Salih Cengiz

Comparison of total plasma lysophosphatidic acid and serum CA-125 as a tumor marker in the diagnosis and follow-up of patients with epithelial ovarian cancer

OBJECTIVE To evaluate the role of lysophosphatidic acid (LPA) as a tumor marker in diagnosis and follow-up of patients with epithelial ovarian cancer. METHODS Eighty-seven epithelial ovarian cancer patients, 74 benign ovarian tumor patients, and 50 healthy women were enrolled in the study. Twenty-nine of 87 epithelial ovarian cancer patients were followed up for 6 cycles of paclitaxel-carboplatin chemotherapy. CA-125 and total plasma LPA levels were measured preoperatively and before each chemotherapy cycle. RESULTS Preoperative total plasma LPA and serum CA-125 levels were significantly higher in patients with epithelial ovarian cancer compared to patients with benign ovarian tumors and healthy women. Cut-off value for LPA was determined as 1.3 µmol/L and sensitivity, specificity, positive predictive value and negative predictive value were 95%, 92%, 95% and 92%, respectively. Mean total plasma LPA level of 29 patients who received chemotherapy was 7.21±6.63 µmol/L preoperatively and 6.84±6.34 µmol/L, 6.34±5.92 µmol/L, 6.14±5.79 µmol/L, 5.86±5.68 µmol/L, 5.23±5.11 µmol/L and 5.21±5.32 µmol/L in measurements held just before the 1st, 2nd, 3rd, 4th, 5th and 6th chemotherapy cycles, respectively (ANOVA, p=0.832). Total plasma LPA levels decreased slightly with chemotherapy administration and there was a weak negative correlation (Spearman, r(s)=-0.151, p=0.034), compared to a significant negative correlation in CA-125 (Spearman, r(s)=-0.596, p<0.001). CONCLUSION LPA is a better biomarker for diagnosis of epithelial ovarian cancer compared to CA-125. However, measurement of total plasma LPA levels during chemotherapy administration have no superiority to the serum CA-125 levels.

N-acetyl-β-glucosaminidase and β-galactosidase activity in children receiving antiepileptic drugs

To evaluate renal tubular function in children receiving antiepileptic drugs the urinary activity of two lysosomal enzymes, N-acetyl-β-glucosaminidase and β-galactosidase, were measured. The enzyme levels were determined before the administration of antiepileptic drugs and 8 months after. Fourteen epileptic children received valproate, and 17 received carbamazepine. The urinary activity of these enzymes in 25 healthy control patients also was examined. Increased N-acetyl-β-glucosaminidase activity was found in 50% of patients taking valproate and in 17.6% of patients taking carbamazepine. Increased β-galactosidase activity was found in 28.5% of patients taking valproate and 11.7% of patients taking carbamazepine compared with the results before treatment. On the basis of these results, it is suggested that patients taking antiepileptic drugs, especially valproate, may demonstrate minor signs of tubular dysfunction. In those patients who use these drugs at increased dosage levels or for long periods, the possibility of tubular dysfunction may be increased, and these dysfunctions may manifest in clinical symptoms.

Age-related changes in GM1, GD1a, GT1b components of gangliosides in Wistar albino rats.

In this study, age‐related changes of GM1, GD1a, GT1b fractions of gangliosides were investigated in whole brain of male Wistar albino rats. Insignificant increases were detected in GM1 values from the third to the 24th month, whereas GD1a and GT1b concentrations of ganglioside in 24‐month‐old rats decreased significantly as compared to 6‐month‐old rats. Although there were no significant differences in the GD1a/GT1b ratio of any groups, GM1/GD1a and GM1/GT1b ratios were significantly increased as compared to 6‐month‐old rats. The increase in the ratios of gangliosides are not due to an increase of GM1 fractions; they result from a decrease of GD1a and GT1b fractions of gangliosides. In conclusion, the concentration of ganglioside decreased with ageing. Copyright

Quantitative lead determination in coating paint on children׳s outwear by LA-ICP-MS: A practical calibration strategy for solid samples

Lead is a hazardous compound that affects the central nervous system in people, particularly children, and may cause some reversible and irreversible diseases. Legal regulations try to prevent the exposure from products especially produced for children such as coating paints, jewelry, toys, bed linen, textile, etc. The aim of this study was to determine the lead levels of coating paints on children׳s outwear selling in district bazaar by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and to specify the percent of non-complying samples. Here we described the solid matrix calibration method and confirmed the results with the microwave-assisted acid digestion method. Both comparative methods were validated by analysis of the certified reference materials (NIST SRM-612 glass matrix, NIST SRM-2582 powdered paint and ERM-EC681k) and bias% for accuracy and RSD% for precision were calculated lower than 6.8% and 7.3%, respectively. The recovery ranges of laser ablation and microwave-assisted acid digestion method for Pb were found to be between 88.2-98.1% and 95.3-101.3%, respectively. The limits of detection values were determined as 0.162 mg kg(-1) for direct sampling in the ablation chamber and 0.002 ng mL(-1) for aqueous solutions. Correlation result of 16 samples (r=0.99) examined in both methods was satisfactory. In coating paint samples, 14.65% of 198 (n=29) did not comply with the 90 mg kg(-1) lead limit according to regulation. Validated quantitative laser ablation method may be preferred to quickly and reliably determine the Pb levels in other solid samples as well as coating paints.

Pro198Leu polymorphism in the oxidative stress gene, glutathione peroxidase-1, is associated with a gender-specific risk for panic disorder.

Abstract Objective. Panic disorder (PD) is an anxiety disorder characterized by sudden attacks of intense fear. Biochemical studies suggest that oxidative stress (OS) index is significantly higher in PD, and OS genes may participate in development of anxiety-like behavioral phenotypes. We aimed to investigate role of polymorphisms in OS gene, glutathione peroxidase-1 (GPX1), and DNA repair enzyme gene, 8-oxoguanine glycosylase-1 (OGG1), in PD patients. Methods. GPX1 Pro198Leu (rs1050450) and OGG1 Ser326Cys (rs1052133) polymorphisms of 127 patients with PD and 151 disease-free controls were analyzed with real-time polymerase chain reaction. Severity of PD symptoms was assessed by Panic and Agoraphobia Scale (PAS). Results. No significant relationship was found in genotype distributions of OGG1 Ser326Cys and GPX1 Pro198Leu polymorphisms between PD and control groups (p > 0.05). There was no significant relationship between OGG1 or GPX1 polymorphisms, and age of onset, agoraphobia, or PAS scores in PD group (p > 0.05). However, in GPX1 Pro198Leu polymorphism, C allele (Pro) was found to be more frequent in female subgroup of PD patients compared with that in males (p = 0.027). Conclusions. GPX1 Pro198Leu and OGG1 Ser326Cys polymorphisms were not associated with PD risk in Turkish patients. However, a gender-specific effect of GPX1 Pro198Leu C allele may be associated with PD development.

Rapid and simple analysis of trace levels of three explosives in soil by liquid chromatography—tandem mass spectrometry

The analysis of trace levels of explosives in post-blast debris is critical in homeland security, environmental analysis, and crime scene forensic investigations. A fast and a selective determination method with high recovery was developed for the common explosives 2,4,6-trinitrotoluene (TNT), 3,5-trinitro-1,3,5-triazacyclohexane (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in soil, using liquid chromatography—tandem mass spectrometry (LC—MS/MS). An easy and practical sample preparation method was developed using 4.00 mL acidified acetone with 0.25% HCl. After the easy evaporation of acetone extract, 10 min LC—MS/MS analysis provided a clear separation in column. Short duration of the whole procedure allows the use of this method in routine analysis. As a result of the analysis performed in spiked soils in 50.0, 100.0, and 250.0 ng g−1 concentrations, high recoveries such as 100.4 (±8.8)% for RDX, 96.9 (±10.5)% for HMX, and 97.6 (±13.9)% for TNT were obtained. Limit of detection (LOD)...

Simultaneous analysis method for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin in urine, using C18 poroshell column.

Date-rape drugs have the potential to be used in drug-facilitated sexual assault, organ theft and property theft. Since they are colorless, tasteless and odorless, victims can drink without noticing, when added to the beverages. These drugs must be detected in time, before they are cleared up from the biofluids. A simultaneous extraction and determination method in urine for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin (an anticonvulsant and antiepileptic drug) with LC-MS/MS was developed for the first time with analytically acceptable recoveries and validated. A 4 steps liquid-liquid extraction was applied, using only 1.000mL urine. A new age commercial C18 poroshell column with high column efficiency was used for LC-MS/MS analysis with a fast isocratic elution as 5.5min. A new MS transition were introduced for barbital. 222.7>179.8 with the effect of acetonitrile. Recoveries (%) were between 80.98-99.27 for all analytes, except for GHB which was 71.46. LOD and LOQ values were found in the ranges of 0.59-49.50 and 9.20-80.80ngmL(-1) for all the analytes (except for GHB:3.44 and 6.00μgmL(-1)). HorRat values calculated (between 0.25-1.21), revealed that the inter-day and interanalist precisions (RSD%≤14.54%) acceptable. The simultaneous extraction and determination of these 8 analytes in urine is challenging because of the difficulty arising from the different chemical properties of some. Since the procedure can extract drugs from a wide range of polarity and pKa, it increases the window of detection. Group representatives from barbiturates, z-drugs, ketamine, phenytoin and polar acidic drugs (GHB) have been successfully analyzed in this study with low detection limits. The method is important from the point of determining the combined or single use of these drugs in crimes and finding out the reasons of deaths related to these drugs.

An HPTLC Method for the Determination of Oleandrin in Nerium Plant Extracts and Its Application to Forensic Toxicology

The study reported in this paper was aimed to develop an accurate, specific, and precise high-performance thin-layer chromatography (HPTLC) method for the determination of oleandrin in Nerium oleander (Linn.) extracts as well as biological samples of an intoxication case for the first time. Also, extraction, isolation, and purification methods of oleandrin from the sticky juice of Nerium plant leaves were presented. The retention factor (RF value) of oleandrin was found to be 0.24 ± 0.01. The linearity range was between 2 and 75 ng spot−1 (r = 0.9993), the limit of detection was 2.2 ng spot−1, the limit of quantification was 6.7 ng spot−1, and the recovery in urine and serum was found 89% and 83%, respectively. Isolated compounds from both plant material and biological samples were also applied to mass spectrometry (MS). The reported HPTLC method was sensitive, rapid, and suitable for the analysis of oleandrin and was applied to a non-fatal case of oleander poisoning. Oleandrin was detected in urine and serum samples of the intoxicated patient at concentrations of 3.2 and 8.4 ng mL−1, respectively. Peak purity of the isolated compound was checked by electrospray ionization-mass spectrometry (EI-MS) and introduced to HPTLC compound library. To the best of our knowledge, this study is the first published HPTLC method and also presents the evaluation of both clinical and toxicological aspect of an oleander posioning case. It can be successfully applied for the determination of oleandrin in clinical and forensic researches as well as in phytochemical investigations.

Development and validation of a densitometric-high-performance thin-layer chromatographic method for quantitative analysis of amitriptyline in gastric lavage

Drug overdose is the most common method in suicide attempts. Amitriptyline (AMT), a tricyclic antidepressant agent, known for potentially lethal cardiovascular and neurological effects, is used especially by intoxicated patients. The aim of this study was to validate a method for the determination of AMT in gastric lavage samples by high-performance thin-layer chromatography (HPTLC). Artificial gastric lavage was used to obtain a better extraction procedure for AMT. The method was also applied to patients who attempted suicide with AMT. A validated, accurate, and rapid HPTLC-based method was developed for quantitation of AMT in gastric content of intoxicated patients. Extraction was done from 3 mL gastric lavage sample by liquid-liquid extraction procedure with ethyl acetate-n-heptane (1:1, w / w) in alkaline pH with 10.8. The mobile phase was an isocratic solvent system consisting of methanol-ammonia (25%) (98.5:1.5, v / v). 3,4-Methylenedioxy-Nmethamphetamine (MDMA) was used as internal standard (IS). Analytes were quantified by TLC Scanner operating under 209 nm. The retardation factors of AMT and MDMA were determined as 0.49 and 0.25, respectively. The analytical range was set as 10–250 ng spot−1 for AMT. Calibration was linear within the selected range in gastric lavage (r > 0.9995). Limit of detection and limit of quantification of AMT were found to be 5.1 and 17.3 ng spot−1, respectively. Recoveries of 25 ng spot−1 and 100 ng spot−1 concentrations were found 83.12% and 91.89%; bias% values were 10.91 and 3.19, respectively. The validated method was also applied on samples of five patients who attempted suicide by AMT, and concentrations in gastric lavage samples of 5 patients were found 7.1, 8.3, 9.9, 14.6, and 36.6 ng mL−1. This successfully validated method was applied to suicide cases, and it can be conveniently employed on both antemortem and postmortem cases suspected by amitriptyline.

A Fast Liquid Chromatography Tandem Mass Spectrometric Analysis of PETN (Pentaerythritol Tetranitrate), RDX (3,5-Trinitro-1,3,5-triazacyclohexane) and HMX (Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) in Soil, Utilizing a Simple Ultrasonic-Assisted Extraction with Minimum Solvent

Direct analyses of explosives in soil using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are very limited in the literature and require complex procedures or relatively high amount of solvent. A simple and rapid method was developed for the determination of pentaerythritol tetranitrate (PETN), 3,5-trinitro-1,3,5-triazacyclohexane (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), which are among the explosives used in terrorist attacks. A one-step extraction method for 1.00 g soil with 2.00 mL acetonitrile, and a 8-min LC-MS/MS method was developed. The detection limits for PETN, RDX and HMX were 5.2, 8.5 and 3.4 ng/g and quantitation limits were 10.0, 24.5, 6.0 ng/g. The intermediate precisions and Horwitz Ratios were between 4.10 - 13.26% and 0.24 - 0.98, in order. This method was applied to a model post-blast debris collected from an artificial explosion and real samples collected after a terrorist attack in Istanbul. The method is easy and fast and requires less solvent use than other methods.