Добірка наукової літератури 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.

Masters of Science
It is well documented that cigarette smoking and nicotine exposure create widespread physiological disorders in humans and animals. The primary tobacco constituent that is responsible for the toxicological consequences associated with the effects of tobacco smoke is nicotine (Van Lancker 1977). After maternal nicotine exposure, the fetal gonads and lungs are the principle sites of nicotine damage (Szuts et al. 1978, Mosier & Jansons 1972). Whilst the fetal lung has received widespread attention in this regard (Maritz 1988), the testis has never been studied. Therefore, I have chosen to explore the effects of maternal nicotine exposure on the testis of male offspring by evaluating various aspects of the male reproductive tract. It is believed that, in adult male smokers (Rosenberg 1987, Handelsman et al. 1984) and sexually mature animals (Mattison 1982) that are exposed to nicotine, male fertility may be compromised. However, these studies provide conflicting data on single parameters. It was therefore my objective to identify the effect of nicotine exposure on the male reproductive tract and to establish possible sites through which these effects may be mediated in adult male rats. The influence of nicotine was then investigated in male offspring after maternal nicotine treatment (MNT), and in sexually mature adult males after direct adult nicotine treatment (ANT). In the former experiment (MNT), 7 day pregnant rats were exposed to Img nicotine/kg body weight/day. Therefore, these offspring were indirectly exposed to nicotine during fetal development and early neonatal development. After weaning the animals were divided into two groups. One group did not receive further treatment (withdrawn group), whilst the other group was continually treated till adulthood (nicotine group), after which both groups were sampled together with the control. In the latter experiment (ANT), the animals were treated daily for 3 weeks and were sampled as above (MNT animals). The fundamental parameter investigated in both experiments to assess reproductive status was sperm quality (motility and morphology). Thereafter, it was necessary to establish a possible site where the effects of nicotine would occur. Testicular growth, epididymal structure, and plasma testosterone content were measured as probable localities of nicotine's effect. The results signify that maternal nicotine exposure poses a greater threat to the male reproductive system than adult nicotine exposure. In the MNT experiment, progressive sperm motility of the nicotine and withdrawn groups were 1.7% and 3.4% respectively. The proportion of abnormal sperm was 72% in each of the above groups. The lower quality sperm that is evident after nicotine exposure implies that the fertilizing ability of the animals may be impaired during adulthood. The data on testicular growth indicates that nicotine exposure during early development results in slower testicular development until maturity. The epididymal lining of these animals also increased after nicotine exposure, indicating increased cellular activity. However, these results from testicular and epididymal studies are inconclusive and need further work. In the ANT experiment, progressive sperm motility of the nicotine group was 1.2%, whilst the proportion of abnormal sperm was 58%. No other parameter was affected after nicotine exposure to adult animals. From the above data it is evident that nicotine exposed animals were subject to greater nicotine damage after maternal nicotine exposure during early development. Moreover, within the maternal nicotine treated experiment, the withdrawal of nicotine after weaning did not appear to reverse the injurious effects of nicotine that were established during early development. These effects were evident since the nicotine and withdrawn groups showed similar levels of damage in all instances. The most profound effects after adult nicotine exposure and maternal nicotine exposure were on sperm quality. The probable site of sperm impairment appears to be via retarded testicular growth and possibly, structural status of the epididymis after maternal nicotine exposure. The results from adult nicotine exposure however, suggest that sperm cells may be directly affected by nicotine exposure. An epidemiological survey was included to validate the basic conclusions established in animal research when compared to clinical data from human patients. No statistically significant changes were observed in this study between the patient's spermiogram results versus his smoking habits, and, that of his mother. From the level of significance it was concluded that cigarette smoking does not appear to be a cause of impaired fertility in already infertile patients. However, the data does suggest that cigarette smoking may well be a precipitating agent in male infertility. Experimentally, nicotine exposure impairs the male reproductive system to some extent. The effects of which are irreversible after indirect exposure (MNT) during development and may begin with poor testicular development. The effects of adult nicotine exposure implies that nicotine exposure in mature animals (ANT) acts directly on sperm cells to incapacitate them. It is well advised that cigarette smoking should be curbed in pregnant women and in adult males to alleviate contributing effects to male infertility.