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Copyright of Archives Medical Review Journal / Arsiv Kaynak Tarama Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Methyldopa and amlodipine were the most frequently prescribed in the first trimester. • Nifedipine was the most frequently prescribed antihypertensive during pregnancy. • The MCM risk of first-trimester antihypertensives was not suggested. • The MCM risk of first-trimester amlodipine and methyldopa was not suggested. To evaluate the major congenital malformation (MCM) risk of first-trimester antihypertensive exposure, specifically of amlodipine and methyldopa. A large administrative claims database was used. The prevalence of antihypertensive prescriptions during pregnancy was described in 91,390 women giving birth between 2010 and 2019. The MCM risk of first-trimester antihypertensives was evaluated in 1,185 women diagnosed with hypertensive disorders in the first trimester. The MCM risk of first-trimester amlodipine and methyldopa was evaluated in 178 women who were prescribed antihypertensives in the first trimester. Antihypertensives were prescribed to 278 (0.30%) women during their first trimester. The prescription prevalence in the first trimester was highest for methyldopa (115, 0.13%), followed by amlodipine (55, 0.06%). Antihypertensives were prescribed to 2,955 (3.23%) women during pregnancy. Nifedipine (903, 0.99%) and nicardipine (758, 0.83%) were the most frequently prescribed oral and injectable antihypertensives during pregnancy, both with a significant increase in annual prevalence. Of the 1,185 women diagnosed with hypertensive disorders in the first trimester, antihypertensives were prescribed to 178 women. The adjusted odds ratio (aOR) of MCMs in the first-trimester prescription of any antihypertensive medication was 1.124 (95% confidence interval [CI], 0.618–2.045). Amlodipine and methyldopa were prescribed to 44 and 93 of the 178 women, respectively. The aORs of MCMs in the first-trimester prescription of amlodipine and methyldopa were 1.219 (95% CI, 0.400–3.721) and 0.921 (0.331–2.564), respectively. The MCM risk of first-trimester exposure to antihypertensives, including amlodipine and methyldopa, was not suggested. [ABSTRACT FROM AUTHOR]

Introduction/Background: Acitretin is a second-generation systemic retinoid. Its clinical applications are virtually exclusively limited to dermatology. It has anti-inflammatory, antiproliferative, and antikeratinizing effects. However, there is a lack of articles summarizing the relevant literature in a systemic way. Methods: A PubMed search was performed using keywords such as "retinoids," "acitretin," "etretinate," and "retinoid embryopathy" to identify relevant original articles, case series, and case reports. Results: The most commonly used application of acitretin, a second-generation systemic retinoid is in the treatment of psoriasis. It has been used in various other dermatological disorders (keratoderma, ichthyosis, pityriasis rubra pilaris, and lichen planus) as a stand-alone therapy or may be combined with other topical and systemic agents. As the drug is not an immunosuppressive agent, hence can be given safely to patients suffering from human immunodeficiency virus and taking highly active antiretroviral therapy. The drug can be given safely in the pediatric as well as the adult population. Although adverse effects are common usually minor and self-limiting and can be managed easily without stopping the drug. The main side effects of the drug include teratogenicity, hepatotoxicity, and hyperlipidemia which should be monitored regularly. It should be avoided or used cautiously in patients taking methotrexate, cyclosporine, and corticosteroids. Conclusions: This article has discussed various uses of acitretin in dermatology, its side effect profile, indication, contraindication, and drug interactions. The drug can be administered safely and successfully with the right patient selection, progressive dose increase, careful monitoring, and appropriate patient counseling. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Accumulating studies have demonstrated the potential activity of ginger in treating and manage several diseases whoever little is known about its protective effects against teratogenicity of chemical toxins. Thus, in this study, we have evaluated the protective effect of gingerol fraction (GF) against methyl ethyl ketone (MEK) induced teratogenic effects in newborn of mice. MATERIALS AND METHODS: A total of 30 mature females and fifteen male mice (Mus musculus) weighing 25-30 g were included in this study. The pregnant mice were divided into three groups (10 mice each); control group (GI, mice received normal drinking water; NDW), methyl ethyl ketone (MEK) treated group (GII, received MEK at a dose of 350 mg/kg body weight in NDW), and GF treated group (GIII; mice received GF at a dose of 25 mg/kg in NDR). Histological analysis, cellular oxidative, and antioxidant enzymes, fibrosis, and apoptosis of brain, liver, and kidney tissues were estimated by histological and immunoassay techniques. RESULTS: In this study, the treatment of pregnant female mice with gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. A significant improvement in cellular antioxidant enzymes GSH, SOD, and peroxidase activities along with a reduction in the initiation of cellular oxidative free radicals (TBARS) was reported in GF treated mice compared to mice intoxicated with MEK (350 mg/kg). In addition, a significant reduction in cellular fibrosis and apoptosis was reported in all tissues of mothers and their offspring's following treatment with GF. HPLC analysis of ginger extracts estimated a set of polyphenolic compounds such [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol which are responsible for the antioxidant, anti-fibrotic, and anti-apoptotic protective effects against teratogenic effects of MEK. CONCLUSIONS: Gingerol fractions (GF) at a dose of 25 mg/kg significantly predicted all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. The beneficial effects of ginger phenolic compounds; [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol against teratogenic effects of MEK proceeded through their antioxidant, anti-fibrotic, and anti-apoptotic properties. [ABSTRACT FROM AUTHOR]

Acne vulgaris is quite common during adolescence but also occurs in children, adults, and pregnant women. It is a condition in which androgens are produced during puberty and induce hypertrophy of the sebaceous glands, and the excess secretory rate in predisposed individuals triggers acne. Sebum promotes the growth of a resident anaerobic bacterium on the skin, Propionibacterium acnes (P. acnes) also known as Cutibacterium acnes (C. acnes). Acne affects areas of the skin with large numbers of sebaceous glands. Treatment of acne can be done topically with retinoids, azelaic acid, benzoyl peroxide or topical antibacterials or systemically with oral antibacterials, hormonal therapies or isotretinoin. The pharmacist plays a particularly important role in educating patients about correct skin care products and medications used to treat acne, especially in women of childbearing age. This article is an update of the 2020 version and includes new insights regarding acne vulgaris. [ABSTRACT FROM AUTHOR]

Valproate (VPA) is an effective treatment for epilepsy and also used in bipolar disorder. However, VPA is associated with a significant risk of birth defects and developmental disorders if used during pregnancy. This has led to the introduction of measures to reduce the use of valproate in women of childbearing potential such as the 'Prevent' pregnancy prevention program (PPP) and the completion of an annual risk acknowledgement form (ARAF). The aim of the current audit was to assess compliance with the guidance. An audit tool was made available to neurologists registered with the Association of British Neurologists (ABN) and to epilepsy nurse specialists via the Epilepsy Nurses Association (ESNA) in the UK. Data were collected between November 2020 and March 2021. The main indication for valproate was generalised epilepsy (55.8%), followed by focal (22.5%). For most, there was documentation that the woman had been informed about the risks associated with taking valproate during pregnancy (93.1%) and the need to be on highly effective contraception or that this was not deemed appropriate (92.2%). A signed ARAF was available in the notes for 81.2% although only 66% were <12 months old. Although information had been made available for most women, there were still individuals where this was not documented. Further work is needed to facilitate identification of women taking valproate and implementation of a digital ARAF. For clinicians, the audit highlights a need to carefully counsel women about the teratogenic risks of continuing to take valproate versus the risk of deteriorating seizure control if the drug is withdrawn. This is particularly true of women with focal epilepsy, where there may be safer, equally effective, alternative anti-seizure medication (ASM). The aim should be to create a partnership of trust between the patient and clinician in order to arrive at the best clinical decision for that individual. [ABSTRACT FROM AUTHOR]

Copyright of Actualités Pharmaceutiques is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: We aim to report the major congenital malformation (MCM) rates for new and old anti-epileptic drugs (AED) exposures during the first trimester of pregnancy in women with epilepsy (WWE).Methods: We extracted relevant data on drug exposure and malformation rate from the records of a prospective observational registry (Kerala Registry of Epilepsy and Pregnancy) for all completed pregnancies between 1998 and 2019. A comprehensive and uniform criterion with detailed guideline was used for assessment of malformations. We employed generalised linear model to generate adjusted incidence rate ratios (aIRR) of MCM in AED exposed group as compared to AED unexposed group, after adjustment for age and educational status of mothers' and epilepsy classification.Results: The unadjusted MCM rate was 6.2% for all the infants included in the study (148/2328); 4.7% for the unexposed group (16/340), and 6.6% for the exposed group (132/1988). The aIRR of MCM as compared to unexposed group was similar for all monotherapies; lamotrigine (0.50; 95% CI 0.07-3.68), levetiracetam (1.16; 0.43-3.11), oxcarbazepine (1.61; 0.62-4.21) valproate (1.71, 0.93-3.19), phenytoin (1.21, 0.51-2.90), carbamazepine (0.99, 0.54-1.82), and phenobarbitone (1.20, 0.52-2.74). However, the point estimates suggest least risk with lamotrigine and highest risk with valproate. Polytherapy with high-dose valproate carried significantly higher risk of MCM as compared to the unexposed group (aIRR=4.12; 2.18-7.79, p<0.001). The aIRR of GTCS during pregnancy was 1.63 (95% CI 1.12-2.37, p = 0.011) for monotherapy with new AEDs (lamotrigine, levetiracetam or oxcarbazepine) as compared to old AEDs (phenobarbitone, phenytoin, carbamazepine, or valproate).Conclusion: The MCM risk was significantly higher for polytherapy with high dose valproate. It did not differ substantially between different AED monotherapies although point estimate was lowest with lamotrigine. Pregnant women on new AEDs report higher likelihood of GTCS than women on old AEDs during pregnancy. [ABSTRACT FROM AUTHOR]

Medication use (both over the counter and prescribed) is common during pregnancy and lactation. However, prescribing in pregnancy can be challenging for several reasons. Firstly, there are physiological changes associated with pregnancy which impact on the pharmacokinetics of medications and, secondly, there is a lack of information regarding potential adverse fetal effects of new medications. Adherence to the safe Principles of prescribing together with patient involvement in decision making is essential when prescribing in pregnancy. In this article, we present three case scenarios devised to illustrate the key principles of safe prescribing antiepileptic drugs, immunosuppression and anticoagulants in pregnancy and their potential teratogenic effects. In addition, we discuss the management of pregnancy complicated with potential teratogenicity. [ABSTRACT FROM AUTHOR]

Background: Animal data suggest teratogenic effects with zonisamide use and risk of pregnancy losses. Human data following zonisamide exposure are presently limited, but suggest low risk of malformation with elevated risk of low birth weight.Objective: To calculate the major congenital malformation (MCM) rate of zonisamide in human pregnancy and assess for a signal of any specific malformation pattern and associations with birth weight.Methods and Materials: Data were obtained from the UK and Ireland Epilepsy and Pregnancy register (UKIEPR) which is an observational, registration, and follow up study from December 1996 to July 2020. Eligibility criteria were use of zonisamide and to have been referred to the UKIEPR before the outcome of the pregnancy was known. Primary outcome was evidence of MCM.Results: From December 1996 through July 2020 there were 112 cases of first trimester exposure to zonisamide, including 26 monotherapy cases. There were 3 MCM for monotherapy cases (MCM rate 13.0% (95% confidence interval 4.5-32.1)), and 5 MCM for polytherapy cases (MCM rate 6.9% (95% confidence interval 3.0-15.2)). While the median birth weight was on 71st and 44th centile for monotherapy and polytherapy cases respectively, there was a high rate of infants born small for gestational age (21% for both).Conclusion: These data raise concerns about a signal for potential teratogenicity with zonisamide in human pregnancy. Given the low numbers reported, further data will be required to adequately counsel women who use zonisamide in pregnancy. [ABSTRACT FROM AUTHOR]

To evaluate the incidence of congenital malformations in children exposed prenatally to antiseizure medications (ASMs), to assess other perinatal and fetal complications, and to determine the potential predictors for these complications. A retrospective review of pregnancy outcomes of women with epilepsy. Patients were followed up at the King Faisal Specialist Hospital and Research Centre, Riyadh and Jeddah, Saudi Arabia, between Dec 1993 and Oct 2020. Of 162 pregnancies included, 10 (6.17%) congenital malformations were observed, 6.82% in ASM-exposed babies versus 3.33% in babies of epilepsy-untreated mothers (P = 0.69). The overall incidence of perinatal and fetal complications was 53%; most frequent were low birth weight (24%), preterm birth (19%), transfer to neonatal intensive care unit (18%) and abortion (8%). These complications were higher in the untreated group (66.67%) than in the ASM group (50%). The use of other non-antiseizure medications during pregnancy was the only factor that significantly increased the risk of complications. Prenatal exposure to ASMs was associated with increased risk of congenital malformations. However, overall perinatal and fetal complications were higher in the untreated group than in the ASM group, which could be explained by maternal seizures. Therefore, taking ASMs to control epilepsy and prevent perinatal complications may outweigh the risks of teratogenicity. [ABSTRACT FROM AUTHOR]

Although Nanoalumina is widely used in many biomedical applications, its potential toxic effect on pregnant women and developing embryos/fetuses has not been reported. In this investigation, the maternal and developmental toxicity caused by Nanoalumina during gestation and the potential preventive role of the pumpkin seed oil (PSO) were evaluated. Four groups of pregnant rats were orally administered during days 5–19 of gestation as follows: control group, Nanoalumina group (70 mg/kg b.w), PSO- group (4 ml/kg b.w.), and Nanoalumina plus PSO- group. Nanoalumina induced detrimental impacts in pregnancy outcomes, fetal growth retardation, morphological anomalies, hepatic and neural DNA damage, and histopathological changes in hepatic and neural tissues of both mother and fetus, respectively. Furthermore, the level of MDA is significantly increased and activities of GSH and CAT are significantly reduced in both tissues of nanoalumina‐administered rats. PSO co administration improved pregnancy outcomes, fetal growth parameters, DNA damage, antioxidant defenses the histopathological changes of nanoalumina‐gavaged rats and significantly diminished MDA level. Finally, PSO has a preventive role against the detrimental impacts of nanoalumina in dams and fetuses probably via its potential to prevent reactive oxygen species. [ABSTRACT FROM AUTHOR]

Oral isotretinoin is an effective agent for the treatment of severe cystic acne. Isotretinoin is a teratogen; there is an increased risk of congenital defects in infants exposed to the drug in the uterus. The Saudi Food and Drug Authority (SFDA) has implemented a pregnancy prevention program (PPP) to protect females from those teratogenic effects. To investigate the awareness of women, of reproductive age who were using Isotretinoin or used it previously, about isotretinoin use and the SFDA-approved PPP in Riyadh, Saudi Arabia. This cross-sectional study was conducted during the period from June to October 2019. A questionnaire was developed based on the published literature and the PPP recommendations. The study was carried out online among female patients who were on Isotretinoin therapy or have used it previously in Riyadh city. The Statistical Package for Social Sciences (SPSS for Windows, version 24) was used to analyze the study data. During the study period, 483 patients participated in the study. Among them, 97.3% reported that they used the drug based on a doctor's prescription, 94.6% were aware of Isotretinoin's teratogenic effect, and 30.6% confirmed their awareness of the PPP. Amongst the participants, 9.1% (n = 44) used Isotretinoin while being married or planning to get married within a one-month period after using it. Concerning the use of two contraceptive methods according to the PPP guidelines, of the participants, 43.2% reported that they have been informed by their healthcare providers to use two contraceptive methods before starting the medication. Also 43.2% reported that they have been informed to use two contraceptive methods while using the medication, and 50% reported that they have been informed to use two contraceptive methods for one month after stopping the medication. Regardless of the information they had, participants' actual practice, was as follow: 15.9% used two contraceptive methods before starting the medication, 15.9% used two contraceptive methods during the treatment, and 13.6% used two contraceptive methods for one month after stopping the medication. Although this study revealed that the vast majority of participants were aware of isotretinoin's teratogenic effect, still a considerable number of them had no idea about the PPP. This issue needs to greatly be addressed to minimize the risk of teratogenicity. [ABSTRACT FROM AUTHOR]

Following recent European Medication Agency restrictions on valproate (VPA) use in girls and women of childbearing potential (WOCP), the Commission on Epilepsy and Gender of the Italian League against Epilepsy integrated current literature and legislative data in order to provide clinicians with guidance on antiseizure medication (ASM) prescription for Idiopathic Generalized Epilepsies (IGEs) in this population, avoiding VPA. We reviewed the updated literature on ASMs and examined the teratogenicity of those showing efficacy in IGEs. For all relevant ASMs, we considered the indications for use and the pregnancy and contraception-related recommendations given in the Italian Summary of Product Characteristics (SmPC) and on the websites of the European Medicines Agency (EMA) and other European Union (EU) countries' regulatory agencies. With the exception of absence seizures, the literature lacks high quality studies on ASMs in IGEs. In girls and WOCP, levetiracetam and lamotrigine should be considered the first-choice drugs in Generalized Tonic-Clonic Seizures Alone and in Juvenile Myoclonic Epilepsy, lamotrigine in Juvenile Absence Epilepsy, and ethosuximide in Childhood Absence Epilepsy. Although supported by the literature, several ASMs are off label, contraindicated or burdened by special warnings in pregnancy. Some discrepancies emerged between the various SmPC warnings for different brands of the same active principle. We provided a therapeutic algorithm for each IGE syndrome and highlighted the need for revised prescription rules, consistent with the latest literature data, uniformity of SmPC warnings for the same active principle, and more data on the efficacy of new ASMs in IGEs and their safety in pregnancy. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of diabetes mellitus (DM) in pregnancy is increasing which may be due to gestational diabetes (diagnosed in second or third trimester) or pre-existing DM like type2. The aim of this systematic review was to discuss the safety and efficacy of the oral anti-diabetic medications in pregnant women. Materials and Methods: Primary and secondary search strategies were used. PubMed, Cochrane and Scopus, EMBASE were used. The search was made using medical subject headings (MeSH) "Diabetes and/or Pregnancy", "Treatment with/and Metformin", "Glyburide and Effectiveness", "Safety and/or Malformations", "Diabetes and/or Teratogenicity". Results: Metformine comparing to the other drugs from the different OAD was the safest drug as it has the less neonatal hypoglycemia affect, lowest risk to develop neonatal malformation, lower rate of gestational hypertension and lower postprandial blood glucose. Also metformine does not cause any alteration in embryonic, no major malformations and no teratoginic effect. Moreover patients on glyburide had significantly higher weight gain compared to patients on metformin. Conclusion: Metformin was found to be effective and the safest option among others with weight benefits for obese and nonobese patients. Also, combining glyburide with metformin can give better glycemic control and better efficacy rate. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are amongst the more frequently prescribed medicines in pregnant women and the use of antibiotics is increasing. However, with limited studies available in this population, the safe use of antibiotics in pregnancy remains a concern. Aim: To evaluate the use of antibiotics amongst pregnant women attending a public health care facility. The main objective of this study was to quantify the types of antibiotics used in pregnant women. Setting: A public hospital classified as a referral hospital located in Durban, KwaZulu-Natal. Methods: Demographic and treatment information of women were collected retrospectively from January 2019 to July 2019. A total of 184 pregnant patients, who received antibiotic therapy, were included in this study. Descriptive and analytical measures were used to analyse both patient demographics and treatment variables. Results: A total of 416 antibiotic prescriptions, issued to 184 patients, were reviewed. Penicillins (39.7%), macrolides (13.0%) and combination penicillin- and beta-lactam inhibitors (12.3%) were reported as the most commonly prescribed antibiotics. Rifamycin (2.9%), hydrazides (2.2%) and aminoglycosides (1.9%) were less frequently prescribed. Most antibiotics were prescribed for diseases of the circulatory system (36.1%). Conclusion: Several classes of antibiotics were used in pregnancy despite the lack of available safety data and clinical evidence. Informing women of the potential side effects and keeping abreast with new information played an important role in the safe, rational and effective use of medicines that contributed to improving maternal health. [ABSTRACT FROM AUTHOR]

Aim: Valproic acid (VPA) is a widely used anti-epileptic drug (AED) of demonstrated efficacy. However, its teratogenic effects have resulted in many regulatory agencies recommending that it should not be administered to women of childbearing age unless they are taking contraceptives. The aim of this study was to determine the willingness of candidate patients to change their treatment and to monitor the evolution of their attitude.Methods: We identified patients aged between 15 and 45 years old who had been diagnosed with epilepsy and were being treated with VPA. A shared decision-making visit was arranged, during which variables related to their epilepsy were recorded. The patients were informed about the teratogenic effects of VPA and the risks/benefits of a change in treatment. The patient, or legal guardian, then freely chose the course of treatment that they wished to follow. On a follow-up visit, six months later, seizure control and tolerance to the chosen treatment were recorded. The variables related to each patient's willingness to their change treatment were analysed.Results: A total of 60 patients, with a median age of 32.7 years, were included in the study. Of these, 25 (41.7%) suffered some form of intellectual disability. Only one (1.7%) had poor seizure control. After the initial visit, 41 patients (68%) opted to continue with the VPA treatment, six opted to stop receiving VPA, and 13 decided to switch to another AED. The median age of the patients who opted to change treatment was significantly lower than that of those who opted to continue with the VPA treatment (29.1 vs. 34.4, p = 0.024). The absence of intellectual disability (p = 0.047) and a length of treatment of less than five years (0.016) were both significantly associated with the decision to change treatment. Of the 19 patients who changed treatment, nine (47%) returned to the initial treatment with VPA.Conclusions: Despite being informed of the teratogenic risk associated with VPA, a significant number of patients and legal guardians opted to continue with this treatment; the reasons given for this were the low possibility of pregnancy and the risk of breakthrough seizures. In almost half the cases studied, the pharmacological alternatives to VPA were poorly tolerated and did not provide a good level of seizure control. [ABSTRACT FROM AUTHOR]

Acne vulgaris is quite common during adolescence but also occurs in children, adults and pregnant women. It is a condition in which androgens are produced during puberty and induce hypertrophy of the sebaceous glands and the excess secretory rate in predisposed individuals, triggers acne. Sebum promotes the growth of a resident anaerobic bacterium on the skin, Propionibacterium acnes (P. acnes). Acne affects areas of the skin with large numbers of sebaceous glands. Treatment of acne can be done topically with retinoids, azelaic acid, benzoyl peroxide or topical antibacterials or systemically with oral antibacterials, hormonal therapies or isotretinoin. The pharmacist plays a particularly important role in educating patients about correct skin care products and medications used to treat acne, especially in women of child-bearing age. [ABSTRACT FROM AUTHOR]

Purpose: On 24/04/2018, the United Kingdom (UK) Medicines and Healthcare Products Regulatory Agency (MHRA) clarified previous policies by issuing a statement, that the use of sodium valproate is contraindicated in women of childbearing potential unless the conditions of a pregnancy prevention programme are met, and only if other treatments are ineffective or not tolerated. We evaluated the impact of this over the first year of implementation in a tertiary epilepsy centre.Methods: Cross-sectional study of all women under active follow up, or newly referred, of childbearing age (16-55 years), taking valproate for the treatment of epilepsy, over 12 months from 01/05/2018.Results: We identified 125 cases, with 31 newly referred in response to MHRA regulations. 9.6% of patients did not attend their appointment, 35.2% had a learning disability (LD), which in 19.2% was sufficiently severe that they could not consent to a sexual relationship. Patients with LD prescribed valproate were significantly younger, and more likely to have a focal or uncharacterised epilepsy than patients without LD. In 46.4% of patients, MHRA regulations were followed: women were already using highly active contraception (HAC), HAC was started, or valproate withdrawn. In 24.8% of cases, women elected to continue valproate, and were not willing to use HAC.Conclusions: In 53.6% of cases, MHRA regulations contraindicating the use valproate in women of childbearing potential could not be followed fully, due to lack of patient attendance, lack of applicability in severe LD, or ethical concerns relating to patient choice. [ABSTRACT FROM AUTHOR]

Purpose: Valproic acid (VPA) is a widely used anticonvulsant that is effective against most seizure types. Due to its teratogenic effects, its use should be avoided among females of childbearing age, unless other treatments are ineffective or not tolerated. This study aimed to determine the prevalence of VPA use in 2005-2018 in Estonia, with special attention to females of childbearing age.Methods: In this retrospective nationwide population-based cohort study, outpatient prescription data from the national health insurance provider were used. Annual sex- and age-specific prevalence rates were calculated, and changes therein during the study period were evaluated.Results: The annual rates of VPA use among females of childbearing age increased significantly in 2005-2014. After 2014, the increasing trend stopped; in 2014-2018, the prevalence rates declined slightly [prevalence rate ratio (PRR), 0.94; P = 0.136]. In males of the same age, the increasing trend continued (PRR, 1.08: P = 0.028). Among neurologists, the rate of VPA prescription to females aged <15 and 15-44 years decreased during 2014-2018 (PRR, 0.74; P < 0.001 and PRR 0.72; P < 0.001, respectively); no change in prescription frequency was seen among psychiatrists during this period.Conclusions: The increasing trend in VPA usage among females of childbearing age in Estonia stopped after 2014, when the European Medicines Agency's strengthened restrictions on VPA use in females were communicated extensively in Estonia. The level of awareness of VPA's harmful effects during pregnancy is lower in the psychiatric community. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is one of the commonest neurological conditions affecting women of reproductive age. Epilepsy management during pregnancy is a clinical conundrum, requiring a balance between seizure control and risk minimization for the women with epilepsy (WWE) as well as for their fetuses. The objective of this comprehensive review is to explore the reproductive health challenges of WWE in sub-Saharan Africa (SSA) and ways to address them.Method: Relevant documentation published until June 2019 were retrieved via literature searches performed in PubMed and Google Scholar, as well as a manual search to identify grey literature.Results: WWE in SSA are generally more stigmatized and sexually exploited than women without epilepsy. Contraception use among WWE was reported only in Senegal (51%) and Kenya (14.7%). Only two prospective studies (one in Senegal and one in Nigeria) investigated pregnancy outcomes for a total of 97 WWE. The prevalence of convulsive epilepsy in pregnancy was estimated at 3.33 per 1000. Among pregnant WWE treated with first line anti-epileptic drugs, 16.2% had miscarriages, 41.9% premature births, and 4.1% had babies with malformations. Carbamazepine, which is frequently prescribed to pregnant WWE in SSA, still entails a 2.1-fold increased risk of congenital malformation. No reports were found concerning pre-conceptual counseling and post-natal outcomes in WWE in SSA.Conclusion: Our review underscores the need for contextualized evidence-based clinical guidelines and a collaborative approach to treat WWE in SSA. High risks of congenital malformations and drug interactions with first line AED warrant the provision of safer second line alternatives. [ABSTRACT FROM AUTHOR]

La prise médicamenteuse au cours de la grossesse peut avoir des conséquences sur le développement de l'embryon et du fœtus, mais aussi sur la santé du nouveau-né. La femme enceinte doit faire le point sur son traitement chronique avec le prescripteur et solliciter le conseil officinal en cas de doute, notamment dans le cadre de l'automédication. Taking medication during pregnancy can have consequences on the development of the embryo and the fetus, but also on the health of the newborn. Pregnant women should review their chronic treatment with their prescriber and seek the advice of their pharmacist if they have any doubt, particularly in the case of self- medication. [ABSTRACT FROM AUTHOR]

Nanotechnology and use of nanomaterials (NMs) improve life quality, economic growth and environmental health. However, the increasing production and use of NMs in commercial products has led to concerns about their potential toxicity on human and environment health, as well as its toxicological classification and regulation. In this context, there is an urgent need to standardize and validate procedures for nanotoxicity testing. Since the zebrafish embryotoxicity test (ZET) has been indicated as a suitable approach for the toxicity assessment of traditional and emergent pollutants, the aim of this review is to summarize the existing literature on embryotoxic and teratogenic effects of NMs on zebrafish. In addition, morphological changes in zebrafish embryos induced by NMs were classified in four reaction models, allowing classification of the mode of action and toxicity of different types of NM. Revised data showed that the interaction and bioaccumulation of NMs on zebrafish embryos were associated to several toxic effects, while the detoxification process was limited. In general, NMs induced delayed hatching, circulatory changes, pigmentation and tegumentary alterations, musculoskeletal disorders and yolk sac alterations on zebrafish embryos. Recommendations for nanotoxicological tests are given, including guidance for future research. This review reinforces the use of the ZET as a suitable approach to assess the health risks of NM exposure. Image 1 • Systematic review on the use of the ZET in NM toxicity assessment. • ZET shown to be an excellent test to assess NM toxicity. • Inorganic NMs more studied (90%) than organic NMs (10%). • Morphological alterations induced by NM were classified in reaction patterns. • Further studies on NM toxicity under environmental conditions are suggested. A critical review about the use of the zebrafish embryotoxicity test (ZET) on nanotoxicity assessments. [ABSTRACT FROM AUTHOR]

Copyright of Archives Medical Review Journal / Arsiv Kaynak Tarama Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Madín Dam is a reservoir located in the municipalities of Naucalpan and Atizapán, in the metropolitan area adjacent to Mexico City. The reservoir supplies drinking water to nearby communities and provides an area for various recreational activities, including kayaking, sailing and carp fishing. Over time, the number of specimens of common carp has notably diminished in the reservoir, which receives direct domestic drainage from two towns as well as numerous neighborhoods along the Tlalnepantla River. Diverse studies have demonstrated that the pollutants in the water of the reservoir produce oxidative stress, genotoxicity and cytotoxicity in juvenile Cyprinus carpio , possibly explaining the reduction in the population of this species; however, it is necessary to assess whether these effects may also be occurring directly in the embryos. Hence, surface water samples were taken at five sites and pharmaceutical drugs, personal care products (especially sunscreens), organophosphate and organochlorine pesticides, and other persistent organic pollutants (e.g., polychlorinated biphenyls and polycyclic aromatic hydrocarbons) were identified. Embryos of C. carpio were exposed to the water samples to evaluate embryolethality, modifications in embryonic development, lipoperoxidation, the quantity of hydroperoxide and oxidized proteins, and antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase). It was found that the polluted water of the Madín Dam gave rise to embryolethality, embryotoxicity, congenital abnormalities, and oxidative stress on the common carp embryos. Image 1 • The water of the Madin dam contains hydrocarbons of various types. • These hydrocarbons in combination with other contaminants from the site produce embryotoxicity in the common carp. • Cyprinus carpio is at risk in the Madín reservoir. The water of the Madín dam contains a complex mixture of pollutants, including hydrocarbons, which produce oxidative stress and embryotoxicity on Cyprinus carpio. [ABSTRACT FROM AUTHOR]

Background This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark. Objective To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men. Methods Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure. Results A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications. Limitations We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects. Conclusions Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better-quality studies are required in this area, particularly studies assessing potential teratogenicity. [ABSTRACT FROM AUTHOR]

Bismuth intoxication is a rare cause of acute kidney injury (AKI) and is usually reversible by appropriate therapeutic measures. We present here a case of an adolescent pregnant girl who developed AKI due to an overdose of colloidal bismuth subcitrate (CBS, total amount of 6 g). She received parenteral chelating agent dimercaprol for 14 days. Continuous venovenous hemodiafiltration (CVVHD) with high-flux membrane was carried out in the first 3 days of chelating therapy and intermittent hemodialysis for 11 days, thereafter. The patient recovered clinically and was discharged after 21 days. She gave birth to a healthy term boy. At the last visit, the baby was 6 months old with normal growth and development as well as normal kidney functions. Neither deterioration in renal functions nor emergence of proteinuria was recorded in the patient during follow-up care after hospital discharge. In cases of AKI due to an overdose of CBS, treatment with dimercaprol combined with high flux hemodiafiltration and subsequently hemodialysis appears to be both useful and safe for bismuth elimination. [ABSTRACT FROM AUTHOR]

Background. Antiepileptic drugs (AEDs), which are commonly used as a treatment for acute phases and prevention of relapses in bipolar disorder (BD) and schizoaffective disorder (SAD), have been often associated to adverse outcomes in pregnancy and major congenital malformations (MCM). We aimed to summarize available evidence assessing these outcomes when AEDs are used in pregnant women with BD and/or SAD. Methods. We searched four databases from inception to 18 January, 2019. We included peer-reviewed observational studies on the use of AEDs in pregnant women with BD or SAD. We excluded studies not reporting data on BD or SAD, not specifying the AED or not assessing pregnancy outcomes or MCM. Results. The pooled records amounted to 2,861. After duplicate removal and inclusion/exclusion criteria application, we included 9 observational studies assessing patients with BD and SAD. The AEDs evaluated were lamotrigine (LTG), valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPR) and gabapentin (GBP). VPA and CBZ were the AED most commonly associated to MCM. LTG showed the best safety profile. Higher rates of complications during pregnancy were observed in treated and untreated women with BD compared to healthy controls. Conclusions. AEDs may produce adverse outcomes in pregnancy and MCM in children of pregnant women with BD or SAD, showing higher risks at higher doses. LTG could be considered in this type of patients, given the low rate of adverse events. VPA and CBZ use should be avoided during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: This paper reports additional data supplementing earlier publications based on Australian Pregnancy Register (APR) data.Method: Over 20 years, the APR has collected Information on pregnancies in Australian women with epilepsy (WWE), untreated WWE and those taking AEDs for other indications. Contact is by telephone, at set intervals. Treatment is not interfered with. Data are analysed using conventional statistical techniques, confidence interval methods, and logistic regression.Results: By 2018, the APR contained details of 2148 pregnancies. AEDs were taken throughout 1972 of the pregnancies (91.8%). The remaining 176 (8.2%) did not receive AEDs, at least early in pregnancy. There were (i) dose-related increased incidences of pregnancies carrying foetal malformations associated with maternal intake of valproate and topiramate when topiramate was a component of AED polytherapy (P < .05), (ii) a similar dose-related trend in relation to carbamazepine intake, (iii) no evidence that levetiracetam and lamotrigine were unsafe from the foetal standpoint, (iv) insufficient data to permit conclusions regarding teratogenicity in relation to other AEDs, and (v) no evidence that pre-conception folate supplementation reduced the hazard of AED-associated foetal malformation. AED polytherapy did not increase foetal hazard unless valproate or topiramate was involved in the AED combination. Genetic factors probably contributed to the malformation hazard. Seizures occurring in earlier pregnancy probably did not contribute to the malformation hazard.Conclusions: If it were not for the importance of maintaining seizure control, the above findings suggest that it would be better to avoid using certain AEDs, particularly valproate and topiramate, during pregnancy. [ABSTRACT FROM AUTHOR]

Mycotoxins are secondary metabolites produced by varieties of fungi that contaminate food and feed resources and are capable of inducing a wide range of toxicity. In the current study, we investigated developmental and behavioural toxicity in zebrafish larvae after exposure to six different mycotoxins; ochratoxin A (OTA), type A trichothecenes mycotoxin (T-2 toxin), type B trichothecenes mycotoxin (deoxynivalenol - DON), and zearalenone (ZEN) and its metabolites alpha-zearalenol (α-ZOL) and beta-zearalenol (β-ZOL). Developmental defects, hatching time, and survival were monitored until 96 h post fertilisation (hpf). The EC 50 , LC 50 , and IC 50 values were calculated. Subsequently, to assess behavioural toxicity, new sets of embryos were exposed to a series of non-lethal doses within the range of environmental and/or developmental concern. Results indicated that all the tested mycotoxins were toxic, they all induced developmental defects, and with the exception of OTA, all affected hatching time. Behavioural effects were only observed following exposure to OTA and ZEN and its metabolites, α ZOL and β ZOL. These results demonstrate that mycotoxins are teratogenic and can influence behaviour in a vertebrate model. [ABSTRACT FROM AUTHOR]

Isotretinoin is an acne medication regulated by the Food and Drug Administration (FDA) iPledge Risk Evaluation and Mitigation Strategy program due to its potential for birth defects. This program enforces monthly pregnancy tests and comprehension quizzes, among other requirements, which results in disproportionate medication access barriers. In December 2021, the iPledge system underwent a series of changes, which resulted in systemwide malfunctions and hour-long phone support line waiting times. Due to growing challenges to isotretinoin access, patients may turn to unregulated over-the-counter vitamin A dietary supplements marketed for acne, despite evidence of similar risk of teratogenicity to isotretinoin. While the FDA has understandably focused its attention to isotretinoin regulation, it should increase oversight of the dietary supplement industry, and practitioners should remain informed of risks of vitamin A supplements. [ABSTRACT FROM AUTHOR]

Highlights • Survey revealed low awareness of teratogenic risk during disease modifying therapy. • Knowledge of potential exposure to healthy partners of male patients was absent. • 10% of female multiple sclerosis patients had experienced unplanned pregnancies. • The internet and the neurologist were key sources of information on family planning. Abstract Background The purpose of the survey was to assess the knowledge of family planning issues associated with disease modifying therapies (DMTs) among patients diagnosed with multiple sclerosis (MS). Methods 590 Danish MS patients responded to an online questionnaire about family planning in MS, collecting demographics, disease characteristics, disease modifying treatment, knowledge of potential teratogenic effects in DMTs, number of children, occurrence of unplanned pregnancies and outcome, and sources of information. Results 488 females and 102 males, mean age 40 years, responded. On average, it was 6.5 and 10.9 years since diagnosis and first symptoms, respectively. 16% of female and 19% of male respondents did not receive DMT at the time of responding to the survey. 30% of all had received only one DMT, 37%, 19%, 8%, and 5% had received two, three, four, and five different treatments, respectively. 42% of female and 74% of male respondents said they did not know if the medication they were taking had teratogenic risks. 83% of females and 85% of males responded that they did not know, whether DMT in male MS patients may expose healthy partners to teratogenic risks; hereto, 13% and 10%, respectively, answered that no transmission occurs. On average respondents had two children; three of four children reported in the study were born prior to the respondents being diagnosed with MS. 50% of both female and male respondents without children wanted a family and 25% of females and 16% of males wanted to start a family within the next two years. 91% of female respondents would discontinue DMT during pregnancy. Among male respondents 32% would continue treatment during a partner's pregnancy and 47% did not know whether they would continue or discontinue treatment. 10% of the female patients had had unplanned pregnancies during MS treatment, of these 49% chose to have an abortion. 53% of all felt they were well informed about MS treatment and family planning. 22% and 41% of the respondents received information from the neurologist about teratogenic risks in female MS patients and about teratogenic risks in women with male MS patients as partners, respectively; 27% and 34%% retrieved information from the internet on these two issues. Conclusion This survey uncovered a low level of knowledge about DMTs’ teratogenic risks among MS patients irrespective of sex. Knowledge about potential teratogenic risks for male MS patients receiving DMTs while planning to start a family was largely absent. 10% of female patients had experienced unplanned pregnancies on MS treatment. In general, patients use the internet and their neurologist to the same extent for information on parenthood planning. [ABSTRACT FROM AUTHOR]

The decline in amphibian populations is a critical threat to global biodiversity, and pesticide pollution is considered as one of the major factors. Although effects of single pesticides on amphibians have been documented, toxicological interactions prevailing in mixtures of pesticides have not been well elucidated. Strobilurin and succinate dehydrogenase inhibitor (SDHI) fungicides are new types of commonly used pesticides. In this study, effects of three strobilurins (pyraclostrobin, trifloxystrobin and azoxystrobin), two SDHIs (isopyrazam and bixafen), and their mixtures on X. tropicalis embryos were fully investigated. Results showed that exposure to individual fungicides induced lethal and teratogenetic effects; and malformed embryos displayed similar phenotypes including microcephaly, hypopigmentation, somite segmentation and narrow fin. Exposure to two strobilurins or two SDHIs at equitoxic concentrations caused additive or synergetic effects at environmentally relevant concentrations. TU for mixtures of isopyrazam and bixafen was 0.53 and 0.30 for lethal and teratogenic toxicity, respectively. Finally, binary mixtures of strobilurins and SDHIs also exhibited additive or synergetic effects on amphibian embryos. Overall, these results reveal that the mixtures of multiple fungicides caused a higher incidence of lethality and teratogenicity of amphibian embryos, compared to a single fungicide at the corresponding doses. Our findings provide important data about the ecotoxicology of agricultural fungicides on non-target organisms, which is useful for guiding management practices for pesticides. [ABSTRACT FROM AUTHOR]

Purpose: Antiepileptic drugs (AEDs), particularly valproate (VPA), are known to be teratogens when taken by women with epilepsy (WWE), but the risk in women who take these drugs for indications other than epilepsy have been little studied. This study aims to investigate the incidence of birth defects in children born to mothers taking AEDs for non-epilepsy indications.Methods: The Australian Pregnancy Register (APR), established in 1998, is a prospective observational study operating with ethical approval and informed written consent for participation. Of the 2066 pregnancies enrolled in the Register, 98% are WWE and the remainder received AEDs for other indications. Data from this Register was analysed to study the rates of congenital malformations (CM) in infants exposed to AEDs in utero in WWE compared to those women taking AEDs for other indications.Results: The malformation rates in pregnancies of WWE taking AEDs (5%), is higher than the rates of infants born to untreated WWE (2%). There were 32 pregnancies enrolled from 29 mothers taking AEDs for indications other than epilepsy (2 women/2 pregnancies were lost to follow up). Out of 30 pregnancies, 9 of which were exposed to VPA, 1 resulted in a child with a malformation (3%) (cleft palate) on 1700 mg/day of valproate.Conclusions: This is the first attempt to assess the use of AEDs in a prospective study of women who are pregnant but do not have active epilepsy. Although underpowered, this study suggests that women taking AEDs for non-epilepsy indications have a similar risk of having a child with a CM as compared with women taking AEDs for epilepsy. Larger numbers are required to investigate the risk of AED-associated malformations in this important group. [ABSTRACT FROM AUTHOR]

Background: Concerns have been raised about prenatal exposure to magnetic resonance imaging with gadolinium-based contrast agents because of nonclinical findings of gadolinium retention in fetal tissue and 1 population-based study reporting an association with adverse pregnancy outcomes.Objective: This study aimed to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death and neonatal intensive care unit admission.Study Design: We constructed a retrospective cohort of >11 million Medicaid-covered pregnancies between 1999 and 2014 to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death (primary endpoint) and neonatal intensive care unit admissions (secondary endpoint). Medicaid claims data were linked to medical records, Florida birth and fetal death records, and the National Death Index to validate the outcomes and gestational age estimates. Pregnancies with multiples, concurrent cancer, teratogenic drug exposure, magnetic resonance imaging focused on fetal or pelvic evaluation, undetermined gadolinium-based contrast agent use, or those preceded by or contemporaneous with congenital anomaly diagnoses were excluded. We adjusted for potential confounders with standardized mortality ratio weighting using propensity scores.Results: Among 5991 qualifying pregnancies, we found 11 fetal or neonatal deaths in the gadolinium-based contrast agent magnetic resonance imaging group (1.4%) and 73 in the non-gadolinium-based contrast agent magnetic resonance imaging group (1.4%) with an adjusted relative risk of 0.73 (95% confidence interval, 0.34-1.55); the neonatal intensive care unit admission adjusted relative risk was 1.03 (0.76-1.39). Sensitivity analyses investigating the timing of magnetic resonance imaging or repeat magnetic resonance imaging exposure during pregnancy and simulating the impact of exposure misclassification corroborated these results.Conclusion: This study addressed the safety concerns related to prenatal exposure to gadolinium-based contrast agents used in magnetic resonance imaging and the risk thereof on fetal and neonatal death or the need for neonatal intensive care unit admission. Although the results on fatal or severe acute effects are reassuring, the impact on subacute outcomes was not evaluated. [ABSTRACT FROM AUTHOR]

Cancer in pregnancy is an uncommon event and the diagnosis may be delayed. Presenting signs and symptoms may be masked by the pregnancy and there may be reluctance to investigate because of fears of harming the pregnancy. Optimal treatments for the malignancy may conflict with the potential wellbeing of the fetus and a truly multidisciplinary approach is needed to create a treatment plan which minimises the risk to mother and baby, in both the short and long term. [ABSTRACT FROM AUTHOR]

Purpose: Valproate is one of the most commonly used anticonvulsive drugs. Despite its significant benefits, the teratogenicity of valproate is a relevant problem in the treatment of women of childbearing age. In addition to major congenital malformations, such as neural tube defects, reduced intelligence and attention after intrauterine valproate exposure are reported. Until now the mechanisms of teratogenicity of VPA are poorly understood and concepts how to reduce valproate teratogenicity are lacking.Methods: In a rat model of valproate teratogenicity we examined hippocampal cell structure in 4 week old animals with a stereological approach. As potential mechanisms of VPA teratogenicity we examined histone acetylation by western blotting and metabolites of the folate metabolism as well as global DNA methylation by tandem mass spectrometry in the brain and liver tissue of newborn pups (p0).Results: We found an increase in the number of neurons in the hippocampal areas CA1/2 (p=0.018) and CA3 (p=0.022), as well as a decreased number of astrocytes in CA1/2 (p=0.004) and CA3 (p=0.003) after intrauterine VPA exposure, as a possible indication of altered cell differentiation during intrauterine VPA exposure. Valproate exposure was also associated with an increase in 5-methyl-tetrahydrofolate (THF) (p=0.002) and a decrease in 5-10-methenyl-THF in the brain of newborn pups, as well as a reduced homocysteine plasma level (p<0.001). The described changes in hippocampal cell numbers and folate metabolism were only significant after high-dose intrauterine VPA exposure indicating a dose-dependent effect. VPA exposure was not associated with changes in histone acetylation or global DNA methylation in brain tissue in newborn pups.Conclusion: This study shows that intrauterine VPA exposure is associated with changes in hippocampal cell numbers in the CA1/2 and CA3 region and in folate metabolism. [ABSTRACT FROM AUTHOR]

In recent years, the environmental presence of pharmaceuticals - including anticancer drugs - is an emerging issue. Because of the lack of appropriate critical studies about anticancer drug effects in frogs, the aim of the present study was to investigate lethal and teratogenic effects of five anticancer drugs widely used in large quantities, i.e. 5-flourouracil, capecitabine, cisplatin, etoposide, and imatinib, in the embryos of the South African clawed frog, Xenopus laevis , using FETAX - Frog Embryo Teratogenesis Assay in Xenopus . None of the studied anticancer drugs induced statistically significant mortality within the concentrations tested (0.01–50 mg/L, depending on the studied compound), and no growth inhibition of embryos after a 96-h exposure was observed. Except for cisplatin, the other pharmaceuticals induced an increase of developmental malformations such as abdominal edema, axial flexure, head, eyes, gut and heart malformations with statistically significant effects observed at the highest concentrations tested (50 mg/L for 5-flourouracil; 30 mg/L for etoposide and 20 mg/L for capecitabine and imatinib). The results indicate that anticancer drugs can affect embryogenesis mechanisms. [ABSTRACT FROM AUTHOR]

Agricultural chemical inputs have been considered as a risk factor for the global declines in amphibian populations, yet the application of agricultural fungicides has increased dramatically in recent years. Currently little is known about the potential toxicity of fungicides on the embryos of amphibians. We studied the effects of ten commonly used fungicides (four strobilurins, two SDHIs, two triazoles, fludioxonil and folpet) on Xenopus tropicalis embryos. Lethal and teratogenic effects were respectively examined after 48 h exposure. The median lethal concentrations (LC50s) and the median teratogenic concentrations (TC50s) were determined in line with actual exposure concentrations. These fungicides except two triazoles showed obvious lethal effects on embryos; however LC50s of four strobilurins were the lowest and in the range of 6.81–196.59 μg/L. Strobilurins, SDHIs and fludioxonil induced severe malformations in embryos. Among the ten fungicides, the lowest TC50s were observed for four strobilurins in the range of 0.61–84.13 μg/L. The teratogenicity shared similar dose–effect relationship and consistent phenotypes mainly including microcephaly, hypopigmentation, somite segmentation and narrow fins. The findings indicate that the developmental toxicity of currently-used fungicides involved with ecologic risks on amphibians. Especially strobilurins are highly toxic to amphibian embryos at μg/L level, which is close to environmentally relevant concentrations. [ABSTRACT FROM AUTHOR]

Introduction: Greater risks of congenital malformation as well as cognitive and behavioral development in later childhood occur as a result of in utero exposure to antiepileptic drugs (AEDs). We examined the effects of AEDs on behavioral characteristics and cognitive development among school age children born to women with epilepsy. Methods: Children aged 6-15 years and born to women with epilepsy were enrolled in the study. Information was collected on the women's demographics and the details of their usage/non-usage of AEDs during pregnancy. The Wechsler Intelligence Scale for the Children-Revised (WICS-R) test was administered to the children. The Alexander IQ test and the Conner Parent Rating Scale (CPRS) were administered to the mothers. Comparisons were made between children who had been exposed and not exposed to AEDs in utero and if exposed, according to exposure to AED monotherapy or polytherapy. The mother's education level and IQ score and data from the same parent's siblings were evaluated with respect to consanguinity. Results: Forty-one children born to 28 women with epilepsy were enrolled. Seven mothers had multiple pregnancies. Twenty-three pregnancies (56%) were exposed to monotherapy and five (12.1%) to polytherapy. The remaining 13 (31.7%) were not exposed to AEDs. Maternal education level was a significant major factor in child IQ development (P , 0.05). The performance IQ-coding scale results were lower in children exposed to polytherapy than in children exposed to monotherapy in utero (P < 0.05). Although it is difficult to assert with confidence, the sibling assessment indicated a negative effect of valproate on IQ. Conclusion: It is important that the AED dosage be reduced to a minimum to maintain seizure control for healthy cognitive and behavioral development of a child. [ABSTRACT FROM AUTHOR]

Benz[ a ]anthracene (BaA) is a ubiquitous polycyclic aromatic hydrocarbon found in numerous aquatic ecosystems. However, ecotoxicological data in aquatic organisms are scarce. To remedy this lack of data, Japanese medaka ( Oryzias latipes ) embryos were exposed to BaA and toxic effects were investigated at multiple toxicological endpoints. Japanese medaka embryos were incubated onto BaA-spiked artificial sediment for 9 days at low or moderate environmental concentrations ranging from 0.9 to 12 µg g −1 dw. BaA-exposed embryos exhibited significant tachycardia. BaA exposure was also shown to increase CYP1A activity in the hepato-biliary tissue as well as craniofacial deformities and DNA damage in pro-larvae. The photomotor response of BaA-exposed larvae was reduced in comparison to the control group. According to this set of tests, the lowest tested and observed effect concentration (LOEC) for Japanese medaka early life stages was equivalent to 0.92 µg g −1 dw of BaA. This concentration fall into the range of concentrations frequently encountered in sediments of polluted aquatic ecosystems. Taking into consideration these results, BaA represents a threat for fish early life stages in particular those developing onto or into contaminated sediments. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of GSM-like radiofrequency electromagnetic radiation (RF EMR) and nicotine sulfate (NS) exposure on Xenopus embryonic development.The developmental effects of GSM-like RF-EMR (900–1800 MHz, at a SAR value of 1 W/kg and NS on Xenopus laevis embryos were investigated). Following the application of radiofrequency radiation and/or NS administration, the embryos were closely examined in order to determine their possible teratogenic effects. Xenopus frogs obtained from the Department of Physiology of the Cukurova University, in accordance described by the Standard Guide of the American Society for Testing and Materials (ASTM). Following the exposure of Xenopus embryos to RF-EMR at 900 and 1800 MHz (1.0 W/kg) for 4, 6 and 8 h; the whole body specific energy absorption rate (SAR) of the embryos was calculated. With the exception of irradiation at 1800 MHz no dramatic developmental anomalies were observed in the Xenopus embryos in association with RF-EMR applications. Combined RF-EMR and NS applications resulted in dramatic abnormalities and death among the Xenopus embryos. The study results indicated that GSM-like RF-EMR (e.g. radiation from cell phones) was not as harmful to Xenopus embryos as might have been expected. However, the combined effects of GSM-like RF-EMR and NS on Xenopus embryos were more severe than the effect of RF-EMR or NS alone. In conclusion, the study results appear to suggest that the combined use of nicotine and cell phones might result in more pronounced detrimental effects on the health of smokers. [ABSTRACT FROM AUTHOR]

Copyright of Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales is the property of Academia Colombiana de Ciencias Exactas, Fisicas y Naturales and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tremendous progress has been made in the field of toxicology leading to the advance of developmental toxicity assessment. Conventional animal models and in vitro two-dimensional models cannot accurately describe toxic effects and predict actual in vivo responses due to obvious inter-species differences between humans and animals, as well as the lack of a physiologically relevant tissue microenvironment. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived three-dimensional organoids are ideal complex and multicellular organotypic models, which are indispensable in recapitulating morphogenesis, cellular interactions, and molecular processes of early human organ development. Recently, human organoids have been used for drug discovery, chemical toxicity and safety in vitro assessment. This review discusses the recent advances in the use of human organoid models, (i.e., brain, retinal, cardiac, liver, kidney, lung, and intestinal organoid models) for developmental toxicity and teratogenicity assessment of distinct tissues/organs following exposure to pharmaceutical compounds, heavy metals, persistent organic pollutants, nanomaterials, and ambient air pollutants. Combining next-generation organoid models with innovative engineering technologies generates novel and powerful tools for developmental toxicity and teratogenicity assessment, and the rapid progress in this field is expected to continue. • Advances in stem cell techniques for toxicity assessment. • Human organoids can decipher the embryonic development and morphogenesis. • Organoid technologies for developmental toxicology assessment. • Advanced next-generation human organoids toward next-level toxicity testing. [ABSTRACT FROM AUTHOR]

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed. [ABSTRACT FROM AUTHOR]

Extracts from leaves of Ginkgo biloba are among the most widely used and best investigated phytopharmaceuticals worldwide. Almost all clinical trials and the majority of preclinical studies have been performed with a specifically defined extract (EGb 761®) standardized to contain confined concentrations of active ingredients and limited quantities of potentially harmful substances. Besides pharmaceutical grade extracts poorly characterized Ginkgo preparations are now increasingly appearing on the market as nutraceuticals. While the safety of EGb 761® has been evaluated in an extensive set of toxicology studies, adverse effects of Ginkgo extracts of non-pharmaceutical quality on reproductive functions in mice have been reported in several publications in recent years. As this species has not previously been used in reproductive toxicity studies with EGb 761®, the present investigation was conducted to examine the influence of EGb 761® (100, 350 and 1225mg/kg/day) on embryo-fetal development in mice during the critical period of organogenesis. During external and internal inspection of the fetuses as well as examination of skeletal and soft tissues no embryotoxic properties were noted. In particular, the incidence of malformations, variations or retardations was not increased and the general condition of dams was not influenced. Thus, the no-observed-effect level (NOEL) was above 1225mg/kg/day for the dams and the fetuses. [ABSTRACT FROM AUTHOR]

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Abstract: Health care practitioners utilize the United States-Food and Drug Administration (US-FDA) pregnancy categorization (A, B, C, D, X) for making decision on the appropriateness of certain medications during pregnancy. Many non US-FDA approved medications are registered and marketed in Saudi Arabia. However, these medications do not have an assigned pregnancy risk categorization like those approved in the US. The objective of this review is to evaluate, report, and categorize the foetal risk associated with non-US-FDA approved medications registered by the Saudi Food and Drug Authority (S-FDA) according to the US-FDA pregnancy risk categorization system. We identified 109 non-US-FDA approved medications in the Saudi National Formulary (SNF) as of October 2007. We searched for data on functional or anatomical birth defects or embryocidal-associated risk using different databases and references. An algorithm for risk assessment was used to determine a pregnancy risk category for each medication. Out of 93 eligible medications, 73% were assigned category risk C, 10 medications (11%) were assigned category risk D, and 12 medications (13%) were assigned category risk B. Only three medications were judged to be safe during pregnancy based on the available evidence and were assigned category risk A. Inconsistencies in defining and reporting the foetal risk category among different drug regulatory authorities could create confusion and affect prescribing. We believe that standardization and inclusion of this information in the medication package insert is extremely important to all health care practitioners. [Copyright &y& Elsevier]

Abstract: Because of their high capacity to accumulate contaminants such as persistent organic pollutants and heavy metals, aquatic sediments are considered as a long-term source of contamination for aquatic organisms. In compliance with the increasing interest both for sediment quality evaluation and the use of fish early life stage (ELS) toxicity assays, we proposed an embryo-larval test to evaluate embryotoxicity and genotoxicity of sediment-bound contaminants. Pre-blastula stage medaka (Oryzias latipes) embryos were exposed by static sediment contact to two model heavy metals (cadmium and copper) at environmental concentrations during the whole 10-day embryonic development. Lethal and sub-lethal effects were recorded in both embryos and larvae for 20days post fertilisation (dpf) using several global toxicity and phenotypic endpoints. The comet assay was also performed on medaka prolarvae to evaluate genotoxic effects of the tested chemicals. Environmental concentrations of cadmium (Cd) and copper (Cu) did not affect embryo and larval survival. However, both heavy metals significantly induced morphological abnormalities, particularly spinal and cardiovascular deformities. Cd but not Cu induced tachycardia. Both heavy metals induced a significant increase in DNA damage at all tested concentrations. Resulting LOEC values for Cd and Cu corresponded to 1.9 and 8.5μg/g d.w. sediment, respectively. Although metal bioavailability is probably lower for naturally contaminated sediments, the relatively low toxicity thresholds for both Cd and Cu raise the question of possible risk for fish embryos developing in direct contact to sediments. This study demonstrates the applicability, sensitivity and relevance of the Japanese medaka embryo-larval assay (MELA) to evaluate sediment hazardous potency at environmental concentrations of heavy metals. [Copyright &y& Elsevier]