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Introduction: Altered epigenetic map is frequently observed in cancer and recent investigations have demonstrated a pertinent role of epigenetic modifications in the response to many anticancer drugs including the DNA damaging agents. Topoisomerase I (Top I) is a well-known nuclear enzyme that is critical for DNA function and cell survival and its inhibition causes DNA strand breaks and cell cycle arrest. Inhibitors of human Top I have proven to be a prosperous chemotherapeutic treatment for a vast number of cancer patients. While the treatment is efficacious in many cases, resistance and altered cellular response remain major therapeutic issues., Areas Covered: This review highlights the evidence available till date on the influence of different epigenetic modifications on the response to Top I inhibitors as well as the implications of targeting epigenetic alterations for improving the efficacy and safety of Top I inhibitors., Expert Opinion: The field of epigenetic research is steadily growing. With its assistance, we could gain better understanding on how drug response and resistance work. Epigenetics can evolve as possible biomarkers and predictors of response to many medications including Top I inhibitors, and could have significant clinical implications that necessitate deeper attention.HIGHLIGHTSEpigenetic alterations, including DNA methylation and histone modifications, play a pertinent role in the response to several anticancer treatments, including DNA damaging agents like Top I inhibitors.Although camptothecin derivatives are used clinically as Top I inhibitors for management of cancer, certain types of cancer have inherent and or acquired resistance that limit the curative potential of them.Epigenetic modifications like DNA hypomethylation can either increase or decrease sensitivity to Top I inhibitors by different mechanisms.The combination of Top I inhibitors with the inhibitors of histone modifying enzymes can result in enhanced cytotoxic effects and sensitization of resistant cells to Top I inhibitors.MicroRNAs were found to directly influence the expression of Top I and other proteins in cancer cells resulting in positive or negative alteration of the response to Top I inhibitors.lncRNAs and their genetic polymorphisms have been found to be associated with Top I function and the response to its inhibitors.Clinical trials of epigenetic drugs in combination with Top I inhibitors are plentiful and some of them showed potentially promising outcomes.

Exposure to the deleterious effects of silver nanoparticles (AgNPs) is inevitable due to their wide use in medicine and daily life. The current study aimed to delineate the histomorphological changes and the molecular mechanisms underlying the ameliorative effect of Resveratrol (RSV) on rats' livers exposed to AgNPs. Fifty healthy adult male Wistar albino rats were divided into four groups: control, AgNPs-exposed, RSV-treated after AgNPs exposure, and recovery groups. Liver sections were examined by light and electron microscopes, and immunohistochemistry was performed for detection of activated caspase3 and TNFα. Serum ALT and AST, plasma levels of TNFα, IL-6, GSH and SOD were measured. mRNA expression of SIRT1, ADORA3, PAI, CDK1, Nrf2 and NFκB genes in liver tissue homogenate was performed using qRT-PCR. AgNPs-exposure for 28 days caused marked liver tissue damage with trapping in hepatocytes and Kupffer cells, while RSV treatment ameliorated liver ultrastructure and function. Our results clarified the molecular basis of RSV ameliorative effect on liver tissue by significant upregulation of SIRT1-NrF2 signaling pathway with increased levels of the antioxidant GSH and SOD, which represent the antioxidant effect of RSV. Significant upregulation of the protective ADORA3 with downregulation of the proinflammatory PAI-1 and NFκB mRNA expression levels besides decreased plasma levels of TNFα, IL-6 and decreased immunoexpression of TNFα in liver tissue, represent the anti-inflammatory effect of RSV. In addition, decreased immunoexpression of caspase3 and downregulation of CDK1 expression, represent its antiapoptotic effect. In conclusion: RSV ameliorates AgNPs-induced liver damage by antioxidant, anti-inflammatory and antiapoptotic effects. Abbreviations: AgNPs: Silver nanoparticles, RSV: Resveratrol, ROS: Reactive oxygen species, ESR: Electron spin resonance, DMPO: 5,5-Dimethyl-1-pyrroline-N-oxide, H 2 O 2 : Hydrogen peroxide, SOD: Superoxide dismutase, CAT: Catalase, GPx: Glutathione peroxidase, MPTP: Methyl-4-phenyl-1.2.3.6-tetrahydropyridine, MDA: Malondialdehyde, TNF: Tumor necrosis factor, GSH: Glutathione, Nrf2: Nuclear factor-erythroid 2-related factor 2, ARE: Antioxidant response elements, KEAP1: Kelch-1ike ECH-associated protein l, AMPK: AMP-activated protein kinase, HO-1: Heme oxygenase-1, NF-κB: Nuclear factor-kappa B, SIRT1: Sirtuins, FOXO: Forkhead box, UCP2: Uncoupling protein 2, STZ: Streptozotocin nicotinamide, HSC: hepatic stellate cells, ECM: extracellular matrix.

Ever since gadolinium was found to deposit in the brain of patients with normal kidney function by Kanda et al. in 2014, several studies have been conducted to evaluate its effect on the patients' health. However, conflicting results were obtained regarding imaging in gadolinium retention. These finding were attributed to the chelating structure of the administered gadolinium-based contrast agent (GBCA): linear agents were found to accumulate in the dentate nucleus (DN) and the globus pallidus (GP) of subjects even after one dose. There are some contradictory results when assessing macrocyclic agents. In the following article, we review the basis of GBCAs characteristics and their side effects, as well as, the MRI studies that assessed the accumulation of gadolinium in the brain. Based on the results of several studies, in 2017, the European Medicine Agency requested the suspension of the marketing authorizations for three linear GBCAs: gadodiamide (Omniscan®), gadoversetamide (Optimark®) and gadopentate dimeglimine (Magnevist®) and limited the use of gadoxetate disodium (Primovist/Eovist®) and gadobenate dimeglumine (MultiHance®) to hepatic uptake for imaging poorly vascularized hepatic lesions. Accordingly, the FDA did not restrict GBCA use, but will continue to study their safety and urged clinicians to use these agents sparingly. All macrocyclic GBCAs continued however to be used as no available valid evidence linked them to brain gadolinium retention. Regardless of possible accumulation in the brain, there is no evidence to-date that gadolinium retention leads to any disease or disorders in subjects with normal renal function. Further investigations with long-term follow-up are needed.

Aims: To determine maternal and perinatal outcome of eclampsia patients over a decade., Methods: Analysis of case records of all eclampsia cases from January 2005 to December 2014., Results: There were 30 cases of eclampsia. The most significant risk factors for developing pre-eclampsia are unbooked cases (97%), nulliparity, young age, marriage ≤4 months, history of pre-eclampsia in previous pregnancy, remarriage, preexisting diabetes mellitus, interval between pregnancies ≥10 years, positive family history. The incidence of eclampsia was 0.05%, antepartum eclampsia 15 (50%), intrapartum 6 (20%) and postpartum 9 (30%) with no maternal deaths, and 1 perinatal death. Perinatal mortality was 33.3/1000. 22 (73%) patients received magnesium sulphate (MgSO4) and 8 patients (27%) received Diazepam, of which 1 had recurrence of convulsions. All 15 antepartum cases were delivered by cesarean section as were 2 intrapartum. 13 (43%) of women delivered vaginally. Only 6 (20%) patients were of low socio-economic status and were primary school educated. Severe maternal complications occurred in 8 (27%), with abruptio placentae being the most common 3 (38%)., Conclusions: Incidence of eclampsia was low, with no maternal deaths. MgSO4 was found to be highly effective. Lack of antenatal care is a major risk factor.

Objective: To determine whether cervical membrane sweeping during labor induction is beneficial., Methods: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes "swept" or "not swept" at the initiation of labor induction., Results: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 "swept", 202 "not swept"] and 400 multiparas (Group B) (201 "swept" and 199 "not swept"]. Among group A who received intravaginal prostaglandin (PG) E2, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9 ± 1.3 versus 16.2 ± 1.1 hours, p = 0.046), lower mean dose of oxytocin (6.6 ± 0.6 versus 10.11 ± 1.4 mU/minute, p = 0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p = 0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9 ± 2.9 versus 10.9 ± 2.6 hours p = 0.04, mean maximum dose of oxytocin 9.8 ± 1.1 versus 15.2 ± 1.1 mU/min, p = 0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping., Conclusion: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE2 or Oxytocin alone.

Objectives: (1) To evaluate maternal and fetal outcome after motor-vehicle injury during pregnancy. (2) To determine if there was prenatal care provider counseling for seat belt use., Methods: Retrospective chart analysis of materno-fetal outcome following motor vehicle injury in 728 pregnant women between 2009 and 2012. Women attending antenatal clinics over these years were asked if they were counseled regarding correct seat belt use by prenatal health care providers during their antenatal visits., Results: In these pregnant women, 80 (11%) sustained minor injuries/sprains. 648 women (89%) had severe adverse materno-fetal pregnancy outcomes. Important causes being: (1) placental abruption 58.8%; (2) preterm labor (40%); and (3) uterine rupture (1.6%). There were 100 (13.7%) maternal and 78 (10.7%) fetal deaths. 91 (12.5%) perimortem cesarean deliveries were performed and 74 (81%) fetus survived, as did 31 women. Prenatal care provider counseling for seat belt use occurred in 44.8% of prenatal visit. Only 125 (21%) were using seat belt during the accident., Conclusion: Important causes of adverse pregnancy outcome were: abruptio placenta, preterm labor and uterine rupture. There were 100 maternal and 78 fetal deaths with 97 preterm births. Counseling occurred in 44.8% of women. Those using seat belts during the accidents sustained minor injuries.

Objective: To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section (CS), so that the safety of labor induction could be assessed., Methods: In 102 women (study group), labor was induced and the outcome was compared with 280 women (control group) who went into spontaneous labor. All 382 women were grand multiparous and had one previous CS., Results: There were no significant difference in oxytocin augmentation, CS, scar dehiscence, fetal birth weight or apgar scores between groups. There was one neonatal death, two still births, one early neonatal death and one congenital malformation in the study group and this was not significant. There was no significant difference in vaginal birth in the study (80.9%) and the control group (83.8%)., Conclusion: In this moderate-sized study, induction of labor may be a safe option in grand multiparous women, if there is no absolute induction for repeating CS.

Unlabelled: This study aims at (1) Assessing trends in maternal mortality in kuwait (2) Define strategies for prevention., Methods: Retrospective analysis of maternal deaths that occurred among, 55,979 live births at a tertiary hospital, between 1980 and 2009., Results: There were 14 maternal deaths, and 55,979 live births, giving a maternal mortality rate of 25 per 100,000 live birth. In terms of decades maternal mortality declined from 54.8 in 1980-90 to 28.4 in 1990-2000 and continued to decline to 12.2 in 2000-2009. Thromboembolism (28.6%), Obstetric haemorrhage (21.5%) and Eclampsia (14.3%) were the leading causes of direct deaths. Cardiac disease is the most common cause of indirect deaths (14.3%) followed by H1N1 pneumonia 7.1%. Eclampsia contributed to 40% of deaths, only in the 1980s. Thromboembolism caused 28.6% of deaths, 50% of which were in the last 9 years. Indirect deaths from cardiomyopathies (66.7%) gained prominence in the 1990s. No deaths from puerperal sepsis were reported after the 1980s (14.3%)., Conclusions: Maternal mortality rates are decreasing significantly (p<0.01) at our institution over the last 29 years. Obstetric haemorrhage and thromboembolism remain important causes of maternal mortality. Substandard care was identified in 70% of Direct and 55% of indirect deaths.

Objective: Data on the effect of coconut oil intake on various hematologic and metabolic parameters in pregnant women or animals are scanty. Hence we attempted to assess the effect of oral administration of graded doses of this edible oil during pregnancy, on various hematologic and metabolic parameters in rats., Methods: Groups of pregnant Sprague Dawley rats were given oral doses of 1 ml, 2 ml, and 4 ml coconut oil twice per day, respectively. Control group of rats were given tap water. Oral feeding of oil was done continuously for a period of 20 days and at the end of the study period the animals were lightly anaesthetized with ether and sacrificed to collect blood samples for analysis. Various hematologic parameters such as red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (Hg), platelets, lymphocytes, and mean corpuscular hemoglobin concentration (MCHC) were analyzed by a hematology blood analyzer, while metabolic parameters such as cholesterol, triglycerides, urea, uric acid, creatinine, and protein were analyzed by specific analytical kits. Activities of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant activity (TAO) were assessed by specific analytical kits. Statistical analysis of data was performed using a SPSS data analytical package., Results: Oral administration of coconut oil for 20 continuous days of pregnancy did not significantly alter any of the hematologic parameters studied, compared to control group even when the oil was administered at a relatively massive dose of 4 ml/day. Administration of coconut oil appeared to decrease WBC, Hg, platelet, and lymphocyte blood concentrations in treated rats, but the difference, however, was not statistically significant (ANOVA test; p > 0.05). However, platelet concentration was significantly lower (p < 0.05) in rats receiving 1 ml/day of coconut oil compared to control group rats. Administration of coconut oil did not alter the concentrations of protein, cholesterol, urea, triglycerides, uric acid, and creatinine in treated groups of rats significantly (Student's t-test, p > 0.05) compared to those of control rats. SOD, GPX, and TAO levels in control and treated groups were not significantly different (ANOVA test, p > 0.05) than controls., Conclusions: We conclude that oral administration of coconut oil during pregnancy in rats, even in massive doses, does not cause any significant alterations in hematologic and metabolic parameters. More detailed studies, however, are warranted before extrapolating these results to human situations.

Objectives: To assess the incidence of female circumcision/female genital cutting (FGC) among pregnant women and describe the obstetrical and psychological sequelae of female circumcision., Method: Four thousand eight hundred pregnant women over a 4-year period were assessed for female circumcision. Odd ration (OR) and 95% confidence interval (CI) were calculated to measure association between female circumcision, maternal morbidity, and birth outcome. Variables included prolonged maternal hospitalization, low birth weight, prolonged labor, obstructed labor, cesarean section, and fetal outcome. Assessment measures to determine cognitive and emotional effects included the Mini international Neuro-psychiatric interview and Rey memory test., Results: The prevalence of female circumcision was 38%; women who were circumcised were more likely have extended hospital stay. There was a positive association between such women and prolonged labor, cesarean section, post-partum hemorrhage, early neonatal death, and hepatitis C infection. Psychiatric sequelae included: 80% continued to have flashbacks to the FGC event; 58% had a psychiatric disorder (affective disorder); 38% had other anxiety disorders, and 30% had post-traumatic stress disorder., Conclusion: Female circumcision is associated with adverse materno-fetal outcome and psychiatric sequelae. Many will need psychiatric as well as gynecological care.

Objectives: (a) To review the cases of ruptured uterus over the last 25 years and analyze the causative factors with a view to its prevention (b) To analyze subsequent pregnancy outcome with a view to its safety., Method: The case notes were reviewed for all patients with ruptured uterus over a period of 25 years from January 1982 to January 2007. Relevant dates relating to the characteristics of labor, delivery, maternal, perinatal, and subsequent pregnancy outcomes were assessed., Results: The incidence of ruptured uteri was calculated to be 0.03%. Total deliveries included in the study were 152,426. There were 46 cases of ruptured uteri and 44 were available for study. Twenty-two (52%) ruptured uteri occurred in patients with previous caesarean scars, of which 10 occurred in women with previous four or more caesarean sections. In 12 cases (27%), uterine rupture occurred due to oxytocin; PGE2 and oxytocin were used in 3 of these 12 cases. Two (4.5%) ruptures occurred due to non-removal of cervical cerclage during labor. Two (4.5%) primigravidae ruptured their uterus following road traffic accident, resulting in maternal and fetal deaths. Malpresentation in labor resulted in eight (18%) ruptures. Rupture occurred at the fundus in 10 cases and in the lower segment in the remaining 34. Fetal heart abnormalities were observed in all cases in which the uterus ruptured during labor. Abdominal hysterectomy was performed in 20 cases (45%) of which 13 were subtotal and 7 (10%) were total. Of the remaining 24 (55%) patients, 10 had suture repair and in addition 14 patients underwent hypogastric artery ligation. Later, 22/24 (92%) women became pregnant. Twenty (91%) were delivered by planned caesarean section. There were no maternal or fetal complications. The remaining two women had previous classical scar, undetected malpresentation, and sparse antenatal care. Their uteri ruptured spontaneously at 32 and 35 weeks at home. They died intra-operatively due to intractable hemorrhage along with their fetus., Conclusion: In the previous caesarean section, the indiscriminate use of oxytocin and malpresentation are the risk factors for uterine rupture. Child birth after uterine rupture is not to be recommended routinely. Most women with a previous uterine rupture with meticulous tertiary level antenatal care had a favorable outcome in subsequent pregnancies.

Objective: Folate antagonists are widely used in the treatment of various cancerous states. Paucity of data on effect of administration of one such widely used drug, methotrexate (MTX), on the status of essential trace elements and antioxidant enzymes in pregnant women or in pregnant animals prompted us to undertake this study., Methods: MTX at a concentration of 5 mg/kg body weight was administered intraperitoneally as single dose to pregnant Sprague-Dawley rats for three consequitive days from day 17 of pregnancy. Control group of pregnant rats received single dose of saline instead of the anti-cancer drug on all the 3 days. After receiving the third dose of drug, the treated rats and control group rats were sacrificed, 1 h after intraperitoneal injection of a cocktail of essential trace elements namely, Cu, Se and Zn administered as a single bolus dose. Blood samples were collected 30 min of trace element cocktail injection, after decapitation and concentrations of trace elements in serum samples were determined by atomic absorption spectrophotometry. Concentrations of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and total antioxidant status were determined by specific analytical kits, using spectrophotometry., Results: In control group(n = 6), serum concentrations of Cu, Se and Zn averaged 2330.5, 614.8 and 2773.2 microg/l, while in study group (n = 6) the concentrations of trace elements averaged 2294, 596 and 2713 microg/l, respectively. Student's t-test did not show any statistical significance (p > 0.05) between various trace element concentrations in control and treated groups. Cu:Zn ratios of control and treated group of rats did not vary significantly as well. Concentrations of superoxide dismutase, glutathione peroxidase in whole blood samples in control rats averaged 165 and 43,260 U/ml, respectively, while in MTX-treated group of animals the corresponding antioxidant enzymes averaged 330.6 and 67,101 U/ml respectively. SOD and GPX values were significantly higher in drug-treated animals compared to controls (Student's t-test, p < 0.05) However, total antioxidant activity was shown to be significantly lower (Student's t-test; p < 0.05) in the drug-treated group compared to control., Conclusions: We report for the first time that effect of MTX administration in pregnancy is not associated with significant alteration in disposition of essential trace elements. However, the effect of drug administration on antioxidant enzyme status in pregnant women cannot be excluded while using the drug in clinical states.

Objective: Platinum-containing drugs are used extensively in the treatment of various malignancies in humans. Data are scarce on the maternal-fetal transport characteristics in humans of one such widely used drug, cisplatin, and this prompted us to study its transport characteristics in the human placenta in vitro., Methods: Placentae from normal pregnancies were collected after delivery. Cisplatin, along with antipyrine as an internal reference marker, was injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution, was used as the perfusate. The concentration of cisplatin in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was quantified by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters., Results: The differential transport rate of cisplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.49 +/- 0.02, 1.23 +/- 0.03, 2.41 +/- 0.04, 3.67 +/- 0.03, and 4.48 +/- 0.07 minutes in 12 perfusions, while corresponding rates for antipyrine, for above mentioned efflux fractions averaged 0.51 +/- 0.01, 1.26 +/- 0.05, 2.52 +/- 0.01, 3.78 +/- 0.01, and 4.52 +/- 0.01 minutes, respectively. Cisplatin transport rates averaged 0.97, 0.97, 0.96, 0.97, and 0.99 times the antipyrine reference value. Analysis of variance (ANOVA) did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of cisplatin, expressed as a fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.6 +/- 2.01% of injected bolus dose, representing 13.10% of reference marker value. The Student's t-test showed cisplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, and elimination rate of study and reference substances also varied significantly (p < 0.05)., Conclusions: We report for the first time that cisplatin transport is negligible in the human placenta at term. It is reasonable to assume that the risk for the neonate from cisplatin use in pregnancy is minimal when it is used in emergency clinical situations.

Objective: Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal-fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro., Methods: Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters., Results: The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 +/- 0.10, 1.06 +/- 0.06, 1.00 +/- 0.02, 0.98 +/- 0.01, and 0.99 +/- 0.01, respectively, times the antipyrine reference value. Student's t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.60 +/- 2.01% of injected bolus dose, representing 13.1% of reference marker value. Student's t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences., Conclusions: We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.

Objective: Folate antagonists are widely used in the treatment of diverse cancerous states. A paucity of data on transport characteristics of one such widely used drug, methotrexate, in the human placenta, prompted us to study its permeation characteristics in vitro., Methods: Placentas from normal pregnancies were collected post-partum. Methotrexate, along with antipyrine as reference marker were injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules; perfusate samples were collected from both maternal and fetal circulations over a study period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. The concentration of methotrexate in various samples was determined by high performance liquid chromatography, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using standard parameters., Results: Differential transport rate of methotrexate for 10, 25, 50, 75 and 90% efflux fractions in fetal venous effluent averaged 0.52, 1.30, 2.37, 3.57 and 4.43 minutes in 12 perfusions, representing 1.01 + 0.08, 1.03 + 0.06, 0.95 + 0.03, 0.93 + 0.03, 0.93 + 0.03 respectively times antipyrine reference value. Student's t-test showed varying differences between the control and study group data. Transport Fraction (TF) of methotrexate, expressed as fraction of the drug appearing in fetal vein, during study period of 5 minutes averaged 24.00 + 2.50% of bolus dose while antipyrine TF averaged 68.73 + 2.01% of injected bolus dose, representing 24.00 percent of reference marker value. Student's t-test showed methotrexate and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, absorption and elimination rates of study and reference substances showed varying differences., Conclusions: We report for the first time that the transport of methotrexate from maternal to fetal circulation is not negligible in human placenta at term. It is reasonable to assume that a direct risk for the fetus from methotrexate use in pregnancy cannot be excluded, and caution is warranted when it is used in emergency clinical situations.

Objective: To assess maternal-fetal status of essential trace elements such as copper, iron, molybdenum, selenium and zinc, in experimentally induced diabetic and control pregnant rats, and to correlate the findings with those observed in human diabetic pregnancies. Fetal-maternal ratios of the elements and Cu:Zn and Cu:Fe ratios were also computed in control and study groups., Methods: Diabetes was experimentally induced in pregnant Sprague Dawley rats by injection of streptozotocin. A cocktail of essential trace elements along with antipyrine as internal reference marker were then injected intra-peritoneally to diabetic and matched control pregnant rats on the 20th day of pregnancy. Maternal and fetal blood and tissue samples were collected after sacrificing the animals at 30- and 60-minutes following cocktail injection. Concentrations of trace elements and antipyrine in various blood and tissue samples were then determined by atomic absorption spectrophotometry and colorimetry, respectively., Results: Concentrations of Cu, Fe, Mo, Se, Zn, and antipyrine averaged 2907.0 +/- 212.0 microg/L, 3950.0 +/- 766.0 microg/L, 15.8 +/- 1.7 microg/L, 74.8 +/- 6.5 microg/L, 726.4 +/- 67.4 microg/L, and 170.5 +/- 8.2 mg/L, respectively, in maternal blood in control pregnant rats (n = 5) at day 20 in the 30-minute study phase, while in the diabetic group (n = 5) the values of the various trace element concentrations and antipyrine averaged 2875.0 +/- 225.0 microg/L, 5875.0 +/- 688.0 microg/L, 21.2 +/- 2.1 microg/L, 116.0 +/- 3.6 microg/L, 753.0 +/- 71.3 microg/L, and 171.7 +/- 4.2 mg/L, respectively. Unpaired student's t-test showed that Fe and Se levels were significantly higher (p < 0.05) in the diabetic pregnant rats compared to controls. Cu, Mo and Zn values, however, were not significantly different (p > 0.05) between the two groups. Cu:Zn and Cu:Fe ratios showed varying differences between maternal and fetal samples in the control and study groups., Conclusions: Considering the disparity of results in pregnant diabetic rats and pregnant diabetic women, we urge exercising caution when comparing data from animal studies to human situations.

Objective: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal-maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population., Methods: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry., Results: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2 microg/l, respectively, in maternal venous blood in the pregnant women (n=39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p>0.05) in the mother-child pairs studied. However, neonatal weight correlated negatively (p<0.05) with umbilical venous Cu level. Placental weight correlated positively (p<0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood., Conclusions: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.

Objective: The status of essential trace elements such as copper, iron, zinc, selenium and molybdenum was investigated in gestational diabetic pregnancies at term, and data were compared to control pregnancies. Fetal/maternal ratios of the elements and copper/zinc ratio were also computed in control and study populations., Methods: Samples from maternal venous, umbilical artery and umbilical vein were collected from gestational diabetic and control pregnant women, at the time of spontaneous delivery or Cesarean section, and concentrations of various trace elements were determined by atomic absorption spectrophotometry., Results: The concentrations of copper, iron, molybdenum, selenium and zinc averaged 2156.2 microg/l, 2020.1 microg/l, 13.1 microg/l, 102.3 microg/l and 656.2 microg/l, respectively, in maternal venous blood in control pregnant women at term (n=15) while in the corresponding gestational diabetic group (n=15), concentrations of the trace elements averaged 2345.8 microg/l, 2061.6 microg/l, 15.0 microg/l, 75.2 microg/l and 610.3 microg/l, respectively. Student's t test showed that the selenium concentration was significantly lower (p<0.05)in the diabetic group compared to controls. Values of other elements were not significantly different. Umbilical blood/maternal blood ratios of the trace elements showed varying differences. The Cu/Zn ratio was found to be significantly different between umbilical and maternal samples of control and study groups, indicating a possibility of compromised antioxidant function in diabetic pregnancies., Conclusions: We speculate that altered maternal-fetal status of some essential trace elements in gestational diabetes patients could have deleterious influences on the health of the mother as well as the fetus and newborn.