Serap Annette Akgür

Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis.

Although doxorubicin (DOX) is a commonly used chemotherapeutic agent its clinical use is restricted due to its organ toxicities. The present investigation relates to reducing DOX induced side effects to the liver, kidney and ileum by usage of the antioxidant, anti-inflammatory agent, resveratrol (RES) and to investigate the role of nitric oxide synthase (NOS) in the process. Wistar rats were divided into four groups: control (saline i.p); DOX (20 mg/kg i.p), RES (20 mg/kg i.p) and DOX (20mg/kg i.p)+RES (20 mg/kg i.p). Immunohistochemical activity of both iNOS and eNOS were evaluated after DOX treatment and ultrastructural changes such as cellular damage and mitochondrial degeneration were evaluated. Degenerative ultrastructural changes were demonstrated especially in the DOX treated group. Variations in biochemical marker levels of oxidative stress on ischemia in tissues were not observed. Our data indicate that RES may prevent cellular damage in the early phase of DOX induced toxicity. RES could be used with its beneficial effects during early cellular damage in organ toxicity after DOX treatment in cancer patients.

Human serum paraoxonase (PON1) activity in acute organophosphorous insecticide poisoning.

Human serum paraoxonase (PON1) and perhaps other mammalian paraoxonases catalyzes the hydrolysis of certain organophosphorus (OP) insecticides and nerve gases and so may alter significantly an individuals susceptibility to the toxicity of these chemicals. Serum PON1 exhibits a substrate dependent polymorphism and this polymorphism shows great interethnic variability. This study focused on the investigation of PON1, arylesterase and cholinesterase activities in 28 acute OP insecticide poisoning cases. Insecticide analysis were performed by GC-NPD and activities of enzymes were measured by using spectrophotometer. The activity levels for salt stimulated PON1, basal PON1 and arylesterase were found as 78.83 (35.39-186.13), 39.97 (2.49-80.43) micromol/min/l and 126.26 (36.34-288.24) mmol/min/l respectively. On the other hand the activity levels for butyrylcholinesterase (BTC) and acetylcholinesterase (AchE) were found as 797.23 (106.3-3823)U/l and 4.65 (0.21-30.29)U/ml. There was a correlation between percent stimulation of PON1 and BTC activities (r=0.446, P<0.05), but this correlation was lower than in cases who exposed to OP insecticides chronically. As a conclusion, in chronic and acute OP exposure, both PON1 level and phenotype must be taken into consideration.

Paraoxonase and acetylcholinesterase activities in humans exposed to organophosphorous compounds.

Different kinds of organophosphorous compounds (OP) are used as pesticides in Turkish agriculture. Suicidal, accidental, or occupational exposure may occur in developing countries. OP inhibit acetylcholinesterase (AChE) activities; on the other hand, serum paraoxonase (PON1) hydrolyzes the toxic metabolites of a variety of OP. In recent years, some studies have shown that PON1 activity is an important marker in individuals who are exposed to OP. Both serum cholinesterase and PON1 activities were measured spectrophotometrically from 18 male agricultural workers who were chronically exposed to azinphos methyl, chlorpyriphos, or malathion and other pesticides during cereal spraying, transportation, and storage. The individuals were classified according to PON1 phenotypes using the antimode 60% stimulation method to determine the dividing point between non-salt-stimulated, A type (homozygotes for the low-activity allele), and salt-stimulated AB (heterozygotes) and B types (homozygotes for the high-activity allele). A positive correlation was found between AChE activities and percent of PON1 stimulation. The individuals with phenotype A had the lowest enzyme activities. This study suggests that individuals with phenotype A might be more sensitive to OP-induced toxicity.

Rapid Communication: Postmortem Distribution of Organophosphate Insecticides in Human Autopsy Tissues Following Suicide

Organophosphate insecticides (OP) are used widely in Turkey and are the most common agent employed for suicidal poisoning. At present there are limited data available on the distribution of OP in humans, and the aim of the study was to report insecticide concentrations in human autopsy tissues. With the use of gas chromatography-nitrogen phosphorous detector, the levels of fat, liver, and blood OP were determined from 32 suicide victims. In all cases OP were present and usually more than one OP was found. The concentration of OP was highest in fat and least in blood. Even 20 d postmortem OP could be detected in human autopsy tissues, but the correlation to fat content and mortality needs to be addressed.

Prevalence of Alcohol in Blood Samples from Traffic Accident Cases in Turkey

Alcohol is one of the main causes of traffic accidents worldwide. With a population of 70 million, 12 million vehicles, and 18 million drivers (16% women), Turkey is one of the European countries that has a high incidence of road traffic accidents.In accordance with Turkish laws, subjects were considered to be positive when alcohol blood concentration exceeded 50 mg/100 mL. The objective of the present study was to obtain reliable and comparable data about alcohol use in traffic cases in Turkey. All cases are admitted to the emergency department at Ege University Medical Faculty. The cases from police officers are described as traffic control cases. Alcohol was detected in the blood of about 54.4% of the traffic-related cases during October 2005 to March 2007. It has been observed that, in 17.4% of the traffic accident cases, the blood alcohol level was 50 mg/dL or less, which is the legal limit in Turkey for car drivers. Alcohol prevalence was 57.2% in male cases and 43.6% in female cases. In alcohol-positive cases; the ratios for males were 1.73 times more frequent in traffic-related cases. Prevalence data will help traffic safety professionals to adequately allocate resources and plan future efforts in reducing drinking-and-driving behavior and thereby reduce traffic accidents.

Platelet aggregation and atrial natriuretic peptide

1. Isolated human platelets were used to investigate the effect of atrial natriuretic peptide (ANP) on in vitro platelet aggregation induced by epinephrine, ADP, collagen and 5-hydroxytryptamine. As a direct stimulant of particulate guanylate cyclase, ANP is known to have no direct effect on platelets which contain soluble guanylate cyclase. 2. In our experiments ANP inhibited epinephrine- and partially ADP-induced aggregation in vitro and this effect was suggested to be the result of an interaction of the peptide with adenylate cyclase in platelets. However, the concentrations required to produce this effect were higher than those expected to be found in the circulation both physiologically and pathologically. 3. We therefore conclude that though the peptide may inhibit-aggregation via adenylate cyclase activation, it is unlikely that ANP may play a direct role in preventing platelets aggregating.

Gas chromatographic analysis of alcohols in blood with a chemometric approach

The objective of the present study is to examine the main and interactive effects of different factors related with headspace-solid phase extraction (HS-SPME) and gas chromatography (GC) conditions for the simultaneous determination of alcohols (ethanol, methanol, isopropanol, n-propanol) and acetone in blood samples. In order to evaluate the simultaneous effects of the significant variables, a chemometric approach was utilized to reveal the important parameters. The factors affecting the headspace extraction of alcohols on the SPME fiber was first deduced in a screening study by applying a Plackett–Burman design. According to the screening results, the factors that possess a positive effect on peak areas are sample concentration, inlet temperature, flow rate for the carrier gas and volume of the solution. Based on the results of the screening study, to continue optimization, six insignificant values were fixed at the appropriate amounts (oven temperature: 50 °C; detector temperature: 250 °C; H2 gas flow rate: 35 mL min−1; split flow rate: 30 mL min−1; equilibrium temperature: 55 °C, extraction time: 4 min). Subsequently, a central composite design (CCD) was constructed for optimization and response surface methodology (RSM) was used to interpret the effect of each pair of independent variables on the response. The optimized method for alcohol and acetone analysis via HS-SPME-GC was validated through spike recovery tests.

Adult respiratory distress syndrome in human organophosphate poisoning cases

Adult respiratory distress syndrome (ARDS) is a clinical syndrome which occurs due to various direct or indirect noxious agents and pyhsical mechanisms. One of the etiological factors is ingested chemicals (e.g. paraquat, ethylene glycol). The organophosphorous (OP) insecticides are the most toxic and frequently encountered chemicals that produce poisoning in humans. Studies were undertaken to investigate whether OP insecticides may produce ARDS. Fifteen autopsy cases due to suicidal OP insecticide poisoning were investigated. Toxicological analyses were performed with a gas chromatography-nitrogen phosphorous detector (GC-NPD). Methamidophos, dimefox and dichlorvos were the detected OP. Lungs were examined macroscopically. Two cases showed features compatible with ARDS in which the only cause of death was OP poisoning. Due to the severity of ARDS it is important to assess insecticidal exposure in an attempt to enhance survival patterns following OP poisoning in patients in order to initiate therapy.

Comparison of Extraction Methods for 11-Nor-Delta-9-Tetrahydrocannabinol-9-Carboxylic Acid (Thc-Cooh) in Urine Samples Prior to GC-MS Analysis

Amac: Gunumuzde kotuye kullanilan yasadisi maddeler arasinda en yaygin kullanilan madde esrardir. Esrarin saptanmasina yonelik yapilan calismalarda, idrarda ana metaboliti olan THC-COOH’un kat-faz (SPE) ve sivi-faz (ELE) ekstraksiyon teknikleri ile analizi yer almaktadir. Bu calismanin amaci, sentetik idrar orneklerinde THC-COOH analizi icin GC-MS ile tayini oncesinde SPE ve LLE metodlarini kullanarak ornekleri analize hazirlamak ve bu yontemlerin ornek hazirlamadaki verimleri ve etkinlikleri karsilastirmaktir. Ayni zamanda bu yontemlerin tekrarlanabilirlik, secimlilik, dogruluk, kesinlik ve dogrusallik gibi validasyon parametreleri inceleyerek yontem gecerliligini degerlendirmektir.Gerec ve Yontem: Ana standart olarak (±)-ll-nor-9-carboxy-A9-THC ve ic standart olarak (±)-ll-nor-9-carboxy-A9-THC-D3 kullanilmistir. LLE icin Toxi-tube B, SPE icin Clean Screen THC kartuslari kullanilmistir. Turevlendirme icin BSTFA+%1 TMCS kullanilmistir. Analizler Thermo Finnigan Trace Gaz Kromatografisi-Kutle Spektrometrisi (GC-MS) cihazi ile yapilmistir. SPE ve LLE metodlarinin karsilastrilmasi Minitabll istatistik paket programi ile yapilmistir.Bulgular: Calismamizda en dusuk tayin siniri olarak (LOD) 2 pg/L elde edilmistir. Elde edilen sonuclarda geri kazanim degerleri %90’nin uzerinde ve %RSD degerleri %10’nun altinda bulunmustur. 25-500 pg/L arasindaki konsantrasyonlarda kantitatif tayin yapilabilmesi icin gerekli olan dogrusalligin var oldugu tespit edilmistir. Uygulanan Anderson-Darling testi ile LLE ve SPE sonuclarinin normal bir dagilima uymadigi goruldugunden non-parametrik test olan Wilcoxon signed-rank testi uygulanmistir.Sonuc: Calismamizda bulunan dogrusallik, tekrarlanabilirlik ve geri kazanilabilirlik degerleri, biyoanalitik validasyon kriterleri dogrultusunda kabul edilebilir duzeyde bulunmustur. Elde edilen istatiksel sonuclara gore, LLE ve SPE metodlari arasinda istatistiksel olarak anlamli bir fark bulunmustur (p<0.005). Yapilan calisma ile analiz oncesinde ornekhazirlamabasamaginin onemi gosterilmistir.Anahtar Kelimeler: TCH_COOH, Sivi-Sivi Ekstraksiyon, Kati Faz Ekstraksiyon, Idrar, Gaz Kromatografi Kutle Spektrometri.