Статті в журналах з теми "Maternal Nicotine Treatment (MNT)"

Cadmium, a common environmental pollutant and a major constituent of tobacco smoke, has been identified as a new class of endocrine disruptors with a wide range of detrimental effects on mammalian reproduction. During human pregnancy, maternal cadmium exposure, via the environment and/or cigarette smoking, leads to fetal growth restriction (FGR), but the underlying mechanisms are unknown. Although a substantial amount of evidence suggests that cadmium may affect fetal growth indirectly via the placenta, the molecular targets remain to be identified. Given that reduced placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2, encoded by HSD11B2 gene) is causally linked to FGR, the present study was undertaken to examine the hypothesis that cadmium induces FGR in part by targeting placental HSD11B2. Using cultured human trophoblast cells as a model system, we showed that cadmium exposure resulted in a time- and concentration-dependent decrease in 11β-HSD2 activity, such that an 80% reduction was observed after 24-h treatment at 1 μM. It also led to a similar decrease in levels of 11β-HSD2 protein and mRNA, suggesting that cadmium reduced 11β-HSD2 expression. Furthermore, cadmium diminished HSD11B2 promoter activity, indicative of repression of HSD11B2 gene transcription. In addition, the effect of cadmium was highly specific, in that other divalent metals (Zn2+, Mg2+, and Mn2+) as well as nicotine and cotinine (a major metabolite of nicotine) did not alter 11β-HSD2 activity. Taken together, these findings demonstrate that cadmium reduces human placental 11β-HSD2 expression and activity by suppressing HSD11B2 gene transcription. Thus the present study identifies placental 11β-HSD2 as a novel molecular target of cadmium. It also reveals a molecular mechanism by which this endocrine disruptor may affect human placental function and, consequently, fetal growth and development.

Abstract Introduction Both smoking and infection adversely impact pregnancy. Previously, our group identified in a rodent model that 6 mg/kg/d nicotine increased the risk of fetal infection at gestation day (GD) 18. Here, we investigate lower nicotine doses. Methods Pregnant Sprague-Dawley rats received nicotine infusion at 0, 1, or 3 mg/kg/d (no, low-, and mid-dose nicotine, respectively) from GD 6, with intravenous inoculation with Mycoplasma pulmonis (MP) at 107 CFU (N = 20) or sterile broth (sham) (N = 11) on GD 14. Uterus and fetuses were retrieved on GD 18 for MP culture and histopathologic evaluation of maternal and fetal inflammatory responses (MIR and FIR). Results At 1 mg/kg/d nicotine, MP colonization rates were decreased, from 100% (9 of 9) to 40% (2 of 5) of MP-inoculated dams (p = .03), and 59% (66 of 111) to 39% (24 of 62) of fetuses (p = .01), versus no nicotine. Low-dose nicotine resulted in increased MIR and FIR in the sham-inoculated group; in the MP-inoculated group, this resulted in reduced relative risk (RR) for placental colonization (RR, 95% CI with high MIR = 0.14, 0.02 to 0.65; FIR = 0.38, 0.12 to 0.93). In contrast, 3 mg/kg/d nicotine treatment did not alter colonization rates; furthermore, FIR was completely suppressed, even in the face of placental or amniotic fluid colonization. Conclusion The 1 mg/kg/d nicotine dose decreased risk of intrauterine infection, with increased MIR and FIR. The 3 mg/kg/d nicotine dose inhibited FIR, and increased risk for intrauterine infection. Nicotine alterations of the intrauterine environment were markedly dose-dependent. Implications Nicotine exposure alters intrauterine infection and inflammation in a dose-dependent manner, potentially impacting fetal development and programming. Previous work in a rodent model showed that high-dose nicotine (6 mg/kg/d) exposure exacerbated intrauterine infection during pregnancy. The current study found that low-dose nicotine (1 mg/kg/d) exposure reduced colonization of placenta and amniotic fluid; this decrease was associated with increased intrauterine inflammation. Exposure to mid-dose nicotine (3 mg/kg/d) suppressed fetal inflammation. Elucidation of underlying mechanisms of these phenomena will inform public health and clinical care decisions, particularly in the context of risk assessment of nicotine replacement therapy during pregnancy for smoking cessation.

Maternal cigarette smoking is a major perinatal insult that contributes to an increased risk of cardiovascular and neurodevelopmental diseases in offspring. Our previous studies revealed that perinatal nicotine exposure reprograms a sensitive phenotype in neonatal hypoxic-ischemic encephalopathy (HIE), yet the underlying molecular mechanisms remain largely elusive. The present study tested the hypothesis that perinatal nicotine exposure impacts autophagy signaling in the developing brain, resulting in enhanced susceptibility to neonatal HIE. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps. Neonatal HIE was conducted in 9-day-old male rat pups. Protein kinase B/glycogen synthase kinase- 3β/mammalian target of rapamycin (Akt/GSK-3β/mTOR) signaling and key autophagy markers were determined by Western blotting analysis. Rapamycin and MK2206 were administered via intracerebroventricular injection. Nicotine exposure significantly inhibited autophagy activities in neonatal brain tissues, characterized by an increased ratio of phosphoylated (p-) to total mTOR protein expression but reduced levels of autophagy-related 5, Beclin 1, and LC3βI/II. Treatment with mTOR inhibitor rapamycin effectively blocked nicotine-mediated autophagy deficiency and, more importantly, reversed the nicotine-induced increase in HI brain infarction. In addition, nicotine exposure significantly upregulated p-Akt and p-GSK-3β. Treatment with the Akt selective inhibitor MK2206 reversed the enhanced p-Akt and p-GSK-3β, restored basal autophagic flux, and abolished nicotine-mediated HI brain injury. These findings suggest that perinatal nicotine-mediated alteration of Akt/GSK-3β/mTOR signaling plays a key role in downregulation of autophagic flux, which contributes to the development of hypoxia/ischemia-sensitive phenotype in the neonatal brain.

Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for infant and children diseases. It is concentrated in breast milk and is absorbed by the infant. The purpose of the present study was to investigate the effects of maternal nicotine exposure during lactation on breast-fed rats and at the pubertal age by measuring biomarkers of oxidative stress. Particularly, a new parameter, the thiol concentration was evaluated. Two groups of lactating Wistar rats were used. For the first group, female rats were given an intraperitoenal injection of nicotine or saline (2 mg/kg per day) during lactation. For the second group, we reproduced the same process described above and then the female and male pups were separately kept after weaning without any treatment until the puberty (at 45 days of age). In the liver and lung of the offspring, we examined the malondialdehyde (MDA) level, the thiol concentration, and the activities of two antioxidant enzymes: superoxyde dismutase (SOD) and catalase (CAT). In the plasma, alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were measured. For rats aged 21 days, the treatment significantly reduced the thiol concentration, SOD, and CAT activities but increased MDA level, AST, and ALT activities. For rats aged 45 days, the males and females did not react the same way. In fact, the males were more affected. These results indicate that maternal nicotine exposure during the lactation period induces oxidative stress in the liver and lung of lactating offspring, which is maintained until the puberty, especially for the male rats.

Abstract Tobacco smoke contains polycyclic aromatic hydrocarbons (PAHs) in addition to nicotine. We compared the developmental neurotoxicity of nicotine to that of the PAH archetype, benzo[a]pyrene (BaP), and also evaluated the effects of combined exposure to assess whether PAHs might exacerbate the adverse effects of nicotine. Pregnant rats were treated preconception through the first postnatal week, modeling nicotine concentrations in smokers and a low BaP dose devoid of systemic effects. We conducted evaluations of acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT) systems in brain regions from adolescence through full adulthood. Nicotine or BaP alone impaired indices of ACh presynaptic activity, accompanied by upregulation of nicotinic ACh receptors and 5HT receptors. Combined treatment elicited a greater deficit in ACh presynaptic activity than that seen with either agent alone, and upregulation of nAChRs and 5HT receptors was impaired or absent. The individual effects of nicotine and BaP accounted for only 60% of the combination effects, which thus displayed unique properties. Importantly, the combined nicotine + BaP exposure recapitulated the effects of tobacco smoke, distinct from nicotine. Our results show that the effects of nicotine on development of ACh and 5HT systems are worsened by BaP coexposure, and that combination of the two agents contributes to the greater impact of tobacco smoke on the developing brain. These results have important implications for the relative safety in pregnancy of nicotine-containing products compared with combusted tobacco, both for active maternal smoking and secondhand exposure, and for the effects of such agents in “dirty” environments with high PAH coexposure.

Perinatal exposure to maternal smoke is associated with adverse pulmonary effects, including reduced lung function and increased incidence of asthma. However, the mechanisms underlying these effects are unknown, and there is no effective preventive and/or therapeutic intervention. Recently, we suggested that downregulation of homeostatic mesenchymal peroxisome proliferator-activated receptor-γ (PPARγ) signaling following in utero nicotine exposure might contribute to chronic lung diseases such as asthma. We used an in vivo rat model to determine the effect of perinatal nicotine exposure on 1) offspring pulmonary function, 2) mesenchymal markers of airway contractility in trachea and lung tissue, and 3) whether administration of a PPARγ agonist, rosiglitazone (RGZ), blocks the molecular and functional effects of perinatal nicotine exposure on offspring lung. Pregnant Sprague-Dawley rat dams received placebo, nicotine, or nicotine + RGZ daily from embryonic day 6 until postnatal day 21, when respiratory system resistance, compliance, tracheal contractility, and the expression of markers of pulmonary contractility were determined. A significant increase in resistance and a decrease in compliance under basal conditions, with more pronounced changes following methacholine challenge, were observed with perinatal nicotine exposure compared with control. Tracheal constriction response and expression of mesenchymal markers of airway contractility were also significantly increased following perinatal nicotine exposure. Concomitant treatment with RGZ completely blocked the nicotine-induced alterations in pulmonary function, as well as the markers of airway contractility, at proximal and distal airway levels. These data suggest that perinatal smoke exposure-induced asthma can be effectively blocked by PPARγ agonists.

AbstractAlthough drug-abusing women try to moderate their drug and alcohol use during pregnancy, they often relapse at a time when childcare needs are high and maternal bonding is critical to an infant’s development. In the clinical setting, the search for the neural basis of drug-induced caregiving deficits is complex due to several intervening variables. Rather, the preclinical studies that control for drug dose and regimen, as well as for gestational and postpartum environment, allow a precise determination of the effects of drugs on maternal behaviour. Given the relevance of the issue, this review will gather reports on the phenotypic correlates of maternal behaviour in preclinical studies, and focus on the detrimental consequences on the mother-infant interaction exerted by the perinatal use of alcohol, nicotine, cannabis, cocaine and stimulants and opiates. The drug-induced disruptions of this maternal repertoire are associated with adverse maternal and infant outcomes. A comprehensive overview will help promote the refinement of the treatment approaches toward maternal drug use disorders and maternal misbehaviour, in favour of augmented parenting resiliency.

Background: GDM is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Women with gestational diabetes are characterized by a relatively diminished insulin secretion and pregnancy induced insulin resistance primarily present in the skeletal muscle tissue. Normal pregnancy is a diabetogenic state characterized by exaggerated rate and amount of insulin release, associated with decreased sensitivity to insulin at cellular levels. The objective of the study was to study the maternal, the fetal and the neonatal outcomes of treated patients of GDM in present study.Methods: It was a hospital based clinical study. 1000 patients were enrolled between 24-28 weeks of gestation and DIPSI test was performed. Diagnosis of GDM was done using DIPSI criteria. 80 patients were diagnosed with GDM and followed till delivery to study the maternal, fetal and neonatal outcome.Results: Elderly patients, patients with previous history of GDM, patients with family history of diabetes, patients with high BMI and patients with polyhydramnios are at high risk for GDM.Conclusions: Hypertensive disorders and preterm birth are known to be higher with GDM are similar to the non-GDM group suggesting that early diagnosis and prompt treatment and maintaining strict glycemic control by patient may be beneficial. GDM can be managed well on MNT and lifestyle modifications, only few patients required insulin therapy. In spite of appropriate glycemic control, the incidence of macrosomia found to be high in GDM group. Sudden unexplained stillbirth can occur in spite of strict glycemic control. Neonatal complications have occurred despite well glycemic control.

Diabetes mellitus is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the long-term complications. Moderate to severe maternal hyperglycemia in pregnancy has unique diabetes-related risks to mother and her unborn baby. So Gestational Diabetes mellitus (GDM) is a carbohydrate intolerance that is not diabetes that has developed or been discovered for the first time during pregnancy. Approximately 7% of pregnancies are affected by GDM. Patient with GDM are at higher risk for excessive weight gain, preeclampsia, and cesarean sections. Infants born to mothers with GDM are at higher risk for macrosomia, birth trauma, and shoulder dystocia. After delivery, these infants have a higher risk of developing hypoglycemia, hypocalcemia, hyperbilirubinemia, respiratory distress syndrome, polycythemia and subsequent obesity and type 2 diabetes. So the management of GDM is very important, and its management remains a challenge for the obstetricians and endocrinologists. MNT is the most common therapy which suffices for GDM, but when required. The pharmacological treatment becomes necessary, and the treatment of choice is human insulin. OHAs have also reached the high tables in the management of GDM. Glyburide and metformin have been found to be safe, effective and economical for the treatment of gestational diabetes. Let us join hands to manage the GDM effectively, not only for the present generation but also for the generations to come.

Smoking, alcohol and illicit drug misuse during pregnancy lead to toxic harmful consequences for mother and especially for the fetus, neonate or child. In case of misuse of illicit substances pregnant women mostly suffer from polytoxicomania (3 substances and more) and the misuse of illicit substances is often accompanied by severe smoking and drinking of alcohol. Therefore it is often difficult to methodologically differentiate the single toxic effects. Basing on this knowledge in the presentation a view on the single toxic and /or chronic effects of addictive drugs will be given.1.To clarify single toxic effects of the addictive drugs diagnostic procedure about regulary and/ or ecstatical consume and the diagnose of abuse or dependence acc. to DSMIV or ICD 10 and the analysis of relapse behaviour for each substance should be done.2.The toxic effects of the different substances in pregnancy will be reported. Nearly al addictive substances (nicotine (+CO, +tar), alcohol, THC, psychostimulants, heroine) go into placenta and thereby have multiple toxic effects like f.e. decreased perfusion and infarct of the placenta leading f.e. to intrauterine retardation of growth, premature detaching of placenta, premature birth, to deformities, various later heavy postpartal effects (lung and breath diseases, sudden death, fetal alcohol syndrome, neurological dysdevelopment, cardial malformations, learning disturbances, ADHD etc). The toxic effects of the various substances will be differentiated so far it is possible.3.The different therapeutic approach of the various addictive drugs during pregnany (withdrawl treatment, opioid substitution) will be discussed.

Thyroid disorders are a frequently encountered issue during pregnancy and a cause of maternal and fetal morbidity. In regions like Appalachia that are particularly susceptible to health disparities, descriptive studies are needed to assist in identifying pathologic derangements. We sought to characterize fetal thyroid hormone levels at delivery and investigate whether or not maternal demographic characteristics affect the prevalence of neonatal thyroid disease. A cross-sectional analysis was conducted on 130 pregnant women recruited from the Tri-State region, incorporating areas of Kentucky, Ohio, and West Virginia. Total triiodothyronine (T3) (p = 0.4799), free T3 (p = 0.6323), T3 uptake (p = 0.0926), total thyroxine (T4) (p = 0.8316), free T4 (p = 0.0566), and Thyroid stimulating hormone (TSH) (p = 0.8745) levels were comparable between urban and rural newborns. We found no effect of hypertension status or nicotine levels on fetal umbilical cord thyroid hormone levels. Maternal diabetic status was associated with lower T4 (p = 0.0099) and free T4 (p = 0.0025) levels. Cotinine affected levels of T4 (p = 0.0339). In regard to maternal Body Mass Index (BMI), there was an increase in total T3 as BMI increased (p = 0.0367) and no significant difference in free T3, T3 uptake, T4, free T4, or TSH. There was a negative correlation between TSH and 1 min Apgar scores (p = 0.0058). Lead and cadmium have been implicated to alter TSH levels, but no correlation was found in our study (r2 = 0.0277). There were no differences in cord blood between urban (37.3 ± 10.3 fmol/ug DNA) and rural (70.5 ± 26.8 fmol/ug DNA) benzo(a)pyrene DNA adducts (p = 0.174). Thyroid disorders present a unique opportunity for the prevention of perinatal morbidity and mortality, since maternal treatment, as well as maternal demographic characteristics, can have direct fetal effects.

ObjectiveTo investigate relationships between maternal smoking status in pregnancy and infant development. The largest randomised controlled trial of nicotine replacement therapy (NRT) for smoking cessation in pregnancy, the smoking, nicotine and pregnancy (SNAP) trial, found that at 1 month after randomisation, smoking cessation rates were doubled in the NRT group compared with the placebo group. At delivery, there was no significant difference in cessation rates between groups. Surprisingly, infants born to women randomised to NRT were more likely to have unimpaired development at 2 years. We hypothesised that this apparently protective effect was due to smoking cessation caused by NRT and so, investigate this relationship using the same cohort.DesignSecondary analysis of a randomised controlled trial.SettingSeven antenatal hospitals in the Midlands and North-West England.ParticipantsEight hundred and eighty-four pregnant smokers randomised to receive either NRT patches or visually-identical placebo in the SNAP trial. Participants’ smoking behaviour were recorded at randomisation, 1 month after their target quit date and at delivery.MethodsUsing logistic regression models, we investigated associations between participants’ smoking measures and infant development (assessed using the Ages and Stages questionnaire) at 2 years.Main outcome measures2 year infant development.ResultsDevelopmental impairment was reported for 12.7% of study 2 year olds. Maternal heaviness of smoking at randomisation (OR: 1.26, 95% CI: 0.82 to 1.96, p=0.091), validated smoking abstinence recorded at 1 month after a quit date (OR: 1.02, 95% CI: 0.60 to 1.74, p=0.914) and validated smoking abstinence recorded at both 1 month after a quit date and at the end of pregnancy (OR: 1.52, 95% CI: 0.81 to 2.85, p=0.795) were not independently associated with infant developmental impairment at 2 years.ConclusionWe found no evidence that NRT treatment improved infants' developmental outcomes through smoking cessation.Trial registration numberCTA03057/0002/001-0001; Post-results

OBJECTIVE: To examine the pattern of tobacco use and knowledge about tobacco-related diseases, as well as to identify popular types of electronic media, in pregnant women, in order to improve strategies for the prevention or cessation of smoking among such women. METHODS: A cross-sectional study involving 61 pregnant women, seen at primary care clinics and at a university hospital, in the city of Botucatu, Brazil. For all subjects, we applied the Hospital Anxiety and Depression Scale. For subjects with a history of smoking, we also applied the Fagerström Test for Nicotine Dependence, and we evaluated the level of motivation to quit smoking among the current smokers. RESULTS: Of the 61 pregnant women evaluated, 25 (40.9%) were smokers (mean age, 26.4 ± 7.4 years), 24 (39.3%) were former smokers (26.4 ± 8.3 years), and 12 (19.8%) were never-smokers (25.1 ± 7.2 years). Thirty-nine women (63.9%) reported exposure to passive smoking. Of the 49 smokers/former smokers, 13 (26.5%) were aware of the pulmonary consequences of smoking; only 2 (4.1%) were aware of the cardiovascular risks; 23 (46.9%) believed that smoking does not harm the fetus or newborn infant; 21 (42.9%) drank alcohol during pregnancy; 18 (36.7%) reported increased cigarette consumption when drinking; 25 (51.0%) had smoked flavored cigarettes; and 12 (24.5%) had smoked a narghile. Among the 61 pregnant women evaluated, television was the most widely available and favorite form of electronic media (in 85.2%), as well as being the form most preferred (by 49.2%). CONCLUSIONS: Among pregnant women, active smoking, passive smoking, and alternative forms of tobacco consumption appear to be highly prevalent, and such women seem to possess little knowledge about the consequences of tobacco use. Educational programs that include information about the consequences of all forms of tobacco use, employing new and effective formats tailored to this particular population, should be developed, in order to promote smoking prevention and cessation among pregnant women. Further samples to explore regional and cultural adaptations should be evaluated.

IntroductionWhile tobacco smoking prevalence is falling in many western societies, it remains elevated among high-priority cohorts. Rates up to 95% have been reported in women whose pregnancy is complicated by other substance use. In this group, the potential for poor pregnancy outcomes and adverse physical and neurobiological fetal development are elevated by tobacco smoking. Unfortunately, few targeted and effective tobacco dependence treatments exist to assist cessation in this population. The study will trial an evidence-based, multicomponent tobacco smoking treatment tailored to pregnant women who use other substances. The intervention comprises financial incentives for biochemically verified abstinence, psychotherapy delivered by drug and alcohol counsellors, and nicotine replacement therapy. It will be piloted at three government-based, primary healthcare facilities in New South Wales (NSW) and Victoria, Australia. The study will assess the feasibility and acceptability of the treatment when integrated into routine antenatal care offered by substance use in pregnancy antenatal services.Methods and analysisThe study will use a single-arm design with pre–post comparisons. One hundred clients will be recruited from antenatal clinics with a substance use in pregnancy service. Women must be <33 weeks’ gestation, ≥16 years old and a current tobacco smoker. The primary outcomes are feasibility, assessed by recruitment and retention and the acceptability of addressing smoking among this population. Secondary outcomes include changes in smoking behaviours, the comparison of adverse maternal outcomes and neonatal characteristics to those of a historical control group, and a cost-consequence analysis of the intervention implementation.Ethics and disseminationProtocol approval was granted by Hunter New England Human Research Ethics Committee (Reference 17/04/12/4.05), with additional ethical approval sought from the Aboriginal Health and Medical Research Council of NSW (Reference 1249/17). Findings will be disseminated via academic conferences, peer-reviewed publications and social media.Trial registration numberAustralia New Zealand Clinical Trial Registry (Ref: ACTRN12618000576224).

ABSTRACT Introduction Gestational diabetes is a common medical disorder in pregnancy. So long, it has been usually treated by insulin. Now it has been found that oral glibenclamide can be used instead of insulin with similar glycemic control and without any adverse maternal and fetal effect. Methods A comparative study between oral glibenclamide and insulin for the management of gestational diabetes mellitus (GDM) was conducted. It was a prospective randomized study and patients attending the antenatal clinic were screened with 75 gm oral glucose between 20 to 28 weeks and GDM was diagnosed based on WHO criteria of 2 hours blood glucose ≥140 mg/dl. Women with gestational diabetes were given medical nutritional therapy (MNT) for 2 weeks. Out of this, 60 women did not achieve the target blood glucose. The goal of treatment was maintenance of mean plasma glucose (MPG) of about 105 mg%. For this the fasting plasma glucose should be around 90 mg/dl and postprandial peaks around 120 mg/dl. Patients were randomly assigned to receive glibenclamide (group A, n = 30) or insulin (group B, n = 30). In group A, glibenclamide was given 2.5 mg orally in morning and doses were increased weekly by 2.5 mg up to a maximum of 20 mg and doses >7.5 mg were given in two divided doses. In group B, insulin 0.7 units per kilogram of body weight at admission was given subcutaneously three times daily and increased weekly as necessary. Self monitoring of blood glucose with glucometer was done. Blood glucose was also measured from the laboratory every week. Glycosylated hemoglobin (HbA1c) was measured before initiation of therapy and repeated in the third trimester before confinement. Terminations of pregnancy in both the groups were done between 37 and 38 weeks. The infant birth weight, blood glucose and serum bilirubin were also recorded in all cases. Results The present study showed that the two groups had similar glycemic status (fasting blood sugar in group A was 103.5 ± 14.62 mg/dl and postprandial blood sugar was 184.1 ± 20.46 mg/dl whereas in group B it was109.3 ± 19.63 mg/dl and 194.3 ± 18.47mg/dl) at the time of entry into the study. The two groups also showed similar levels of glycemic control just before confinement (fasting blood sugar in group A was 88.23 ± 6.55 mg/ dl and postprandial blood sugar was 122.7 ± 10.3 mg/dl whereas in group B it was 88.17 ± mg/dl and 128 ± 12.38 mg/dl) and there was no significant statistical difference in the two groups (p > 0.05). The perinatal outcomes in both the groups were also nearly same. There was no significant difference in birth weight, blood sugar level of neonates and complications between the two groups. There was no case of macrosomia in the two groups and the number of infants large for gestational age (LGA) was four in group A and two in group B. Hypoglycemia in newborn was slightly higher in the group A compared to group B (4 and 3 respectively). Conclusion From our study, it is evident that the use of oral agents is a pragmatic alternative to insulin therapy in cases of gestational diabetes because of similar glycemic control, ease of administration and better patient compliance due to noninvasive treatment. How to cite this article Mukhopadhyay P, Bag TS, Kyal A, Saha DP, Khalid N. Oral Hypoglycemic Glibenclamide: Can it be a Substitute to Insulin in the Management of Gestational Diabetes Mellitus? A Comparative Study. J South Asian Feder Obst Gynae 2012;4(1):28-31.

BackgroundSmoking during pregnancy causes many adverse pregnancy and birth outcomes. Nicotine replacement therapy (NRT) is effective for cessation outside pregnancy but efficacy and safety in pregnancy are unknown. We hypothesised that NRT would increase smoking cessation in pregnancy without adversely affecting infants.ObjectivesTo compare (1) at delivery, the clinical effectiveness and cost-effectiveness for achieving biochemically validated smoking cessation of NRT patches with placebo patches in pregnancy and (2) in infants at 2 years of age, the effects of maternal NRT patch use with placebo patch use in pregnancy on behaviour, development and disability.DesignRandomised, placebo-controlled, parallel-group trial and economic evaluation with follow-up at 4 weeks after randomisation, delivery and until infants were 2 years old. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio. Participants, site pharmacies and all study staff were blind to treatment allocation.SettingSeven antenatal hospitals in the Midlands and north-west England.ParticipantsWomen between 12 and 24 weeks’ gestation who smoked ≥ 10 cigarettes a day before and ≥ 5 during pregnancy, with an exhaled carbon monoxide (CO) reading of ≥ 8 parts per million (p.p.m.).InterventionsNRT patches (15 mg per 16 hours) or matched placebo as an 8-week course issued in two equal batches. A second batch was dispensed at 4 weeks to those abstinent from smoking.Main outcome measuresParticipants: self-reported, prolonged abstinence from smoking between a quit date and childbirth, validated at delivery by CO measurement and/or salivary cotinine (COT) (primary outcome). Infants, at 2 years: absence of impairment, defined as no disability or problems with behaviour and development. Economic: cost per ‘quitter’.ResultsOne thousand and fifty women enrolled (521 NRT, 529 placebo). There were 1010 live singleton births and 12 participants had live twins, while there were 14 fetal deaths and no birth data for 14 participants. Numbers of adverse pregnancy and birth outcomes were similar in trial groups, except for a greater number of caesarean deliveries in the NRT group. Smoking: all participants were included in the intention-to-treat (ITT) analyses; those lost to follow-up (7% for primary outcome) were assumed to be smoking. At 1 month after randomisation, the validated cessation rate was higher in the NRT group {21.3% vs. 11.7%, odds ratio [OR], [95% confidence interval (CI)] for cessation with NRT, 2.05 [1.46 to 2.88]}. At delivery, there was no difference between groups’ smoking cessation rates: 9.4% in the NRT and 7.6% in the placebo group [OR (95% CI), 1.26 (0.82 to 1.96)]. Infants: at 2 years, analyses were based on data from 888 out of 1010 (87.9%) singleton infants (including four postnatal infant deaths) [445/503 (88.5%) NRT, 443/507 (87.4%) placebo] and used multiple imputation. In the NRT group, 72.6% (323/445) had no impairment compared with 65.5% (290/443) in placebo (OR 1.40, 95% CI 1.05 to 1.86). The incremental cost-effectiveness ratio for NRT use was £4156 per quitter (£4926 including twins), but there was substantial uncertainty around these estimates.ConclusionsNicotine replacement therapy patches had no enduring, significant effect on smoking in pregnancy; however, 2-year-olds born to women who used NRT were more likely to have survived without any developmental impairment. Further studies should investigate the clinical effectiveness and safety of higher doses of NRT.Trial registrationCurrent Controlled Trials ISRCTN07249128.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 18, No. 54. See the NIHR Journals Library programme website for further project information.

Epidemiologic evidence indicates an increase in cleft lip with or without cleft palate [CL(P)] in infants of mothers who smoke cigarettes. It appears that the principle mechanism is through carbon monoxide (CO) decreasing the oxygen (O2) available to the embryo. Previous studies have shown that maternal respiratory hypoxia can increase the incidence of CL(P) in mice. The present investigation was designed to analyze the effects of altered levels of CO and O2 in respiratory gases on the incidence of CL(P) in genetically susceptible A/J mice. Results from blood gas analysis, after a 24-hour exposure of pregnant mice during the time of primary palate development, showed that CO levels of 180 ppm in air decreased oxyhemoglobin (%O2Hb) and increased carboxyhemoglobin (%COHb) to slightly above the high end of the range found in human studies of cigarette smokers. Interestingly, the control COHb levels were higher in our CL(P) sensitive mouse strain compared with those of the range of increases found in human smokers, versus nonsmoker studies, and that the increase for treated mice (3x) was at the low end of the range for smokers. Decreasing O2 levels to 10% from 21% (normal percentage in air) more severely decreased %O2Hb and moderately decreased %COHb. At 24 hours of exposure, the incidence of CL(P) and resorption was approximately the same for both the CO and the control groups, but there were significant increases in the incidence of resorptions in the hypoxia group and of CL(P) in relation to the CO group. A statistically significant increase in CL(P), but not resorptions was found for a longer CO treatment time (48 hours vs. 24 hours of exposure). Also, an increase in the severity of clefting was noted with the carbon monoxide treated groups having more bilateral CL(P) than unilateral CL(P). The low incidences of CL(P) in the control groups prevented statistical analysis, although results from other studies indicate that the increased severity is real. CO exposure longer than 48 hours seems to give no additional increase in clefting incidence. We conclude that chronic exposure to moderate levels of CO increases the incidence and severity of CL(P) in A/J mice. The possible additional effects of nicotine in cigarette smoke and of other confounding factors related to smoking and CL(P) are discussed.

Abstract Background Negative symptoms in schizophrenia (SCZ) are poorly treated and interfere with the function of patients. Studies focusing on structural and functional imaging and non-invasive electrophysiology implicate perturbations of the frontocortico-temporal circuits and disruption of cortico-striatal loops to negative symptoms in SCZ. GPR139 is an orphan GPCR that is specifically expressed in the CNS and enriched in the habenula, a brain structure involved in reward and motivation. Structural and functional alterations of the habenula have been found in SCZ patients, who show deficits in feedback processing and lack habenula activation in response to negative outcomes. Rodent experiments demonstrate the involvement of direct projection from the cortex to the habenula controlling social behavior. Alteration in habenula activity have been correlated with depression, and normalization of aberrant habenula activity has been proposed as therapeutic strategy to reverse anhedonia. Building on data previously reported at SIRS2018, we further explored modulation of GPR139 receptors and habenula circuitry in vivo as a novel mechanism to treat negative symptoms in SCZ. Methods Animals were submitted to an unpredictable chronic mild stress (uCMS) protocol, an animal model of depression that produces deficits in several behavioral domains affected in depressed patients. The three-chamber (Crawley’s) paradigm has been used to study social interaction in rodents. Induction of the immediate early gene c-fos expression was studied as marker for habenula neuron activation in vivo. Dopamine release in the nucleus accumbens (NAc) was studied by standard in vivo microdialysis in freely moving rats. Results The selective GPR139 agonist TAK-041 increased cFOS expression in the habenula in wild type mice, but not in GPR139 knock out mice. No desensitization of cFOS in the habenula was observed after chronic dosing of TAK-041. Microdialysis studies showed that TAK-041 reduced amphetamine- and nicotine-induced dopamine release in the NAc in rats. TAK-041 dosed acutely and chronically reversed anhedonia caused by uCMS in rats. TAK-041 also reversed anxiety related behavior assessed in the novelty suppressed feeding test and depressive-like behavior in the forced swim test in the uCMS model. uCMS-exposed animals develop a disrupted circadian regulation of corticosterone secretion, which was also normalized by TAK-041 treatment. Furthermore, TAK-041 reversed the uCMS-induced atrophy in the basal dendrites of pyramidal neurons in the hippocampus and the uCMS-induced hypertrophy of medium-spiny neurons in the NAc. These results suggest a potential benefit of TAK-041 in the treatment of anhedonia and possibly depression. TAK-041 also completely reversed social interaction (SI) deficits in the maternal immune activation poly-I:C model of SCZ, the subchronic PCP-SI model and in Balb/C and BTBR mice. Discussion The GPR139 agonist TAK-041 is proposed as a modulator of habenula circuitry to treat negative symptoms in SCZ based on efficacy in reversing anhedonia and social interaction deficits in multiple rodent models related to negative symptoms in SCZ. *Employed by Takeda when the study was done.

<p><strong>List of abstracts and authors:</strong></p><p><strong>1. Bipolar disorder not otherwise specified -overdiagnosed or underdiagnosed?</strong></p><p>E Allers</p><p><strong>2. The prognosis of major depression untreated and treated: Does the data reflect the true picture of the prognosis of this very common disorder?</strong></p><p>E Allers</p><p><strong>3. Can we prolong our patients' life expectancy? Providing a better quality of life for patients with severe mental illness</strong></p><p>O A Betencourt</p><p><strong>4. The scope of ECT practice in South Africa</strong></p><p>J Benson-Martin, P Milligan</p><p><strong>5. Biomarkers for schizophrenia: Can we evolve like cancer therapeutics?</strong></p><p>P Buckley<strong></strong></p><p><strong>6. Relapse in schizophrenis: Major challenges in prediction and prevention</strong></p><p>P Buckley</p><p><strong>7. Informed consent in biological treatments: The right to know the duty to inform</strong></p><p><strong></strong>I Chetty</p><p><strong>8. Effectiveness of a long-acting injectable antipsychotic plus an assertive monitoring programme in first-episode schizophrenia</strong></p><p><strong></strong>B Chiliza, L Asmal, O Esan, A Ojagbemi, O Gureje, R Emsley</p><p><strong>9. Name, shame, fame</strong></p><p>P Cilliers</p><p><strong>10. Can we manage the increasing incidence of violent raging children? We have to!</strong></p><p>H Clark</p><p><strong>11. Serotonin, depression and antidepressant action</strong></p><p>P Cowen</p><p><strong>12. Prevalence and correlates of comorbid psychiatris illness in patients with heroin use disorder admitted to Stikland Opioid Detoxification Unit</strong></p><p>L Dannatt, K J Cloete, M Kidd, L Weich</p><p><strong>13. Investigating the association between diabetes mellitus, depression and psychological distress in a cohort of South African teachers</strong></p><p>A K Domingo, S Seedat, T M Esterhuizen, C Laurence, J Volmink, L Asmal</p><p><strong>14. Neuropeptide S -emerging evidence for a role in anxiety</strong></p><p>K Domschke</p><p><strong>15. Pathogenetics of anxiety</strong></p><p>K Domschke</p><p><strong>16. The effects of HIV on the fronto-striatal system</strong></p><p>S du Plessis, M Vink, J Joska, E Koutsilieri, C Scheller, B Spottiswoode, D Stein, R Emsley</p><p><strong>17. Effects of acute antipsychotic treatment on brain morphology in schizophrenia</strong></p><p>R Emsley, L Asmal, B Chiliza, S du Plessis, J Carr, A Goosen, M Kidd, M Vink, R Kahn</p><p><strong>18. Development of a genetic database resource for monitoring of breast cancer patients at risk of physical and psychological complications</strong></p><p>K Grant, F J Cronje, K Botha, J P Apffelstaedt, M J Kotze</p><p><strong>19. Unipolar mania reconsidered: Evidence from a South African study</strong></p><p><strong></strong>C Grobler</p><p><strong>20. Antipsychotic-induced movement disorders: Occurence and management</strong></p><p>P Haddad</p><p><strong>21. The place of observational studies in assessing the effectiveness of long-acting injectable antipsychotics</strong></p><p>P Haddad</p><p><strong>22. Molecular mechanisms of d-cycloserine in fear extinction: Insights from RNS sequencing</strong></p><p>S Hemmings, S Malan-Muller, L Fairbairn, M Jalali, E J Oakeley, J Gamieldien, M Kidd, S Seedat</p><p><strong>23. Schizophrenia: The role of inflammation</strong></p><p>DC Henderson</p><p><strong>24. Addictions: Emergent trends and innovations</strong></p><p>V Hitzeroth</p><p><strong>25. The socio-cultural-religious context of biological psychiatric practice</strong></p><p>B Janse van Rensburg</p><p><strong>26. Biochemical markers for identifying risk factors for disability progression in multiple sclerosis</strong></p><p><strong></strong>S Janse van Rensburg, M J Kotze, F J Cronje, W Davis, K Moremi, M Jalali Sefid Dashti, J Gamieldien, D Geiger, M Rensburg, R van Toorn, M J de Klerk, G M Hon, T Matsha, S Hassan, R T Erasmus</p><p><strong>27. Alcohol-induced psychotic disorder: Brain perfusion and psychopathology - before and after antipsychotic treatment</strong></p><p>G Jordaan, J M Warwick, D G Nel, R Hewlett, R Emsley</p><p><strong>28.'Pump and dump': Harm reduction strategies for breastfeeding while using substances</strong></p><p>L Kramer</p><p><strong>29. Adolescent neuropsychiatry - an emerging field in South African adolescent psychiatric services</strong></p><p>A Lachman</p><p><strong>30. Recovery versus remission, or what it means to be healthy for a psychiatric patient?</strong></p><p>B Latecki</p><p><strong>31. Holistic methods utilised to normalise behaviours in youth diagnosed with neuro-biochemical disorders</strong></p><p>P Macqueen</p><p><strong>32. Candidate genes and novel polymorphisms for anxiety disorder in a South African cohort</strong></p><p>N McGregor, J Dimatelis, S M J Hemmings, C J Kinnear, D Stein, V Russel, C Lochner</p><p><strong>33. Higher visual functioning</strong></p><p>A Moodley</p><p><strong>34. The effects of prenatal methylmercury exposure on trace element and antioxidant levels in rat offspring following 6-hydroxydopamine-induced neuronal insult</strong></p><p>Z M Moosa, W M U Daniels, M V Mabandla</p><p><strong>35. Paediatric neuropsychiatric movement disorders</strong></p><p>L Mubaiwa</p><p><strong>36. The South African national female offenders study</strong></p><p>M Nagdee, L Artz, C de Clercq, P de Wet, H Erlacher, S Kaliski, C Kotze, L Kowalski, J Naidoo, S Naidoo, J Pretorius, M Roffey, F Sokudela, U Subramaney</p><p><strong>37. Neurobiological consequences of child abuse</strong></p><p>C Nemeroff</p><p><strong>38. What do Stellenbosch Unviversity medical students think about psychiatry - and why should we care?</strong></p><p>G Nortje, S Suliman, K Seed, G Lydall, S Seedat</p><p><strong>39. Neurological soft skins in Nigerian Africans with first episode schizophrenia: Factor structure and clinical correlates</strong></p><p><strong></strong>A Ojagbemi, O Esan, O Gureje, R Emsley</p><p><strong>40. Should psychiatric patients know their MTHFR status?</strong></p><p>E Peter</p><p><strong>41. Clinical and functional outcome of treatment refractory first-episode schizophrenia</strong></p><p>L Phahladira, R Emsley, L Asmal, B Chiliza</p><p><strong>42. Bioethics by case discussion</strong></p><p>W Pienaar</p><p><strong>43. Reviewing our social contract pertaining to psychiatric research in children, research in developing countries and distributive justice in pharmacy</strong></p><p>W Pienaar</p><p><strong>44. The performance of the MMSE in a heterogenous elderly South African population</strong></p><p>S Ramlall, J Chipps, A I Bhigjee, B J Pillay</p><p><strong>45. Biological basis addiction (alocohol and drug addiction)</strong></p><p>S Rataemane</p><p><strong>46. Volumetric brain changes in prenatal methamphetamine-exposed children compared with healthy unexposed controls</strong></p><p><strong></strong>A Roos, K Donald, G Jones, D J Stein</p><p><strong>47. Single voxel proton magnetic resonance spectroscopy of the amygdala in social anxiety disorder in the context of early developmental trauma</strong></p><p>D Rosenstein, A Hess, S Seedat, E Meintjies</p><p><strong>48. Discussion of HDAC inhibitors, with specific reference to supliride and its use during breastfeeding</strong></p><p>J Roux</p><p><strong>49. Prevalence and clinical correlates of police contact prior to a first diagnosis of schizophrenia</strong></p><p>C Schumann, L Asmal, K Cloete, B Chiliza, R Emsley</p><p><strong>50. Are dreams meaningless?</strong></p><p>M Solms</p><p><strong>51. The conscious id</strong></p><p>M Solms<strong></strong></p><p><strong>52. Depression and resilience in HIV-infected women with early life stress: Does trauma play a mediating role?</strong></p><p>G Spies, S Seedat</p><p><strong>53. State of affairs analysis for forensic psychiatry in SA</strong></p><p>U Subramaney</p><p><strong>54. Escitalopram in the prevention of post-traumatic stress disorder: A pilot randomised controlled trial</strong></p><p>S Suliman, S Seedat, J Pingo, T Sutherland, J Zohar, D J Stein</p><p><strong>55. Epigenetic consequences of adverse early social experiences in primates</strong></p><p>S Suomi</p><p><strong>56. Risk, resilience, and gene x environment interactions in primates</strong></p><p>S Suomi</p><p><strong>57. Biological aspects of anorexia nervosa</strong></p><p>C Szabo</p><p><strong>58. Agents used and profiles of non-fatal suicidal behaviour in East London</strong></p><p>H Uys</p><p><strong>59. The contributions of G-protein coupled receptor signalling to opioid dependence</strong></p><p>J van Tonder</p><p><strong>60. Emerging trend and innovation in PTSD and OCD</strong></p><p>J Zohar</p><p><strong>61. Making the SASOP treatment guidelines operational</strong></p><p>E Allers</p><p><strong>Poster Presentations</strong></p><p><strong>62. Neuropsychological deficits in social anxiety disorder in the context of early developmental trauma</strong></p><p><strong></strong>S Bakelaar, D Rosenstein, S Seedat</p><p><strong>63.Social anxiety disorder in patients with or without early childhood trauma: Relationship to behavioral inhibition and activation and quality of life</strong></p><p><strong></strong>S Bakelaar, C Bruijnen, A Sambeth, S Seedat</p><p><strong>64. Exploring altered affective processing in obssessive compulsive disorder symptom subtypes</strong></p><p>E Breet, J Ipser, D Stein, C Lochner<strong><br /></strong></p><p><strong>65. To investigate the bias toward recognising the facial expression of disgust in obsessive compulsive disorder as well as the effect of escitalopram</strong></p><p>E Breet, J Ipser, D Stein, C Lochner</p><p><strong>66. A fatal-case of nevirapine-induced Stevens-Johnson's syndrome in HIV mania</strong></p><p>A Bronkhorst, Z Zingela, W M Qwesha, B P Magigaba<strong></strong></p><p><strong>67. Association of the COMT G472A (met/met) genotype with lower disability in people diagnosed with multiple sclerosis</strong></p><p>W Davis, S J van Rensburg, L Fisher, F J Cronje, D Geiger, M J Kotze</p><p><strong>68. Homocycsteine levels are associated with the fat mass and obesity associated gene FTO(intron 1 T&gt;A) polymorphism in MS patients</strong></p><p>W Davis, S J Van Rensburg, M J Kotze, L Fisher, M Jalali, F J Cronje, K Moremi, J Gamieldien, D Geiger, M Rensburg, R van Toorn, M J de Klerk, G M Hon, T Matsha, S Hassan, R T Erasmus</p><p><strong>69. Analysis of the COMT 472 G&gt;A (rs4680) polymorphism in relation to environmental influences as contributing factors in patients with schizophrenia</strong></p><p>D de Klerk, S J van Rensburg, R A Emsley, D Geiger, M Rensburg, R T Erasmus, M J Kotze</p><p><strong>70. Dietary folate intake, homocysteine levels and MTHFR mutation detection in South African patients with depression: Test development for clinical application </strong></p><p>D Delport, N vand der Merwe, R Schoeman, M J Kotze</p><p><strong>71. The use ofexome sequencing for antipsychotic pharmacogenomic applications in South African schizophrenia patients</strong></p><p>B Drogmoller, D Niehaus, G Wright, B Chiliza, L Asmal, R Emsley, L Warnich</p><p><strong>72. The effects of HIV on the ventral-striatal reward system</strong></p><p>S du Plessis, M Vink, J Joska, E Koutsilieri, C Scheller, B Spottiswoode, D Stein, R Emsley</p><p><strong>73. Xenomelia relates to asymmetrical insular activity: A case study of fMRI</strong></p><p>S du Plessis, M Vink, L Asmal</p><p><strong>74. Maternal mental helath: A prospective naturalistic study of the outcome of pregancy in women with major psychiatric disorders in an African country</strong></p><p>E du Toit, L Koen, D Niehaus, B Vythilingum, E Jordaan, J Leppanen</p><p><strong>75. Prefrontal cortical thinning and subcortical volume decrease in HIV-positive children with encephalopathy</strong></p><p>J P Fouche, B Spottiswoode, K Donald, D Stein, J Hoare</p><p><strong>76. H-magnetic resonance spectroscopy metabolites in schizophrenia</strong></p><p>F Howells, J Hsieh, H Temmingh, D J Stein</p><p><strong>77. Hypothesis for the development of persistent methamphetamine-induced psychosis</strong></p><p><strong></strong> J Hsieh, D J Stein, F M Howells</p><p><strong>78. Culture, religion, spirituality and psychiatric practice: The SASOP Spirituality and Psychiatry Special Interest Group Action Plan for 2012-2014</strong></p><p>B Janse van Rensburg</p><p><strong>79. Cocaine reduces the efficiency of dopamine uptake in a rodent model of attention-deficit/hyperactivity disorder: An <em>in vivo</em> electrochemical study</strong></p><p><strong></strong>L Kellaway, J S Womersley, D J Stein, G A Gerhardt, V A Russell</p><p><strong>80. Kleine-Levin syndrome: Case in an adolescent psychiatric unit</strong></p><p>A Lachman</p><p><strong>81. Increased inflammatory stress specific clinical, lifestyle and therapeutic variables in patients receiving treatment for stress, anxiety or depressive symptoms</strong></p><p>H Luckhoff, M Kotze, S Janse van Rensburg, D Geiger</p><p><strong>82. Catatonia: An eight-case series report</strong></p><p>M Mabenge, Z Zingela, S van Wyk</p><p><strong>83. Relationship between anxiety sensitivity and childhood trauma in a random sample of adolescents from secondary schools in Cape Town</strong></p><p>L Martin, M Viljoen, S Seedat</p><p><strong>84. 'Making ethics real'. An overview of an ethics course presented by Fraser Health Ethics Services, BC, Canada</strong></p><p>JJ McCallaghan</p><p><strong>85. Clozapine discontinuation rates in a public healthcare setting</strong></p><p>M Moolman, W Esterhuysen, R Joubert, J C Lamprecht, M S Lubbe</p><p><strong>86. Retrospective review of clozapine monitoring in a publica sector psychiatric hospital and associated clinics</strong></p><p>M Moolman, W Esterhuysen, R Joubert, J C Lamprecht, M S Lubbe</p><p><strong>87. Association of an iron-related TMPRSS6 genetic variant c.2007 C&gt;7 (rs855791) with functional iron deficiency and its effect on multiple sclerosis risk in the South African population</strong></p><p>K Moremi, S J van Rensburg, L R Fisher, W Davis, F J Cronje, M Jalali Sefid Dashti, J Gamieldien, D Geiger, M Rensburg, R van Toorn, M J de Klerk, G M Hon, T Matsha, S Hassan, R T Erasmus, M Kidd, M J Kotze</p><p><strong>88. Identifying molecular mechanisms of apormophine-induced addictive behaviours</strong></p><p>Z Ndlazi, W Daniels, M Mabandla</p><p><strong>89. Effects of lifestyle factors and biochemistry on the major neck blood vessels in patients with mutiple sclerosis</strong></p><p>M Nelson, S J van Rensburg, M J Kotze, F Isaacs, S Hassan</p><p><strong>90. Nicotine protects against dopamine neurodegenration and improves motor deficits in a Parkinsonian rat model</strong></p><p>N Ngema, P Ngema, M Mabandla, W Daniels</p><p><strong>91. Cognition: Probing anatomical substrates</strong></p><p>H Nowbath</p><p><strong>92. Chronic exposure to light reverses the effects of maternal separation on the rat prefrontal cortex</strong></p><p>V Russel, J Dimatelis</p><p><strong>93. Evaluating a new drug to combat Alzheimer's disease</strong></p><p>S Sibiya, W M U Daniels, M V Mabandla</p><p><strong>94. Structural brain changes in HIV-infected women with and without childhood trauma</strong></p><p>G Spies, F Ahmed, C Fennema-Notestine, S Archibald, S Seedat</p><p><strong>95. Nicotine-stimulated release of hippocampal norepinephrine is reduced in an animal model of attention-deficit/ hyperactivity disorder: the spontaneously hypertensive rat</strong></p><p>T Sterley</p><p><strong>96. Brain-derive neurotrophic factor (BDNF) protein levels in anxiety disorders: Systematic review and meta-regression analysis</strong></p><p>S Suliman, S M J Hemmings, S Seedat</p><p><strong>97. A 12-month retrospective audit of the demographic and clinical profile of mental healthcare users admitted to a district level hospital in the Western Cape, South Africa</strong></p><p>E Thomas, K J Cloete, M Kidd, H Lategan</p><p><strong>98. Magnesium recurarization: A comparison between reversal of neuromuscular block with sugammadex v. neostigmine/ glycopyrrolate in an <em>in vivo</em> rat model</strong></p><p><strong></strong>M van den Berg, M F M James, L A Kellaway</p><p><strong>99. Identification of breast cancer patients at increased risk of 'chemobrain': Case study and review of the literature</strong></p><p>N van der Merwe, R Pienaar, S J van Rensburg, J Bezuidenhout, M J Kotze</p><p><strong>100. The protective role of HAART and NAZA in HIV Tat protein-induced hippocampal cell death</strong></p><p>S Zulu, W M U Daniels, M V Mabandla</p>

Abstract Background Advanced maternal age, family history of diabetes, pre-gestational obesity, increased level of HbA1c, history of gestational diabetes mellitus (GDM), and poor pregnancy consequences are considered risk factors for antenatal insulin requirement in women with GDM. However, the role of assisted reproductive technology (ART) in increasing the risk of insulin therapy in pregnancies complicated with GDM remained elusive. The current study aimed to determine the role of ART in predicting insulin therapy in GDM women and investigate the clinical and biochemical factors predicting the need for insulin therapy in pregnancies complicated with GDM. Methods In this prospective cohort study, 236 Iranian women with GDM were diagnosed by one-step oral glucose tolerance test (OGTT) between October 2014 and June 2017. They were mainly assigned to two groups; the first group (n = 100) was designated as ART which was further subdivided into two subgroups as follows: 60 participants who received medical nutrition therapy (MNT) and 40 participants who received MNT plus insulin therapy (MNT-IT). The second group (n = 136) was labeled as the spontaneous conception (SC), consisting of 102 participants receiving MNT and 34 participants receiving MNT in combination with IT (MNT-IT). The demographic, clinical, and biochemical data were compared between groups. Multivariate logistic regression was performed to estimate prognostic factors for insulin therapy. Results A higher rate of insulin therapy was observed in the ART group as compared with the SC group (40% vs. 25%; P < 0.001). Multivariate logistic regression demonstrated that maternal age ≥ 35 years [OR: 2.91, 95% CI: (1.28–6.62)], high serum FBS [1.10: (1.04–1.16)], HbA1c [1.91 (1.09–3.34)], and ART treatment [2.94: (1.24–6.96)] were independent risk factors for insulin therapy in GDM women. Conclusions Apart from risk factors mentioned earlier, ART may be a possible prognostic factor for insulin therapy in pregnancies complicated with GDM.

Abstract Prenatal exposure to nicotine, tobacco’s major addictive constituent, has been shown to reduce birth weight and increases apoptosis, oxidative stress, and mitochondrial dysfunction in the postnatal pancreas. Given that upregulated levels of the pro-oxidative adapter protein p66shc is observed in growth-restricted offspring and is linked to beta-cell apoptosis, the goal of this study was to investigate whether alterations in p66shc expression underlie the pancreatic deficits in nicotine-exposed offspring. Maternal administration of nicotine in rats increased p66shc expression in the neonatal pancreas. Similarly, nicotine treatment augmented p66shc expression in INS-1E pancreatic beta cells. Increased p66shc expression was also associated with decreased histone H3 lysine 9 methylation. Finally, nicotine increased the expression of Kdm4c, a key histone lysine demethylase, and decreased Suv39h1, a critical histone lysine methyltransferase. Collectively, these results suggest that upregulation of p66shc through posttranslational histone modifications may underlie the reported adverse outcomes of nicotine exposure on pancreatic function.

Neurodevelopmental disorders can stem from pharmacological, genetic, or environmental causes and early diagnosis is often a key to successful treatment. To improve early detection of neurological motor impairments, we developed a deep neural network for data-driven analyses. The network was applied to study the effect of maternal nicotine exposure prior to conception on 10-day-old rat pup motor behavior in an open field task. Female Long-Evans rats were administered nicotine (15 mg/L) in sweetened drinking water (1% sucralose) for seven consecutive weeks immediately prior to mating. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams vs. control dams (87 vs. 64% classification accuracy). Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in “warm-up” behavior (repeated movements along specific body dimensions) that were predictive of nicotine exposure. The results suggest novel findings that maternal preconception nicotine exposure delays and alters offspring motor development. Similar behavioral symptoms are associated with drug-related causes of disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder in human children. Thus, the identification of motor impairments in at-risk offspring here shows how neuronal networks can guide the development of more accurate behavioral tests to earlier diagnose symptoms of neurodevelopmental disorders in infants and children.

AbstractDespite persistent public health initiatives, many women continue to smoke during pregnancy. Since maternal smoking has been linked to persisting sex-dependent neurobehavioral deficits in offspring, some consider nicotine to be a safer alternative to tobacco during pregnancy, and the use of electronic nicotine delivery systems is on the rise. We presently show, however, that sustained exposure to low doses of nicotine during fetal development, approximating plasma levels seen clinically with the nicotine patch, produces substantial changes in developing corticostriatal dopamine systems in adolescence. Briefly, pregnant dams were implanted on gestational day 4 with an osmotic minipump that delivered either saline (GS) or nicotine (3 mg/kg/day) (GN) for two weeks. At birth, pups were cross-fostered with treatment naïve dams and were handled daily. Biochemical analyses, signaling assays, and behavioral responses to cocaine were assessed on postnatal day 32, representative of adolescence in the rodent. GN treatment had both sex-dependent and sex-independent effects on prefrontal dopamine systems, altering Catechol-O-methyl transferase (COMT)-dependent dopamine turnover in males and norepinephrine transporter (NET) binding expression in both sexes. GN enhanced cocaine-induced locomotor activity in females, concomitant with GN-induced reductions in striatal dopamine transporter (DAT) binding. GN enhanced ventral striatal D2-like receptor expression and G-protein coupling, while altering the roles of D2 and D3 receptors in cocaine-induced behaviors. These data show that low-dose prenatal nicotine treatment sex-dependently alters corticostriatal dopamine system development, which may underlie clinical deficits seen in adolescents exposed to tobacco or nicotine in utero.

Changes in decidual macrophage polarization affect local inflammatory microenvironment and lead to adverse pregnancy outcomes. However, the regulatory mechanism of macrophage polarization in preeclampsia (PE) remains unclear. In this study, we found that α7nAChR expression was significantly down-regulated in decidual macrophages in PE patients compared to normal pregnant women, accompanied by a reduced proportion of M2 phenotype and an increased proportion of M1 phenotype; these results suggested that the reduced α7nAChR activity might contribute to changes in the polarization of decidual macrophages. Then, we further investigated the regulatory role of α7nAChR activation by nicotine on decidual macrophage polarization and placental remodeling in the PE-like mouse model. The PE mice were obtained by i.p. injection of 10 µg/kg lipopolysaccharide (LPS) gestational day (GD) 13, and 40 µg/kg LPS daily until GD16. Subcutaneous injection of 1.0 mg/kg nicotine was administrated from GD14 to GD18. Nicotine treatment increased the decreased M2 phenotype and inhibited the increased M1 phenotype in decidua of pregnant mice induced by LPS. The levels of pro-inflammatory cytokines in decidua were higher but the levels of anti-inflammatory cytokines were lower in PE mice compared to the controls, nicotine reversed these changes. The level of choline acetyltransferase (CHAT) was reduced in the LPS-treated group, it was increased following nicotine treatment. Damage of spiral artery remodeling and down-regulation of markers related to trophoblast invasion in placentas were found in PE mice; nicotine improved these pathological structures of placentas. α-bungarotoxin (α-BGT) which is specific antagonist for α7nAChR could abolish the effects of nicotine on decidual macrophage polarization, trophoblast arrangement and vascular structure in placental tissue in PE mice. These results suggest that α7nAChR plays an important regulatory role in maternal-fetal inflammation and placental remodeling in preeclampsia and may provide a theoretical basis for the discovery of new strategies for preeclampsia.

The objective of this paper was to identify the factors associated with moderate to high nicotine dependence in a sample of pregnant smokers from Romania. Data was collected through an ongoing cross-sectional pilot study from 130 pregnant smokers. The questionnaire included five main sections: socio-demographic information, medical and reproductive history, alcohol and smoking behaviors, emotional health and information regarding the relationship with the partner. Older age, first pregnancy, a negative screening for anxiety and depression, and negative partner interactions related to smoking were significantly correlated with increased odds of moderate to high nicotine dependence during pregnancy. In addition, high dyadic efficacy, low self-efficacy, high pregnancy-related anxiety, and a non-smoking life partner were correlated with increased odds of moderate to high nicotine dependence, although the results did not reach statistical significance. Once the level nicotine dependence is established, cessation treatment should target specific risks that are associated with this dependence. Maternal risk factors, spousal smoking status, and interactions in the couple hold promise in future tobacco cessation interventions. Future research should focus on both the prenatal smoking cessation and on postnatal relapse prevention among highly dependent women.

IntroductionStudies in the general population suggest that varenicline is more effective than nicotine replacement therapy (NRT) for smoking cessation. However, clinical guidelines recommend against the use of varenicline during pregnancy and suggest NRT be used when the expected benefits outweigh the potential risks. Objectives and ApproachWe evaluated whether varenicline was more effective than NRT for smoking cessation when used during pregnancy. Routinely-collected records of all births (01/01/2011-12/31/2012) in New South Wales and Western Australia were used to identify a cohort of women who smoked during the first 20 weeks of pregnancy. Pharmaceutical dispensing data were then linked to identify varenicline or NRT dispensing in the first 20 weeks of pregnancy. Smoking cessation was defined as women reported not smoking after the first 20 weeks of pregnancy. Inverse probability of treatment weighting with propensity scores were used to account for differences between the two treatment groups. ResultsOverall, 117 women used varenicline and 135 NRT in the first 20 weeks of pregnancy. In the unweighted sample, more women who used varenicline quit smoking after the first 20 weeks than women using NRT (28.2% vs. 11.1%, crude rate difference:17.1%, 95% confidence intervals[CI]:7.4-26.8%). In the weighted sample, quitting rate was 12.7% (95%CI:0.8-24.6%) higher in pregnant smokers who used varenicline (27.4% vs. 14.7%) when compared to those who used NRT. Conclusion/ImplicationsPregnant smokers using varenicline were more likely to quit smoking than those using NRT. This information will assist healthcare providers to make informed recommendations, but data regarding safety of varenicline in pregnancy are also urgently needed. Future studies with greater statistical power are required to confirm our results.

Abstract Background Acceptance of smoking cessation support during antenatal care and associated quitting behaviours of pregnant Aboriginal women or women having an Aboriginal baby has not been investigated. This study aimed to determine, among pregnant women who smoke and attended AMIHS for their antenatal care: The acceptance of smoking cessation support, factors associated with acceptance and barriers to acceptance; The prevalence of quitting behaviours and factors associated with quitting behaviours. Methods A cross-sectional telephone survey of women who attended 11 AMIHSs for their antenatal care during a 12 month period in the Hunter New England Local Health District of New South Wales. Results One hundred women contacted consented to complete the survey (76%). Of those offered cessation support, 68% accepted NRT, 56% accepted follow-up support and 35% accepted a Quitline referral. Participants accepting NRT had greater odds of quitting smoking at least twice during the antenatal period [OR = 6.90 (CI: 1.59–29.7)] and those reporting using NRT for greater than eight weeks had six times the odds of quitting smoking for one day or more [OR = 6.07 (CI: 1.14–32.4)]. Conclusions Aboriginal women or women having an Aboriginal baby who smoke make multiple attempts to quit during pregnancy and most women accept smoking cessation support when offered by their antenatal care providers. Acceptance of care and quitting success may be improved with increased focus on culturally appropriate care and enhanced training of antenatal care providers to increase skills in treating nicotine addiction and supporting women to use NRT as recommended by treatment guidelines.

AbstractIt is widely accepted that narcotic use during pregnancy and specific environmental factors (e.g., maternal immune activation and chronic stress) may increase risk of neuropsychiatric illness in offspring. However, little progress has been made in defining human-specific in utero neurodevelopmental pathology due to ethical and technical challenges associated with accessing human prenatal brain tissue. Here we utilized human induced pluripotent stem cells (hiPSCs) to generate reproducible organoids that recapitulate dorsal forebrain development including early corticogenesis. We systemically exposed organoid samples to chemically defined “enviromimetic” compounds to examine the developmental effects of various narcotic and neuropsychiatric-related risk factors within tissue of human origin. In tandem experiments conducted in parallel, we modeled exposure to opiates (μ-opioid agonist endomorphin), cannabinoids (WIN 55,212-2), alcohol (ethanol), smoking (nicotine), chronic stress (human cortisol), and maternal immune activation (human Interleukin-17a; IL17a). Human-derived dorsal forebrain organoids were consequently analyzed via an array of unbiased and high-throughput analytical approaches, including state-of-the-art TMT-16plex liquid chromatography/mass-spectrometry (LC/MS) proteomics, hybrid MS metabolomics, and flow cytometry panels to determine cell-cycle dynamics and rates of cell death. This pipeline subsequently revealed both common and unique proteome, reactome, and metabolome alterations as a consequence of enviromimetic modeling of narcotic use and neuropsychiatric-related risk factors in tissue of human origin. However, of our 6 treatment groups, human-derived organoids treated with the cannabinoid agonist WIN 55,212-2 exhibited the least convergence of all groups. Single-cell analysis revealed that WIN 55,212-2 increased DNA fragmentation, an indicator of apoptosis, in human-derived dorsal forebrain organoids. We subsequently confirmed induction of DNA damage and apoptosis by WIN 55,212-2 within 3D human-derived dorsal forebrain organoids. Lastly, in a BrdU pulse-chase neocortical neurogenesis paradigm, we identified that WIN 55,212-2 was the only enviromimetic treatment to disrupt newborn neuron numbers within human-derived dorsal forebrain organoids. Cumulatively this study serves as both a resource and foundation from which human 3D biologics can be used to resolve the non-genomic effects of neuropsychiatric risk factors under controlled laboratory conditions. While synthetic cannabinoids can differ from naturally occurring compounds in their effects, our data nonetheless suggests that exposure to WIN 55,212-2 elicits neurotoxicity within human-derived developing forebrain tissue. These human-derived data therefore support the long-standing belief that maternal use of cannabinoids may require caution so to avoid any potential neurodevelopmental effects upon developing offspring in utero.

Background: Approximately 40% of the population reports sleep problems such as poor quality sleep and insufficient sleep duration. Physical activity (PA) can help improve sleep, but data on whether PA intensity or duration is most strongly associated with sleep are lacking. In addition, given that sedentary behaviour (e.g., TV, computer use) is distinct from physical inactivity, the association between sedentary behaviour and sleep in young adults needs to be characterized. Objective: To describe the relationships between sleep quality and sleep duration and (1) frequency and duration of light, moderate, and vigorous PA, and (2) different types of sedentary behaviours (TV, computer, reading) in young adults. Methods: Self-report data for 658 participants were from the 22nd wave of the Nicotine Dependence in Teens (NDIT) cohort study (mean age=24.0 years, 46% male [300 of 658]). PA measures assessed frequency (number of days) and minutes of light, moderate and vigorous PA in the past week. Sedentary measures assessed number of hours spent reading, watching TV, and using the computer per day. Sleep measures included (1) the Pittsburgh Sleep Quality Index (PSQI) which assessed seven dimensions of sleep (daytime dysfunction, disturbances, duration, efficiency, latency, quality, use of sleeping medications), (2) general sleep quality, and (3) sleep duration in the past month. General sleep quality and sleep duration were two separate additional measures distinct from similar PSQI items (r=0.73 between general sleep quality and PSQI score; r=0.69 between sleep duration and PSQI score). Data were analyzed using multiple linear regression. Due to evidence of non-normality the PSQI score was log-transformed. Results: Controlling for age, sex, and maternal education, each additional day of light or vigorous PA was associated with 3 minutes less sleep per night (p<0.05). Each additional 10 minutes of moderate PA was associated with greater general sleep quality (β=0.004, p=0.04). TV was associated with a poorer PSQI score (β=0.01, p<0.05) and each additional hour of reading was associated with 2 minutes less sleep per night (p=0.04). Computer use was associated with a poorer PSQI score (β=0.02, p=0.005) and poorer sleep quality (β=-0.02, p=0.05). Results were similar when sedentary and PA measures were included in the same model. The inclusion of body mass index, self-rated mental and general health, and stress did not affect the results and were omitted from the final models. Conclusion: PA and sedentary behaviours are independently associated with sleep duration and quality. Sedentary behaviours are associated with poorer sleep duration and quality. In contrast, PA frequency may decrease sleep duration while PA duration may improve sleep quality. Clinicians who treat sleep problems in young adults may need to take PA and sedentary behavior into account in treatment plans.