The association of HLA-G and immune markers in recurrent miscarriages.

OBJECTIVE: To determine role of human leukocyte antigen (HLA)-G, CD8, CD16, CD56, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for recurrent miscarriages in feto-maternal interface. METHOD: Chorion and decidua samples were obtained from 11 women with unwanted pregnancies (healthy pregnancy, HP) and 10 women with missed abortion diagnosis after at least two pregnancy losses (recurrent miscarriage, RM). In addition, endometrial tissues were obtained from 10 non-pregnant women (NonP). The expressions of markers were evaluated using the Western blot analysis. The values obtained between different groups were compared. RESULTS: The highest protein expression of CD56 was found in the HP compared to NonP and RM. Meanwhile, the lowest protein expression of CD16 was observed in the NonP compared to HP and RM. The HLA-G expression exhibited the highest level in HP; however, there was no statistically significant difference between groups. CD8 and IFNγ expressions were lowest in the NonP group; however, TNF-α was highest in the RM group. CONCLUSIONS: The CD56 expression of uterine NK cells may be an indicator of a HP. However, not statistically significant, the increased expression of CD16, CD8, and also significantly increased expression of TNF may be associated with the predominant cytotoxic activity in the maternal immune system in patients with RM. Although there was no change in the expression of HLA-G, this finding may mean that the maternal immune system is unresponsive to HLA-G-mediated immunosuppressive signals originating from the fetus in these cases.

Montelukast is effective in preventing of ovarian hyperstimulation syndrome; an experimental study.

OBJECTIVES: To determine the efficacy of montelukast in comparison with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in rats. MATERIAL AND METHODS: An experimental OHSS model was formed in 35 female Wistar rats. Rats (22 days old) were randomized into 5 groups, each containing 7 animals. The control group received no therapy; the mild OHSS group was administered pregnant mare serum gonadotropin (PMSG) 10 IU for 4 days, hCG 10 IU on the 5th day; the severe OHSS group received PMSG 10 IU for 4 days, hCG 30 IU on the 5th day The montelukast group: received montelukast 10 mg/kg/day and the cabergoline group was administered cabergollne 100 microg/kg/day via oral gavage for 6 days (days 22-27), in addition to those of severe OHSS. All groups were sacrificed on 28th day Body weight, ovarian diameter and weight, vascular permeability vascular endothelial growth factor (VEGF), semiquantitative VEGF receptor-1, and VEGF receptor-2 (VEGFR-2) immunohistochemistry were evaluated. RESULTS: Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression. CONCLUSIONS: The VEGF/VEGFR-2 interaction plays an important role in OHSS pathogenesis. Montelukast limits VEGF expression, and cabergoline reduces both VEGF and VEGFR-2 expressions; they are both effective therapies for the prevention of severe OHSS.

Modification of the radial beam port of ITU TRIGA Mark II research reactor for BNCT applications.

This paper aims to describe the modification of the radial beam port of ITU (Istanbul Technical University) TRIGA Mark II research reactor for BNCT applications. Radial beam port is modified with Polyethylene and Cerrobend collimators. Neutron flux values are measured by neutron activation analysis (Au-Cd foils). Experimental results are verified with Monte Carlo results. The results of neutron/photon spectrum, thermal/epithermal neutron flux, fast group photon fluence and change of the neutron fluxes with the beam port length are presented.

Environmental radioactivity and high incidence rates of stomach and esophagus cancer in the Van Lake region: a causal relationship?

This study examined the incidence rates of cancer cases (averages for 2006-2010) and relationships with environmental radioactivity levels. Soil and water samples were collected from provincial and district centers of Van city and the outdoor gamma doses were determined using a portable gamma scintillation detector. Gross alpha and beta, (226)Ra, (232)Th, and (40)K activities were measured in both tap water and soil samples. Although high rates of stomach and esophagus cancers have been reported previously in Van the underlying reasons have not hitherto been defined. Incidences of cancers were highest in the Gurpinar (326.0) and Ozalp (377.1) counties (p<0.001). As to the results of the gross alpha and gross beta radioactivity measurements in the drinking water, these two counties also had high beta radionuclide levels: Gurpinar (140 mBq/dm3) and Ozalp (206 mBq/dm3). Even if within the normal range, a relation between the higher rate of the incidence of stomach and esophagus cancers with that of the higher rate of beta radionuclide activity was clear. On Spearman correlation analysis, the relation between higher beta radionuclide levels and cancer incidence was found to be statistically significant (p<0.01). According to the results of the analysis, Van residents receive an average 1.86 mSv/y annual dose from outdoor gamma radiation, ingestion of radionuclides in the drinking water, and indoor 222Rn activity. Moreover, gross alpha and beta activities were found to be extremely high in all of the lakes around the city of Van, Turkey. Further investigations with long-term detailed environmental radiation measurements are needed regarding the relationship between cancer cases and environmental radioactivity in the city of Van.

Analysis of radiofrequency ablation of small renal tumors in patients at high anesthetic and surgical risk: urologist experience with follow-up results in the initial six months.

BACKGROUND: To evaluate the results of various types of radiofrequency ablation (RFA) treatment of renal tumors in patients with excessive anesthetic and surgical risk. MATERIALS AND METHODS: Data for RFA performed in in high risk patients were retrospectively evaluated. Other RFA applications in patients with no anesthetic and/or surgical risk were excluded. RFA was by ultrasound or CT guided percutaneous (USG/CT-PRFA) and retroperitoneally or transperitoneally laparoscopic (R/T-LRFA) techniques under general or local anethesia. Follow-up data of enhanced CT or MRI after 1, 3 and 6 months were analysed for twelve RFA applications. RESULTS: The RFA applications included 4 (40%) left-sided, 5 (50%) right-sided and 1 (10%) bilaterally RFA (simultaneously 1 right and 2 left). The localizations of tumors were 2 (16.6%) upper, 5 (41.6%) mid and 5 (41.6%) lower pole. The RFA applications included 9 (75%) USG-PRFA, 1 (8.3%) CT-PRFA, 1 (8.3%) T-LRFA and 1 (8.3%) R-LRFA. The mean age was 65.3 ± 8.5 (52-76) years. The mean tumor size was 29.6 ± 6.08 (15-40) mm. No complications related to the RFA were encountered in any of the cases. Failure (residual tumour) was determined in 8.3% (1/12) of USG-RFA application. The success rate was thus 91.7% (11/12). Other 1st, 3rd and 6th months follow-up data revealed no residua and recurrence. CONCLUSIONS: RFA application appears to be safe as a less invasive and effective treatment modality in selected cases of small renal tumors in individuals with excessive anesthetic and also surgical risk.

The Effect of Bisphosphonates on Bone Mineral Density in Metastatic Prostate Cancer Patients Who Are Treated with Anti-Androgen Drugs and Radiotherapy.

OBJECTIVE: To evaluate the potential effect of bisphosphonates on bone mineral density (BMD) in patients who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer. MATERIALS AND METHODS: The data of 31 patients with metastatic prostate cancer who were treated with anti-androgen drugs and radiotherapy during a 1-year period were retrospectively reviewed. Patients were divided in 2 groups, in which 17 patients in group 1 were treated with zoledronic acid (4 mg/month, intravenous) and 14 patients in group 2 who did not receive zoledronic acid. BMD was measured before the treatment and at the end of the 1st year by dual energy X-ray absorptiometry. Statistical analyses were performed with the T test. RESULTS: Mean age of the patients was 71.42 ± 6.7(range 59-85) years. A significant increase was noted for pelvic bone, femoral neck, and lumbar vertebrae t scores when pretreatment and 1st year measurements were compared in group 1 (p < 0.05). In group 2 a significant decrease was noted for pelvic bone and femoral neck t scores at the end of the 1st year (p < 0.05). A significant increase was noted for pelvic bone and femoral neck follow-up in BMD values at the end of the 1st year compared to initial measurements in group 1. A significant decrease was noted for lumbar vertebrae follow-up in BMD values at the end of the 1st year when compared to initial values in group 2. CONCLUSION: Zoledronic acid significantly increases BMD and delays unfavorable outcomes for bones in men who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer.

Characterization of polymeric microneedle arrays for transdermal drug delivery.

Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs) were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS), where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN) precision was ranging from ± 0.18 to ± 1.82% for microneedle height, ± 0.45 to ± 1.42% for base diameter, and ± 0.22 to ± 0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

Antioxidants may protect cancer cells from apoptosis signals and enhance cell viability.

Quercetin is one of the most abundant dietary flavonoids widely present in many fruits and vegetables. Previous in vitro studies has shown that quercetin acts as an antioxidant and anti-inflammatory agent and it has potent anticarcinogenic properties as an apoptosis inducer. In this study we examined apoptotic effects of quercetin on the K562 erythroleukemia cell line. K562 cells were induced to undergo apoptosis by hydrogen peroxide. Cell viability and apoptosis level were assessed by annexin V and PI staining methods using flow cytometry. Viability of K562 cells was increased by low dose of quercetin (5-100 µM) for 3 hours. High doses of quercetin proved toxic (100-500 µM, 24 hours) and resulted in decrease of K562 cell viability as expected (P<0.01). As to results, 100 µM quercetin was defined as a protective dose. Also, K562 cell apoptosis due to hydrogen peroxide was decreased in a dose dependent manner. As indicated in previous studies, reduction of superoxides by free radical scavengers like quercetin could be beneficial for prevention of cancer but consumption of such flavonoids during cancer treatment may weaken effects of chemotherapeutics and radiotherapy. Especially cancer patients should be carefully considered for traditional phytotherapy during cancer treatment, which can lead to controversial results.

Sodium alginate microneedle arrays mediate the transdermal delivery of bovine serum albumin.

BACKGROUND: The "poke and release" strategy for the delivery of macromolecules using polymeric microneedle (MN) is of great importance because it eliminates microneedle reuse, the risks of biohazardous sharps and cross contamination, and it requires no special disposal mechanism. The main objective of this study was the determination of the stability and delivery of bovine serum albumin (BSA) that was transported across human skin via sodium alginate (SA) microneedle arrays (MNs) and SA needle free patches using two different analytical methods. METHODOLOGY AND FINDINGS: The capability of two analytical methods, the bicinchoninic acid (BCA) assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), to precisely detect and quantify BSA within different types of polymeric MNs was assessed. The ex vivo protein release of BSA across dermatomed human abdominal skin from 10 w/w SA MNs was compared to that from needle-free patches using Franz diffusion cells. The developed applicator was mechanically characterized using a Texture Analyzer. The patch mold and its components were fabricated using a rapid prototyping machine. CONCLUSIONS/SIGNIFICANCE: The BCA method was able to precisely detect BSA that had been loaded into SA MNs. However, the use of SDS-PAGE as the analytical method resulted in significantly different amounts of BSA recovered from differently conditioned polymeric MNs. The permeation of BSA across dermatomed human abdominal skin by SA MNs, which were composed of 100 pyramidal needles, increased by approximately 15.4 fold compared to the permeation obtained with SA needle-free patches. The ease of use of the applicator during the release studies was also demonstrated, as was its mechanical characterization.

WITHDRAWN: Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays.

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Lipid peroxidation, DNA damage and coenzyme Q10 in lung cancer patients--markers for risk assessment?

OBJECTIVES: Early diagnosis and prevention is very important for lung cancer patients. Previous studies have emphasized that the level of coenzyme Q10 (CoQ10), present primarily in mitochondria, decreases with age and is low in patients with chronic diseases. Our goal was to find out if there is any relationship between lung cancer and CoQ10 and lipid peroxidation levels. DESIGN AND METHODS: Blood samples from lung cancer patients were collected. Total and oxide CoQ10 levels, 8-OHdG (product of DNA damage), and malondialdehyde (MDA) levels (lipid peroxidation) were analyzed with high performance liquid chromatography (HPLC). RESULTS: The MDA level (P<0.001) and DNA damage rate (8-OHdG) (P<0.001) was higher in cancer patients than in the control group; in contrast, theCoQ10 enzyme level was significantly lower (P<0.001). CONCLUSION: The results suggest that the aforementioned parameters can be useful for lung cancer risk assessment.

Effect of extremely low frequency electromagnetic fields on growth rate and morphology of bacteria.

PURPOSE: To determine the effect of extremely low frequency (<300 Hz) electromagnetic fields (ELF-EMF) on the growth rate of Gram-positive and Gram-negative bacteria and to determine any morphological changes that might have been caused by ELF-EMF. MATERIALS AND METHODS: Six bacterial strains, three Gram-negative and three Gram-positive were subjected to 50 Hz, 0.5 mT ELF-EMF for 6 h. To determine growth rate after ELF-EMF application, bacteria exposed to ELF-EMF for 3 h were collected, transferred to fresh medium and cultured without field application for another 4 h. Growth-rate was determined by optical density (OD) measurements made every hour. Morphological changes were determined with Transmission electron microscopy (TEM) for two gram-negative and two gram-positive strains collected after 3 h of field application. RESULTS: A decrease in growth rate with respect to control samples was observed for all strains during ELF-EMF application. The decrease in growth-rate continued when exposed bacteria were cultured without field application. Significant ultrastructural changes were observed in all bacterial strains, which were seen to resemble the alterations caused by cationic peptides. CONCLUSION: This study shows that ELF-EMF induces a decrease in growth rate and morphological changes for both Gram-negative and Gram-positive bacteria.

Effects of noise pollution over the blood serum immunoglobulins and auditory system on the VFM airport workers, Van, Turkey.

Noise pollution is a common health problem for developing countries. Especially highways and airports lead to noise pollution in different levels and in many frequencies. In this study, we focused on the effect of noise pollution in airports. This work aimed measurements of noise pollution levels in Van Ferit Melen (VFM) airport and effect of noise pollution over the immunoglobulin A, G, and M changes among VFM airport workers in Turkey. It was seen that apron and terminal workers were exposed to high noise (>80 dB(A)) without any protective precautions. Noise-induced temporary threshold shifts and noise-induced permanent threshold shifts were detected between the apron workers (p < 0.001) and terminal workers (p < 0.005). IgA values of apron terminal and control group workers were approximately the same in the morning and increased in a linear manner during the day. This increase was statistically significant (p < 0.001). IgG and IgM values of apron, terminal, and control group workers were approximately same in the morning. Apron and terminal workers IgG and IgM levels were increased until noon and then decreased until evening as compare to control group, but these changes were not statically significant (p > 0.05). These findings suggested that the noise pollution in the VFM airport could lead to hearing loss and changes in blood serum immunoglobulin levels of airport workers. Blood serum immunoglobulin changes might be due to vibrational effects of noise pollution. Airport workers should apply protective precautions against effect of noise pollution in the VFM airport.

Extremely low-frequency electromagnetic fields affect the immune response of monocyte-derived macrophages to pathogens.

This study aimed to determine the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on the physiological response of phagocytes to an infectious agent. THP-1 cells (human monocytic leukemia cell line) were cultured and 50 Hz, 1 mT EMF was applied for 4-6 h to cells induced with Staphylococcus aureus or interferon gamma/lipopolysaccharide (IFγ/LPS). Alterations in nitric oxide (NO), inducible nitric oxide synthase (iNOS) levels, heat shock protein 70 levels (hsp70), cGMP levels, caspase-9 activation, and the growth rate of S. aureus were determined. The growth curve of exposed bacteria was lower than the control. Field application increased NO levels. The increase was more prominent for S. aureus-induced cells and appeared earlier than the increase in cells without field application. However, a slight decrease was observed in iNOS levels. Increased cGMP levels in response to field application were closely correlated with increased NO levels. ELF-EMF alone caused increased hsp70 levels in a time-dependent manner. When cells were induced with S. aureus or IFγ/LPS, field application produced higher levels of hsp70. ELF-EMF suppressed caspase-9 activation by a small extent. These data confirm that ELF-EMF affects bacterial growth and the response of the immune system to bacterial challenges, suggesting that ELF-EMF could be exploited for beneficial uses.

Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress.

Mammalian Timeless is a multifunctional protein that performs essential roles in the circadian clock, chromosome cohesion, DNA replication fork protection, and DNA replication/DNA damage checkpoint pathways. The human Timeless exists in a tight complex with a smaller protein called Tipin (Timeless-interacting protein). Here we investigated the mechanism by which the Timeless-Tipin complex functions as a mediator in the ATR-Chk1 DNA damage checkpoint pathway. We find that the Timeless-Tipin complex specifically mediates Chk1 phosphorylation by ATR in response to DNA damage and replication stress through interaction of Tipin with the 34-kDa subunit of replication protein A (RPA). The Tipin-RPA interaction stabilizes Timeless-Tipin and Tipin-Claspin complexes on RPA-coated ssDNA and in doing so promotes Claspin-mediated phosphorylation of Chk1 by ATR. Our results therefore indicate that RPA-covered ssDNA not only supports recruitment and activation of ATR but also, through Tipin and Claspin, it plays an important role in the action of ATR on its critical downstream target Chk1.