Effects of leucocytospermia on semen parameters and outcomes of intracytoplasmic sperm injection

Leucocytes are present throughout the male reproductive tract but the clinical significance of leucocytic infiltration in the human ejaculate is controversial. The World Health Organization (WHO) defines leucocytospermia as the presence of peroxidase-positive leucocytes in concentrations of > or =1 x 10(6)/mL of semen. The goals of this study were to clarify the relationship between leucocytospermia and semen parameters including sperm concentration, progressive and total motility before and after semen preparation, and intracytoplasmic sperm injection (ICSI) outcomes, including fertilization, embryo development, embryo morphology, cleavage and pregnancy rates. We compared the semen parameters and ICSI outcome of 34 leucocytospermic and 36 non-leucocytospermic control couples who were undergoing ICSI because of male factor infertility including oligo and/or astheno and/or teratozoospermia. Semen parameters including progressive motility rate (1.5% vs. 3%) and sperm concentrations (12 vs. 29 million/mL) were significantly lower in the leucocytospermic group compared with the control group. Other semen parameters were not affected by the presence of leucocytes. ICSI outcome, including fertilization (82% vs. 87%) and embryo development rates (79% vs. 86%) were significantly lower in the leucocytospermic group compared with the control group although there were no statistical difference for embryo quality, embryo cleavage and pregnancy rates. These results indicate that some semen parameters and the outcome of ICSI were negatively affected by the presence of leucocytospermia.     

Sodium fusidate-poly(D,L-lactide-co-glycolide) microspheres: Preparation,characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis

Purpose: The aim of this study was to prepare poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing sodium fusidate (SF) using a double emulsion solvent evaporation method with varying polymer:drug ratios (1:1, 2.5:1, 5:1) and to evaluate its efficiency for the local treatment of chronic osteomyelitis.

Methods: The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations had been carried out. Sterilized SF-PLGA microspheres were implanted in the proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay.

Results: PLGA microspheres between the size ranges of 2.16–4.12?µm were obtained. Production yield of all formulations was found to be higher than 79% and encapsulation efficiencies of 19.8–34.3% were obtained. DSC thermogram showed that the SF was in an amorphous state in the microspheres and the glass transition temperature (T_g) of PLGA was not influenced by the preparation procedure. In vitro drug release studies had indicated that these microspheres had significant burst release and their drug release rates were decreased upon increasing the polymer:drug ratio (p?<?0.05). Based on the in vivo data, rats implanted with SF-PLGA microspheres and empty microspheres showed 1987?±?1196 and 55526?±?49086 colony forming unit of MRSA in 1?g bone samples (CFU/g), respectively (p?<?0.01).

Conclusion: The in vitro and in vivo studies had shown that the implanted SF loaded microspheres were found to be effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting.     

Efficacy of various activation techniques on tubule penetration of resin-based and bioceramic root canal sealers: An in vitro confocal microscopy study

To compare the penetration of Ah Plus and MTA Fillapex after irrigation activation with sonic, passive ultrasonic, SWEEPS and XP-Endo Finisher using confocal microscopy. Instrumented root canals of 160 mandibular premolar teeth were allocated randomly to four groups (n = 40/group) and eight subgroups according to the activation techniques and canal sealers (n = 20/subgroup). After the obturation, three sections at 1–2, 5–6 and 9–10 mm levels from the apex were examined. Penetration area and maximum penetration depth values were represented as mean and standard deviation, and results below 0.05 were considered statistically significant. For penetration area and maximum penetration depth, the statistical difference was found in terms of material, device and region (Maximum penetration depth: p = 0.006, p < 0.001, p < 0.001; Penetration area: p = 0.004, p < 0.001, p < 0.001). SWEEPS was found to be relatively higher than other groups. Sealers presented similar results when evaluated independently of the region. The use of SWEEPS for irrigation activation is promising in terms of tubule penetration.     

1,3,4-Thiadiazole and 1,2,4-triazole-5-thione derivatives bearing 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one ring: Synthesis,molecular docking,urease inhibition,and crystal structure

Two series of 1,3,4-thiadiazole ( 40a–o ) and 1,2,4-triazole-5-thione ( 41a–l ) derivatives bearing a 2-pentyl-5-phenyl-1,2,4-triazole-3-one ring were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. Among the two groups, the first group ( 40a–o ) did not show good activity while the second group ( 41a–l ) showed excellent activity. Compound 41j (1091.24 ± 14.02 µM) of the second series of compounds showed lower activity than thiourea, while the remaining 11 compounds ( 41a–i , k , and l ) showed better activity than thiourea (183.92 ± 13.14 µM). Among the 11 compounds, 41b (15.96 ± 2.28 µM) having the 3-F group on the phenyl ring showed the highest inhibitory activity. Urease kinetic studies of 41b , which is the most active compound, determined it to have an un-competitive inhibition potential. Moreover, in silico analysis against urease from jack bean with 27 new heterocyclic compounds and the reference molecule was carried out to see the necessary interactions responsible for urease activity. The docking calculations of all compounds supported stronger binding to the receptor than the reference molecule, with high inhibition constants. In addition, compound 40m was characterized by single-crystal X-ray diffraction analysis. X-ray analysis reveals that the structures of the compound 40m crystallize in the monoclinic P21/c space group with the cell parameters: a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0(7) ų. X-ray diffraction analyses were also performed to gain insights into the role of weak intermolecular interactions and C-H…X (halogen) interactions in compound 40m that influence the crystal packing.     

Long‐term efficacy and safety of etanercept in children with polyarticular‐course juvenile rheumatoid arthritis: Interim results from an ongoing multicenter,open‐label,extended‐treatment trial

Objective

To evaluate the long‐term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open‐label, extended‐treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept.

Methods

Etanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3–4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of ≥30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%.

Results

At the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low‐dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population.

Conclusion

Children with severe, longstanding, methotrexate‐resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well‐tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections.