Stem cells for reproductive medicine

The generation of various pluripotent stem cell lines provides a new route to investigate developmental process of germ cell and embryo development, which until now was difficult to access in the human. In the future these cells may be used for new therapies in reproductive medicine. This brief review outlines the development of germ cells and their pluripotent capabilities, how embryonic and germline stem cells can mimic developmental processes in vitro and generate gamete and trophoblast phenotypes for research and potential treatments.     

9‐month results of polymer‐free sirolimus eluting stents in young patients compared to a septuagenarian and octogenarian all‐comer population

Objectives

To evaluate the 9‐month safety and efficacy of polymer‐free sirolimus eluting drug eluting stents in septuagenarians and octogenarians.

Methods

An all‐comer, worldwide single armed trial ( ClinicalTrials.gov Identifier NCT02629575) was conducted to demonstrate the safety and efficacy of an ultra‐thin strut, polymer‐free sirolimus eluting stent (PF‐SES). The primary endpoint was the 9‐month target revascularization rate (TLR). Secondary endpoints included the rates of major adverse cardiac events (MACE), stent thrombosis (ST) and bleeding (BARC) in septuagenarians (≥70 years, <80 years), and in octogenarians (≥80 years) to be compared to the younger patient group (<70 years).

Results

A total of 1607 patients were treated with PF‐SES in the sub‐70‐year‐old age group, 694 in septuagenarians, and 371 in the octogenarian patient group. At 9 months, the MACE rates were 7.2% in octogenarians, 5.3% in septuagenarians, and 3.0% in the younger patient group (P = 0.001). These were mostly driven by all‐cause mortality (4.4% vs 1.9% vs 0.6%, P < 0.001) while the TLR rates were only numerically lower in the younger age group (P = 0.080). BARC 1‐5 bleeding events were more frequent in the older age group (1.9% vs 2.7% vs 4.6%, P = 0.012) whereas the rates for ST were not different (0.7% vs 0.6% vs 0.6%, P = 0.970).

Conclusions

In octogenarians treated with PF‐SES, the rates for MACE, overall mortality, and bleeding are higher as compared to the younger age groups. However, the rates for TLR and ST were not significantly different across the investigated age groups. PF‐SES are safe and effective in octogenarians.

     

Human leukocyte antigen profile in the Zaboli ethnic group living in the South-East region of Iran

The human leukocyte antigen has become a key component in investigating the genetic relationships between populations. The aim of this study was to determine the genetic diversity of HLA class I and II alleles among Zaboli ethnic group of South-east Iran to establish a database for further investigations on ancestry and the genetic factors contributing to complex diseases in this region.Unrelated individuals from the Southeast geographic location throughout Iran were serologically typed using standard microcytotoxicity assays with commercial and local trays. The ethnic background of each individual was self-defined. HLA profiles were determined in 41 Zaboli populations. The most frequent class I alleles of the Zaboli ethnic group being the following: HLA-A1 (34.1%), -A2 (58.5%), -A11 (29.3%), -A24 (23.9%), -B5 (70.7%), -B16 (26.8%), and -Cw4 (24.4%). The class II alleles more frequently observed in this group were HLA-DR1 (26.8%), -DR2 (26.8%), -DR3 (31.7%), -DR4 (29.3%), -DR7 (24.4%), -DR8 (22%), -DR11 (48.8%), -DRw52 (73.2%), -DRw53 (53.7%), -DQ1 (53.7%), -DQ2 (31.7%), and -DQ3 (29.3%). This report utilized a first study of HLA class I and II typed individuals, from widely dispersed areas of Iran. This will help in studies related to disease associations and cadaver organ allocation programmes.     

Mice lacking alpha-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration

The functional role of alpha-synuclein in the pathogenesis of Parkinson's disease (PD) is not fully understood. Systemic exposure of alpha-synuclein-deficient mice to neurotoxins provides a direct approach to evaluate how alpha-synuclein may mediate cell death in a common murine model of PD. To this end, wild-type and homozygous alpha-synuclein knock-out mice were treated with sub-chronic and prolonged, chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the sub-chronic model, wild-type and alpha-synuclein knock-out mice were treated for five consecutive days with MPTP (1-25 mg/kg, s.c.) or vehicle, and sacrificed 3 days following the last injection. The prolonged, chronic model consisted of two injections of MPTP (1-20 mg/kg, s.c.) per week for 5 weeks, with co-administration of probenecid (250 mg/kg, i.p.), and animals were sacrificed 3 weeks following the last injection. Sub-chronic administration of MPTP caused a dramatic, dose-dependent decrease in striatal dopamine (DA) concentrations, while an attenuated response was observed in alpha-synuclein knock-out mice. Similarly, prolonged, chronic administration of MPTP produced a dose-dependent decrease in striatal DA concentrations, and a corresponding loss of striatal vesicular monoamine transporter (VMAT-2) protein in wild-type mice. However, mice lacking alpha-synuclein had an attenuated loss of striatal DA concentrations, while no loss of striatal VMAT-2 protein was observed. Both sub-chronic and prolonged, chronic administration of MPTP caused an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC) to DA ratio in wild-type mice, but not in mice lacking alpha-synuclein. Despite attenuated toxicity, elevated lactate concentrations were observed in alpha-synuclein knock-out mice following prolonged, chronic MPTP administration. The results of this study provide evidence that alpha-synuclein null mice have an attenuated response to the toxic effects of MPTP exposure, even over prolonged periods of time and that the biochemical sequela of a protracted insult to nigrostriatal DA neurons are distinct between mice with and without alpha-synuclein expression.     

Effects of intraoperative steroid injection on the outcome of pterygium surgery

Purpose

To evaluate the effects of intraoperative triamcinolone injection on the outcome of pterygium surgery.

Methods

This prospective study included 54 eyes with primary nasal pterygia that underwent pterygium surgery with a bare-sclera technique and intraoperative mitomycin C application. Patients were randomized into two groups; the steroid group that received subconjunctival injection of 12 mg triamcinolone acetonide at the end of surgery, and the control group that did not receive such steroid injection. Main outcome measures included presence of conjunctival inflammation at 1 month postoperatively as well as recurrence of pterygium.

Results

Twelve-month follow-up was completed in 48 eyes (23 in the steroid group and 25 in the control group). At 1 month postoperatively, different grades of conjunctival inflammation were present in 11 (47.8%) of the steroid group and in 14 (56%) of the control group (P=0.39). For eyes with moderate or severe postoperative inflammation, subconjunctival triamcinolone was injected; these included 6 (26.1%) and 9 (36%) in the steroid and control groups, respectively (P=0.54). During follow-up, surgical area showed fine episcleral vessels without fibrous tissue in 1 (4.3%) of the steroid group and 3 (12.0%) of the control group (P=0.33), which all regressed after triamcinolone injection. Conjunctival recurrence of pterygium was seen in 2 (8.7%) of the steroid group and in 1 (4.0%) of the control group (P=0.47). No eye developed corneal recurrence in either group.

Conclusions

In pterygium surgery with a bare-sclera technique and mitomycin C application, intraoperative triamcinolone injection did not significantly reduce postoperative conjunctival inflammation or pterygium recurrence.     

Age-related loss of the DNA repair response following exposure to oxidative stress

Young (4- to 6-month-old) and aged (24- to 28-month-old) mice were exposed to 2-nitropropane (2-NP), a DNA oxidizing agent, and the ability to induce DNA polymerase beta (beta-pol) and AP endonuclease (APE) was determined. In contrast to the inducibility of these gene products in response to oxidative damage in young mice, aged mice showed a lack of inducibility of beta-pol and APE. APE protein level and endonuclease activity were both reduced 40% (p<.01) in response to 2-NP. Accordingly, the accumulation of DNA repair intermediates in response to 2-NP differed with age. Young animals accumulated 3'OH-containing DNA strand breaks, whereas the aged animals did not. A role for p53 in the difference in DNA damage response with age is suggested by the observation that the accumulation of p53 protein in response to DNA damage in young animals was absent in the aged animals. Our results are consistent with a reduced ability to process DNA damage with age.     

Chromene-Based Synthetic Chalcones as Potent Antileishmanial Agents: Synthesis and Biological Activity

Two types of regioisomeric chromene-based chalcones namely, 1-(6-methoxy-2H-chromen-3-yl)-3-phenylpropen-1-ones and 3-(6-methoxy-2H-chromen-3-yl)-1-phenylpropen-1-ones were prepared and investigated for their antileishmanial activity against promastigotes form of Leishmania major. The obtained results from in vitro biological assays indicated that chloro-substituted 1-(6-methoxy-2H-chromen-3-yl)-3-phenylpropen-1-ones exhibited excellent activity against Leishmania major at non-cytotoxic concentrations.