Zafer Akan

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.

Effect of ELF-EMF on number of apoptotic cells; correlation with reactive oxygen species and HSP

It is by now accepted that extremely low frequency electromagnetic fields ELF-EMF (0-300 Hz) affect biological systems although the mechanism has not been elucidated yet. In this study the effect of ELFEMF on the number of apoptotic cells of K562 human leukemia cell line induced or not with oxidative stress and the correlation with heat-shock protein 70 (hsp70) levels was investigated. One sample was treated with H 2 O 2 while the other was left untreated. ELF-EMF (1 mT, 50 Hz) was applied for 3 hours. ELF-EMF alone caused a decrease in the number of apoptotic cells and a slight increase in viability. However, it increased the number of apoptotic cells. In cells treated with H 2 O 2 . hsp70 and reactive oxygen species (ROS) levels were increased by ELF-EMF. These results show that the effect of ELF-EMF on biological systems depends on the status of the cell: while in cells not exposed to oxidative stress it is able to decrease the number of apoptotic cells by inducing an increase in hsp levels, it increases the number of apoptotic cells in oxidative stress-induced cells.

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.

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.

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

Abstract 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.

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 (İstanbul 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.

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.

The treatment of metastatic prostate carcinoma with BNCT in the ITU TRIGA MARKII reactor on rat model

Received 06-12-2016 Accepted 22-12-2016 Available Online 30-12-2016 1 Celal Bayar University School of Medicine, Department of Biophysics, Manisa, TR 2 Yüzüncü Yıl University School of Medicine, Department of Pharmacology, Van, TR 3 Istanbul Medeniyet University, School of Medicine, Department of Nuclear Medicine, Istanbul, TR 4 Hacettepe University, Faculty of Engineering, Dept. of Nuclear Engineering, Ankara, TR 5 Celal Bayar University School of Medicine, Department of Urology, Manisa, TR * Corresponding Author: Zafer Akan E-mail: zaferakan@marmara.edu.tr Phone: +44 020 3289 9294 The treatment of metastatic prostate carcinoma with BNCT in the ITU TRIGA MARKII reactor on rat model

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.