influencing neuronal mitochondrial transmembrane potentials and apoptosis in hippocampus or not and what is the related action mechanism of APP17-mer peptide.OBJECTIVE: To observe the effects of APP17-mer peptide on neuronal mitochondrial transmembrane potentials (△ψm) and apoptosis in hippocampal area of diabetic rats.DESIGN: A completely randomized, grouping and controlled trial.SETTING: Beijing Research Laboratory for Brain Aging, Beijing Xuanwu Hospital, Capital University of Medical Sciences; the Department of Endocrine, the First Central Hospital of Baoding.MATERIALS: The data measurement of the experiment was carried out in the Instrument Testing Center, the General Hospital of Chinese PLA between May 2002 and August 2002. The modeling and intervention of the experiment was carried out in the Animal Laboratory of Xuanwu Hospital, Capital University of Medical Sciences. Eighteen male Wistar rats were enrolled and randomized into control group, model group and APP17-mer peptide group with 6 rats in each group.METHODS: ① Diabetic models in the model and APP17-mer peptide groups were established by intraperitoneal injection of 60 mg/kg streptozotocin (pH=4.4) in fasted rats(fasting for 12 hours). Three days later, modeling was successful if blood sugar level in caudal vein was more than 15 mmol/L. Rats in the control group were not subjected to modeling.Then, the rats in the APP17-mer peptide group were subjected to the subcutaneous injection of APP17-mer peptide (3.4 μg for each rat once) three times a week and totally for ten weeks, whereas rats in the other groups were given saline of the same volume. ② After ten weeks, rats were anesthetized and decapitated to take out brain tissues, and then hippocampal tissues were isolated in ice bath for preparation of single cell suspension.JC-1 labeled mitochondrial transmembrane potentials and cell apoptosis in hippocampal area were measured by means of flow cytometry. ③ One-way analysis of variance was adopted in the comparison among groups.RESULTS: Eighteen rats were involved in the results analysis. ①Neuronal mitochondrial transmembrane potential was lower in the model group as compared with the control group [(551.91±53.36) vs (809.88±82.41) △ψm,P＜0.01] while it was higher in the APP17-mer peptide group as compared with the model group [(705.99±89.92) vs (551.91±53.36) △ψm, P ＜ 0.05].There was no difference between the APP17-mer peptide group and control group (P=0.146). ②) Apoptotic percentage of single cell in hippocampus was significantly higher in the model group than in the control and APP17-mer peptide groups [(5.32±1.37)%, (1.03±0.55)%, (2.80±0.92)%, P＜0.01, 0.05].CONCLUSION: Neuronal mitochondrial transmembrane potential and cell apoptosis in hippocampus may be involved in the occurrence and development of diabetes mellitus, and APP17-mer peptide plays an improved role in the process.

Humans ; Tinnitus

In Alzheimer's disease there is obvious evidence of insulin resistance in the brain. Thiazolidinediones,a kind of insulin sensitizer,not only improves insulin sensitivity,but also decreases inflammation,promotes release and clearance of?-amyloid protein,all are beneficial to the improvement of memory.

ObjectiveTo investigate the correlation of MRI features and phenotypes and genetic mutations in Pelizaeus-Merzbacher disease.Methods Sixteen boys with clinical diagnosis of PelizaeusMerzbacher disease (PMD) were included in this study.Their ages ranged from 22 months to 9 years.They were examined by pediatric neurologists,and clinical classification was made according to the symptoms and physical signs.An experienced radiologist reviewed the cranial MRI images and analyzed the brain involvement,including pallidus globus,pyramidal tract,corpus callosum,cerebellar white matter,semiovale centrum,brain atrophy and ‘ tigroid sign’.ResultsThere were 8 patients with classic form,7 patients with transitional form and one patient with connatal form.They all showed diffuse delayed myelination in the white matter,with involvement of pallidus globus in 13 cases,pyramidal tract in 7 cases,corpus callosum in 11 cases,cerebellar white matter in 7 cases,semiovale centrum in 12 cases.Cerebral atrophy was found in 5 patients and eerebellar atrophy was found in one patient.Five cases depicted ' tigroid sign'.In patients with PLP1 gene point mutation,pyramidal tract and cerebellar white matter involvement showed a high incidence.Cerebellar white matter lesions were relatively frequent in children with transitional form and connatal form.In contrast,‘ tigroid sign' was often related to classic form,which indicated a better myelination and outcome.ConclusionPMD patients show distinct imaging features in their brains,which may be correlated with the phenotype and genetic mutation.

Percutaneous coronary intervention(PCI) can effectively restore reperfusion of ischemic myocardium in patients with coronary artery disease.But currently PCI treatment is just available for a small proportion of the patients with coronary artery disease,so there was an insufficiency of PCI in patients with coronary artery disease.From the perspective of ethics,the reasons for the phenomenon and some feasible strategies for the problem are also analyzed in this paper.

Objective To investigate vascular endothelial growth factor receptor-2(VEGFR-2)and its phosphorylated state in cancerous and peri-cancerous tissues of hepatocellular carcinoma(HCC)after transcatheter arterial chemoembolization(TACE).Methods Forty-three cases of second-stage surgery of HCC after TACE(TACE & surgery group)and twenty cases of surgery without TACE(direct surgery group)were performed.Surgical specimens were made into paraffin-embedded slices.VEGFR-2,phosphorylated VEGFR-2,hypoxia induced factor-1α(HIF-1α)and microvessel density(MVD,labeled by CD31)were detected using immunohistochemical method.All data was statistically processed with SPSS for Windows.Results The absorption factor(A factor)of phosphorylated VEGFR-2 and HIF-1α in the cancerous tissue of HCC were(0.034±0.016)and(0.047±0.021)in TACE & surgery group,and(0.024±0.009)and(0.035±0.016)in direct-surgery group,which showed statistically significant difference(F=6.75,4.77,P＜0.05).The A factors of VEGFR-2,phosphorylated VEGFR-2 and HIF-1α in the peri-cancerous tissue were(0.040±0.017),(0.031±0.011)and(0.037±0.015)respectively in TACE & surgery group,and(0.030±0.015),(0.020±0.008)and(0.024±0.014)respectively in direct-surgery group,all of which showed statistically significant difference(F=4.60,13.72,11.65,P＜0.05).MVD of the peri-cancerous tissue was(58.3±15.2)/HP in TACE & surgery group and(44.4±10.5)/HP in direct-surgery group,which showed statistically significant difference(χ2=13.64,P＜0.05).Conclusion The cancerous and peri-cancerous tissues in HCC after TACE showed more hypoxic changes.Both expression and function of VEGFR-2 were enhanced following TACE.

OBJECTIVETo investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.

METHODSA total of 45 male New Zealand white rabbits (10 months old, weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group (muscle injection of saline solution, n = 15, group NC), model group (muscle injection of dexamethasone, n = 15, group GIOP), and treatment group (muscle injection of dexamethasone combined with oral perindopril, n = 15, group GIOP+ACEI). All rabbits put to death after 12 weeks' treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology, biomechanics, metabolic bone related serological indexes and mRNA expression.

RESULTSAt 12 weeks, the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC (P < 0.05); after perindopril treatment, the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP (P < 0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however, osteoclast number, osteoclast surface, eroded surface, and urinary deoxypyridinoline in group GIOP increased than group NC (P < 0.05); these changes were inhibited after perindopril treatment (P < 0.05). Quantitative RT-PCR revealed that after dexamethasone treatment, the ratio of SOST mRNS expression and RANKL/OPG mRNA expression obviously increased than that of group NC (P < 0.05); and Runx2 expression decreased significantly (P < 0.05); while the changes of mRNA expression were improved by perindopril treatment.

CONCLUSIONPerindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid-induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.

Animals ; Biomechanical Phenomena ; Glucocorticoids ; adverse effects ; Male ; Osteoporosis ; chemically induced ; prevention & control ; Perindopril ; therapeutic use ; Rabbits