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GİRİŞ ve AMAÇ: Bu çalışmanın amacı, faktöriyel tasarım yaklaşımını kullanarak Flutikazon propiyonat (FP) yüklü katı lipid nanopartikül formülasyonları geliştirmektir.
YÖNTEM ve GEREÇLER: Bu amaçla faktöriyel tasarımda Tristearin yüzdeleri (X1) (% 1, % 2 ve % 4) ve homojenizasyon döngüleri (X2) (2, 4 ve 8 döngü) bağımsız değişkenler olarak seçilmiştir. Seçilen işlem ve formülasyona ait bağımsız değişkenlerin, katı lipid nanopartikül formülasyonların enkapsülasyon etkinliği (Q1) ve partikül boyututları (Q2) üzerindeki etkisini değerlendirmek için çoklu regresyon analizi (MLR) ile optimize edilmiştir. Çalışmada ayrıca nanopartiküllere ait polidispersite indeksi ve yüzey yükleri de değerlendirilmiştir. Bunun yanı sıra optimum katı lipid nanopartikül formülasyonu üzerinde geçirimli elektron mikroskopu, difransiyel taramalı kalorimetre analizi ve in vitro etkin madde salım çalışmaları da yapılmıştır.
BULGULAR: MLR analizi, üretim sürecinde homojenizasyon döngüsü (X2) arttıkça, ortalama partikül boyutunun azaldığını göstermiştir.
TARTIŞMA ve SONUÇ: Bu araştırma, istenen özelliklere sahip FP yüklenmiş katı lipid nanopartiküllerin, formülasyonların üretim ve içerik değişkenlerini değiştirerek üretilebileceğini göstermektedir.

INTRODUCTION: The aim of this study was to develop Fluticasone propionate (FP)-loaded solid lipid nanoparticle (SLN) formulations using the factorial design approach.
METHODS: Tristearin percentages (X1) (1%, 2% and 4%) and homogenization cycles (X2) (2, 4, 8 cycles) were selected as independent variables in the factorial design. SLN formulations were optimized by multiple regression analysis (MLR) to evaluate the influence of the selected process and formulation independent variables on SLNs characteristics namely as encapsulation efficiency (Q1) and particle size (Q2). Polydispersity index and surface charge of the SLNs were also evaluated in this research. Besides, transmission electron microscopy, Differential scanning calorimetry and in vitro drug relase studies were carried out on the optimum SLN formulation.
RESULTS: MLR analysis indicated that as homogenization cycle (X2) increased in the production process, the mean particle size was decreased.

DISCUSSION AND CONCLUSION: This research displayed that FP-encapsulated SLNs with desired characteristics can be produced by varied the production and content variables of the formulations.

GİRİŞ ve AMAÇ: Compaction simulator (CS) toz sıkıştırma prosesi sırasında veri kaydı yapan tek zımbalı bir cihazdır. Bu çalışmanın amacı laktoz bazlı doğrudan tabletleme ajanlarının (DTA) davranışlarını bu cihazı (CS) kullanarak belirlemektir. Kaydedilen veriler tozların basılabilme ve akış özelliklerini değerlendirmede kullanılmaktadır.
Çalışmanın odağında % 85 alfa laktoz monohidrat ve %15 mısır nişastası içerikli StarLac® ve püskürterek kurutulmuş alfa laktoz monohidrat yapısındaki FlowLac® kullanılarak zayıf akış özelliğine sahip parasetamol içeren tabletlerin basılabilirlik özelliklerinin mukayesesi vardır.

YÖNTEM ve GEREÇLER: Laktoz bazlı iki doğrudan basım ajanı bu çalışmalarda kullanılmıştır. Bu tozların küme, sıkıştırılmış ve gerçek dansiteleri yansıra fizisel özellikleri Elektron mikroskopla görüntülenmiştir. Tozların yığın açısı, Hausner Indeks ve Carr Indeks değerleri hesaplanmıştır. Kuvvet, sıkışmış tozun zımba içindeki kalınlığı, zımba ötelemesi verileri proses sırasındaki CS cihaz çıktılarıdır. Heckel eşitliği kullanılarak basılabilirlik hesaplanmıştır.
BULGULAR: iki doğrudan tabletleme ajanı arasındaki fiziksel karakterizasyon test sonuçlarına göre anlamlı bir fark tesbit edilememiştir. FlowLac® içeren formülasyonların tablet sertlik sonuçları StarLac® içeren formülasyonlarla mukayese edildiğinde FlowLac®’ın baskı kuvveti artışına daha fazla duyarlı olduğu anlaşılmıştır.
Compaction simulatorün 5 kN baskı kuvveti ile çalışması sırasında Py değerleri FlowLac® ve StarLac® için Heckel eşitiği ile FlowLac® için 87.5 MPa, StarLac® için 85,2 MPa olarak hesaplanmıştır. Bu veriler her iki tozun da basılabilme özelliğinde ve kırılgan-gevrek yapıda olduğunu göstermiştir.
TARTIŞMA ve SONUÇ: StarLac® ‘ın daha az kırılgan, gevrek yapıya sahip olduğu ve baskı kuvveti uygulamasına karşı daha az duyarlı olduğu gösterilmiştir. Compaction simulator ile çalışma sırasında elde edilen Py değeri bilgisi ile doğrudan tabletleme ajanları hakkında basılabilme ve esneklik kesin bilgisi elde edilebilir.

INTRODUCTION: Compaction Simulator (CS) is an single punch equipment that records data during powder compaction process. The aim of the study is to determine the behavior of lactose-based direct tableting agents (DTA’s) by CS. Recorded data used to evaluate the flowability and compressibility of powders. The focus of the study was to compare the compressibility of StarLac® [alpha lactose monohydrate (85%)and white maize starch (15%)] and FlowLac®100 (spray-dried alpha lactose monohydrate) in order to make tablets containing poorly flowable Paracetamol.
METHODS: Two lactose based DTA were used in this study. Physical characterization of these powders was done by measuring bulk, tapped and true densities along side SEM analysis. Flow properties were then calculated by Angle of Repose, Hausner Ratio and Carr’s Compressibility Index. Force, in-die thickness, and punch displacement data produced by compaction simulator were captured during in-die compression. Compressibility was calculated using Heckel equation.
RESULTS: Physical characterization tests results showed no significant difference between the two DTAs. Hardness results revealed that tablet formulations containing FlowLac® had higher sensitivity to increase in compression force in comparison with StarLac®. From the Heckel plots generated by compaction simulator during compression cycle yield pressure (Py) values were calculated for FlowLac®100 and StarLac®. The Heckel parameter (Py) for FlowLac®100 and StarLac® were calculated as 87.5MPa and 85.2MPa respectively during compaction cycle at 5kN. These data indicated that both powders are compressible and have brittle behavior.
DISCUSSION AND CONCLUSION: StarLac® has less brittle properties which was shown by the lower sensitivity to compression force. Py values obtained from Heckel equation described the plasticity of particles which gives distinct information on the compressibility of both DTA’s in real time during compaction cycle.

INTRODUCTION: The present attempt is aimed to discover the best Poloxamer grade as solid dispersion carrier by taking Thiocolchicoside as a model drug.
METHODS: The compatibility of Thiocolchicoside with excipients used was studies by differential scanning calorimetry and Fourier Transform Infra-red Spectroscopy. Different formulations of solid dispersions were prepared by using Poloxamer carriers viz., Poloxamer-108, Poloxamer-188, Poloxamer-237, Poloxamer-338 and Poloxamer-407 were prepared by taking Thiocolchicoside: Poloxamer in the ratios ranged from 1: 1, 1: 2, 1: 4 and 1: 6. The solid dispersions were prepared by a novel microwave fusion method and compressed using 8 station tablet compression machine. The fabricated solid dispersion tablets were evaluated for physicochemical characteristics and dug release rates. The release of Thiocolchicoside from the prepared solid dispersions was further analyzed by kinetic models.
RESULTS: Thiocolchicoside was found to be compatible with the Poloxamer carriers used. The solid dispersion formulations were shown satisfactory physicochemical characteristics and Thiocolchicoside release which follows first order release.
DISCUSSION AND CONCLUSION: Among the Poloxamer carriers used, Poloxamer-188 was found to be the best carrier for increasing the solubility and release rate of Thiocolchicoside form the solid dispersions.

GİRİŞ ve AMAÇ: Metilen mavisi (MV) yakın infrared (NIR) görüntüleme ve ışığa maruziyet sonrası reaktif oksijen radikalleri üreterek apoptozu indükleyen foto-dinamik tedavi (PDT) için sıklıkla kullanılan bir boyadır. MV’sinin hücre membranlarından zayıf penetrasyonu etkinliğini kısıtlayan bir faktördür. MV’sinin azalmış hücresel tutulumu lipozomlar gibi ilaç taşıyıcı sistemlerde enkapsülasyonu ile önlenebilir. Ek olarak, tümörün artmış geçirgenlik ve tutulum (EPR) etkisi nanotaşıyıcıların hedef bölgede tutulumunu artırır.
YÖNTEM ve GEREÇLER: Bu çalışmada, nanoboyutlu, MV enkapsüle edilen, Tc-99m radyoişaretli Lipoid S PC: PEG2000-PE: Chol: DTPA-PE ve DPPC: PEG2000-PE: Chol: DTPA-PE lipozomları multifonksiyonel teranostik nanotaşıyıcıları daha kesin görüntüleme ve cerrahiye yardımcı olabilecek tedavi sağlayabilmek amacıyla; 1. NIR görüntüleme, 2. Sentinal lenf nodlarının (SLN) gama prob ile tayini ve 3. PDT’yi aynı tek lipozomal sistemde dizayn edilecek formülasyonlar hazırlanmıştır. Lipozomların karakterizasyonu partikül boyutu, zeta potansiyel, fosfolipid içeriği ve enkapsülasyon etkinliği ölçülerek yapılmıştır. Ek olarak, MV’sinin in vitro salım profili ve fiziksel stabilitesi altı aylık sürede belirli zamanlarda ortalama partikül boyutu, zeta potansiye, enkapsülasyon etkinliği ve fosfolipid içeriği oda sıcaklığı (25 ͦC) ve 4 ͦC’de ölçülerek değerlendirilmiştir.
BULGULAR: Tc-99m işaretli, nanoboyutlu Lipoid S PC: PEG2000-PE: Chol: DTPA-PE ve DPPC: PEG2000-PE: Chol: DTPA-PE lipozomları uygun partikül boyutu (100 nm civarında), zata potansiyel (-9 - -13 mV), enkapsülasyon etkinliği (%10 civarında), fosfolipid etkinliği (%85-90 civarında) ve salım profili göstermiştir. Ayrıca, 4°C’de saklanan MV hapsedilmiş lipozomlar 3 ay boyunca stabil bulunmuştur.
TARTIŞMA ve SONUÇ: MV enkapsüle edilen, Tc-99m işaretli, nanoboyutlu Lipoid S PC: PEG2000-PE: Chol: DTPA-PE ve DPPC: PEG2000-PE: Chol: DTPA-PE lipozomlar SLN’nın gama probla tayin edilme, NIR görüntüleme ve PDT için potansiyel olarak bulunmuştur. Daha doğru ve kesin sonuçlara ulaşmak için in vitro ve in vivo görüntüleme ve tedavi etkinliği değerlendirilmesi gereklidir ve çalışmalarımız devam etmektedir.

INTRODUCTION: Methylene blue (MB) is a commonly used dye which can be used for near-infrared (NIR) imaging and photodynamic therapy (PDT) by producing reactive oxygen species after light exposure, inducing apoptosis. The limiting factor of MB is the poor penetration through the cell membranes. Its decreased cellular uptake can be prevented by encapsulating in drug delivery systems such as liposomes. Additionally, EPR effect of tumor gives chance to enhance accumulation of nanocarriers in target site.
METHODS: In this study, nanosized, MB encapsulated, Tc-99m radiolabeled Lipoid S PC: PEG2000-PE: Chol: DTPA-PE and DPPC: PEG2000-PE: Chol: DTPA-PE liposomes were formulated to design multifunctional theranostic nanocarriers for; 1. NIR imaging, 2. Gamma probe detection of SLN and 3. PDT which can provide accurate imaging and therapy helping surgery with a single liposomal system. The characterization of liposomes was performed by measuring particle size, zeta potential, phospholipid content, and encapsulation efficiency. Additionally, in vitro release profile of MB and physical stability were also evaluated for six months at determined time intervals by measuring mean particle size, zeta potential, encapsulation efficiency and phospholipid content of liposomes kept at room temperature (25 ͦC) and 4 ͦC.
RESULTS: Tc-99m radiolabeled, nanosized Lipoid S PC: PEG2000-PE: Chol: DTPA-PE and DPPC: PEG2000-PE: Chol: DTPA-PE liposomes designated proper particle size (around 100 nm), zeta potential (-9 - -13 mV), encapsulation efficiency (around 10%), phospholipid efficiency (around 85-90%) and release profile. Additionally, liposomes were observed stable for 3 months especialy when kept at 4°C.
DISCUSSION AND CONCLUSION: MB encapsulated, Tc-99m radiolabeled, nanosized Lipoid S PC: PEG2000-PE: Chol: DTPA-PE and DPPC: PEG2000-PE: Chol: DTPA-PE liposomes were found potential for SLN imaging by gamma probe detection, NIR imaging and PDT. In vitro and in vivo imaging and therapeutic efficiency should be definitely evaluated to give a final desicion and our studies are continuing.

INTRODUCTION: In the present investigation, bio-adhesive buccal tablets were prepared using sustained-release polymer HPMC K100M, bio-adhesive polymer neem gum and an impervious backing layer of ethyl cellulose. Nicorandil is sensitive to first-pass metabolism effect; therefore, the formulation of buccal-adhesive dosage form can avoid this effect.
METHODS: We used the direct compression technique to prepare tablet formulation. A 32 Full Factorial Design was composed in which the amount of HPMCK100M (X1) and NEEM GUM (X2) were chosen as the independent variables and the dependent variables were being the percentage drug release at 6 h (Y1) and mucoadhesive strengths in grams (Y2). Various in vitro parameters viz. thickness, friability, hardness, weight variation, surface pH, moisture absorption ration, dissolution studies, and drug release kinetics and ex vivo parameters like mucoadhesive strengths and mucoadhesion time were performed for prepared tablets. We subjected the optimized batch to comparison with the marketed formulation and stability studies.
RESULTS: Formulation (F5) containing a 50: 50 ratio of neem gum and HPMC K100M was considered to be optimum. Zero-order release kinetics model best fitted the optimized batch release profile that suggested the system would release the drug at a constant rate.
DISCUSSION AND CONCLUSION: The optimized formulation releases the drug at a sustained rate along with bio-adhesive nature deduced that the buccal route can be an elective for the administration of Nicorandil.

GİRİŞ ve AMAÇ: Bu çalışmanın amacı, rifampisinin elektrokimyasal davranışını çok duvarlı karbon nanotüp ile modifiye edilmiş camsı karbon elektrotlar kullanarak anodik yönde incelemektir.
YÖNTEM ve GEREÇLER: Rifampisinin anodik incelemesi dönüşümlü, diferansiyel puls ve kare dalga voltametri teknikleri ile yapıldı. Çalışma elektrotu olarak MWCNT'nin bir modifikasyonuna sahip camsı bir karbon elektrot, karşı elektrot olarak bir platin tel ve referans olarak bir Ag/AgCl elektrotundan oluşan üç elektrotlu sistem, deneyler için kullanıldı.
BULGULAR: Rifampisin anodik süreci geri dönüşümsüzdü ve difüzyon kontrollü idi. Destek elektrolit olarak pH 3.5'te asetat tamponunda her iki teknik için de 0.04 ila 10 µM arasında doğrusal cevaplar elde edildi. Tespit limiti değerleri diferansiyel puls ve kare dalga voltametri teknikleri için sırasıyla 7.51 ve 11.3 nM olarak bulundu. Önerilen yöntemlerin tekrarlanabilirliği, tekrar üretilebilirliği, kesinliği ve doğruluğu da incelendi. Rifampisinin tayini, farmasötik dozaj formlarından yapıldı ve sonuçlar, literatürdeki diğer elektrokimyasal sensörler ve ayrıca sıvı kromatografik ve spektrofotometrik yöntemlerle karşılaştırıldı.
TARTIŞMA ve SONUÇ: Bu valide edilmiş teknikler, terapötik ilaç izlemede sıvı kromatografik ve spektrofotometrik yöntemlere alternatif teknikler olarak rifampisinin seçici, hızlı, hassas, kesin ve ucuz bir şekilde tayinini sağladı.

INTRODUCTION: The aim of the study was to investigate the electrochemical behavior of rifampicin in the anodic direction using multiwalled carbon nanotube modified glassy carbon electrodes.
METHODS: The anodic investigation of rifampicin was carried out with cyclic, differential pulse and square wave voltammetry techniques. The three-electrode system consisting of a glassy carbon electrode with a modification of MWCNT as working electrode, a platinum wire as counter electrode, and an Ag/AgCl electrode as reference was used for the experiments.
RESULTS: The anodic process of rifampicin was irreversible and diffusion controlled. Linear responses were obtained between 0.04 and 10 µM for both techniques in acetate buffer at pH 3.5 as supporting electrolyte. Limit of detection values were 7.51 and 11.3 nM for differential pulse and square wave voltammetry techniques, respectively. The repeatability, reproducibility, precision, and accuracy of the proposed methods were also investigated. Determination of rifampicin was carried out from its pharmaceutical dosage forms and the results were compared with other electrochemical sensors and also the liquid chromatographic and spectrophotometric methods in the literature.
DISCUSSION AND CONCLUSION: These validated techniques provided selective, rapid, sensitive, precise, and cheap determination of rifampicin as alternative techniques to the liquid chromatographic and spectrophotometric methods in therapeutic drug monitoring.

INTRODUCTION: Therapy of pain syndromes involves exposure to its source, receptors and peripheral fibers. Treatment of acute pain and inflammation involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) and non-narcotic analgesics (NNA). An alternative to obsolete analgesics is combined compositions. Analysis of experimental results clearly indicates that caffeine effectively enhances the analgesic activity of the peripheral origin when combined in a pharmaceutical composition.
The aim of the present study was to evaluate the peripheral analgesic activity of meloxicam, piroxicam and their pharmacological compositions with caffeine.

METHODS: The peripheral analgesic activity of piroxicam, meloxicam and their composition with caffeine was studied using the abdominal writhing test. This method used to induce pain of peripheral origin by intraperitoneal injection of 0.6 % acetic acid solution. Investigated drugs, their composition and 3 % starch mucilage were administrated 1 hour before the introduction of the algogene. The cumulative number of writhing responses induced by acetic acid were determined over next 20 min.
RESULTS: All investigated drugs showed a decrease of writhing in rats. Meloxicam and caffeine showed peripheral analgesic activity 63.6% and 64.5% respectively (Р < 0,05). The pharmaceutical composition of meloxicam and caffeine showed the analgesic potential 76.4%. Thus, the caffeine potentiates the analgesic activity of meloxicam. Obtained results exceeded the corresponding value of diclofenac sodium (67.3%).
DISCUSSION AND CONCLUSION: Analysis of experimental results clearly indicates that caffeine effectively enhances the analgesic activity of the peripheral analgesic action of meloxicam when combined in a pharmaceutical composition. Results can serve as foundation for development of new domestic combined drugs.

INTRODUCTION: The present investigation was conducted to green synthesize copper nanoparticles (CuNPs) from aqueous extract of Capparis spinosa L. fruit and evaluate their effects on liver function and hematological parameters of mice.
METHODS: The green synthesis of CuNPs by means of C. spinosa extract was performed according to the method described elsewhere. UV-vis spectroscopy analyses, Fourier transform of infrared (FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) were used to identify the synthesized nanoparticles. The mice were orally administrated with CuNPs at the doses of 1000, 2000, and 5000 µg/kg for two weeks. Afterward, the effects of CuNPs on liver function of the treated mice were evaluated by measuring the serum levels of enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin as well as hematological parameters including hemoglobin (Hb), hematocrit (Hct), white blood cell counts (WBC), red blood cell counts (RBC), and platelet (PLT) counts.
RESULTS: A maximum peak at the wavelength of 414 nm approved the biosynthesis of the copper nanoparticles. FTIR spectrum analysis revealed that the factor groups shaped a coating extract on the surface of the nanoparticles. SEM images demonstrated the particle size between 17 and 41 nm. It was found that although some liver enzymes and hematological parameters increased with increasing dosage of extract, there is no significant difference (p> 0.05) between oral administrations of CuNPs at the doses of 1000, 2000, and 5000 g/kg and control group.
DISCUSSION AND CONCLUSION: The findings revealed that copper nanoparticles biosynthesized from aqueous extract of C. spinosa fruit have no toxic effect on the liver of the studied mice; as well as no significant toxicity was observed on hematological parameters in mice. However, more studies need to be done for evaluation of hepatoprotective effect of CuNPs.

INTRODUCTION: CDK2 is a protein that plays a role in regulating the cell cycle where its overexpression contributes to uncontrolled cell proliferation. Inhibition of CDK2 has been known to be one of the mechanisms of various anticancer drugs. Curcumin is an active compound of Curcuma Longa which have been reported to inhibit the activity of Cyclin D, Cyclin E, CDK2, CDK4, and CDK6.
METHODS: This study aims to design more active curcumin derivatives as anticancer drugs by targeting CDK2 through a molecular modelling approach. In brief, the process consist of receptor and ligand preparation, method validation, pharmacophore modelling, and docking simulation.
RESULTS: The results of molecular docking simulation show that the free bonding energy (∆G) of curcumin and kurkumod 23 and 24 (the best modification of curcumin) are -7.80, -9.15, and -9.36 kcal/mol respectively. The hydrogen interaction between kurkumod 23 and 24 with CDK occurred on Lys33 residue which is considered as a potential interaction side for CDK2 inhibitor compounds. Pharmacophore modelling showed that kurkumod 23 and 24 have a pharmacophore-fit value of 45.20% and 47.26% respectively.
DISCUSSION AND CONCLUSION: Based on the study result, it can be considered that kurkumod 23 and 24 are the best and most potential modifications of curcumin as CDK-2 antagonist, which is based on the interactions that occur between these two derivatives with amino acid residues from the CDK2 receptor

INTRODUCTION: This study designed to verify the antiangiogenic activity of ferulic acid (FA) and its potency to inhibit COX-2 and VEGF expression on CAM model. Moreover besides, we verified its mechanism of action by docking the molecule on COX-2, tyrosine kinase and VEGF-2 proteins in silico
METHODS: Anti-angiogenesis assay of FA at the doses of 30, 60 and 90 μg were performed using CAM of chicken eggs with nine-day old which were stimulated by 60 ng basic fibroblast growth factor (b-FGF). Celecoxib 60 μg was used as reference drug. The inhibitory activity on VEGF and COX-2 expressions were conducted by immunohistochemistry assay (IHC). Molecular docking of FA were accomplished by Molegro Virtual Docker program ver. 5.5. on COX-2 enzyme (PDB ID 1CX2), tyrosine kinase receptor (PDB ID 1XKK) and VEGF-2 receptor (PDB ID 4ASD).
RESULTS: FA at doses 30, 60, 90 μg significantly prevented angiogenesis on CAM model (p<0.05), which were represented as inhibitory activities against endothelial cell of blood vessels (42.6-70.7%) and neovascularization (43.0-86.6%). Inhibitory activities of FA against VEGF expression were stronger than its action on COX-2 expression. Molecular docking on VEGF-2 receptor result in RS value of FA was -73,844 kcal/mol, and celecoxib was -94.557 kcal/mol. RS value on tyrosine kinase of FA was -84.954 kcal/mol, while celecoxib was -93.163 kcal/mol. Docking on COX-2 receptor denoted RS value of FA was -73,416 kcal/mol, while celecoxib was -118,107 kcal/mol.
DISCUSSION AND CONCLUSION: Reduction of VEGF-2 & COX-2 expression due to treatment with FA at dose range 30–90 μg seem to be related to angiogenesis inhibition, which is presented by two parameters, namely inhibition of neovascularization and endothelial cell growth in blood vessels It was concluded that FA is promising anti-angiogenic therapeutic agent especially at early stage, and this activity can be resulted from inhibitory action on COX-2 and VEGF-2 proteins.

GİRİŞ ve AMAÇ: Vanillik asit, bir lezzetlendirici madde, fenolik asit ve ferulik asitten vanilin üretimi sürecinde bir ara üründür. Çeşitli farmakolojik etkiler araştırılmış ve Çin tıbbında on yıllardan beri kullanılan ancak uzun süreli kullanımda toksisite mekanizması mevcut literatürde bulunmadığından, akut toksisite çalışması yapılması kararlaştırılmıştır.
YÖNTEM ve GEREÇLER: OECD TG407'ye göre (OECD, 2008), sıçanlar 12 hayvandan oluşan 3 gruba (6 erkek ve 6 dişi) ayrıldı. Subakut toksisite çalışması için vanillik asit dozuna limit testi yapıldıktan sonra karar verildi. Birinci sıçan grubuna vanilya asidi (1000 mg / kg / gün, p.o 14 gün boyunca) uygulanmış, kontrol grubuna eşit miktarda taşıt verilmiştir. Tersinirliğe erişebilmek için, uydu gruplarına vanilinik asit (1000 mg / kg / gün, p.o 14 gün boyunca) verildi ve işlemden sonraki 14 gün boyunca tutuldu. Toksik belirtiler, mortalite ve vücut ağırlığı değişiklikleri kaydedildi. 15. ve 29. günlerde, hematolojik ve biyokimyasal parametrelerin tahmininde kan toplamak için kan ve anestezi, tartım ve histopatolojik çalışmalar için iç vücut organlarını toplamak için kurban edildikten sonra.
BULGULAR: Uydu grubunun hematolojik parametreleri artmış bulundu; Tedavi grubu ve uydu grubunda serum sodyum düzeyi kontrol grubuna göre diğer biyokimyasal parametrelerde önemli bir değişiklik olmadan azaldı. Göreceli organ ağırlığı ve iç vücut organlarının histopatolojik yapısı büyük bir değişiklik olmadan bulundu.
TARTIŞMA ve SONUÇ: Vanilin asidinin eritropoezi, lökopezi süreci ve çeşitli biyokimyasal parametreler ve histopatolojik çalışmalar değerlendirilerek doğrulanan iç vücut organları üzerinde olumsuz etkisi yoktur. Ciddi veya majör toksik etki olarak kabul edilemeyecek serum sodyum seviyesindeki düşüş gözlendi.

INTRODUCTION: Vanillic acid is a flavouring agent, phenolic acid and an intermediate product in the process of production of vanillin from ferulic acid. It has been investigated for diverse pharmacological actions and used in Chinese medicine since decades but the mechanism of toxicity on long term use is lacking in present literature therefore it was decided to conduct a subacute toxicity study.
METHODS: According to OECD TG407 (OECD, 2008), rats were divided into 3 groups of 12 animals (6 male and 6 female). The dose of vanillic acid for subacute toxicity study was decided after conducting limit test. The vanillic acid (1000 mg/kg/day, p.o for 14 days) was administered to the first group of rats, whereas an equal volume of vehicle was given to the control group. In order to access reversibility, satellite groups were given vanillic acid (1000 mg/kg/day, p.o for 14 days) and kept for another 14 days post-treatment. The toxic signs, mortality and the body weight changes were recorded. On day 15 and 29 the rats were anesthetized to collect blood for estimation of hematological and biochemical parameters than after sacrificed to collect internal body organs for weighing and histopathological studies.
RESULTS: The hematological parameters of satellite group were found to be increased; serum sodium level was decreased in treatment and satellite group with no major change in other biochemical parameters as compared to control group. Relative organ weight and histopathological structure of internal body organs were found with no major alteration
DISCUSSION AND CONCLUSION: Vanillic acid has no adverse effect on process of erythropoiesis, leucopoiesis and on internal body organs which was confirmed by evaluating various biochemical parameters and histopathological studies. Decrease in serum sodium level was observed which may not be considered as severe or major toxic effect.

INTRODUCTION: Osteoporosis is a disease described by a skeletal degradation of bone tissue domination to increase risk of fracture. Traditionally, Rusa unicolor antler from East Kalimantan is used to treat many kinds of diseases, and one of them is disease related to bone turnover. The present research aims to analyze the effects of 70% ethanol and aqueous extracts of Rusa unicolor antler from East Kalimantan on nitric oxide inhibition, osteoblast differentiation, and mineralization related to bone turnover.
METHODS: The nitric oxide inhibition of the extracts in LPS-stimulated RAW 264.7 cells were evaluated by Griess reagent while osteoblast differentiations of extracts were evaluated by measuring alkaline phosphatase in p-nitrophenyl phosphate and their mineralization was determined using Alizarin Red Staining method.
RESULTS: The 70% ethanol and aqueous extracts inhibited cells inflammation (40% and 80%) and stimulated osteoblast differentiation (65% and 52%), respectively. In mineralization test, the aqueous extract showed two times higher effect than that of 70% ethanol extract.
DISCUSSION AND CONCLUSION: The extracts can be considered to successfully reduce expression of inflammatory markers on osteoblasts and maintain osteoblast functions.

GİRİŞ ve AMAÇ: Nikel oksit nanopartikülleri (NiO-NP), olağanüstü özellikleri nedeniyle farklı alanlarda geniş kullanıma sahiptir. Ancak, NiO-NP’nin, özellikle oral maruziyet durumunda, toksisiteleri hakkındaki bilgiler henüz yeterli değildir. Özellikle NiO-NP'nin intestinal sistem üzerine toksik etkisi ile ilgili herhangi bir çalışma bulunmadığından çalışmada NiO-NP’nin (ortalama boyut 15.0 nm) Caco-2 (insan intestinal epitel) hücreleri üzerine toksisitesi araştırılmıştır.
YÖNTEM ve GEREÇLER: Partikül boyutu dağılımı ve hücresel alım potansiyeli belirlendikten sonra NiO-NP'nin sebep olduğu hücresel morfolojik değişiklikler, sito- ve genotoksik potansiyeller, oksidatif hasar ve apoptoz indüksiyonu gibi kritik toksisite profilleri değerlendirilmiştir.
BULGULAR: Sonuçlarımıza göre; NiO-NP 351,6 µg/mL konsantrasyonda hücre canlılığında %50 azalmaya ve 30-150 µg/mL'de DNA ve oksidatif hasar indüksiyonuna sebep olmuştur. NiO-NP'e maruz bırakılan intestinal hücrelerde ana hücre ölüm yolunun apoptoz olabileceği gözlenmiştir.
TARTIŞMA ve SONUÇ: NiO-NP gastrointestinal sistem üzerine risk oluşturabilir. Elde edilen sonuçlara göre; gıdayla temas eden cihazların yapımında NiO-NP'in kullanımı ve NiO-NP içeren atıklar nedeniyle oluşan kaygıyı artırmalıdır. NiO-NP’in spesifik mekanizmalarını aydınlatmak ve insan sağlığı üzerine risklerini azaltmak için ayrıca ileri in vivo ve in vitro araştırmaların yapılması gereklidir.

INTRODUCTION: The superior properties of nickel oxide nanoparticles (NiO-NPs) lead to wide uses in various fields; however, there has been little comprehensive knowledge about their toxicity, especially oral exposure. Because there was no study on the intestinal toxicity of NiO-NPs, the toxicity of NiO-NPs (average size 15.0 nm) was investigated in Caco-2 (human intestinal epithelial) cells.
METHODS: Following identification of their particle size distribution and cellular uptake potential, the risk of NiO-NPs’ exposure have been evaluated with the crucial toxicity features including the cellular morphologic changes, the cyto- and genotoxic potentials, oxidative damage and apoptotic induction.
RESULTS: According to our results, NiO-NPs caused 50% decrease in cell viability at 351.6 µg/mL, and induced DNA damage and oxidative damage at 30-150 µg/mL. It was observed that apoptosis could be the main cell death pathway at in intestinal cells exposed to NiO-NPs.
DISCUSSION AND CONCLUSION: The exposure to NiO-NPs could be hazardous to the gastrointestinal system. The results should rise the concerns about using NiO- NPs in food-contacts appliance and NiO-NPs containing wastes. Further in vivo and in vitro research should be conducted to explain the specific mechanism of these particles and reduce their risk to the human.

GİRİŞ ve AMAÇ: MikroRNA’lar (miRNA) kısa, endojen ve kodlamayan RNA molekülleri olup hedef mRNA’lara bağlanarak gen ekspresyonunu düzenlerler. Az sayıdaki çalışmada, alerjik deri hasalıklarında miRNA’ların yüksek veya düşük ekpresyonları gösterilmiştir ancak daha ileri çalışmalara ihtiyaç vardır. Bu çalışmada, p-fenilendiamine reaksiyon gösteren hastalarda ana alerjen madde olan ve aynı zamanda yaygın bir kontakt alerjen olan Bandrowski’s base (BB) maruziyeti sonrası miRNA’ların ekspresyon profillerinin incelenmesi amaçlanmaktadır.
YÖNTEM ve GEREÇLER: İnsan promiyelositik hücreleri (THP-1), 1 µg/ml dozunda BB’e 24, 48 ve 72 saat maruz bırakılmıştır. Bu doz sitotoksisite deneylerinin sonuçlarına göre seçilmiştir. RNA saflaştırılarak, miRNA ekspresyon profili ve gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) ile yüksek veya düşük ekspresyona sahip miRNA’lar ortaya konulmuş ve sonrasında bu değişimler doğrulanmıştır.
BULGULAR: Farklı ekspresyonlara sahip miRNA’lar arasında, immün sistem ile ilişkili oldukları için, miRNA-155’in yüksek ve miRNA-21’in ise düşük ekspresyona sahip olması önemli bulunmuştur. Ayrıca bu ekspresyon profili RT-PCR ile doğrulanmıştır.
TARTIŞMA ve SONUÇ: Bu ön sonuçlar, miR-155 ve miR-21’in alerjik kontakt dermatit patogenezinde rolü olabileceğini göstermektedir. Ancak bu rollerin açıklanabilmesi için ileri çalışmalara ihtiyaç vardır

INTRODUCTION: MicroRNAs (miRNAs) are short, endogenous noncoding RNA molecules that can bind to parts of target mRNAs, thereby regulating gene expression. Few studies have shown that microRNAs can be up or down-regulated in allergic skin conditions but still, there is a need for further studies. The aim of this study was to investigate the expression of miRNAs in response to the common contact allergen Bandrowski’s base (BB), the principal allergen in patients reacting to p-phenylenediamine (PPD).
METHODS: The human promyelocytic cell line (THP-1) was exposed to BB at the concentration of 1 µg/ml for 24, 48 and 72 hours. The dose was selected from the results of cytotoxicity assays. RNA was purified, and miRNA expression profile and real-time polymerase chain reaction (RT-PCR) were performed to identify up or down-regulated miRNAs and after, to confirm their modulation.
RESULTS: Among the different modulated miRNAs, the up-regulation of miRNA-155 and the down-regulation of miRNA-21 were found to be important because these are related to immune systems. This expression profile of miRNAs was also confirmed by RT-PCR.
DISCUSSION AND CONCLUSION: These preliminary results showed that miR-155 and miR-21 may have a role in the pathogenesis of allergic contact dermatitis. But further studies are needed to clarify their roles

Bisfenol A (BFA) endokrin aktiviteye sahip bilinen en eski bileşiklerden biridir. BFA epoksi reçinelerin, polikarbonatların, dental dolguların, yemek saklama kaplarının, bebek biberonlarının ve mineral su konteynırlarının üretiminde yaygın olarak kullanılmaktadır. BFA diabet, obezite, kardiyovasküler hastalıklar, kronik solunum hastalıkları, renal hastalıklar, meme kanseri, davranış bozuklukları, diş gelişimi bozuklukları ve üreme bozuklukları gibi çeşitli sağlık problemleriyle ilişkilendirilmiştir. Artan sağlık endişeleri endüstriyi BFA alternatifleri aramaya yönlendirmiştir, BFA ürünlerden çıkarılmaya başlandıkça alternatif bisfenollerin kullanımı artmıştır. Ancak BFA yerine kullanılan kimyasallarda bisfenoldür ve organizmalar üzerinde benzer fizyolojik etkileri olabilmektedir. Araştırmalara göre BFA analoglarınında BFA’ya kıyasla benzer veya daha yüksek toksik etkiler oluşturabileceği gösterilmektedir.

Bisphenol A(BPA) is known as one of the oldest sentetic compounds with endocrine activity. BPA is commonly used in production of epoxy resins, policarbonates, dental fillings, food storage containers, baby bottles and mineral water containers. BPA is associated with various health problems such as diabetes, obesity, cardiovascular diseases, chronic respiratory diseases, renal diseases, breast cancer, behaviour disorders, teeth development disorders and reproductive diorders. Increasing health concerns led the endustry to seek alternatives for BPA, as BPA has begun to be excluded from the products, the use of alternative bisphenols has been increased. However the chemicals used as a replacement of BPA are also bisphenols and may have similar physiological effects on organisms. According to the researches, it is demonstrated that BPA analogs may result in similar or higher toxic effects compared to BPA.