Switchable reflection/transmission utilizing polarization on a plasmonic structure consisting of self-assembly polystyrene spheres with silver patches.

We report a plasmonic structure for switchable reflection and transmission by polarization. The structure is composed of a hexagonal-packed polystyrene sphere array with silver patches on them. Simulations and experiments demonstrated that the conversions between reflected beams and transmitted ones can be performed when the polarization directions of incident beams vary from 0° to 90°. A switchable reflection and transmission at a given wavelength can be obtained, as long as sizes of PS spheres and azimuthal angles are properly chosen. Such a patchy plasmonic structure serving as a switch between reflection and transmission have potential applications in photoelectric control devices.

Integrity of the blood-testis barrier in healthy men after suppression of spermatogenesis with testosterone and levonorgestrel.

STUDY QUESTION: Do exogenous male hormonal contraceptives that suppress intratesticular testosterone and spermatogenesis interfere with the blood-testis barrier integrity in men? SUMMARY ANSWER: When spermatogenesis was suppressed by testosterone alone or combined with levonorgestrel (LNG) treatment in men, the structural appearance of Sertoli cell tight junctions remained intact in the human testis. WHAT IS ALREADY KNOWN: Testosterone promotes the integrity of the blood-testis barrier. Intratesticular androgen deprivation induced by exogenous testosterone plus a progestin to suppress spermatogenesis in a contraceptive regimen may disturb the structural and functional integrity of the blood-testis barrier. STUDY DESIGN, SIZE AND DURATION: Testicular biopsies were obtained from a sub-study of a randomized clinical trial of 36 healthy Chinese men who were treated for 18 weeks and followed for at least a 12-week recovery period. PARTICIPANTS/MATERIAL, SETTING, METHODS: Healthy Chinese male volunteers (27-48 years) were randomized to two treatment groups (n = 18/group) for 18 weeks: (1) testosterone undecanoate (TU) 1000 mg i.m. injection followed by a 500 mg injection every 6 weeks and (2) TU + LNG 250 µg orally daily. Blood samples were obtained from all participants before and during treatment and at the end of the recovery phase. Open testicular biopsies for this study were obtained from four men before treatment and from four men in each of the TU and TU + LNG groups at 2 and 9 weeks of treatment. The presence of antisperm antibodies was checked in the archived serum samples of the subjects at baseline, during treatment and at the end of the recovery period. Stored testicular biopsy samples from cynomolgus monkeys treated with either sub-cutaneous testosterone or placebo for 12 weeks were used for additional protein expression studies. MAIN RESULTS AND ROLE OF THE CHANCE: Expression of blood-testis barrier associated proteins quantified by immunohistochemistry (claudin 3, claudin 11, junctional adhesion molecule-A, zonula occludens-1) remained unchanged despite a significant decrease in the numbers of pachytene spermatocytes and round spermatids in the seminiferous tubules at 9 weeks in the TU + LNG group. This was confirmed by immunoblots showing a lack of quantitative change in these tight junction proteins in monkeys after testosterone treatment. There were no increases in serum antisperm antibodies in the volunteers during the study. LIMITATIONS/REASONS FOR CAUTION: The duration of the study was short and the long-term effects of male hormonal contraceptive treatments on the integrity of the blood-testis barrier remain to be determined. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the safety of male hormonal contraceptive treatment and does not corroborate the previous findings of disturbed immunological integrity of the blood-testis barrier from animal studies such as androgen receptor knockout mice and exogenous hormonal treatment in rats. STUDY FUNDING/COMPETING INTEREST: The study was supported by grants from the Contraceptive Research and Development Program and the Mellon Foundation (MFG-02-64, MFG-03-67), Endocrine, Metabolism and Nutrition Training Grant (T32 DK007571), the Clinical and Translational Science Institute at Los Angeles Biomedical and Harbor-UCLA Medical Center (UL1RR033176 and UL1TR000124) and the Los Angeles Biomedical Research Institute Summer High School Student Program.

Highly selective and potent mu opioid ligands by unexpected substituent on morphine skeleton.

Unexpected substituent on the well-known morphine skeleton is described to be account for highly selective and potent mu opioid ligands, which is strongly connected to substituted aromatic groups on this omitted 8alpha-position.

[A study on population-based prenatal screening and diagnosis of Down's syndrome in Jiangsu province].

OBJECTIVE: To screen and diagnose Down's syndrome during mid-term pregnancy to reduce the number of babies with Down's syndrome. METHODS: With the multi-level of stratified cluster sampling, twenty thousand and eight hundred and three women at 15-20 weeks gestation were screened by maternal serum AFP and beta-hCG using the time resolved fluoroimmunoassay (TRFIA). Then the screened high-risk women were diagnosed by amniocentesis, cell culture and chromosome analyses. The born children were diagnosed by follow-up and peripheral blood chromosome analyses. RESULTS: Six fetuses were diagnosed by serum screening and amniotic fluid chromosome analyses, and 3 born children were diagnosed by follow-up and peripheral blood chromosome analyses. Nine cases of Down's syndrome were detected in total, with the positive prenatal screen rate being 67% (6/9). CONCLUSION: The prenatal screening and diagnosis can reduce the birth of Down's syndrome patients and improve the population quality. However, the diagnosis accuracy still needs to be improved to further reduce the false negative rate and prevent misdiagnosis.

(3S,4R)-3-Ethyl-4-hydr-oxy-3-(3-methoxy-phen-yl)-1-methyl-azepanium (2R,3R)-2,3-bis-(benzo-yloxy)-3-carboxy-propionate.

The crystal structure of the title compound, C(16)H(26)NO(2) (+)·C(18)H(13)O(8) (-), is stabilized by an extensive network of classical N-H⋯O and O-H⋯O hydrogen bonding. The crystal structure also shows an ammonium-driven diastereo-isomerism.

[Long-term toxicity of Shen Yan Ling tablet and its effect on male reproductive function in rats].

OBJECTIVE: Shen Yan Ling Tablet is an innovative compound of traditional Chinese medicine, scientifically prepared with Tripterygium wilfordii, Radix Astragali, and others, with precise efficacy on renal diseases and reduced adverse effects of Tripterygium wilfordii. Based on the Guiding Principles for New Drug Toxicity Research Before Clinical Application, we investigated the long-term toxicity of Shen Yan Ling Tablet and its effect on the reproductive function in rats. METHODS: According to the clinical therapeutic dose and the results of the acute toxicity test of Shen Yan Ling Tablet, we equally divided 80 rats (males and females half-and-half) into a low-dose (1.25 g/kg body wt), a medium-dose (2.50 g/kg body wt), a high-dose (5.00 g/kg body wt) and a control group. After a 3-month medication, we conducted standardized long-term toxicity tests and observed the effects of Shen Yan Ling on the serum sexual hormones and epididymal sperm count. RESULTS: After 3 months of treatment with Shen Yan Ling, no death occurred, the general status remained unchanged, and the parameters of blood cytology and biochemistry fluctuated within the normal range, without any significant changes (P > 0.05). Some blood parameters, RBC, WBC, HGB, AST and TBIL, showed statistic changes (P < 0.05), but with no clinical significance. There were no significant differences in the mass coefficients of the main organs between the medication and control groups. The high-dose group exhibited slight hepatic and pulmonary pathological changes and significantly reduced sperm counts in the epididymis, but no significant changes in serum sexual hormones (P < 0.05). CONCLUSION: Three-month medication of Shen Yan Ling at 1.25 - 5.00 g/kg produced no significant accumulated toxicity on rats, but it had a negative effect on their reproductive function at a higher dose of > or = 5.00 g/kg.

Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis.

CONTEXT: Male hormonal contraceptive methods require effective suppression of sperm output. OBJECTIVE: The objective of the study was to define the covariables that influence the rate and extent of suppression of spermatogenesis to a level shown in previous World Health Organization-sponsored studies to be sufficient for contraceptive purposes (< or =1 million/ml). DESIGN: This was an integrated analysis of all published male hormonal contraceptive studies of at least 3 months' treatment duration. SETTING: Deidentified individual subject data were provided by investigators of 30 studies published between 1990 and 2006. PARTICIPANTS: A total of 1756 healthy men (by physical, blood, and semen exam) aged 18-51 yr of predominantly Caucasian (two thirds) or Asian (one third) descent were studied. This represents about 85% of all the published data. INTERVENTION(S): Men were treated with different preparations of testosterone, with or without various progestins. MAIN OUTCOME MEASURE: Semen analysis was the main measure. RESULTS: Progestin coadministration increased both the rate and extent of suppression. Caucasian men suppressed sperm output faster initially but ultimately to a less complete extent than did non-Caucasians. Younger age and lower initial blood testosterone or sperm concentration were also associated with faster suppression, but the independent effect sizes for age and baseline testicular function were relatively small. CONCLUSION: Male hormonal contraceptives can be practically applied to a wide range of men but require coadministration of an androgen with a second agent (i.e. progestin) for earlier and more complete suppression of sperm output. Whereas considerable progress has been made toward defining clinically effective combinations, further optimization of androgen-progestin treatment regimens is still required.

(3S,4S)-3-Ethyl-4-hydr-oxy-3-(3-methoxy-phen-yl)-1-methyl-azepan-1-ium d-tartrate dihydrate.

In the title compound, C(16)H(26)NO(2) (+)·C(4)H(5)O(6) (-)·2H(2)O, a meptaz-inol derivative, three C atoms of the azepane ring are disordered over two positions, with site-occupancy factors of 0.80 and 0.20; the major disorder component adopts a twist-chair conformation, while the minor component has a chair conformation. The benzene ring is axially substituted on the heterocyclic ring, resulting in a folded conformation of the cation. The absolute configuration was determined with reference to d-tartaric acid. The crystal structure is stabilized by an extensive network of intra- and inter-molecular O-H⋯O hydrogen bonds.

[Changes of semen parameters in Chinese fertile men in the past 25 years].

OBJECTIVE: To analyze the changes of seminal parameters in Chinese fertile men during the past 25 years. METHODS: We collected semen samples from 5,834 fertile men in 14 different provinces (including Beijing) between 1980 and 2005 and retrospectively studied their seminal parameters, abstinence durations and total testis volumes by meta-analysis. RESULTS: Compared with the first 15 years, a significant decrease was observed in both sperm density and total number of sperm per ejaculate in the semen samples collected between 1996-2000 (P < 0.0001 and P < 0.05), but not obvious in those between 1996-2000 and after 2005 (P > 0.05). As for sperm motility, no time-related changes were noted (P > 0.05) except a reduction with the increase of age. CONCLUSION: There was a decline in sperm density and total number of sperm per ejaculate in Chinese fertile men over the past 25 years, although not significant in the latter 10 years since 1996, but with no time-related changes in sperm motility.

transient scrotal hyperthermia and levonorgestrel enhance testosterone-induced spermatogenesis suppression in men through increased germ cell apoptosis.

CONTEXT: In rodents and monkeys, a combination of hormonal and physical agents accelerates germ cell death. OBJECTIVE: A "proof of concept" study was performed to investigate whether addition of heat exposure or a progestin to an androgen induces germ cell death and more complete and rapid spermatogenesis suppression. DESIGN AND SETTINGS: A randomized clinical trial was performed at academic medical centers. PARTICIPANTS: We treated four groups of healthy male volunteers (18 per group) for 18 wk: 1) testosterone undecanoate (TU) 1000 mg im (first dose), followed by 500 mg im every 6 wk; 2) submersion of scrota at 43 C in water for 30 min/d for 6 consecutive days; 3) TU plus heat; and 4) TU plus oral levonorgestrel (LNG) 250 microg/d. MAIN OUTCOME MEASURES: Semen parameters, testicular histology, and germ cell apoptosis were the main outcome measures. RESULTS: Heat alone and TU plus heat suppressed sperm counts more than TU alone by wk 6. By wk 9, recovery began in the heat only group, whereas spermatogenesis remained suppressed in the TU plus heat group. Oral LNG plus TU suppressed spermatogenesis earlier and more severely than TU alone. At wk 2, significantly greater germ cell apoptosis occurred in heat and heat plus TU subjects, but not in subjects without heat treatment, compared with pretreatment subjects. By 9 wk, markedly smaller seminiferous tubule diameters and fewer spermatocytes and spermatids were noted in all 12 biopsies from men receiving TU, TU plus LNG, with most dramatic differences for the TU plus heat group, whereas no differences from pretreatment biopsies were observed in men who received heat treatment only. CONCLUSIONS: Heat causes a rapid and transient suppression of spermatogenesis. TU plus heat resulted in low-sperm output that was maintained by continuous treatment with TU. Addition of an oral progestin accelerated spermatogenesis suppression by TU alone. Increased germ cell apoptosis contributed to suppression of spermatogenesis.

QSAR study of 4-phenylpiperidine derivatives as mu opioid agonists by neural network method.

A nonlinear QSAR study was conducted on a series of 4-phenylpiperidine derivatives (4PPs) acting as mu opioid agonists by three-layer back-propagation neural network (NN) method. At first a variety of molecular descriptors were calculated and then selected with two-stage least squares combining partial least squares (PLS) method. The selected four molecular descriptors, out of 292 ones, were correlated with the known analgesic activities of 38 4PPs by NN method. The established QSAR model was further validated by five additional 4PPs, as an external testing set. Moreover, a pharmacophore model was hypothesized based on the results, which would be helpful for structural optimization of 4PPs.

[Effect of selective 5alpha-reductase inhibitor or/and testosterone undecanoate on the reproductive function of male rats].

OBJECTIVE: To investigate whether 5alpha-reductase inhibitor and dihydrotestosterone (DHT) play a role in spermatogenesis in male rats. METHODS: Thirty-two male rats were divided into 4 groups (Groups C, T, F and FT). Group C received plant oil injection and oral starch perfusion, Group T testosterone undecanoate (TU, 20 mg/kg) injection and oral starch perfusion, Group F plant oil injection and oral Finasteride perfusion, and Group FT TU (20 mg/kg) injection and oral Finasteride perfusion. Data on serum T and DHT, sperm count, sperm mobility and reproductive function were collected and analysed. RESULTS: (1) 5alpha-reductase inhibitor, Finasteride and TU reduced the weight of the testis and epididymis in the experiment groups compared with the negative control (Group C), but TU increased the weight of the prostate while Finasteride decreased it compared with the positive control (Group T). TU combined with Finasteride could counteract the effect of the weight increase of the prostate, but not that of the testis. (2) Finasteride, or Finasteride combined with TU, reduced the DHT but increased the testosterone level in comparison with the control group. (3) Both Finasteride and TU could inhibit epididymal sperm count and reproductive function compared with the control, but the effect was less significant in Group FT than in Group F. CONCLUSION: High dosages of 5alpha-reductase inhibitor, Finasteride, can suppress male reproductive function, but the inhibiting effect could be counteracted by administration of 5alpha-reductase inhibitor along with TU.

[Effect of large-dosage of 5alpha-reductase inhibitors on the spermatogenesis of male rats].

OBJECTIVE: To identify the role of 5alpha-reductase in the spermatogenesis of male rats by studying the effect of two 5alpha-reductase inhibitors, Epristeride and Finasteride, on the spermatogenesis in male Sprague-Dawley (SD) rats. METHODS: Changes in the weight of the testis, serum testosterone and dihydrotestosterone levels, epididymal sperm count, and reproductive function were observed and analyzed after the two 5alpha-reductase inhibitors were administered to male SD rats orally. RESULTS: The experiment showed that in comparison with control animals, both the two 5alpha-reductase inhibitors: 1. suppressed the development of the prostate and reduced the weight of the testis in the experimental groups (P < 0.05); 2. decreased the serum level of dihydrotestosterone and enhanced testosterone; 3. inhibited epididymal sperm count and productive function. CONCLUSION: High dosages of the 5alpha-reductase inhibitor, Epristeride, can suppress the development of the prostate and reduce the weight of the testis, decrease dihydrotestosterone, and inhibit spermatogenesis and productive function in male rats.

[Experiment on the sexual virility of immature mice immunized with LHRH fusion protein vaccine].

OBJECTIVE: To observe the sexual virility of immature immature male mice were divided into a pre-ablactation group (n 10). The first two groups were immunized with the LHRH fusion proportion of pregnant female mice, the morphological and histological examined to conform the emasculating effect of the vaccine. When ted with testosterone (1.0 ml each) , the post-ablactation ones were rameters. RESULTS: The sexual virility of the immature mice immunized in 3 -4 months. CONCLUSION: The LHRH fusion protein vaccine mice after ablactation, and the sexual virility can recover in the pre-ablactation decrease.

A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men.

This report describes a Phase II, multicenter, contraceptive efficacy clinical trial using monthly injections of testosterone undecanoate (TU) alone at a dose of 500 mg in healthy Chinese men. Three hundred eight healthy men were recruited in six centers distributed throughout China. Volunteers underwent a control period with no treatment, then a 12-month treatment period including a 6-month suppression phase followed by a 6-month efficacy phase and a 12-month recovery period. During the suppression phase, an initial loading dose of 1000 mg TU, followed by 500 TU at monthly intervals were given until azoospermia or severe oligozoospermia was achieved, up to a maximum of six injections. During the efficacy phase, 500 mg TU were administered at monthly intervals for 6 months. Nine of 308 men did not achieve azoospermia or severe oligozoospermia (<3 x 10(6)/ml) within the 6-month suppression phase. This gave a methodological failure rate of 2.9/100 couple years (95% confidence interval of 1.0-4.8/100 couple years). Two hundred ninety-six men entered the efficacy phase. The continuation rate during the efficacy phase was 95/100 couple years. There were no pregnancies caused by men who achieved azoospermia or severe oligozoospermia. Reappearance of sperm occurred in six men during the efficacy phase, and one pregnancy was attributed to sperm rebound. This gave a secondary failure rate of 2.3/100 couple years (95% confidence interval of 0.5-4.2/100 couple years). Thus, the total failure rate was 5.2%, and total efficacy was 94.8%. Spermatogenesis in all subjects returned to the normal reference range within the recovery period. The mean serum testosterone concentration increased 131%, and the mean serum LH and FSH concentrations decreased 72% and 70%, respectively, after TU injections during the treatment period. The mean level of serum high density lipoprotein cholesterol decreased (14%), and the mean hematocrit increased 6% compared with baseline. No serious adverse events and no significant changes in serum chemistry occurred during the study. The results showed that monthly TU injection at a dose of 500 mg after an initial loading dose of 1000 mg can effectively, safely, and reversibly suppress spermatogenesis in healthy Chinese men without serious adverse effects.

Male hormonal contraception: effects of injections of testosterone undecanoate and depot medroxyprogesterone acetate at eight-week intervals in chinese men.

Surveys indicate that one form of acceptable male hormonal contraception would consist of injections given at 2- to 3-month intervals. This report describes a study of depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-wk intervals for suppression of spermatogenesis in healthy Chinese men. After screening, 30 healthy volunteers were enrolled and randomly assigned to one of three dose groups (n = 10/group): 1000 mg TU (group A); 1000 mg TU plus 150 mg DMPA (group B); 1000 mg TU plus 300 mg DMPA (group C). All doses were given as im injections at 8-wk intervals. The study consisted of an 8-wk control (baseline) period, a 24-wk treatment period, and a 24-wk recovery period. Consistent azoospermia or severe oligozoospermia was achieved and maintained in all volunteers during the treatment period, except for two men in the TU-alone group who experienced a rebound in sperm concentrations. An 8-wk regimen of TU plus DMPA at both tested combination doses effectively suppressed spermatogenesis to azoospermia in Chinese men. All volunteers tolerated the injections; no serious adverse effects were reported. The lower-dose combination is recommended for further testing in an expanded clinical trial or contraceptive efficacy study.

Quantitative (stereological) study of incomplete spermatogenic suppression induced by testosterone undecanoate injection in rats.

AIM: To evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment. METHODS: Adult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 days for 130 days. The numbers of all types of cells (nuclei) in the seminiferous tubules and the interstitial tissue were estimated using a contemporary stereological tool, the optical disector. RESULTS: In response to TU treatment, the numbers of non-type B spermatogonia, type B spermatogonia and late elongated spermatids per testis were reduced to 51 %, 66 % and 14 % of the controls, respectively. The conversion ratios from type B spermatogonia to early spermatocytes and pachytene spermatocytes were not significantly affected and the ratios to the later germ cell types fell to 51 % - 65 % of the controls. Less than 1.0 % of immature round spermatids were seen sloughing into the tubule lumen, 4.0 % of elongated spermatids retained in the seminiferous epithelium, and about half of the elongated spermatid nuclei appreciably malformed. Leydig cells were atrophied but their number and the peritubular myoid cell number per testis were unchanged. CONCLUSION: Double inhibition of spermatogenesis (i.e. inhibition at spermiation and spermatogonial conversion to type B spermatogonia), a scenario seen in the monkey and human following gonadotrophin withdrawal, was not sufficiently effective for a complete spermatogenic suppression in the rat after TU treatment, probably due to ineffective inhibition of the Leydig cell population and therefore the intra-testicular testosterone levels.

[Research report of experimental database establishment of digitized virtual Chinese No.1 female].

OBJECTIVE: To establish digitized virtual Chinese No.1 female (VCH-F1) image database. METHODS: A 19 years old female cadaver was scanned by CT, MRI, and perfused with red filling material through formal artery before freezing and em- bedding. The whole body was cut by JZ1500A vertical milling machine with a 0.2 mm inter-spacing. All the images was produced by Fuji FinePix S2 Pro camera. RESULTS: The body index of VCH-F1 was 94%. We cut 8 556 sections of the whole body, and each image was 17.5 MB in size and the whole database reached 149.7 GB. We have totally 6 versions of the database for different applications. CONCLUSIONS: Compared with other databases, VCH-F1 has good representation of the Chinese body shape, colorful filling material in blood vessels providing enough information for future registration and segmentation. Vertical embedding and cutting helped to retain normal human physiological posture, and the image quality and operation efficiency were improved by using various techniques such as one-time freezing and fixation, double-temperature icehouse, large-diameter milling disc and whole body cutting.

[Androgen replacement therapy for hypogonadal men].

Male hypogonadism is a group of syndromes in clinic andrology characterized by complete or partial androgen deficiency. It can be divided into primary and secondary hypogonadism. Besides the etiological treatment, androgen replacement therapy should be adopted in all patients of primary hypogonadism and patients of secondary hypogonadism who do not have the need of having a child. For patient's benefits, androgen should be used and selected properly as there are so many androgen preparation at present.

[Studies and progress of male hormonal contraception].

It has become more and more urgent to develop a safe, effective, recoverable and acceptable contraceptive for males. Decades of studies have made much progress on male hormonal contraception, one of the promising contraceptive methods. The principle is based on the suppression of pituitary gonadotropin and intratesticular testosterone, then the suppression of spermatogenesis, and the supplement of androgen to maintain the male characteristics and sexual function. There are many male hormonal contraceptive methods being studied include androgen, androgen combined with progesterone, GnRH antagonists combined with androgen, as well as immunological methods. To develop a safe and convenient androgen preparation with longer action and fewer side effects is also one of the key items of present research in this field.