Ahmet Basaran

Modulating effects of flavonoids on food mutagens in human blood and sperm samples in the Comet assay

The flavonoids silymarin, myricetin, quercetin, kaempferol, rutin, and kaempferol-3-rutinoside have been examined in combination with the food mutagens 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp) and 2-amino-3-methylimidazo-4,5-f)quinoline (IQ) in the Comet assay in human lymphocytes from donors A and B and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in human lymphocytes and sperm over a similar dose range in the absence of metabolic activation. Only quercetin and kaempferol were examined in blood with metabolic activation, but there was no difference in response to that obtained without activation. In the blood there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm this was also the case with silymarin and myricetin. With kaempferol there was no antigenotoxic effect and quercetin protected below baseline levels. Since the effects were observed in lymphocytes and sperm over a similar dose range, it would suggest that the Comet assay responses occur in somatic and germ cells in a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.

Flavonoids modulate Comet assay responses to food mutagens in human lymphocytes and sperm

The flavonoids, silymarin, myricetin, quercitin, kaempferol, rutin and kaempferol-3-rutinoside have been examined in combination with the food mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp-P-2) and 2-amino-3-methylimidazo-(4,5-f) quinoline (IQ), in the Comet assay in human lymphocytes from donor A and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in lymphocytes and sperm. The assays were performed in the absence of metabolic activation, since when quercetin and kaempferol were examined in blood with metabolic activation, there was little or no difference in response to that obtained in its absence. In the blood, there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm, with silymarin, myricetin and quercitin, antigenotoxic effects only were observed, but with kaempferol, in general, there were no protective effects. The food mutagen, 2-amino-1-methyl-6-phenylimadazo (4,5-b)pyridine (PhIP), was also examined in addition to Trp-P-2 and IQ in combination with silymarin and myricetin in donors A and C in human lymphocytes only. Similar exacerbation of effects were found at low doses of these flavonoids with antigenotoxic effects at high doses. This was confirmed in the Ames test. There were slightly different profiles in lymphocytes and sperm, but antigenotoxic effects were observed over a similar dose range. This would suggest that effects occur in somatic and germ cells on a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.

Combined vitamin C and E supplementation for the prevention of preeclampsia: a systematic review and meta-analysis.

Objective. To perform a systematic review and meta-analysis of the effectiveness of combined vitamin C and E (vitCE) supplementation for the prevention of preeclampsia. Data Sources. PubMED, Web of Science, and Cochrane Central Register of Controlled Trials from inception through June 2010, and bibliographies of review articles and eligible studies. Methods of Study Selection. Fifteen eligible studies that evaluated vitCE supplementation for the prevention of preeclampsia were identified. On the basis of prespecified inclusion and exclusion criteria, 9 were included in the meta-analysis. All were randomized controlled trials. The reporting and methodologic quality of the included studies was assessed with the CONSORT checklist and the Jadad scale. Tabulation, Integration, and Results. The 9 included studies had moderate-to-high CONSORT and Jadad scores. The incidence of preeclampsia was 9.7% (949 of 9833) in the vitCE group and 9.5% (946 of 9842) in the placebo group. A random effects model was used for pooling and no difference was found in the relative risk (RR) of preeclampsia between the vitCE and placebo groups (RR: 0.98; 95% confidence interval [CI]: 0.87–1.10). The incidence of gestational hypertension was 22.6% (1915 of 8491) in the vitCE group and 20.3% (1728 of 8500) in the placebo group (RR: 1.11, 95% CI: 1.05–1.17). The incidence of placental abruption was 0.58% (43 of 7379) in the vitCE group and 0.87% (64 of 7361) in the placebo group (RR: 0.67, 95% CI: 0.46–0.98). No significant differences were observed for other maternal and neonatal outcomes. Conclusion. Combined VitCE supplementation does not decrease the risk of preeclampsia and should not be offered to gravidas for the prevention of preeclampsia or other pregnancy induced hypertensive disorders. Furthermore, combined supplementation with vitCE increased the risk of GH but decreased the risk of placental abruption. However, these latter associations may not be causal, especially since they were the product of multiple statistical comparisons, and the 95% CI around the point estimates almost included one. Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to assess the causes of preeclampsia and related conditions; evaluate and interpret the evidence regarding the use of combined vitamins C and E in prevention of preeclampsia and related conditions; and interpret and understand the effects of the supplementation of vitamins C and E for the prevention of preeclampsia or other pregnancy induced hypertensive disorders. Target Audience: Obstetricians & Gynecologists, Family Physicians

A case of acromegaly in pregnancy: Concomitant transsphenoidal adenomectomy and cesarean section

The case of a 32-year-old woman at 29 weeks gestational age with acromegaly initially diagnosed in pregnancy is presented. During follow-up at 34 weeks of gestation, concomitant emergency cesarean section and transsphenoidal surgery were performed because of advancing vision loss. In tertiary centers, success in pregnancy can be made possible for a patient with acromegaly under the constant supervision of an obstetrician and neurosurgeon.

An oocyte pick-up procedure complicated with pseudoaneurysm of the internal iliac artery.

OBJECTIVE To describe a patient with a pseudoaneurysm of the internal iliac artery after oocyte retrieval, during an intracytoplasmic sperm injection (ICSI) and embryo transfer cycle. DESIGN Case report. SETTING Tertiary center for assisted reproductive technologies (ART). PATIENT(S) A 22-year-old woman with a duration of 6 years of primary infertility. INTERVENTION(S) The evaluation of the pseudoaneurysm with ultrasonography and angiography. The management of pregnancy complicated with pseudoaneurysm and viable treatment modalities. MAIN OUTCOME MEASURE(S) Healthy baby and treatment of pseudoaneurysm. RESULTS(S) A healthy female infant with a birth weight of 1,470 g was born by cesarean section at 32 weeks of gestation. The pseudoaneurysm of the left inferior pudental artery was completely embolized with 1 mL (50%) of N-butyl-2-cyanoacrylate. CONCLUSION(S) The pseudoaneurysm of the iliac vessels is an extremely rare complication of the oocyte retrieval procedure. With a multidisciplinary approach, optimal management should depend on the diameter and localization of the pseudoaneurysm, week of gestation, hemodynamic status of the mother and infant, and the available technologies.

Measurement of choroid thickness in pregnant women using enhanced depth imaging optical coherence tomography

PURPOSE To investigate choroidal thickness in healthy pregnant women during different trimesters using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS This prospective study included 90 healthy pregnant women in their first, second, or third trimester (groups 1, 2, and 3, respectively) and 30 non-pregnant healthy women (group 4). The age range for all groups was 18-40 years. Spectral domain optical coherence tomography scans were obtained to estimate the average choroidal thickness. Using EDI-OCT, we measured choroidal thickness manually from the outer border of the retinal pigment epithelium to the inner scleral border at the subfovea, 3 mm temporal, and 3 mm nasal to the fovea. Differences among groups were analyzed by one-way ANOVA. RESULTS We found a statistically significant difference between groups 2 and group 4 for subfoveal, temporal, and nasal mean choroidal thickness (p=0.007, p<0.001, p=0.026, respectively). The mean choroidal thickness for group 2 was 395 ± 80 μm, 338 ± 74 μm, and 233 ± 61 μm at the regions subfoveal, temporal, and nasal to the fovea, respectively. In comparison, the mean choroidal thickness for group 4 was 335 ± 86 μm, 274 ± 54 μm, and 200 ± 53 μm at the regions subfoveal, temporal, and nasal to the fovea, respectively. No statistically significant differences were found for choroidal thickness among groups 1-4 (p=0.214, p=0.177, p=0.094, respectively) and between groups 3-4 (p=0.105, p=0.261, p=0.695, respectively) for all measured points. CONCLUSION Our results suggest that choroidal thickening can occur at the regions subfoveal, temporal, and nasal to the fovea in the second trimester.

Does rosmarinic acid treatment have protective role against sepsis-induced oxidative damage in Wistar Albino rats?

Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated rats was significantly lower than that in the sepsis-induced rats. RA treatment also decreased the MDA levels and increased the GSH levels and SOD and GSH-Px activities in the livers and kidneys of the sepsis-induced rats. Plasma TNF-α level was found to be decreased in the RA-treated rats. It seems that RA might have a role in the attenuation of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing the antioxidant status and DNA repair capacity of the animals.

Use of in vitro assays to assess the potential cytotoxic, genotoxic and antigenotoxic effects of vanillic and cinnamic acid

Abstract Vanillic acid (VA) found in vanilla and cinnamic acid (CA) the precursor of flavonoids and found in cinnamon oil, are natural plant phenolic acids which are secondary aromatic plant products suggested to possess many physiological and pharmacological functions. In vitro and in vivo experiments have shown that phenolic acids exhibit powerful effects on biological responses by scavenging free radicals and eliciting antioxidant capacity. In the present study, we investigated the antioxidant capacity of VA and CA by the trolox equivalent antioxidant capacity (TEAC) assay, cytotoxicity by neutral red uptake (NRU) assay in Chinese Hamster Ovary (CHO) cells and also the genotoxic and antigenotoxic effects of these phenolic acids using the cytokinesis-blocked micronucleus (CBMN) and the alkaline comet assays in human peripheral blood lymphocytes. At all tested concentrations, VA (0.17–67.2 μg/ml) showed antioxidant activity but CA (0.15–59.2 μg/ml) did not show antioxidant activity against 2,2-azino-bis (3-ethylbenz-thiazoline-6-sulphonic acid) (ABTS). VA (0.84, 4.2, 8.4, 16.8, 84 and 168 μg/ml) and CA (0.74, 3.7, 7.4, 14.8, 74, 148 μg/ml) did not have cytotoxic and genotoxic effects alone at the studied concentrations as compared with the controls. Both VA and CA seem to decrease DNA damage induced by H2O2 in human lymphocytes.

Plasma total oxidant and antioxidant status after oral glucose tolerance and mixed meal tests in patients with polycystic ovary syndrome

PurposeInsulin resistance (IR) and increased oxidative stress (OS) are the characteristics of polycystic ovary syndrome (PCOS). In this study, we aimed to evaluate the effects of oral glucose tolerance (OGTT) and mixed meal tests (MMT) on plasma total oxidant (TOS) and total antioxidant status (TAS) in patients with PCOS and the relationship between these parameters and IR, calculated via homeostasis of model assessment-IR (HOMA-IR) and Matsuda’s insulin sensitivity index (ISI) derived from OGTT and MMT.MethodsTwenty-two patients with PCOS, and age- and body mass index (BMI)-matched 20 women as controls were enrolled into the study. Five-hour OGTT and MMT were performed on different days, and before and after these tests, plasma TOS and TAS levels were investigated. IR was calculated with HOMA-IR and Matsuda’s ISI.ResultsHOMA-IR levels were higher in patients with PCOS, compared to controls, while Matsuda’s ISI derived from OGTT and MMT was higher in controls. Plasma TOS levels before OGTT and MMT were higher in patients with PCOS than controls, while TAS levels were similar. After OGTT, plasma TOS levels became decreased at 5th hour, when compared to baseline values in PCOS group. Likewise, the same decrement was found in controls, but the decrement was not significant. After OGTT and MMT at 5th hour, no changes were observed in TAS levels, compared to baseline.ConclusionMatsuda’s ISIs derived from OGTT and MMT can be used instead of each other, and interestingly, we found a decrease in TOS levels after OGTT in patients with PCOS.

Chorionic villus sampling and the risk of preeclamspia: a systematic review and meta-analysis

ObjectiveTo perform systematic review and meta-analysis to evaluate the risk of preeclampsia after chorionic villus sampling (CVS).Data sourcesA systematic search of PubMED and Web of Science from inception through August 2010, and bibliographies of review articles and eligible studies were performed.Methods of study selectionSix studies reported the risk of preeclampsia after CVS. All of the identified studies were retrospective and included in analysis.Tabulation, integration, and resultsReporting quality of the identified studies according to quality assessment scale for methodology in retrospective clinical reporting was moderate. Pooling was performed in two strata for control: (1) patients without any invasive prenatal diagnostic procedure served as control group: no significant difference was found in the odds ratio (OR) of preeclampsia (OR 0.79, 95% CI 0.38–1.64), severe preeclampsia (OR 0.49, 95% CI 0.04–5.78), gestational hypertension (OR 0.76, 95% CI 0.46–1.26), all pregnancy-induced hypertensive disorders (OR 0.80, 95% CI 0.46–1.41) between CVS and control groups. (2) Patients with amniocentesis combined with patients without any invasive prenatal diagnostic procedure served as control group: no significant difference was found in the OR of preeclampsia (OR 0.76, 95% CI 0.37–1.53), severe preeclampsia (OR 0.83, 95% CI 0.14–4.85), all pregnancy-induced hypertensive disorders (OR 0.92, 95% CI 0.55–1.53) between CVS and combined control groups.ConclusionNone of the included studies were randomized prospective trials designed to investigate the effect of CVS on preeclampsia. Accordingly, this review is limited by the heterogeneity, small number and retrospective nature of the available studies. CVS does not seem to increase the risk of preeclampsia or other pregnancy-induced hypertensive disorders. However, randomized prospective trials that are designed to investigate the risk of preeclampsia after CVS are needed to make a definite conclusion.