Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

Maternal serum Sortilin-1 level as a potential biomarker for intrahepatic cholestasis of pregnancy.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease related to pregnancy in women. Sortilin-1 is a sorting receptor belonging to the vacuolar protein sorting 10 (Vps10p) domain family, and recent studies have shown that Sortilin-1 has a distinct role in the pathogenesis of biliary fibrosis and cirrhosis. We aimed to evaluate maternal serum Sortilin-1 level as a potential biomarker in pregnant women with intrahepatic cholestasis.Materials and methods: A prospective observational cohort study was conducted. We enrolled 80 pregnant women, 49 with the diagnosis of intrahepatic cholestasis of pregnancy and 31 healthy controls. Then, we measured maternal serum Sortilin-1 levels using an enzyme-linked immunosorbent assay method and compared them between groups.Results: The mean Sortilin-1 level in the ICP group was higher than control group (3.3 ± 1.7 ng/mL vs. 2.0 ± 0.6 ng/mL, respectively, p < .001). The receiver operating characteristic curve (ROC) analysis based on maternal serum Sortilin-1 levels to predict the presence of ICP was 85.3% controls [area under the curve (AUC), 0.853; 95% CI, 0.738-0.938, p < .001]. The optimal cutoff value of Sortilin-1 was 2.24 ng/mL (71.4% sensitivity and 74.2% specificity) to detect intrahepatic cholestasis of pregnancy.Conclusion: Elevated maternal serum Sortilin-1 levels are associated with ICP and can be used as a disease biomarker. Sortilin-1 levels can be combined with total bile acids, transaminases, and blood coagulation profile in the follow-up of ICP.

Evaluation of right side foetal myocardial performance index in pregestational and gestational diabetes mellitus.

The aim of our study is to investigate the myocardial performance index (MPI) of the right side of the foetal heart in pregestational and gestational diabetes mellitus and to compare it with non-diabetic pregnancies. This prospective cross-sectional study was conducted between August 2018 and March 2019 at Kanuni Sultan Suleyman Research and Training Hospital. Women with pregestational or gestational diabetes mellitus at 24-34 weeks of gestation were included in the study and non-diabetic pregnant women were included as the control group. MPI of the right side of the foetal heart were evaluated and compared between the groups. A total of 65 pregestational or gestational diabetic patients and 65 non-diabetic patients were included in the study. Isovolumetric contraction time and isovolumetric relaxation time values were significantly longer in the diabetic group (p < .001). Ejection time values were significantly shorter in the diabetic group (p < .001). MPI values were significantly higher in the diabetic group than the non-diabetic group (p < .001). In conclusion, MPI of the right side of the foetal heart is significantly higher in pregestational and gestational diabetes than in the non-diabetic group.IMPACT STATEMENTWhat is already known on this subject? Gestational diabetes mellitus causes foetal cardiomyopathy and foetal diastolic dysfunction. Myocardial performance index (MPI) is a non-invasive, Doppler-derived myocardial performance assessment that is independent of both heart rate and ventricular anatomy.What do the results of this study add? MPI of the right side of the foetal heart was significantly higher in pregestational and gestational diabetes than in the non-diabetic group. There was no difference in right ventricular MPI between pregestational and gestational groups in diabetic pregnancies, and between insulin using and not insulin using groups.What are the implications of these findings for clinical practice and/or further research? Our study results are promising. MPI of the right side of the foetal heart is significantly higher in pregestational and gestational diabetes than in the non-diabetic group. Prospective cohort studies evaluating serial MPI and evaluating by postpartum foetal echocardiography are needed to evaluate possible adverse effects of diabetes on foetal cardiac functions.

Maternal Serum Placental Protein-13 Levels in the Prediction of Pregnancies with Abnormal Invasive Placentation.

OBJECTIVE: To evaluate whether placental protein-13 (PP-13) measured in the serum of pregnant women could predict abnormal invasive placentation (AIP) detected by color Doppler ultrasound (US) and magnetic resonance imaging scan in addition to the routine US scan during the third trimester. MATERIALS AND METHODS: The prospective case-control study included patients subdivided in 2 groups: 42 pregnant women with a singleton pregnancy at 28-32 weeks of gestation with only suspected AIP, and 32 healthy pregnant women. The serum PP-13 levels were measured in both groups using an enzyme-linked immunosorbent assay (ELISA) method and statistically compared. The cases of AIP were confirmed by placental histopathological examination and/or the uterus removed by hysterectomy after elective caesarean section. RESULTS: Serum PP-13 levels of pregnant women with AIP were significantly higher (p<0.001) than those of controls (650.32±387.33 vs. 231.43±94.33). Statistical analysis of maternal serum PP-13 levels above the threshold of 312 pg/ml (measured in the early third trimester) predicted AIP with 76.2% sensitivity and 75% specificity. CONCLUSION: Maternal serum PP-13 may have a role in the pathophysiology of AIP owing to its high serum value in the AIP group. The maternal serum dosage of PP-13 levels could improve pregnancy management in those patients suspected of having AIP.

Increased pancreatic-derived factor (PANDER) levels in gestational diabetes mellitus.

The aim of the study was to investigate the pancreatic-derived factor (PANDER) levels in healthy pregnant women and in pregnant women with gestational diabetes mellitus (GDM). A total of 50 women consecutively diagnosed with GDM and 30 randomly selected age-matched and gestational-age-matched healthy pregnant women were included in this cross-sectional study. Serum PANDER levels and other variables were analyzed. The age, the gestational age at the time, the blood sample was obtained and the hemoglobin A1c (HbA1c) levels of the GDM and control groups were similar. The body mass index (BMI), fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and serum PANDER levels were significantly higher in the GDM group than the control group. The optimal PANDER cutoff value was 227.2 ng/ml, and the ratios above this value were 100 and 86.6% for sensitivity and specificity, respectively (p=.0001). Serum PANDER levels were higher in women with GDM compared to the control group and were positively correlated with insulin, HOMA-IR, and HbA1c levels. These results suggest that PANDER might be considered a new biomarker for GDM.

Agency Problems and Airport Security: Quantitative and Qualitative Evidence on the Impact of Security Training.

We analyze the issue of agency costs in aviation security by combining results from a quantitative economic model with a qualitative study based on semi-structured interviews. Our model extends previous principal-agent models by combining the traditional fixed and varying monetary responses to physical and cognitive effort with nonmonetary welfare and potentially transferable value of employees' own human capital. To provide empirical evidence for the tradeoffs identified in the quantitative model, we have undertaken an extensive interview process with regulators, airport managers, security personnel, and those tasked with training security personnel from an airport operating in a relatively high-risk state, Turkey. Our results indicate that the effectiveness of additional training depends on the mix of "transferable skills" and "emotional" buy-in of the security agents. Principals need to identify on which side of a critical tipping point their agents are to ensure that additional training, with attached expectations of the burden of work, aligns the incentives of employees with the principals' own objectives.

Drugst.One - A plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

A promising novel biomarker for early-onset preeclampsia: soluble trigger receptor expressed on myeloid cells-1 (sTREM-1).

BACKGROUND: We aimed to explore TREM-1 activation in pregnant women who has preeclampsia through the measurement of its soluble form sTREM. METHODS: A prospective cohort study was conducted. Participants were recruited from antenatal clinic between 1 May 2019 and 31 August 2019, and they all provided written informed consent for participation. Women between 18 and 42 years of age who were diagnosed with early or late-onset preeclampsia (LOP) were offered participation if they did not have any known systemic disease (chronic hypertension, diabetes, hypothyroidism, chronic renal-liver diseases, etc.); autoimmune disorders; multiple pregnancies; presence of fetal structural and chromosomal anomalies; placenta previa; cholestasis of pregnancy; preterm delivery; evidence of chronic and active infection. The primary outcome of the study was to assess any difference between groups in terms of the diagnostic value of sTREM level. RESULTS: A total of 80 patients were enrolled; proven early-onset preeclampsia (EOP) (n = 20), LOP (n = 30), and control (n = 30) groups. There was no significant difference among the groups in terms of age and BMI. Mean gestational age at diagnosis of EOP; 30 ± 1.9 and LOP; 34.7 ± 1.9 weeks gestation. The mean sTREM level was 160.130 ± 1.65 pg/ml in the EOP group, 119.337 ± 2.04 pg/ml in LOP group, and 87.764 ± 1.69 pg/ml in the control group. According to subgroup analysis, sTREM levels were significantly higher in EOP group than control group. CONCLUSIONS: sTREM might be a promising biomarker for early detection of EOP. However, future studies are necessary to confirm this hypothesis.

Increased sulfiredoxin-1 levels as compensatory mechanism against reactive oxygen species in women with gestational diabetes mellitus

Objective: This study aimed to investigate the correlation between serum Sulfiredoxin-1 (Srx-1) levels and gestational diabetes mellitus (GDM). Materials and Methods: A total of 40 patients diagnosed with GDM according to the American Diabetes Association Criteria and 40 age matched and gestational age-matched healthy pregnant women as a control group were included in this cross-sectional study. Serum Srx-1 levels and other demographic and laboratory variables were analyzed. Results: Fasting plasma glucose, first and second-hour plasma glucose levels, fasting insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), and Srx-1 levels were significantly different in patients with GDM than control (p<0.05). Plasma Srx-1 levels significantly correlated with fasting plasma glucose, first and second-hour plasma glucose levels, fasting insulin levels, and HOMA-IR of patients with GDM (p<0.05), whereas no correlation in the control group. Conclusion: This is the first study demonstrating an association between serum Srx-1 levels and GDM. Our results suggest increased serum Srx-1 levels may be a novel predictive marker for GDM. More randomized-controlled trials are needed to evaluate Srx-1 as a marker for adverse fetal results; closer monitoring is warranted with high Srx-1 levels.

The association between increased maternal PARK7 (DJ-1) levels and the occurrence of preterm premature rupture of membranes - A randomized prospective study

Objective: Parkinson's disease protein 7 (PARK7/DJ-1) is an important antioxidant multiprotein against inflammation and oxidative stress. We therefore planned this study to demonstrate the association between maternal PARK7 levels and the occurrence of preterm premature rupture of membranes (PPROM). Materials and Methods: We enrolled 80 pregnant women; 50 PPROM patients and 30 healthy controls, into this cross- sectional study between the 24th and 36th gestational weeks. Furthermore, we measured serum PARK 7 levels using enzyme-Linked immunosorbent assay method. Results: Plasma PARK7 levels were higher in PPROM patients compared to those in the healthy controls (p<0.001). With a cutoff value of 2.57 pg/mL; PARK 7 had a 92% sensitivity, 86% specificity, 88% positive predictive value and 83% negative predictive value (p<0.01) for PPROM. PARK7 had positive correlation with blood leukocyte levels (p<0.001), C-reactive protein levels (p<0.001), and negatively correlated with birth weight and birth week. Conclusion: PARK 7 is overexpressed in PPROM patients. Due to its anti-inflammatory and antioxidant properties, PARK7 may be a novel marker in better understanding the pathophysiology and prediction of the prognosis PPROM. Further large-scale studies are needed.

Lysyl oxidase like protein-2 (LOXL-2); a novel marker for prediction of intrahepatic cholestasis of pregnancy.

OBJECTIVE: Lysyl oxidase like protein 2 (LOXL-2) is an enzyme that is involved in the development of hepatic fibrosis and bile duct epithelial injury in hepatic cholestasis. Our aim was to investigate maternal serum levels of LOXL-2 and their relationship with fasting total bile acid (FTBA) levels in patients with intrahepatic cholestasis of pregnancy (ICP). MATERIALS AND METHODS: Thirty-five pregnant women with ICP and 35 healthy women with uncomplicated pregnancies as the control group, were included in this cross-sectional study. Maternal serum LOXL-2, FTBA and other liver function test levels were compared between the two groups. The predictive cutoff value for LOXL-2 level in ICP was specified. RESULTS: Serum LOXL-2 levels were found to be higher in the ICP group compared to the control group (225.699 ± 142.453 vs. 127.731 ± 63.419 pg/mL, p = .001). There was a significant positive correlation between serum LOXL-2 levels and FTBA levels (r = 0.330, p = .003). The optimal cutoff point for LOXL-2 for identifying increased risk of ICP was found to be ≥102 pg/mL, for which the sensitivity and specificity were 96.87% and 48.57%, respectively (p < .001). CONCLUSIONS: Maternal serum LOXL-2 levels were significantly higher in women with ICP. LOXL-2 may be both an initiating factor in the pathophysiology of ICP and a marker in the prediction. It may also be a target in terms of preventing strategies in ICP.

Assessment of fetal right ventricular myocardial performance index changes following intrauterine transfusion.

INTRODUCTION: Severe fetal anemia may cause cardiac ischemia, reduced contractility, and dysfunction. The purpose of our study is to evaluate right ventricular myocardial performance index (MPI) before and after intrauterine transfusion (IUT) in patients who underwent this procedure because of fetal anemia due to Rh-D alloimmunization. MATERIALS AND METHODS: This prospective cohort study was conducted between January 2018 and June 2019 at Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey. The pregnant women who were applied IUT because of fetal anemia due to Rh-D alloimmunization in our perinatology clinic were included in the study. Fetal right ventricular MPI before and 24 h after IUT were evaluated. RESULTS: A total of 28 IUTs were performed in 17 pregnant women during the study period. The isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) values measured before IUT, were found to be significantly longer compared to the ICT and IRT values measured after IUT. The MPI values measured after transfusion was found to be higher than before transfusion. CONCLUSIONS: The fetal right ventricular MPI increases 24 h after IUT. This increase in the right ventricular MPI might be used as a marker for predicting adverse fetal outcomes following IUT.

A Comparative Multicentric Study on Serosal and Endometrial Myomectomy During Cesarean Section: Surgical Outcomes.

OBJECTIVE: This multi-center study aims to determine the efficiency and safety of endometrial myomectomy (EM) for the removal of uterine fibroids during cesarean section (CS). METHODS: Retrospective review of 360 women diagnosed for fibroids during pregnancy. They all delivered by CS between 2014 and 2019. The study groups included 118 women who only underwent EM, 120 women who only had subserosal myomectomy by traditional technique and 122 women with fibroids who decided to avoid cesarean myomectomy, as control group. They were analyzed and compared the surgical outcomes. RESULTS: The EM, subserosal myomectomy and control groups were statistically (p > 0.05) similar for to age, body mass index (BMI), gravidity, parity, gestational age at delivery, indications for CS, number of excised fibroids, size of the largest myoma. Postoperative hemoglobin values and ? (?) hemoglobin concentrations were lower in SM group (10.39gr/dl vs 9.98 gr/dl vs 10.19 - 1.44 gr/dl vs 1.90 gr/dl vs 1.35; p = 0.047, p = 0.021; respectively) Hybrid fibroids were significantly more frequent in the EM group than subserosal myomectomy and control groups (respectively, 33.1% vs 23.3% vs 27.0%, p = 0.002). Surgery time was significantly longer in the subserosal myomectomy group than EM and control groups (respectively, 46.53 min vs 37.88 min vs 33.86 min, p = 0.001). Myomectomy took significantly longer time in the subserosal myomectomy than EM group (13.75 min vs 8.17 min, p = 0.001). CONCLUSIONS: Endometrial myomectomy is a feasible choice for treatment of fibroids during CS, and, basing on our results could be an alternative to traditional cesarean subserosal myomectomy.

Maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes.

Objective: To investigate maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes (PPROM) and to compare with pregnancies delivered at term.Materials and methods: In this cross-sectional study, 40 women with singleton pregnancies complicated with PPROM between 24 and 34 weeks of gestation were compared with gestational age-matched 40 pregnant women with no obstetrics complications, who delivered at term. The maternal serum galectin-1 and galectin-3 levels were measured.Results: Patients complicated with PPROM had significantly higher levels of galectin-1 (p = .001) and galectin-3 (p = .003) than the control group. Maternal serum galectin-3 levels were found significantly negatively correlated with the gestational age at delivery and birth weight.Conclusion: Maternal serum galectin-1 and galectin-3 levels were significantly higher in pregnancies complicated with PPROM. Galectin-1 and galectin-3, with their regulatory effects in key biological processes, may be both an initiating factor in the pathophysiology of PPROM, a marker in the prediction, and a target of preventing strategies of PPROM.

Maternal serum TXNDC5 levels and thiol/disulfide homeostasis in preeclamptic pregnancies.

Objective: To investigate thiol/disulfide homeostasis (TDH) and thioredoxin domain-containing 5 (TXNDC5) level in early and late-onset preeclampsia.Material and methods: In this cross-sectional study, 24 pregnant women with early-onset preeclampsia and 26 pregnant women with late-onset preeclampsia were compared with 30 pregnant women with no obstetric complications. The serum TXNDC5 levels and thiol/disulfide homeostasis were measured.Results: Serum TXNDC5 levels were significantly higher in the early-onset and late-onset preeclampsia groups compared with the control group (p < .05). Native thiol and total thiol levels were significantly lower in the early-onset and late-onset preeclampsia groups than control group. The disulfide levels were found as significantly high in early preeclamptic patients compared to control group (p < .05). The highest levels of TXNDC5 and the lowest levels of native thiol and total thiol were found in early-onset preeclampsia group. No significant difference was found between the patients with early onset and late onset preeclampsia regarding TXNDC5 levels and thiol/disulfide homeostasis (p > .05).Conclusion: Serum TXNDC5 levels were significantly higher in patients with early-onset and late-onset preeclampsia. The dynamic thiol/disulfide homeostasis was impaired in favor of the oxidized state in patients with preeclampsia.

A multimodal and signals fusion approach for assessing the impact of stressful events on Air Traffic Controllers.

Stress is a word used to describe human reactions to emotionally, cognitively and physically challenging experiences. A hallmark of the stress response is the activation of the autonomic nervous system, resulting in the "fight-freeze-flight" response to a threat from a dangerous situation. Consequently, the capability to objectively assess and track a controller's stress level while dealing with air traffic control (ATC) activities would make it possible to better tailor the work shift and maintain high safety levels, as well as to preserve the operator's health. In this regard, sixteen controllers were asked to perform a realistic air traffic management (ATM) simulation during which subjective data (i.e. stress perception) and neurophysiological data (i.e. brain activity, heart rate, and galvanic skin response) were collected with the aim of accurately characterising the controller's stress level experienced in the various experimental conditions. In addition, external supervisors regularly evaluated the controllers in terms of manifested stress, safety, and efficiency throughout the ATM scenario. The results demonstrated 1) how the stressful events caused both supervisors and controllers to underestimate the experienced stress level, 2) the advantage of taking into account both cognitive and hormonal processes in order to define a reliable stress index, and 3) the importance of the points in time at which stress is measured owing to the potential transient effect once the stressful events have ceased.

Stress Assessment by Combining Neurophysiological Signals and Radio Communications of Air Traffic Controllers.

Air Traffic Control (ATC) has been classified as the fourth most stressful job. In this regard, sixteen controllers were asked to perform ecological ATC simulation during which behavioral (Radio Communications with pilots - RCs), subjective (stress perception) and neurophysiological signals (brain activity and skin conductance - SC) were collected. All the considered parameters reported significant changes under high stress conditions. In particular, the theta, alpha, and beta brain rhythms increased significantly (all p<0.05) all over the brain areas, and both the SC components exhibited higher values (p<0.01). Additionally, the number of speech under high stress decreased significantly (p<10-4) while both the mean and median value of the F0 component of the RC increased (p<0.01). The results can be employed to objectively measure and track the controller's stress level while dealing with ATC activities to better tailoring the workshift and maintaining high safety levels.

Maternal serum AMP-activated protein kinase levels in mild and severe preeclampsia.

OBJECTIVE: To investigate Phosphorylated adenosine monophosphate activated protein kinase (AMPK) levels in healthy pregnant women and pregnant women with preeclampsia (PE). METHODS: Twenty-eight women with mild-PE, 22 with severe-PE, and 30 normotensive controls were included in this cross-sectional study. The serum AMPK levels of these patients were analyzed. The patients were followed up to delivery. RESULTS: No statistically significant difference was found between the groups for age, gravida, parity, and gestational age at the time the blood samples were obtained (p > .05). No significant difference between the group with mild-PE and the control group was found, while in the severe-PE group, serum AMPK levels were significantly higher relative to both the mild-PE and control groups (p < .001 and p < .001, respectively). No correlation was detected between serum AMPK levels and age, body mass index (BMI), and gestational age at the time the blood samples were collected. A negative correlation was found between AMPK levels and gestational week and birthweight at delivery, while a positive correlation was detected between systolic and diastolic blood pressures and AMPK levels. CONCLUSIONS: Serum AMPK was higher in patients with severe-PE compared with healthy pregnant women and patients with PE without severe features so it might be a new biomarker for the prediction of disease and its severity.

Targeted fetal cell-free DNA screening for aneuploidies in 4,594 pregnancies: Single center study.

BACKGROUND: Next-generation sequencing (NGS) and discovery of fetal cell-free DNA (cfDNA) in the maternal circulation render possible prenatal screening for trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and sex chromosome aneuploidies. The approach is called "fetal cfDNA screening" and in contrast to noninvasive conventional serum screening, it provides the identification of 98%-99% of fetuses with Down syndrome. METHODS: Retrospective analysis of targeted noninvasive prenatal testing (NIPT) (Clarigo Test) pregnancies with moderate risk, which we have reported between 2016 and 2018 years is presented. Two separate laboratory workflows and NGS platforms are used for the same targeted NIPT analysis. RESULTS: In total, 4,594 pregnant women were investigated. Initial 3,594 cases are studied by MiSeq platform, the last 1,000 cases by NextSeq. Failure rate for MiSeq platform is 10.9% and for NextSeq is 8.7%. Automatically reported cases constitute 75% of the MiSeq group and 87% of the NextSeq group. CONCLUSIONS: Targeted NIPT results suggest that MiSeq platform could be used for NIPT which would be an essential option particularly for laboratories with low sample flow. And, the NextSeq platform has easier wet lab process and also increased success rate in automatic reporting which is suitable for centers with high number of NIPT cases.

Investigation of the effect of gestational diabetes on fetal cardiac tissue in streptozotocin induced in rats.

PURPOSE: To investigate the cause of congenital anomalies resulted from gestational diabetes on fetal cardiac tissue in experimental animal study model. METHODS: Totally 12 female Wistar albino rats were divided into two groups, each consisting of 6 rats. Streptozotocin (60 mg/kg) was administered intraperitoneally to the study group by dissolving in citrate solution. The rats with a blood glucose level of 200 mg/dL and above were considered to be diabetic rats. Total antioxidant status (TAS), total oxidative stress (TOS) and oxidative stress index (OSI) values were calculated in the cardiac tissues and maternal serum samples of the fetuses delivered by cesarean section after the mating process. The cardiac tissues were also subjected to histopathological examination. RESULTS: TOS and OSI values in fetal cardiac tissues of the diabetic rats were found to be significantly higher than that of the control group (p=0.026 and p=0.005). Histopathological examination revealed that the mitotic index was lower and the cell organization was found to be damaged in the fetuses of the study group rats. CONCLUSION: Increased levels of free oxygen radicals considered to be due to hyperglycemia may cause congenital anomalies, especially during organogenesis period, by disrupting cell homeostasis and adversely affecting mitosis.