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The objective of the present research was to examine the possible usage of terbinafine loaded hydrogels for vaginal application as part of vaginal candidiasis treatment. Vaginal candidiasis belongs to the most frequent gynecological disorders. Various antifungal drugs are used for its treatment, with Terbinafine being one of them. In this study, new gel formulations were prepared for Terbinafine vaginal delivery. Natural polymers such as chitosan, sodium carboxymethylcellulose, and Carbopol were used for the development of Terbinafine vaginal gels. The developed gels were examined for their viscosity and spreadability, pH and mechanical properties. The most optimal formulations were further evaluated for their in vitro release behavior and antifungal activities. In further, the cytotoxicity and irritation inducing capacity of optimum gel formulations were evaluated. In vitro drug release studies demonstrated that terbinafine release was prolonged whereas anti-candida activity in several species showed the superiority of the gels compared to the marketed product. G-5 and G-8 gels did not cause lysis, hemorrhage and coagulation, therefore, classified as non-irritant. The optimal formulations were also studied for their stability, demonstrating that they were stable for 3 months. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Objective: The aim of this study was to investigate the effects of naringin, a known flavonoid, on in vitro cytotoxicity, irritation and in vivo potential efficacy when topically applied to the diabetic wound. Material and Method: In vitro direct contact assay and hen's egg chorio-allantoin membrane tests were used to evaluate irritation, and cytotoxicity potential of Naringin. In vitro antimicrobial activity was also tested. Topical treatments were administered once a day on the wound. Wound lesions were photographed and statistically analyzed. After the 10th day, histopathological parameters of tissues were assessed. Result and Discussion: The results showed that naringin gel has no cytotoxicity and irritation potential. Also, it displayed a weak antimicrobial effect. Aside from these, in vivo studies revealed that naringin gel showed statistically higher wound contraction and re-epithelialization, the thickness of granulation tissue, angiogenesis scores. The results indicated that naringin gel effectively enhanced diabetic wound healing, and so this formulation could be considered a promising therapeutic alternative for treating diabetic wounds. Amaç: Bu çalışmanın amacı, bir flavonoid olan Naringin’in in vitro sitotoksisite, irritasyon ile diyabetik yara üzerindeki in vivo potansiyel etkilerini araştırmaktı. Gereç ve Yöntem: Naringin'in irritasyon ve sitotoksisite potansiyelini değerlendirmek için in vitro doğrudan temas deneyi ve tavuk yumurtası korio-allantoin membran testleri kullanıldı. Aynı zamanda in vitro antimikrobiyal etkinlikte test edildi. Topikal tedaviler günde bir kez yaraya uygulandı. Yara lezyonları fotoğraflandı ve istatistiksel olarak analiz edildi. 10. günden sonra dokuların histopatolojik parametrelerideğerlendirildi.Sonuç ve Tartışma: Sonuçlar, naringin jelin sitotoksisite ve tahriş potansiyeli olmadığını göstermiştir. Ayrıca, zayıf bir antimikrobiyal etki gösterdi. Bunların yanı sıra, in vivo çalışmalar naringin jelin istatistikselolarak daha yüksek yara kapanması ve re-epitelyalizasyon, granülasyon dokusunun kalınlığı ve anjiyogenezskorları gösterdiğini ortaya koymuştur. Sonuçlar, naringin jelin diyabetik yara iyileşmesini etkili bir şekilde arttırdığını gösterdi ve bu nedenle bu formülasyon, diyabetik yaraların tedavisi için umut verici bir terapötik alternatif olarak düşünülebilir.

A series of five –CH3, -NO2, -OCH3 and -Cl substituted 2-hydroxy-2,2-bis(4-phenyl)-N'-[(1E)-(3/4-phenyl)methylene]acetohydrazide (1a-1e) was synthesized by the reaction of 2-hydroxy-2,2-diphenylacetohydrazide with substituted aromatic aldehydes to give intermediate Schiff bases. Structures of the synthesized compounds were characterized using NMR (1D; 1H, 13C/APT and 2D 1H-1H COSY, and NOESY), FT-IR, UV, LC-MS/MS spectral data and elemental analysis. The geometry of compounds 1a-1e were determined to be “E” by NOESY. All the tested compounds showed cytotoxic activity on MCF-7 and PC-3 cell line at highest experimental concentration (100 µM). Compounds 1b (18.24 ± 7.62 µM) and 1e (7.62 ± 1.85 µM) have strong anti-proliferative activity on MCF-7 cell line, while compound 1b (45.81 ± 1.10 µM) has the strongest activity on PC-3 cell line.

Objectives: Occupational lead (Pb) exposure is still an important health problem in the world. Long-term Pb exposure causes several adverse effects. The aim of this study was to investigate the changes of inflammation markers with chronic Pb exposure by analyzing neopterin levels and kynurenine (Kyn) to tryptophan (Trp) ratio that reflects indolamine 2,3-dioxygenase activity and to compare with healthy volunteers' parameters. Methods: Blood lead levels (BLLs) were analyzed by atomic absorption spectrometry. Urinary neopterin and serum Kyn and Trp levels were analyzed by high-performance liquid chromatography. Results: According to our results, mean BLL of the 29 workers was 20.4±9.6 μg/dl. Urinary neopterin levels, serum Kyn levels, and Kyn/Trp of Pb workers (188±52 μmol/mol creatinine, 2.70±0.66 μM, and 43.19±10.38 μmol/mmol, respectively) were significantly higher than controls (144±35 μmol/mol creatinine, 2.08±0.34 μM, and 32.24±7.69 μmol/mmol, respectively). Pb-exposed workers were divided into further three groups according to their BLLs: as 10-19 μg/dl (n=18), 20-29 μg/dl (n=8), and 30-49 μg/dl (n=3). Neopterin levels of the workers with BLL of 30-49 μg/dl were significantly higher than those of BLL with 10-29 μg/dl, while Trp levels decreased. Kyn/Trp of workers with BLL of 30-49 μg/dl were elevated significantly compared with the workers with BLL

Energy drinks (ED) are containing large doses of metabolic stimulants and its use with ethanol has increased dramatically among young adults. In this study, we examined the effects of ED exposure either alone or in combination with ethanol on oxidative stress parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and lipid peroxidation parameter malondialdehyde (MDA) in rat. Some histopathological findings were also evaluated. ED exposure led to a dose-dependent increase in liver MDA compared to the control indicating oxidative damage. Histopathological findings also revealed that ED alone may generate liver damage. Ethanol exposure increased MDA level and SOD, CAT, and GSH-Px activity in both the brain and the liver. The combination of ethanol and ED produced greater damage which is considered by further increases in SOD and GSH-Px activity in the brain. Similar results for MDA were observed in both the liver and brain as well. Our findings suggest that ED consumption alone or combination with ethanol may represent a significant public health concern.

[Image: see text] Tevarud designates two poets coincidently writing a same verse in the Ottoman Divan literature. This study aims to analyze the structural similarity of molecules independently designed for inflammation and depression to determine if coincidentally we are building similar molecules for comorbid diseases. For this purpose, a molecule library was first constituted with structures that were developed as anti-inflammatory (AI) and antidepressant (AD) agents these last decades. Then, the similarity of the structures was determined by calculating the Tanimoto and Cosine similarity coefficients for each AD/AI pair. The highest scores were obtained for two theophylline derivatives: AD17 (for which some AI activity was found to be mentioned) and AI42. The study also pointed out the similarity of some AD coumarins with some AI flavonoids interestingly found to be highly similar to some AI coumarins and AD flavonoids, respectively. Thus, our investigation demonstrated that structures independently developed as AD and AI derivatives can present extremely high structural similarity, a finding that can suggest mechanistic interconnection for these comorbid diseases and also guide for the design of novel bioactive compounds.

Dinc, Ozge/0000-0002-3029-7840; sipahi, hande/0000-0001-6482-3143; Reis, Rengin/0000-0002-3484-2201 WOS: 000476210100001 PubMed: 31303057 Electrolyzed water (EW) is a widely used disinfectant agent with high oxidation-reduction potential (ORP). Although EW has been used in many areas, such as food hygiene, agriculture, and animal husbandry, the studies presented in the literature are not enough to clarify the toxic effects of EW. The aim of this study is, therefore, to produce EWs at different pH, ORP, and chlorine concentrations and to assess their safety in terms of toxicology. At the beginning of the study, the antimicrobial activity of the EW types with respect to bacteria and fungus was investigated. EWs below pH 7 were all effective in inactivating Enterococcus hirae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans completely. In vitro studies of cell cultures revealed that different concentrations of EWs were not cytotoxic for the L929 cells under 10- to 80-fold dilutions. In addition, it has been determined that produced EWs did not have irritation potential, according to the in vitro EpiDerm((TM)), reconstituted skin irritation test in the frames of biocompatibility tests. For the mucous membrane irritation test, the hen's egg test-chorioallantoic membrane experiment was performed, and EWs were found to have no eye irritation. In conclusion, it has been shown that produced EWs with antimicrobial efficacy were found to be safe for skin and eye according to in vitro biocompatibility study studies. Thus, the establishment of a technological infrastructure for the EW production and the use of produced EW as an effective disinfectant in the food, medical, and agricultural areas should be encouraged. Scientific and Technological Research Council of Turkey (TUBITAK) 1002 programTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116Z169] The author(s) disclosed financial support for the research, authorship, and/or publication of this article: This project is financially supported by the Scientific and Technological Research Council of Turkey (TUBITAK) 1002 program (116Z169).

Rosmarinus officinalis L. (rosemary) is a common culinary spice and herbal drug, which is used for centuries all over the world. In this present study, apolar to polar fractions of R. officinalis flowers were evaluated for their in vitro antioxidant, antibacterial, cytotoxic, anti-inflammatory and analgesic activities, respectively. Phytochemical compositions of R. officinalis extract fractions were analyzed by GC–MS and LC–MS. The antioxidant capacity of the fractions was evaluated by using the DPPH• and ABTS• methods. The antibacterial potential was determined using the in vitro broth microdilution assay against a panel of human pathogens. The analgesic and anti-inflammatory activities were investigated measuring nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-stimulated cells, respectively. In addition, in vitro cytotoxicity of the extract fractions was evaluated on RAW 264.7 murine macrophage cells by using the MTT assay. The constituents of the polar fractions were identified as rosmarinic acid, luteolin, quercetin and apigenin by LC techniques, whereas the n-hexane fraction was analyzed by GC–MS to determine the main volatile components camphor (19.6%), 1,8-cineole (11.7%), verbenone (11.5%), borneol (10.6%), ?-pinene (5.8%), and linalool (5.7%). According to the bioactivity results, the polar fraction showed the highest antioxidant activity, whereas n-hexane fraction was found to be most effective against Staphylococcus aureus (78 µg/mL). The n-hexane fraction (100 µg/mL) reduced the LPS-induced NO and PGE2 production capability. In conclusion, R. officinalis flower n-hexane and ethyl acetate fractions exhibited remarkable in vitro antibacterial, antioxidant, anti-inflammatory and analgesic activities possibly due to their polyphenol content, to the best of our knowledge for the first time. © 2019 South African Association of Botanists

Early and accurate prediction of adverse drug reactions (ADRs) by computer-aided methods is extremely important for decreasing health threats, along with preventing product withdrawal after clinical trials which need long time and high cost. In this study, we built a model to predict 329 known ADRs of 27 approved antidepressant drugs, and we examined three machine learning algorithms (multilayer perceptron, k-nearest neighbour and support vector machine) in order to find which one is better for this duty. We integrated the known ADRs of a drug with the drug’s chemical structures and biological properties, including drug targets, enzymes and transporters for prediction of ADR in our predictive model. In addition, 329 known ADRs were grouped according to their system organ classes (SOCs) and compared the performances of ADR predictions. This assessment, based on a ten-fold cross-validation, showed that the multilayer perceptron (MLP) algorithm surpassed the others. 248 out of 329 ADRs were successfully predicted. The best performing attribute group was the chemical plus biological, followed by the chemical and biological. The mean AUC values are 0.623, 0.676, and 0.695 for the feature groups of chemical, biological, and chemical plus biological, respectively. Among ADRs of the 21 SOCs, only ADRs belonging to 5 SOCs were predicted successfully by chemical, biological or combined attributes. Also, the ADRs related to withdrawal of indalpine, pheniprazine, medifoxamine, zimelidine and amineptine were successfully predicted by our model constructed using MLP with the CfsSubsetEval and BestFirst, based on chemical properties of the approved antidepressants. The results showed the external validity of our approach, predicting satisfactory amount of previously known ADRs from the literature. In conclusion, the proposed approach is an efficient and promising tool for predicting ADRs of antidepressants.

Coumarins (2H-1-benzopyran-2-one), derivatives that can be isolated from several plants, have been reported for their anticoagulant, antimicrobial, anti-inflammatory, or anticancer activity. Some of these structures are currently approved for the treatment of cardiovascular diseases, as antibiotics or as an anticancer drug. Given the great potential of this structure and the limited number of studies that focus on molecules derived from carbon 8 of the benzopyranone heterocycle, we synthesized in this project 38 coumarin derivatives by substituting carbon 8 of the benzopyran ring with some aromatic and aliphatically substituted piperidines and piperazines. As a few of these structures were already shown to exhibit some carbonic anhydrase (CA) inhibition and as CA enzymes are reported to be closely related to inflammation, the synthesized derivatives were evaluated for their anti-inflammatory activity in vitro. The results indicated that compounds 20 and 31 revealed promising anti-inflammatory activity, as they demonstrated better activity than the reference drugs.

Ethnopharmacological relevance Styrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. Aim of study In spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of the present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. Materials and methods In vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10– 30,000 µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500–2000 mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. Results Genotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000 mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77 µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95 mg/g), while in its ethanolic extract not only p-coumaric acid (11.46 mg/g), but also gallic acid (1.60 mg/g) were found to the main components. Conclusion The findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity.

ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4-carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro. On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.

Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine presents some toxicity and therefore is usually supplemented in a prodrug approach. Here, some thiazolidine-4-carboxylic acids were synthesized and evaluated for their antioxidant properties via the DDPH and CUPRAC assays. Then, the cysteine releasing capacity of the obtained compounds was investigated in aqueous and organic medium in order to correlate the relevant antioxidant properties of the molecules with their cysteine releasing pattern. As a result, the structures' antioxidative properties were not only attributed to cysteine release but also to the thiazolidine cycle itself.

The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 &micro, g/mL, whereas the DPPH&bull, assay showed IC50 = 0.89 mg/mL, and the ABTS&bull, assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC&ndash, FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.

Background: The discovery of novel potent molecules for both cancer prevention and treatment has been continuing over the past decade. In recent years, identification of new, potent, and safe anticancer agents through drug repurposing has been regarded as an expeditious alternative to traditional drug development. The cyclooxygenase-2 is known to be over-expressed in several types of human cancer. For this reason cyclooxygenase-2 inhibition may be useful tool for cancer chemotherapy. Objective: The first aim of the study was to develop a validated linear model to predict antitumor activity. Subsequently, applicability of the model for repurposing these cyclooxygenase-2 inhibitors as antitumor compounds to abridge drug development process. Method: We performed a quantitative structure-toxicity relationship (QSTR) study on a set of coumarin derivatives using a large set of molecular descriptors. A linear model predicting growth inhibition on leukemia CCRF cell lines was developed and consequently validated internally and externally. Accordingly, the model was applied on a set of 143 cyclooxygenase-2 inhibitor coumarin derivatives to explore their antitumor activity. Results: The results indicated that the developed QSAR model would be useful for estimating inhibitory activity of coumarin derivatives on leukemia cell lines. Electronegativity was found to be a prominent property of the molecules in describing antitumor activity. The applicability domain of the developed model highlighted the potential antitumor compounds. Conclusion: The promising results revealed that applied integrated in silico approach for repurposing by combining both the biological activity similarity and the molecular similarity via the computational method could be efficiently used to screen potential antitumor compounds among cyclooxygenase-2 inhibitors.

Acyl glucuronidation is an important Phase II biotransformation, which is an efficient detoxification mechanism for the metabolism of carboxylic acid group-containing drugs. However, the reactivity of acyl glucuronide (AG) metabolites associated with short half-lives may be an indication of idiosyncratic drug toxicity. The degradation half-lives of AGs elucidate several important reactions such as hydrolysis, acyl migration and covalent binding to proteins. Prediction of degradation half-life using computational methods is a promising alternative approach to costly and time-consuming experiments, enabling

Growing evidence links inflammation to depression and the combination of antiinflammatory drugs with an antidepressant to treat depressive symptoms is currently suggested. There are only few studies concerning the molecular mechanism underlying this comorbidity, and many of them point out the importance of the tryptophan pathway. There is yet no data that analyzes the structural similarity of the molecules used for the treatment of these comorbid diseases. This review aimed first to classify current antidepressant drugs and Non-steroidal Anti-inflammatory Drugs (NSAIDs) according to their structure. Molecules with two aromatic rings linked with a heteroatom or a carbonyl group (vortioxetine, ketoprofen, diclofenac), or presenting a naphtyl moiety in their structure (duloxetine, agomelatine, naproxen, nabumetone) were found to be structurally related. The antidepressant activity of these NSAIDs and the anti-inflammatory activity of these antidepressants were investigated. The literature search interestingly revealed reports indicating a serotonin-related antidepressant activity of the NSAIDs for structures found to be structurally similar to some antidepressants. Similarly, the antiinflammatory activity of the corresponding antidepressants was found to be correlated to the tryptophan metabolism pathway. These findings suggest a common molecular mechanism involved in both of the diseases and exhibit the importance of the molecular structure for a drug to be a potent antidepressant and/or anti-inflammatory agent.

Phytochemical investigations on the EtOH extract of

Phytochemical investigations on the EtOH extract of Clematis viticella led to the isolation of six flavonoid glycosides, isoorientin (1), isoorientin 3′-O-methyl ether (2), quercetin 7-O-α-L-rhamnopyranoside (3), quercetin 3,7-di-O-α-L-rhamnopyranoside (4), manghaslin (5) and chrysoeriol 7-O-β-D-glucopyranoside (6), one phenylethanol derivative, hydroxytyrosol (7), along with three phenolic acids, caffeic acid (8), (E)-p-coumaric acid (9) and p-hydroxybenzoic acid (10). The structures of the isolates were elucidated on the basis of NMR and HR-MS data. All compounds were isolated from C. viticella for the first time. Compounds 7 and 8 showed significant anti-inflammatory activity at 100 μM by reducing the release of NO in LPS-stimulated macrophages comparable to positive control indomethacin. Compounds 3 and 7 exhibited anti-inflammatory activity through lowering the levels of TNF-α while 1, 3 and 5 decreased the levels of neopterin better than the positive controls.

Natural products can present remarkable biological and pharmacological activities. In traditional medicine, plants have been used historically in treating cancer, infections, and other inflammatory conditions.Verbascoside and catechin are widespread polyphenolic plant compounds that could play a role in the anti-inflammatory and health-promoting effects of plants and plant extracts.This study compares the potential cytotoxic effects of polyphenols verbascoside and catechin (6.25-200 µM) on human peripheral blood mononuclear cells (PBMC) for 48 h and myelomonocytic THP-1 and THP-1 Blue cells for 24 h. The effects of the compounds on immune activation markers such as indoleamine 2,3-dioxygenase (IDO) activity as well as on neopterin formation and nuclear factor-κB (NF-κB) activation were investigated. Cytotoxicity of the compounds was tested using Cell-Titer Blue assay.Verbascoside exhibited significant suppressive effects in mitogen-stimulated PBMC on tryptophan breakdown (50 µM; IC50 value: 58.6 µM) and the production of neopterin (6.25 µM; IC50 value: 217 µM). These effects correlated with a decline in cell viability, while THP-1 Blue cells were less sensitive. NF-κB activity was slightly enhanced at lower concentrations (50 µM verbascoside) in stimulated cells and at the highest concentration used in unstimulated cells. Catechin had no relevant effects on cell viability and on the tested inflammation markers, except NF-κB activation in THP-1 Blue cells.The results obtained show that verbascoside and catechin represent effective compounds which interfere with immunobiochemical pathways that are highly relevant for immunosurveillance and competing virus infections.

Folates are crucial cofactors involved in the de novo generation of purine and deoxythymidine monophosphate, which are essential for DNA synthesis. Antifolates are structural analogues of folate derivatives that act as inhibitors of folate-dependent enzymes and constitute the oldest antimetabolite class of anticancer agents. This review focuses on antifolates with remarkable anticancer activities that include a terminal alkyne function in their molecular structure. The properties of CB3717, a tremendous inhibitor of thymidylate synthase, are described, and the development of raltitrexed and pralatrexate, a dihydrofolate reductase inhibitor approved by the U.S. Food and Drug Administration (FDA) as the first drug for the treatment of relapsed and refractory peripheral T cell lymphoma are presented.

This study was designed to evaluate the effects of acetaminophen (APAP) and N-acetylcysteine (NAC) in combination on the protective effect of NAC for possible APAP toxicity determining oxidative stress and inflammation parameters in a rat model. DMSO as vehicle, 50 mg/kg APAP and 50 mg/kg APAP plus 100 mg/kg NAC were administrated to Wistar Albino rats by intra-peritoneal for five days. Plasma TNF-α, IL-2 and IL-6 levels and level of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities in liver and kidney were analyzed. APAP administration produced an increase in hepatic and renal MDA levels and co-administration of APAP plus NAC resulted in decreases in the kidney MDA levels and an increase in hepatic and renal superoxide scavenging enzyme, SOD, activity. Taken together, the results of this study suggest that combination of APAP and NAC may be a valuable combination to protect hepatotoxicity and nephrotoxicity induced by APAP. Furthermore, pharmaceutical preparation with combination of APAP and NAC may be useful alternative to prevent from possible APAP related toxicity. However, further investigations are needed to understand the underlying protection mechanism of NAC combination with APAP

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR

[No abstract available]

Increased neopterin concentrations and altered tryptophan degradation are observed in diseases concomitant with cellular immune activation. This may be involved in the pathogenesis of several age-related disorders such as neurodegenerative disorders, autoimmune diseases, cardiovascular system disorders and malignancies. Therefore, in the present study, the evaluation of immune system activation by determination of tryptophan degradation and serum neopterin levels was carried out in volunteers aged ≥65 and 0.05). Effects of gender, smoking habit, pathology and drug use on measured parameters were also evaluated. In conclusion, our findings show that aging is associated with immune activation, and immune activation may be induced by the number of existing pathologies as well as the number of drugs used.

Purpose: The study aims to evaluate changes in neopterin levels and tryptophan degradation which are induced by Th1-type immune response and nitric oxide metabolism which may be involved in allergic inflammation. Methods: Serum nitrite, kynurenine, tryptophan and neopterin levels were evaluated in 36 patients with seasonal allergic conjunctivitis, along with these values in 41 healthy subjects. All these parameters have been compared with symptom and sign scores. Results: Tryptophan and kynurenine concentrations were not significantly changed, while serum nitrite concentrations were significantly low, and neopterin levels were significantly increased in patients compared to healthy subjects (p

Background Evaluations of silver in both nanoparticle (Ag-NPs) and ionic forms indicate some adverse effects on living organisms, but little is known about their potential for developmental toxicity. In this study, developmental toxicity of Ag-NPs (from 0.2 to 20 mg/kg/day) and ionic Ag (AgNO3, 20 mg Ag/kg/day) were investigated in rats. Methods Animals were dosed by gavage from gestation day 7 − 20. The day after parturition, dams and pups were sacrificed and Ag level assessed in several maternal and pup organs. In addition, hepatotoxicity and oxidative stress parameters and histopathology were evaluated. Results No treatment related effects were found for gestational parameters including pregnancy length, maternal weight gain, implantations, birth weight and litter size at any dose level of Ag-NPs. Maternal weight gain was lower in dams receiving AgNO3 compared to the other groups, suggesting that the ionic form may exert a higher degree of toxicity compared to the NP form. Tissue contents of Ag were higher in all treated groups compared to control dams and pups, indicating transfer of Ag across the placenta. The findings furthermore suggest that Ag may induce oxidative stress in dams and their offspring, although significant induction was only observed after dosing with AgNO3. Histopathological examination of brain tissue revealed a high incidence of hippocampal sclerosis in dams treated with nanoparticle as well as ionic Ag. Conclusion The difference in offspring deposition patterns between ionic and NP Ag and the observations in dam brain tissue, requires scrutiny, and, if corroborated, indicate that ionic and NP forms maybe need separate risk assessments and that the hazard ratings of silver in both ionic and nanoparticle forms should be increased, respectively. Trial registration Not applicable. Graphical abstract Developmental Toxicity of Ag-NPs.

Energy drinks (ED) are containing large doses of metabolic stimulants and its use with ethanol has increased dramatically among young adults. In this study, we examined the effects of ED exposure either alone or in combination with ethanol on oxidative stress parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and lipid peroxidation parameter malondialdehyde (MDA) in rat. Some histopathological findings were also evaluated. ED exposure led to a dose-dependent increase in liver MDA compared to the control indicating oxidative damage. Histopathological findings also revealed that ED alone may generate liver damage. Ethanol exposure increased MDA level and SOD, CAT, and GSH-Px activity in both the brain and the liver. The combination of ethanol and ED produced greater damage which is considered by further increases in SOD and GSH-Px activity in the brain. Similar results for MDA were observed in both the liver and brain as well. Our findings suggest that ED consumption alone or combination with ethanol may represent a significant public health concern.

Cosmetics are one of the most common reasons for hospital referrals with allergic contact dermatitis. Because of the increased use of cosmetics within the population and an increase in allergy cases, monitoring of heavy metals, especially allergen metals, is crucial. The aim of this study was to investigate the concentration of allergen metals, nickel (Ni), cobalt (Co), and chromium (Cr), in the most commonly used cosmetic products including mascara, eyeliner, eye shadow, lipstick, and nail polish. In addition, for safety assessment of cosmetic products, margin of safety of the metals was evaluated. Forty-eight makeup products were purchased randomly from local markets and large cosmetic stores in Istanbul, Turkey, and an atomic absorption spectrometer was used for metal content determination. Risk assessment of the investigated cosmetic products was performed by calculating the systemic exposure dosage (SED) using Scientific Committee on Consumer Safety guideline. According to the results of this investigation in all the samples tested, at least two of the allergen metals, Ni and/or Co and/or Cr were detected. Moreover, 97% of the Ni-detected products, 96% of Cr- and 54% of Co-detected products, contained over 1 μg/g of this metals, which is the suggested ultimate target value for sensitive population and thereby can be considered as the possible allergen. On the basis of the results of this study, SED of the metals was negligible; however, contact dermatitis caused by cosmetics is most probably due to the allergen metal content of the products. In conclusion, to assess the safety of the finished products, postmarketing vigilance and routine monitoring of allergen metals are very important to protect public health.

Suyun kalitesi halk sağlığı için çok önemlidir. Ancak sularda nitrit ve nitrat düzeyleri hala önemli bir kontaminasyon problemidir. Bu çalışmanın amacı İstanbul'un farklı bölgelerinden toplanan musluk suyu ve çeşme sularında toplam nitrit ve nitrat düzeylerini tespit etmektir. Bu amaçla çeşitli bölgelerden musluk suyu örnekleri Kasım 2013'den Mart 2014'e kadar toplanmış ve değerlendirilmiştir. Su örneklerinde ortalama toplam nitrit ve nitrat düzeyleri Kasım, Aralık 2013 ve Şubat 2014 ile karşılaştırıldığında Mart 2014'te en yüksektir. ABD Çevre Koruma Ajansına göre, musluk sularından iki tanesi ve kuyu sularından üç tanesi toplam nitrat ve nitrit için maksimum kabul edilebilir konsantrasyonu (10 ppm) aşmaktadır. Ancak tüm örneklerde bu düzeyler Türkiye'nin resmi dökümanlarında bildirilen maksimum kabul edilebilir düzeylerin altındadır. Ayrıca, yıllar arası değişimi saptamak için, bir önceki yıla ait su örnekleri de değerlendirilmiştir. Sonuçlar Aralık 2013-Şubat 2014 döneminde toplam nitrit ve nitrat düzeylerinin Aralık 2012-Şubat 2013 dönemine göre %2, 10 ve 18 oranında azalma göstermiştir. Sonuçlarımıza göre, mevsimsel değişim göz önüne alınarak, halk sağlığının korunması için sularda nitrit/nitrat düzeyleri rutin olarak kontrol edilmelidir. Water quality has a major importance for public health. However, nitrite and nitrate levels in water are still an important contamination issue in the world. The aim of this study was to determine the levels of total nitrite and nitrate in public water (tap water) and wells from different districts of Istanbul city and to evaluate the seasonal variation from November 2013 to March 2014. The average levels in tap waters were highest in March 2014 compared with November, December 2013 and February 2014. Two of the tap water and 3 of the well water samples exceed the maximum acceptable concentration according to the U.S. Environmental Protection Agency (10 ppm). However, these levels were still lower than the maximum allowable limits reported in official documents of Turkey. Also, in order to determine the annual variation, tap water samples were collected between December 2012 and February 2013 and evaluated for total nitrite and nitrate levels. Results showed that total nitrite and nitrate levels during December 2013 and February 2014 were decreased in the ratio of 2, 10 and 18% compared to the same months during December 2012 and February 2013. In conclusion, our results suggested that due to seasonal and annual variations, nitrite and nitrate levels of waters should be routinely controlled to prevent various health hazards.

The aim of the study was to determine folate reserve in patients with thyroid and breast diseases. Erythrocyte folate concentrations of ninety-eight patients and thirty healthy subjects were determined by a modified microbiological assay. An increase in folate levels was observed in of both thyroid (n = 15) and breast (n = 22) cancer patients compared to controls, while a decrease was observed in benign breast disease patients (n = 24) compared to both control group and breast cancer patients. Patients with benign thyroid diseases (n = 37) had significantly lower folate concentrations as compared to both control and thyroid cancer groups. The results pointed out the elevated erythrocyte folate levels in the patients with malignant tumors.

The present study was undertaken to evaluate urinary neopterin in intensive care unit patients.Urinary neopterin levels were determined in systemic inflammatory response syndrome (n = 10), sepsis (n = 18), septic shock (n = 9), and multiple organ dysfunction syndrome (n = 5). It was tested whether neopterin is a differential parameter among the patient groups. Furthermore, the results were also evaluated by comparing with a healthy control group (n = 30), and the relationship between neopterin and mortality or Acute Physiology and Chronic Health Evaluation II scores were investigated.Neopterin levels of the control group and patients were detected as 111 +/- 11 and 3850 +/- 1081 mumol/mol creatinine, respectively (P.05). It was significantly increased in the sepsis and septic shock groups compared to the systemic inflammatory response syndrome group (P.05). Neopterin levels were significantly higher in the patients with mortality and lower Acute Physiology and Chronic Health Evaluation II scores.This study showed that monitoring of urinary neopterin profile can be used in intensive care units to show the degree and prognosis of the disease.

Background Dried fruits of Berberis crataegina (Berberidaceae) have been frequently consumed as food garniture in Turkish cuisine, while its fruit paste has been used to increase stamina and in particular to prevent from cardiovascular dysfunctions in Northeastern Black Sea region of Turkey. This study investigated this folkloric information in order to explain the claimed healing effects as well as to evaluate possible risks. Methods Total phenolic, flavonoid and proanthocyanidin contents and antioxidant capacity of the methanolic fruit extract were evaluated through several in vitro assays. The cytotoxic and genotoxic effects of B. crataegina fruit extract were also assessed in both cervical cancer cell line (HeLa) and human peripheral blood lymphocytes. Results The extract showed protective effects against ferric-induced oxidative stress and had a relatively good antioxidant activity. It also ameliorated the H2O2 mediated DNA damage in lymphocytes, suggesting the protective effect against oxidative DNA damage. Conclusion The methanolic extract of B. crataegina fruits may be a potential antioxidant nutrient and also may exert a protective role against lipid peroxidation as well as oxidative DNA damage.

The aim of this study was to assess toxic metal (Cd, Pb and Al) contamination and levels of three essential trace elements (Mn, Cr and Co) in 63 infant formulas. In addition, the levels of these metals in the study samples were compared with the acceptable limits of toxic heavy metals and the recommended daily allowances (RDAs) of essential trace elements. According to our results, the toxic metal levels measured in the formulas were within the acceptable limits, with the exception of Al levels in 8 of the 63 samples. In 16 samples, Mn levels exceeded 600 μg/day, and the Cr content in 7 samples was higher than 5.5 μg/day, these amounts being the adequate intake levels for infants. Cobalt levels in 10 formulas were higher than the RDA. In view of these findings, which indicate that metal levels in infant formulas are generally much higher than those found in breast milk, breast milk should be preferred for infant feeding. Moreover, since infants are potentially more susceptible to metals, infant foods should be monitored regularly and checked for contamination by toxic metals as well as for levels of essential trace elements.

Biomimetic three-layered monolithic scaffold (TLS) intended for treatment of osteochondral defects was fabricated by using freeze drying method. The multilayered material was prepared with chitosan (C) and alginate (A) polyelectrolyte complex (CA/PEC) as a cartilaginous layer, a combination of CA/PEC (60 wt%) and beta-tricalcium phosphate (beta-TCP) (40 wt%) as an intermediate layer and a combination of CA/PEC (30 wt%) and beta-TCP (70 wt%) as a subchondral layer in order to mimic the inherent gradient structure of healthy osteochondral tissue. Characterization of the scaffolds was performed using Fourier transform infrared (FT-IR) spectroscopy analysis, swelling and scanning electron microscopy (SEM) tests. In vitro cytotoxicity assay with L929 cells and EpiDerm skin irritation test (SIT) using the EpiDerm reconstructed human epidermal (RHE) model were performed to analyze biocompatibility of the scaffolds. Characterization results showed that there were strong ionic interactions among chitosan, alginate and beta-TCP and the layers showed interconnected porous structure with different swelling ratios. The relative cell viability and SIT results were greater than 70% indicating that the scaffolds are considered nontoxic according to the International Organization for Standardization (ISO) standard. All results taken together, biomimetic TLS can be considered to be suitable for osteochondral applications. (C) 2015 Elsevier B.V. All rights reserved. Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [50792] We sincerely thank Zehra Yilmaz and Ece Gurdal, Yeditepe University, Turkey. This work was supported by Scientific Research Projects Coordination Unit of Istanbul University. Project number: 50792.

Cosmetics are one of the most common reasons for hospital referrals with allergic contact dermatitis. Because of the increased use of cosmetics within the population and an increase in allergy cases, monitoring of heavy metals, especially allergen metals, is crucial. The aim of this study was to investigate the concentration of allergen metals, nickel (Ni), cobalt (Co), and chromium (Cr), in the most commonly used cosmetic products including mascara, eyeliner, eye shadow, lipstick, and nail polish. In addition, for safety assessment of cosmetic products, margin of safety of the metals was evaluated. Forty-eight makeup products were purchased randomly from local markets and large cosmetic stores in Istanbul, Turkey, and an atomic absorption spectrometer was used for metal content determination. Risk assessment of the investigated cosmetic products was performed by calculating the systemic exposure dosage (SED) using Scientific Committee on Consumer Safety guideline. According to the results of this investigation in all the samples tested, at least two of the allergen metals, Ni and/or Co and/or Cr were detected. Moreover, 97% of the Ni-detected products, 96% of Cr- and 54% of Co-detected products, contained over 1 µg/g of this metals, which is the suggested ultimate target value for sensitive population and thereby can be considered as the possible allergen. On the basis of the results of this study, SED of the metals was negligible; however, contact dermatitis caused by cosmetics is most probably due to the allergen metal content of the products. In conclusion, to assess the safety of the finished products, postmarketing vigilance and routine monitoring of allergen metals are very important to protect public health. © 2015 Society of Cosmetic Chemists. All Rights Reserved.

… European Soc Toxicol

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a–d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively.

This study evaluated the content of cadmium (Cd), lead (Pb), and nickel (Ni) in 105 hair care products commercially available in Turkey. Cd, Pb, and Ni were detected in 40%, 21.91%, and 94.29% of the samples, respectively. Maximum Cd concentrations were detected in two shampoo samples, and the highest Pb level was found in a hair conditioner, all of them were herbal-based formulations. The highest mean levels of Ni were detected in hairstyling agents. The overall results were lower than the Canadian and German regulatory limits; however, according to the European Council Directive and Turkish Cosmetic Legislation, Cd, Pb, and Ni are listed as the substances that are prohibited in any amounts in cosmetics. Moreover, Ni content of 17.14% of the samples was above the limit of allergic contact dermatitis. It is known that these toxic metals tend to accumulate in body and prolonged use of them may potentially pose threat to human health. Thus, regular market monitoring and safer limits should be seriously considered especially for susceptible groups of the population like the pediatric group.

Son yillarda yurutulen bilimsel arastirmalar bitki caylarinin ve balin tasidiklari antioksidan etkili bilesenlerin bircok akut ve kronik hastaliklarin gelisme riskini azaltmaya yardimci olabilecegini gostermektedir. Ancak bitki caylarinin icerisine tatlandirici olarak bal ilave edilmesi ile antioksidan kapasitede ne gibi bir degisim olabilecegi konusu aydinliga kavusmamistir. Bu calismanin amaci, Turkiye’de satilan 9 farkli karisik veya saf bitki cay orneginin total antioksidan kapasitesinin hem tek baslarina hem de cam bali veya cicek bali ilavesinden sonra TOAK degerlerindeki olasi degisimin tespit edilmesidir. Bir fincana esdeger 100 ml caydaki en yuksek TOAK degeri melisa, siyah cay ve beyaz cayda gorulmustur. Bunlari sirasiyla yesil cay > adacayi > ekinezya > papatya > zencefil > ihlamur takip etmistir. Bitki caylarinin antioksidan etkisinin hem cam hem de cicek bali ilavesi ile paralel olarak arttigi, 7 g bal ilavesinin 3 g bala gore daha yuksek etkinlik gosterdigi gozlemlenmistir. Bazi bitki caylarinda (melisa, adacayi, ihlamur, papatya, limonlu zencefil) cam bali ilavesinin cicek balina oranla antioksidan etkinin daha fazla yukseldigi gorulurken, bazilarinda (ekinezya) cicek bali ilavesinin daha etkili oldugu tespit edilmistir. Sonuc olarak, calismamizda bitki caylarina bal ilavesinin antioksidan aktiviteyi onemli olcude artirdigi ve gunde en az 1 defa balli cay icmenin vucudu serbest radikallere karsi koruyucu etki gosterebilecegi ve ozellikle oksidatif strese bagli gelisen hastaliklarda destekleyici tedavi olarak kullanilabilecegi dusunulmektedir. Ancak bu kombinasyonunun koruyucu mekanizmasinin anlasilmasi icin ileri/ek calismalar gerekmektedir

Physiologically, zinc is an essential element that has many important functions such as maintenance of immunity, cell integrity, signalling, cellular respiration, and neuromodulation. Besides zinc, folate also plays a crucial role in basic cellular reactions. Exposure to some xenobiotics may lead to folate deficiency. The aim of this study was to evaluate the effect of zinc fume on erythrocyte folate levels. For this purpose, erythrocyte folate levels and serum zinc concentrations were evaluated in 63 galvanization workers, who were exposed to zinc fume during the galvanization procedure, and 23 office personnel as a control group. Erythrocyte folate levels were found to be decreased, while blood zinc levels were increased in workers compared to the controls (both, pR s=–0.335; p

The potential effects of globularifolin, an acylated iridoid glucoside, on cell survival, inflammation markers and free radicals scavenging were investigated. Viability assay on human myelomomonocytic cell line THP-1 and human peripheral blood mononuclear cells (PBMC) using the Cell-Titer Blue assay proved that globularifolin had no toxic effect at the tested concentrations. Conversely, it is proportional to the dose globularifolin increased growth of THP-1 cells (p

Due to their small size, nanotechnology based materials have unique characteristics such as magnetic, optical, thermal, mechanical, electrical, electron configuration density when compared with macromolecules. Nanomaterials are generally at the 1–100 nm scale and have a vast range of applications such as in medicine, electronics and energy production. Cosmetics, sunscreens, coatings, batteries, fuel additives, paints, pigments, tires and cement are the examples of consumer products that based on nanotechnology. Nanomaterials may also used for special medical purposes such as to produce novel drug delivery systems, to enhance the performance of medical devices, or to produce diagnostic-imaging materials [1].

Neopterin production provides information about the extent of cellular immune activation. Measurement of neopterin levels may also provide predictive and prognostic information in patients with malignant thyroid diseases. In the present study, neopterin levels were investigated in patients with thyroid disorders (no.=68). Twenty-four patients had papillary thyroid cancers and the rest of them benign thyroid disorders. Results were compared with a healthy control group (no.=30). It was observed that there was a significant difference in neopterin levels between the control group and the thyroid disorders group (p

Cadmium (Cd) is a heavy metal most commonly responsible for a number of pathologies, such as end-stage renal failure, early onset of diabetic renal complications, osteoporosis, and increased cancer risk. The aim of this study was to investigate Cd levels in tobacco, the main route exposure, and their ash of different cigarette samples marketed in Turkey and to evaluate the inhaled amounts of Cd exposure. The level of Cd in tobacco and their ash of 20 different brands of cigarettes were determined by Graphite Furnace Atomic Absorption Spectrometry. Regarding to the measurements, Cd levels in tobacco were found between 503-2742 ng/cigarette. Considering the Cd amounts measured in ash of tobacco, 1.29% - 14.3% of Cd stayed in ash without combustion, so it can be figured out that 85.7% - 98.71% of Cd spreads into the air and inhaled by the smokers. As a result, this study proved us much of Cd levels in tobacco were released into the air and lungs during smoking. For this reason smokers and passive smokers exposed to Cd in excessive amounts during their smoking habits.

Pteridines are natural heterocyclic compounds and they are generally divided into two main groups which are denominated as conjugated and unconjugated pteridines. Conjugated pteridines are the folate derivatives containing p-aminobenzoate and glutamate. Folate is a normal component of the cell. Folate derivatives play a crucial role in important biochemical pathways such as purine and pyrimidine biosynthesis, conversion of serine to glycine, histidine catabolism, methionine synthesis and detoxification reactions of certain xenobiotics, in which single carbon transfer is required. Folate deficiency has been proven to play a role in the pathogenesis of certain diseases. Additionally, exposure to some xenobiotics and prolonged use of some drugs may lead to folate deficiency. Serum, plasma and especially erythrocyte folate concentrations are generally used as biomarkers of folate pool. Therefore the present study was undertaken to establish an easy applicable, economic, accurate, sensitive, specific and reproducible microbiological method by using L. rhamnosus in our laboratory. Following the establishment of the method its application was carried out in blood samples of 46 volunteers. Mean value of folate levels in erythrocyte were found 359.7 ± 133.3 ng/ml, while mean plasma folate levels were determined 27.3 ± 12.4 ng/ml. In erythrocyte, the average recovery was 103.0 ± 17.7% (mean ±SD), in plasma the average recovery was 101.0 ± 1.7% (mean ±SD) for folinic acid concentrations at 10, 25 and 50 ng/ml. The CVs were 15.1 ± 5.6% (mean ± SD) for within-run and 7.2 ± 3.9% (mean ± SD) for between-run precisions. In the present study, a modified microbiological method for folate analysis which can be applied to biological material, has been established.