Andrology: Relationship between stimulated hyperactivated motility of human spermatozoa and pregnancy rate in donor insemination: a preliminary report

The proportion of spermatozoa exhibiting the vigorous motilitybehaviour termed ’hyperactivation‘ (HA) has beenshown to be increased following removal of seminal plasma andstimulation with chemical agents such as pentoxifylline. Theaim of this study was to examine the relationship between theproportion of HA in cryopreserved semen samples from sperm donorsand the corresponding pregnancy rates achieved by donor insemination.Cryopreserved samples from 20 men were incubated in the presenceor absence of 3 mM pentoxifylline for 1 h and the %HA determinedin each sample. The relationship between pregnancy rate, theproportion of HA spermatozoa in control and pentoxifyllinetreatedgroups and the change in %HA following pentoxifylline treatment(HA) as well as the mean semen characteristics for each donor[sperm count, motility (%), motility index, normal morphology(%), post-thaw motility (%) and post-thaw motility index] wereexamined by logistic regression of the occurrence of clinicalpregnancy with each insemination. Both HA and mean post-thawmotility index were significantly related to pregnancy ratesand together accounted for 64% of the observed variation inpregnancy rates.     

In vitro antitumor activity of MIC2 protein-doxorubicin conjugates

The pseudoautosomal encoded MIC2 glycoprotein is a tumor-associated antigen of Ewing's sarcoma (ES) and closely related tumors of unknown function. To investigate the use of this protein as selective drug carrier recombinant MIC2 was coupled to doxorubicin by a two step glutaraldehyde method (molar ratio DOX/MIC2 of 32 and 16). The conjugates showed dose-dependent cytostatic activity against the ES cell line SK-ES1, the peripheral neuroectodermal line KAL and the prostate cancer cell line PC-3 concurrent with reduced toxicity against normal lymphoblasts. In comparison to free doxorubicin the MIC2-doxorubicin conjugates exhibited highest activity against the PC-3 cell line. Confocal microscopy showed intracellular accumulation of MIC2 conjugates.     

Inhibitory effect of antagonists of bombesin and growth hormone-releasing hormone on orthotopic and intraosseous growth and invasiveness of PC-3 human prostate cancer in nude mice.

PURPOSE: To determine whether antagonists of growth hormone-releasing hormone (GHRH) and bombesin/gastrin-releasing peptide (BN/GRP) can inhibit the orthotopic and metastatic growth of PC-3 human androgen-independent prostate cancers. EXPERIMENTAL DESIGN: The effects of administration of GHRH antagonist MZ-J-7-118, BN/GRP antagonist RC-3940-II, and their combination on the growth and metastatic spread of PC-3 tumors implanted orthotopically into nude mice were evaluated. The efficacy of this treatment on PC-3 tumors implanted intratibially and s.c. was also determined. RESULTS: Treatment with MZ-J-7-118, RC-3940-II, or their combination significantly inhibited the growth of PC-3 tumors implanted orthotopically, intraosseously, and s.c. The combination of the two antagonists had the greatest effect, inhibiting orthotopic tumor growth by 77%, intratibially implanted tumors by 86%, and s.c. tumors by 86%. The therapy with BN/GRP and GHRH antagonists, especially in combination, also reduced the local tumor spread and distant metastases in animals bearing orthotopic tumors. Combination therapy was likewise the most effective in reducing the incidence and severity of tibial osteolytic lesions and pathologic fractures in intraosseously implanted tumors. High-affinity binding sites for BN/GRP and GHRH were found in s.c. and orthotopic PC-3 tumor samples. MZ-J-7-118, RC-3940-II, and the combination of both compounds inhibited in vitro growth of PC-3 cells. CONCLUSIONS: Our findings show the efficacy of BN/GRP antagonists and GHRH antagonists for the treatment of advanced prostate cancer in preclinical metastatic models. As BN/GRP antagonists are already in clinical trials and GHRH antagonists are effective in androgen-independent prostate cancer models, these analogues could be considered for the management of advanced prostate carcinoma.     

Control of Dielectric and Mechanical Properties of Styrenic Block Copolymer by Graphite Incorporation

The structure–property relationship of dielectric elastomers, as well as the methods of improving the control of this relationship, has been widely studied over the last few years, including in some of our previous works. In this paper, we study the control, improvement, and correlation, for a significant range of temperatures, of the mechanical and dielectric properties of polystyrene-b-(ethylene-co-butylene)-b-styrene (SEBS) and maleic-anhydride-grafted SEBS (SEBS-MA) by using graphite (G) as filler in various concentrations. The aim is to analyze the suitability of these composites for converting electrical energy into mechanical energy or vice versa. The dielectric spectroscopy analysis performed in the frequency range of 10 to 1 MHz and at temperatures between 27 and 77 °C emphasized an exponential increase in real permittivity with G concentration, a low level of dielectric losses (≈10⁻³), as well as the stability of dielectric losses with temperature for high G content. These results correlate well with the increase in mechanical stiffness with an increase in G content for both SEBS/G and SEBS-MA/G composites. The activation energies for the dielectric relaxation processes detected in SEBS/G and SEBS-MA/G composites were also determined and discussed in connection with the mechanical, thermal, and structural properties resulting from thermogravimetric analysis, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses.     

Birth outcomes of patients with isolated anorectal malformations: A population‐based case‐control study

In most patients affected by isolated anorectal malformation (IARM) the etiology is largely unknown. Thus, the aim of our project was to analyze possible risk factors for IARM. In the first step, birth outcomes of cases with IARM were analyzed on the basis of maternal socio‐demographic variables, and these data are presented in this paper. Gestational age at delivery, birthweight, preterm birth, low birthweight and small for gestational age of cases with IARM were evaluated in the function of maternal age, birth/pregnancy order, marital and employment status of mothers in the population‐based large dataset of the Hungarian Case‐Control Surveillance of Congenital Abnormalities, 1980–1996. The study samples included 231 live‐born cases with IARM, 361 matched and 38 151 population controls without any defect. IARMs are more frequent in males, twins and newborn infants with low birthweight and small‐for‐gestational‐age, the latter being the consequence of intrauterine growth restriction. In addition, mothers of cases were younger but with higher birth order, and had lower socio‐economic status. These maternal variables are characteristic for the gypsy population in Hungary. The higher proportion of gypsy women among the mothers of cases with IARM was confirmed during the home visits of the study. Male sex and intrauterine growth restriction of cases, in addition to low socioeconomic status and gypsy origin of mothers may have a role in the risk of IARMs.     

A new intraocular lens design to reduce spherical aberration of pseudophakic eyes

PURPOSE: The aim of this study was to design and evaluate in the laboratory a new intraocular lens (IOL) intended to provide superior ocular optical quality by reducing spherical aberration. METHODS: Corneal topography measurements were performed on 71 cataract patients using an Orbscan I. The measured corneal surface shapes were used to determine the wavefront aberration of each cornea. A model cornea was then designed to reproduce the measured average spherical aberration. This model cornea was used to design IOLs having a fixed amount of negative spherical aberration that partially compensates for the average positive spherical aberration of the cornea. Theoretical and physical eye models were used to assess the expected improvement in optical quality of an eye implanted with this lens. RESULTS: Measurements of optical quality provided evidence that if this modified prolate IOL was centered within 0.4 mm and tilted less than 7 degrees, it would exceed the optical performance of a conventional spherical IOL. This improvement occurred without an apparent loss in depth of focus. CONCLUSION: A new IOL with a prolate anterior surface, designed to partially compensate for the average spherical aberration of the cornea, is intended to improve the ocular optical quality of pseudophakic patients.     

Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents, but more precise estimates of their effects on major adverse cardiovascular events (MACE), mortality, and safety are needed. We systematically reviewed and meta-analyzed randomized controlled trials with durations ≥ 6 months comparing MACE, mortality, and safety with PCSK9 inhibitors vs control. We searched CENTRAL, Embase, MedLine and the grey literature to November 7, 2018. From 2048 articles, we included 23 trials (n = 60,723). PCSK9 inhibitors reduced MACE (relative risk, 0.83; 95% confidence interval, 0.78-0.88), but did not clearly reduce mortality (relative risk, 0.93; 95% confidence interval, 0.85-1.02) or increase adverse events. In conclusion, PCSK9 inhibitors reduce nonfatal MACE, are well tolerated, but effects on mortality remain unclear.