Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Recent Insights and Recommendations for Preventing Excessive Gestational Weight Gain.

Recommendations for weight gain during pregnancy are based on pre-pregnancy body mass index (BMI). Pregnancy is a risk factor for excessive weight gain and many endocrine problems, making it difficult to return to pre-pregnancy weight and increasing the risk of postpartum obesity and, consequently, type 2 diabetes and metabolic syndrome. Both excessive gestational weight gain (EGWG) and obesity are associated with an increased risk of gestational hypertension, pre-eclampsia, gestational diabetes, cesarean section, shoulder dystocia, and neonatal macrosomia. In the long term, EGWG is associated with increased morbidity and mortality, particularly from diabetes, cardiovascular disorders, and some cancers. This study aims to present recommendations from various societies regarding weight gain during pregnancy, dietary guidance, and physical activity. In addition, we discuss the pathophysiology of this complication and the differential diagnosis in pregnant women with EGWG. According to our research, inadequate nutrition might contribute more significantly to the development of EGWG than insufficient physical activity levels in pregnant women. Telehealth systems seem to be a promising direction for future EGWG prevention by motivating women to exercise. Although the importance of adequate pre-pregnancy weight and weight gain during pregnancy is well known, an increasing number of women gain excessive weight during pregnancy.

Association of DPP-4 Concentrations with the Occurrence of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain.

Gestational diabetes mellitus (GDM) is considered one of the most common diseases that occur during pregnancy. In addition to increasing the risk of numerous complications throughout gestation, it is also believed to have a long-term potential to impact the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease for the mother and her offspring. While there are clear guidelines for healthy weight gain in pregnancy depending on pre-pregnancy BMI, as well as dietary and training recommendations to achieve this, an increasing number of women are experiencing excessive gestational weight gain (EGWG). Such patients have a higher risk of developing GDM and gestational hypertension, as well as requiring caesarian delivery. Dipeptidyl peptidase-4 (DPP-4) is a glycoprotein that seems to play an important role in glucose metabolism, and inhibition of its activity positively affects glucose regulation. The aim of our study was to compare DPP-4 concentrations in patients with GDM and EGWG with healthy women. DPP-4 levels were assessed in serum and urine samples collected on the day of delivery. The bioelectrical impedance analysis (BIA) method was also used to analyze the body composition of patients on the second day of the postpartum period. DPP-4 serum concentrations were significantly higher in patients in the GDM and EGWG groups compared to healthy women. Urinary DPP-4 concentrations were significantly higher in the control and GDM groups than in the EGWG group. Serum DPP-4 levels were positively correlated with BMI measured before pregnancy, on the delivery day, and in the early postpartum period, among other factors. According to our knowledge, this is the first study to determine DPP-4 levels in EGWG patients. DPP-4 may be related to the occurrence of GDM and EGWG; however, this requires further research.

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus 2.0.

Gestational diabetes mellitus (GDM) has become a major public health problem and one of the most discussed issues in modern obstetrics. GDM is associated with serious adverse perinatal outcomes and long-term health consequences for both the mother and child. Currently, the importance and purposefulness of finding a biopredictor that will enable the identification of women with an increased risk of developing GDM as early as the beginning of pregnancy are highly emphasized. Both "older" molecules, such as adiponectin and leptin, and "newer" adipokines, including fatty acid-binding protein 4 (FABP4), have proven to be of pathophysiological importance in GDM. Therefore, in our previous review, we presented 13 novel biomolecules, i.e., galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, FABP4, fibroblast growth factor 21, and lipocalin-2. The purpose of this review is to present the potential and importance of another nine lesser known molecules in the pathogenesis of GDM, i.e., 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), angiopoietin-like protein-8 (ANGPTL-8), nesfatin-1, afamin, adropin, fetuin-A, zonulin, secreted frizzled-related proteins (SFRPs), and amylin. It seems that two of them, fetuin-A and zonulin in high serum levels, may be applied as biopredictors of GDM.

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women. Its early diagnosis seems to have a significant impact on the developing fetus, the course of delivery, and the neonatal period. It may also affect the later stages of child development and subsequent complications in the mother. Therefore, the crux of the matter is to find a biopredictor capable of singling out women at risk of developing GDM as early as the very start of pregnancy. Apart from the well-known molecules with a proven and clear-cut role in the pathogenesis of GDM, e.g., adiponectin and leptin, a potential role of newer biomolecules is also emphasized. Less popular and less known factors with different mechanisms of action include: galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, fatty acid-binding protein 4 (FABP4), fibroblast growth factor 21, and lipocalin-2. The aim of this review is to present the potential and significance of these 13 less known biomolecules in the pathogenesis of GDM. It seems that high levels of FABP4, low levels of irisin, and high levels of under-carboxylated osteocalcin in the serum of pregnant women can be used as predictive markers in the diagnosis of GDM. Hopefully, future clinical trials will be able to determine which biomolecules have the most potential to predict GDM.

Local elasticity of the aorta in patients with type 2 diabetes mellitus.

OBJECTIVE: Arterial elasticity is important for assessing the state of an artery. This cross-sectional study aimed to non-invasively examine stiffness parameters of the ascending aorta in patients with type 2 diabetes mellitus (T2DM). METHODS: We studied 58 patients, including 38 with T2DM and 20 controls. The stiffness of the aorta was evaluated during transthoracic echocardiography. Aortic parameters of stiffness, such as the stiffness index, elasticity index, and compliance index, were calculated using the aortic maximal diameter, aortic minimal diameter, and blood pressure. RESULTS: Pulse pressure values were significantly higher patients with T2DM than in controls. The ß index was significantly higher in patients with T2DM lasting for >7 years compared with those with T2DM lasting for <7 years. Mean aortic compliance was significantly lower in patients with a longer duration of diabetes than in those with a shorter duration of diabetes. Aortic elasticity was significantly lower in patients with diabetes and arterial hypertension compared with patients without diabetes with concomitant arterial hypertension. CONCLUSIONS: Patients with T2DM, especially when T2DM is long-term, have increased stiffness and decreased compliance of the ascending aorta. Pulse pressure, which is a cardiovascular risk factor, is also significantly increased in patients with T2DM.

Circulating Endothelial Microparticles and Aortic Stiffness in Patients with Type 2 Diabetes Mellitus.

Diabetes mellitus represents a metabolic disorder the incidence of which has been on the increase in recent years. The well-known long-term complications of this disease encompass a wide spectrum of renal, neurological and cardiovascular conditions. The aim of the study was to investigate the serum concentration of endothelial microparticles (EMPs) as well as selected noninvasive parameters of the ascending aorta stiffness calculated with echocardiography. In this study, 58 patients were enrolled-38 subjects diagnosed with type 2 diabetes mellitus (T2DM) and 20 healthy controls. The analyzed populations did not differ significantly with respect to age, renal function, systolic and diastolic blood pressure. The patients with diabetes and concomitant hypertension presented higher levels of EMPs in comparison with diabetic normotensive subjects. Among patients with diabetes and hypertension, aortic stiffness assessed with the elasticity index (Ep) was higher and the aortic compliance index (D) lower than in the diabetic normotensive group. No correlation between the amount of EMPs and lipid profile, C-reactive protein (CRP) level and glycemia, was observed in the studied group. There was, however, a statistically significant positive correlation between the creatinine level and amount of EMPs, while the negative relationship was documented for EMPs level and the estimated glomerular filtration rate (eGFR).

Leptin and Ghrelin in Excessive Gestational Weight Gain-Association between Mothers and Offspring.

Two-thirds of pregnant women exceed gestational weight gain recommendations. Excessive gestational weight gain (EGWG) appears to be associated with offspring's complications induced by mechanisms that are still unclear. The aim of this study was to investigate whether umbilical cord leptin (UCL) and ghrelin (UCG) concentrations are altered in full-term neonates born to EGWG mothers and whether neonatal anthropometric measurements correlate with UCL and UCG levels and maternal serum ghrelin and leptin as well as urine ghrelin concentrations. The study subjects were divided into two groups, 28 healthy controls and 38 patients with EGWG. Lower UCL and UCG levels were observed in neonates born to healthy mothers but only in male newborns. In the control group UCG concentrations correlated positively with neonatal birth weight, body length and head circumference. In the control group maternal serum ghrelin levels correlated negatively with neonatal birth weight, body length and head circumference as well as positively with chest circumference. In the EGWG group UCG concentrations correlated negatively with neonatal birth weight and birth body length. UCL correlated positively with birth body length in EGWG group and negatively with head circumference in the control group. In conclusion, EGWG is associated with disturbances in UCL and UCG concentrations.

Associations between Fatty Acid-Binding Protein 4⁻A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus.

There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.

Vaspin in Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain.

Background and objectives: Data concerning vaspin in obstetric aspects are limited and conflicting. The aim of the study was to evaluate vaspin concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) in the early post-partum period (i.e., 48 h after delivery), when placental function no longer influences the results. Materials and Methods: The study subjects were divided into two groups of 28 healthy controls and 38 mothers with EGWG. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of vaspin, fatty acid-binding protein 4 (FABP4), leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Results: Serum vaspin levels were lower in the EGWG group, whereas no significant differences were noted between the groups, with regard to the urine vaspin concentrations. In both studied groups, the serum vaspin concentrations correlated positively with the urine FABP4 levels and negatively with gestational weight gain, body mass index gain in the period from pre-pregnancy to 48 h after delivery (ΔBMI), and fat tissue index (FTI). In the multiple linear regression models, the serum vaspin concentrations were positively dependent on the serum FABP4 levels, as well as negatively dependent on triglycerides, FTI, and ΔBMI. Conclusions: Our study revealed that the EGWG mothers were characterized by significantly lower serum vaspin concentrations in the early post-partum period compared with the subjects that had appropriate gestational weight gain. Our observation supports previous hypotheses that vaspin might be used as a marker of lipid metabolism in pregnancy and maternal adipose tissue. Considering the fact that FABP4 is widely referred to as a pro-inflammatory adipokine, further research on the protective role of vaspin seems crucial, especially in the context of its relationship to FABP4.

FABP4 in Gestational Diabetes-Association between Mothers and Offspring.

Fetuses exposed to gestational diabetes mellitus (GDM) have a higher risk of abnormal glucose homeostasis in later life. The molecular mechanisms of this phenomenon are still not fully understood. Fatty acid binding protein 4 (FABP4) appears to be one of the most probable candidates involved in the pathophysiology of GDM. The main aim of the study was to investigate whether umbilical cord serum FABP4 concentrations are altered in term neonates born to GDM mothers. Two groups of subjects were selected-28 healthy controls and 26 patients with GDM. FABP4, leptin, and ghrelin concentrations in the umbilical cord serum, maternal serum, and maternal urine were determined via an enzyme-linked immunosorbent assay. The umbilical cord serum FABP4 levels were higher in the GDM offspring and were directly associated with the maternal serum FABP4 and leptin levels, as well as the prepregnancy body mass index (BMI) and the BMI at and after delivery; however, they correlated negatively with birth weight and lipid parameters. In the multiple linear regression models, the umbilical cord serum FABP4 concentrations depended positively on the maternal serum FABP4 and negatively on the umbilical cord serum ghrelin levels and the high-density lipoprotein cholesterol. There are many maternal variables that can affect the level of FABP4 in the umbilical cord serum, thus, their evaluation requires further investigation.

Umbilical Cord SFRP5 Levels of Term Newborns in Relation to Normal and Excessive Gestational Weight Gain.

Among the new adipokines, secreted frizzled-related protein 5 (SFRP5) is considered to prevent obesity and insulin resistance. The umbilical cord SFRP5 levels have not yet been investigated. The main aim of the study was to investigate whether the umbilical cord SFRP5 concentrations are altered in term neonates born to mothers with excessive gestational weight gain (EGWG). Two groups of subjects were selected depending on their gestational weight gain, i.e. 28 controls and 38 patients with EGWG. Umbilical cord and maternal serum SFRP5 levels were lower in the EGWG group. Umbilical cord SFRP5 concentrations were directly associated with the maternal serum SFRP5, hemoglobin A1c and lean tissue index, umbilical cord leptin levels, as well as newborns' anthropometric measurements in the EGWG subjects. In multiple linear regression models performed in all the study participants, umbilical cord SFRP5 concentrations depended positively on the maternal serum SFRP5, ghrelin, and leptin levels and negatively on the umbilical cord ghrelin levels, low-density lipoprotein cholesterol, pre-pregnancy body mass index, and gestational weight gain. EGWG is associated with disturbances in SFRP5 concentrations. Obstetricians and midwives should pay attention to nutrition and weight management during pregnancy.

Fatty Acid-Binding Protein 4-An "Inauspicious" Adipokine-In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus.

The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

Ghrelin in Serum and Urine of Post-Partum Women with Gestational Diabetes Mellitus.

Women with a previous history of gestational diabetes mellitus (GDM) have a significantly increased risk of developing type 2 diabetes, obesity, and cardiovascular diseases in the future. The aim of the study was to evaluate ghrelin concentrations in serum and urine in the GDM group in the early post-partum period, with reference to laboratory results, body composition, and hydration status. The study subjects were divided into two groups, that is, 28 healthy controls and 26 patients with diagnosed GDM. The maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. The concentrations of ghrelin in the maternal serum and urine were determined via enzyme-linked immunosorbent assay (ELISA). The laboratory and BIA results of the mothers with GDM were different from those without GDM. Urine ghrelin positively correlated with serum ghrelin and high-density lipoprotein cholesterol (HDL) levels in healthy mothers. There were direct correlations between urine ghrelin and HDL as well as triglycerides levels in the GDM group. Neither the lean tissue index nor body cell mass index were related to the serum ghrelin concentrations in this group. Only the urine ghrelin of healthy mothers correlated with the fat tissue index. Our results draw attention to urine as an easily available and appropriable biological material for further studies.

Is glyburide safe in pregnancy?

The clinical recognition and adequate treatment of women with hyperglycemia during pregnancy is significant in order to reduce neonatal complications correlated with gestational diabetes mellitus (GDM). The traditional management of pregnant patients with GDM in whom diet restriction is not sufficient enough involves subcutaneous insulin administration. However, insulin therapy has several disadvantages. It is therefore highly desirable to find an effective alternative to insulin. Glyburide (also known as glibenclamide) is currently classified as Category C by the U.S. Food and Drug Administration (FDA) for use in pregnancy. Despite the fact that the FDA does not approve glyburide for the treatment of GDM, the American College of Obstetricians and Gynecologists (ACOG) recommended in 2013 that: "when pharmacologic treatment of GDM is indicated, insulin and oral medications are equivalent in efficacy, and either can be an appropriate first-line therapy". These conflicting standpoints result from published contradictory data concerning the risks and benefits of the use of glyburide for the treatment of women with GDM. In this focused review we first present the current state of knowledge about the pharmacokinetics and pharmacodynamics of glyburide, including aspects of the transplacental transport and placental metabolism of the drug, and then we comment on several clinical studies describing the use of glyburide for the treatment of women with GDM. Since the contradictory data primarily concern the transfer of glyburide across the placenta, further rigorous scientific researches focusing on this issue are required in order to develop evidence-based recommendations for the use of glyburide for the treatment of women with GDM.

Rational for statin use in psoriatic patients.

Psoriasis represents a common skin disease which is clinically manifested by chronic cutaneous lesions. It has been observed that psoriasis is associated with an increased risk of cardiovascular diseases, which is contributed to the inappropriate lipid metabolism. Statins are commonly used in clinical practice to lower cholesterol concentration and, accordingly, decrease the individual risk of developing a cardiovascular episode. There have been reports that statin administration could also result in better management of psoriasis. The observed beneficial effects are contributed to the effects on lipid metabolism, including that in skin, as well as anti-inflammatory and immunomodulatory properties of statins. Simvastatin and atorvastatin were found to improve the clinical outcome in patients with psoriatic skin lesions. Clinically, the effectiveness of this novel treatment was confirmed by the significant reduction in PASI score. To date several cases have been reported in which atorvastatin or pravastatin worsened psoriasis. Based on these results, it seems that statins represent a promising class of medications which could be extensively used in psoriasis.

[Treatment of obstetric cholestasis with polyunsaturated phosphatidylcholine and ursodeoxycholic acid]. / Leczenie cholestazy ciarnmych za pomoc4 wielonienasyconej fosfatydylocholny i kwasu ursodezoksycholowego.

OBJECTIVE: Analysis of obstetric outcomes and laboratory results depending on blood serum level of bile acids (BA) in patients with obstetric cholestasis before treatment. MATERIAL AND METHODS: The study was conducted among 43 pregnant women with obstetric cholestasis. The study population was divided into 3 groups, depending on blood serum level of bile acids before treatment: I group (n = 15)--BA 11-15 micromol/l, II group (n = 13)--BA 15-20 micromol/1 and III group (n = 15)--BA > 20 micromol/. Polyunsaturated phosphatidylcholine (PPC) treatment was used in I group, ursodeoxycholic acid (UDCA) in II group and combination of them in III group. Blood serum levels of transaminases, alkaline phosphatase and bilirubin were determined before treatment and during delivery Bile acids concentrations were also assessed during delivery in maternal serum and cord blood. RESULTS: No significant statistical difference was observed in patients age, number of primiparas, delivery method, neonatal birth weight and Apgar score. The earliest obstetric cholestasis diagnosis was observed in III group. Earlier pregnancy termination, higher transaminases and bile acids levels before treatment, larger differences (A) of transaminases and bile acids levels before treatment and during delivery as well as larger A in bile acids levels before treatment and in cord blood during delivery were observed in III group in comparison to I group. CONCLUSIONS: It seems that combined therapy with UDCA and PPC could be considered in obstetric cholestasis, especially in case of its early onset and/or severe course.

A comparative analytical assessment of iodides in healthy and pathological human thyroids based on IC-PAD method preceded by microwave digestion.

The aim of the study was to examine correlations between the content of iodides in 66 nodular goiters and 100 healthy human thyroid tissues (50- frozen and 50 formalin-fixed). A fast, accurate and precise ion chromatography method on IonPac AS11 chromatographic column (Dionex, USA) with a pulsed amperometric detection (IC-PAD) followed by alkaline digestion with tetramethylammonium hydroxide (TMAH) in a closed system and with the assistance of microwaves was developed and used for the comparative analysis of two types of human thyroid samples. Statistical analysis revealed over eightfold reduction of iodine concentration in the pathological tissues (the mean value was 77.13±14.02 ppm) in comparison with the control group (622.62±187.11 ppm for frozen samples and 601.49±192.11 ppm for formalin-fixed ones). A good correspondence (for 10 additional determinations) between the certified (3.38±0.02 ppm with variation coefficient (V.C.) of 0.59% for Standard Reference Material (SRM) NIST 1549-non-fat milk powder) and the measured iodine concentrations (3.52±0.29 ppm; V.C.=10%) was achieved. It was pointed out that the way of tissue preservation (either in formalin or by freezing) had no significant effect on the iodine determination result (α=0.1). Significantly lower iodide content was found in nodular goiter thyroid samples. The applied conditions of digestion, reinforced by the action of microwaves, brought about a decidedly shorter (less than 20 min) sample preparation time. Suitability of the developed IC method was supported by validation results.

Glyburide for the treatment of gestational diabetes mellitus.

Insulin is the traditional treatment for gestational diabetes mellitus (GDM) unresponsive to dietary interventions. Until recently, oral hypoglycemic drugs had been contraindicated due to concerns regarding teratogenicity and the possibility of neonatal hypoglycemia. In contrast to other sulfonylurea drugs, in vitro and in vivo investigations have demonstrated very low transplacental transport of glyburide to the fetal circulation. The mechanisms preventing glyburide from crossing the human placenta are not completely understood. A combination of extremely high protein binding and a relatively short elimination half-life might partially explain it. It has also been demonstrated that glyburide is effluxed from the fetal to the maternal circulation by the breast cancer resistance protein (BRCP) and the human multidrug resistance protein 3 (MRP3). Since 2000, several studies have reported an 80-85% success rate of glyburide treatment. However, some authors have noticed glyburide-related increased risk of preeclampsia, macrosomia, neonatal hypoglycemia, admission to a neonatal intensive care unit and need for phototherapy. These possible maternal as well as neonatal adverse outcomes warrant further investigations. Until that time, the use of glyburide should remain inadvisable in pregnancy.

Effects of amlodipine, diltiazem, and verapamil on the anticonvulsant action of topiramate against maximal electroshock-induced seizures in mice.

To assess the effect of 3 calcium channel antagonists (amlodipine, diltiazem, and verapamil) on the anticonvulsant action of topiramate (a new generation antiepileptic drug) in the mouse maximal electroshock seizure (MES) model. Amlodipine (20 mg/kg) significantly enhanced the anticonvulsant activity of topiramate in the MES test in mice, reducing its ED50 value from 54.83 to 33.10 mg/kg (p < 0.05). Similarly, diltiazem (5 and 10 mg/kg) markedly potentiated the antiseizure action of topiramate against MES, lowering its ED50 value from 54.83 to 32.48 mg/kg (p < 0.05) and 28.68 mg/kg (p < 0.01), respectively. In contrast, lower doses of amlodipine (5 and 10 mg/kg) and diltiazem (2.5 mg/kg) and all doses of verapamil (5, 10, and 20 mg/kg) had no significant impact on the antiseizure action of topiramate. Pharmacokinetic verification of the interaction of topiramate with amlodipine and diltiazem revealed that neither amlodipine nor diltiazem affected total brain topiramate concentration in experimental animals, and thus, the observed interactions were concluded to be pharmacodynamic in nature. The favorable combinations of topiramate with amlodipine or diltiazem deserve more attention from a clinical viewpoint because the enhanced antiseizure action of topiramate was not associated with any pharmacokinetic changes in total brain topiramate concentration.