Effect of cigarette smoking on vascular flows in pregnancies complicated by intrauterine growth restriction

Exposure to tobacco smoke during pregnancy may result in intrauterine growth restriction (IUGR). In the study, the effect of tobacco smoke on vascular flows in the middle cerebral artery, umbilical artery, ductus venosus in fetuses and uterine artery in pregnancies complicated by IUGR was investigated.The study subjects were divided into three groups: smoking women with IUGR (n = 31), women with idiopathic IUGR (n = 28) and healthy controls (n = 50). Fetal biometry and flow parameters were measured. Concentration of heavy metals and antioxidants was tested in maternal blood and fetal umbilical cord blood. The Student t test and multiple regression analysis were used.Cotinine and cadmium concentrations were significantly higher in smokers (55.23 ± 54.23, 1.52 ± 0.9), while metallothionein was significantly higher (22.94 ± 8.64) in the idiopathic IUGR group. Strong correlations between cotinine and cadmium concentrations and cerebral–umbilical index were found.Long-term exposure to tobacco smoke deteriorates flows in vital fetal vessels.     

Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression

Experimental data suggest that the endogenous cannabinoid system is involved in mood regulation, but no study has been performed so far to investigate the role of endocannabinoid genes in the susceptibility to major depression (MD) and/or bipolar disorder (BD). We assessed the CB1 receptor gene (CNR1) single nucleotide polymorphism (SNP) rs1049353 (1359 G/A) and the fatty acid amide hydrolase (FAAH) gene rs324420 SNP (cDNA 385C to A) for their associations with MD and/or BD in 83 Caucasian patients with recurrent MD, 134 Caucasian individuals with BD, and 117 Caucasian healthy subjects. The distribution of the CNR1 1359 G/A genotypes and alleles significantly differed among the groups (χ² = 12.595; df = 4, P = 0.01 for genotypes; χ² = 13.773; df = 2, P = 0.001 for alleles) with MD patients showing a higher frequency of both AG, GG genotypes and A allele as compared to healthy controls. The distribution of the FAAH cDNA 385C to A genotypes, according to the CC dominant model (AA + AC vs. CC), significantly differed among the groups (χ² = 6.626; df = 2, P = 0.04), with both BD patients and MD patients showing a non-significant slightly higher frequency of the AC genotype. These findings, although preliminary, suggest that the CNR1 1359 G/A and the FAAH cDNA 385C to A gene variants may contribute to the susceptibility to mood disorders.     

Examining the effects of drinking and interpersonal protective behaviors on unwanted sexual experiences in college women

IntroductionRecent evidence suggests interpersonal protective behaviors (IPBs) may be more effective than alcohol-based strategies at decreasing alcohol-related sexual consequences. However, no studies have examined individual IPBs to assess their unique influences on specific sexual consequences. The current study used a longitudinal design to examine the direct effects of typical weekly drinking and specific IPBs on unwanted sex. IPBs were also examined as moderators of the relationship between drinking and unwanted sex.MethodsRandomly sampled female drinkers attending a northeastern university (N = 191) completed a baseline survey measuring typical weekly drinking and IPBs and a six-month follow-up assessing unwanted sex. Bootstrapped regression examined the effects.ResultsDrinking predicted unwanted sex after accounting for IPBs (range of bs = .008–.009, SE = .005, 95% CI [.000, .02]). Vigilance-related IPBs were negatively associated with unwanted sex after controlling for drinking (b = −.052, SE = .025, 95% CI [−.107, −.008]). The IPB “Talking to people who know one's potential dating or sexual partner to find out what s/he is like” significantly moderated the drinking–unwanted sex relationship (b = −.009, SE = .004, 95% CI [−.018, −.003]). At above-average drinking levels, women who used this IPB more frequently reported fewer episodes of unwanted sex.ConclusionFindings revealed obtaining information about a potential partner significantly reduced the impact of drinking on unwanted sex for heavier drinkers. Future research examining how women implement this IPB may clarify its role in reducing unwanted sex.     

X-Ray Diffraction and Infrared Spectroscopy of N,N- Dimethylformamide and Dimethyl Sulfoxide Solvatomorphs of Betulonic Acid

X-ray diffraction and infrared spectroscopy measurements for the N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) solvatomorphs of betulonic acid (BA) were investigated. BA [3-oxolup-20(29)-en-28-oic acid, C₃₀H₄₆O₃] exhibits a wide spectrum of biological activities and is considered to be a promising natural agent for the treatment of various cancer diseases. BA as a noncrystalline substance was obtained by oxidation of betulin. Crystal structures and the spectral data allowed analysis of hydrogen bonding (H-bonding), molecular conformation, and crystal packing differences in the solvatomorphs. Crystals of BA solvates were grown from the DMF–acetone (1:10, v/v) and DMSO–water (9:1, v/v) solutions. BA–DMF (1:1) solvate crystallizes in the monoclinic P2₁ space group, Z = 2. The unit cell parameters are as follows: cell lengths a = 13.2458(5) Å, b = 6.6501(2) Å, c = 17.9766(7) Å, and β = 110.513(4)°. BA–DMSO (1:1) solvate crystallizes in the orthorhombic P2₁2₁2₁ (Z = 4) space group with the following unit cell parameters: a = 6.6484(4) Å, b = 13.3279(8) Å, and c = 32.6821(19) Å. Conformational analysis of the six-membered rings, cyclopentane ring, and isopropenyl group showed differences in comparison with other betulin derivatives examined earlier. For both solvates, the intermolecular packing arrangement was governed mainly by H-bonds. The shortest H-bonds with D?A distances of 2.604 and 2.657 Å, and almost linear DH?A connection occurred between OH of carboxylic group of BA and oxygen atoms from OC and O = S groups of DMF and DMSO, respectively.     

Aging-Driven Decomposition in Zolpidem Hemitartrate Hemihydrate and the Single-Crystal Structure of Its Decomposition Products

The “aging-driven” decomposition of zolpidem hemitartrate hemihydrate (form A) has been followed by X-ray powder diffraction (XRPD), and the crystal and molecular structures of the decomposition products studied by single-crystal methods. The process is very similar to the “thermally driven” one, recently described in the literature for form E (Halasz and Dinnebier. 2010. J Pharm Sci 99(2): 871–874), resulting in a two-phase system: the neutral free base (common to both decomposition processes) and, in the present case, a novel zolpidem tartrate monohydrate, unique to the “aging-driven” decomposition. Our room-temperature single-crystal analysis gives for the free base comparable results as the high-temperature XRPD ones already reported by Halasz and Dinnebier: orthorhombic, Pcba, a = 9.6360(10) Å, b = 18.2690(5) Å, c = 18.4980(11) Å, and V = 3256.4(4) Å³. The unreported zolpidem tartrate monohydrate instead crystallizes in monoclinic P2₁, which, for comparison purposes, we treated in the nonstandard setting P112₁ with a = 20.7582(9) Å, b = 15.2331(5) Å, c = 7.2420(2) Å, γ = 90.826(2)°, and V = 2289.73(14) Å³. The structure presents two complete moieties in the asymmetric unit (z = 4, z′ = 2). The different phases obtained in both decompositions are readily explained, considering the diverse genesis of both processes.     

Effects of environmental endocrine disruptors,including insecticides used for malaria vector control on reproductive parameters of male rats

The male reproductive system is sensitive to endocrine disrupting chemicals (EDCs) during critical developmental windows. Male Sprague-Dawley rats were exposed in utero-, during lactation- and directly to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and a mixture of DDT, deltamethrin (DM), p-nonylphenol (p-NP) and phytoestrogens, at concentrations found in a malaria-area. After dosing for 104 days, histological assessments and reproductive-endpoints were assessed. The anogenital distance (AGD) (P = 0.005) was shorter in the mixture-exposed group, while the prostate mass (P = 0.018) was higher in the DDT-exposed group. A higher testicular mass and abnormal histology was observed in the DDT-(P = 0.019), DDE-(P = 0.047) and mixture-exposed (P < 0.005) groups. This study shows that in utero-, lactational- and direct exposure to EDCs present in a malaria-area negatively affects male reproductive parameters in rats. These findings raise concerns to EDC-exposures to mothers living in malaria-areas and the reproductive health of their male offspring.     

Lisinopril Dihydrate: Single-Crystal X-Ray Structure and Physicochemical Characterization of Derived Solid Forms

Screening for new solid forms of the antihypertensive lisinopril was performed by recrystallization of the commercial form, lisinopril dihydrate, from various solvents and by exposing the product of its dehydration to a series of vapors under controlled conditions. Modifications other than the dihydrate encountered in the study included new anhydrous and amorphous forms, with intrinsic dissolution rates significantly greater than that of the dihydrate. Further physicochemical characterization included constant and programmed temperature powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, and Fourier transform infrared spectroscopy. In the course of this study, the single-crystal X-ray structure of lisinopril dihydrate, [a = 14.550(2), b = 5.8917(8), c = 14.238(2) Å, β = 112.832(3)° at T = 173(2) K , space group P2₁, Z = 2], was determined for the first time, revealing its double zwitterionic character in the solid state.     

Changes in plasma levels of asymmetric dimethylarginine,symmetric dimethylarginine,and arginine after a single dose of vardenafil in patients with pulmonary hypertension

ObjectiveWe investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine.Patients and methodsADMA, SDMA, and arginine were measured (0–540 min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60 min.ResultsA reduction in ADMA was observed at 30 and 45 min with a median change of − 11.1% (P = 0.021) and − 12.5% (P = 0.002). SDMA decreased with a median − 5.3% change (P = 0.032) at 45 min. An increase in arginine, median 40.3% (P = 0.002), 45.0% (P = 0.010), and 77.1% (P = 0.008) was observed at 120, 300, and 540 min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P = 0.012), 32.5% (P = 0.003), 26.5% (P = 0.021), 33% (P = 0.007), 48.5% (P = 0.007), and 63.1% (P = 0.008) was observed at 15, 45, 60, 120, 300, and 540 min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540 min (r = 0.80; P = 0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r = 0.65; P = 0.023), and baseline SDMA (r = 0.61; P = 0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r = 0.59; P = 0.045) and baseline cardiac index (CI) (r = 0.61; P = 0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r = − 0.79; P = 0.002). A correlation between change (0–60 min) in CI and change in arginine (r = 0.77; P = 0.003) as well as change in the arginine/ADMA ratio (r = 0.61; P = 0.037) was observed.ConclusionsVardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in CI.     

Visceral sensitivity,anxiety, and smoking among treatment-seeking smokers

It is widely recognized that smoking is related to abdominal pain and discomfort, as well as gastrointestinal disorders. Research has shown that visceral sensitivity, experiencing anxiety around gastrointestinal sensations, is associated with poorer gastrointestinal health and related health outcomes. Visceral sensitivity also increases anxiety symptoms and mediates the relation with other risk factors, including gastrointestinal distress. No work to date, however, has evaluated visceral sensitivity in the context of smoking despite the strong association between smoking and poor physical and mental health. The current study sought to examine visceral sensitivity as a unique predictor of cigarette dependence, threat-related smoking abstinence expectancies (somatic symptoms and harmful consequences), and perceived barriers for cessation via anxiety symptoms. Eighty-four treatment seeking adult daily smokers (M_age = 45.1 years [SD = 10.4]; 71.6% male) participated in this study. There was a statistically significant indirect effect of visceral sensitivity via general anxiety symptoms on cigarette dependence (b = 0.02, SE = 0.01, Bootstrapped 95% CI [0.006, 0.05]), smoking abstinence somatic expectancies (b = 0.10, SE = 0.03, Bootstrapped 95% CI [0.03, 0.19]), smoking abstinence harmful experiences (b = 0.13, SE = 0.05, Bootstrapped 95% CI [0.03, 0.25]), and barriers to cessation (b = 0.05, SE = 0.06, Bootstrapped 95% CI [0.01, 0.13]). Overall, the present study serves as an initial investigation into the nature of the associations between visceral sensitivity, anxiety symptoms, and clinically significant smoking processes among treatment-seeking smokers. Future work is needed to explore the extent to which anxiety accounts for relations between visceral sensitivity and other smoking processes (e.g., withdrawal, cessation outcome).     

The effect of FT500 Plus® on ovarian stimulation in PCOS women

Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus^®). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5-month follow-up in the Group A (11.1 ± 0.9 versus 13.5 ± 1; P = 0.0001). Group A showed a significant increase in the number of MII oocytes (6.3 ± 2.5 versus 4.5 ± 2; P = 0.03) and glutathione peroxidase activity in follicular fluid (15.4 ± 6.2 versus 11 ± 2.2; P = 0.04). FT500 Plus^® may be considered in PCOS patient for improving oocyte quality.     

Progressive vascular remodelling,endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease

Chronic kidney disease (CKD) and hypertension are co-morbid conditions both associated with altered resistance artery structure, biomechanics and function. We examined these characteristics in mesenteric artery together with renal function and systolic blood pressure (SBP) changes in the Lewis polycystic kidney (LPK) rat model of CKD. Animals were studied at early (6-weeks), intermediate (12-weeks), and late (18-weeks) time-points (n = 21), relative to age-matched Lewis controls (n = 29). At 12 and 18-weeks, LPK arteries exhibited eutrophic and hypertrophic inward remodelling characterised by thickened medial smooth muscle, decreased lumen diameter, and unchanged or increased media cross-sectional area, respectively. At these later time points, endothelium-dependent vasorelaxation was also compromised, associated with impaired endothelium-dependent hyperpolarisation and reduced nitric oxide synthase activity. Stiffness, elastic-modulus/stress slopes and collagen/elastin ratios were increased in 6 and 18-week-old-LPK, in contrast to greater arterial compliance at 12 weeks. Multiple linear regression analysis highlighted SBP as the main predictor of wall–lumen ratio (r = 0.536, P < 0.001 n = 46 pairs). Concentration–response curves revealed increased sensitivity to phenylephrine but not potassium chloride in 18-week-LPK. Our results indicate that impairment in LPK resistance vasculature is evident at 6 weeks, and worsens with hypertension and progression of renal disease.     

The association between reduced folate carrier-1 gene 80G/A polymorphism and methotrexate efficacy or methotrexate related-toxicity in rheumatoid arthritis: A meta-analysis

Methotrexate (MTX), the most commonly used anti-rheumatic drug against RA, enters the cell via the action of the reduced folate carrier 1(RFC1). A major polymorphism of the RFC1 gene, 80G/A, has been reported to influence the activity of RFC1, resulting in variable intracellular MTX-polyglutamate (MTX-PG) levels. However, the association studies addressing the RFC1 80G/A polymorphism and MTX efficacy or toxicity in Rheumatoid arthritis (RA) has yielded conflicting results. In the present meta-analysis, we aimed to evaluate the association between the RFC1 80G/A polymorphism and MTX efficacy or toxicity in RA patients. A total 17 studies met our inclusion criteria. Among them, 12 studies with 2049 subjects reported the association between the RFC1 80G/A and MTX response, and 12 studies involving 2627 subjects were on MTX-related toxicity. Meta-analysis revealed significant association between RFC1 80G/A polymorphism and MTX efficacy (odds ratio (OR) for the A allele =  1.29, 95% confidence interval (CI) 1.05–1.67, P = 0.02; for AA genotype: OR =  1.49, 95%CI 1.17–1.907, P = 0.001). However, no association could be detected in the analysis of MTX-related toxicity. Stratification by ethnic population also indicated an association between this polymorphism and MTX efficacy in Asian group (P = 0.002 for A allele; P = 0.003 for AA genotype), but not in the Caucasian group (P = 0.15 for A allele; P = 0.05 for AA genotype). In both Asian and Caucasian sub-groups, no influence of the RFC1 80G/A polymorphism on MTX toxicity can be detected. In conclusion, the RFC1 G80A polymorphism is associated with responsiveness to MTX therapy, but may not be associated with MTX toxicity in RA patients.     

Dialkyl phosphates in amniotic fluid as a biomarker of fetal exposure to organophosphates in Crete,Greece; association with fetal growth

The aim of this study was to evaluate fetal exposure to organophosphate pesticides (OPs) by measuring their non-specific dialkyl-phosphate metabolites (DAPs) in amniotic fluid (AF), and to examine the potential association between prenatal exposure and fetal growth. AF samples were collected from 415 women during the second gestational trimester. The determined OPs metabolites were DMP, DMTP, DEP, DETP, and DEDTP. DAPs were extracted by liquid–solid extraction, derivatized and analyzed by gas chromatography–mass spectrometry. 97.8% of AF samples were positive for at least one DAP. DAPs levels did not differ between urban and rural areas. Macrosomic neonates have significantly higher sum levels of DMPs (p = 0.043), which exerted a linear positive association with birth-weight centile (b = 4.43, p = 0.016). Conclusively, as DAPs are detectable in AF they may be used as a potential biomarker of fetal exposure to OPs. Sum levels of DMPs appear to be associated with birth weight independently of other covariates.     

Assessing cerebrospinal fluid abnormalities in neurosyphilis patients without human immunodeficiency virus infection

Neurosyphilis (NS) caused by Treponema pallidum (T. pallidum) subspecies pallidum, can affect the central nervous system during any stage of the disease. To assess several laboratory parameters for NS diagnosis, we performed a case control study on 42 hospitalized NS patients negative for human immunodeficiency virus (HIV) and 40 syphilis/non-NS patients, excluding NS patients at Xiamen Zhongshan Hospital from June 2010 to June 2011. Multivariate logistic regression model showed that the cerebrospinal fluid white blood cell (CSF-WBC, P = 0.009) levels, the CSF-LDH (P = 0.006) levels, the albumin quotient (P = 0.009) and the IgA index (P = 0.042) were independently associated with high risk of NS. The receiver operator characteristic (ROC) curve analysis revealed that the optimal cut-offs were 10 × 10⁶ cells/L for the CSF-WBC concentration, 19.3 U/L for the CSF lactate dehydrogenase (LDH) concentration, 7.08 for the albumin quotient, and 0.14 for the IgA index. Combining the CSF-WBC level, the CSF-LDH level, the albumin quotient and the IgA index increased the NS diagnosis sensitivity to 97.6%. T. pallidum particle agglutination (TPPA) index significantly correlated with the CSF-WBC (r = 0.453, P = 0.000), the IgA index (r = 0.446, P = 0.000), the albumin quotient (r = 0.262, P = 0.017), and the CSF-LDH (r = − 0.278, P = 0.012), respectively. In addition, there were correlations between the CSF-WBC and the IgA index (r = 0.329, P = 0.003), and between the CSF-WBC and the albumin quotient (r = 0.306, P = 0.005). Our results indicated that simultaneous testing of CSF-WBC levels, albumin quotient, IgA index and CSF-LDH can help predict the likelihood of NS in HIV-negative patients.     

Combined expectancies of alcohol and e-cigarette use relate to higher alcohol use

Electronic cigarettes (e-cigs) were created to approximate the look, feel, and experience of using a cigarette. Since cigarette and alcohol use co-occur, we hypothesized that e-cig and alcohol use also co-occur, likely due to shared positive drug expectations. Using self-report data from two independent samples of community-dwelling alcohol using adults, the present study: (1) modified the Nicotine and Other Substance Interaction Expectancy Questionnaire (NOSIE) to assess expectancies of combined e-cig and alcohol use (i.e. the individuals perceived likelihood of using e-cigs and alcohol together; NOSIE-ER); and (2) examined the relationships among e-cig use, expectancies, and alcohol use across e-cig use status. In the first sample (N = 692, mean age = 32.6, SD = 9.74, 50.7% female, 82.2% Caucasian), exploratory factor analysis suggested the presence of two factors: (1) alcohol use leads to e-cig use (Scale 1; α = 0.85); and (2) e-cig use leads to alcohol use (Scale 2; α = 0.91). In the second sample (N = 714, mean age = 34.1, SD = 10.89, 47.8% female, 75.6% Caucasian), confirmatory factor analysis supported this factor structure (χ² = 47.00, p < 0.01, df = 19; RMSEA = 0.08, 90% CI = 0.05–0.11; TLI = 0.99; CFI = 0.99). Compared to non e-cig users, e-cig users had significantly higher problematic alcohol use in both samples (b's = 0.09 to 0.14, p's < .05). Expectancies of combined e-cig and alcohol use were significantly related to problematic alcohol use (b's = − 0.92 to 0.26, p's < .05). In sum, e-cig use is related to alcohol use and expectancies of combined e-cig and alcohol use; consequently, reshaping of beliefs about needs or desires to co-use could be a prime point of intervention.     

Alteration of serum sex hormonal profile in male gasoline filling station workers in respect to their polymorphism of glutathione S-transferase M1

Alterations in offspring sex ratio at birth and level of serum testosterone in filling-station workers have been reported. To determine the association of glutathione S-transferase M1 (GSTM1) polymorphism with serum levels of total testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) of male filling-station workers, the present study was carried out on 114 gasoline workers and 100 age- and sex-matched controls with no occupational exposure to gasoline. We have found no significant difference between the workers and controls for levels of sex hormones in the presence of active GSTM1 genotype. Among subjects with the GSTM1 null genotype, there was significant difference between exposed and unexposed subjects for the concentration of testosterone (t = 4.37, df = 97, P < 0.001). To investigate whether one null genotype could be compensated by an active genotype for the other isoenzyme, the mean concentrations of sex hormones was compared between the exposed and control groups with respect to their combinations of the GSTM1 and GSTT1 genotypes. The exposed group having either “null GSTM1/positive GSTT1” (t = 2.76, df = 72, P = 0.007) or “null GSTM1/null GSTT1” (t = 4.91, df = 23, P < 0.001) combinations had a lower testosterone compared with the controls. It seems that GSTM1 polymorphism has more effect on serum testosterone compared to the GSTT1 polymorphism, in exposed workers.     

Safety evaluation of daidzein in laying hens: Part I. Effects on laying performance,clinical blood parameters,and organs development

Daidzein, an estrogen-like product, becomes increasingly popular as a dietary supplement, particularly for postpeak-estrus animals seeking a safe natural alternative to play a role of estrogen. However, there is little available safety data of it for raisers and consumers. A subchronic laying hen safety study was conducted to examine if the high-dose daidzein could affect the safety of hens selves, including laying performance, clinical blood parameters and organs development. Seven hundred and sixty-eight 56-week-old Hyline Brown were randomly assigned to 4 groups with 8 replicates of 24 birds each and 3 weeks later fed diets supplemented with 0, 10, 50 and 100 mg of daidzein/kg for 12 weeks. The mortality was significantly decreased (P < 0.05). No treatment related adverse clinical signs were observed. Mean egg production, egg mass and feed conversion of whole experiment period was significantly influenced by dietary daidzein supplement (P < 0.05), showing significant quadratic response to increasing dietary daidzein supplement (P = 0.029, P = 0.003 and P = 0.019, respectively). There was no statistically significant changes in haematology (P > 0.05). In clinical chemistry parameters, total protein, total cholesterol, calcium and phosphorus were significantly affected by dietary daidzein supplement (P < 0.05). The no observed adverse effect level (NOAEL) is considered to be 50 mg/kg.     

Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation

Alcohol dysregulates the regulation of reproductive vascular adaptations. We herein investigated chronic in vitro binge-like alcohol effects on umbilical endothelial nitric oxide synthase (eNOS) multi-site phosphorylation and related redox switches under basal (unstimulated) and stimulated (with ATP) states. Alcohol decreased endothelial excitatory ^Pser1177eNOS (P < 0.001), whereas excitatory ^Pser635eNOS exhibited a main effect of alcohol (↓P = 0.016) and ATP (↑P < 0.001). Alcohol decreased ^Pthr495eNOS (P = 0.004) levels, whereas inhibitory ^Pser116eNOS exhibited an alcohol main effect in both basal and stimulated states (↑P = 0.005). Total eNOS was reduced by alcohol (P = 0.038). In presence of ATP, alcohol inhibited ERK activity (P = 0.002), whereas AKT exhibited no alcohol effect. Alcohol main effect on S-nitroso-glutathione reductase (↓P = 0.031) and glutathione-S-transferase (↓P = 0.027) were noted. Increased protein glutathiolation was noted, whereas no alcohol effect on GSH, GSSG, NOX2 or SOD expression was noted. Thus, alcohol effects on multi-site post-translational modifications and redox switches related to vasodilatory eNOS underscore the necessity for investigating alcohol-induced gestational vascular dysfunction.     

How does tobacco smoke influence the morphometry of the fetus and the umbilical cord?—Research on pregnant women with intrauterine growth restriction exposed to tobacco smoke

Proper structure of the umbilical cord is important for the fetal development. We evaluated effects of toxic factors from tobacco smoke on fetal and umbilical cord morphometry. 109 women in weeks 29–40 of pregnancy (31 smokers with intrauterine growth restriction (IUGR); 28 non-smoking women with IUGR; 50 healthy pregnancies) were included. In smokers with IUGR, cotinine, cadmium and lead concentrations were significantly higher than in controls (mean 55.23 ng/l; 1.52 ng/ml; 14.85 ng/ml vs 1.07; 0.34; 9.42) and inverse correlation between lead concentration and uncoiled umbilical cord was significant (r = −0.80). In smokers with IUGR, area of Wharton’s jelly was increased compared to nonsmokers and controls. Inverse correlations occurred between cotinine and cadmium concentration and fetal percentile in smokers (r = −0.87; r = −0.87) and non-smokers (r = −0.47; r = −0.78) with IUGR. Exposure to tobacco smoke measured by cotinine, cadmium and lead concentration has an impact on fetal growth and umbilical cord morphometry and correlates with intensity of IUGR.