Hande Sipahi

Neopterin as a prognostic biomarker in intensive care unit patients

PURPOSEnThe present study was undertaken to evaluate urinary neopterin in intensive care unit patients.nnnMATERIALS AND METHODSnUrinary 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.nnnRESULTSnNeopterin 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.nnnCONCLUSIONnThis study showed that monitoring of urinary neopterin profile can be used in intensive care units to show the degree and prognosis of the disease.

Biocompatibility of biomimetic multilayered alginate–chitosan/β-TCP scaffold for osteochondral tissue

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 β-tricalcium phosphate (β-TCP) (40 wt%) as an intermediate layer and a combination of CA/PEC (30 wt%) and β-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 β-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.

Effects of developmental exposure to silver in ionic and nanoparticle form: A study in rats

BackgroundEvaluations 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 20xa0mg/kg/day) and ionic Ag (AgNO3, 20xa0mg Ag/kg/day) were investigated in rats.MethodsAnimals 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.ResultsNo 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.ConclusionThe 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 registrationNot applicable.Graphical abstractDevelopmental Toxicity of Ag-NPs.

Neopterin, Catalase and Superoxide Dismutase in Females with Benign and Malignant Breast Tumors

Abstract The aim of the present study was to evaluate the relationship between the levels of neopterin among patients with benign and malignant breast disease and the relation with the stage of the malignant process. In this study, neopterin concentrations and enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were determined in malign (n=30) and benign breast tumor patients (n=30) by high performance liquid chromatographic and spectrophotometric methods, respectively. Results were compared with a healthy control group (n=20). The correlations between neopterin, CAT and SOD were also evaluated in controls and patients. Urinary neopterin level of the control group was (mean value ± S.D.) 128.6 ± 64.6 μmol/mol creatinine. Neopterin concentrations in patients with breast malignancy were 153.6 ± 71.2 μmol/mol creatinine and 107.8 ± 32.1 μmol/mol creatinine in benign disorders patients. The mean neopterin level in the benign group was found to be statistically different from the malign tumor group (p = 0.039). SOD and CAT activities in controls were found as 3.57 ± 0.84 U/mg protein and 2.19 ± 0.20 U/mg protein, respectively. In patients with malignancy, the SOD activity was 3.84 ± 0.73 U/mg protein while CAT activity was 1.03 ± 0.13 U/mg protein. Patients with benign breast disorders, SOD activity was 4.09 ± 1.00 U/mg protein and CAT activity was 1.02 ± 0.18 U/mg protein. Whereas SOD activity did not differ between the groups of patients and controls, the mean catalase level in the control group was higher than in the benign and malign tumor groups (both p <0.001). Urinary neopterin concentration seems to be an important and useful biomarker in diagnosis of breast tumors in clinical practice.

Is neopterin level a predictive and differential biomarker in patients with thyroid disorders

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<0.05). The mean neopterin levels in malignant and benign patients were also significantly different (p<0.05). Monitoring of urinary neopterin profile may be used in early diagnosis of papillary thyroid cancer. Neopterin seems to be a differential biomarker for malignant and benign thyroid disorders.

Nanoparticles Toxicity and Their Routes of Exposures

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].

Energy Drink Induced Lipid Peroxidation and Oxidative Damage in Rat Liver and Brain When Used Alone or Combined with Alcohol

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.

Effects of globularifolin on cell survival, nuclear factor-κB activity, neopterin production, tryptophan breakdown and free radicals in vitro.

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 <0.01). On human PBMC, globularifolin at 6.25 and 12.5 μM concentrations showed a stimulatory effect, while at 12.5-200 μM it suppressed response of PBMC to stimulation with phytohemagglutinin (PHA). Globularifolin (50-200 μM) enhanced neopterin formation dose-dependently, whereas tryptophan breakdown was not influenced. At 50-200 μM in unstimulated PBMC in THP-1 cells, globularifolin induced a significant expression of nuclear factor-κB (NF-κB) as was quantified by Quanti-Blue assay. By contrast, in lipopolysaccharide (LPS)-stimulated cells, the higher concentrations of globularifolin suppressed NF-κB expression dose-dependently and a significant decrease was observed at 200 μM concentration. A positive correlation was found between increased neopterin and NF-κB activity (p <0.01). Similarly, a positive correlation was observed between neopterin levels in mitogen-induced cells and NF-κB activity in LPS-stimulated cells after treatment with globularifolin (p=0.001). The free radical scavenging capacity of globularifolin evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay showed relative ORAC values of 0.36±0.05 μmol Trolox equivalent/μmol. All together, results show that natural antioxidant globularifolin might represent a potential immunomodulatory as well as proliferative agent, which deserves further in vitro and in vivo studies.

The cysteine releasing pattern of some antioxidant thiazolidine-4-carboxylic acids.

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.

Urinary Biopterin Levels and Blood Dihydropteridine Reductase Activities in Patients with Thyroid and Breast Disorders

Abstract Biopterin as a stable metabolite is produced by oxidation of 5,6,7,8-tetrahydrobiopterin (BH4). It is known that many diseases may cause changes in BH4 concentration and/or dihydropteridine reductase (DHPR) enzyme activity. There is only a limited number of studies correlating DHPR activity in malignancies. The main goal of the present study was to evaluate alterations in the DHPR activity and biopterin levels in patients with breast and thyroid cancers. The breast cancer patients (n=24) were compared to patients with benign breast diseases (n=19) and controls (n=30). In addition; the patients with thyroid cancer (n=17) were compared to patients with benign thyroid diseases (n=42) and the control group. We did not observe any significant difference between the benign disorders and the malignancies. Biopterin concentrations in patients with benign and malign thyroid and breast diseases were lower than the controls (all p <0.05). DHPR activities in thyroid diseases were significantly higher than the controls while insignificant decreases in DHPR activities in breast patients were detected. Our results suggested significant alterations in unconjugated pteridine pathway in thyroid and breast disorders.